Syllabus Abdomen

Diseases of the Abdomen and Pelvis 2010-2013
Diagnostic Imaging and Interventional Techniques

J. Hodler • G.K. von Schulthess • Ch.L. Zollikofer (Eds)
DISEASES OF THE ABDOMEN

AND PELVIS 2010-2013
DIAGNOSTIC IMAGING
AND INTERVENTIONAL TECHNIQUES
42nd International Diagnostic Course

in Davos (IDKD)
Davos, March 21-26, 2010
including the
Nuclear Medicine Satellite Course “Diamond”
Pediatric Satellite Course “Kangaroo”

IDKD in Greece
presented by the Foundation for the

Advancement of Education in Medical Radiology, Zurich
Editors
J. HODLER G. K. VON SCHULTHESS

Radiology, Nuclear Medicine,
University Hospital, University Hospital,
Zurich, Switzerland Zurich, Switzerland
CH. L. ZOLLIKOFER
Kilchberg/Zurich, Switzerland
ISBN 978-88-470-1636-1 e-ISBN 978-88-470-1637-8
DOI 10.1007/978-88-470-1637-8
Springer Dordrecht Heidelberg London Milan New York
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IDKD 2010-2013
Preface
The International Diagnostic Course in Davos (IDKD) offers a unique learning

experience for imaging specialists in training as well as for experienced radio-
logists and clinicians wishing to be updated on the current state of the art and the
latest developments in the fields of imaging and image-guided interventions.
This annual course is focused on organ systems and diseases rather than on
modalities. This year’s program deals with diseases of the abdomen and pelvis.
During the course, the topics are discussed in group workshops and in plenary
sessions with lectures by world-renowned experts and teachers. While the work-
shops present state-of-the-art summaries, the lectures are oriented towards future
developments. Accordingly, this Syllabus represents a condensed version of the
contents presented under the 20 topics dealing with imaging and interventional
therapies in abdominal and pelvic diseases. The topics encompass all the relevant
imaging modalities including conventional X-rays, computed tomography, nu-
clear medicine, ultrasound and magnetic resonance angiography, as well as
image-guided interventional techniques.
The Syllabus is designed to be an “aide-mémoire” for the course participants
so that they can fully concentrate on the lecture and participate in the discussions
without the need of taking notes.
Additional information can be found on the IDKD website: www.idkd.org
J. Hodler
G.K. von Schulthess
Ch.L. Zollikofer
IDKD 2010-2013
Table of Contents
Workshops
Emergency Radiology of the Abdomen: The Acute Abdomen . . . . . . . . . . . . . . . . . . . . . . . 3
Jean-Michel Bruel, Borut Marincek, Jay P. Heiken
Trauma of the Abdomen and Pelvis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Philip J. Kenney, Stuart E. Mirvis
Diseases of the Esophagus and Stomach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Marc S. Levine, Ahmed Ba-Ssalamah
Small-Bowel Imaging: Pitfalls in Computed Tomography Enterography/Enteroclysis 28

Marc J. Gollub
Diseases of the Small Bowel, Including the Duodenum – MRI . . . . . . . . . . . . . . . . . . . . . . 32

Karin A. Herrmann
Imaging of the Colon and Rectum: Inflammatory and Infectious Diseases . . . . . . . . . . 37

Jaap Stoker, Richard M. Gore
CT Colonography: Updated . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Daniel C. Johnson, Michael Macari
Imaging of Diffuse and Inflammatory Liver Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

Pablo R. Ros, Rendon C. Nelson
Focal Liver Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

Wolfgang Schima, Richard Baron
Imaging Diseases of the Gallbladder and Bile Ducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Angela D. Levy, Celso Matos
Diseases of the Pancreas, I: Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

Thomas Helmberger
Diseases of the Pancreas, II: Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

Ruedi F. Thoeni
Adrenal Imaging and Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96

William W. Mayo-Smith, Isaac R. Francis
Renal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Richard H. Cohan, Ronald J. Zagoria
Urinary Tract Obstruction and Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

Parvati Ramchandani, Julia R. Fielding
VIII Table of Contents
Benign Diseases of the Female Genital Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

Caroline Reinhold, Rahel A. Kubik-Huch
Malignant Diseases of the Female Genital Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

Evis Sala, Susan Ascher
Magnetic Resonance Imaging of Prostate Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

Jelle O. Barentsz, Stijn W.T.P.J. Heijmink, Christina Hulsbergen-van der Kaa,
Caroline Hoeks, Jurgen J. Futterer
Imaging of the Male Pelvis: The Scrotum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

Brent J. Wagner
Spread of Metastatic Disease in the Abdomen and Pelvis . . . . . . . . . . . . . . . . . . . . . . . . . . . 146

James A. Brink, Ali Shirkhoda
Abdominal Vascular Disease: Diagnosis and Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154

Johannes Lammer
Non-vascular Abdominal Disease: Diagnosis and Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . 162

Carlo Bartolozzi, Valentina Battaglia, Elena Bozzi
An Approach to Imaging the Acute Abdomen in the Pediatric Population . . . . . . . . . . . 167

Alan Daneman, Simon G. Robben
Imaging Uronephropathies in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

Jeanne S. Chow, Fred E. Avni
Integrated Imaging in Genitourinary Oncology: PET/CT Imaging . . . . . . . . . . . . . . . . . . . . 183

Gerald Antoch
Integrated Imaging in Gastrointestinal Oncology: PET/CT Imaging . . . . . . . . . . . . . . . . . 190

Thomas F. Hany
Nuclear Medicine Satellite Course “Diamond”

Lymphoma: Diagnostic and Therapeutic Applications of Radiopharmaceuticals . . . . . 199
Angelika Bischof Delaloye
Conventional Nuclear Medicine in the Evaluation of Gastrointestinal

and Genitourinary Tract Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
Ariane Boubaker
PET in Hepatobiliary-Pancreatic Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215

Stefano Fanti, Anna Margherita Maffione, Vincenzo Allegri
PET in Tumors of the Digestive Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219

Thomas F. Hany
Tumors of the Adrenergic System: Imaging and Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . 226

Cornelis A. Hoefnagel
Neuroendocrine Tumors of the Abdomen: Imaging and Therapy . . . . . . . . . . . . . . . . . . . . 231

Dik J. Kwekkeboom
Table of Contents IX
Pediatric Satellite Course “Kangaroo”

Imaging Cystic Kidneys in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
Fred E. Avni
Understanding Duplication Anomalies of the Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243

Jeanne S. Chow
Malrotation: Techniques, Spectrum of Appearances, Pitfalls, and Management . . . . . 247

Alan Daneman
Pediatric Intestinal Ultrasonography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252

Simon G. Robben
IDKD 2010-2013
List of Contributors
Allegri V., 215 Hoefnagel C.A., 226

Antoch G., 183 Hoeks C., 125
Ascher S., 119 Hulsbergen-van der Kaa C., 125
Avni F.E., 174, 239 Johnson D.C., 48
Ba-Ssalamah A., 22 Kenney P.J., 14
Barentsz J.O., 125 Kubik-Huch R.A., 110
Baron R., 63 Kwekkeboom D.J., 231
Bartolozzi C., 162 Lammer J., 154
Battaglia V., 162 Levine M.S., 22
Bischof Delaloye A., 199 Levy A.D., 75
Boubaker A., 205 Macari M., 48
Bozzi E., 162 Maffione A.M., 215
Brink J.A., 146 Marincek B., 3
Bruel J.-M., 3 Matos C., 75
Chow J.S., 174, 243 Mayo-Smith W.W., 96
Cohan R.H., 99 Mirvis S.E., 14
Daneman A., 167, 247 Nelson R.C., 50
Fanti S., 215 Ramchandani P., 104
Fielding J.R., 104 Reinhold C., 110
Francis I.R., 96 Robben S.G., 167, 252
Futterer J.J., 125 Ros P.R., 50
Gollub M.J., 28 Sala E., 119
Gore R.M., 37 Schima W., 63
Hany T.F., 190, 219 Shirkhoda A., 146
Heiken J.P., 3 Stoker J., 37
Heijmink S.W.T.P.J., 125 Thoeni R.F., 89
Helmberger T., 81 Wagner B.J., 142
Herrmann K.A., 32 Zagoria R.J., 99
WORKSHOPS
IDKD 2010-2013
Emergency Radiology of the Abdomen: The Acute Abdomen

Jean-Michel Bruel1, Borut Marincek2, Jay P. Heiken3
1 Medical Imaging Department, Hôpital Saint-Eloi, CHRU de Montpellier, Montpellier, France
2 Instituteof Diagnostic Radiology, University Hospital, Zurich, Switzerland
3 Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
Introduction 1. The multidetector CT (MDCT) image data volume

should be obtained from the dome of the diaphragm
The term “acute abdomen” defines a clinical syndrome to the inferior aspect of the pubic symphysis (with
characterized by a history of hitherto undiagnosed ab- thin collimation and a short acquisition time). CT da-
dominal pain lasting less than one week. A large range of ta are reconstructed with thin, overlapped slices for
disorders, from benign, self-limited diseases to condi- multiplanar (coronal and sagittal planes) reformation
tions that require immediate surgery, can cause acute ab- and 3- to 5-mm thick contiguous axial slices. The
dominal pain. Eight conditions account for over 90% of image series is sent to a dedicated workstation and/or
patients who are referred to the hospital and who are seen PACS.
on surgical wards with acute abdominal pain: acute ap- 2. Vascular enhancement by iodinated contrast medium
pendicitis, acute cholecystitis, small bowel obstruction (CM) is mandatory in most cases, unless contraindi-
(SBO), urinary colic, perforated peptic ulcer, acute pan- cated. Special attention should be paid to older pa-
creatitis, acute diverticular disease, and non-specific, tients and those with metabolic disorders (dehydration
non-surgical abdominal pain (dyspepsia, constipation). in SBO) in assessing the renal impact of CM admin-
istration. In general, the most helpful scanning phase
is the late portal phase (70 s), but other scanning phases
Imaging Techniques are useful in selected circumstances: arterial phase
in bowel ischemia, bleeding, or visceral infarction;
Clinical assessment of the acute abdomen is often diffi- delayed phase (3 min) for assessing the lack of en-
cult because the findings of the physical examination hancement in a patient with suspected acute mesen-
and laboratory investigations are often non-specific. teric ischemia. A pre-contrast CT scan allows demon-
Traditionally, plain abdominal radiographs have served stration of calcifications, lithiasis, and acute or sub-
as the initial imaging approach; however, because of acute hemorrhage; multiphasic scanning should be
their diagnostic limitations, plain radiographs now play used only for specific indications in order to limit ra-
only a limited role in this clinical setting. Currently, the diation dose.
major indications for plain radiography are to determine 3. Changes in the CT protocol should be decided accord-
the presence of bowel obstruction, perforated viscus, ing to the clinical conditions and/or the preliminary re-
urinary tract calculi, or a foreign body. The convention- sults of the CT examination. In selected cases, colo-
al radiographic examination consists of supine and ei- rectal opacification and/or image acquisition with the
ther upright or left lateral decubitus images. Computed patient in the prone position may be helpful to clarify
tomography (CT) now serves as the imaging test of equivocal findings. In most cases, the systematic use
choice for most adult patients with acute abdominal of ingested oral contrast is not recommended.
pain. It has been shown to be superior to plain radio- 4. The method of image evaluation is critical to optimize
graphy for diagnosing nearly all causes of acute abdom- interpretation. Additional window level (M) and width
inal pain. Several studies have demonstrated that the use (W) settings are useful to identify tiny bubbles of ex-
of CT to evaluate patients with acute abdominal pain intraluminal gas (CT lung windows) or hyperattenuation
creases the accuracy of clinical diagnosis by >20% and from recent hemorrhage (narrow CT windows). The
results in management changes in up to 60% of patients. systematic use of multiplanar reformation (MPR), par-
The major obstacles to replacing plain abdominal radio- ticularly in the coronal plane, is recommended, and 3D
graphy with CT are its higher cost, more limited avail- imaging may be helpful.
ability, and higher radiation dose. The use of CT in pa- Ultrasonography (US) is the initial imaging technique of
tients with an acute abdomen requires careful attention choice for patients with suspected acute cholecystitis or
to the CT protocol. acute gynecological abnormalities. It also is the primary
4 Jean-Michel Bruel, Borut Marincek, Jay P. Heiken
method for evaluating pregnant women and pediatric pa- wall. Gallbladder perforation and complicating peri-
tients. Although less sensitive and specific than CT, US cholecystic abscess typically occur adjacent to the gall-
is an excellent imaging test for diagnosing acute appen- bladder fundus because of the sparse blood supply. CT
dicitis, when employed by experienced individuals. It can may be useful for confirmation of the sonographic diag-
also be used to evaluate the presence or absence of the nosis, but usually is not necessary. Emphysematous
layered structure of the digestive tract wall or to assess cholecystitis is a rare complication of acute cholecystitis
the structure of a lesion identified at CT. that generally is associated with diabetes mellitus. US or
Until recently, magnetic resonance imaging (MRI) has CT demonstrates gas in the wall and/or lumen of the gall-
played a very limited role in patients with acute abdomi- bladder, which implies underlying gangrenous changes
nal pain; however, it is now established in the imaging of (Fig. 1). Acalculous acute cholecystitis accounts for only
pregnant women with abdominal pain who have had a approximately 5% of cases of acute cholecystitis but is
negative or equivocal US examination. Recent studies as- especially common in patients in the intensive care unit.
sessing the use of MRI to evaluate all patients with acute Prolonged bile stasis results in increased viscosity of the
lower abdominal pain have shown promising results. MRI bile that ultimately leads to functional cystic duct ob-
may also have a role in patients with biliary diseases struction.
and/or pancreatitis. Both US and CT are accurate techniques for diagnos-
The differential diagnosis in a patient with an acute ab- ing liver abscesses. US usually demonstrates a round or
domen is influenced greatly by the nature and location of oval hypoechoic mass with low-level internal echoes. Al-
the pain. Therefore, the imaging strategies for acute pain though the lesion may mimic a solid hepatic mass, the
localized to an abdominal quadrant should be discussed presence of through transmission is a clue to its cystic na-
separately from those for acute pain that is diffuse or lo- ture. Pyogenic liver abscesses most commonly are the re-
calized to the flank or epigastric region. sult of seeding from appendicitis or diverticulitis or direct
extension from cholecystitis or cholangitis. Amebic ab-
scesses result from primary colonic involvement, with
Acute Pain in an Abdominal Quadrant seeding through the portal vein. In most cases, the US ap-
pearances of pyogenic and amebic abscess are indistin-
In many cases, acute abdominal pain can be localized to guishable. The CT appearances of pyogenic and amebic
one either the right upper, left upper, right lower, or left abscesses also overlap substantially. Amebic abscesses
lower abdominal quadrant. are cystic masses of low attenuation. An enhancing wall
and a peripheral zone of edema surrounding the abscess
Right Upper Quadrant are common but not universally present. Extrahepatic ex-
tension of the amebic abscess with involvement of the
Acute cholecystitis is by far the most common disease to chest wall, pleura, or adjacent viscera is a frequent find-
involve the right upper quadrant. Other important dis- ing. Whereas amebic abscesses usually are solitary and
eases that can have a clinical presentation similar to that unilocular, pyogenic abscesses may be multiple or multi-
of acute cholecystitis are pyogenic or amebic liver ab-
scess, spontaneous rupture of a hepatic neoplasm (usual-
ly hepatocellular adenoma or carcinoma), hepatitis, and
myocardial infarction.
The preferred imaging method for evaluating patients
with acute right upper abdominal pain is US. It is a reli-
able technique for establishing the diagnosis of acute cal-
culous cholecystitis. The imaging criteria include the de-
tection of gallstones, the sonographic Murphy sign, gall-
bladder wall thickening ≥3 mm, and pericholecystic flu-
id. The association of three of these signs is highly sug-
gestive of acute cholecystitis. Isolated gallbladder wall
thickening may be secondary to other conditions, such as
gallbladder adenomyomatosis, gallbladder carcinoma,
HIV cholangitis, sclerosing cholangitis, acute hepatitis,
cirrhosis, ascites, portal hypertension, hypoproteinemia,
pancreatitis, and cardiac failure. In acute calculous chole-
cystitis, typically a calculus obstructs the cystic duct. The
trapped concentrated bile irritates the gallbladder wall,
causing increased secretion, which in turn leads to dis-
tention and edema of the wall. The rising intraluminal Fig. 1. Diabetic patient with emphysematous cholecystitis and gan-
pressure compresses the vessels, resulting in thrombosis, grene of the gallbladder. CT shows air-fluid level in the gallblad-
ischemia, and subsequent necrosis and perforation of the der lumen and air in the gallbladder wall (arrows)
Emergency Radiology of the Abdomen: The Acute Abdomen 5
loculated and may demonstrate an irregular contour. diseases that can present with acute right lower quadrant
Some pyogenic abscesses have a mixed cystic and solid pain include acute terminal ileitis (Crohn’s disease), ty-
appearance on US, CT, or MRI; rarely, they appear com- phlitis, right-sided colonic diverticulitis and, in women,
pletely solid. A small percentage of hepatic abscesses, pelvic inflammatory disease, complications of ovarian
particularly those secondary to Klebsiella infection, are cyst (hemorrhage, torsion, and leakage), endometriosis,
associated with portal vein thrombosis. or ectopic pregnancy. Less common causes of right low-
Spontaneous rupture of a hepatocellular carcinoma er quadrant pain include segmental infarction of the
with subsequent hemoperitoneum is a frequent complica- greater omentum, mesenteric adenitis, epiploic ap-
tion in countries with a high incidence of this tumor, but pendagitis, perforated cancer, and ileal or Meckel’s di-
is less commonly seen in Western countries. Subcapsular verticulitis.
location and tumor necrosis have been implicated in the The diagnosis of acute appendicitis is uncertain in up
pathogenesis. US, and especially CT, are the most useful to one-third of patients. Thus, pre-operative imaging
techniques for diagnosing a ruptured hepatocellular car- plays an important role in confirming or excluding the
cinoma, which appears as a peripheral or subcapsular diagnosis. With the increasing use of medical imaging
mass. Transcatheter embolization of either the tumor or to evaluate patients with suspected acute appendicitis,
the bleeding hepatic artery is the treatment of choice. the rate of both false-positive (unnecessary appendecto-
Spontaneous hemorrhage within a hepatocellular adeno- my) and false-negative (leading to complications from
ma occurs most commonly in women taking oral contra- perforated appendicitis) diagnoses has decreased. The
ceptives. Capsular rupture with subsequent hemo- standard surgical teaching is that patients with typical
peritoneum is an uncommon complication. On CT, high- clinical findings should undergo immediate appendec-
density intraperitoneal fluid confirms the diagnosis of tomy without pre-operative imaging. Nevertheless, at
hemoperitoneum. Extravasation of CM, when present, is most medical centers pre-operative imaging is obtained
indicative of active bleeding. even when the clinical presentation is typical. The most
specific CT finding of acute appendicitis is a thick-
Left Upper Quadrant walled appendix that contains an appendicolith (Fig. 2).
The inflamed appendix often is dilated and fluid-filled.
Although infrequent, acute left upper quadrant pain is Additional helpful findings are stranding of the peri-
most often seen in splenic infarction, splenic abscess, appendiceal fat and thickening of the cecal apex. Find-
gastritis, and gastric or duodenal ulcer. US is most fre- ings that indicate appendiceal perforation include peri-
quently used for screening, while CT enables accurate appendiceal abscess, extraluminal gas, a right lower
further evaluation. The diagnosis of gastric pathology is quadrant inflammatory mass, a defect in the appen-
established by endoscopy, with imaging playing a minor diceal wall, and SBO.
role. In the evaluation of suspected acute appendicitis in
Common causes of splenic infarction include bacteri- children, pregnant women, and women of reproductive
al endocarditis, portal hypertension, and marked age, US is an important imaging option. Demonstration
splenomegaly. Pancreatitis or tumors that extend into the of a swollen, noncompressible appendix >7 mm in di-
splenic hilum can also result in infarction. Splenic in- ameter with a target configuration is the primary sono-
farction may be focal or global. Typical focal splenic in- graphic criterion (Fig. 3). Additional helpful US find-
farcts appear as peripheral wedge-shaped defects, hypo- ings are “MacBurney’s sign” (maximum tenderness
echoic or isoechoic at US and hypoattenuating at CT. found with graded compression of the inflamed appen-
Most splenic abscesses are secondary to hematogenous dix) and demonstration of an appendicolith. These US
dissemination of infection, e.g., bacterial endocarditis or signs may also be demonstrated by transvaginal high-
tuberculosis. Intravenous drug abusers and immunocom- resolution US. The advantages of US include the lack
promised individuals are predominantly affected. US and of ionizing radiation, relatively low cost, and wide-
CT are sensitive, but the specificity of either one is low. spread availability. However, US requires considerable
On US, most abscesses appear as hypo- or anechoic, skill and is difficult to perform in obese patients, pa-
poorly defined lesions; on CT, they typically appear as tients with severe pain, and patients likely to have a
rounded lesions of low attenuation and with rim en- complicating periappendiceal abscess. When the sono-
hancement. Spontaneous splenic rupture can occur in pa- graphic findings are unclear, CT can provide a rapid
tients with hematological malignancy or secondary to and definitive diagnosis. Due to its exceptional accura-
rapid splenic enlargement from viral infections such as cy, CT has emerged in many centers as the primary
mononucleosis. imaging test for patients with suspected acute appen-
dicitis.
Right Lower Quadrant In a small percentage of patients, diverticulitis mani-
fests itself as a right-sided condition. Right-sided colonic
Acute appendicitis is not only the most frequent cause of diverticula are often congenital, solitary, and true diver-
acute right lower quadrant pain, it is also the most com- ticula, unlike sigmoid diverticula. In right-sided divertic-
monly encountered cause of an acute abdomen. Other ulitis the normal appendix should be visible.
a c
Fig. 2 a-c. Acute appendicitis. Axial (a, b)

and sagittal (c) views of multidetector CT
demonstrate a dilated appendix in retroce-
cal position, a calcified appendicolith at
the base of the appendix (arrowheads), and
inflammatory changes of the mesenteric
fat (arrow)
a b c
Fig. 3 a-c. Ultrasonography of acute appen-

dicitis in a 12-year-old girl. Oblique (a, b)
and transverse (c) views show swollen ap-
pendix (diameter 10 mm, arrowheads)
with a target configuration
Left Lower Quadrant flammatory changes, such as fat stranding, inflammatory

mass, gas bubbles, or free fluid (Figs. 4, 5). Complications
Diverticulitis is the most common cause of acute left low- of acute diverticulitis include abscess, fistula (most com-
er quadrant abdominal pain. The condition occurs in monly colovesical), SBO, peritonitis, septic thrombo-
10–20% of patients with diverticulosis and most common- phlebitis, colonic obstruction, and ureteral obstruction.
ly involves the sigmoid colon. CT is very sensitive and ap- In patients with left lower quadrant pain, alternative diag-
proaches 100% specificity and accuracy in the diagnosis or noses that should be considered are colitis (infectious/
exclusion of diverticulitis; it has therefore largely replaced inflammatory or ischemic), colonic carcinoma, epiploic ap-
barium enema examinations. CT is also very useful in es- pendagitis, neutropenic colitis, functional colonic disor-
tablishing the presence of pericolic complications. The CT ders, and extragastrointestinal disorders (pyelonephritis or
diagnosis of acute diverticulitis is based on the identifica- gynecological diseases). Epiploic appendagitis is a clinical
tion of segmental colonic wall thickening and pericolic in- condition mimicking acute colonic diverticulitis, with focal
exquisite lower abdominal pain. It is diagnosed with CT (or

US) by the demonstration of an ovoid lesion within the
pericolonic fat, surrounded by inflammatory changes and
abutting the colonic wall. As this disease resolves sponta-
neously within a few days, its correct diagnosis on CT im-
ages is important to avoid unnecessary surgery.
Distinguishing sigmoid diverticulitis from carcinoma
is a major differential diagnostic consideration but is of-
ten difficult on CT images despite CT findings sugges-
tive of colon carcinoma, such as marked thickening of the
colonic wall, focal thickening (length <5 cm), and the
presence of pericolonic lymph nodes. The distinction be-
tween perforated colon carcinoma and diverticulitis may
be especially difficult because many patients with colon
carcinoma also have diverticulosis. Therefore, it is crucial
to perform colonoscopy 3-4 weeks after the onset of
Fig. 4. Sigmoid diverticulitis with pericolic abscesses. CT shows
fine linear strands within pericolic fat, diverticula filled with air, acute diverticulitis to rule out a colonic carcinoma.
barium, or fecal material, circumferential bowel thickening, and
frank abscesses (arrows)
Gynecological Disorders
a These are important causes of acute lower abdominal
pain (right lower quadrant, left lower quadrant, or central
pelvic) in female patients, particularly young women.
Acute uterine and ovarian disorders, pelvic inflammatory
disease, endometriosis, and ectopic pregnancy are diag-
nostic considerations in women of child-bearing age who
present with an acute abdomen.
Pelvic inflammatory disease (PID) is the most frequent
gynecological cause of an acute abdomen. Its manifesta-
tions may include salpingitis, tubo-ovarian abscess, and
peritonitis. The most common causative organisms are
Neisseria gonorrhoeae and Chlamydia trachomatis. Since
b PID most commonly results from an ascending infection,
it usually involves both adnexa. US is the imaging test of
choice for patients with suspected PID; however, CT is
helpful when the clinical diagnosis is equivocal. CT find-
ings may include fluid within the cul-de-sac, endometrial
thickening, fluid within the uterine cavity, and thickening
and dilation of the fallopian tubes (pyosalpinx) (Fig. 6).
Fig. 5 a, b. Perforated sigmoid diverticulitis. a CT demonstrates tiny

bubbles of extraluminal gas within the left subphrenic space (ar-
rows, 1) and hepatic pedicle (arrow, 2). The determination of a
pneumoperitoneum from the perforated sigmoid diverticulitis (b)
requires dedicated window settings. b Coronal reformat shows the
patterns indicating the severity of the local extent of this case of
sigmoid diverticulitis: thickened bowel wall with diverticula asso-
ciated with dramatic changes of the pericolic fat and thickened root Fig. 6. Pelvic inflammatory disease. Transaxial CT image shows
of the sigmoid mesocolon. Note the tiny bubble of extraluminal gas thickened, dilated fluid-filled fallopian tubes indicative of bilateral
(arrow) within the hepatic pedicle pyosalpinx
With progression to tubo-ovarian abscesses, unilateral or may be found in numerous alternative diagnoses. The di-
bilateral cystic adnexal masses may be seen, usually in as- agnosis of ectopic pregnancy is based on an association
sociation with pyosalpinx. In advanced cases of PID, the of the β-hCG level with the transvaginal US findings:
intrapelvic spread of purulent material may result in peri- 1. a normal β-hCG level rules out an ectopic pregnancy;
tonitis. Patients with Fitz-Hugh-Curtis syndrome present 2. an intrauterine gestational sac with a live embryo (car-
with right upper quadrant pain due to perihepatic inflam- diac activity) rules out an ectopic pregnancy (but in
mation from intraperitoneal exudates stretching between patients with assisted reproduction by ovulation induc-
the liver capsule and the peritoneum, which can mimic tion the rate of “heterotopic pregnancy”, defined as the
carcinomatosis on CT. simultaneous occurrence of an intrauterine and an ex-
In adult patients, ovarian torsion (adnexal torsion) usu- trauterine pregnancy, has been reported to be 1–3%);
ally occurs in association with an ovarian mass, which 3. an elevated β-hCG level (>1000 IU/L) without an in-
acts as a fulcrum to potentiate torsion. Teratoma is the trauterine gestational sac, associated with an abnormal
most common cause of ovarian torsion. The typical pre- adnexal pattern and/or heterogeneous pelvic fluid, in-
sentation is non-specific, consisting of acute lower ab- dicates an ectopic pregnancy.
dominal pain associated with nausea, vomiting, and
leukocytosis. If ovarian torsion is suspected, Doppler US
is the initial imaging test of choice; however, because the Acute Abdomen with Diffuse Pain
clinical presentation usually is non-specific, CT is often
the first imaging test requested. A CT finding helpful in Any disorder that irritates a large portion of the gastroin-
making the diagnosis of ovarian torsion is an enlarged testinal (GI) tract and/or the peritoneum can cause diffuse
ovary that is displaced from its normal location. Sec- abdominal pain. The most common disorder is gastro-
ondary signs include a thickened fallopian tube, a twist- enterocolitis. Other important disorders are bowel obstruc-
ed vascular pedicle, hemoperitoneum, and deviation of tion, ischemic bowel disease, and GI tract perforation.
the uterus toward the affected side.
Complications of ovarian cysts such as hemorrhage Bowel Obstruction
and rupture also can cause acute lower abdominal pain.
Hemorrhagic cysts contain fluid that is high in attenua- Bowel obstruction is a frequent cause of abdominal pain
tion, sometimes with a fluid-fluid level. In a small per- and accounts for approximately 20% of surgical admis-
centage of patients, the cyst may rupture, resulting in sions for acute abdominal conditions. The small bowel
hemoperitoneum. Correlation with β-human chorionic is involved in 60-80% of cases. Frequent causes of SBO
gonadotropin (hCG) levels is important as a ruptured are postoperative adhesions, hernias, and neoplasms.
ectopic pregnancy may present with similar clinical and Mechanical large bowel obstruction is most commonly
imaging features. due to colorectal carcinoma, but volvulus and diverticuli-
Endometriosis is characterized by the presence of tis are also important causes. Colonic volvulus most
functioning endometrial tissue outside of its normal in- commonly involves the sigmoid region, followed by the
trauterine location. It presents as acute abdominal pain in cecum.
only a small percentage of women and is usually caused The diagnosis of bowel obstruction is established on
by rupture or hemorrhage of an endometrioma or by tor- clinical grounds and usually confirmed with plain ab-
sion of an ovary that contains endometrial implants. On dominal radiographs. Due to the diagnostic limitations of
CT, endometriomas have a variable appearance, ranging plain radiography, CT is increasingly used to establish the
from cystic to solid adnexal masses. diagnosis, identify the site, level, and cause of obstruc-
Ectopic pregnancy remains the leading cause of death tion, and determine the presence or absence of associat-
during the first trimester of pregnancy, with a mortality ed bowel ischemia. CT can be useful for differentiating
of 9-14%. The main risk factors for ectopic pregnancy in- between simple and closed-loop obstruction. Closed-loop
clude a history of ectopic pregnancy, tubal surgery, and obstruction is a form of mechanical bowel obstruction in
PID. The initial evaluation of patients suspected of hav- which two points along the course of the bowel are ob-
ing an ectopic pregnancy requires quantitative measure- structed at a single site. It is usually secondary to an ad-
ment of serum β-hCG level and transvaginal US. The lat- hesive band or a hernia. Since a closed loop tends to in-
ter should be used to search for the presence of an ad- volve the mesentery and is prone to produce a volvulus,
nexal mass (with or without highly specific signs such as it represents the most common cause of strangulation.
adnexal gestational sac with a live embryo, suggested by However, only colonic volvulus is associated with classic
the demonstration of cardiac activity and/or a “tubal ring features on plain abdominal radiography.
sign”), hematosalpinx, pelvic free fluid (highly sugges- CT is particularly reliable in higher grades of bowel
tive if heterogeneous), and hemoperitoneum, enlarged obstruction. It has proved useful in characterizing bowel
uterus (with a pseudo-gestational sac), and symmetrical- obstruction from various causes, including adhesions,
ly enlarged ovaries. The diagnosis of ectopic pregnancy hernia, neoplasm, extrinsic compression, inflammatory
often is difficult, since transvaginal US may be normal in bowel disease, radiation enteropathy, intussusception,
up to 25% of these patients and adnexal abnormalities gallstone ileus, or volvulus. The essential CT finding of
bowel obstruction is the delineation of a transition zone Ischemic Bowel Disease

between the dilated and decompressed bowel. Careful in-
spection of the transition zone and luminal contents usu- Predominant causes of bowel ischemia are arterial or ve-
ally reveals the underlying cause of obstruction. Howev- nous occlusion and hypoperfusion. Occlusive disease in-
er, the presumed point of transition from dilated to non- volves the mesenteric arteries, most commonly the supe-
dilated bowel can be difficult to determine in the transax- rior mesenteric artery, in the large majority of cases.
ial plane. MDCT facilitates this task by providing the ra- Bowel ischemia secondary to venous thrombosis is much
diologist with a volumetric data set that can be viewed in less common. The only direct sign of vascular impair-
the transaxial, sagittal, or coronal plane or any combina- ment of the bowel is diminished bowel wall enhancement,
tion of the three. These MPR views centered on the an- which is due to inadequate arterial inflow to the bowel.
ticipated transition point help to determine the site, level, Increased bowel wall enhancement may be seen in some
and cause of obstruction. cases secondary to reactive hyperemia or compromised
Mechanical obstruction of the small bowel (SBO) has venous outflow. Other CT findings are direct visualiza-
to be differentiated from paralytic ileus, large bowel ob- tion of a thrombus in the superior mesenteric artery or
struction (LBO), and non-obstructive massive distention vein. Bowel distention and bowel wall edema are non-
of the colon. specific findings and may accompany inflammatory or
Paralytic ileus is a common problem after abdominal infectious causes. Bowel distention reflects the interrup-
surgery. It may be diffuse or localized and has numerous tion of peristaltic activity in ischemic segments. Non-
causes, e.g., secondary to ischemic conditions, inflam- occlusive acute mesenteric ischemia usually is due to
matory or infectious disease, abnormal electrolyte, hypoperfusion secondary to severe cardiac disease, but
metabolite, drug or hormonal levels, or innervation de- also occurs in patients with end-stage renal or hepatic
fects. disease. An important radiographic manifestation of non-
In LBO, CT demonstrates distension of the large bow- occlusive acute mesenteric ischemia due to low arterial
el to the point of obstruction, with collapse of the distal flow is mesenteric arterial vasoconstriction. A less com-
large bowel. The distal small bowel loops may also be mon form of non-occlusive acute mesenteric ischemia is
distended if the ileocecal valve is incompetent. Luminal severe vasculitis, which often affects younger individuals.
obstruction by a colonic carcinoma and colonic volvulus Mesenteric vasculitis usually results in bowel edema and
(Fig. 7) are the main causes of LBO. Perforation of the mucosal hyperenhancement. The small and the large
cecum, due to gross distention resulting in ischemia of bowel often are both involved. The duodenum is involved
the cecal wall, is the main complication of severe LBO. in approximately one-quarter of patients.
A massively dilated colon may be seen in toxic mega- The most common mechanical cause of bowel is-
colon and Ogilvie’s syndrome. In toxic megacolon sec- chemia is obstruction. A closed-loop SBO is more likely
ondary to severe colitis, CT demonstrates a thickened than other types of obstruction to result in vascular com-
wall with “thumbprinting” caused by wall edema and in- promise (strangulation obstruction). Strangulation ob-
flammation. Ogilvie’s syndrome is an acute pseudo- struction has a reported prevalence of 5-40% and is a
obstruction with dilation of the colon in the absence of a predominantly venous disease. The most frequent abnor-
colonic transition zone. It may occur in severely ill pa- mality seen on CT is bowel wall thickening. The thick-
tients after surgery and/or with neurological disorders, ened bowel wall sometimes is associated with a target
serious infections, cardiorespiratory insufficiency, and sign, consisting of alternating layers of high and low at-
metabolic disturbances. Drugs that disturb colonic motil- tenuation within the thickened bowel wall, which results
ity (e.g., anticholinergics or opioid analgesics) contribute from submucosal edema and hemorrhage. The bowel seg-
to the development of this condition. ment proximal to an obstruction can become ischemic
a b
Fig. 7 a, b. Cecal volvulus. Trans-

axial CT (a) and coronal vol-
ume-rendered (b) CT demon-
strate a markedly dilated cecum
(C) in the left side of the pelvis.
The arrow points to the area of
twist of the ascending colon.
Note the dilated small bowel
loops due to the proximal
colonic obstruction
due to severe distention. CT findings that suggest sub- peritoneum is often difficult. As CT is far more sensitive
sequent infarction are non-enhancement of the bowel than conventional radiography in demonstrating a small
wall, gas in the bowel wall, mesenteric or portal veins, pneumoperitoneum, it has become the imaging test of
edema/hemorrhage in the mesentery adjacent to thick- choice when the results of conventional radiography are
ened and/or dilated bowel loops, and ascites (Fig. 8). equivocal. Viewing the CT images at “lung window”
settings improves the demonstration of small amounts of
Perforation of the Gastrointestinal Tract extraluminal gas.
Retroperitoneal perforations (duodenal loop beyond
Gastrointestinal perforation usually causes localized pain the bulbar segment, or involving the appendix; posterior
initially, and culminates in diffuse pain if peritonitis de- aspect of the ascending and descending colon, or the rec-
velops. Gastroduodenal perforation associated with pep- tum below the peritoneal reflection) tend to be contained
tic ulcer disease or a necrotic neoplasm has become less locally and remain clinically silent for several hours or
frequent in recent decades due to earlier diagnosis and days. Retroperitoneal gas has a mottled appearance and
improved therapy. At the same time, the incidence of gas- may extend along the psoas muscles. In contrast to in-
troduodenal perforation resulting from endoscopic intraperitoneal gas, retroperitoneal gas does not move
strumentation has increased. Perforation of the small freely when the patient’s position is changed from supine
bowel is relatively uncommon but may be secondary to a to upright for plain abdominal radiographs.
foreign body, small bowel diverticulitis, or trauma. Spon-
taneous rupture of the colon is more frequent and can oc-
cur when the colon becomes markedly dilated proximal Acute Abdomen with Flank or Epigastric Pain
to an obstructing lesion (tumor, volvulus) or when the
bowel wall is friable (ischemic or ulcerative colitis, Acute flank or upper abdominal pain radiating to the
necrotic neoplasm). Fiberoptic colonoscopy with or with- back is commonly a manifestation of retroperitoneal
out biopsy is another cause of colonic perforation. pathology, especially urinary colic, acute pancreatitis, or
Pneumoperitoneum can be recognized by the presence leaking abdominal aortic aneurysm.
of subdiaphragmatic gas on an upright chest radiograph
or an upright or left lateral decubitus abdominal radio- Urinary Colic
graph. A large pneumoperitoneum generally is indicative
of colonic perforation, whereas moderate quantities of For decades, intravenous urography was the primary
free gas are seen with gastric perforation. Small bowel imaging technique used to evaluate patients with sus-
perforation usually results in either a limited amount of pected urinary colic. Plain abdominal radiography and
peritoneal gas or none, because the small bowel usually US may be useful for patients with a contraindication to
does not contain gas. Detection of subtle pneumo- radiation or iodinated intravenous CM. However, because
a c
Fig. 8 a-c. Strangulating small bowel ob-

struction due to an adhesive band that de-
veloped after cholecystectomy and appen-
dectomy. Axial (a, b) and sagittal (c) views
of multidetector CT show bowel wall thick-
ening, enhancing bowel wall with submu-
cosal edema, and/or hemorrhage giving a
target sign (long arrows), indicating is-
chemia. Non-enhancement of the bowel
wall of the jejunum (short arrow) corre-
sponds to segmental infarction. A Ascites
of the low sensitivity of abdominal radiographs and US When no stone is detected, an alternative diagnosis
in the detection of urinary tract calculi, the role of unen- must be established. Non-calculus urinary tract abnor-
hanced CT has become well established over the past 15 malities causing symptoms of colic include acute
years. On CT, virtually all ureteral stones are radiopaque, pyelonephritis, renal cell carcinoma, acute renal vein
regardless of their chemical composition. Uric acid thrombosis, spontaneous dissection of the renal artery,
stones have attenuation values of 300-500 Hounsfield and renal infarction. Extraurinary diseases, such as retro-
units (HU), and calcium-based stones >1000 HU. In ad- cecal appendicitis, diverticulitis, SBO, pancreatitis, gyne-
dition to the direct demonstration of a ureteral stone, sec- cological disorders, and retroperitoneal hemorrhage, may
ondary signs of ureterolithiasis, including hydroureter, also simulate acute urinary colic.
hydronephrosis, perinephric stranding, and renal enlarge-
ment, may be visible (Fig. 9). Perinephric stranding and Acute Pancreatitis
edema result from reabsorbed urine infiltrating the per-
inephric space along the bridging septa of Kunin. The An important disease causing upper abdominal pain is
more extensive the perinephric edema shown on unen- acute pancreatitis. US may be helpful for the demonstra-
hanced CT, the higher the degree of urinary tract ob- tion of choledocolithiasis as a cause of acute pancreatitis
struction. Focal periureteral stranding resulting from a lo- and for the follow-up of known fluid collections.
cal inflammatory reaction or irritation and induced by the Since the CT findings correlate well with the clinical
passage of a stone helps to localize subtle calculi. Occa- severity of acute pancreatitis, CT has become the imag-
sionally, a repeat CT examination using intravenous CM ing test of choice to stage the extent of disease (CT sever-
may be required, particularly if infectious complications ity index of Balthazar) and to detect complications. The
are suspected. For the diagnosis of such complications initial CT should be performed 48-72 h after disease on-
(pyelonephritis), CT is helpful as it reveals a “striated set (a CT examination performed too early in the course
nephrogram” after CM administration, as well as global of the disease may not demonstrate any abnormality).
enlargement of the kidney, renal and/or perirenal ab- Pancreatic enlargement due to interstitial parenchymal
scesses, or emphysematous pyelonephritis. edema may progress to pancreatic exudate collecting in
b c
Fig. 9 a-c. Right-sided urinary colic. Axial

(a), coronal (b), and oblique (c) views of
multidetector CT show dilatation of the
proximal urinary tract due to a ureteral
stone (arrow). Note slight secondary peri-
uretral and perinephric stranding
Fig. 10 a-c. Severe acute pancreatitis. Axial

(a, b) and coronal (c) views of MDCT
demonstrate an enlarged pancreatic area.
a Only small areas of enhanced pancreatic
parenchyma (p) remain within b extensive
pancreatic necrosis (n). Note the tiny
hyperattenuating calculi within the
gallbladder and the lower bile duct (arrows).
c The large amount of pancreatic necrosis
contrasts sharply with the minimal extra-
pancreatic changes at this phase
the abdominal ligaments and potential spaces surround-

ing the pancreas. The pancreatic parenchyma may under-
go necrosis or hemorrhage (Fig. 10). Severe pancreatitis
is often complicated by infection of the necrotic site
and/or thrombosis of the splenic and portal vein. Identi-
fying infectious complications in patients with pancreati-
tis may be difficult; the demonstration of gas bubbles
within peripancreatic collections is neither sensitive nor
specific. CT-guided fluid aspiration for bacteriological
examination is often the best technique to establish the
presence of infection.
Acute pancreatic and peripancreatic fluid collections
may evolve into pseudocysts, which exhibit defined
walls. A pseudocyst can erode peripancreatic vessels,
thus causing bleeding or the formation of a pseudo-
aneurysm (Fig. 11). Fig. 11. Recurrent pancreatitis. CT shows a pseudocyst of the pan-
creatic tail (PC) and a pseudoaneurysm of the gastroduodenal
Leaking Abdominal Aortic Aneurysm artery (PA). The splenic vein is indicated by the arrowhead
One of the most life-threatening diagnoses in patients

with acute flank pain is a leaking abdominal aortic or il- the diagnosis, such as a high-attenuating crescent sign. If
iac artery aneurysm. When a patient with suspected rup- endoluminal stent graft repair of the aorta is planned,
ture of an abdominal aortic aneurysm is hemodynamical- contrast-enhanced CT should be performed.
ly unstable, US is the initial imaging technique. The ex-
amination can be performed rapidly with portable equip-
ment in the emergency room. However, para-aortic hem- Conclusions
orrhage is poorly diagnosed by US. Instead, in hemo-
dynamically stable patients, non-contrast-enhanced CT is The imaging evaluation of patients with an acute abdomen
the initial imaging test of choice as it is almost always has changed dramatically in the past decade. Plain ab-
able to demonstrate a para-aortic hematoma, if present, dominal radiographs largely have been replaced with US
and may show additional findings helpful in establishing and CT. MDCT permits a rapid examination with high
diagnostic accuracy. Close cooperation with the referring Novelline RA, Rhea JT, Rao PM, Stuk JL (1999) Helical CT in
physician prior to imaging remains essential for rapid and emergency radiology. Radiology 213:321-339
accurate diagnosis, as the character and location of the pa- Paulson EK, Jaffe TA, Thomas J et al (2004) MDCT of patients with
acute abdominal pain: a new perspective using coronal refor-
tient’s abdominal pain strongly influences the differential mations from submillimeter isotropic voxels. AJR 183:899-906
diagnosis and the choice of initial imaging test. Singh AK, Gervais DA, Hahn PF et al (2005) Acute epiploic ap-
pendagitis and its mimics. Radiographics 25:1521-34
Smith RC, Varanelli M (2000) Diagnosis and management of acute
Suggested Reading ureterolithiasis. AJR 175:3-6
Stoker J, van Randen A, Lameris W, Boermeester MA
Ahn SH, Mayo-Smith WW, Murphy BL et al (2002) Acute non- (2009) Imaging Patients with acute abdominal pain. Radiolo-
traumatic abdominal pain in adult patients: abdominal radiog- gy 253:31-46
raphy compared with CT evaluation. Radiology 225:159-64 Taourel P, Kessler N, Lesnik A et al (2003) Helical CT of large
Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH (1990) Acute bowel obstruction. Abdom Imaging 28:267-275
pancreatitis: value of CT in establishing prognosis. Radiology Urban BA, Fishman EK (2000) Tailored helical CT evaluation of
174:331-336 acute abdomen. Radiographics 20:725-749
Freeman AH (2001) CT and bowel disease. Br J Radiol 74:4-14 Werner A, Diehl SJ, Farag-Soliman M, Düber C. (2003) Multi-slice
Gore RM, Miller FH, Pereles FS et al (2000) Helical CT in the spiral CT in routine diagnosis of suspected acute left-sided
evaluation of the acute abdomen. AJR 174:901-913 colonic diverticulitis: a prospective study of 120 patients. Eur
Mindelzun RE, Jeffrey RB (1997) Unenhanced helical CT for eval- Radiol 13:2596-2603
uating acute abdominal pain: a little more cost, a lot more in- Wiesner W, Khurana B, Ji H, Ros PR (2003) CT of acute bowel is-
formation. Radiology 205:43-47 chemia. Radiology 226:635-650
IDKD 2010-2013
Trauma of the Abdomen and Pelvis

Philip J. Kenney1, Stuart E. Mirvis2
1 University of Arkansas for Medical Sciences, Little Rock, AR, USA
2 University of Maryland School of Medicine, Baltimore, MD, USA
Introduction with abnormal US findings often require further evalua-

tion with CT. In a large study, US had 86% sensitivity and
Trauma is a major health problem in all age groups but it 98% specificity but with 43 false-negative and 23 inde-
is especially true in the young, due to high-velocity trans- terminate studies, including six splenic, one liver, one
portation, altercations, including with weapons and re- renal, one pancreatic, and one bowel injury [2].
sulting in penetrating injuries, as well as falls and sports- In traumatized pregnant women, US should be the first
related injuries. In addition, both the elderly and pregnant examination as it can evaluate the pregnancy, document-
women are vulnerable to trauma. Improvements in the ing fetal death or viability. US is nearly as accurate in de-
management of trauma include more rapid rescue, better tecting the abnormal presence of fluid in pregnant patient
organization of trauma centers, and advances in treat- as in non-pregnant patients [4]. If US shows fluid or oth-
ment. Current trends include increased non-operative er injury, CT is justified for further evaluation (Fig. 1).
management of trauma-related injuries, accurate imaging- The best outcome for the fetus is assured by best care of
based diagnosis, and greater emphasis on the efficient but the mother. The radiation risk is reasonable if there is life-
cost-effective use of imaging. One aspect of the trend to threatening injury, such that prompt diagnosis and treat-
non-operative care is the desire to avoid non-therapeutic ment are paramount [5].
surgery; this is possible if imaging can identify those
patients who require surgery. Another is the realization
that non-operative care can result in better long-term Urinary Tract
outcome, such as splenic salvage.
The nearly universal use of CT has altered the assessment
of urinary tract trauma. While significant hematuria has
Computed Tomography vs. Ultrasound been shown to be the best indicator of urinary tract injury,
presently the decision to perform CT has little to do with
Controversy exists about the appropriate use of comput- the presence or absence of hematuria. CT is a primary in-
ed tomography (CT) vs. ultrasound (US), although each vestigation, after standard radiographs, in those with sig-
modality has its advantages and disadvantages [1, 2]. In nificant mechanisms of injury or any signs or symptoms
general, CT has the best statistical accuracy for detect- of significant injury. Intravenous urography has been re-
ing, characterizing, and excluding injuries. In modern placed by CT (Fig. 2).
high-volume trauma centers, the CT apparatus must be The ability of US to evaluate renal injury is limited [6]
located in the trauma suite such that even unstable pa- whereas CT has excellent negative predictive value for re-
tients can be examined quickly without compromise. nal injury. CT also accurately indicates the presence and
This allows for the efficient use of CT in rapid and ac- type of renal injury [7]. Renal contusion appears as an ill-
curate diagnostics and obviates the need for outmoded defined region of diminished enhancement. Segmental re-
studies, such as diagnostic peritoneal lavage. CT is also nal infarction is identified as a wedge-shaped, well-defined
more reliable at excluding injury, allowing the patient to area of non-enhancement. Renal artery occlusion can be
be discharged home and avoiding the expense of obser- accurately diagnosed by its complete lack of either contrast
vation in hospital. enhancement or excretion by the kidney, usually with little
However CT may be overused; indeed, in one study to no associated hematoma. Angiography is thus not need-
only three of 100 patients had alterations of clinical man- ed, and conservative therapy is most often used today. Most
agement due to follow-up CT [3]. US can detect signifi- renal injuries are lacerations, with simple lacerations lim-
cant injury which can then be appropriately treated; con- ited to the cortex and deep lacerations extending into the
versely, low-risk patients with normal sonograms may be collecting system, which may show extravasation. Delay
observed and possibly avoid CT [2]. However, patients scans of 2-10 min aid in demonstrating or excluding
Trauma of the Abdomen and Pelvis 15
a b
Fig. 1 a-c. A pregnant woman suffered a high-speed motor vehicle

collision. a US demonstrates intrauterine fetus (heart motion doc-
umented) and free pelvic fluid. b US shows perisplenic fluid with
hypoechoic defect. c CT confirms splenic laceration; note the high-
er density of the perisplenic hematoma compared to the rim of flu-
id about liver (sentinel clot sign) c
a b
Fig. 2 a, b. Hematuria
and left upper quadrant
pain after a football-
related injury. a Intra-
venous urogram shows
no abnormality. b Sub-
sequent CT for persis-
tent pain showed free
fluid in the pelvis and
extensive splenic lacera-
tion with extensive
“blush”. Surgery con-
firmed a grade 4
splenic injury
extravasation (Fig. 3), although in most cases small follow-up scans [7]. Renal fracture indicates a single com-
amounts of extravasation will resolve with conservative plete fracture plane, often extending through the collecting
therapy. Subcapsular hematoma is delimited by the renal system; multiple planes of disruption are seen in a shat-
cortex and may deform the renal surface; perinephric tered kidney. CT can also diagnose avulsion of the uretero-
hematoma extends from the renal surface to fill Gerota’s pelvic junction (UPJ) or ureteral injury, demonstrating lack
space but does not deform the renal contour, although it of opacification of the ureter, retroperitoneal water attenu-
may displace the kidney. CT is excellent at demonstrating ation collections adjacent to the pelvis or ureter, and pos-
the extent of hematoma and in evaluating enlargement on sibly extravasation of contrast on delay scans (Fig. 4) [7].
16 Philip J. Kenney, Stuart E. Mirvis
a a
b
b
Fig. 4 a, b. Routine trauma CT image shows fluid and stranding

about the right ureter. a Note that contrast filling of the ureter has
not yet occurred. Delay image shows extravasation medial to the
Fig. 3 a, b. Hematuria after fall from a power line. a Initial CT shows kidney typical, of UPJ avulsion. b Note the intact parenchyma
left renal laceration with perinephric hematoma. b Delay image
shows no leak from the collecting system
due to compressive force and resultant pubic bone frac-
tures, although both anterior and posterior urethral injury
Ureteral injuries, including UPJ avulsion, are uncom- can result from penetrating injury. Retrograde urethro-
mon. They can occur either with penetrating trauma or graphy is the only accurate diagnostic imaging procedure.
high-velocity blunt trauma and have no specific signs or If a urethral injury is strongly suspected, a urethrogram
symptoms, but can be detected with CT. Routine CT should be performed before passage of a catheter (Fig. 5).
scans show subtle suggestive signs, such as perinephric However, in patients with moderate risk, a urethral
and peripelvic stranding or fluid, that indicate the need catheter may be gently passed so that the patient may go
for delay scans, if not routinely done, to demonstrate ex- on to CT. A pericatheter urethrogram may then be per-
travasation. In a study based on over 4,000 trauma pa- formed after any other injuries have been stabilized. Five
tients, CT enabled the correct identification of seven of types of urethral injuries are recognized. In type 1, the
eight UPJ avulsions [8]. posterior urethra is stretched but intact; in type 2, there is
The AAST Organ Injury severity scale for the kidney a tear of the membranous urethra above the urogenital di-
includes lesions with different appearances in each cate- aphragm; in type 3, the posterior urethral tear is above
gory (1: contusion, small subcapsular hematoma; 2: <1 cm and below the urogenital diaphragm; type 4 is defined as
laceration without extravasation; 3: >1 cm laceration a bladder-neck injury and type 5 as an anterior urethral
without extravasation; 4: deep laceration with extravasa- injury [10].
tion or main renal artery or vein injury; 5 shattered kid- Bladder injuries consist of contusions and ruptures;
ney or UPJ avulsion) and has been shown to correlate classically, they have been detected with standard radi-
with need for surgery and outcome [9]. ographic cystography (Fig. 6). They may be extraperi-
Urethral injuries are predominantly seen in males. An- toneal, most commonly, intraperitoneal, less commonly,
terior urethral ruptures most commonly occur due to or combined in about 5%. While CT with only intra-
straddle injury. Posterior urethral ruptures most often are venous contrast may fail to identify extravasation from
Fig. 5. Blunt trauma resulted in pubic rami fractures. Retrograde

urethrogram reveals type 3 posterior urethral rupture
Fig. 7 a, b. Gross hematuria following motor-vehicle collision re-

sulting in extensive pelvic fractures. a Standard CT shows pelvic
fluid but no extravasation. b CT cystogram documents extraperi-
toneal bladder rupture (note the clot in the bladder)
bladder catheter clamped is performed. If there is no

extravasation, the bladder is drained and then re-filled
with 300-500 mL of dilute contrast and the pelvis
rescanned. Bladder ruptures are virtually always associ-
ated with fluid or hematoma in the pelvis, but such
blood or fluid may be due to splenic or other injuries or
to pelvic fracture. Extravasation confined to the lower
pelvis and not outlining bowel loops (and which may
extend up the retroperitoneum) indicates extraperi-
toneal rupture, which most often is managed conserva-
tively. Extravasation high near the dome and outlining
bowel loops or extending to the gutters or higher indi-
cates intraperitoneal rupture, which is more often man-
aged surgically [11]. In a study of 495 patients with po-
Fig. 6. Gross hematuria after gunshot wound to the pelvis. Standard tential pelvic injuries, CT-cystography detected 98% of
cystogram shows extraperitoneal rupture (X marks entry site, O exit) the bladder injuries while standard cystography detect-
ed 95%. Of the patients with bladder injury (65%
extraperitoneal, 35% intraperitoneal, 5 combined), 89%
had gross hematuria and pelvic fracture, 9% had gross
a ruptured bladder, several studies have shown very hematuria with no pelvic fracture, and one patient had
high accuracy for CT-cystography (Fig. 7), which is microscopic hematuria and pelvic fracture [12]. CT-
now the standard in our institutions. In patients with cystography carried out with multidetector CT allows
suspected bladder rupture (primarily those with gross for reformatting, which can more clearly demonstrate
hematuria, over 25 RBC/hpf, with pelvic fractures or the point of leakage and allows more accurate charac-
unexplained pelvic fluid), a standard CT with the terization of the type of injury [13].
Bowel and Mesenteric Injuries is noted, the likelihood of injury is low; a combination of
findings, particularly free fluid without obvious source in
Bowel and mesenteric injuries are found in about 5% of combination with focal bowel wall thickening and/or
patients undergoing surgery for trauma and are seen in mesenteric stranding, is very suggestive of bowel injury
0.7% of all traumatized patients [1, 14]. The mechanism and such patients should be explored or followed very
of injury is direct compressive force, including from seat- carefully [14-16]. In our practice, we have found that per-
belts, although deceleration may play a role. Morbidity forming a repeat abdominal-pelvic CT 4-6 h after the ad-
and mortality can occur, with peritonitis and abscess remission scan can be helpful in patients with suspicious
sulting if the injury is missed. Clinical signs and symp- but non-diagnostic findings for full-thickness bowel in-
toms are non-specific. Although diagnosis by CT is not jury, by demonstrating injury progression such as the de-
as straightforward as is the case for other abdominal or- velopment of free air, increasing intraperitoneal fluid, or
gan injuries, CT is the most accurate diagnostic modali- stability of findings. Of course, management decisions
ty, with >90% sensitivity and specificity reported [14, are made in conjunction with any evolution of the clini-
15]. The use of orally administered contrast is now some- cal findings.
what controversial; while extravasation of oral contrast
can be a very specific sign of bowel injury, it is rarely
seen. Contrast administration delays performance of the Splenic Injuries
scan, and most bowel injuries will be evident based on
other signs. There is no one CT sign that is both sensitive The spleen is the most frequently injured abdominal
and specific for bowel or mesenteric injury. Focal bowel organ in blunt trauma. There may be signs of blood loss
wall thickening, mesenteric stranding, interloop fluid, and or left upper quadrant pain, but the diagnosis largely
hematoma are common but less specific, particularly for rests on imaging or surgical exploration. A trend to non-
surgically important injuries (Fig. 8). Active bleeding, operative management is supported by evidence that
vessel beading, abrupt termination of mesenteric vessels, long-term health is better in those who have had splenic
and bowel wall defect are more specific but less sensitive function preserved. This necessitates accurate non-
signs [16]. Active bleeding is seen as a focal extralumi- invasive diagnosis and is aided by signs predictive of the
nal collection with attenuation similar to that of the aor- success or failure of conservative management.
ta at the same level and different from the adjacent or- Splenic injuries can cause free fluid, perisplenic or
gans. Free air is considered a good sign of perforated elsewhere, which can readily be detected by sonography.
bowel, but in fact it has limited value. It is infrequently Splenic injury may alter echo-texture: lacerations may be
seen in those with bowel injury and may represent air anechoic if there is rapid bleeding, but more commonly
tracking into the peritoneum from thoracic injuries. In a are more echogenic than normal spleen [2]. With such
study reported in 2008, free air had a sensitivity of 24% findings on sonography, the decision whether to further
albeit a specificity of 95%. There were three false-posi- evaluate with CT or to proceed to surgery can be made
tives with intraperitoneal air instead resulting from supra- on clinical grounds. Splenic injuries may be missed by
diaphragmatic or bladder injuries [16]. If a single finding sonography, particularly if they are not associated with
free fluid. In one large study, there were 43 false-negative
sonograms, including six splenic ruptures that required
surgery [2].
CT is quite sensitive in the detection of splenic injuries
[17]. Subcapsular hematoma is seen as a crescentic, low-
attenuation, peripheral rim; intraparenchymal hematoma
as a rounded area within the spleen with low attenuation
and no enhancement. Lacerations are common, appearing
as linear or branching low-attenuation lesions that often
extend to the surface; if so, they are often associated with
perisplenic or free fluid. Hemoperitoneum tends to be of
higher attenuation close to the source of bleeding; thus,
when the spleen is the source, the collection adjacent to
the spleen may be higher in attenuation than elsewhere, a
finding referred to as the sentinel clot sign. Lacerations
may involve the vasculature. There can be devasculariza-
tion of the spleen by hilar injury, or active extravasation
into the peritoneal cavity, or a confined area of extrava-
sation (pseudoaneurysm) (Fig. 9). Both types of extrava-
sation indicate that non-operative management may not
Fig. 8. Motor-vehicle collision. Focal hematoma and thickening of succeed, although angiographic embolization may control
cecum; at surgery, cecal laceration found the bleeding and allow splenic salvage [18].
a b
Fig. 9 a, b. Blunt trauma. a Routine trauma CT

image shows area of hyperdensity (arrow-
head). b Delay image shows that the hyper-
intensity is no longer visible; the lesion has
become isodense with blood pooling, indi-
cating confined pseudoaneurysm rather than
free active bleeding
A number of schemes have been devised to grade of the liver and the difficulty in clearly imaging all por-
splenic injury on CT in an attempt to predict outcome, tions of the organ ultrasonographically.
with variable correlation with the need for surgery [1]. Injuries to the liver include contusion, seen on CT as
One of the commonest is the AAST scoring system. In a an ill-defined area of low attenuation; subcapsular
large study, failure of non-operative management corre- hematoma, a crescentic collection limited by the capsule;
lated with splenic injury grade: the failure rate was <10% and intraparenchymal hematoma, a collection of blood
with grades 1 or 2, while one-third of the grade 4 injuries within a liver laceration. Laceration is commonest, seen
and three-fourths of the grade 5 injuries required surgery as linear or branching low-attenuation regions, some-
[19]. Nevertheless, in occasional cases of low-grade times with jagged margins, that can extend to the hepat-
injury, the patient suffered delayed rupture, while some ic surface or to vessels. Superficial lacerations are <3 cm
high-grade injuries have been successfully managed con- in size. Periportal low attenuation is usually edema, a dis-
servatively. Attempts have been made to develop CT- tended inferior vena cava and renal veins, and subserosal
based criteria that may be more predictive: one referred edema of the gallbladder wall, but on occasion may rep-
to three key features: devascularization, laceration of resent blood tracking along the portal veins (Fig. 10). It
>50% of the parenchyma; contrast blush >1 cm; or large is rare that periportal low attenuation is the only sign of
hemoperitoneum; however, further study showed that this liver injury, and patients with only this finding should be
approach also had limited predictive value with poor sen- managed conservatively [24].
sitivity although fair specificity [20]. The additional find- Liver injuries may require surgery but most can
ing of traumatic pseudoaneurysm or active extravasation be managed non-operatively. The liver, with its dual
(which does not confer a specific stage in the AAST scor- blood supply, is relatively resistant to infarction and
ing system) increased the likelihood of failure of non- has considerable functional reserve. Grading systems
operative management, regardless of grade [21]. Delayed
images can help distinguish between active bleeding,
which persists as a hyperdense area, and confined vascu-
lar injury (pseudoaneurysm), which washes out [22].
Patients with active bleeding are more likely to require
surgery or other forms of intervention.
Hepatic Injuries
The liver is the second most frequently injured abdomi-
nal organ, accounting for about 20% of abdominal in-
juries [1, 17]. The right lobe is more often affected than
the left, with the posterior right lobe the most commonly
injured segment. Hepatic injuries may be associated with
intraperitoneal hemorrhage, but injury may be confined
to the liver, or hemorrhage may be limited by an intact
capsule. Lacerations involving the bare area may be as-
sociated with retroperitoneal hematoma. US may show
liver lacerations, which appear similar to splenic injuries Fig. 10. Blunt trauma, shock, and aggressive resuscitation followed by
but this modality has limited sensitivity (67%, compared trauma CT. Note the periportal low attenuation tracking throughout
to 93% for CT) [23]. This is in part due to the large size the liver with intact parenchyma and no perihepatic hematoma
(e.g., AAST) have less direct correlation with the need Adrenal Injuries
for intervention than is the case for the spleen. Although
not included in the AAST scheme, active extravasation Adrenal injuries are uncommon, seen in about 2% of pa-
may predict the need for surgery or angioembolization. tients with blunt abdominal trauma, and are rarely isolat-
Sub-classification of extravasation can be useful: extra- ed, but their presence indicates a high-energy mechanism.
vasation into the peritoneal cavity is highly correlated In a review of 73 cases, 71% were right adrenal only, 15%
with the need for intervention; intraparenchymal extra- left, and 8% bilateral [27]. The right adrenal is more
vasation with significant hemoperitoneum may also prone to injury due to its location between the liver and
require intervention; extravasation limited within a spine, resulting in crush injury; also, the short right
hepatic hematoma without hemoperitoneum usually can adrenal vein can transmit increased pressure. Acute
be managed conservatively. Actually, the success rate of adrenal hematomas are usually 2-4 cm in diameter, round
non-operative management is >80%, and clinical signs or oval lesions with relatively high attenuation (40-60
of hemodynamic instability dictate the need for inter- HU, mean 55), often with stranding. Active bleeding may
vention more than imaging features. However in one be seen and correlates with poor outcome. If there is any
recent study of 214 patients with hepatic injury, all 14 concern that a lesion represents an adrenal adenoma or
who showed intraperitoneal contrast extravasation on CT pre-existing mass, such as adenoma, repeat exam with
required surgery [25]. Massive hemoperitoneum in six pre- and post-contrast technique can be done, or the pa-
compartments also correlated independently with the tient simply followed-up at 6-8 weeks as hematomas will
need for surgical intervention. decrease in size and attenuation.
Gallbladder injuries occur in <2% of major blunt ab-
dominal traumas and are usually seen with concurrent
liver injury. Injuries to the gallbladder include wall con- Pancreatic and Duodenal Injuries
tusion, intraluminal hemorrhage, laceration, and partial
or complete avulsion. CT findings may consist of focal or Pancreatic and duodenal injuries are also uncommon, to-
diffuse wall thickening, pericholecystic fluid (blood gether accounting for about 2% of all abdominal injuries
and/or bile), ectopic position, intraluminal clot or mucos- [28]. The mechanism of injury is anteroposterior com-
al flaps, and focal mass effect on the adjacent duodenum
pression, with compression against the spine leading to
(Fig. 11). Full wall thickness tears result in a collapsed
the actual injury; thus, pancreatic injuries usually are at
lumen [26].
the mid-body. Like adrenal injuries, they are also often
associated with other injuries, including hepatic, vascu-
lar, splenic, renal, and gastric. Morbidity and mortality
are relatively high in part due to the multisystem trauma
seen in these patients. Significant complications are com-
mon and include pancreatitis, pseudocysts, abscess, fis-
tulas, and pneumonia. A delay in diagnosis is not unusu-
al as the initial findings can be subtle but it contributes
to high morbidity and mortality. Clinical signs include
upper abdominal pain, with laboratory signs of leukocy-
tosis and elevated amylase, but amylase also may be nor-
mal for 2-48 h in up to 40% of patients with pancreatic
injuries [28].
Duodenal contusion may be present when there is
hematoma or edema limited to the duodenal wall, per-
haps with intramural gas and focal mural thickening.
Duodenal perforation should be diagnosed when there is
an extraluminal retroperitoneal collection of contrast,
gas, or fluid, or loss of continuity of the wall. Stranding
of the retroperitoneal fat can be seen with either condi-
tion. While use of oral contrast may aid in the diagnosis,
it is not absolutely necessary; if needed, additional im-
ages can be obtained with oral contrast if it was not used
initially.
It has been reported that the pancreas appears normal
on CT for the first 12 h after injury in some 40% of pa-
Fig. 11. Gallbladder rupture. Coronal reformation in blunt trauma
patient shows ectopic location and tear in gallbladder. Note en-
tients, but this conclusion was based on older CT tech-
hancement of the gallbladder mucosa. Hematoma fills the gall- nology and most trauma scans do not include a pancre-
bladder fossa atic parenchymal phase. However, a recent multicenter
8. Ortega SJ, Netto FS, Hamilton P et al (2008) CT scanning for

diagnosing blunt ureteral and uretropelvic junction injuries.
BMC Urology 8:3-7
9. Santucci RA, McAninch JW, Safir M et al (2001) Validation
of the American Association for the Surgery of Trauma organ
injury severity scale for the kidney. J Trauma 50:195-200
10. Goldman SM, Sandler CM, Corriere JN et al (1997) Blunt ure-
thral trauma: a unified anatomical mechanical classification. J
Urol 157:85-89
11. Morgan DM, Nallamalla LK, Kenney PJ et al (2000) CT cys-
tography: radiographic and clinical predictors of bladder rup-
ture. AJR 174:89-95
12. Quagliano PV, DeLair SM, Malhotra AK (2006) Diagnosis of
blunt bladder injury: a prospective comparative study of CT
Cystography and conventional retrograde cystography. J Trau-
ma 61:410-422
13. Chan DPN, Abujudeh HH, Cushing GL et al (2006) CT Cys-
tography with multiplanar reformation for suspected bladder
rupture. AJR 187:1296-1302
Fig. 12. High-speed deceleration injury with blunt-force trauma. 14. Malhotra AK, Fabian TC, Katsis SB et al (2000) Blunt bowel
Note the discrete linear low attenuation defect crossing the entire and mesenteric injuries: the role of screening CT. J Trauma
diameter of the body of the pancreas, consistent with a pancreatic 48:991-998
transection. Given the extent of the defect, involvement of the pan- 15. Butela ST, Federle MP, Chang PJ et al (2001) Performance of
creatic duct is likely CT in Detection of bowel injury. AJR 176:129-135
16. Atri M, Hanson JM, Grinblat L et al (2008) Surgically impor-
tant bowel and or mesenteric injury in blunt trauma: accuracy
of multidetector CT for evaluation. Radiology 249:524-533
17. West OC (2000) Intraperitoneal abdominal injuries. ARRS
study using 16- or 64-slice scanners showed a sensitiv- Categorical course syllabus. ARRS, Reston, VA, p 87
ity of 60 and 47% and a specificity of 95 and 90%, re- 18. Davis KA, Fabian TC, Croce MA et al (1998) Improved suc-
spectively, in 206 subjects [29]. Fracture or laceration of cess in nonoperative management of blunt splenic injuries:
the pancreatic parenchyma, active hemorrhage in the embolisation of splenic artery pseudoaneurysms. J Trauma
44:1008-1013
pancreas, and hematoma between the splenic vein and 19. Peitsman AB, Heil B, Rivera L et al (2000) Blunt splenic in-
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hypoattenuating linear lesions; if crossing more than ation for the Surgery of Trauma. J Trauma 49:177-187
half the diameter, pancreatic duct injury should be sus- 20. Cohn SM, Arango JL, Myers JG et al (2009) Computed to-
pected (which correlates with increased complications) mography grading systems poorly predict the need for inter-
vention after spleen and liver injuries. American Surgeon
(Fig. 12). Hematoma and contusion are diffuse or local- 75:133-139
ized, ill-defined, mixed-attenuation regions within the 21. Gavant ML, Schurr M, Flick PA et al (1997) Predicting clini-
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jury: using CT to reveal abnormalities of splenic vasculature.
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IDKD 2010-2013
Diseases of the Esophagus and Stomach

Marc S. Levine1, Ahmed Ba-Ssalamah2
1 Department of Radiology, Penn Radiology at the Hospital of the University of Pennsylvania, Philadelphia, PA, USA
2 Department of Radiology, Medical University of Vienna, General Hospital of Vienna, Wien, Austria
Introduction
The esophagus and stomach are susceptible to a wide
spectrum of diseases, including benign and malignant tu-
mors, inflammatory diseases, and other conditions. For
the diagnosis of this large variety of disorders, multi-
modality imaging is required. Barium studies, particular-
ly double-contrast studies, continue to have a major role
in the diagnostic work-up of inflammatory diseases and
in post-operative follow-up, whereas cross-sectional
imaging studies, particularly multidetector computed
tomography CT (MDCT), is used in the pre-operative Fig. 1. Candida esophagitis.
staging of oncological disorders. In this chapter, we Upright, left posterior-oblique
review the most frequent diseases and describe the use of spot image from double-
different imaging modalities for their diagnostic work-up. contrast esophagogram shows
multiple, discrete, plaque-like
lesions in the mid-esophagus.
Note the linear configuration
Gastroesophageal Reflux Disease of the lesions and their sepa-
ration by segments of normal,
intervening mucosa. These
Mild reflux esophagitis may be manifested on double- findings are characteristic of
contrast studies by small, shallow ulcers or granularity of fungal esophagitis
the mucosa in the distal esophagus [1]. In advanced
disease, the esophagus can have an irregular contour,
with serrated margins and decreased distensibility from
ulceration, edema, and spasm. Subsequent scarring can epidemic has led to a more fulminant form of candidiasis,
lead to the development of smooth, tapered, or ring-like characterized by a “shaggy” esophagus that has a grossly
peptic strictures in the distal esophagus, almost always irregular contour due to multiple plaques and pseudo-
above a hiatal hernia [2]. membranes [5]. In contrast, herpes esophagitis is manifest-
Barrett’s esophagus is a well-recognized complication ed by small, shallow ulcers (Fig. 2) [6] whereas esophagi-
of reflux esophagitis, and it is associated with an in- tis due to cytomegalovirus (CMV) or human immunodefi-
creased risk of esophageal adenocarcinoma. The classic ciency virus (HIV) can be associated with the development
radiological features of Barrett’s esophagus include a dis- of giant, flat ulcers [7]. Since CMV ulcers are treated with
tinctive reticular pattern of the mucosa or a high antiviral agents, and HIV ulcers with steroids, endoscopy is
esophageal stricture or ulcer occurring at a discrete dis- required to differentiate CMV- from HIV-mediated
tance from the gastroesophageal junction [3]. esophagitis before treatment in these patients is instituted.
Infectious Esophagitis Drug-Induced Esophagitis

By far the most common cause of opportunistic esophageal Drug-induced esophagitis is caused by various oral med-
infection is Candida albicans. Candida esophagitis is man- ications, including tetracycline, doxycycline, potassium
ifested on double-contrast studies by discrete, plaque-like chloride, quinidine, alendronate sodium, aspirin, and oth-
lesions separated by normal mucosa (Fig. 1) [4]. The AIDS er non-steroidal anti-inflammatory drugs (NSAIDs).
Diseases of the Esophagus and Stomach 23
Fig. 2. Herpes esophagitis. Up-

right, left posterior-oblique
spot image from double-
contrast esophagogram shows
multiple small ulcers sur-
rounded by radiolucent
mounds of edema in the mid- Fig. 3. Adenocarcinoma of the esophagus. Prone, right anterior-
esophagus. These findings are oblique spot image from single-contrast esophagogram shows a
characteristic of viral (espe- polypoid mass (arrows) in the distal esophagus in this patient with
cially herpes) esophagitis adenocarcinoma arising in Barrett’s esophagus
These patients often have a history of ingesting the pills superficially spreading carcinomas may be manifested by
with little or no water immediately before retiring. As a poorly defined nodules, producing confluent nodularity
result, the pills tend to lodge in the mid-esophagus where of the mucosa [10]. In contrast, the lesions of advanced
it is compressed by the aortic arch or left main bronchus. esophageal carcinomas are polypoid (Fig. 3), ulcerated,
This can result in contact esophagitis, manifested by or infiltrating, with irregular luminal narrowing and
small, discrete ulcers in the mid-esophagus [8]. Affected shelf-like borders. Rarely, these tumors have a varicoid
individuals may present with odynophagia, but there is appearance due to submucosal spread of tumor; in such
rapid clinical improvement after withdrawal of the of- cases, they can be mistaken for esophageal varices.
fending agent.
Erosive Gastritis
Idiopathic Eosinophilic Esophagitis
Erosive gastritis is usually manifested on double-con-
Idiopathic eosinophilic esophagitis (IEE) usually occurs trast studies by varioliform erosions with punctate or
in adolescent or young men with a long history of com- slit-like collections of barium surrounded by radiolu-
pensated dysphagia and occasional food impactions. cent mounds of edema. Varioliform erosions tend to be
These patients often have an atopic history, asthma, or located in the gastric antrum and are often aligned on
peripheral eosinophilia. Barium studies may reveal a the crests of the folds. Aspirin and other NSAIDs are by
“ringed esophagus”, with multiple distinctive ring-like far the most common cause of erosive gastritis. Occa-
indentations, or a “small-caliber esophagus”, with diffuse sionally, NSAID-induced erosive gastritis may also
loss of distensibility of the esophagus in the absence of a manifest as distinctive linear or serpiginous erosions
discrete stricture [9]. The diagnosis can be confirmed by clustered together on or near the greater curvature of the
endoscopic biopsies showing >20 eosinophils per high- gastric body [11]. It has been postulated that these ero-
powered field. These patients usually have a dramatic sions result from localized mucosal injury, as the dis-
positive response to oral steroids or inhaled steroid prepa- solving NSAID tablets collect by gravity in the most de-
rations. pendent portion of the stomach.
Esophageal Carcinoma Helicobacter Pylori Gastritis

Early esophageal cancers classically appear on double- Gastritis caused by the bacterium Helicobacter pylori can
contrast studies as small, protruded tumors [10]. They be diagnosed on barium studies by the presence of thick-
may be plaque-like or small polypoid lesions. Other, ened folds in the antrum, body, or, less commonly, the
24 Marc S. Levine, Ahmed Ba-Ssalamah
change in its shape. Usually, ulcer healing produces a

visible scar manifested by a central pit or depression, ra-
diating folds, and/or retraction of the adjacent gastric
wall [13].
Gastric Carcinoma
Advanced gastric carcinomas may appear on barium
studies as polypoid, ulcerated, or infiltrating lesions. Oth-
er primary scirrhous carcinomas can have a “linitis plas-
tica” appearance, with luminal narrowing, irregularly
thickened folds, and nodularity of the mucosa [15]. Scir-
rhous carcinomas classically involve the gastric antrum,
but 40% of these lesions are confined to the gastric body
or fundus (Fig. 5) [15]. Early gastric cancers may be man-
ifested by small polypoid or ulcerated lesions. However,
Fig. 4. Helicobacter pylori gastritis. Left posterior-oblique spot im- in the western world, the vast majority of patients with
age from double-contrast upper gastrointestinal examination gastric carcinoma already have advanced lesions at pre-
shows thickened, irregular folds in the gastric body due to chronic sentation. As a result, early gastric cancer is unlikely to
H. pylori gastritis be detected as long as barium studies are performed pre-
dominantly on symptomatic patients [16].
fundus of the stomach (Fig. 4) [12]. Other patients with Gastric Lymphoma
H. pylori infection may have a polypoid form of gastritis,
with grossly thickened, lobulated folds such that the Chronic H. pylori gastritis can lead to the development of
lesions resemble those of Menetrier’s disease, lymphoma, mucosa-associated lymphoid tissue (MALT) in the stom-
or a submucosally infiltrating carcinoma [12]; thus, en- ach. This lymphoid tissue is the precursor of low-grade,
doscopy and biopsy are required for a definitive diagnosis. B-cell gastric MALT lymphomas, which, if untreated,
may undergo blastic transformation to more high-grade
lymphomas. Gastric MALT lymphomas may sometimes
Gastric Ulcers be recognized on double-contrast studies by variably
sized, rounded, confluent nodules in the stomach [17]. In
Benign gastric ulcers classically appear en face as contrast, advanced gastric lymphomas may be manifest-
round or ovoid collections of barium, often surrounded ed by thickened folds, multiple submucosal masses, ul-
by a smooth mound of edema or thin, straight folds ra- cerated bull’s-eye lesions, or giant, cavitated lesions.
diating to the edge of the ulcer crater [13]. When
viewed in profile, benign ulcers project beyond the
contour of the adjacent gastric wall and are often asso-
ciated with an ulcer mound or collar. In contrast, ma-
lignant gastric ulcers appear en face as irregular ulcer
craters within a discrete mass, sometimes associated
with nodularity or clubbing of adjoining folds due to
tumor infiltration of the folds [13]. When viewed in
profile, malignant ulcers project inside the lumen with-
in a mass that forms acute angles with the gastric wall
rather than the obtuse, gently sloping angles expected
for a benign mound of edema.
Most benign ulcers are located on the lesser curvature
or posterior wall of the gastric antrum or body [13]. Oc-
casionally, benign gastric ulcers may occur on the
greater curvature of the distal stomach, in which case the
vast majority are caused by aspirin or other NSAIDs Fig. 5. Scirrhous adenocarcinoma of the stomach. Front spot image
[13]. As these NSAID-induced greater-curvature ulcers from double-contrast upper gastrointestinal examination shows ir-
regular narrowing of the gastric body and fundus due to infiltration
enlarge, they can penetrate inferiorly into the transverse of the wall by tumor. Note transition (arrows) to uninvolved gas-
colon, producing a gastrocolic fistula [14]. Ulcer healing tric antrum distally. About 40% of scirrhous carcinomas are con-
may be seen as a decrease in the size of the ulcer or a fined to the body or fundus of the stomach with antral sparing
Gastrointestinal Stromal Tumors [22, 23]. Furthermore, MDCT with water filling (hydro-
MDCT, HMDCT) provides information about esophageal
Gastrointestinal stromal tumors (GISTs) are the most com- and gastric wall infiltration, extramural extent of disease,
mon mesenchymal tumors of the gastrointestinal tract. lymph node involvement, and distant metastases (Fig. 7)
Approximately 70% of all GISTs are found in the stomach [23, 24]. Inadequately distended hollow viscera on CT
and only 2-5% originate from the esophagus. GISTs have a may hide large lesions and may even mimic pseudole-
wide clinical spectrum, ranging from benign, incidentally sions. Thus, optimal distention of the esophagus and
detected nodules to large malignant tumors, and must be stomach is a necessary prerequisite for achieving good di-
distinguished from other mesenchymal tumors [18]. The agnostic imaging. When water is used as the oral contrast
most frequent symptom related to gastric or esophageal tu- agent, subtle pathology is easier to visualize. Gas or CO2
mor is dysphagia or heartburn; thus, most patients undergo resulting from the administration of effervescent granules
endoscopy of the esophagus, stomach and duodenum, with can be used for hollow-organ distention alone or in com-
simultaneous biopsy if tumor is seen [19]. If the histopatho- bination with water. The use of negative rather than posi-
logical results reveal a tumor, accurate staging is required. tive contrast media is preferred, especially if CT angio-
Endoscopic ultrasound (EUS) can depict the normal graphy images are needed. Subtle pathology is easier to
gastric and esophageal wall with its five-layered internal visualize, especially when an adequate intravenous con-
structures, thus allowing detailed evaluation of the depth trast material bolus is administered [23, 24]. Three-
of tumor penetration even in early-stage disease. EUS is dimensional reconstructions of CT data sets with multi-
useful in the diagnostic work-up of early cancer, as it can planar reconstruction, curved planar reformations, or
distinguish between T1a tumors, in which only mucosec- other protocols are mandatory to exploit the full potential
tomy is needed, and T1b tumors, in which a complete re- of MDCT. Three-dimensional virtual gastroscopy prov-
section is indicated [20]. However, because ultrasound ides an endoluminal image similar to conventional fiber-
penetration is not deep enough when transducers with optic gastroscopy. Therefore, HMDCT is a valuable tool
higher frequencies are used to visualize fine structures, for the complete staging of gastric and esophageal tumors
evaluation of deep tumor infiltration may be difficult and and serves as an adjunct to endoscopy.
assessment of metastases may be limited by the finite However, EUS and MDCT are anatomically based di-
depth of penetration [21]. EUS also is examiner-depen- agnostic techniques with certain drawbacks. These in-
dent, time-consuming, and unable to pass stenotic tumors. clude limited sensitivity with false-negative findings due
These limitations can be overcome using multidetector
CT technology (MDCT), with its ability to cover a large
volume in a very short scan time with a single breath-
hold. Thin collimation and isotropic voxels allow imaging
of the entire esophagus and stomach with high-quality
multiplanar reformation and 3D reconstruction (Fig. 6)
Fig. 7. Hydro-MDCT of the esophagus in coronal reformation

shows a huge mass with inhomogeneous enhancement in the me-
Fig. 6. Hydro-MDCT of the esophagus in coronal reformation to fol- diastinum arising from the esophageal wall, with infiltration of the
low the course of the esophagus, demonstrating normal wall thick- left main bronchus (arrow) and the left diaphragm (arrowhead),
ening of the esophagus (≤3 mm) and homogeneous enhancement with regard to the T4 tumor. Note the pleural effusion
26 Marc S. Levine, Ahmed Ba-Ssalamah
to non-enlarged, tumor-involved lymph nodes, and limit- a

ed specificity with false-positive findings due to enlarged
lymph nodes not involved by tumor. Furthermore, after
neo-adjuvant chemotherapy and re-evaluation, it is not
possible with these techniques to distinguish between fi-
brotic changes or remaining vital tumor due to their mor-
phological similarities [25].Thus, there is an urgent need
for additional functional examination techniques.
Positron emission tomography (PET) yields physio-
logical information that provides a means to diagnose
cancer based on altered tissue metabolism. PET takes ad-
vantage of the principle that biochemical changes often
precede or are more specific than the structural changes b
associated with any given disease process [26]. There-
fore, PET offers the potential to show early esophageal
cancer or small lymph node metastases before any struc-
tural abnormality is detectable or to exclude the presence
of tumor in an anatomically altered structure. For exam-
ple, FDG-PET can detect metastatic lymph nodes that are
not enlarged on CT, and can help differentiate pathologi-
cal from non-specifically enlarged lymph nodes, which
usually show no uptake of FDG. Tumor uptake of FDG,
measured as the maximal standardized uptake value
(SUVmax) in FDG-PET, even provides a quantitative
estimate of tumor aggressiveness [27]. Fig. 8 a, b. Hydro-MDCT PET scan of an early cervical esophageal
Recent studies demonstrated that FDG-PET can be carcinoma and enlarged right-sided lymph node. a On the axial
HMDCT scan of the upper thorax, the small esophageal cancer is
used not only for pre-treatment staging, but also for as- not clearly seen and the enlarged lymph appears suspicious. b Cor-
sessment of treatment response, detection of recurrence, responding axial fused HMDCT-PET image shows increased ac-
and prediction of survival in patients with adenocarcino- tivity in the region of the small primary tumor (arrow) and an en-
ma of the esophagus or stomach [27]. However, for mu- larged metastatic lymph node (arrowhead)
cinous and signet-ring cell adenocarcinoma of the stom-
ach, it is less useful. This may be due to low or absent
FDG activity in these tumors, which is the result of a high
content of metabolically inert mucus, leading to a refor patients with esophageal and gastric tumors. HMDCT
duced FDG concentration. Another reason could be the may help distinguish surgical candidates with limited dis-
lack of expression of the glucose transporter Glut-1 on ease from patients in need of pre-operative chemoradia-
the cell membrane of most signet-ring cell and mucinous tion for down-sizing a tumor or from patients who need
adenocarcinomas [28]. palliative therapy for advanced, unresectable tumor.
The spatial resolution of FDG-PET is lower than that When HMDCT shows definite advanced disease with ex-
of CT scans. When metastatic nodes exist around the pri- tensive tumor spread, pre-surgical chemotherapy or ra-
mary tumor, it can be difficult to distinguish uptake in diochemotherapy is used to improve the prognosis. After
these nodes from the intense activity of the primary tu- completion of neo-adjuvant treatment, the tumor can then
mor. However, the advent of PET/CT imaging, enabling be restaged to determine whether surgical resection is in-
co-registration of both anatomical and functional infor- dicated. Thus, pre-operative staging of esophageal and
mation, has overcome this disadvantage and improved the gastric tumors is by far the most important indication for
localization of increased FDG uptake (Fig. 8) [29]. FDG- HMDCT. This technique also plays an important role in
PET/CT shows the extent of disease more accurately than the evaluation of postoperative complications such as fis-
other imaging methods, and this frequently leads to a rad- tulas when the findings on barium studies are equivocal.
ical change in patient management. Combined PET/CT
imaging is therefore a valuable diagnostic tool for the pri-
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Am J Surg Pathol 24:211-222
IDKD 2010-2013
Small-Bowel Imaging: Pitfalls in Computed Tomography

Enterography/Enteroclysis
Marc J. Gollub
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Computed Tomography Enterography liver-type setting (W215, L135) and an “enterographic-

type” setting (W430, L155). Since CTEG does not create
Computed tomography enterography (CTEG) is a fo- an enteral challenge, in contrast to CTEC, its use in the
cused CT scan examination of the small intestine that setting of low-grade small-bowel obstruction should be
combines the advantages of isotropic, thin-section multi- discouraged in favor of CTEC or magnetic resonance en-
planar CT; the large volumes of neutral-density oral con- teroclysis. However, even during a non-obstructive
trast; and rapid administration of intravenous contrast. episode, CTEG may confer an advantage by delineating
Oral contrast agents such as 0.1% barium, polyethylene a subtle, underlying cause such as a mass or stricture.
glycol (PEG) and methylcellulose contain additives that Fastidious technique and timing are basic requirements
inhibit fluid reabsorption and allow maximal bowel dis- in CTEG. Inadequate oral intake, early or late scanning,
tention. Intravenous contrast is injected at the “enteric poor intravenous enhancement (low rate, reduced dose), or
phase” (about 45 s) to provide maximum wall enhance- underlying hypo- or hypermotility disorders can interfere
ment against the neutral-density lumen (0-30 HU) [1]. with good distention and wall conspicuity. Some of these
Pharmacological manipulation to interrupt small-bowel technical pitfalls can be overcome with low-kVp imaging,
spasm and encourage gastric emptying is commonly close monitoring of the drinking schedule, and pharmaco-
used, including glucagon and metoclopramide, respec- logical manipulation. Poor jejunal distention is a generally
tively. The indications for CTEG include Crohn’s disease expected limitation compared with other examinations.
and other enteritides, obscure gastrointestinal bleeding Fortunately, many abnormalities are diagnosed at CTEG
(OGIB), detection of intestinal masses, and sprue. A solely by virtue of mural hyperenhancement.
prospective blinded comparison of CTEG with wireless
capsule endoscopy (WCE) using clinical consensus as the Crohn’s Disease
gold-standard found similar sensitivities (82 vs. 83%) for
active small-bowel Crohn’s disease, but CTEG was far Proof of disease, grading of severity, and assessment of
more specific than WCE (89 vs. 53%). Although there is penetrating disease are important tasks prior to surgical
less experience in using CTEG for OGIB, one study planning and even prior to medical treatment, since the
found a bleeding source in 45% of 22 patients, in three of therapeutic anti-tumor necrosis factor alpha (TNFα) an-
whom the source had been missed by initial WCE [2]. No tibodies (e.g., infliximab) are expensive and have side ef-
comprehensive reports of mass detection have been pub- fects of infection and drug-induced immune disease [3].
lished yet, but in our experience CTEG appears to repre- The classic findings at CTEG in patients with active
sent a first-line test for suspected carcinoid. This chapter Crohn’s disease have been well described [2]. The Amer-
will discuss the pitfalls and limitations of CTEG and CT ican College of Radiology has deemed CTEG to be the
enteroclysis (CTEC). most appropriate imaging test for Crohn’s disease [4].
Nonetheless, studies testing the accuracy of CTEG com-
pared with other radiological and endoscopic tests have
Pitfalls of Computed Tomography Enterography identified some clear limitations and pitfalls for CTEG in
the setting of suspected Crohn’s disease, including:
General 1. non-specificity of certain findings, such as mural hy-
perenhancement without skip areas;
Even with the aid of neutral-density oral contrast to as- 2. in known Crohn’s disease, signs of very early disease,
sist in mass conspicuity, mildly enhancing masses or such as aphthous ulcers, which will not be detected un-
mural inflammation may be subtle and overlooked with- less a mucosal study is done;
out proper adjustment of the window and level. We rec- 3. measurement of disease severity, including quantita-
ommend, in addition to standard abdominal settings, a tion of ulcers or fistulas; and
4. correlation with clinical findings. contrast, and 1800 mL of neutral-density contrast. With
Wold et al. found CTEG to be superior to small-bow- this approach, the majority of patients with a source of
el follow-through for the detection of abscesses and fis- OGIB were detected compared with WCE, surgery, or fol-
tulas, with a sensitivity and specificity of 78/83% vs. low up. Ten of 22 (43%) studies showed positive findings,
62/90%, respectively [5]. including the detection of angioectasias [12]. Huprich et
Vogel et al. showed that, although CTEG is accurate for al. emphasized that, while three-phase CTEG can be done
determining the presence or absence of strictures and fis- with the goal of detecting angioectasias and other arterial-
tulas (sensitivity 100, 92% respectively), it is less accurate phase dominant lesions, the radiation incurred is substan-
in determining their number (sensitivity 67%, both). This tial (effective dose 59 mSv per exam) such that the relative
may be clinically significant since uncorrected strictures risks and benefits have to be weighed, including patient
or fistulas can result in postoperative symptoms [6]. age, necessity of repeat examinations, and the known risk
Solem et al. found that the sensitivity of WCE and CTEG of radiation with multiple CT exams, especially in younger
in the detection of active small-bowel Crohn’s disease was patients [12, 13]. A follow-up prospective study using
identical (both 83%), and there was no significant differ- three-reader comparisons, presented by Huprich at RSNA
ence with ileocolonoscopy (74%) or small-bowel follow- 2009, indicated that two out of three phases are often ade-
through (65%) [7]. Hara et al., investigating disease activ- quate, but conclusive results have not been published. In a
ity, showed that findings at CTEG correlated with symp- similar study by Hara, using three-phase CTEG, 33% of le-
toms in 80% of patients, indicating CTEG’s excellence as sions were detected (specificity 89%) and 52% were de-
a monitoring test [8]. In a study by Higgins et al., clini- tectable in retrospect. Some of the missed lesions were in
cians suspected only 84% of CTEG-identified strictures the stomach and colon, emphasizing the advantage of
and CTEG excluded strictures in >50% of patients with a CTEG in depicting abnormalities throughout the GI tract.
clinically suspected stricture [9]. Furthermore, a survey of Currently, the conditions that appear to be undetectable by
clinicians showed that, following the use of CTEG, clini- CTEG, as proven by other tests, include ulcers, vascular le-
cal management changes 50% of the time [10]. sions, and non-bleeding lesions [14].
Obscure Gastrointestinal Bleeding Neoplasms
In the search for sources of gastrointestinal (GI) bleeding, The accuracy of CTEG in the detection of masses such as
CTEG has found increasing use since it may be a more carcinoid, adenocarcinoma, lymphoma, gastrointestinal
sensitive, non-invasive method – using intravenous con- stromal tumor, and polyps is not known. Capsule en-
trast and CT angiography techniques – made possible by doscopy, an examination being used more frequently to
neutral-density oral contrast. However, its application is examine the small bowel, has several documented limita-
limited to being a diagnosis-only test, with no therapeu- tions, such that CTEG plays an important ongoing role for
tic capability. Abstracts from the 2009 Radiological So- small-bowel mass detection and is especially important
ciety of North America (RSNA) meeting in which the de- for masses that may have a predominant extraluminal
tection of bleeding rates using various techniques was component [15]. A recent RSNA 2009 Abstract indicated
compared suggested equal sensitivity with tagged RBC that masses in the setting of OGIB were better detected at
and catheter digital subtraction angiography, such that CTEG than at WCE. Hyperenhancing lesions (e.g., some
bleeds of as little as 0.3 mL/min were detected. melanoma metastases or carcinoid tumors) will be easily
The search for bleeding sources in the small bowel detected with careful observation and windowing; howev-
may be subsequent to an apparently negative upper- and er, the detection of isoattenuated masses (some melanoma
lower-GI endoscopy. It should be kept in mind that metastases, polyps, and even some primary adenocarcino-
missed gastric and colonic pathology may still be discov- mas) and smaller masses may require excellent luminal
ered at imaging if these areas are well-filled, since endo- distention and perusal for secondary findings, such as in-
scopic examinations are performer-dependent, imperfect creased wall thickening, increased luminal caliber, or
gold-standards. complications (intussusception, obstruction). CTEG may
Conventional barium studies do not identify mucosal underestimate the number of lesions due to their smaller
erosions or vascular ectasia and have yields of 6% for size or the lower degree of vascularity of small tumors.
small-bowel follow-through and 10% for small-bowel en-
teroclysis [11]. Angioectasias are the most common cause
of OGIB in patients over the age of 50. These lesions are Computed Tomography Enteroclysis
typically small, may be multiple, and are sessile or slight-
ly raised. They are typically only visible at endoscopy or This fused test combines the advantages of enteral chal-
potentially at arterial-phase catheter-based or CT angio- lenge from a catheter small-bowel examination (entero-
graphy. A major limitation of CTEG is its relative insensi- clysis) with the isotropic, multiplanar, cross-sectional im-
tivity to these small, flat, vascular lesions. The most recent ages obtained at helical CT. Indications for CTEC include
study used optimized thin-sections, three scanning phases small-bowel obstruction, small-bowel masses, OGIB,
(arterial, enteric, and delayed), rapid boluses of intravenous Crohn’s disease, and malabsorption.
30 Marc J. Gollub
Pitfalls of Computed Tomography Enteroclysis minimally enhancing, or <5 mm in size may be difficult
to detect. As such, the use of CTEC for patients with poly-
General posis syndromes (familial adenomatous polyposis and
Peutz-Jeghers) may be somewhat limited [22, 23]. Voder-
Careful attention to technique, including the use of infu- holzer et al. found that, compared with WCE, polyps, ero-
sion rates that allow uniform bowel distention; catheter sions, angioectasia, and lymphangiectasia were missed by
placement in the proper location, with correct balloon in- CTEC but seen on WCE [17]. Careful perusal of thin-sec-
sufflation and tip placement; the appropriate administra- tions at CTEC might prevent overlooking of these lesions.
tion of pharmacological agents; and proper use of multi- Careful perusal of wall enhancement is necessary in pa-
detector CT with reformatted images, will obviate many tients with Crohn’s disease, to avoid missing more focal,
sources of misinterpretation. Spasm and inadequate filling concurrent masses (secondary malignancy), as these can
should be easily recognized and addressed by adjustment be overlooked as well. In the diagnosis of OGIB, there are
of the pump flow-rate and use of spasmolytics (glucagon few reported series in which CTEC was used. In fact, in
or Buscopan). Variable window and level settings are ad- the workup of OGIB, Fillipone et al. reported that in
vised to adjust for high-attenuation contrast or, in the in- patients over age 50 OGIB is more commonly caused by
terpretation of a neutral-density exam, to appreciate sub- angioectasia than by small-bowel masses. Here too, WCE
tle differences in enhancement of the bowel wall. may be the more appropriate modality due to the non-
elevated nature of these often subtle, small lesions [18].
Crohn’s Disease
Obstruction
In the diagnosis of suspected or known Crohn’s disease,
a comparison of WCE with neutral-density oral contrast In the context of small-bowel-obstruction, Walsh et al.
CTEC (nCTEC) in 56 patients showed that 27 could not concluded that CTEC has greater sensitivity and speci-
undergo WCE due to strictures (≤10 mm) for fear of cap- ficity (89 and 100%, respectively) than conventional CT
(50 and 94%, respectively) [23]. Pitfalls in technique spe-
sule retention. In the other 41 patients, the limitations of
cific to patients with obstruction include: failure to per-
nCTEC included its inability to detect very early, mini-
form suctioning prior to examination of the patient, fail-
mal inflammatory changes or small mucosal lesions such
ure to place the balloon in the jejunum (as opposed to the
as villous denudation, aphthoid ulcerations, or erosions.
duodenum, for better suctioning and the prevention of
These were far better detected by WCE than CTEC
back-flow into the stomach), and failure to properly ad-
(p = 0.004) [16-18]. Since the detection of non-elevated just the infusion rate so as to elicit the transition point in
or non-depressed lesions in Crohn’s disease and superfi- low-grade obstructions. Overzealous infusion can cause
cial erosions in NSAID enteropathy will be limited, these spasm, which may be misinterpreted as a site of stricture
entities would probably be best investigated using others and obstruction. This can be avoided to some extent with
methods, such as push enteroscopy, single- or double-bal- the administration of glucagon or Buscopan. Problem-
loon endoscopy, WCE or “air” (C02) double-contrast flu- solving regarding possible strictures can be accomplished
oroscopic enteroclysis without CT [19, 20]. In addition, with repeat limited CT slices through the area of interest;
in late-stage Crohn’s disease, nCTEC may show fewer however, this can be a costly approach given the radia-
fistulae than positive oral contrast CTEC (pCTEC), as tion-burden. The use of multidetector CT with 40 or more
the higher-density contrast may fill the GI tract more channels can reduce radiation by 10-66% because of
conspicuously. more efficient detector configurations, automatic expo-
sure controls, improved filters, and the availability of im-
Masses age post-processing algorithms [24].
In the workup of small-bowel masses or OGIB, several
pitfalls may be encountered. False-positive masses may be Summary
seen in patients with Kerkring fold thickening or even
transient intussusception [21]. Unfortunately, the findings The workup of small intestinal abnormalities is changing
may be so convincing as to necessitate surgery to prove rapidly due to technological advances in cross-sectional
the lack of a mass. In Pilleul’s study of 219 patients with imaging and endoscopic techniques. Although improve-
possible small-bowel neoplasms, the overall accuracy was ments are still being made, certain early conclusions re-
84.7%. There were five false-positive masses (2.3%) rang- garding the detection of small-bowel pathologies can be
ing from 6 to 25 mm in size. In two of these, small-bowel offered:
fold thickening was found at surgery and in the others no 1. CTEG, the most rapidly investigated new technique,
mass could be detected [22]. CTEC may also fail to iden- appears to be comparable if not superior to most endo-
tify jejunal polyps <10 mm, angioectasias, and ectopic scopic methods in determining disease presence, sever-
pancreas 3-5 mm in size. A false-negative rate of 4.1% ity, extent, complications, and activity status, as well as
was reported as well, as any lesion that is sessile, response to treatment; however, pitfalls exist, including
non-specificity of early findings, the enumeration of 9. Higgins PDR, Caoli E, Zimmerman M et al (2007) Computed
fistulous tracts, and the detection of aphthous ulcers. tomographic enterography adds information to clinical man-
agement in small bowel Crohn’s disease. Inflamm Bowel Dis
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surgery or catheter embolization immediately, if at all, 10. Bruining DH, Siddicki H, Fletcher JG (2008) Clinical benefit
should be offered CTEG using two or more phases to of CT enterography in suspected or established Crohn’s dis-
search for a source of blood – with the known pitfalls ease: impact on patient management and physician level of
of the technique’s inability to detect shallow gastric or confidence. Gastroenterology S1211
11. Singh V, Alexander JA (2008) The evaluation and management
small-bowel ulcers, small angioectasias, or flat lesions. of obscure and occult gastrointestinal bleeding. Abdom Imag-
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mass is not hyperenhancing, perfect bowel distention trointestinal bleeding: Evaluation with 64-section multiphase
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especially in the proximal jejunum. ing source of radiation exposure. N Engl J Med 357:2277-2284
4. CTEC, performed in limited centers in the USA and 14. Hara AK, Walker FB, Silva AC, Leighton JA (2009) Prelimi-
perhaps more widely in Europe, is subject to mostly nary estimate of triphasic CT enterography performance in he-
technique-related pitfalls but has the advantage of an modynamically stable patients with suspected gastrointestinal
enteral challenge, which is not available with other bleeding. AJR 193:1252-1260
15. Postgate A, Despott E, Burling D et al (2008) Significant
non-catheter/pump methods and which may define its small-bowel lesions detected by alternative diagnostic modali-
predominant indication as the best test for low-grade, ties after negative capsule endoscopy. Gastrointest Endosc
intermittent small-bowel obstruction not detectable by 68:1209-1214
other means. 16. Voderholzer WA, Beinhoelzl J, Rogalla P et al (2005) Small
bowel involvement in Crohn’s disease: a prospective compari-
son of wireless capsule endoscopy and computed tomography
References enteroclysis. Gut 54:369-373
17. Voderholzer WA, Ortner M, Rogalla P et al (2003) Diagnostic
1. Colombel JF, Solem CA, Sandborn WJ et al (2006) Quantita- yield of wireless capsule enteroscopy in comparison with com-
tive measurement and visual assessment of ileal Crohn’s dis- puted tomography enteroclysis. Endoscopy 35:1009-1014
ease activity by computed tomography enterography: correla- 18. Fillipone A, Cianci R, Milano A et al (2008) Obscure gas-
tion with endoscopic severity and C reactive protein. Gut trointestinal bleeding and small bowel pathology) comparison
55:1561-1567 between wireless capsule endoscopy and multidetector-row
2. Paulsen SR, Huprich JE, Hara AK (2007) CT enterography: CT enteroclysis. Abdom Imaging 33:398-406
Noninvasive evaluation of Crohn’s Disease and obscure gas- 19. Romano S, De Lutio E, Rollandi GA et al (2005) Multidetec-
trointestinal bleed. Radiol Clin N Am 45:303-315 tor computed tomography enteroclysis (MDCT-E) with neutral
3. Huprich JE, Fletcher JG (2009) CT enterography: Principles, enteral and IV contrast enhancement in tumor detection. Eur
technique and utility in Crohn’s disease. Eur J Radiol 69:393-397 Radiol 15:1178-1183
4. Dave-Verma H, Moore S, Singh A et al (2008) Computed to- 20. Maglinte DDT, Lappas JC, Heitcamp DE et al (2003) Techni-
mographic enterography and enteroclysis: pearls and pitfalls. cal refinements in enteroclysis. Radiol Clin North Am 41:
Curr Probl Diagn Radiol 37:279-287 213-229
5. Wold PB, Fletcher JG, Johnson CD et al (2003) Assessment of 21. Boudiaf M, Jaff A, Soyer P et al (2004) Small-bowel diseases:
small bowel Crohn disease: Noninvasive peroral CT entero- Prospective evaluation of multi-detector row helical CT ente-
graphy compared with other imaging methods and endoscopy- roclysis in 107 consecutive patients. Radiology 233:338-344
feasibility study. Radiology 229:275-281 22. Pilleul F, Penigaud M, Milot L et al (2006) Possible small-
6. Vogel J, Moreira A, Baker M (2007) CT enterography for bowel neoplasms: contrast-enhanced and water-enhanced mul-
Crohn’s disease: Accurate preoperative diagnostic imaging. tidetector CT enteroclysis. Radiology 241:796-801
Dis Colon Rectum 50:1761-1769 23. Walsh D, Bender G, Timmons H (1998) Comparison of com-
7. Solem CA, Loftus Jr EV, Fletcher JG et al (2008) Small-bow- puted tomography enteroclysis and traditional computed to-
el imaging in Crohn’s disease: a prospective, blinded, 4-way mography in the setting of suspected partial small bowel ob-
comparison trial. Gastrointest Endosc 68:255-266 struction. Emerg Radiol 5:29-37
8. Hara AK, Alam S, Heigh RI et al (2008) Using CT enterogra- 24. Mannudeep K, Rizzo SMR, Novelline RA (2005) Technologic
phy to monitor Crohn’s disease activity: a preliminary study. innovations in computer tomography dose reduction: implica-
AJR 190:1512-1516 tions in emergency settings. Emergency Radiology 11:127-128
IDKD 2010-2013
Diseases of the Small Bowel, Including the Duodenum – MRI

Karin A. Herrmann
Institute of Clinical Radiology, University Hospitals Munich, Munich, Germany
Introduction using a nasojejunal tube, aided by an automatic infusion

pump. In CT-enteroclysis, scanning is typically performed
For decades, barium fluoroscopy studies have been the just after completion of the filling process; this results in a
standard of reference to investigate small bowel diseases. static, high-resolution data set that allows 3D post pro-
Since the small bowel was not accessible to endoscopic cessing. MR-enteroclysis has the advantage that it provides
techniques, these studies represented the only non-invasive not only static but also functional information, since repet-
diagnostic approach to the intestine. Both bowel follow- itive scanning can be carried out during the filling process.
through and small bowel enteroclysis yielded fairly good The diagnosis of small bowel diseases with CT and
results, with sensitivities and specificities of, respectively, MRI is fundamentally based on morphological criteria.
98.3% and 99.3% for Crohn’s disease (CD) [1] and 61-95% Distinct imaging findings allow disease detection, diag-
for neoplastic disease [2], notably in the assessment of the nosis, and staging. This chapter is designed to familiarize
intestinal mucosa due to the high spatial resolution ob- the reader with the typical imaging features indicating in-
tained with these techniques. However, their limitations are flammatory, neoplastic, and ischemic small bowel dis-
that they provide almost exclusively intraluminal informa- eases, with special focus on their MRI appearances.
tion and are associated with considerably high radiation
exposure, up to 10-18 mSv. The technical advances in
cross-sectional imaging achieved with computed tomogra- The Duodenum
phy (CT) and magnetic resonance imaging (MRI) over the
past 10 years have tremendously improved image quality Since the upper gastrointestinal tract is readily accessible
in the abdomen, thus encouraging small bowel imaging. to endoscopic techniques, imaging techniques are less im-
Thin-section multi-detector row CT with 3D multiplanar portant to establish a diagnosis. Yet, cross sectional imag-
reformations and accelerated image acquisition, in addi- ing is helpful to assess the intra- and extraluminal extent
tion to breath-hold techniques in MRI, has fostered imag- of disease. Since the duodenum is likely to be involved in
ing of the bowel with no or few limitations. Consequently, entities affecting surrounding organs, such as the pan-
CT and MRI are nowadays considered as state-of-the-art creas, bile duct, ampulla, and papilla, these should always
imaging modalities. Both not only provide insight into the be considered in the differential diagnosis of duodenal
bowel lumen but also depict mural and extramural patholo- pathology. Embryological anomalies include ectopic and
gy, which is essential for a comprehensive diagnostic as- annular pancreas, webs, and choledochoceles. Annular
sessment and the staging of small bowel diseases. More- pancreas occurs in 1:20,000 births and is typically diag-
over, CT and MRI convey far more information than ob- nosed in the early days after birth due to intestinal ob-
tained with conventional barium techniques [3]. MRI, in struction. During pregnancy, it can be discovered during
addition, has the advantage of obviating radiation exposure, evaluation of the polyhydramnion. Less frequently, it is
and is therefore preferable in children, young individuals, in found in young adults or incidentally later in life; in both
pregnancy, and if multiple follow-up studies are required cases it then has to be distinguished from neoplasm. Oth-
such as in patients with inflammatory bowel disease. er benign non-neoplastic conditions in the duodenum in-
In order to appropriately assess the intestine, bowel dis- clude ulcerative and inflammatory disease (i.e., CD) and
tention is essential. This can be achieved with contrast pseudoinflammatory polyps. These pathologies are typi-
agents that typically have osmotic effects and enhance the cally worked up endoscopically.
contrast between the bowel lumen and the bowel wall. De-
pending on the mode of application, the corresponding ex- Neoplasms of the Duodenum
amination is called MR- or CT-enterography if the contrast
medium is administered orally prior to the examination, Lipoma, leiomyoma, neurofibroma, adenoma, Brunner
and MR- or CT-enteroclysis if the contrast agent is injected gland adenoma, and polyps are benign neoplasms occur-
Diseases of the Small Bowel, Including the Duodenum – MRI 33
ring in the duodenum. Patients are typically asymptomatic disease, especially CD. CD is a chronic inflammatory au-
until a late stage of disease. While MRI is helpful in char- toimmune disorder that frequently involves the small bow-
acterizing fat-containing lesions, it is less useful in the fi- el but may affect the entire gastrointestinal tract. It is most
nal histopathological diagnosis of most of these neo- commonly located in the terminal ileum (40-80%) and the
plasms. Malignant neoplasms of the duodenum include colon. Involvement of the proximal ileum and the jejunum
adenocarcinoma, lymphoma, neuroendocrine tumors, is less frequent (22-40%). In imaging, CD manifestations
gastrointestinal stromal tumors (GIST), and metastases. have been classified by Maglinte et al. in three categories:
Duodenal adenocarcinoma accounts for only 0.4% of acute inflammatory disease, fibrostenotic disease, and fis-
gastrointestinal tumors. By the time it is clinically appar- tulizing disease [5]. Due to its chronically recurrent char-
ent, there is often advanced disease. Clinical symptoms are acter, different stages of CD may coexist. Discontinuity of
indicative of high bowel obstruction, vomiting, chronic multiple disease manifestations (skip lesions) is a charac-
bleeding and, if close to the ampulla, obstructive jaundice. teristic feature. The morphological spectrum ranges from
The duodenum is the most common site for adenocarcino- early superficial mucosal disease with disruption, flatten-
ma, which may appear as a defined nodular mural mass or ing, thickening, and distortion of the fold pattern, to mild
a diffusely infiltrating mass with spiculated borders. An- or pronounced longitudinal or transverse fissures and ul-
other pattern is that of a diffuse or annular wall thickening cerations resulting in a cobblestone appearance, to trans-
causing constrictive narrowing of the lumen. On T1- mural disease characterized by wall thickening, stenosis,
weighted imaging, the tumor may be homogeneously and mesenteric hypervascularity. Eventually, extramural
isointense or hypointense compared to the wall and slight- extension of the inflammation into the mesentery may oc-
ly hyperintense or isointense in T2-weighted imaging. cur, accompanied by the development of blind sinus tracts,
Contrast enhancement is moderate, mostly homogeneous. fistulas, and micro- or macro abscesses.
Lymphoma: in the duodenum, as in the small and large
bowel, the most frequent form of lymphoma is non- Crohn’s Disease: Acute Inflammatory Type
Hodgkin’s lymphoma (NHL). In 50% of nodal NHLs,
there are concomitant intestinal manifestations. Typical A number of imaging findings in MRI have been reported
imaging features of duodenal and intestinal lymphoma are to determine inflammatory activity in CD: increased small
marked asymmetrical circumferential wall thickening with bowel wall thickening (typically >4 mm), increased mural
mild pre-lesional luminal dilatation. Luminal stenosis is contrast enhancement [6], submucosal edema with high
not always predominant. Lymphoma may also appear as signal intensity on T2-weighted images [7] (Fig. 1), the
multiple polypoid intraluminal protrusions or an exophyt- presence of deep mucosal ulcers and fissures [8], mesen-
ic extraluminal mass. Ulceration and fistula formation are teric hypervascularity (comb sign) [9], and contrast-
not uncommon. An extraluminal desmoplastic reaction is enhancing enlarged lymphadenopathy [8]. The most recent
unlikely. Associated lymphadenopathy is a helpful diag- literature describes increased mural thickening, increased
nostic hint but is not always present. Compared to normal wall signal intensity on T2-weighted fat-saturated images,
bowel wall, intestinal lymphoma shows moderately in- and layered mural enhancement, but not mural enhance-
creased and homogeneous signal intensity on T2-weighted ment alone, as the strongest indicators for active disease.
images. On T1-weighted imaging, it is isointense or hypo- Layered mural enhancement, however, is also commonly
intense and exhibits mild and slightly inhomogeneous associated with coexisting fibrostenosis and scar formation
contrast enhancement after gadolinium administration [4]. [10]. Early and mild stages of CD may present at MRI as a
Unlike neuroendocrine tumors (NET) of the small focal or regional disruption of the fold pattern, showing on-
bowel, the role of CT and MRI in detecting duodenal ly subtle or no increased enhancement. Superficial erosions
NET is minor compared to endoscopic techniques, in- may not be detected at all. In contrast to overt wall thick-
cluding endoscopic ultrasound. Along with the stomach, ening and stenosis, these lesions can easily be missed at
duodenum is a common location for NET. Typically, the MRI especially when distention is suboptimal. This is why
lesions are small; they occasionally can be detected on MR-enterography or MR-enteroclysis (MRE), compared to
CT and MRI as single or multiple hypervascular nodules capsule endoscopy or invasive double balloon endoscopy,
in arterial-phase imaging. Luminal distention, e.g., with reaches an overall sensitivity of only 75-80% [11, 12]. In
hydro-CT of the stomach, is recommended and may help subacute CD and under effective treatment, wall thickening
to achieve a detection rate of up to 89%. may persist initially but decreases over time. The hyper-
GISTs are most commonly located in the stomach and intense signal intensity from submucosal edema disappears
small bowel and are described in the following section. and becomes intermediate signal intensity. Likewise, the
formerly increased contrast enhancement decreases.
The Small Intestine Crohn’s Disease: Fibrostenosing Type
Inflammatory Bowel Disease
Fibrostenotic lesions are less conspicuous and more dif-
Currently, the most frequent clinical application of small ficult to identify on MRI since they typically show no
bowel MRI is in patients with inflammatory bowel wall thickening or increased enhancement. The seemingly
34 Karin A. Herrmann
a b
Fig. 1 a, b. MR-enteroclysis study with bipha-

sic intraluminal contrast in a 32 year-old pa-
tient with Crohn’s disease showing typical
signs of active inflammatory disease. a Wall
thickening, luminal narrowing and sub-
mucosal edema (arrow) is seen on T2-
weighted single-shot fast spin-echo (SSFSE)
(HASTE) imaging in a loop with prominent
active inflammation. b Slightly further up,
the loop shows increased transmural en-
hancement on contrast-enhanced T1-weight-
ed imaging with fat suppression, mesenteric
hypervascularity (arrow), and inflammatory
extramural stranding of the mesentery
normal wall thickness and contrast enhancement in fibro-

stenosis mimics the normal bowel wall. Low signal in-
tensity on T2-weighted images with and without fat sup-
pression has been described [9]. Persistent focal and
fixed circumscript intestinal stenosis and marked pre-
stenotic dilatation are the most conspicuous and reliable
indicators and indirect signs of fibrous strictures.
Crohn’s Disease: Fistulizing Type
Fistulas and peri- extramural abscesses represent the

most severe complications and can be diagnosed accu-
rately with MRI (accuracy 92%). Fistulas are tubular in-
flammatory pathways between bowel loops, bowel, and
other organs or bowel and the abdominal wall. They are
defined as internal fistulas (IF) when located between
bowel loops (entero-enteric) or internal organs (e.g., en-
tero-vesical). External fistulas (EF) are those that abut
the skin (entero-cutaneous). A vast majority of IF remain
asymptomatic or cause non-specific symptoms, especial-
ly if located in distal bowel segments. Complex IF typi- Fig. 2. MR-enteroclysis study of a 45-year-old patient with negative
intraluminal contrast (Lumirem®, Guerbet, France) shows an ex-
cally involve multiple bowel loops [13] and bowel ob- ample of a typical stellate appearance of converging bowel loops
struction due to concomitant stenosis. Abnormal tubular in an entero-enteric fistula involving the cecum, terminal ileum,
tracts within the mesentery containing air or fluid are sigmoid, and the middle ileum. Note the pre-stenotic dilatation of
highly indicative of IF and are well seen on SSFP the bowel loops proximal to it, indicating a mechanical stenosing
(steady-state free precession; e.g., TrueFISP) imaging. effect of the fistula complex (T2-weighted SSFSE)
The outlines of IF are of intermediate signal intensity on
T2-weighted images, similar to the intestinal wall, and
may show moderate enhancement after intravenous
gadolinium. A characteristic, somewhat stellate arrange- Differential Diagnosis of Crohn’s Disease
ment of the bowel loops is referred to as the “star-sign”
and is reportedly a strong indicator for the presence of Although less frequently a reason for imaging than CD, in-
complex IF (Fig. 2) [14]. The inflamed bowel loops con- fectious enteritis is an important differential diagnosis to
verge to a common center, which often is the origin of ab- consider. Infectious enteritis is typically of bacterial origin,
scess formation. Urinary bladder involvement is likely such as Enterococcus, Salmonella, Yersinia, and tubercu-
when there is marked thickening of the bladder wall in lous bacillae. In immunocompromised patients, viral and
the vicinity of an inflamed bowel segment [13]. A con- fungal infections such as Cytomegalovirus (CMV) have to
tiguous inflammatory tract between the inflamed bowel be considered. In patients who have undergone bone mar-
and the bladder wall may or may not be visualized. row transplant, CMV and graft-versus-host reactions are
Diseases of the Small Bowel, Including the Duodenum – MRI 35
likely. The appearance of infectious enteritis on CT or MRI (85%) as well as in the pancreas and lung (10%). The
is non-specific, the main feature being submucosal edema. appendix (50%) and the ileum (~30%) are the most com-
For tuberculosis, mesenteric lymphadenopathy is a major mon primary locations. Up to 30% of intestinal carcinoids
finding and a helpful clue to the diagnosis. Ischemic bow- are multifocal. Carcinoids have a tendency to metastasize
el disease is to be considered if arteriosclerosis and vascu- early to lymph nodes and the liver, even when they only
lar obstruction are observed additionally to altered bowel are 1-2 cm in size [16]. Therefore, distention of the bowel
wall with submucosal edema. lumen in MRE is required for better detection. Carcinoids
are typically hypervascularized and therefore are best
Small Bowel Neoplasms identified on contrast-enhanced T1-weighted fat saturated
GRE (gradient-recalled echo) sequences (Fig. 4). SSFSE
Small bowel neoplasms are rare and account for less than and SSFP sequence types depict these tumors less well as
5% of all gastrointestinal tumors. Adenocarcinoma, carci- slightly hyperintense or isointense to muscle and bowel
noid, lymphoma, GIST, and metastases constitute the ma- wall. Approximately half the tumors appear as a nodular
lignant component. MR-enteroclysis has recently been re- intraluminal mass, one third as focal circumferential wall
ported to be an effective diagnostic tool for the detection thickening, and 20% with both characteristics [17]. If only
of small bowel tumors, with a sensitivity, specificity, and wall thickening is present, carcinoids may easily be con-
accuracy of 86, 98, and 97%, respectively [15]. The inci- founded with inflammatory disease. A desmoplastic reac-
dence of small bowel cancer has risen in the past 30 years, tion in the adjacent mesentery occurs in up to 73% of the
with the greatest increase for carcinoid tumors. Adeno- cases of small tumors and may cause vascular engorge-
carcinoma is the most common among the intestinal ma- ment.
lignant neoplasms, followed by carcinoid tumors. After the
duodenum, the jejunum is the second most frequent loca- Gastrointestinal Stromal Tumors
tion for adenocarcinoma typically involving the ileum. The
imaging morphology for both adenocarcinoma and lym- Gastrointestinal stromal tumors represent 0.3-3% of all gas-
phoma (Fig. 3) is as previously described (see duodenal trointestinal tumors. They derive from the intestinal cells of
neoplasms). Both may occur as complications of CD. Cajal and originate most often from the stomach (~70%) or
the small bowel wall (20-30%). After appropriate immuno-
Neuroendocrine Tumors: Carcinoid histochemical preparation, they can be shown to strongly
express the KIT protein (CD 117), which is a characteristic
Carcinoid tumors are neuroendocrine neoplasms and ac- feature of GISTs. These tumors are well delineated, non-in-
count for approximately 2% of all gastrointestinal tumors. filtrative masses located in or arising from the intestinal
They may be found along the entire gastrointestinal tract wall, typically extraluminally at the serosal side [18]. When
<5 cm in diameter, they are slightly heterogeneous and
mildly hyperintense on T2. Larger masses are heteroge-
neous,with a soft-tissue rim encompassing a necrotic cen-
ter. This rim is isointense or slightly hyperintense to muscle
on T2-weighted images and hypointense on T1-weighted
images, showing heterogeneous enhancement after contrast
administration. In the majority of cases, GISTs do not show
signs of infiltration, vessel encasement, or lymphatic
spread. The primary sites of metastases from malignant
GISTs are the liver and peritoneum. Treatment with tyro-
sine kinase inhibitors induces a loss of vascularization, and,
consequently, reduced contrast enhancement of the tumor
and its metastases [19], but no necessarily change in size.
Other Small Bowel Pathologies
For some small bowel pathologies, MRE has so far not

proven to be useful. For superficial mucosal pathologies
and angiodysplasia, MRI of the small bowel cannot be
recommended. The detection of acute ischemia and oc-
Fig. 3. MR-enteroclysis study of a 63-year-old male with occult cult gastrointestinal bleeding is the domain of CT, main-
bleeding at fecal occult blood test. T2-weighted SSFSE image af- ly because of its availability in an emergency setting,
ter biphasic intraluminal contrast administration shows an ileal short examination time, and spatial resolution.
segment of marked circumferential wall thickening with mass
effect preserving the lumen (arrow). The intraluminal surface is Post-operative or post-inflammatory small bowel ad-
irregular; contrast enhancement (not shown) was moderate. This hesions represent another important condition, formerly
example shows the typical features of intestinal lymphoma investigated with conventional enteroclysis using manual
36 Karin A. Herrmann
a b
Fig. 4 a, b. T1-weighted contrast-enhanced

coronal GRE image after MRE with biphasic
intraluminal contrast depicts a 1.5-cm U-
shaped intraluminal mass (arrow) in the ileum
with increased enhancement (a; zoomed in b)
which after surgical removal proved to be car-
cinoid. No mesenteric desmoplastic reaction
is seen
compression and mobilization of the bowel loops. This 9. Prassopoulos P, Papanikolaou N, Grammatikakis J et al (2003)
manipulation is not practicable in MRI due to the limited MR enteroclysis imaging of Crohn disease. Radiographics 21
Spec No:S161-172
access to the patient inside the magnet. To date, no liter- 10. Punwani S, Rodriguez-Justo M, Bainbridge A et al (2009) Mur-
ature is available to support the usefulness of MRE for al inflammation in Crohn disease: location-matched histologic
small bowel adhesions. validation of MR imaging features. Radiology 252:712-720
11. Tillack C, Seiderer J, Brand S et al (2008) Correlation of mag-
netic resonance enteroclysis (MRE) and wireless capsule en-
doscopy (CE) in the diagnosis of small bowel lesions in
References Crohn’s disease. Inflamm Bowel Dis 14:1219-1228
1. Maglinte DD, Chernish SM, Kelvin FM et al (1992) Crohn 12. Seiderer J, Herrmann K, Diepolder H et al (2007) Double-bal-
disease of the small intestine: accuracy and relevance of ente- loon enteroscopy versus magnetic resonance enteroclysis in di-
roclysis. Radiology 184:541-545 agnosing suspected small-bowel Crohn’s disease: results of a
2. Bessette JR, Maglinte DD, Kelvin FM, Chernish SM (1989) pilot study. Scand J Gastroenterol 42:1376-1385
Primary malignant tumors in the small bowel: a comparison of 13. Herrmann KA, Michaely HJ, Zech CJ et al (2006) Internal fis-
the small-bowel enema and conventional follow-through ex- tulas in Crohn disease: magnetic resonance enteroclysis. Ab-
amination. AJR Am J Roentgenol 153:741-744 dom Imaging 31:675-687
3. Lee SS, Kim AY, Yang SK et al (2009) Crohn disease of the 14. Herrmann KA, Michaely HJ, Seiderer J et al (2006) The “star-
small bowel: comparison of CT enterography, MR enterogra- sign” in magnetic resonance enteroclysis: a characteristic find-
phy, and small-bowel follow-through as diagnostic techniques. ing of internal fistulae in Crohn’s disease. Scand J Gastroen-
Radiology 251:751-761 terol 41:239-241
4. Kim KW, Ha HK (2004) MRI for small bowel diseases. Magn 15. Masselli G, Polettini E, Casciani E et al (2009) Small-bowel
Reson Imaging Clin N Am 12:637-650 neoplasms: prospective evaluation of MR enteroclysis. Radiol-
5. Maglinte DDT, Gourtsoyiannis N, Rex D et al (2003) Classi- ogy 251:743-50
fication of small bowel Crohn’s subtypes based on multi- 16. Horton KM, Kamel I, Hofmann L, Fishman EK (2004) Carci-
modality imaging. Radiol Clin North Am 41:285-303 noid tumors of the small bowel: a multi-technique imaging ap-
6. Sempere GAJ, Sanjuan VM, Chulia EM et al (2005) MRI eval- proach. AJR Am J Roentgenol 182:559-567
uation of inflammatory activity in Crohn’s disease. AJR Am J 17. Schmid-Tannwald C, Zech CJ, Panteleon A et al (2009). Char-
Roentgenol 184:1829-1835 acteristic imaging features of carcinoid tumors of the small
7. Maccioni F, Bruni A, Viscido A et al (2006) MR imaging in bowel in MR enteroclysis. Radiologe 49:242-245
patients with Crohn disease: value of T2- versus T1-weighted 18. Burkill GJ, Badran M, Al-Muderis O et al (2003) Malignant
gadolinium-enhanced MR sequences with use of an oral su- Gastrointestinal Stromal Tumor: Distribution imaging features
perparamagnetic contrast agent. Radiology 238:517-530 and pattern of metastatic spread. Radiology 226:527-532
8. Gourtsoyiannis N, Papanikolaou N, Grammatikakis J et al 19. Schlemmer M, Sourbron SP, Schinwald N et al (2009) Perfu-
(2004) Assessment of Crohn’s disease activity in the small sion patterns of metastatic gastrointestinal stromal tumor
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results. Eur Radiol 14:1017-1024 278-284
IDKD 2010-2013
Imaging of the Colon and Rectum: Inflammatory and Infectious Diseases

Jaap Stoker1, Richard M. Gore2
1 Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
2 Department of Radiology, North Shore University Health System, Evanston Hospital, Evanston, IL, USA
Introduction of ulcerative colitis are beneath the spatial resolution of

CT. With progressive disease, submucosal edema pro-
Infectious and inflammatory diseases of the colon and rec- ducing a “target sign” may be seen. Severe mucosal ul-
tum are common disorders that are becoming increasingly ceration can denude certain portions of the colonic wall,
prevalent. Diverticulitis, appendicitis, and the inflammato- leading to inflammatory pseudopolyps (Fig. 1), which,
ry and infectious colitides are among the commonest caus- when sufficiently large, can be visualized on CT. Mural
es of acute abdominal pain. These patients frequently pre- thickening and luminal narrowing are the CT hallmarks
sent with non-specific symptoms. Since in most cases of of the subacute and chronic ulcerative colitides. Mural
acute abdominal pain clinical and laboratory assessments thinning, unsuspected perforations, and pneumatosis can
cannot confidently identify a specific etiology, cross-sec- be detected on CT in patients with toxic megacolon. In
tional imaging plays an important part in the work-up and this regard, CT can be quite helpful in determining the ur-
management of these patients. Ultrasound (US) and com- gency of surgery in patients with stable abdominal films
puted tomography (CT) are the primary means of evaluat- yet a deteriorating clinical course [1-3].
ing acute abdominal pain, as both modalities provide in- In chronic ulcerative colitis, the muscularis mucosa
sight into the pathological changes in the colon wall, becomes markedly hypertrophied, often by a factor of 40.
serosa, surrounding mesentery, and peritoneum. US is a Forceful contraction of this hypertrophied longitudinal
readily available, real-time technique with reasonable ac- muscle may pull the mucosa away from the submucosa,
curacy that uses no ionizing radiation. CT provides rapid
assessment with high accuracy, optimal field of view, and
good reproducibility. Magnetic resonance imaging (MRI)
in patients with acute abdominal pain offers great clinical
potential by virtue of its global imaging perspective, ex-
quisite soft-tissue resolution, and high accuracy without
the need for ionizing radiation. In patients with perirectal
and perianal inflammatory conditions, MRI is the pre-
ferred imaging technique, as the combination of high in-
trinsic contrast resolution and large field of view provides
detailed information on the presence and extent of disease.
This chapter describes the imaging features of these
infectious and inflammatory disorders, provides differen-
tial diagnostic guidelines, and presents the advantages
and disadvantages of the various imaging modalities in
the context of optimizing patient management.
Ulcerative Colitis
Ulcerative colitis is characterized pathologically by ex-
tensive confluent and circumferential ulceration and by
diffuse inflammation of the mucosa. The disease charac-
Fig. 1. Acute ulcerative colitis. CT demonstrates deep ulcerations
teristically begins in the rectum and extends proximally (arrows) of the fluid-filled rectosigmoid. Inflammatory pseudo-
in a contiguous fashion to involve part or all of the colon. polyps appear as residual islands of inflamed mucosa that protrude
The pathological changes found in the very early stages above the denuded colonic surface
38 Jaap Stoker, Richard M. Gore
producing diffuse or segmental narrowing of the lumen. aphthoid ulceration with adjacent cobblestoning, an often
The contraction also causes shortening of the colon. The transmural inflammatory reaction with lymphoid aggre-
submucosa becomes thickened due to the deposition of gates and granuloma formation, fissures, fistulas, and si-
fat or, in acute and subacute cases, edema. Submucosal nus tracts. The chronic and resolving phase of this disor-
thickening further contributes to narrowing of the lumen. der is associated with fibrosis and stricture formation.
Additionally, in acute and in chronic ulcerative colitis, the The presence and extent of Crohn’s disease can be de-
lamina propria is thickened due to round-cell infiltration. termined by US, CT, or MRI. The accuracy of each of
On CT, these mural changes produce a “target” or these examinations is comparable but each technique has
“double-halo” appearance when axially imaged. The lu- its strength and limitations [4]. When Crohn’s disease is
men is surrounded by a ring of soft-tissue density (mu- limited to the mucosa, the CT scan is often normal. Al-
cosa, lamina propria, hypertrophied muscularis mu- though inflammatory and post-inflammatory pseudo-
cosae), then by a low-density ring (fatty infiltration of the polyps may be identified on CT, the assessment of the
submucosa), and in turn by a ring of soft-tissue density mucosa is best reserved for barium studies and colono-
(muscularis propria). This mural stratification is not spe- scopy, which are more direct and sensitive. Crohn’s dis-
cific and can also be seen in Crohn’s disease, infectious ease is manifested on CT by bowel wall thickening of 1-
enterocolitis, pseudomembranous colitis, ischemic and 2 cm. This thickening, which occurs in up to 83% of pa-
radiation enterocolitides, mesenteric venous thrombosis, tients, is most frequently observed in the terminal ileum,
bowel edema, and graft-versus-host disease [1-3]. but other portions of the small bowel, colon, duodenum,
There are certain CT findings that can help differenti- stomach, and esophagus may be similarly affected [1-3].
ate granulomatous from ulcerative colitis. Mural stratifi- During the acute, non-cicatrizing phase of Crohn’s dis-
cation, i.e., the ability to visualize individual layers of ease, the small bowel and colon maintain mural stratifi-
bowel wall, is seen in 61% of patients with chronic ul- cation and often have a target or double-halo appearance.
cerative colitis but only in 8% of patients with chronic As in ulcerative colitis, there is a soft-tissue density ring
granulomatous colitis. Also, mean colon wall thickness in (corresponding to mucosa), which is surrounded by a
chronic ulcerative colitis is 7.8 mm, significantly less low-density ring with an attenuation near that of water or
than that observed in Crohn’s colitis (11 mm). Finally, the fat (corresponding to submucosal edema or fat infiltra-
outer contour of the thickened colonic wall is smooth and tion, respectively), which in turn is surrounded by a high-
regular in 95% of ulcerative colitis patients while serosal er density ring (muscularis propria). Inflamed mucosa
and outer mural irregularities are present in 80% of pa- and serosa may show significant contrast enhancement
tients with granulomatous colitis [1-3]. following bolus intravenous contrast administration, and
Rectal narrowing and widening of the presacral space the intensity of enhancement correlates with the clinical
are hallmarks of chronic ulcerative colitis. CT depicts the activity of the disease [1-3].
anatomical alterations that underlie these rather dramatic CT demonstration of mural stratification, i.e., the abil-
morphological changes. The rectal lumen is narrowed ity to visualize distinct mucosal, submucosal, and mus-
due to the previously described mural thickening that at- cularis propria layers, indicates that transmural fibrosis
tends chronic ulcerative colitis. As a result, the rectum has not occurred and that medical therapy may be suc-
has a target appearance on axial scans, which should not cessful in ameliorating lumen compromise. Additionally,
be mistaken for the external anal sphincter, mucosal pro- prior to the onset of fibrosis, the edema and inflammation
lapse, or the levator ani muscles. The increase in the pre- of the bowel wall responsible for mural thickening and lu-
sacral space is caused by proliferation of the perirectal men obstruction are reversible to some extent. A modest
fat, which on CT is characterized by an increased num- decrease in wall thickness often produces a dramatic in-
ber of nodular and streaky soft-tissue densities and an ab- crease in lumen cross-sectional area as well as resolution
normal attenuation value, 10-20 HU higher than the nor- of the patient’s obstructive symptoms.
mal extraperitoneal or mesenteric fat. These fatty changes Loss of mural stratification is indicative of transmural
relate to a number of factors, including ex vacuo re- fibrosis [1-3]. In the background of long-standing
placement by fat of the void produced by rectal lumen Crohn’s disease, this is typically visualized on CT as ho-
narrowing and lipodystrophy resulting from an influx of mogeneous attenuation in the affected bowel wall. If this
inflammatory cells and edema. Edematous adipose tissue finding occurs against a background of good levels of
and enlarged lymph nodes are often observed in the intravascular contrast medium and thin-section recon-
perirectal region at the time of abdominoperineal resec- structions, then the fibrosis is most likely irreversible. In
tions in patients with chronic ulcerative colitis [1-3]. these patients, anti-inflammatory agents may not provide
a significant reduction in bowel wall thickness. If these
segments become sufficiently narrow, surgery or stricturo-
Crohn’s Disease plasty will be necessary to relieve the obstruction.
In a patient with Crohn’s disease, the palpation of an ab-
Crohn’s disease most commonly affects the terminal dominal mass or the separation of bowel loops as seen on
ileum and proximal colon. The acute, active phase of a barium study evokes a large differential diagnosis: ab-
Crohn’s disease is characterized by focal inflammation, scess, phlegmon, “creeping fat” or fibrofatty proliferation
Imaging of the Colon and Rectum: Inflammatory and Infectious Diseases 39
of the mesentery, bowel wall thickening, and enlarged

mesenteric lymph nodes. Each of these disorders has sig-
nificantly different prognostic and therapeutic implications.
This diagnostic dilemma is further complicated by the fact
that many of these patients are receiving immunosuppres-
sive therapy, which can mask other signs and symptoms.
CT can readily differentiate the extraluminal manifes-
tations of Crohn’s disease. Fibrofatty proliferation, also
known as “creeping fat” of the mesentery, is the most
common cause of bowel-loop separation seen on barium
studies in patients with Crohn’s disease. On CT, the sharp
interface between bowel and mesentery is lost and the at-
tenuation value of the fat is elevated by 20-60 HU due to
the influx of inflammatory cells and fluid. Mesenteric
adenopathy, with lymph nodes ranging in size between
3 and 8 mm, may also be present. If these lymph nodes
are larger than 1 cm, the presence of lymphoma or carci-
noma, both of which occur with greater frequency in
Crohn’s disease, must be excluded [1-3].
Contrast-enhanced CT scans often show hypervascu-
larity of the involved mesentery, manifesting as vascular
dilatation, tortuosity, prominence, and wide spacing of
the vasa recta. These distinctive vascular changes have Fig. 2. Acute Crohn’s colitis. Sagittal reformatted image from a CT
been called the “comb sign” and its identification should enterography study reveals marked mural thickening of the de-
scending colon with markedly prominent vasa rectae
suggest active disease. In addition, it may be useful in dif-
ferentiating Crohn’s disease from lymphoma or metas-
tases, which tend to be hypovascular lesions.
With the advent of novel biological therapeutic agents mulative radiation dose of multiple CT examinations is
such as infliximab, CT enterography has become an im- substantial [6]. Accordingly, accurate technique without
portant technique for evaluating small bowel disease ac- ionizing radiation is preferable. For small bowel imaging
tivity in patients with Crohn’s disease, because of its ac- in IBD, there is a considerable body of evidence showing
curacy and non-invasive nature. Since colonic involve- the comparable accuracy of US, CT, scintigraphy, and
ment is common in patients with inflammatory bowel dis- MRI [4]. The lack of ionizing radiation exposure thus fa-
ease (IBD), the capability of CT enterography in evaluat- vors the use of either US or MRI (Fig. 3). US gives real-
ing colorectal involvement (Fig. 2) is being intensively time information on peristalsis in addition to the mor-
studied, and the preliminary results are encouraging [5]. phological features. While contrast-enhanced US corre-
Since patients with Crohn’s disease are often young lates well with colonoscopic disease activity [7, 8], this
and typically will require multiple examinations, the cu- technique is operator-dependent. The major advantages
a b
Fig. 3 a, b. Acute Crohn’s colitis of the descending colon shows a thickened de-
scending colon at (a) ultrasound and (b) MR enterography (coronal T2-weight-
ed turbo spin-echo). The arrow indicates the thickened descending colon
of MRI over US are its unlimited field of view and good

reproducibility; however, its lack of availability and high
cost may be prohibitive.
Optical colonoscopy can directly visualize the colon,
but the impetus for cross-sectional imaging studies of the
colon in patients with IBD has lagged behind imaging
evaluation of the small bowel. Indeed, there is a large body
of data concerning MR enterography and MR enteroclysis,
but very few studies have evaluated colonic disease [9, 10].
In MR evaluations of the colon, lumen distention is
mandatory [11, 12] to achieve optimal imaging results.
However, the experience with dedicated examinations of
the colon in IBD is limited and conflicting [13]. While
use of the bright lumen technique is preferred, in a series
of 15 healthy volunteers and 23 patients with known IBD
dark lumen MR colonography resulted in high sensitivi-
ty (87%) for identifying segmental IBD changes [14].
However, no biopsies were obtained of endoscopically Fig. 4. Pseudomembranous colitis. Coronal reformatted CT image
normal mucosa, which might have influenced the results. shows marked mural thickening and submucosal edema of the dis-
Several studies have evaluated the efficacy of MRI in tal colon. Note the ascites
determining small bowel disease activity in Crohn’s dis-
ease, with bowel wall thickening and bowel wall en-
hancement employed as markers of disease activity. Al- CT shows a pancolitis with mural thickening that may
though severe disease activity is well depicted, limited be irregular or polypoid and characterized by a shaggy
disease activity and non-active disease are less reliably endoluminal contour. The thickened wall (Fig. 4), which
demonstrated [15]. is usually 1.6-1.8 cm, is a result of submucosal edema.
Data regarding the assessment of colonic disease activ- Mucosal and serosal enhancement is seen following in-
ity are sparse and partly conflicting. In one study, increased travenous contrast administration. The haustra are also
contrast enhancement of the bowel wall was significantly thickened and edematous, producing the “accordion pat-
related to colonoscopically active disease in patients with tern” highly suggestive of pseudomembranous colitis.
IBD [16]. In another series, combining increased contrast This pattern, which is the result of contrast trapped be-
enhancement of the bowel wall with other MRI features tween thickened haustral folds aligned in a parallel fash-
(bowel wall thickening, presence of mesenteric lymph ion, can sometimes simulate deep ulcerations or fissures.
nodes, loss of the normal haustral pattern), the sensitivity Pericolic stranding, ascites, pleural effusions, and sub-
was poor (32%) but the specificity was good (88%) [17]. cutaneous edema are other ancillary CT findings. Com-
The combination of MR enterography with a water-based plications of untreated pseudomembranous colitis in-
enema seems to be a valuable approach to assess disease clude toxic megacolon and intestinal perforation with
activity in patients with established Crohn’s disease [18]. subsequent peritonitis. CT is also useful in monitoring
Data comparing MRI with other techniques are sparse, nor the response to medical therapy with oral vancomycin
is it possible to recommend the routine use of water-based and metronidazole [20, 21].
enema or other colon distention techniques for evaluating
the colon in patients with IBD.
AIDS-Related Colitis
Pseudomembranous Colitis Cytomegalovirus and cryptosporidiosis are common
pathogens seen in patients with acquired immunodefi-
Pseudomembranous colitis is being encountered with in- ciency syndrome (AIDS). Patients with CD4 lymphocyte
creasing frequency as a nosocomial infection complicating counts of ≤200 mm–3 are at greatest risk for these infec-
antibiotic therapy [19]. This potentially life-threatening dis- tions. Typically, the cecum and proximal ascending colon
order is caused by overgrowth of Clostridium difficile. The are involved by these organisms; however, a pancolitis
bacteria release a cytotoxic enterotoxin that causes ulcera- with continuous lesions may occur as well. CT shows
tion of the colonic mucosa and the formation of 2-3 mm mural thickening of the involved segments of colon, with
pseudomembranes consisting of fibrin, mucus, sloughed low attenuation in the region of the submucosa due to ede-
epithelial cells, and leukocytes. Mild cases may demon- ma as well as pericolonic fluid and stranding of the adja-
strate only mucosal irregularity and nodularity, with the for- cent fat. Pneumatosis and ascites have also been described
mation of small plaques that cannot be detected radiologi- [21]. AIDS-related colitis is being encountered with de-
cally whereas in advanced cases there is thickening of the creasing incidence in industrialized countries due to the
haustral folds, a shaggy wall contour, and mucosal plaques. efficacy of highly active anti-retroviral therapy (HAART).
Typhlitis involvement, and the presence or absence of small bow-

el disease, abscess, fistula, and fibrofatty mesenteric
Typhlitis (neutropenic colitis) is a potentially fatal in- proliferation.
fection of the cecum and ascending colon caused by en- Idiopathic IBD must also be differentiated from the in-
teric pathogens in patients with severe immunosuppres- fectious colitides. Although there is considerable overlap in
sion. It is most frequently seen in patients with acute the CT findings of these disorders, there are certain differ-
leukemia receiving chemotherapy but also occurs in the entiating features [24]. For example, the presence of ascites
setting of AIDS, aplastic anemia, multiple myeloma, is more suggestive of an acute rather than a chronic cause
and bone marrow transplantation. Bacteria, viruses, and of colonic inflammation. Peritoneal fluid is commonly
fungi penetrate the damaged cecal mucosa and are able found in the acute colitides, particularly pseudomembra-
to proliferate due to the profound neutropenia. Edema nous, infectious, and ischemic colitis, but not in chronic
and inflammation involve the cecum, ascending colon, IBD. Ascites is only infrequently seen in patients with
and, occasionally, the ileum. Fever, abdominal pain, acute IBD. Submucosal fat deposition, seen on CT, is pri-
nausea, and diarrhea are presenting symptoms. Prompt marily found in the subacute and chromic colitides, usual-
diagnosis and supportive therapy with intensive anti- ly ulcerative colitis, but not in acute disease.
biotics and fluids are required to prevent transmural
necrosis and perforation. Surgical resection is indicated
in patients with transmural necrosis, intramural perfora- Appendicitis
tion, abscess, or uncontrolled sepsis and gastrointestinal
hemorrhage. Acute appendicitis is the most common abdominal surgi-
cal emergency, affecting 250,000 individuals in the USA
Due to the inherent risks in these critically ill patients
annually. The lifetime risk of developing acute appen-
of bowel perforation during barium enema administration
dicitis is 8.6% for men and 6.7% for women. Radiologists
and colonoscopies, CT is the study of choice in typhlitis.
play a critical role in evaluating patients with suspected
CT demonstrates circumferential mural thickening
appendicitis and in minimizing its complications by con-
(1-3 cm) of the cecum, low-density areas within the colonic
firming or excluding the diagnosis in atypical cases. They
wall secondary to edema, pericolonic inflammation and also can reduce the number of misdiagnoses and negative
fluid, and, in severe cases, pneumatosis. Clinically, CT is laparotomies, provide a correct alternate diagnosis, and
used to monitor the decrease in mural thickness with manage appendiceal abscesses and postoperative compli-
therapy and to detect subtle pneumoperitoneum in cases cations. For example, one study reported a drop in the
of silent perforation or necrosis [22, 23]. negative appendectomy rate from 24 to 3% after the
widespread use of CT [25].
Of the cross-sectional imaging tests, CT has been the
Graft-Versus-Host Disease most extensively studied in terms of accuracy, impact on
patient management, length of hospital stay, and cost sav-
Colonic complications of graft-versus-host disease ings. Contrast-enhanced helical CT has a sensitivity,
(GVHD) are common. In this disorder, mature donor specificity, and accuracy of >95% in the diagnosis of
lymphocytes attack recipient tissue in bone marrow trans- acute appendicitis [26-28]. US, when carried out with the
plantation patients. Acute GVHD may manifest with pro- graded compression technique, has been shown to be a
fuse diarrhea, nausea, vomiting, intestinal hemorrhage, valuable approach as well (Fig. 5) [29], although head-to-
and cramping abdominal pain. Transmural inflammation head comparative studies show that CT has a significant
is common but frank perforation is unusual. higher accuracy than US [30].
Initially, CT shows diffuse mural thickening of the On CT, the abnormal appendix presents as a slightly
colon with submucosal edema and increased intraluminal distended, fluid-filled (Fig. 6) or collapsed structure ap-
secretions. In chronic GVHD, submucosal fat may be proximately 0.5-2 cm in diameter. The fluid level within
rapidly deposited and is readily identified on CT [20]. the lumen is >2.6 mm [31]. As a result of the inflamma-
tory hyperemia, the wall of the diseased appendix shows
hyperenhancement during the arterial phase of contrast
Differential Diagnosis of the Colitides administration. The wall is circumferentially and asym-
metrically thickened (usually 1-3 mm). Periappendiceal
The differentiation of granulomatous colitis and ulcera- inflammation, the hallmark of appendicitis, is character-
tive colitis is important in terms of medical management, ized by increased hazy density or linear fat stranding in
surgical options, and prognosis. This distinction can usu- the adjacent mesoappendix, by fluid-containing abscesses,
ally be made on the basis of colonoscopy, with biopsy and by ill-defined, heterogeneous soft-tissue densities
histology, double-contrast barium enema, disease distri- representing a phlegmon [26-28]. There may be sec-
bution, and clinical course. CT can occasionally help ondary inflammatory and edematous changes – with
distinguish these disorders by demonstrating differences thickening of the wall of the adjacent ileum and cecum –
in mural thickness, wall density, distribution of colonic that may mimic primary ileocolic inflammatory disease.
The combination of right lower quadrant inflammation,

phlegmon, and an abscess adjacent to the cecum is sug-
gestive but not diagnostic of appendicitis. Indeed, if an ab-
normal appendix or an appendicolith is not shown, the dif-
ferential diagnosis also must include Crohn’s disease, ce-
cal diverticulitis, ileal diverticulitis, perforated cecal or ap-
pendiceal carcinoma, and pelvic inflammatory disease.
Abscesses may be found in locations distant from the
cecum because of the length and position of the appendix
and the patterns of fluid migration in the peritoneal cavity.
It should be noted that (depending on referral patterns)
the majority (60-70%) of patients with suspected appen-
dicitis who are referred for cross-sectional imaging do
not have this disease. Instead, most of these patients have
benign, self-limited gastrointestinal disorders such as vi-
ral gastroenteritis. CT and US often can suggest a spe-
Fig. 5 Acute appendicitis. Ultrasound shows a thickened, fluid- cific alternate diagnosis [26-28]. Adnexal cysts, masses,
filled appendix, surrounding infiltration and free fluid salpingitis, and tubo-ovarian abscesses are readily shown
on US. Ureteral calculi and pyelonephritis can be detect-
ed on CT and US. Enlarged lymph nodes in the right low-
er quadrant suggest mesenteric adenitis or infectious
ileitis; mural thickening of the terminal ileum can be seen
in Crohn’s disease or infectious ileitis.
Although CT has a higher accuracy than US, the latter
technique can be used initially, to reduce radiation expo-
sure. Only those patients with a negative or inconclusive
examination should proceed to CT [34]. Another approach
is to use MRI instead of CT, which combines the benefits
of a lack of ionizing radiation exposure with high-contrast
resolution cross-sectional imaging [35, 36]. Initial reports
on MRI in diagnosing acute appendicitis are encouraging,
particularly concerning pregnant women (Fig. 7) [37, 38].
Fig. 6. Acute appendicitis. Coronal reformatted CT image shows a

thickened, fluid-filled appendix (arrow) along the lateral aspect of
the right psoas muscle
CT after intravenous contrast medium administration

is the preferred technique, as it facilitates identification
of the inflamed appendix and suggests alternative diag-
noses. In patients with (imminent) renal insufficiency, a
non-contrast CT can be performed. The diagnosis of
acute appendicitis on non-contrast CT scans requires the
detection of a thickened appendix (diameter >6 mm) with
associated inflammatory changes in the periappendiceal
fat or abnormal thickening of the right lateroconal fascia,
with or without a calcified appendicolith.
The addition of coronal and sagittal reformatted im-
ages increases diagnostic confidence by virtue of the Fig. 7. Acute appendicitis. Coronal HASTE (half-Fourier acquisi-
more reliable demonstration of the entire appendix, sur- tion single-shot turbo spin-echo) in a 28-year-old woman at
rounding fat and lymph nodes, and periappendiceal in- 18 weeks gestation, clinically suspected of having appendicitis but
in whom ultrasound was non-diagnostic. MRI shows a thickened
fection and inflammation [32]. Confidence in image in- retrocecal appendix (arrow) with increased signal intensity and
terpretation also improves with the use of thinner recon- minimal infiltration of the surrounding fat. The MRI diagnosis of
struction sections [33]. appendicitis was confirmed at surgery
Scan times are short, namely 10-15 min. At present, how- crease in the density of the fat adjacent to the involved
ever, MRI is not widely used in the Emergency Depart- colon or as fine linear stranding with small fluid col-
ment for the diagnostic work-up of patients with acute ab- lections or bubbles of extraluminal air. In sigmoid di-
dominal pain, due to a lack of availability and expertise verticulitis, the fluid is typically decompressed into the
and the uncertainly as to its cost-effectiveness. Further inferior interfascial plane. Due to the hypervascularity
studies should be directed at better defining the role of of the inflamed area, contrast-enhanced CT scans often
MRI in acute abdominal pain, especially its role compared reveal engorged mesenteric vessels in the involved peri-
to US and CT. Nonetheless, in pregnant women with an colic fat. Pericolic heterogeneous soft-tissue densities
inconclusive US, MRI is currently the preferred imaging representing phlegmons and partially loculated fluid
technique. collections indicating abscess are seen in more severe
cases. The abscess cavities usually contain air bubbles
or air-fluid levels. They develop within the sigmoid
Diverticulitis mesocolon or are sealed off by the sigmoid colon and
adjacent small bowel loops. Less commonly, they may
It is estimated that 10-25% of individuals with diverticu- form in the groin, flank, thigh, psoas muscle, sub-
losis will suffer from episodes of peridiverticular inflam- phrenic space, or liver [40].
mation during their lifetime. In the USA, this complica- On CT, diverticula are seen at the site of perforation
tion accounts for approximately 200,000 hospitalizations or adjacent to it in about 80% of cases. They appear as
and a health-care expenditure of four billion dollars an- small outpouchings of air, contrast, or fecal material
nually. Among the patients who are hospitalized, 10-20% projecting through the colonic wall. Symmetrical mural
require emergency surgery [39]. Clinical signs indicative thickening of the involved colon of approximately
of diverticulitis are inaccurate, although the combination 4-10 mm is found in about 70% of cases; however, if
of direct tenderness only in the left lower quadrant, the there is marked muscular hypertrophy, the wall of the
absence of vomiting, and an elevated C-reactive protein colon can measure up to 2-3 cm in thickness. CT can
level is suggestive in 25% of these patients (Laméris et also demonstrate intramural abscesses and fistula, and
al., personal communication). is helpful in patients with suspected colovesical fistu-
Inflammatory change in the pericolic fat (Fig. 8) is las. In the latter case, a pericolic inflammatory mass
the hallmark of diverticulitis on CT and is seen in 98% involves the bladder wall; the presence of intraluminal
of patients with the disease. The extent of the inflam- gas confirms the diagnosis.
matory reaction is related to the size of the perforation, CT has a reported sensitivity of up to 98% in the di-
degree of bacterial contamination, and the host re- agnosis of diverticulitis [40]. Additionally, it can demon-
sponse. Mild cases may manifest as areas of slight in- strate disease extent, such as abscess and peritonitis re-
mote from the colon, and can guide percutaneous abscess
drainage. The diagnosis of other pathological conditions
that may clinically simulate diverticulitis can also be
achieved with CT.
Although the accuracy of US in most prospective
studies is not inferior to that of CT [41], it has its limi-
tations and a recent large cohort study demonstrated the
superiority of CT. Moreover, CT is more accurate in in-
dicating alternative diagnoses [41] and provides a better
overview of disease extent, which is important for clini-
cal management (Hinchey classification). An initial
study demonstrated that MRI is also accurate in diag-
nosing diverticulitis [42], but further studies are needed
to evaluate its role. The major advantage of MRI in
middle-aged patients with diverticulitis is avoidance of
intravenous contrast medium and thus of contrast-
induced nephropathy.
Epiploic Appendagitis
Primary epiploic appendagitis is a relatively uncommon
condition that results from acute ischemia and inflamma-
Fig. 8. Acute diverticulitis. Coronal reformatted CT image shows tion of the appendices epiploicae. This disorder is often
mural thickening of the sigmoid colon, inflammatory changes, and associated with torsion and infarction of these appendices
a gas bubble (arrow) in the sigmoid mesocolon and can simulate diverticulitis if it occurs in the sigmoid
diagnostic accuracy of clinical evaluation (from 70 to

83%) and resulted in changes in management in 22% of
patients [47-49]. CT has a significant impact on the di-
agnosis, as shown in one series in which the accuracy im-
proved from 71% in the pre-CT clinical diagnosis to 93%
in the post-CT diagnosis, with a change in management
of 46% [50]. Also, the level of confidence increases sig-
nificantly with CT [51]. In two randomized controlled tri-
als from the same institution, CT was studied: (1) within
24 h versus routine workup by plain X-ray or (2) when
considered necessary, US, CT, or fluoroscopy and CT
within 1 h versus routine workup. The first study demon-
strated significantly fewer deaths (0 vs. 7; p=0.014) [52].
Length of hospital stay was not significantly different but
with CT there was a significant overstatement of serious
diagnoses. In the second study, routine CT significantly
improved diagnostic certainty, but there were no other
significant differences to routine workup in patient man-
agement [53]. The overall inter-observer agreement of
abdominal CT is good [54], and for specific urgent diag-
noses it is very good (e.g., for appendicitis, diverticulitis,
Fig. 9. Epiploic appendagitis at the junction of the descending colon
and sigmoid colon. A fatty density mass is surrounded by increased and bowel obstruction the values are 0.84, 0.90, and 0.81,
attenuation. Thrombosed vessels (arrow) can be seen in the central respectively).
portion of the epiploic appendage A cohort study evaluated 11 diagnostic strategies of
clinical diagnosis, plain radiography (supine abdominal
X-ray and upright chest X-ray), US, and CT in 1021 pa-
tients with acute abdominal pain [34]. Clinical diagnosis
and appendicitis if located in the proximal colon. A char- (performed by surgical residents) had a sensitivity of
acteristic appearance of a small, round, or oval fat- 88% and a specificity of 41% for urgent diagnoses. Plain
containing mass with an associated inflammatory reac- radiography did not contribute to a higher sensitivity or
tion of the pericolic fat is seen on US and CT (Fig. 9) specificity for urgent cases of acute abdominal pain. Re-
[43]. The thrombosed vessels within the affected garding the clinical diagnosis, US reduced the number of
appendage epiploica can sometimes be visualized. false-positive urgent diagnoses to 85%, but at the ex-
Epiploic appendagitis is a self-limited process with clin- pense of a lower sensitivity (70%, thus missing 30% of
ical resolution in a few days. Follow-up CT examination the urgent conditions). CT had the highest sensitivity
may show total resolution, shrinkage, and eventual calcifi- (89%) and specificity (77%) as a single imaging strate-
cation of the inflamed and infarcted epiploic appendix. gy. The best strategy for the detection of urgent diag-
noses was an initial US, reserving CT for patients with
negative or inconclusive US examinations [34]. This
Acute Abdominal Pain strategy led to a sensitivity for urgent diagnosis of 94%.
Initial US reduced CT use and associated radiation bur-
Inflammatory conditions of the colon are the most fre- den by 51% compared to CT in all patients. Strategies
quent causes of acute abdominal pain requiring urgent driven by body mass index, age, or location of the pain
treatment (e.g., appendicitis, diverticulitis). In the major- had a lower sensitivity for urgent diagnoses than
ity of patients with acute abdominal pain, the clinical di- achieved with this conditional strategy. The use of MRI
agnosis is unclear or incorrect such that imaging is in acute abdominal pain primarily has been studied in
mandatory [44]. In this setting, imaging tests give differ- acute appendicitis and diverticulitis [36].
ent results when used in a setting of a specific disease
(e.g., acute appendicitis) than when referring to all pa-
tients with acute abdominal pain (a myriad of diagnoses). Perianal Fistulas
Thus, papers reporting on a specific diagnosis are less in-
formative than those relatively scarce papers reporting on Perianal fistulas mostly occur either as the result of fis-
patients with acute abdominal pain in general. Plain ab- tulous disease originating from the anal glands near the
dominal radiographs have a low accuracy in this setting anal crypts (cryptoglandular hypothesis) or in patients
and result in management changes in only 4% of the pa- with Crohn’s disease [55]. Infection of the anal glands
tients [45, 46]. may result in abscess formation. This is a relatively com-
In the majority of patients, further imaging is warrant- mon condition, with a prevalence of approximately
ed after plain radiography. US was shown to increase the 0.01%, predominantly affecting young adults. The course
of the fistula track may be simple and superficial or com- to assess. Digital palpation frequently cannot distinguish
plicated. The latter may be intersphincteric (through the between scarring due to repeated surgery and induration
internal anal sphincter and then downward through the due to an underlying extension.
intersphincteric space) or trans-sphincteric (transversing EUS, which can be enhanced by hydrogen peroxide in-
not only the internal sphincter but also the external stillation within the track, may be used to determine disease
sphincter or puborectis muscle) or have a supralevator ex- extent. Although initial reports were encouraging, later
tent or an extrasphincteric extension to the rectum, with- studies have been less sanguine especially when EUS was
out involvement of the anal sphincter. These complicated compared to MRI. This discrepancy probably relates to
tracks need detailed imaging for proper therapy, as inad- operator expertise since EUS is highly operator-dependent.
equate treatment may lead to recurrent disease. The sur- Insufficient penetration beyond the external sphincter,
geon must be aware both of the presence and number of especially with high-frequency transducers, limits the abil-
tracks and of their extent, the location of the internal ity of EUS to resolve ischioanal and supralevator sepsis,
opening, and the presence of abscesses. with the result that it may miss extensions from the prima-
Pre-operative evaluation of perianal fistulas may in- ry tract. This technique is impressive in demonstrating the
clude physical examination, examination under anesthe- internal opening whereas infection is distinguished only
sia (EUA), endoscopic ultrasound (EUS), or MRI. Phys- with difficulty from postoperative fibrosis; however, hydro-
ical examination has significant shortcomings, especially gen peroxide instillation facilitates this differentiation. Low
in patients with recurrent disease. While EUA can be simple tracks presumably can be identified by EUS as
used for determining disease extent, immediately fol- accurately as by MRI, but the latter is definitely superior in
lowed by treatment, it has limitations and disadvantages, cases involving complex or high tracks [56].
mostly related to probing. Firstly, not all fistulas have an MRI has been proven to provide the most compre-
external opening that can be probed, and probing may hensive assessment of patients with perianal fistulas, fa-
miss secondary tracks. It is well-recognized that missed cilitating accurate identification of tracks and exten-
extensions are the commonest cause of recurrence, which sions as well as abscesses. MRI examination for peri-
reaches 25% in some series. Forceful probing may lead anal fistulas should include T2-weighted sequences in
to perforation of the levator plate, worsening the extent of multiple planes, a fat-saturation sequence, and a contrast-
the disease. Patients with recurrent disease are most like- enhanced (fat-saturation) T1-weighted sequence [57].
ly to harbor missed disease but are also the most difficult Tracks (Figs. 10, 11) are identified on T2 as hyper-
a b
Fig. 10 a, b. Crohn’s disease and perianal fistu-

las. a Axial T2-weighted turbo spin-echo
demonstrates multiple tracks (arrowheads),
intersphincteric and outside the anal sphinc-
ter. On the right, an abscess (A) is seen in the
ischioanal space. b Coronal T2-weighted tur-
bo spin-echo demonstrates a trans-sphincteric
track in the ischioanal space (arrowhead) and
extension of the abscess (A) in the levator ani
at both sides and in the rectal wall (arrow)
a b
Fig. 11 a, b. Cryptoglandular perianal fistula.

a Coronal T2-weighted turbo spin-echo with
endoanal coil shows a fibrous track (arrow-
head) extending through the left external
sphincter. Normal sphincter anatomy is seen
on the right. E External sphincter, I internal
sphincter, PR puborectal muscle, LA levator
ani plate. b Axial T2-weighted turbo spin-
echo demonstrates the hyperintense track
(arrow), surrounded by fibrous tissue (arrow-
head), along the left external sphincter (E)
intense longitudinal structures, often with a hypointense, 2. Markose G, Ng CS, Freeman AH (2003) The impact of helical
fibrous wall. Collateral inflammation is often appreciat- computed tomography on the diagnosis of unsuspected inflam-
matory bowel disease in the large bowel. Eur Radiol 13:107-113
ed on fat saturation sequences. After the administration 3. Furukawa A, Saotome T, Yamasaki M et al (2004) Cross-sec-
of intravenous contrast medium, the lining of the wall tional imaging in Crohn disease. Radiographics 24:689-702
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the center of the track or the track can be completely ry bowel disease diagnosed with US, MR, scintigraphy, and
obliterated by granulation tissue. In the latter case, there CT: Meta analysis of prospective studies. Radiology 247:64-79
5. Johnson KT, Hara AK, Johnson CD (2009) Evaluation of col-
is complete enhancement of the part of the track that is itis: usefulness of CT enterography technique. Emerg Radiol
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readily appreciated on fat saturation sequences, al- 6. Desmond AN, O’Regan K, Curran C et al (2008) Crohn’s dis-
though some small fluid collections may be more diffi- ease: factors associated with exposure to high levels of diag-
cult to identify. The use of external phased array coils nostic radiation. Gut 57:1524-1529
7. Ripolles T, Martinez MJ, Pardes JM et al (2009) Crohn dis-
may result in limitations in detecting superficial exten- ease: Correlation of findings at contrast-enhanced US with
sions and difficulty in locating the precise level of the severity at endoscopy. Radiology 253:241-248
internal opening. In such cases, endoluminal MRI may 8. Migaleddu V, Scanu AM, Quaia E et al (2009) Contrast-en-
provide more information (Fig. 11). hanced ultrasonographic evaluation of inflammatory activity
A prospective triple-blinded comparison of the accura- in Crohn’s disease. Gastroenterology 137:43-61
9. Ziech M, Stoker J (2010) MRI of the small bowel: enterogra-
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IDKD 2010-2013
CT Colonography: Updated
Daniel C. Johnson1, Michael Macari2
1 Department of Radiology, Mayo Clinic, Scottsdale, AZ, USA
2 Department of Radiology, New York University Langone School of Medicine, New York, NY, USA
Computed tomography (CT) colonography has been in ACRIN trial. Although some participants required more
development for more than a decade, with hundreds of training than others, all of them received a passing score
articles now published on its performance and technical of 90% for easy and moderately difficult to detect lesions
capabilities. With the conclusion and publication of the [6]. The ACRIN trial also insisted on strict adherence to
National CT Colonography trial [1] and endorsement of protocol requirements, including stool tagging regimens,
the technique for screening by a multi-society task force mechanical insufflation of the colon, and thin-section and
(including the American Cancer Society, American Col- low-dose CT techniques [7]. It is clear that meticulous at-
lege of Radiology, US Multi-society Task Force on Colo- tention to all aspects of the examination is required to
rectal Cancer) [2], the clinical validation of CT colono- achieve optimal results.
graphy in the prepared colon has been completed. This Extracolonic abnormalities are common in patients of
chapter highlights the most important current issues for screening age [8-11]. A pragmatic approach to these find-
CT colonography. ings is needed; for example, radiologists should recom-
Patient acceptance of routine colorectal screening, in- mend follow-up studies for those patients with findings
cluding CT colonography, remains a major barrier. In most likely to be of clinical significance. Patients (and
2000, only 43% of US adults age 50 or older had under- clinicians) will be grateful if additional testing is mini-
gone a sigmoidoscopy or colonoscopy within the previous mized; for those that need addition studies, the recom-
10 years or had used a fecal occult blood home test kit mended optimal follow-up should be included in the
within the preceding year [3]. The major disincentive for report.
patients considering CT colonography as a screening op- It is unfortunate that the risk associated with the low
tion is the laxative purgation (the same as that required for radiation dose required for CT colonography has been
colonoscopy) [4]. Advantages include the lack of required misunderstood. The standard dose at CT colonography is
sedation and intravenous line placement for CT colono- about half of the dose used for a standard body CT ex-
graphy, a quick return to work following the examination, amination. This results in an average dose of approxi-
and no need to inconvenience others for transportation to mately 5 mSv. The real risk of this exposure is unknown,
and from the exam. The risk of perforation at CT colono- but the Health Physics Society has stated that for doses
graphy is considerably less than at colonoscopy. Further- in this range the risks for the development of radiation-
more, the examination only requires two breath-holds on induced cancer are too small to measure or are non-
the CT scanner (in the supine and prone positions), with existent [12]. Even if a very small risk is assumed from
the completion of most average examinations in 10 min, radiation exposure at CT, it must be balanced against the
which may help reassure hesitant patients. Still, the reali- risk of developing colon cancer and of other alternative
ty of a full bowel preparation, an enema tip, and full (al- procedures. The risk of perforation (1:1000) and death
though brief) colonic insufflation is likely to delay the de- (1:17,000) at colonoscopy are real and can be measured
cision for screening for some people. [13], but as a society there is a consensus that these risks
The performance of CT colonography has undergone are outweighed by the risk of developing colon cancer
exhaustive testing. The Pickhardt trial demonstrated a (about 1 in 13 without screening) [14].
sensitivity similar to colonoscopy [5], but concerns were Maintaining high-quality interpretations is a responsi-
raised that community practices might not be able to bility that each individual, each practice, and our special-
achieve these results. The National CT Colonography tri- ty should assume. The American College of Radiology
al (ACRIN 6664) studied 2531 individuals nationally has established a national CT colonography database
across 15 centers, including academic and private prac- within the National Radiology Data Registry (NRDR)
tices. The findings of this trial were similar to those of [15]. Selected process and outcome metrics can be quick-
the Pickhardt trial and have reassured many groups [1]. ly entered on-line and compared to national benchmarks.
Radiologist’s training and testing were required for the These measures include process metrics related to the CT
CT Colonography: Updated 49
technique and the adequacy of patient preparation, and 2. Levin B, Lieberman DA, McFarland B et al (2008) Screening
outcome metrics related to colon perforation, true-posi- and surveillance for the early detection of colorectal cancer
and adenomatous polyps, 2008: a joint guideline from the
tive and false-positive rates for large (≥1 cm) polyps, and American Cancer Society, the US Multi-Society Task Force on
the prevalence of significant extracolonic findings. Prac- Colorectal Cancer, and the American College of Radiology.
tices seriously interested in providing the best care should Gastroenterology 134:1570-1595
be encouraged to participate in this data registry and 3. Colorectal (Colon) Cancer. http://cdcgov/cancer/colorectal/
manage their practice such that benchmark metrics are statistics/screening_rateshtm
4. Beebe TJ, Johnson CD, Stoner S et al (2007) Assessing atti-
achieved. tudes toward laxative preparation in colorectal cancer screen-
A spirit of cooperation between radiologists and gas- ing and effects on future testing: potential receptivity to com-
troenterologists is needed for optimal patient care. Guide- puted tomographic colonography. Mayo Clinic Proceedings
lines will need to be jointly developed for the proper use 82:666-671
of colonography and colonoscopy, and for processes to 5. Pickhardt PJ, Choi JR, Hwang I et al (2003) Computed tomo-
graphic virtual colonoscopy to screen for colorectal neoplasia
efficiently transfer patients with polyps to colonoscopy. in asymptomatic adults. New Eng J Med 349:2191-2200
Those practices that are able to do this effectively will of- 6. Fletcher JG, Johnson CD, Toledano A et al (2005) ACRIN
fer patients a service of high value – and will likely find 6664: Lessions for CT colonography (CTC) training and cer-
themselves very busy. tification. Radiological Society of North America Scientific
In summary, CT colonography has completed its clin- Assembly and Annual Meeting Program, Chicago, IL
7. Johnson CD, Chen MH, Toledano A et al. The National CT
ical validation and is now ready for widespread clinical Colonography Trial Protocol, ACRIN 6664. http://wwwacrinorg/
application. Radiologists committed to performing the Portals/0/Protocols/6664/Protocol-ACRIN%206664%20
examination to the highest quality must obtain the edu- Amendment%201,%207706pdf
cation and equipment needed. We must focus our efforts 8. Gluecker TM, Johnson CD, Wilson LA et al (2003) Extra-
colonic findings at CT colonography: evaluation of prevalence
on the best in patient care, and ignore the political dis- and cost in a screening population. Gastroenterology 124:911-
tractions that will come. We have an obligation to educate 916
referring physicians on the correct use of the technique. 9. Hara AK, Johnson CD, MacCarty RL, Welch TJ (2000) Inci-
Collaborations with gastroenterologists to ensure same- dental extracolonic findings at CT colonography. Radiology
day polypectomy for selected patient will enhance patient 215:353-357
10. Hellstrom M, Svensson MH, Lasson A (2004) Extracolonic
care. Extracolonic findings must be vigilantly and prop- and incidental findings on CT colonography (virtual
erly reported so that only those patients with highly sig- colonoscopy). AJR Am J Roentgenol 182:631-638
nificant lesions are recommended for additional follow- 11. Rajapaksa RC, Macari M, Bini EJ (2004) Prevalence and im-
up testing. Lastly, we should be committed to ongoing pact of extracolonic findings in patients undergoing CT
quality measures to both improve and maintain the high- colonography. Journal of Clin Gastroenterol 38:767-771
12. Radiation risk in perspective (2004) Position Statement of the
est standards of care. Radiology has another exciting op- Health Physics Society
portunity to serve the public, and to potentially help re- 13. Waye JD, Kahn O, Auerbach ME (1996) Complications of
duce the incidence of a common cancer killer. colonoscopy and flexible sigmoidoscopy. Gastrointest Endosc
Clin N Am 6:342-377
14. Lifetime Probability of Developing or Dying From Cancer.
References http://wwwcancerorg/docroot/CRI/content/CRI_2_6x_Life-
time_Probability_of_Developing_or_Dying_From_
1. Johnson CD, Chen MH, Toledano A et al (2008) Accuracy of Cancerasp?sitearea=&level=
CT colonography for detection of large adenomas and cancer. 15. National Radiology Data Registry. https://nrdracrorg/portal/
N Engl J Med 359:1207-1217 Nrdr/Main/pageaspx
IDKD 2010-2013
Imaging of Diffuse and Inflammatory Liver Diseases

Pablo R. Ros1, Rendon C. Nelson2
1 Department of Radiology, University Hospitals Health System, Case Western Reserve University, Cleveland, OH, USA
2 Department of Radiology, Duke University, Durham, NC, USA
Introduction siderable research has been devoted to the non-invasive

quantification of fibrosis using ultrasound (US) and mag-
The category of diffuse liver diseases includes a variety netic resonance imaging (MRI). Some of these techniques
of disorders that typically involve the liver in a non-focal use elastography, in which a mechanical impulse is used
fashion. It is important to note, however, that even with- to push or distort the liver followed by measurement of the
in this group there may be focal abnormalities, repre- amount of liver movement. A stiffer, more fibrotic liver
senting unusual expression of a disease that typically has will move less than a soft, less fibrotic liver.
a diffuse manifestation. At the same time there may be fo-
cal neoplasms, some of which are benign and others ma- Regenerative Nodules
lignant. With recent advances in cross sectional imaging,
the detection, characterization, and follow-up of diffuse Regenerative nodules are classified as micro-regenerative
liver disease has been greatly facilitated. or macro-regenerative. Micro-regenerative nodules mea-
This chapter is divided along the traditional classifica- sure <3 mm in diameter while macro-regenerative nod-
tion of cirrhosis, vascular disorders, congenital, metabol- ules are those ≥3 mm. Macro-regenerative but not micro-
ic and storage, and neoplastic diseases. In addition, dif- regenerative nodules are large enough to be visualized
fuse and focal inflammatory/infectious diseases are dis- with US, computed tomography (CT), or MRI. Further-
cussed. more, in 10-20% of patients (not 10-20% of regenerative
nodules), iron deposition occurs within the cytoplasm of
the regenerating hepatocytes, leading to the formation of
Fibrous Tissue Deposition (Cirrhosis) so-called siderotic nodules. This is in contradistinction to
transfusional hemosiderosis, in which excess iron is
Background phagocytized by the reticuloendothelial cells or Kuppffer
cells, not the hepatocytes. Although somewhat controver-
The preliminary events that lead to cirrhosis involve a sial, there is evidence that intracellular iron has a toxic ef-
mechanism of injury whereby there is repeated exposure fect that may increase the risk of hepatocellular carcino-
of some noxious agent to the liver, resulting in hepatocyte ma (HCC) development later in life. Since 7-10% of pa-
injury and/or death. Etiological noxious agents include al- tients with cirrhosis develop HCC and 10-20% of pa-
cohol, viral infection (specifically hepatitis B and hepati- tients with cirrhosis develop siderotic nodules, there may
tis C), non-alcoholic steatohepatitis, autoimmune disor- well be a correlation between the two entities.
ders (such as primary sclerosing cholangitis and primary
biliary cirrhosis), and toxic agents (such as aflatoxin and Confluent Hepatic Fibrosis
iron, specifically, primary hemochromatosis). Pathologi-
cally, the liver attempts to repair itself from the injury by The coalescence of fibrous tissue leads to the formation
regenerating hepatocytes and depositing collagen. With of a large fibrous scar in the liver; this is referred to as
repeated exposure to the noxious agent, there is ongoing confluent hepatic fibrosis. It typically occurs in the mid-
hepatocyte regeneration and collagen deposition, resulting dle of the liver, specifically, the anterior segment of the
in the formation of regenerative nodules and, eventually, right hepatic lobe (segments V and VIII) and the medial
the formation of fibrous scars, respectively. Note that fi- segments of the left hepatic lobe (segments IVa and IVb).
brous tissue deposition, specifically in the form of colla- The large fibrous scar emanates from the more central
gen, can be treated and is reversible to a point. However, portion of the liver and is associated with peripheral cap-
with more severe or profound degrees of collagen and fi- sular atrophy and retraction, which at times can be pro-
brous tissue deposition, this process is no longer re- found. The enhancement pattern of confluent hepatic fi-
versible and is henceforth referred to as cirrhosis. Con- brosis on CT is similar to that of fibrous tissue elsewhere;
Imaging of Diffuse and Inflammatory Liver Diseases 51
that is, the scar is usually hypoattenuating during the un- ing the ratio between the size of the caudate lobe and
enhanced state, hypo- to iso-enhancing during the late he- right hepatic lobe. The transverse measurement of the
patic arterial phase, hypo- to iso-enhancing during the caudate lobe medially to the bifurcation of the right por-
portal venous phase, and iso-to hyper-enhancing during tal vein, divided by the transverse dimension of the entire
the equilibrium phase (Fig. 1). The hyper-enhancement right hepatic and caudate lobes, shows low sensitivity but
phenomenon noted during the equilibrium phase occurs high specificity for cirrhosis when exceeding 0.60-0.65.
as a result of slow accumulation and then slow wash-out Nodularity of the capsular surface of the liver is also a
of contrast material within fibrous tissue. On MRI, the feature of cirrhosis. The appreciation of nodularity, how-
appearance of confluent hepatic fibrosis may be different ever, is related to the size of the regenerative nodules. With
than that of fibrous tissue elsewhere in the body, such as smaller regenerative nodules, as may occur in alcoholic
ligaments and tendons. Due to the high water content cirrhosis, it may be difficult to detect capsular nodularity.
within this fibrous scar, hepatic fibrosis is typically hypo- Among the disorders characterized by the development of
intense on T1-weighted images and hyper-intense on T2- large regenerative nodules, such as primary sclerosing
weighted images. Whereas the signal-intensity character- cholangitis, there may be deep nodularity. Furthermore,
istics parallel those of hepatic neoplasms, the location, well-defined clefts can be identified in the capsular sur-
shape, and capsular retraction aid in distinguishing the face, particularly on the gastric side of the lateral segment
two entities. Following Gd-chelate administration, the of the left hepatic lobe and the renal side of the posterior
scan reveals slow wash-in and slow wash-out, similar to segment of the right hepatic lobe. Lastly, there tends to be
the pattern obtained with iodinated agents on CT. prominence of the hepatic fissures, specifically, the gall-
bladder fossa and the fissure for the falciform ligament.
Hepatic Morphology in Cirrhosis
Portal Hypertension
The morphology and shape of the liver typically change
in patients as they develop progressive fibrosis. Although Signs of portal hypertension in patients with cirrhosis in-
there are variations from patient to patient and from dis- clude splenomegaly and/or porto-systemic shunts. A
ease to disease, the most typical pattern is atrophy of the spleen with a volume exceeding 250 mL or with a longi-
right hepatic lobe and hypertrophy of the left hepatic and tudinal dimension >12 cm or an anteroposterior dimen-
caudate lobes. As a result of right hepatic lobar atrophy, sion >9 cm is considered enlarged. In some patients with
there is a decrease in the angle of the gallbladder fossa splenomegaly, focal iron deposits can be appreciated
with the horizontal. Furthermore, caudate lobe hypertro- within the parenchyma of the spleen. These are seen on
phy can be quantified with US, CT, or MRI by measur- MRI as hypointense foci on either T1-weighted gradient
a b
Fig. 1 a-d. Confluent hepatic

fibrosis in a 55-year-old
man with cirrhosis. Axial
images through the liver
during the a unenhanced c d
state, b late hepatic arterial
phase, c portal venous
phase, and d equilibrium
phase. There is a wedge-
shaped area in the sup-
capsular portion of the me-
dial segment of the left he-
patic lobe that demonstrates
hypoattenuation pre-con-
trast and slow wash-in and
slow wash-out post-con-
trast. There is also associat-
ed capsular retraction
52 Pablo R. Ros, Rendon C. Nelson
echo or T2-weighted pulse sequences and are referred to Vascular Disorders

as Gamna-Gandy bodies.
Porto-systemic shunts can occur either intrahepatical- Arterial-Portal Shunts
ly or extrahepatically. Intrahepatic porto-systemic shunt-
ing is a result of high-pressure, low-volume arterial blood Although some arterial-portal shunts appear to arise spon-
that mixes at the level of the hepatic sinusoids with low- taneously, many of them are due to prior liver intervention,
pressure, high-volume venous blood. In the cirrhotic liv- such as a biopsy, or in the setting of cirrhosis, as noted
er, arterial flow is increased and portal venous flow is above. Furthermore, they are often associated with other
decreased, thereby increasing the prevalence of these vascular malformations, such as focal nodular hyperplasia
shunts. During the arterial phase of imaging, there is typ- and cavernous hemangiomas. On contrast-enhanced CT or
ically a parenchymal blush that is associated with early MRI, findings include a focal or wedge-shaped parenchy-
portal venous enhancement. mal blush, a large hepatic artery, early portal venous en-
Extrahepatic porto-systemic shunts are also seen in hancement, and a possible increase in the luminal diame-
the setting of cirrhosis. The most common is a sponta-
ter of the portal vein (Fig. 2). Most of these arterial portal
neous spleno-renal shunt whereby venous blood from the
shunts are subclinical and do not require intervention.
spleen is shunted to the left renal vein via the left inferi-
or adrenal vein. In this setting, a prominent collateral
vein is usually seen draining directly into an enlarged
Perfusion Abnormalities
left renal vein. Porto-systemic varices are also common
in patients with cirrhosis and portal hypertension. These Perfusion abnormalities are common following the ad-
include esophageal varices, splenic hilar varices, peri- ministration of contrast agents. They are seen as focal,
gastric varices, and peripancreatic varices. In some pa- often web-shaped, areas of hyperenhancement that are
tients, profound shunting of blood from the splenic vein most pronounced during the late hepatic arterial phase,
retrograde into the inferior mesenteric vein precludes the hence the term transient hyperattenuation defect
development of splenomegaly. (THAD) for CT and transient hyperintensity defect
(THID) for MRI. Although the etiology of these defects
Ancillary Findings in Cirrhosis is not always apparent, many of them are due to alter-
ations in portal venous flow. For example, they are
Other findings that often occur in the setting of cirrhosis often visualized in the setting of liver tumors (either
include ascites, mesenteric edema, and bowel wall ede- primary or metastatic) that block flow from a branch of
ma, particularly in the small bowel. Some of these the portal vein. They can also be seen when there are
changes are due to portal hypertension although they may aberrant veins draining directly into the liver, leaving
be exacerbated by hypoproteinemia. parenchyma that receives venous blood from the
a b
Fig. 2 a-d. Arterial-portal

shunt in a 49-year-old man
with hepatitis C. Axial im-
c d ages through the liver during
the late hepatic arterial
phase demonstrate a wedge-
shape area of focal paren-
chymal hyperenhancement
in the left hepatic lobe (a), a
large hepatic artery (b) as
well as early and vivid en-
hancement of a large peri-
umbilical collateral vein (c,
d). These findings are con-
sistent with an intrahepatic
arterial-portal shunt
aberrant source only and not from the portal vein. of the portal vein, they are uncommonly associated with
These perfusion abnormalities typically occur: portal vein thrombosis, either bland or malignant. On CT
a) in the subcapsular area; and MRI, occlusive malignant portal vein thrombosis typ-
b) in the periligamentous area (about both the fissure for the ically enlarges the portal vein, the luminal diameter of
falciform ligament and the ligamentus venosum), due to which may exceed 23 mm. Furthermore, the thrombus it-
aberrant internal mammary or periumbilical veins; self may enhance and this enhancement can be quite vivid
c) about the porta hepatis, due to aberrant gastric veins during the late hepatic arterial phase. With Doppler US,
(right more common than left); sampling of the thrombus itself reveals low-resistance arte-
d) about the gallbladder fossa, due to aberrant cholecys- rial wave forms that often flow in the hepatofugal direction.
tic veins. In patients with cirrhosis and HCC who are anticipating
On contrast-enhanced CT or MRI, they appear as tran- liver transplantation, it is important to determine whether
sient areas of hyperenhancement during the late hepatic portal vein thrombosis is bland or malignant. If the throm-
arterial phase and are often web-shaped and subcapsular. bosis is indeed malignant, the patient cannot be considered
There is usually not an appreciable abnormality in this a candidate for transplantation. The best way to confirm the
area on the unenhanced images or during the portal ve- diagnosis is to percutaneously biopsy the intraluminal
nous or equilibrium phases. thrombus itself under direct real-time US guidance.
Portal Vein Thrombosis Budd-Chiari Syndrome
In portal vein thrombosis, the thrombus can be either Budd-Chiari syndrome may occur when there is obstruc-
bland or malignant and either occlusive or non-occlu- tion to the outflow of blood from the hepatic veins. In
sive. Bland thrombosis typically occurs in the setting of Western countries, such as the USA, the majority of these
trauma, cirrhosis, following an orthotopic liver trans- cases (70%) are idiopathic. In the Orient, however, they
plant at the end-to-end anastomosis, in certain hyper- are commonly due to congenital webs that occur within
coagulable states, and in 25% of patients with Budd- the hepatic veins themselves. Other disorders that are as-
Chiari syndrome. If the thrombus is not occlusive, an sociated with Budd-Chiari syndrome include trauma,
eccentric intraluminal filling defect is identified, which pregnancy, certain hypercoagulable states, and malignant
often resolves with anti-coagulant therapy. In this case, hepatic vein thrombosis. The latter is commonly associ-
there is no cavernous transformation (Fig. 3). With oc- ated with primary tumors of the liver, right adrenal gland,
clusive portal vein thrombosis, however, the imaging and right kidney, specifically HCC, adrenal cortical car-
findings are different. Early on, the portal vein demon- cinoma, and renal cell carcinoma, respectively.
strates a non-enhancing intraluminal filling defect that Budd-Chiari syndrome can occur with occlusion of
may distend the vein and increase the luminal diameter. one, two, or all three hepatic veins or with occlusion of
Furthermore, there is often enhancement of the wall of the suprahepatic inferior vena cava. Furthermore, the
the vein via the vaso vasorum. Over time, typically in the imaging findings may differ depending upon whether the
range of 3-6 weeks, the thrombus undergoes retraction, disease is acute or chronic. With acute Budd-Chiari syn-
with the development of cavernous transformation, main- drome, there may be one or more intraluminal thrombi,
ly via collaterals that develop in the vaso vasorum itself. most commonly identified by Doppler US. With chronic
Malignant portal vein thrombosis typically occurs in pa- Budd-Chiari syndrome, however, the hepatic veins are
tients that have HCC, in the setting of either cirrhosis or, small and often difficult to identify, although tortuous
less commonly, non-cirrhosis. Interestingly, although intrahepatic collateral veins or shunts may be apparent. In
metastases to the liver commonly obstruct small branches this setting, shunts may develop from one hepatic vein
a b
Fig. 3 a, b. Non-occlusive
portal vein thrombosis in a
39-year-old woman with a
long history of taking birth
control pills. a Axial T2-
weighted and b post-con-
trast (late hepatic arterial
phase) images through the
liver demonstrate an eccen-
tric intraluminal defect in
the main portal vein
a b
Fig. 4 a-d. Axial images

through the liver during the
c d portal venous phase demon-
strate intense enhancement
of the central portion of the
liver and hypoenhancement
of the peripheral portion
(especially on a and b). The
hepatic veins are not visual-
ized. There is a cleft in the
medial aspect of both the
right and left hepatic lobes
(c, d) consistent with chron-
ic Budd-Chiari syndrome
and peripheral parenchymal
atrophy
that is obstructed to another hepatic vein that is not. may narrow the lumen of the intrahepatic inferior vena
Shunting can also occur from a hepatic vein that is ob- cava. Although this is not the cause of Budd-Chiari syn-
structed to the hepatic vein in the caudate lobe. Finally, drome, it certainly exacerbates the condition.
shunting may occur from a hepatic vein that is obstruc-
ted to the portal vein, one of the reasons why 25% of pa- Passive Hepatic Congestion
tients with Budd-Chiari syndrome develop portal vein
thrombosis. Furthermore, chronic occlusion of the hepat- Right-sided heart failure can result in the delayed
ic vein can result in significant enlargement of the cau- drainage of blood from the liver into the inferior vena ca-
date lobe and atrophy of the peripheral portion of the va and right atrium. Images through the lower chest typ-
right and left hepatic lobes. At times, large intrahepatic ically demonstrate either cardiac enlargement or a large
collateral veins can be seen shunting blood to the hepat- pericardial effusion, although in the setting of restrictive
ic vein in the caudate lobe. Furthermore, on T1-weighted pericarditis the heart may be normal in size. The key
MRI, the caudate lobe is often hyperintense. Following finding with right-sided congestive heart failure or pas-
contrast administration on either CT or MRI, there is of- sive hepatic congestion is enlarged and distended hepat-
ten differential enhancement of the central and peripher- ic veins and inferior vena cava. Secondary signs include
al portions of the liver (Fig. 4); that is, early on, the cen- reflux of contrast material from the superior vena cava in-
tral portion of the liver hyperenhances but the periphery to the hepatic veins, although this is occasionally seen in
does not. Later on, there is a flip-flop phenomenon in normal patients as well. In addition, there may be a mot-
which the central portion washes out and the peripheral tled enhancement pattern in the liver that is more pro-
portion accumulates contrast media. Over time, profound nounced peripherally and more apparent during the late
atrophy of the peripheral parenchyma can be seen. Pa- hepatic arterial phase. This pattern, referred to as the
tients commonly have and first clinically present with as- “nutmeg liver”, may not be apparent during the portal
cites, which develops shortly after hepatic vein occlusion. venous and/or equilibrium phases. Over time, the liver
In suprahepatic inferior vena caval obstruction, the he- can become fibrotic, at which point it may have all of the
patic vein in the caudate lobe cannot be used as a conduit manifestations of cirrhosis and portal hypertension.
to shunt blood from the hepatic veins to the inferior vena
cava. As a result, there is neither hypertrophy of the cau- Macro-regenerative Nodules
date lobe nor development of large intrahepatic collater-
al veins. It is important to note that, in the setting of In a small percentage of patients with outflow obstruction
Budd-Chiari syndrome, the liver is often swollen, which of the hepatic veins, large regenerative nodules develop
that tend to hyperenhance during the late hepatic arterial Metabolic and Storage Diseases
phase. These nodules have been associated with both
Budd-Chiari syndrome and passive hepatic congestion. Steatosis
They typically are iso-enhancing during the portal venous
and equilibrium phases and demonstrate only slow, peri- Hepatic steatosis results from a variety of abnormal
odic growth over time. processes, including the increased production or mobi-
lization of fatty acids (e.g., obesity, steroid use) or the de-
Hepatic Veno-occlusive Disease creased hepatic clearance of fatty acids due to hepatocel-
lular injury (e.g., alcoholic liver disease, viral hepatitis).
Hepatic veno-occlusive disease (VOD) typically occurs Histopathologically, the hallmark of all forms of fatty liv-
in bone marrow transplant recipients who have under- er is the accumulation of fat globules within hepatocytes.
gone total body irradiation. The definition of VOD is pro- The distribution of steatosis can be variable, ranging from
gressive non-thrombotic occlusion of the hepatic venules. focal, to regional, to diffuse. Diffuse steatosis is common
Although some reports have noted sporadic reversal or and estimated to occur in approximately 30% of obese
hepatofugal flow in the portal vein with VOD, there are patients. Patients with steatosis are usually asymptomatic
no reliable imaging findings for this diagnosis. As a re- although some may present with right upper quadrant
sult, VOD can only be reliably diagnosed by microscopic pain or abnormal liver function parameters.
examination of biopsy tissue. The histopathological findings of non-alcohol-related
liver steatosis, also known as non-alcoholic fatty liver
Peliosis Hepatis disease (NAFLD), vary from steatosis alone to steatosis
with inflammation, necrosis, and fibrosis. Non-alcoholic
Peliosis hepatis is a rare entity in which the hepatic sinu- steatohepatitis (NASH), with or without cirrhosis, is po-
soids throughout the liver dilate, resulting in numerous sitioned at the most severe end of the NAFLD spectrum.
blood-filled lacunar spaces ranging in size from 1 to 3 mm. The histopathological findings of NASH include steato-
Similar lacunar spaces can also occur in the spleen, lymph sis (predominately macrovesicular), mixed lobular in-
nodes, bone marrow, and lungs. Although the cause of flammation, and hepatocellular ballooning. Unlike
peliosis is poorly understood, it is believed to be due to steatosis alone, NASH may progress to cirrhosis.
outflow obstruction of the sinusoid. It typically occurs in Diffuse fatty change is easily identified on CT. The at-
patients who use anabolic steroids, corticosteroids, ta- tenuation value of normal liver is usually ~8 HU greater
moxifen, or birth control pills; following cardiac or renal than that of spleen on non-contrast CT images. In patients
transplantation; with chronic debilitating diseases, such as with fatty change, however, an abnormally decreased
tuberculosis, malignancy or AIDS; in association with di- density will be demonstrated, typically 10 and 25 HU less
abetes, sprue, or Hodgkin’s disease; or in patients exposed than the spleen on non-contrast and contrast-enhanced
to arsenic or polyvinyl chloride. Imaging shows numerous CT images, respectively. The diagnosis of hepatic steato-
small cystic lesions that demonstrate an enhancement pat- sis is more reliably made on non-contrast images. Un-
tern similar to that of the blood pool. doubtedly, the most sensitive technique to detect fatty
change of the liver is the use of in-phase and out-phase
Hepatic Infarction gradient echo MRI pulse sequences (Fig. 5).
Hepatic fatty change is, however, not always uniform
Parenchymal infarction in the liver is relatively uncom- but can instead present as a focal area of steatosis in an
mon for two reasons: otherwise normal liver (focal steatosis) or as subtotal fat-
1. the liver has a dual blood supply; ty change with sparing of certain areas (focal sparing).
2. the hepatocytes are relatively insensitive to hypoxia. On imaging, several features allow the correct identifica-
It has been seen, however, in patients with shock, sep- tion of focal fatty change or focal spared areas:
sis, eclampsia, sickle cell disease or trait, or arteritis; in 1. the typical periligamentous and periportal location;
those who have taken birth control pills; and in those who 2. lack of mass effect;
have suffered arterial embolic events such as those due to 3. sharply angulated boundaries of the involved area;
endocarditis, rheumatic heart disease, trauma, intra-arterial 4. non-spherical shape;
chemotherapy, or iatrogenic tumor embolization. With 5. absence of vascular displacement or distortion;
imaging, infarcted parenchyma may be hypoechoic on US: 6. lobar or segmental distribution.
anechoic bile lakes may be visualized as necrosis pro-
gresses. On contrast-enhanced CT, there is a wedge-shaped Iron Overload
subcapsular region of hypoenhancement that later on may
contain bile lakes and gas bubbles. On MRI, the edema of Iron overload states may arise from hemochromatosis,
infarction is typically hypointense on T1-weighted images with the preferential accumulation of iron within hepato-
and hyperintense on T2-weighted images; as with CT, cytes, or hemosiderosis, in which iron is deposited in
hypoenhancement and bile lakes are seen as well. Kupffer cells.
a b c
Fig. 5 a-c. Diffuse fatty liver in a 41-year-old female presenting with epigastric pain. a Axial CECT image demonstrates diffuse low attenu-
ation of the liver without displacement of the hepatic vessels. b In- and c out-of-phase T1-weighted images show significant signal drop
in the liver on the out-of-phase images
Primary Hemochromatosis thalassemia major, sideroblastic anemia, pyruvate kinase

deficiency, chronic liver disease), the excess iron is
Hereditary or primary hemochromatosis is an autosomal processed and accumulates in organs containing reticu-
recessive disorder of iron metabolism that is character- loendothelial cells, including liver, spleen, and bone
ized by the abnormal absorption of iron from the gut, marrow.
with subsequent excessive deposition of iron into hepato- Diffuse, increased attenuation of the liver and spleen is
cytes, pancreatic acinar cells, myocardium, joints, en- seen on CT (Fig. 6). On MRI, the extrahepatic signal in-
docrine glands, and skin. In addition, cells of the reticulo- tensity changes in the spleen and bone marrow allow pri-
endothelial system (RES) in patients with primary hemo- mary hemochromatosis to be distinguished from hemo-
chromatosis are abnormal and unable to store processed siderosis. Although, in general, the clinical significance of
iron effectively. Consequently, these patients do not transfusional iron overload states is negligible, patients
accumulate iron into the RES. The clinical findings of with chronic hemosiderosis can develop symptoms similar
cirrhosis and its complications (portal hypertension, to those of the primary form as well as cirrhosis and HCC.
development of HCC) predominate in patients with long-
lasting disease. Wilson’s Disease
On CT, excessive iron storage within hepatocytes will
result in an overall increased density. However, this CT Wilson’s disease, also known as hepatolenticular degen-
appearance of a hyperdense liver is non-specific, since eration, is a rare autosomal recessive abnormality of cop-
similar features can be seen with gold deposition and in per metabolism that is characterized by the accumulation
Wilson’s disease, type IV glycogen storage disease, and
following amiodarone administration. The use of non-
contrast CT in patients with suspected hemochromatosis
is important because excessive iron cannot be detected in
the setting of enhancing parenchyma.
MRI is far more specific than any other imaging
modality for the characterization of iron overload, due to
the magnetic susceptibility effect of iron. The superpara-
magnetic effect of accumulated iron in the hepatocytes
results in a significant reduction of signal intensity on
T2-weighted images. Comparison of the signal intensity
of liver with that of paraspinal muscles provides a useful
internal control. HCC, seen in 35% of patients with ad-
vanced hemochromatosis, is usually easily detected on
T1- and T2-weighted images due to the background of
decreased signal intensity of the liver.
Hemosiderosis
Fig. 6. Hemosiderosis in a 45-year-old female with long history of
In patients with hemosiderosis or siderosis, due to transfu- sickle cell anemia requiring multiple transfusions. Axial non-
sional iron overload states or dyserythropoiesis (e.g., enhanced CT image demonstrates increased attenuation of the liver
of toxic levels of copper in the brain, cornea (Kayser-

Fleischer rings), and liver, the latter due to impaired bil-
iary excretion. Hepatic deposition of copper, predomi-
nantly seen in periportal areas and along the hepatic si-
nusoids, evokes an inflammatory reaction resulting in
acute hepatitis with fatty change. Subsequently, chronic
hepatitis may result in liver fibrosis and, eventually,
macronodular cirrhosis.
Due to the high atomic number of copper, a hyper-
dense liver may be seen on unenhanced CT scans. How-
ever, this finding is not universally present; instead, usu-
ally only non-specific signs, such as hepatomegaly, fatty
change, and in advanced cases, cirrhosis, are observed.
During the early stage of the disease, and due to the para- Fig. 7. Diffuse metastatic breast cancer (pseudocirrhosis pattern) in
magnetism of ionic copper, MRI can be valuable as it a 43-year-old woman treated for metastatic breast cancer. Axial
demonstrates focal copper depositions, such as multiple contrast-enhanced CT image demonstrate several small low-density
nodular lesions, typically appearing hyperintense and lesions in the liver and a nodular contour of the liver due to hepatic
capsular retraction
hypointense on T1- and T2-weighted images, respectively.
Amyloidosis
Lymphoma
In amyloidosis, fibrils of protein-mucopolysaccharide
complexes are deposited throughout the body. The dis- Lymphoma can infiltrate the liver both primarily and sec-
ease is classified based on the biochemical composition ondarily. Primary lymphoma of the liver is extremely
of the amyloid fibrils. Primary amyloidosis is due to the rare. Conversely, the liver is often secondarily involved in
deposition of immunoglobin light chains and is associat- Hodgkin’s and in non-Hodgkin’s lymphoma. Typically,
ed with multiple myeloma and monoclonal gammopathy. the liver parenchyma is diffusely infiltrated with micro-
Secondary amyloidosis results from the deposition of scopic nests of neoplastic cells, without significant ar-
amyloid A protein and is associated with chronic infec- chitectural distortion. Consequently, lymphomatous in-
tion, rheumatoid arthritis, and malignancies. Exceeded volvement is difficult to detect by imaging alone. Asso-
only by the spleen and kidney, the liver is the third most ciated abnormalities, such as splenomegaly and lym-
common solid organ prone to amyloid deposition. phadenopathy, may narrow the differential diagnosis.
Hepatic amyloidosis has a non-specific imaging ap-
pearance, with the most common finding being diffuse
hepatomegaly. CT sporadically demonstrates focal areas Diffuse Infectious and Inflammatory Diseases
of low attenuation within the liver, corresponding to sites
of amyloid deposition (amyloid pseudotumor). Fungal Infections
Hepatosplenic fungal infection is a clinical manifestation of

Neoplastic Diseases disseminated fungal disease in patients with hematological
malignancies or compromise of the immune system. The
Metastatic Disease reported prevalence of fungal dissemination ranges from 20
to 40%. Most hepatic fungal microabscesses occur in
Neoplastic infiltration due to diffuse metastatic disease leukemia patients and are caused by Candida albicans.
can occur with many primary tumors. Melanoma, malig-
nant neuroendocrine tumors, pancreatic adenocarcinoma, Candidiasis
breast carcinoma, and colonic adenocarcinoma are some
of the more commonly encountered causes of diffuse he- Candida albicans in the liver may evoke little or no in-
patic metastatic disease. flammatory reaction, cause a superlative response, or oc-
The CT appearances of hepatic metastases depend on casionally produce granulomas. The typical histological
the vascularity of the lesions compared with the normal pattern of hepatic candidiasis is characterized by micro-
liver parenchyma. Diffuse metastatic involvement may abscesses, with the yeast or pseudohyphal forms of the
produce only subtle imaging findings and be detectable fungus in the center of the lesion and a surrounding area
only through indirect features, such as diffuse parenchy- of necrosis and polymorphonuclear infiltrate.
mal heterogeneity, vascular and architectural distortion, At contrast-enhanced CT, fungal microabscesses usu-
or alterations of the liver contour. The latter, particularly ally appear as multiple, round, discrete areas of low at-
seen in patients with treated breast cancer metastases, has tenuation, generally ranging in size from 2 to 20 mm
been described as the “pseudocirrhosis” sign (Fig. 7). (Fig. 8). These microabscesses usually enhance centrally
Hepatic contrast-enhanced CT may typically reveal

multiple, diffuse, small, low-density areas in both the liv-
er and spleen. MRI features of hepatic sarcoidosis are al-
so non-specific and include organomegaly, multiple le-
sions of low signal intensity relative to background
parenchyma with all sequences, increased periportal sig-
nal, irregularity of the portal and hepatic vein branches,
and patchy areas of heterogeneous signal.
Tuberculosis
Tuberculosis is one of the most common infectious dis-
eases worldwide. Generally, tuberculosis of the liver pre-
sents as either a miliary form or a local form, which is fur-
Fig. 8. Hepatic candidiasis in a 66-year-old female with leukemia
who presented with abnormal liver function tests. Axial contrast- ther subdivided into nodular tuberculosis (i.e., tuberculous
enhanced CT image demonstrates multiple, small, low-attenuation abscess and tuberculoma) and tubular or hepatobiliary tu-
lesions distributed throughout the liver and spleen. Splenomegaly berculosis (i.e., tuberculosis involving the intrahepatic
and bilateral pleural effusions are also seen ducts). Hepatic miliary tuberculosis is most common and
is reported to occur in 50-80% of all patients with terminal
pulmonary tuberculosis. Miliary tuberculosis is usually not
after intravenous administration of contrast medium, al- detected at imaging. Hepatomegaly may be the only radio-
though peripheral enhancement may occur as well. logical abnormality. In the healing stage of tuberculosis,
At MRI, the untreated nodules are rounded lesions CT may show diffuse hepatic calcifications (approximate-
<1 cm in diameter that are minimally hypointense on T1- ly 50% of cases). Reported CT findings of nodular tuber-
weighted and gadolinium-enhanced images and markedly culosis are non-specific and include hypoattenuating le-
hyperintense on T2-weighted images. After treatment, the sions both before and after intravenous administration. At
lesions appear mildly to moderately hyperintense on T1- MRI, the lesions are hypointense on T1-weighted images
and T2-weighted images and demonstrate enhancement and hypo- to iso-intense on T2-weighted images. Tubercu-
on gadolinium-enhanced images. A dark ring is usually losis lesion differently enhance after gadolinium adminis-
seen around these lesions with all sequences. Completely tration. Given these rather non-specific findings with all
treated lesions are minimally hypointense on T1-weighted imaging techniques, percutaneous liver biopsy is necessary.
images, isointense to mildly hyperintense on T2-weighted
images, moderately hypointense on early gadolinium- Histoplasmosis
enhanced images, and minimally hypointense on delayed
Histoplasmosis is the most common cause of fungal in-
gadolinium-enhanced images. MRI is superior to CT and
fection in the Ohio River Valley of the USA. Fortunately,
US in the detection of these fungal foci.
99% of patients exposed to histoplasmosis develop only
subclinical infections. Liver involvement is common in
Granulomatous Diseases
disseminated histoplasmosis, which usually originates in
the lungs. The most common hepatic findings include
Granulomatous hepatitis is associated with numerous
portal lymphohistiocytotic inflammation and discrete,
conditions, most commonly, sarcoidosis, tuberculosis,
well-delineated granulomas. In patients with healed
and histoplasmosis. Hepatic granulomas usually appear
histoplasmosis, the presence of small, punctate calcifica-
as discrete, sharply defined nodules consisting of aggre-
tions scattered throughout the liver and spleen is typical
gates of epithelioid cells by a rim of mononuclear cells,
but a non-specific finding.
predominantly lymphocytes.
Sarcoidosis Parasitic Infections

Sarcoidosis is a multi-system disorder of unknown patho- Schistosomiasis
genesis, characterized by non-caseating granulomas. Al-
though it may involve almost any organ in the body, pul- Schistosoma japonicum, S. hematobium, and S. mansoni
monary sarcoidosis is the most common. Sarcoidosis of are the three most important species that infect humans.
the liver is also relatively frequently seen, but the granu- The schistosomas live in the bowel lumen and lay eggs in
lomas are usually not macroscopically detectable and the mesenteric veins. The eggs may then embolize to the
thus may not produce focal abnormalities on imaging portal vein. The eggs themselves do not survive and subse-
studies. Classically, the granulomas develop in a peri- quently calcify. Chronic infections with either S. japonicum
portal location, resulting in periportal fibrosis, cirrhosis, or S. mansoni result in the formation of cirrhosis and the
and eventually portal hypertension. risk of development of HCC. Histologically, schistosomiasis
is characterized by white, pinhead-sized granulomas scat- Uncommon Hepatic Infections

tered throughout the liver. At the center of each granuloma
is a schistosome egg. In severe infections, the surface of the Cat-scratch Disease
liver shows granulomatous involvement and widespread fi-
brous portal enlargement (“pipe-stem” fibrosis). Cat-scratch disease is an infection that affects immuno-
At CT, the most pathognomonic pattern is the presence competent children or adolescents. It is caused by Bar-
of calcified septa, usually aligned perpendicular to the liv- tonella henselae, a gram-negative bacillus that is usual-
er capsule (“tortoise shell” or “turtle back” appearance). ly introduced by the scratch of a cat. Cat-scratch disease
takes many forms, from regional lymphadenitis to dis-
seminated infection. The typical clinical manifestation is
Viral Infections painful lymphadenopathy proximal to the site of inocu-
lation. Disseminated infection is seen in 5-10% of cases.
Viral Hepatitis In the abdomen, multiple granulomas ranging from 3 to
30 mm may form in the liver and spleen, with or with-
Acute viral hepatitis is a systemic infection that affects the out hepatosplenmegaly. Histopathological findings in-
liver and is usually caused by one of five viral agents: he- clude vascular proliferative lesions (peliosis hepatis) and
patitis A virus, hepatitis B virus (HBV), hepatitis C virus, necrotizing granulomatous lesions.
the HBV-associated delta agent or hepatitis D virus, and At unenhanced CT, the lesions are hypoattenuating rel-
hepatitis E virus. A vast array of other viruses may also ative to normal parenchyma. Three different patterns at
produce hepatitis, including herpes viruses, yellow fever contrast-enhanced CT have been described:
virus, rubella virus, Coxsackie virus, and adenovirus. The
1. persistent hypoattenuation relative to the liver;
diagnosis of acute hepatitis is usually based on serological,
2. isoattenuation relative to surrounding tissues;
virological, and clinical findings. Probably the most im-
3. marginal enhancement.
portant role of radiology in patients with acute hepatitis is
There are only a few MRI studies of cat-scratch dis-
to help rule out other diseases that produce similar clinical
ease. The lesions appear as nodules of low signal intensi-
and biochemical abnormalities, such as extrahepatic
cholestasis, diffuse metastatic disease, and cirrhosis. ty on T1-weighted images and high signal intensity on
At CT and MRI, the findings in acute viral hepatitis are T2-weighted images. Peripheral enhancement may be
non-specific and include hepatomegaly and periportal ede- seen on gadolinium-enhanced T1-weighted images.
ma. At CT, heterogeneous enhancement and well-defined
regions of low attenuation may be present. At MRI, peri- Bacillary Angiomatosis
portal edema appears as areas of high signal intensity on
T2-weighted images. Involved areas may be normal or Bacillary angiomatosis is also a manifestation of infec-
demonstrate decreased signal intensity on T1-weighted im- tion by Bartonella henselae, the same organism that
ages and increased signal intensity on T2-weighted images. causes cat-scratch disease, but in immunocompromised
There is also impaired uptake of liver-specific agents. patients. The disease is characterized by localized areas
Extrahepatic findings in patients with severe acute hepati- of vascular proliferation that may affect the skin, airway,
tis include thickening of the gallbladder wall due to edema mucous membranes, visceral organs, bone, and brain.
and, infrequently, ascites. On CT and MRI, the features of Contrast-enhanced CT may demonstrate multiple diffuse
chronic hepatitis resemble those of early-stage liver cir- low- or high-attenuation lesions less than 1 cm that are
rhosis. Periportal lymphadenopathy may be the sole de- scattered throughout the hepatic parenchyma. Ascites,
tectable abnormality in both acute and chronic hepatitis. mild periportal edema, and intrahepatic biliary ductal
dilatation may occur. These imaging features are non-
HIV Infection specific and must be distinguished, especially in AIDS
patients, from hepatic abscesses related to other bacteri-
The liver and biliary tracts are frequent sites of involve- al, viral, or fungal infections, AIDS-related lymphoma,
ment during the course of HIV infection. Co-infection Kaposi sarcoma, and, less commonly, disseminated
with HBV and hepatitis C virus is particularly common Pneumocystis carinii infection.
due to the shared means of transmission of these viruses
with HIV. AIDS-related cholangiopathy is the newest
common manifestation. At CT, inflammation of the gall- Focal Infections
bladder or biliary tree manifests as mural thickening or
abnormal contrast enhancement. Magnetic resonance Bacterial (Pyogenic) Abscess
cholangiopancreatography is more sensitive and specific
than US or CT in depicting the mural irregularity of the Pyogenic abscess, although uncommon in the antibiotic
extrahepatic ducts, which results from the exuberant era, is still challenging clinically since its presentation is
periductal inflammation, focal mucosal ulcers, and the quite variable, from profound septicemia to chronic, in-
interstitial edema found in AIDS-related cholangitis. dolent symptoms.
Enhanced CT can reliably diagnose over 90% of he- usually peripheral, round or oval areas of low attenuation
patic pyogenic abscesses, revealing two main patterns: (10-20 HU). A peripheral rim of slightly higher attenua-
multiple microabscesses (disseminated or clustered) and tion can be seen on non-contrast scans and shows
large macroabscesses. By virtue of its good spatial and marked enhancement after the administration of contrast
contrast resolution, CT is the single best method for de- material.
tecting hepatic abscess, with a sensitivity as high as 97%. On MRI, amebic liver abscesses are spherical and usu-
On CT scans, abscesses appear as generally rounded ally solitary lesions with a hyperintense center on T2-
masses that are hypodense on both contrast and non- weighted images and a hypointense center on T1-weighted
contrast scans. Central gas, as air bubbles or an airfluid images. The abscess wall is thick; on gadolinium en-
level, is a specific sign, but it is present in less than 20% hanced images, the enhancement pattern is similar to that
of cases. A thick, enhancing, peripheral rim is also noted. of pyogenic abscess.
At MRI, air within the abscess appears as a signal
void, thus making it more difficult to differentiate from Echinococcal Disease
calcifications. However, the shape and location (air-fluid
level) of the abscess should enable the correct diagnosis. Hydatid disease has two main forms affecting humans,
After the administration of gadolinium-DTPA, abscesses resulting from infection with either Echinococcus granu-
typically show rim enhancement (the “double target” losus or Echinococcus multilocularis or alveolaris. These
sign). Small lesions (<1 cm) may enhance homogeneously, infections have well-defined and different geographical
mimicking hemangiomas. Percutaneous, image-guided distributions. The pathological and imaging findings dif-
aspiration followed by drainage is the method of choice fer dramatically between these parasites.
for definitive diagnosis and treatment, with success On CT scans, E. granulosus-infected sites are seen as
achieved in >90% of cases. unilocular or multilocular, well-defined cysts with ei-
ther thick or thin walls. Daughter cysts are usually de-
Amebic Abscess tected as areas of lower attenuation than the mother cyst
and are usually in the periphery of the lesion. Daughter
Hepatic abscess is the most common extraintestinal man- cysts can also float free in the lumen of the mother cyst;
ifestation of amebiasis, affecting approximately 10% of altering the patient’s position may change the position
patients with the disease. Although rare in the continen- of these cysts, confirming the diagnosis of echinococcal
tal USA, 10% of the world’s population is infected with disease. Curvilinear ring-like calcification is also a
Entamoeba histolytica. Clinically, patients with amebic common feature.
abscess are more acutely ill than those with pyogenic ab- On MRI studies, the appearance of the cyst compo-
scess, with high fever and right upper quadrant pain. Di- nent of echinococcal cysts is similar to that of other
agnosis is made by positive serological amebic titers, al- cysts, with long T1 and T2 relaxation times. However,
though they have false-negative rates of almost 20%. MRI best demonstrates the pericyst, matrix and hydatid
Extrahepatic extensions to the chest wall, pleura, or sand (debris consisting of freed scolices), and the daugh-
adjacent viscera are well demonstrated on CT. Percuta- ter cysts. The pericyst usually has low signal intensity on
neous catheter drainage of an amebic abscess is rarely T1- and T2-weighted images, because of its fibrous
necessary due to the effectiveness of amebicidal therapy. component. This rim and a multiloculated or multicystic
Occasionally, percutaneous drainage is needed in large, appearance are distinctive features. The hydatid matrix
symptomatic abscesses with poor response to medical appears hypointense on T1-weighted images and
therapy, suspected bacterial superinfection, and threaten- markedly hyperintense on T2-weighted images. When
ing intrapericardial rupture. The CT appearance of ame- present, daughter cysts are hypointense relative to the
bic abscess is variable and non-specific. The lesions are matrix on both T1- and T2-weighted images (Fig. 9).
a b Fig. 9 a, b. Echinococcus gran-

ulosus cyst in a 28-year-old
man with right upper quad-
rant pain. a Axial T2-weight-
ed image demonstrates a
large cystic mass in the right
lobe of the liver which is sur-
rounded by a hypointense
rim and contains more hyper-
intense smaller cysts in its
periphery. b On the axial T1-
weighted image, the hypo-
intense rim is well visualized
and the peripheral cysts are
hypointense relative to the
center of the lesion
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IDKD 2010-2013
Focal Liver Lesions

Wolfgang Schima1, Richard Baron2
1 Department of Radiology, KH Göttlicher Heiland, Wien, Austria
2 Department of Radiology, University of Chicago, Chicago, IL, USA
Introduction substantially decreased specificity [3]. The amount of

contrast material administered may depend on the pa-
State-of-the-art multidetector computed tomography tient’s weight, but is typically 42-45 g of iodine (i.e., 120-
(MDCT) and magnetic resonance (MR) imaging tech- 150 mL of contrast at 300 mg iodine/mL, equivalent to
nologies offer detailed insights into the liver’s anatomy 110 mL of contrast at 400 mg/mL). The total amount of
and the pathophysiology of liver disease, such that imag- iodine given determines the quality of portal-venous-
ing has become the pacemaker in the development of new phase imaging, with a goal of increasing liver attenuation
therapeutic techniques. Understanding different imaging through contrast enhancement by 50 HU [4]. To achieve
techniques and the diagnostic potential of different good arterial-phase imaging, the flow rate of the contrast
modalities, including contrast utilization, is essential to material is crucial; a rate of 4-5 mL/s is recommended
optimize patient diagnoses. In the current environment of [5]. Others have used a variable amount of contrast ma-
cost containment, the most appropriate modality should terial (e.g., 2 mL/kg body weight) and a fixed injection
be chosen to answer the clinical question. Ultrasonogra- duration of 30 s, which means that the injection rate
phy (US) is widely available, non-invasive, and the least varies according to the patient’s weight.
expensive, but it is limited by low sensitivity and speci- Timing of image acquisition in relation to contrast ma-
ficity unless US contrast agents are used. Instead, contrast- terial administration depends on whether one needs to im-
enhanced CT has emerged as the modality of choice for age during the early arterial phase (for arterial anatomy on-
routine liver imaging while MR imaging is used primarily ly), late arterial phase (for hypervascular tumor detec-
as a problem-solving technique for liver evaluation when tion/characterization), or portal-venous phase (in some
CT or US results are equivocal or if high concern exists cases of follow-up imaging and hypovascular tumor detec-
for malignancy in certain high-risk populations. This tion). Routinely, late-arterial-phase imaging (with a delay
chapter highlights the imaging of hepatic focal liver le- consisting of the aortic transit time plus 15-18 s) [6, 7] and
sions, focusing on MDCT and MR imaging, but includ- a portal-venous scan (20-30 s interscan delay or with a
ing ultrasonography in selected cases. It aims to provide fixed delay of ~60-70 s) are acquired, although the actual
readers with an understanding of how to optimize their combination of imaging phases will depend on the indi-
CT and MR imaging protocols and to familiarize them vidual indication [8]. Automated methods of measuring ar-
with the different CT and MR imaging appearances of terial (aortic) enhancement on CT (often termed bolus
focal liver lesions. The value of liver-specific MR contrast tracking), rather than fixed scan times, can be helpful [9].
agents for non-invasive characterization of focal lesions
is highlighted as well.
Magnetic Resonance Imaging Technique
MDCT Imaging Techniques Unenhanced T1- and T2-weighted pulse sequences and
contrast-enhanced sequences are mandatory in MR exam-
Organ imaging in multiple planes rather than in single se- ination of the liver. Specific pulse sequences vary by manu-
quential slices is the concept underlying MDCT. Thus, in facturer, and their use depends on patient compliance and
systems consisting of 64 or more detectors the entire liv- the clinical question being addressed. In- and opposed-
er can be scanned within 1-4 s using a sub-millimeter de- phase (or out-of-phase) T1-weighted imaging is recom-
tector configuration to achieve high-quality multiplanar mended to allow for maximal tumor detection and in the
reconstructions [1]. When viewed axially, reconstructed characterization of fatty tumors and steatosis/non-steatosis.
sections of 2.5-4 mm (overlap 0.5-1 mm) are preferred – T2-weighted pulse sequences with fat suppression provide
because thinner slices do not improve lesion conspicuity better lesion contrast than non-fat-suppressed sequences.
– but at the expense of increased image noise [2] and Diffusion-weighted imaging, which is helpful for lesion
64 Wolfgang Schima, Richard Baron
detection, is now available on most scanners. In general, small lesions remain problematic for characterization at
dynamic imaging with extracellular gadolinium-based CT. On MR imaging, cysts are well-defined, homoge-
contrast agents is required for lesion characterization, the neous lesions that are hypointense on T1-weighted im-
detection of tumors in cirrhosis, evaluation of the tumor ages and markedly hyperintense on T2-weighted images.
response to therapy, and the detection of marginal tumor The marked increased in T2 signal intensity of even very
recurrences following tumor ablation. small cysts can be very helpful to confirm the benign na-
Two types of liver-specific MR contrast agents are ture of small lesions.
available. Following their intravenous injection, hepato-
cyte-specific agents (mangafodipir: Teslascan, GE Health- Hemangioma
care, Norway; gadobenate: MultiHance, Bracco, Italy; and
gadoxetic acid: Primovist or Eovist, Bayer-Schering, Hemangioma is the most common benign liver tumor. Its
Germany) are taken up by hepatocytes and provide T1 typical US characteristics include a sharply circum-
enhancement of liver tissue. These compounds are used to scribed, well-defined hyperechoic lesion with distal
improve the detection of metastases and to characterize acoustic enhancement. Small hemangiomas are usually
lesions [10-13]. The reticuloendothelial agent ferumoxide homogeneous in appearance whereas larger ones (>4 cm)
(Endorem, Guerbet), a superparamagnetic iron oxide are frequently heterogeneous and do not demonstrate all
(SPIO), is phagocytosed by Kupffer cells after intravenous of the characteristic features of these lesions.
infusion and leads to a drop in the T2 signal intensity of On unenhanced CT images, hemangiomas are well-
liver tissue but not of most parenchymal masses. defined hypodense masses. On MR imaging, they are
hypointense on T1-weighted sequences and markedly
hyperintense on T2-weighted sequences. In addition, MR
Benign Hepatic Lesions imaging is useful in differentiating hemangiomas from
solid neoplasms based on the long T2 relaxation time
Cyst (= hyperintensity) of hemangioma compared with other
hepatic masses [14, 15]. A relatively long T2 echo time
Cysts are common, usually asymptomatic liver lesions (>140 ms) will demonstrate the presence of a homoge-
with an incidence in the population of 5-14%. At US, he- neously “light-bulb-bright” lesion, which is characteris-
patic cysts are anechoic, with an imperceptible wall and tic of a benign lesion, either cyst or hemangioma. The
increased acoustic enhancement behind the cyst. On CT exceptions to this would include cystic metastases, and
scans, a hepatic cyst appears as a well-circumscribed, ho- gastrointestinal stromal tumor (GIST) and neuro-
mogeneous mass with an attenuation value similar to that endocrine tumor metastases.
of water (<15 HU). Cysts lack any mural thickening or Hemangiomas show three distinctive patterns of en-
nodularity and do not show contrast enhancement after hancement at CT/MR imaging [16], with the common
the administration of intravenous contrast material. Small characteristic feature that areas of lesion enhancement
lesions may appear to have higher attenuation measure- closely follow the enhancement characteristics of blood
ments because of partial-volume averaging. Occasional- pooling elsewhere [17]. Small lesions (up to ~2 cm) may
ly, unenhanced scans will suggest the diagnosis of small show immediate and complete filling in the arterial phase,
cysts if they are well visualized as hypodense lesions, with sustained enhancement in the venous and delayed
whereas very small metastases are usually not discernible phases (type I, also termed flash filling) [18] (Fig. 1). The
on unenhanced scans. In most instances, however, these most common enhancement pattern is one of peripheral
a b c
Fig. 1 a-c. Hemangioma type 1. a Unenhanced CT shows a small hypodense lesion adjacent to the falciform ligament (arrow). b Contrast-
enhanced CT in the arterial phase shows rapid and complete enhancement of the hemangioma, which persists in the venous phase (c). The
attenuation of the hemangioma in the enhanced phases is similar to that of the aorta
Focal Liver Lesions 65
a b c
Fig. 2 a-d. Hemangioma type III. a T2-weighted turbo spin-echo (TSE) MR image shows a
very hyperintense lesion in the right lobe. b-d Dynamic gadolinium-enhanced T1-weighted
gradient-recalled echo (GRE) images: b arterial, c venous, and d equilibrium phases show
peripheral nodular enhancement with progressive centripetal fill-in. d In the equilibrium-
phase, after 5 min, there is no complete fill-in
nodular discontinuous enhancement that progresses with cellular carcinoma, in which the central scar is predomi-
increased fill-in over time (type II). Larger lesions (>5 nately of low signal intensity on T2-weighted MR se-
cm) or lesions with central thrombosis/fibrosis may lack quences. The use of color/power Doppler US may
central fill-in (type III) (Fig. 2). With SPIO agents, the demonstrate blood vessels within the scar [23].
blood pooling effect, with accumulation of contrast mate- On unenhanced CT, FNH are isodense or minimally
rial in the sinuses, may lead to the prolonged enhancement hypodense and are sometimes detectable only by the
of hemangiomas on T1 images and signal intensity loss on mass effect on adjacent vessels. On unenhanced MR im-
T2 images, despite the lack of Kupffer cells in these le- ages, FNH often has a signal intensity similar to that of
sions. This imaging feature helps in the differentiation be- hepatic parenchyma but usually slightly different on ei-
tween hemangiomas and metastases [19]. ther T1- or T2-weighted images (Fig. 3). Due to the
Recent studies have shown that non-contrast diffusion- prominent arterial vascular supply, FNH undergoes
weighted imaging may help to differentiate between he- marked homogeneous enhancement during the arterial
mangioma and solid lesions, as the apparent diffusion co- phase of contrast-enhanced CT/MR imaging, with rapid
efficient of hemangiomas is higher than that of solid le- wash-out of contrast to isodensity/isointensity on venous-
sions [20]. phase images [22]. The central scar often enhances on de-
layed scans [21], a feature typical of a fibrous compo-
Focal Nodular Hyperplasia nent. One key aspect is that, other than the scar, these le-
sions tend to be very homogeneous in appearance.
This benign lesion is usually of no clinical consequence With liver-specific MR contrast agents, FNH shows
other than the confusion it causes when incidentally de- enhancement on delayed images after the administration
tected during abdominal imaging examinations. The of hepatobiliary contrast agents (such as mangafodipir
sonographic appearance of focal nodular hyperplasia (Fig. 3) and signal loss after the administration of reticulo-
(FNH) is non-specific; the lesion may be isoechoic, or endothelial agents [24]. This difference is particularly
slightly hypoechoic [21] to liver, while in patients with helpful for the differentiation between hypervascular
diffuse hepatic steatosis it is always hypoechoic. One metastases (which do not accumulate liver-specific
characteristic feature is the presence of a central scar, agents) or hepatic adenoma and incidentally encountered
seen in approximately two-thirds of large lesions but in FNH [18]. The influence of oral contraceptives on the
only one-third of small lesions (<3 cm) [22]. The central growth of FNH is still discussed controversially. Studies
scar is most often hyperintense on T2-weighted images, with serial imaging have shown FNH growth during
with a comma-shaped or spoke-wheel appearance. This is follow-up to be rare (3-11%) [25, 26] and not stimulated
a key differentiating feature from fibrolamellar hepato- by oral contraceptives [26].
a b c
Fig. 3 a-d. Focal nodular hyperplasia (FNH). a The lesion (arrow) is isointense on T1-weight-
ed imaging, with a small central scar. b On T2, the lesion is also isointense (arrow); the cen-
tral T2-weighted bright scar is better discernible. Mangafodipir-enhanced T1-weighted im-
ages in the axial (c) and coronal (d) planes show homogeneous uptake of the liver-specific
agent, typical for FNH (arrow). The central spoke-wheel scar is nicely depicted
Hepatocellular Adenoma trast-enhanced CT or MR, adenomas usually show

marked arterial-phase enhancement with a rapid transi-
This is an uncommon benign neoplasm of low malignant tion to either isoattenuating or hypoattenuating/intense to
potential [26]. Unlike FNH, the relationship between oral hepatic parenchyma on portal-venous-phase imaging.
contraceptives and the development of hepatocellular Hepatic adenomas may show signal loss after the admin-
adenoma (HCA) is well established. Histologically, HCA istration of reticuloendothelial agents and delayed en-
is composed of cells resembling normal hepatocytes but hancement after hepatobiliary MR contrast agents. How-
lacking bile ducts. This is a key feature in histologically ever, they will not show sustained enhancement on de-
differentiating between adenoma and FNH [26]. Adeno- layed imaging to degrees greater than normal liver
mas are typically hypervascular and, when large, often parenchyma after gadobenate administration, which helps
heterogeneous due to the presence of fat, necrosis, or he- to differentiate FNH from adenoma [28].
morrhage [26, 27] (Fig. 4). These tumors often contain
intratumoral fat, and, as T1-weighted chemical-shift MR Biliary Hamartomas (von Meyenburg Complex)
imaging is sensitive for detecting fat, this technique can
be very helpful in characterizing adenomas. The second Bile duct hamartomas are congenital malformations of
typical feature of adenoma is its propensity for sponta- the ductal plate but they have no connections with the
neous hemorrhage. If no tumor capsule is present, such bile ducts. These lesions are of no clinical significance
hemorrhage may lead to spontaneous rupture, with hy- but are incidentally encountered in patients undergoing
potension and even death. abdominal imaging examinations. They appear as small
The CT and MR imaging appearances of HCA may be cystic lesions of round, oval, or irregular shape, found ei-
non-specific. On unenhanced CT images, the lesion may ther in the periportal region or diffusely spread through-
be hypodense due to the presence of fat or necrosis. On out the liver (Fig. 5). They are usually <10 mm in diam-
T1- and T2- weighted MR images, HCA are non-specif- eter and lack contrast enhancement, but occasional pe-
ic in appearance, being usually mildly hypointense on T1 ripheral rim enhancement may simulate small hypo-
and isointense or mildly hyperintense on T2. If intracel- vascular metastases [27].
lular lipid is present within the lesion, it will often appear
hyperintense on T1 in-phase images, with a drop in sig- Hepatic Abscess and Hydatid Cyst
nal intensity on opposed-phase images [26]. The presence
of intratumoral fat helps to narrow the differential diag- Abscess appearances can vary depending on etiology.
nosis, as hemangioma can be excluded and metastases Peribiliary abscesses tend to be small and scattered adja-
and FNH only very rarely contain fat. On dynamic con- cent to the biliary tree; hematogenous distribution via the
a b c
Fig. 4 a-d. Hepatocellular adenoma. a T1-weighted in-phase GRE image demonstrates a very
large mass in a young woman. The mass is inhomogeneous and shows bright spots, sug-
gestive of hemorrhage (asterisk). b There is a typical drop in signal intensity on the op-
posed-phase image, indicative of intratumoral fat (arrows), whereas the hemorrhage
(methemoglobin, asterisk) does not lose signal intensity. c T2-weighted TSE sequence con-
firms the presence of hemorrhage (asterisk). Intratumoral fat and hemorrhage are typical
for adenoma. d The gadolinium-enhanced image shows moderate and inhomogeneous en-
hancement. In a large, very inhomogeneous adenoma, malignant degeneration cannot be
ruled out radiologically. However, at surgery this lesion was shown to be an adenoma with
central hemorrhage
a b
Fig. 5 a, b. Biliary hamartomas (von

Meyenburg complex). Coronal (a)
and axial (b) T2-weighted images
show multiple small cystic lesions
of different sizes and shapes (“star-
ry sky” appearance), typical for bil-
iary hamartomas
hepatic artery or portal vein in appendicitis or divertic- relative to liver parenchyma whereas on T2-weighted se-
ulitis tends to lead to larger lesions. US reveals a cystic quences they are markedly hyperintense and often sur-
lesion with internal echoes. On CT, hepatic abscess ap- rounded by a local area of slight T2 hyperintensity, rep-
pears as a hypodense lesion with a capsule that may show resenting perilesional edema (Fig. 6).
enhancement. The cluster sign may be noted when multi- Amoebic liver abscess has a non-specific appearance
ple abscesses are present as focal clusters of lesions [29]. on CT, but is usually seen as a solitary, hypodense lesion
The CT appearance of hepatic abscess is non-specific with an enhancing wall that may be smooth or nodular,
and can be mimicked by cystic or necrotic metastases. often associated with an incomplete rim of edema. With
Thus, clinical information and laboratory values play a MR imaging, the lesions are hypointense on T1-weighted
key role in guiding the radiological diagnosis. Although images and heterogeneously hyperintense on T2-weighted
seen in only a small minority of patients, the presence of images [30].
central gas is highly specific for abscess (Fig. 6). On T1- On CT scan, involvement of the liver by Echinococcus
weighted MR images, hepatic abscesses are hypointense granulosus (hydatid cyst) manifests as unilocular or
a b c
Fig. 6 a-c. a Typical large subcapsular abscess with an air-fluid level and a pleural empyema. b In another patient, CT shows a small, thick-
walled abscess after pancreatic surgery. c T2-weighted image of the same patient as in (b) shows the thick indistinct wall of the abscess
and peripheral edema
multilocular cysts, with thin or thick walls and calcifica- imaging-based screening for HCC or frequent liver
tions and usually accompanied by daughter cysts. The lat- imaging due to complications of their chronic disease. In
ter are seen as smaller cysts with septations at the mar- these patients, HCC lesions are typically small (<3 cm)
gins of or inside the mother cyst. This appearance is and homogeneous in appearance. In non-cirrhotic pa-
therefore quite different from that of a “usual” multicys- tients, the disease is usually asymptomatic; thus, by the
tic tumor. On MR imaging, a hypointense rim on T1- and time symptoms occur and imaging is necessarily per-
T2-weighted images and a multiloculated appearance are formed, the lesion is very large and usually heteroge-
considered to be important diagnostic features. neous in appearance.
The US presentation of HCC is quite variable, with
isointensity, hypointensity, or hyperintensity. Smaller le-
Malignant Primary Tumors sions are typically homogeneous and larger ones hetero-
geneous. A surrounding fibrous capsule is often present
Hepatocellular Carcinoma and relatively characteristic for HCC, appearing as a hy-
poechoic rim surrounding the lesion.
Hepatocellular carcinoma (HCC) is the most common On unenhanced CT images, most HCCs are hypo-
primary liver cancer worldwide and is particularly dense. The presence of intratumoral fat can result in the
prominent in Asian and Mediterranean populations. In lowered CT attenuation of these tumors; this finding is
European countries, HCC occurs mostly in patients with characteristic of primary hepatocellular tumors. Due to
chronic liver disease (hepatitis B or C, liver cirrhosis, or their predominant arterial supply, small HCCs enhance
hemochromatosis). These tumors consist of abnormal vividly in the arterial phase of hepatic contrast en-
hepatocytes arranged in a typical trabecular, sinusoidal hancement, becoming isoattenuating or hypoattenuat-
pattern. They may be solitary, multifocal, or diffusely ing with hepatic parenchyma in the portal-venous
infiltrating. phase of enhancement (so-called wash-out). On de-
The imaging appearances of HCC can vary dramati- layed images, most HCC lesions are hypodense with
cally, but generally can be separated into those based on surrounding liver (Fig. 7).
early versus late presentation. Early presentation is typi- There have been several studies addressing the re-
cal of patients with chronic liver disease who undergo quired phases of scanning for optimal HCC detection
a b
Fig. 7 a, b. Detection of hepatocellular carcino-

ma with late-arterial-phase multidetector CT.
a In the late-arterial phase, MDCT shows a
small HCC that was not visible on unen-
hanced scan. b The delayed-phase scan
reveals wash-out of the lesion, which is now
slightly hypodense. The combination of
arterial hypervascularity and wash-out is a
very specific sign of malignancy
a b c
Fig. 8 a-c. Large HCC with tumor thrombus in the inferior vena cava. a Arterial-phase MDCT shows a large HCC with peripheral irregular
rim enhancement. The tumor has grown into the right hepatic vein and the inferior vena cava (IVC). b Arterial- and c venous-phase images
in the coronal plane better demonstrate the extension of the tumor thrombus into the IVC above the diaphragm
and characterization. Arterial-phase imaging is the most cirrhosis may be difficult to detect with CT. Larger HCC
sensitive for the detection of small lesions; as highest lesions typically have a different appearance and are
visibility is achieved in the late arterial phase, to allow visualized as a mosaic, due to hemorrhage and fibrosis.
time for contrast diffusion into the tumor parenchyma, Also, about 10% of small HCCs can appear hypodense to
there is no need for early-arterial-phase imaging [6, 31, liver; these are generally thought to be well-differentiated
32]. A venous phase is always necessary for tumor de- lesions.
tection and the assessment of venous structures (Fig. 8) Typical MR imaging findings of larger HCC consist
as well as other abdominal organs. For HCC detection, of a fibrous capsule, central scar, intratumoral septa,
the delayed phase can visualize a few lesions that would daughter nodules, and tumor thrombus [37]. In addition,
otherwise go unnoticed [33] and also is very helpful in there is often a somewhat organized internal, mosaic-
differentiating HCC from benign enhancing lesions by like pattern that is seen on CT as well as on MR imag-
demonstrating tumor wash-out greater than liver ing [38]. While most large HCCs are hyperintense on
parenchyma [34]. Unenhanced images are important to T2-weighted sequences, small lesions (<2 cm) are often
document siderotic nodules as different from arterial isointense but may also be hypointense. On T1-weighted
enhancing lesions and to detect intratumoral fat. How- sequences, HCC has variable signal intensity relative to
ever, to reduce the radiation dose to the patient, these hepatic parenchyma. A tumor capsule may be seen on
images should be obtained only intermittently during T1-weighted and, less commonly, on T2-weighted im-
serial imaging examinations. Nonetheless, they are ages as hypointense (Fig. 9). Conventional gadolinium
mandatory in the follow-up after chemoembolization or contrast imaging in HCC parallels that described for CT,
tumor ablation and when hemorrhage is suspected. In with characteristic early peak contrast enhancement and
summary, a three- to four-phase MDCT protocol is rec- delayed-phase tumor wash-out. These enhancement fea-
ommended by most centers to optimally detect and tures are useful in differentiating HCC from heman-
characterize HCC. gioma, which generally shows early peripheral en-
The presence of focal hypervascularity in the arterial hancement, marked peak enhancement >2 min after
phase may lead to false-positive results [35]: transient fo- contrast injection, and marked pooling of contrast on
cal enhancement of liver parenchyma during arterial delayed images. Dynamic gadolinium-enhanced MR
phase enhancement, often termed transient hepatic atten- imaging has been found to be superior to MR with liver-
uation differences (THAD), can be caused by a multitude specific contrast agent in terms of HCC detection
of factors. In cirrhotic patients, transient focal enhance- [39, 40], because hypervascularity is the key feature
ment is most often due to arterial-portal shunting, result- marking the transition of dysplastic nodules into early
ing in inappropriately early focal areas of portal-venous HCC [41]. However, double-contrast MR imaging with
distribution enhancement in the liver. These usually are sequential administration of gadolinium and reticulo-
peripheral, often wedge shaped, and not round. Sub- endothelial contrast agents has been found to be the
capsular lesions that do not show a substantial mass most sensitive and specific method to detect HCC and
effect or round nature should be evaluated carefully to differentiate between early HCC and dysplastic
before a diagnosis of HCC is concluded. The combi- nodules [42, 43]. HCC may show enhancement on
nation of hyperdensity on arterial-phase images com- delayed images after the administration of hepatobiliary
bined with wash-out to hypodensity on venous-phase or MR contrast agent (Fig. 9). However, such enhancement
delayed-phase images, although not sensitive (33%), is a is not specific for HCC and can be seen with other
very specific (100%) feature for the presence of HCC primary hepatocellular tumors, such as dysplastic
[36] (Fig. 7). Diffusely infiltrating and small HCCs in nodules, FNH, and adenoma.
a b c
Fig. 9 a-d. Hepatocellular carcinoma. MR imaging with mangafodipir and gadolinium. a Ax-
ial T1-weighted GRE shows an isointense mass with a pseudocapsule and a small hyper-
intense hemorrhage. b The lesion is only minimally hyperintense on T2-weighted images.
c The mangafodipir-enhanced T1-weighted GRE image shows enhancement of this well-
differentiated HCC. The enhancement does not help in the differential diagnosis of hepato-
cellular lesions. d The gadolinium-enhanced sequence in the arterial phase shows typical
hypervascularity. The key features guiding the correct diagnosis in this hypervascular lesion
are the presence of a pseudocapsule (very rare in FNH or adenoma) and cirrhosis (see
enlarged left and caudate lobes)
Fibrolamellar HCC retention of conventional CT and MR contrast agents.

Contrast enhancement patterns in FL-HCC are almost
Fibrolamellar HCC (FL-HCC) is a less aggressive tu- always heterogeneous whereas in FNH they are almost
mor with a better prognosis than HCC. It consists of always homogeneous.
malignant hepatocytes separated into cords by fibrous
strands. On CT, FL-HCC appears as a large, well- Cholangiocellular Carcinoma
defined vascular mass with a lobulated surface and
often a central scar; calcifications are identified in up to Cholangiocellular carcinoma (CCC) is the second most
70% of patients [44, 45]. On MR imaging, FL-HCC is common primary malignancy of the liver. Intrahepatic
hypointense on T1-weighted images and hyperintense CCC originates from the intralobular bile ducts, unlike
on T2-weighted images, with the central scar being hilar CCC, which arises from a main hepatic duct or from
hypointense on both sequences (Fig. 10). This is in con- the bifurcation. Intrahepatic CCC presents as a large
trast to the scar in FNH, which is most often hyper- mass, because the tumor does not cause symptoms in the
intense on T2-weighted images. The fibrous central early stages [46] (Fig. 11). According to its growth char-
zones of both FNH and FL-HCC will show delayed acteristics, CCC is classified as mass-forming, periductal-
a b
Fig. 10 a, b. Fibrolamellar hepatocellular carcinoma. a CT during arterial phase shows a typical heterogeneously enhancing mass in the left
lobe (arrows), with a low-attenuation central fibrous scar containing calcifications (arrowheads). b MR T2-weighted shows a large mass
in the left lobe (arrows) with a heterogeneous appearance and mild to moderately increased signal intensity. The fibrous central scar is of
very low signal intensity (arrowheads)
a b
Fig. 11 a, b. Cholangiocellu-
lar carcinoma. Contrast-en-
hanced CT in the arterial
(a) and venous (b) phases
demonstrates a large hypo-
vascular mass with some
calcifications. Capsular re-
traction is quite often seen
in peripheral CCC
infiltrative, or intraductal-growing, with the mass-form- The greater the presence of papillary excrescences, soft-
ing type being most common in intrahepatic CCC [46]. tissue nodularity, or septations, the more likely it is that
At CT and MR imaging, the lesions tend to be hypodense the lesion is malignant [49]. However, this is a moot point
on unenhanced CT and hypointense on T1-weighted im- as it has been shown that benign lesions can undergo ma-
ages, with peripheral enhancement at dynamic contrast- lignant degeneration. The cystic areas at T1-weighted
enhanced studies [47]. Delayed-phase CT/MR imaging imaging are of variable signal intensity, including hyper-
(after 5-15 min) may show enhancement homogeneously intense to liver, presumably due to proteinaceous content.
or in the center of the lesion due to the rich fibrous stro- Coarse calcifications can be seen at US and CT in both
ma, which is suggestive of the diagnosis of CCC [48]. cystadenoma and cystadenocarcinoma and therefore are
Periductal-infiltrative CCC causes early segmental dilata- not a helpful differentiating feature.
tion of the bile ducts at a stage when the tumor itself may
be difficult to discern [47]. Hepatic Angiosarcoma
Rare Primary Liver Tumors This rare tumor has a strong association with carcino-
gens such as vinyl chloride and Thorotrast and is also
Biliary cystadenoma/cystadenocarcinomas
seen in patients with hemochromatosis. However, the
These tumors have a similar appearance and morphology majority of hepatic angiosarcoma patients have no
as their mucinous counterparts in the pancreas and are known exposure to toxic agents. Pathologically, angio-
seen predominantly in women. Even when benign, they sarcoma may appear as a large solitary mass or with
have a propensity for malignant degeneration, and any multiple tumor nodules of varying size. In addition, the
such tumor should be considered malignant. These tumors may contain vascular channels that create sinus-
unilocular or multilocular cystic masses have a typical oidal spaces; these can result in imaging findings in
anechoic and hypoechoic US appearance; on CT, their some ways simulating those of hemangiomas. The imag-
contents have near-water attenuation, with peripheral ing appearances of angiosarcoma are most often non-
soft-tissue nodularity and traversing septations (Fig. 12). specific, with hypoattenuation on unenhanced CT, hypo-
intensity on T1 MR, and mild hyperintensity on T2
(although if prominent sinusoidal vascular spaces are
present pathologically, these can be of homogeneous
very high T2 signal). Following iodinated or gadolinium-
based contrast administration, most lesions show non-
specific heterogeneous enhancement. Potentially prob-
lematic, however, are those tumors with prominent sinu-
soidal vascular spaces, in that, albeit rarely, the CT or
MR contrast enhancement characteristics of some an-
giosarcomas can simulate those of benign hemangioma.
The high MR T2 signal in such lesions further com-
pounds this problem. In most such cases, however, care-
ful observation will reveal that tumoral enhancement
does not follow the characteristics of blood pooling at all
Fig. 12. Biliary cystadenoma. T2-weighted MR shows a mass of phases or that there are other features, such as innumer-
very high signal intensity (arrow) that is mostly homogeneous in
appearance, with the exception of a few thin internal septations able lesions, that make the diagnosis of hemangioma
(arrowheads) unlikely [50, 51].
Epithelioid Hemangioendothelioma Hepatic Lymphoma
An EHE is a rare tumor of vascular origin and is not to This tumor is most often seen in patients with widespread
be confused with infantile hemangioendothelioma, non-Hodgkin’s lymphoma or, rarely, in those with
which is a very different tumor. EHE is a primary liver Hodgkin’s disease. Although unusual, hepatic lymphoma
tumor characterized by the presence of multiple, constitutes a primary liver tumor; it is usually associated
peripheral-based lesions that progressively become con- with an immunocompromised state, such as in AIDS or
fluent masses (Fig. 13). In addition to its unusual post-transplantation with immunosuppression therapy.
peripheral liver distribution, a key and characteristic The imaging appearances of these lesions are variable,
feature of EHE is the presence of overlying capsular without any unique characteristics. CT, MR, or US imag-
retraction, attributed to fibrosis and scarring within the ing shows focal lesions with an appearance similar to that
tumor [52]. The CT attenuation or MR signal intensity of many other neoplastic lesions. Diffuse infiltrating
characteristics are non-specific and mimic those of forms can be difficult to detect regardless of the imaging
other tumors, although tumoral calcifications may occa- modality, although hepatomegaly may be present.
sionally be seen. Contrast enhancement with CT or MR
gadolinium chelates often shows a central zone of de-
creased enhancement with marked enhancement periph- Hepatic Metastases
erally and, in some cases, concentric zones of marked
enhancement (Fig. 13). The lesions often become con- On US, metastases may appear hypoechoic, isoechoic, or
fluent and may grow large enough to replace nearly the hyperechoic. Dynamic contrast-enhanced CT visualizes
entire liver parenchyma. most metastases as hypovascular and hypodense relative
to liver parenchyma on portal-venous phase (Fig. 14).
Hypervascular metastases are most commonly seen in pa-
tients with renal cell or neuroendocrine tumors, sarcomas,
or breast tumors (Fig. 14). These tumors are best visual-
ized in the arterial phase and may become isodense and
difficult to detect during the redistribution phase of en-
hancement. At MR imaging, metastases are usually hy-
pointense on T1-weighted images and hyperintense on T2-
weighted images [53] (Fig. 15). Peritumoral edema makes
the lesions appear larger on the T2, a finding that is very
suggestive of a malignant mass [54]. High signal intensi-
ty on T1-weighted sequences is typical for melanoma
metastases due to the paramagnetic nature of melanin.
Some lesions may have a central area of hyperintensity
(target sign) on T2-weighted images, which corresponds
to central necrosis. On dynamic contrast-enhanced MR
imaging, metastases demonstrate enhancement character-
Fig. 13. Epithelioid hemangioendothelioma. Contrast CT (portal- istics similar to those described for these tumors on CT.
venous phase) shows multiple, predominantly peripherally based
hypodense lesions, some of which have a laminated appearance Metastases may demonstrate a hypointense rim compared
(arrows). Early development of capsular retraction is present, with with the center of the lesion on delayed images (peripher-
flattening of the capsule overlying some of the lesions (arrowheads) al wash-out sign), which is very specific for malignancy.
a b
Fig. 14 a, b. a Contrast-
enhanced MDCT in the
arterial phase demonstrates
several predominantly hyper-
vascular liver metastases
(arrows) of a neuro-
endocrine cancer of the pan-
creas. b Contrast-enhanced
MDCT in the venous phase
shows typical hypovascular
colorectal metastases
a b c
Fig. 15 a-c. Colorectal liver metastases at gadoxetate-enhanced MR imaging. a Unenhanced T1-weighted MR imaging shows two hypointense
lesions in segments 6/7 and 4. b The T2-weighted TSE pulse sequence shows the lesions to be moderately hyperintense. c The gadoxetate-
enhanced T1-weighted GRE image in the hepatobiliary phase shows two additional small subcapsular metastases (arrows) that were not
seen on unenhanced MR imaging or MDCT
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IDKD 2010-2013
Imaging Diseases of the Gallbladder and Bile Ducts

Angela D. Levy1, Celso Matos2
1 Department of Radiology, Georgetown University Hospital, Washington, DC, USA
2 Department of Radiology, University Clinics of Brussels, Erasme Hospital, Brussels, Belgium
Introduction properties. The functional capabilities of MRI such as

those conferred by contrast-enhanced MRC have ex-
Patients with gallbladder and biliary disease may present panded the clinical applications of magnetic resonance
with complaints of right upper quadrant or mid-epigastric cholangiography.
pain, fever, jaundice, pruritis, nausea, vomiting, or they
may be asymptomatic, with only laboratory abnormali- Technique, Indications, Results
ties. Ultrasound, multidetector computed tomography
(MDCT), and magnetic resonance imaging (MRI) are T2-weighted imaging
used for the non-invasive evaluation of patients with
signs and symptoms of gallbladder and biliary disease. The use of T2-weighted imaging on functional MRC al-
New MRI techniques, such as functional magnetic reso- lows evaluation of the Vaterian sphincter. These types of
nance cholangiography (MRC), have improved visualiza- studies require a sequence with high temporal resolution,
tion of the bile ducts. In many instances, non-invasive as is the case with single-shot single-slice turbo spin echo
imaging will establish the diagnosis prior to endoscopic, (TSE) T2-weighted sequences, which have an acquisition
radiological, surgical intervention. The differential diag- time of about 2-3 s. Serial MRC images (we usually ob-
nosis for these patients is broad and includes infectious, tain 20 consecutive dynamic views) are optimally ob-
non-infectious inflammatory, neoplastic, and congenital tained in the coronal plane to evaluate dynamic changes
disorders of the liver, gallbladder, and bile ducts. This of the sphincteric segment of the pancreaticobiliary junc-
chapter discusses functional MRI of the bile ducts, in- tion. This technique, also called kinematic magnetic res-
cluding the use of functional MRC, and the patterned ap- onance cholangiopancreatography (MRCP), allows nor-
proach to the differential diagnosis of gallbladder and mal physiological sphincter contractions to be distin-
bile-duct disease. guished from biliary stenosis in patients presenting with
bile duct dilatation without an evident cause of obstruc-
tion. In the study of Kim et al., failure to visualize
Functional Magnetic Resonance Imaging of the Bile Ducts sphincteric relaxation had a sensitivity of 88% and a
specificity of 100% in the diagnosis of periampullary ob-
The bile ducts are generally investigated at MRI by us- struction. Schmidt et al. reported high accuracy (similar
ing a heavily T2-weighted sequence. This approach is to that of endoscopic ultrasound) of the same technique
completely non-invasive and is extremely sensitive for for the detection of choledocholithiasis. Kinematic
the diagnosis of anatomical abnormalities of the biliary MRCP may also be used after the intravenous adminis-
tree. However, the assessment of biliary drainage re- tration of cholecystokinin. This hormone, which is
mains challenging with T2-weighted imaging. In T2- formed and secreted by the APUD cells of the duodenum,
weighted MRC, dynamic views of the Vaterian sphincter induces bile flow by contracting the gallbladder and im-
complex can be obtained in addition to functional infor- posing an inhibitory effect on the sphincter of Oddi.
mation when cholecystokinin stimulation is performed. Therefore, a transient or persistent biliary dilatation may
Unfortunately, cholecystokinin is associated with impor- be observed when dilatation of the bile-duct without an
tant side effects (nausea, vomiting) and therefore is not evident cause is evaluated.
widely used. An alternative approach that can be used to
obtain functional information regarding the bile ducts re- Contrast-Enhanced Functional MRC
lies on the intravenous administration of paramagnetic
contrast agents. These compounds are taken up by the This approach takes advantage of the biliary excretion of
hepatocytes and then transported to the bile, where they paramagnetic contrast agents, allowing images to be ob-
cause T1 shortening as a result of their paramagnetic tained with a high-resolution 3D gradient-recalled echo
76 Angela D. Levy, Celso Matos
(GRE) T1-weighted sequence. Three different hepatobil- Therefore, after T2-weighted MRCP, high-resolution fat-
iary contrast agents are available for functional MRC: suppressed 3D GRE T1-weighted sequences are obtained
mangafodipir-trisodium, gadobenate dimeglumine, and without contrast and then again after intravenous admin-
gadolinium ethoxybenzyl diethylenetriaminepentaacetic istration of the contrast agent. First, dynamic axial views
acid (Gd-EOB-DTPA). Proportions of hepatobiliary ex- are acquired, to evaluate the vessels and the liver
cretion are higher for mangafodipir-trisodium and for Gd- parenchyma in the arterial and portal-venous phases. Sub-
EOB-DTPA (about 50%) than for gadobenate dimeglu- sequent scans are acquired in the coronal plane until vi-
mine. Unlike mangafodipir-trisodium, gadobenate dimeg- sualization of the contrast agent in the gallbladder and
lumine and Gd-EOB-DTPA allow evaluation of liver duodenum is noted. If additional delayed imaging is need-
parenchyma and angiographic renderings in the same ex- ed, the transit time of the contrast agent into the biliary
amination. For both reasons (high proportion of biliary tree and gallbladder may be determined; this estimate is
excretion and vascular assessment), we currently use Gd- valuable in the diagnosis of partial obstruction of the bile
EOB-DTPA. It should be emphasized that the degree of duct. Contrast-enhanced functional MRC increases the
biliary excretion of the contrast agent is dependent on liv- diagnostic performance of conventional MRC in detect-
er function. Tschirch et al. reported decreased visualiza- ing bile-duct leaks (Fig. 1), in assessing the patency of
tion or non-visualization of the biliary tree in a substan- biliary-enteric anastomoses (Fig. 2), and in diagnosing
tial percentage of patients with liver cirrhosis. In patients biliary complications of liver transplantation (Fig. 3).
with normal liver function, good visualization of the bil- Bridges et al. reported that, in the evaluation of liver
iary tree is observed 20-30 min after intravenous admin- transplants, delayed excretion (>45 min) was associated
istration of 0.025 mmol Gd-EOB-DTPA/kg body weight. with high-grade strictures. Moreover, neither the type of
Due to the fact that contrast injection indications are gen- anastomosis nor the presence of edema or ascites had any
erally based on the T2-weighted MRCP findings and be- influence on contrast-enhanced fMRC. When no excre-
cause of possible signal extinction in the bile duct on T2- tion is observed in the absence of biliary dilatation, trans-
weighted imaging and lack of visualization of the pancre- plant rejection should be considered as a possible cause.
atic duct, contrast-enhanced functional MRC is always Other potential clinical scenarios include sphincter of
obtained after T2-weighted MRCP has been acquired. Oddi dysfunction and impaired patency of biliary stents.
a b
Fig. 1 a, b. Bile duct leakage after cholecystec-

tomy. a T2-weighted MRCP shows a fluid-
filled collection adjacent to the extrahepatic
bile duct (arrows). b Contrast-enhanced func-
tional MRC confirms the leakage (arrows)
a b
Fig. 2 a, b. Biliary-enteric anastomoses: as-

sessing patency. a T2-weighted MRCP
shows dilatation of the intrahepatic bile duct
(arrow). The anastomoses is not depicted. b
Contrast-enhanced functional MRC shows
the anastomoses and progressive filling of
the jejunal loop (arrow)
Imaging Diseases of the Gallbladder and Bile Ducts 77
a b
Fig. 3 a, b. Liver transplantation: assessment of

biliary anastomoses. a T2-weighted MRCP
shows dilatation of the intrahepatic bile ducts
upstream to the biliary-biliary anastomoses
(arrow). b Contrast-enhanced functional
MRC shows the patency of the anastomoses
(arrow)
Conclusion an unusual pseudotumoral chronic inflammatory condition

of the gallbladder that radiologically simulates gallbladder
Major indications of functional MRC concern the assess- carcinoma. There is a significant overlap in the CT features
ment of complications after bile-duct surgery (diagnosis of XGC and gallbladder carcinoma. Both entities may
of bile duct leakage and determination of the patency of demonstrate wall thickening, infiltration of the surrounding
biliary-enteric anastomoses). Contrast administration fat, hepatic involvement, and lymphadenopathy. Adeno-
should be considered after the biliary morphology has myomatous hyperplasia, also called adenomyomatosis, is a
been evaluated on T2-weighted MRC. more common tumor-like lesion of the gallbladder that may
produce focal, segmental, or diffuse mural thickening.
Sonographically, adenomyomatous hyperplasia is charac-
Patterned Approach to the Diagnosis of Gallbladder terized by focal or diffuse thickening of the gallbladder
and Bile-Duct Diseases wall, with echogenic foci and ring-down artifact emanating
from the wall. The echogenic foci represent bile salts, cho-
lesterol crystals, or small stones in Rokitansky-Aschoff si-
Gallbladder Wall Thickening nuses. On MRI, Rokitansky-Aschoff sinuses are best visu-
alized on breath-hold T2-weighted sequences (Fig. 4). Con-
Focal or diffuse thickening of the gallbladder wall may be sequently, MRI can be useful to distinguish adenomyo-
caused by acute or chronic cholecystitis or non-inflamma- matous hyperplasia from gallbladder carcinoma.
tory conditions such as heart failure, cirrhosis, hepatitis,
hypoalbuminemia, renal failure, and human immunodefi- Gallbladder Polypoid Mass
ciency virus (HIV) infection. Gallbladder carcinoma may
also cause thickening of the gallbladder wall and should be Polypoid gallbladder masses are commonly demonstrated
suggested when there are findings of a focal mass, lym- on ultrasound as incidental findings when the gallbladder is
phadenopathy, extension of the process to adjacent organs, imaged sonographically. Polyps are estimated to be present
hepatic metastases, or biliary obstruction at the level of the in approximately 3% of gallbladders. The differential diag-
porta hepatis. Xanthogranulomatous cholecystitis (XGC) is nosis for a gallbladder polyp includes cholesterol polyp,
a b
Fig. 4 a, b. A 48-year-old man evaluated for

jaundice was found to have a benign stricture
in the distal common bile duct and adeno-
myomatous hyperplasia of the gallbladder.
a Longitudinal sonogram of the gallbladder
shows mural thickening along the anterior
gallbladder wall and echogenic foci in the
gallbladder wall that produce ring-down re-
verberation artifact. b Single-shot fast spin-
echo T2-weighted MR image with fat satura-
tion shows multiple hyperintense foci within
the thickened gallbladder wall, consistent
with adenomyomatous hyperplasia
adenoma, focal adenomyomatous hyperplasia, inflammato- These cysts may have normal intrahepatic bile ducts or
ry polyp, heterotopia, neurofibroma, carcinoma, carcinoid partial dilatation of the intrahepatic bile ducts in a non-
tumor, lymphoma, and metastasis. The majority of gallblad- obstructive pattern. It may be more difficult to differen-
der polyps are benign. Of these, the most common type is a tiate a choledochal cyst with mild or fusiform dilatation
cholesterol polyp, which accounts for ~50% of all polypoid of the extrahepatic duct from a duct that is dilated sec-
lesions. Cholesterol polyps have no malignant potential. On ondary to an obstructing lesion. In these cases, MRCP
sonography, they are typically brightly echogenic, round or and/or endoscopic retrograde cholangiopancreatography
slightly lobulated masses that do not produce acoustic shad- (ERCP) are useful to exclude an obstructing lesion and to
owing. Larger cholesterol polyps are usually less echogenic evaluate the pancreaticobiliary junction, an anomaly
and may contain an aggregation of echogenic foci. which is commonly observed in patients with chole-
The management of gallbladder polyps is based on the dochal cyst. Occasionally, pancreatic pseudocysts,
risk of malignancy, which increases for polyps >10 mm echinococcal (hydatid) cysts, and cystic biliary neo-
in size and in patients over the age of 60. As the incidence plasms, such as biliary cystadenoma or biliary cystade-
of malignancy in polyps >10 mm ranges from 37 to 88%, nocarcinoma, may occur in or around the porta hepatis,
patients with symptomatic polyps >10 mm are encour- simulating biliary dilatation and a choledochal cyst. The
aged to undergo cholecystectomy while those with polyps appearance of rim-like calcification and enhancing sep-
<10 mm should be followed periodically by ultrasound. tations or mural nodules should help in establishing the
At sonography, careful attention should be paid to other diagnosis of a biliary cystadenoma or cystadenocarcinoma.
features that suggest malignancy: thickening or nodular- Likewise, echinococcal (hydatid) cysts generally have
ity of the gallbladder wall, evidence of hepatic invasion evidence of inner membranes, daughter cysts, or rim-like
such as an indistinct margin between the liver and gall- peripheral calcification. T2-weighted MRI of hydatid
bladder, biliary duct dilatation, and peripancreatic hepato- cysts may show a fibrous capsule of low signal intensity
duodenal ligament adenopathy. If there are any features as well as membranes.
suggestive of malignancy, MDCT or MRI should be con-
sidered for further evaluation of the lesion. Cystic Dilatation of Intrahepatic Bile Ducts
Cystic Dilatation of the Extrahepatic Bile Duct Similar to dilatation of the extrahepatic duct, mechanical
biliary obstruction is the most common cause of intra-
Mechanical biliary obstruction is the most common cause hepatic bile duct dilatation. Intrahepatic biliary dilatation
of extrahepatic bile duct dilatation. Upon initial imaging, due to mechanical obstruction is generally tubular and
an obstructive lesion should always be sought when bil- lacks focal stricture formation. Caroli disease, recurrent
iary dilatation is present. Once an obstructive lesion is ex- pyogenic cholangitis, polycystic liver disease, primary
cluded, congenital etiologies of bile duct dilatation should sclerosing cholangitis, choledochal cyst, and peribiliary
be considered. Choledochal cysts, unlike obstructive di- cysts should be included in the differential diagnosis of
latation, generally have more focal extrahepatic bile duct cystic intrahepatic biliary dilatation. Caroli disease is
dilatation or are typically more expansive than what is suggested by focal or diffuse biliary dilatation that is cys-
usually encountered in mechanical dilatation (Fig. 5). tic or fusiform in character (Fig. 6). When diffuse in-
volvement is present, the bile ducts converge toward the
porta hepatis. Echogenic intraductal sludge or inflamma-
tory debris may be seen, as well as echogenic stones with
posterior acoustic shadowing. The most important differ-
ential diagnosis for patients with suspected Caroli disease
is recurrent pyogenic cholangitis, which is characterized
by biliary dilatation with intrahepatic stone formation.
The left hepatic lobe is more commonly involved than the
right in recurrent pyogenic cholangitis. Polycystic liver
disease may also mimic Caroli disease. However, in most
cases, the bile ducts in polycystic liver disease are intrin-
sically normal; only rarely will the cysts communicate
with the bile ducts.
Although intrahepatic bile duct dilatation is a feature
of primary sclerosing cholangitis, the dilatation is typi-
cally fusiform and isolated. In primary sclerosing cholan-
gitis, the degree and extent of duct dilatation is not as se-
vere as that in obstructive biliary dilatation, Caroli dis-
Fig. 5. Choledochal cyst in a 3-year-old boy evaluated for a palpa-
ble right upper quadrant mass. MRCP shows marked extrahepatic ease, or recurrent pyogenic cholangitis; instead, fibrosis,
bile duct dilatation with minimal dilatation of the central intra- stricture formation, and secondary cirrhosis are the ma-
hepatic ducts jor features.
Imaging Diseases of the Gallbladder and Bile Ducts 79
a b
Fig. 6 a, b. Caroli disease in a 23-year-old man

who complained of abdominal pain. a Sagittal
sonogram of the liver shows multiple cystic
spaces in the posterior right lobe. b MRCP
shows high signal intensity within these cysts
Choledochal cyst should be considered in the differen- (in or near the confluence of the right and left hepatic
tial diagnosis if there is both intrahepatic and extrahepat- ducts) may be secondary to hilar cholangiocarcinoma
ic duct dilatation. Generally, in patients with choledochal (Klatskin tumor) (Fig. 7), inflammation, or vascular
cyst the extrahepatic dilatation is more severe than the impressions. Strictures in the mid-portion of the extra-
intrahepatic dilatation. hepatic bile duct are commonly related to diseases of the
Multiple peribiliary cysts in sequence may simulate gallbladder, such as carcinoma, that have invaded the cys-
bile duct dilatation characterized by a beaded or saccular tic duct and hepatoduodenal ligament or to inflammatory
appearance. Since the bile ducts adjacent to peribiliary conditions, such as impaction of a stone in the cystic duct
cysts are normal, correct diagnosis depends upon the vi- (Mirrizi syndrome). Distal extrahepatic strictures may be
sualization of a normal bile duct. Peribiliary cysts are due to inflammatory or neoplastic diseases of the pan-
usually associated with hepatic diseases such as cirrhosis, creas, primary carcinomas of the bile duct or ampulla,
polycystic liver disease, portal hypertension, portal vein sphincter of Oddi dysfunction, or, less commonly, infec-
obstruction, and metastatic disease. tious papillitis such as seen in AIDS cholangiopathy.
Biliary Stricture
Conclusions
Focal narrowing or strictures in the biliary ducts may be
secondary to neoplasia, inflammation, trauma (iatrogenic A patterned approach to differential diagnosis of gall-
or non-iatrogenic), or mass effect from adjacent processes. bladder and biliary duct disease is useful and may be ap-
The location of the biliary stricture narrows the differen- plied to the findings identified on all non-invasive imag-
tial diagnosis. Strictures at the level of the porta hepatis ing techniques.
a b
Fig. 7 a, b. Hilar cholangiocarcinoma in a 40-

year-old man who complained of abdominal
pain. Coronal MRCP (a) and percutaneous
transhepatic cholangiogram (b) show a hilar
stricture and mild intrahepatic biliary di-
latation
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IDKD 2010-2013
Diseases of the Pancreas, I: Pancreatitis

Thomas Helmberger
Institute of Diagnostic and Interventional Radiology and Nuclear Medicine, Klinikum Bogenhausen, Munich, Germany
Introduction importance because of significant differences in progno-

sis and management.
The incidence of pancreatic inflammatory diseases in the The differential diagnosis in terms of solid and cystic
Western world is 110-240 cases/1 million individuals. In tumors is discussed in the chapter by Thoeni (Diseases of
about 80% of these cases, the underlying cause is an un- the Pancreas II: Tumors).
detected gall stone disease or alcohol abuse. The former
is more prevalent in women and the latter in men, espe-
cially those between 30 and 50 years of age. Neverthe- Acute Pancreatitis
less, there are many other factors that can cause pancre-
atitis (Table 1). Acute pancreatitis (AP) is defined as an inflammatory
The manifestations of pancreatitis range from mild, process involving the gland that was normal prior to the
self-limiting disease to severe, lethal forms in acute pan- attack and is normal again once the derangements that
creatitis or permanent loss of exocrine and/or endocrine precipitated the attack have been corrected. AP is a com-
function in chronic pancreatitis [1-5]. Clinically, it can be mon problem, with a rising incidence in the Western
difficult to differentiate cystic changes of the pancreas world. In the USA, it currently accounts for about 200,000
from cystic tumors, and chronic pancreatitis (CP) from admissions/year and about 10,000 deaths/year. The dis-
pancreatic cancer due to similarities in imaging presenta- ease is most frequently seen in individuals in the fifth to
tion. Nevertheless, the differential diagnosis is of ample sixth decade of life, and the most common causes are
Table 1. Potential causes of pancreatitis

Metabolic Alcohol
Drugs (e.g., glucocorticosteroids, azathioprine, hydrochlorothiazide, furosemide, sulfonamides,
estrogens, pentamidine, didanosine (DDI), valproic acid)
Hypertriglyceridemia
Hyperalimentation with lipids
Hypercalcemia
Hyperparathyroidism
Mechanical/obstructive Gall stones
Tumors (carcinoma of the pancreas or common bile duct, tumor in the ampulla and duodenum,
metastases)
Sphincter of Oddi dysfunction
After upper gastrointestinal tract surgery or endoscopy
Following abdominal trauma
Duodenal obstruction/scar (e.g., after ulcer disease)
Infectious Mumps
Coxsackie virus infection
Ascaris infection, with a mechanical component
Vascular Panarteriitis nodosa
After cardiac or pulmonary surgery
Severe arteriosclerosis
Other Hereditary, idiopathic
Anomalies (pancreas divisum, annulare)
Autoimmune
Scorpion sting/gila monster bite
Unknown (microlithiasis??)
82 Thomas Helmberger
cholelithiasis (75%) and alcohol abuse (15%). Other caus- edema and peripancreatic fluid collections can be pre-
es are listed in Table 1. sent. Nonetheless, in 30% of the cases, no morphological
With respect to pathophysiology, the most likely fac- changes can be appreciated. In cholelithiasis, segmental
tors for the sudden onset of AP are pancreatic hyper- pancreatitis, mainly of the pancreatic head, is seen in up
secretion, intra- and extravasation of pancreatic secre- to 20% of cases (Fig. 1).
tions, and premature activation of pancreatic enzymes, Ultrasound (US) may reveal a normal to mildly en-
followed by autodigestion and necrosis of the pancreatic larged gland with homogeneous (hypoechoic) echogenic-
gland and peripancreatic tissues. ity, but sufficient visualization by US is possible only in
AP can be divided clinically into mild and severe 60-70% of cases. In contrast-enhanced computed tomo-
forms, which are almost paralleled by the pathophysio- graphy (CT) and, while generally not necessary, magnetic
logical findings of interstitial (edematous) and necrotiz- resonance imaging (MRI), the gland is diffusely enlarged
ing forms [6, 7]. Mild AP (~50% of cases) is character- and a small amount of fluid is seen outlining the gland.
ized by mild symptoms and transitory elevation of amy- Imaging is needed to rule out other underlying conditions
lase levels that recover rapidly without complications. In that can be accompanied by hyperamylasemia, such as
general, the gland may be enlarged due to a moderate bowel obstruction, bowel infarction, gangrenous chole-
cystitis, and perforated ulcers.
In mild to moderate progressing forms of AP, the con-
tour of the gland becomes shaggy. The appearance of the
parenchyma on CT and MRI may be heterogeneous, and
small intraglandular and/or retroperitoneal fluid collec-
tions adjacent to the organ may develop (Fig. 2).
The severe forms of pancreatitis are determined by a
delayed/absent response to conservative therapy or even
deterioration under therapy. Mortality at the latter stage
can be as high as 100%. Typical findings in severe
(necrotizing) AP are varying degrees of parenchymal
necrosis accompanied by progressive exudation, superin-
fection of necrotic tissue, hemorrhage, abscess forma-
tion, phlegmon (~inflammatory pannus), and vascular
erosion (Fig. 3).
Depending on the particular pathomorphological con-
dition, the pancreas and its surroundings present a rather
Fig. 1. Computed tomography image of acute biliary pancreatitis.
Edematous enlargement of the pancreatic head and an exudation sur-
wide spectrum of imaging findings. In severe cases, US
rounding the duodenum and along the pararenal fascia are seen. The imaging is often compromised by overlying gas, peripan-
cause was a biliary stone trapped in the ampullary region (arrow) creatic exudation, and phlegmonous changes. In necrosis,
a b
Fig. 2 a, b. Magnetic resonance imaging of acute pancreatitis after cholecystectomy and reconstruction of the extrahepatic common bile duct.
a T1-weighted gradient-echo image shows the slightly dilated side branches of the pancreatic duct (arrow). A small fluid rim on the ante-
rior renal fascia is seen. b The heavily T2-weighted image reveals fluid outlining the pancreatic gland and the slightly dilated pancreatic
duct. Note the moderate stenosis (arrow) of the common bile duct after surgical reconstruction
Diseases of the Pancreas, I: Pancreatitis 83
a b
Fig. 3 a, b. Acute severe pancreatitis. a Contrast-enhanced CT obtained at admission shows a fuzzy contour of the pancreatic gland togeth-
er with a peripancreatic exudation (arrows) during the venous phase. Note the hypo- and hyperdense hepatic lesions (arrowheads). b Con-
trol scan 10 days later revealed an almost normal gland with resorption of the peripancreatic fluid. However, an area with a lack of en-
hancement, representing focal necrosis (large arrow), was observed. In the liver, one lesion turned out to be a hemangioma (arrow), while
the other two lesions were small abscesses
the pancreatic appearance becomes increasingly hypoe- Table 2. CT grading in acute pancreatitis (from [26, 27])
choic, without differentiation of vital from necrotic tis- Grade CT findings
sue. Therefore, US is generally used for second-line,
complementary imaging during patient follow-up in or- A Normal
B Focal (~20%), diffuse enlargement of the gland, irregu-
der to detect fluid formations such as pseudocysts. lar contour, inhomogeneous density
Parenchymal necrosis is best displayed on contrast-en- C Grade B + inflammation of the peripancreatic fat
hanced CT during at least the portal-venous phase. Char- D Small, mostly occasional fluid collections or phlegmon
acteristic findings are patchy areas showing a lack of en- E Two or more fluid collections, gas within the pancreas
hancement, (pseudo) fragmentation, and liquid necroses. or retroperitoneum
Additionally, increasing peripancreatic exudations dis-
secting along retroperitoneal fascia planes into the meso-
colon and the small bowel mesentery as well as peri-
pancreatic inflammatory tissue (phlegmon) and infected outcome. Several clinical and laboratory scoring systems
areas are frequently seen. In <10% of cases, small amounts have been established to stage and predict the clinical
of intraperitoneal fluid (ascites) are present, whereas large course of severe AP (Ranson’s score, APACHE II). How-
volumes of intraperitoneal fluids are very rare. ever, these scoring systems are mainly dependent on sys-
According to the literature, there is no significant su- temic alterations and are quite non-specific, as they fail
periority of MRI over CT in the diagnosis of AP and its to address the local condition of the pancreas [18-25].
related complications. The superior tissue resolution and Balthazar et al. [26, 27] showed that contrast-enhanced
higher sensitivity to slightly edematous or necrotic CT is the most helpful diagnostic modality to detect
changes and to hemorrhage or fluid dissection of fat complications that may necessitate medical, surgical, or
planes favor MRI. However, these advantages are often interventional management, and to predict outcome de-
hampered by the impaired study conditions in severely ill pending on the local condition of the pancreas. The pro-
patients that may degrade the image quality. In patients posed 5-grade scoring system (Tables 2, 3), by estimat-
with severe AP who are administered iodinated contrast ing the presence and degree of pancreatic and peripan-
agents, pancreatic flow can be reduced followed by an in- creatic inflammation and fluid accumulation and by de-
creased rate of necrosis and mortality. While this would tecting the presence and extent of pancreatic necrosis to-
seem to favor MRI as a staging tool in AP, this potential gether with estimation of the lack of gland enhancement
complication has not been proved for the non-ionic con- (<30, 30-50, >50%), can be translated into a CT-severity
trast agents that are nowadays used almost exclusively in index (Table 3) that allows estimation of the complica-
CT [8-10]. tions (morbidity) and of mortality (Fig. 4). If >50% of
The local inflammatory conditions are often compli- the pancreatic volume is necrotic, morbidity rises to al-
cated by regional and systemic involvement induced by most 100%. Recently, a modified and simplified CT
autodigestion and activation of systemic inflammatory severity index was proposed by Mortele et al. [28] that
mediators [11-17]. A rapid change in the local pancreat- more closely correlates with patient outcome measures
ic and overall abdominal situation demands an adequate than is the case with the currently accepted CT severity
diagnostic and therapeutic regime to avoid a disastrous index (Table 3).
Table 3. “Classic” and modified CT severity index

CT severity index Points Modified CT severity index Points
Pancreatic inflammation Pancreatic inflammation

Normal pancreas 0 Normal pancreas 0
Focal or diffuse enlargement of the pancreas 1
Intrinsic pancreatic abnormalities with or without 2 Intrinsic pancreatic abnormalities with inflammatory 2
inflammatory changes in peripancreatic fat changes in peripancreatic fat
Single, ill-defined fluid collection or phlegmon 3 Pancreatic or peripancreatic fluid collection or 4
Two or more poorly defined collections or presence 4 peripancreatic fat necrosis
of gas in or adjacent to the pancreas
Pancreatic necrosis Pancreatic necrosis
None 0 None 0
≤30% 2 ≤30% 2
>30-50% 4 >30% 4
>50% 6 Extrapancreatic complications (one or more of 2
pleural effusion, ascites, vascular complications,
parenchymal complications, or gastrointestinal
tract involvement)
100 % In a septic patient, not-water-like fluid collections and

90 rim enhancement on contrast-enhanced CT or MRI stud-
80 ies should be considered as abscesses until proven other-
70 wise. Gas, a characteristic sign of an infected fluid col-
60 lection, is detected in only 20% of patients with pancre-
50 Mortality
atic abscesses. Percutaneous aspiration or drain place-
40 Complications ment is the proper treatment.
30 In contrast to abscess formations, superinfected
20
necrotic areas of the pancreas are much more difficult to
10
treat. Due to the more solid consistency of the infected
0
0-3 4-6 7 - 10 necrosis, percutaneous drainage therapy is mostly frus-
trating; however, biopsy is often needed to prove the di-
Fig. 4. CT severity index related to the degree of necrosis of the
pancreatic parenchyma. Grade A = 0, B = 1, C = 2, D = 3, E = 4; agnosis. In most cases, either percutaneous, endoscopy-
no necrosis = 0, 30% necrosis = 2, <50% necrosis = 4, >50% guided necrosectomy, or surgical intervention has to be
necrosis = 6 (from [26,27]) considered.
Pseudoaneurysm formation and hemorrhage may re-
sult from the extravasated pancreatic enzymes that cause
About a fifth of the patients without necrotic changes vascular injury. They are typically late complications that
of the pancreatic gland will also develop local complica- occur after several episodes of severe AP. While pseudo-
tions. Fluid collections are seen in up to 50% of patients aneurysms are generally easily detected by any kind of
with AP. In about half of these patients, the collections imaging modality, retroperitoneal hemorrhage is best
will resolve spontaneously within several weeks. In the depicted by contrast-enhanced CT or unenhanced MRI.
rest, however, the fluid collections will persist, eventual- Angiography with arterial embolization is the treatment of
ly followed by encapsulation, superinfection (abscess), or choice and in general is superior to surgical therapy [29].
pseudocyst formation.
Groove Pancreatitis
Complications
First described by Becker in 1973, groove pancreatitis is a
Pseudocysts are fluid collections with a noticeable capsule rare, late complication occurring after several attacks of
that typically develop 4-5 weeks after the onset of AP. On AP. It is defined as an inflammatory reaction and fluid col-
US, CT, and MRI, they have a cyst-like appearance, usu- lection located in the groove between the head of the pan-
ally without septations. Since large cysts are prone to creas, the duodenum, and the common bile duct. The an-
complications (e.g., rupture, infection, hemorrhage, bil- terior anlage of the pancreas seems to be mainly affected,
iary obstruction, or fistulization to the gastrointestinal with duodenal stenosis and/or strictures of the common
(GI) tract), cysts >5-7 cm in diameter should be treated by duct in about 50% of the cases. Therefore, this disease may
percutaneous drainage or operative marsupialization. mimic cancer of the pancreatic head, necessitating surgi-
cal exploration. Dynamic CT and MRI with delayed en- Tumor markers such as CA 19-9 and CA-50 may be
hancement of collagen fibrous tissue during the late post- elevated transiently and are non-specific. Laboratory
equilibrium phase may reveal a potential soft-tissue mass tests of secretin-creozyme and secretin-caerulein have a
to be fibrosis and thus, in the absence of complications, high diagnostic accuracy except in early stages of the dis-
obviate the need for surgical exploration [30-33]. ease but are invasive and cumbersome for the patient.
However, these tests are of particular importance in the
diagnostically challenging, newly defined small-duct CP,
Autoimmune Pancreatitis in which chronic inflammation occurs without ductal ab-
normalities.
Autoimmune pancreatitis (AIP) is a relatively new syn- In CP, the most characteristic findings are dilatation of
drome of clinical and histological findings that was first the pancreatic main duct and of the ductal side branches
described by Yoshida in 1995 [34]. The condition has al- (70-90%), small cystic changes, scattered glandular and
so been described as lymphoplasmocytic sclerosing pan- ductal calcifications (40-50%), and ductal protein plugs.
creatitis with cholangitis, non-alcoholic duct-destructive The grade and shape of the ductal dilatation may help to
chronic pancreatitis, and chronic sclerosing pancreatitis. differentiate chronic (benign) obstructions from malig-
The features of AIP include hypergammaglobulinemia, nant occlusions: in CP, the contour of the pancreatic duct
elevation of serum IgG4, IgG4-containing immune com- and its side branches is commonly irregular (73%) while
plexes, and a number of other antibodies as antinuclear this is true only in 15% of pancreatic malignancies. Ad-
antibodies, as well as antibodies against lactoferrin, car- ditionally, the duct usually accounts for <50% of the pan-
bonic anhydrase type II, and rheumatoid factors. Histo- creatic anterior-posterior diameter in CP while the oppo-
logically, there is fibrosis and a lymphoplasmacytic infil- site is true in pancreatic cancers (due to obstructive atro-
tration of the interlobular ducts. The majority of lympho- phy). In some cases, additional secretin-enhanced mag-
cytes are CD8+ and CD4+, while B lymphocytes are less netic resonance cholangiopancreatography (MRCP) can
frequent. In general, the diagnosis of AIP is established be helpful as it provides an improved display of the duct
by clinical signs, together with laboratory and morpho- system and allows assessment of the excretory capacity
logical findings. An association with other autoimmune of the pancreatic gland [43].
diseases, such as Sjögren-syndrome, primary biliary cir- In CP, the gland may have a normal appearance in 15-
rhosis, primary sclerosing cholangitis, Crohn’s disease or 20% of patients, but most common is a diffuse (50%) or
ulcerating colitis, systemic lupus erythematosus, and focal (25%) enlargement that may arouse suspicion of a
retroperitoneal fibrosis is found in a third of the cases. neoplasm. With time, atrophy of the organ will occur in
At imaging, a focal (“mass-forming”) or diffuse 10-50% of these patients. The variable appearance of CP
(“sausage-like”) enlargement of the pancreas may be pre- explains the shortcomings in establishing the diagnosis.
sent. In contrast-enhanced studies, peripancreatic nodular In the absence of gross morphological changes it is very
or rim-like enhancement can be appreciated. Focal AIP of difficult to identify incipient forms of CP. Moreover,
the pancreatic head that involves the pancreatic and dis- morphological changes correlate very poorly with the
tal common bile duct must be differentiated from pan- functional exocrine and endocrine deficits. Consequent-
creatic carcinoma, necessitating biopsy proof [35, 36]. ly, endoscopically guided (endoscopic US) or percuta-
In most patients, the symptoms as well as the labora- neous biopsy may be necessary for the diagnosis.
tory and morphological abnormalities appear to respond
to steroid treatment [34, 37-42]. Complications
These include consolidated cystic degeneration involving

Chronic Pancreatitis dilatation of the cystic and side branches of the pancreat-
ic duct and peripancreatic pseudocyst formation (Fig. 5).
The hallmarks of chronic pancreatitis (CP) are a continu- In addition, there may be obstruction of the common bile
ing (aseptic) inflammation of the gland accompanied by ir- duct secondary to fibrosis, splenic vein thrombosis (note:
reversible morphological and functional damage. The most upper GI tract bleeding may result from gastric varices in
common reasons are chronic alcohol abuse (70%) and the absence of esophageal varices!), and pancreatic fistu-
cholelithiasis (20%), with rare cases arising from cystic fi- lae (communications between the pancreatic duct and ab-
brosis or idiopathically. Patients are typically in their 3rd to dominal organs or the skin).
4th decade of life and present with a history of epigastric
pain (95%), weight loss (95%), and signs of endocrine/ Diagnostic Challenge
exocrine deficiency (diabetes mellitus 58%, malabsorption
syndrome and steatorrhea 80%). Acute exacerbations of In general, the diagnosis of inflammatory and tumorous
CP are accompanied by episodes of pain attacks that pancreatic conditions relies on imaging (US, CT, MRI)
may mimic an acute abdomen. With progressive destruc- and, more invasively, endoscopic retrograde cholan-
tion of the gland, CP may be painless after several years. giopancreatography (ERCP). Imaging findings are deter-
In 1.5-12% of cases it is complicated by pancreatic cancer. mined by the macro-structural changes of the organ and
a b
Fig. 5 a, b. Chronic pancreatitis. Cystic degeneration of the pancreatic head (a) together with irregular dilatation of the pancreatic main duct
(b) is seen on MRI (fast spin-echo T2)
its surroundings. On plain films and US, the calcifica- Table 4. Ranson score based on clinical and laboratory signs at
tions in CP are readily depicted. Additionally, US is able admission and at 48-h follow-up (each sign = 1 point)
to display ductal dilatation, micro- and macrocystic At admission 48-h follow-up
changes, and the gland itself.
Age >55 years Hematocrit decrease >10%
Contrast-enhanced multidetector CT (MDCT) is well
WBC >16,000 Blood urea nitrogen increase
established in the assessment of ductal changes, calcifi- >5 mg/dL
cations, and alterations in the form and shape of the pan- Blood glucose >200 mg/dL Ca (serum) <8 mg/dL
creatic gland, as well as potential concomitant conditions Serum LDH >350 IU/L PO2 <60 mmHg
such as pseudocysts. In addition, multiplanar, curved re- SGOT (AST) >250 U/L Base deficit >4 meq/L
constructions yield high-resolution display of the entire Estimated fluid sequestration
gland and the anatomical course of the duct. Depending >600 mL
on the fibrotic changes in CP, contrast enhancement can Score Mortality (%)
be variable, whereas most ductal carcinomas show no or 0-2 <10
only minor enhancement during arterial-dominant- and 3-5 10-20
parenchymal-phase imaging. However, late enhancement >5 >50
can be seen on delayed imaging without substantial addi-
tional information [44].
In addition to MRI’s superior tissue resolution in the
differentiation of varying “qualities” of pancreatic missed diagnosis of carcinoma. However, if local or re-
parenchyma, using unenhanced and Gd-DTPA-enhanced gional lymph node enlargement, vascular encasement, or
T1-weighted (±fat suppression) and heavily T2-weighted remote metastases is displayed, the differential is ruled by
sequences, it optimally displays the pancreatic gland, the these secondary signs of malignancy, in which case the
pancreatic duct including the first-degree side branches, tumor must be staged correctly for further treatment strat-
and even small stones. Nevertheless, initial, minor ductal ification (Tables 3, 4). In ambiguous cases, biopsy or
changes are best seen on ERCP (Table 3), which in this even surgical exploration may be necessary.
respect is superior to all other imaging modalities. How- CP can cause a focal pancreatic mass indicative of a
ever, the clinical significance of these slight changes re- neoplasm. Moreover, it represents a major risk factor for
mains contentious, further compromised by potentially pancreatic cancer, with a 26-fold increased risk of devel-
“non-physiological” distention of the ducts due to the in- oping cancer, according to an international, multicenter
jected contrast material. cohort study [45]. Therefore, the differential between CP
Pancreatic cancer is the most serious complication of and pancreatic cancer remains challenging and under-
CP and is the major diagnostic challenge because the fo- lines the need for multiple diagnostic approaches. In one
cal enlargement of the gland induced by a fibrotic in- study, US, CT, MRI, and positron emission tomography
flammatory pseudotumor may be indistinguishable from (PET)/CT for pancreatic cancer were shown to have a
carcinoma. A comparison using state-of-the-art MDCT sensitivity of 76-83% and a specificity of 91-93% [46].
and MRI showed no difference in the detection rate of Nevertheless, the rate of incorrect diagnoses is as high as
pancreatic carcinoma, according to the recent literature. 25%. The use of various differential criteria (Table 5)
Nevertheless, the potential tumor-like appearance of CP may help to improve the overall diagnostic accuracy be-
accounts for the fact that it is still the major reason for a yond that achieved based solely on image interpretation.
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36. Weili L, Jiaguo W (2009) Education and imaging: Hepatobil- terol 89:1467-1471
iary and pancreatic: autoimmune pancreatitis. J Gastroenterol 46. Tang S, Huang G, Liu J et al (2009) Usefulness of (18)F-FDG
Hepatol 24:1574 PET, combined FDG-PET/CT and EUS in diagnosing primary
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39. Wakabayashi T, Kawaura Y, Satomura Y et al (2003) Clinical 48. van Kouwen MC, Jansen JB, van Goor H et al (2005) FDG-
and imaging features of autoimmune pancreatitis with focal PET is able to detect pancreatic carcinoma in chronic pancre-
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called tumor-forming pancreatitis and pancreatic carcinoma. 49. Manfredi R, Lucidi V, Gui B et al (2002) Idiopathic chronic
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170:1323-1327 creatitis. Am J Gastroenterol 96:2540-2555
IDKD 2010-2013
Diseases of the Pancreas, II: Tumors

Ruedi F. Thoeni
Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
Introduction the leading causes of cancer death in the western world,

and the overall relative 5-year survival rate of only 5.5%
In the imaging of pancreatic disease and in assessment of is dismal [24]. Late clinical presentation with advanced
the etiology of jaundice, abdominal ultrasound (US) and disease and the aggressiveness of the tumor result in a
computed tomography (CT) traditionally have been em- low rate of surgical intervention and overall poor out-
ployed [1]. These two methods are widely available and come. It is estimated that 42,470 men and women will be
have the advantages of their familiarity to radiologists and diagnosed with cancer of the pancreas in 2009 and that
clinicians and their non-invasiveness. With the introduction over 80% of these patients will die of the disease [25].
of magnetic resonance imaging (MRI), magnetic resonance The tumor serum marker CA 19-9 is sensitive, although
cholangiopancreatography (MRCP), and endoscopic ultra- not specific for the diagnosis of adenocarcinoma of the
sound (EUS), visualization of the pancreatic and biliary pancreas. The treatment approach is based on whether the
ducts improved, allowing tumors to be more accurately tumor can or cannot be resected at presentation. There-
staged and safely sampled [2-12]. This led to a diminishing fore, imaging plays a crucial role in disease management.
role for endoscopic retrograde cholangiography in the diag- The initial diagnosis of pancreatic tumor, particularly
nostic arena but its therapeutic use has remained unchal- if the patient presents with jaundice and the tumor is lo-
lenged. In recent years, technological advances with multi- cated in the head of the pancreas, may be made by US.
detector row CT (MDCT) imaging have improved the abil- The ultrasonographic signs of pancreatic carcinoma in-
ity of CT to detect even small lesions in the pancreas and to clude a focal or diffuse pancreatic mass that is hypo-
stage pancreatic tumors more accurately [13]. Microbubble echoic relative to normal gland parenchyma and dilata-
contrast enhancement and secretin stimulation have in- tion of the pancreatic duct without or with biliary duct
creased the diagnostic acumen of US and MRI, respective- distention (double-duct sign). The accuracy of US for de-
ly, and may widen the utility of these techniques [14, 15]. tecting the level of bile duct obstruction varies greatly,
Nevertheless, MDCT remains the primary tool in as- and ultrasonographic staging of pancreatic carcinoma is
sessing patients with suspected pancreatic disease, while inferior to that of CT. Ultrasonography often fails to pro-
EUS and MRI are used as problem-solving modalities to vide an adequate examination of the entire gland, result-
confirm suspected lesions not identified with CT, to find ing in an overall decrease in the sensitivity of this tech-
additional lesions, and to obtain a definitive tissue diag- nique. Some of these limitations are overcome by en-
nosis with EUS-guided tissue sampling. In recent years, dosonography, but tumors in the tail of the pancreas are
position emission tomography/CT (PET/CT) has been in- not always accessible by EUS.
creasingly employed in the assessment of patients with For optimal evaluation of pancreatic neoplasms, MDCT
suspected pancreatic tumors but its ultimate role still is the modality of choice. A triple-phase protocol is rec-
needs further definition [16-21]. Also, somatostatin re- ommended that includes thin sections (0.625 or 1.25 mm)
ceptor scintigraphy has gained popularity in recent years through the abdomen, initially without intravenous contrast
for neuroendocrine tumors [22, 23]. This discussion will followed by a rapidly delivered bolus of contrast material
focus on diagnosing and staging the various pancreatic (we use bolus tracking and 150 mL at 5 mL/s chased by
neoplasms with CT and MRI, mentioning EUS, PET/CT, 50 mL of saline). It is best to use a neutral oral contrast
and somatostatin receptor scintigraphy where appropriate. agent (water or VoLumen, Bracco Diagnostics, USA) be-
cause it permits optimal assessment of tumor extension to
the stomach and/or duodenum and does not interfere with
Ductal Adenocarcinoma of the Pancreas the determination of vascular invasion. We recommend a
scan delay of 40-45 s (10-s delay from peak aortic enhance-
About 90% of all neoplasms of the pancreas are ductal ment) for the late arterial or pancreatic phase and a scan
adenocarcinomas. Pancreatic adenocarcinoma is one of delay of 80 s for the hepatic phase. Rarely, an arterial phase
90 Ruedi F. Thoeni
at 20-25 s is performed if requested by surgery [26]. Arte- liver, peritoneum (often associated with ascites), and
rial involvement and tumor mass are best detected in the more distant sites. The double-duct sign (dilatation of the
pancreatic phase whereas the hepatic phase enables opti- biliary and pancreatic ducts) occurs in <5% of patients
mal visualization of the liver, veins, and the entire ab- with pancreatic carcinoma. Biductal obstruction is a non-
domen in the search for liver metastases and peritoneal specific sign and may also be seen in bile duct or am-
seeding. One study demonstrated that a single-phase thin- pullary carcinoma, pancreatitis, and ampullary stenosis.
slice MDCT technique is sufficient for accurately assess- For MRI, T1-weighted fat-suppressed sequences and
ing the resectability of pancreatic adenocarcinoma [27]. dynamic gadolinium-enhanced spoiled gradient echo
Pancreatic adenocarcinoma arises from the pancreatic (SPGR) sequences are superior to T2-weighted se-
duct. On MDCT, the tumor usually appears as a low-den- quences, as most pancreatic carcinomas have a signifi-
sity mass, often associated with poorly defined margins cant desmoplastic reaction that renders the tumor less
(Fig. 1) and pancreatic and/or bile duct dilatation. The conspicuous on T2-weighted images. T1-weighted fat-
low-density central zone represents either hypovascular, suppressed images using an early (arterial) gadolinium-
scirrhous tumor surrounded by normal parenchyma or in- enhanced 3D vascular time-of-flight SPGR sequence pro-
flammatory tissue caused by obstructive pancreatitis. Oc- vide optimal delineation of the tumor, particularly if it is
casionally, cystic degeneration is seen within the tumor small and does not change the contour of the pancreas.
[28]. Neoplastic pancreatic duct obstruction frequently Diffusion-weighted imaging appears promising, especial-
produces a dilated duct as well as atrophy of the pancre- ly for metastases to the liver. MRCP sequences consist-
atic parenchyma proximal to the neoplasm. Tumor ob- ing of thin and thick axial and coronal sequences with
struction of the main pancreatic duct can lead to rupture heavy T2-weighting and breath-holding are often added
of the side branches, resulting in the formation of to better assess the pancreatic and biliary ducts.
pseudocysts. Occasionally, a low-density mass cannot be The CT imaging results for pancreatic carcinoma vary
identified because the tumor is isodense to the surround- widely, but with the current generation of scanners and
ing normal parenchyma. In these cases, a dilated duct state-of-the-art scanning techniques a sensitivity of >90%
with abrupt cut-off is often seen proximal to a small im- for detecting pancreatic carcinoma can be achieved [1, 27].
perceptible tumor mass. Ancillary findings are local tu- Small metastatic implants on the liver and peritoneum are
mor extension, including direct invasion of neighboring the lesions most likely to be missed by MDCT. MDCT
organs such as the liver and the stomach, the arteries (loss generally provides accurate information on vascular in-
of fat planes surrounding celiac axis, superior mesenteric volvement as long as a pancreatic protocol is observed; for
artery, etc., vascular “cuffing”) and veins (tear-drop sign, resectability, sensitivities of >80% have been obtained [1].
flattening, irregularity of margins, etc., of the portal vein, The positive predictive values for predicting unresectabili-
superior mesenteric vein and its branches), and metastat- ty are much better than those for predicting resectability.
ic disease to local lymph nodes, as well as spread to the Presently, most studies show a slight advantage of MDCT
a b
Fig. 1 a, b. a Thin-section (1.25 mm) axial MDCT of a pancreas carcinoma in the pancreatic phase (~40 s). A low-attenuation mass is ap-
parent in the head of pancreas near the uncinate process (white arrows), with encasement of the replaced right hepatic artery originating
from the superior mesenteric artery (arrowhead). Retroperitoneal lymphadenopathy also is seen (black arrow). The mass is easily distin-
guished from adjacent normal pancreas. b Thin-section (1.25 mm) axial MDCT of a pancreas carcinoma in the hepatic phase (~80 s) in
the same patient. Note the teardrop-shaped superior mesenteric vein (black arrowhead) as a sign of venous encasement. The low-attenua-
tion pancreatic neoplasm (arrows) is less well seen
Diseases of the Pancreas, II: Tumors 91
over MR for detecting and staging pancreatic adenocarci- and has been shown to improve patient management before
nomas. A meta-analysis comparing CT, MRI, and US possible resection. In one PET/CT study, management was
demonstrated a sensitivity and specificity of 91 and 85% changed in 16% of patients with pancreatic cancers that
for helical CT and a sensitivity and specificity of 84 and were initially staged as being resectable [17]. In suspected
82% for MRI whereas the results for resectability were tumor recurrence, PET reliably detected local recurrence
similar [1]. For US, the sensitivity for diagnosing pancreas and was advantageous in diagnosing distant disease [18].
carcinoma and the specificity for determining resectabili-
ty are much lower. The advantage of MRI is thought to be
in the area of small tumors that do not alter the contour of Neuroendocrine Neoplasms of the Pancreas
the gland [10] and in detecting hepatic metastases. At pre-
sent, MRI appears to be a problem-solving modality. It Hyperfunctioning Neuroendocrine Neoplasms
should be considered in patients with suspected pancreatic Among hyperfunctioning or syndromic neuroendocrine
neoplasms in the presence of: (1) allergy to iodine contrast neoplams (NEN, formerly called islet cell tumors) of the
or other contraindications to iodine contrast administra- pancreas, insulinoma is the most common followed by
tion, (2) a MDCT scan showing focal enlargement of the gastrinoma, glucagonoma, VIPoma, and other rarely en-
pancreas but no definable mass, (3) a clinical history sug- countered secretory neoplasms. In functioning pancre-
gesting malignancy and MDCT images that are equivocal atic adenomas, the clinical diagnosis is based on clinical
or difficult to interpret, and (4) when distinction between data and laboratory tests that usually permit an accurate
chronic pancreatitis with focal enlargement and pancreatic diagnosis, with cross-sectional imaging used only for
cancer is needed. When choosing an imaging modality, one localizing the pancreatic neoplasm [31].
has to take into account that, today, MDCT of the pancreas Insulinomas, and especially extrapancreatic NENs,
requires a small fraction of the time needed for a complete that are small and located in the duodenal or gastric wall
MRI study of the pancreas. (Fig. 2) may be difficult to detect pre-operatively by any
False-positive MDCT diagnoses of pancreatic cancer
can occur, especially in patients with chronic pancreati-
tis; therefore, percutaneous aspiration biopsies are need- a
ed if non-operative treatment is planned. Fine-needle as-
piration biopsy of pancreatic cancer under CT guidance
is a frequently performed procedure and is associated
with severe pancreatitis in <3%. The sensitivity of percu-
taneous CT biopsies reaches 79%, with a positive predic-
tive value of 100% and a negative predictive value of
47% [7]. However, because of possible tumor seeding in
the needle tract, patients with potentially resectable tu-
mors (only 10% of all cases) who are acceptable candi-
dates for surgery should undergo exploratory surgery [7].
While EUS excels in detecting even small pancreatic
adenocarcinomas, reaching sensitivities as high as 97% [9],
and can be used in the differential diagnosis of pancreatic
tumors [29], it demonstrates poor sensitivity and specifici-
ty for diagnosing vascular involvement by the tumor [30].
The technique suffers from limited depth penetration. To- b
day, endoscopic biopsies often replace percutaneous CT
biopsies of the pancreas. They have a sensitivity of 80%
with a positive predictive value of 99% and a negative pre-
dictive value of 73%. They are particularly indicated when
CT is equivocal or negative despite a strong clinical suspi-
cion for tumor and when the lesion is <3 cm in size [7].
PET, and particularly PET/CT, has emerged as an im-
portant modality for effectively managing patients with
suspected pancreatic cancer. Nevertheless, more studies
are needed to demonstrate its true value and cost-effec-
tiveness since at least one study found no benefit over CT Fig. 2 a, b. a Thin-section (1.25 mm) axial MDCT of an ectopic
alone [16]. It was also reported that if helical CT was pos- neuroendocrine tumor of the pancreas (insulinoma) in the pancre-
itive for pancreas carcinoma, PET had a sensitivity of 92% atic phase. A small hypervascular mass (arrow) is seen at the junc-
tion of the second to third duodenum. b Thin-section (1.25 mm)
and a specificity of 68%; if CT was negative, the sensitiv- coronal MDCT of an ectopic neuroendocrine tumor of the pan-
ity of PET was 73% and the specificity 86% [19]. PET/CT creas (insulinoma) in the pancreatic phase, which clearly demon-
allows hot tracer spots to be to more precisely localized strates the mass in the duodenal wall (arrow)
92 Ruedi F. Thoeni
of the radiographic techniques, and even intra-operative often diagnose small lesions only suspected on CT or
US fails to detect some of these lesions. However, MD- MRI and detect metastases not diagnosed with other
CT with 0.5-0.625 mm sections has improved the results. modalities.
These ectopic lesions are more likely to occur in patients
with multiple endocrine adenomatosis (MEA) or multiple Non-hyperfunctioning Neuroendocrine Neoplasms
endocrine neoplasia (MEN). A combination of intra-
operative palpation and intra-operative US was found to Non-hyperfunctioning or non-syndromic NENs are less
achieve the best results during surgery. Intra-operative frequently encountered than insulinomas or gastrinomas,
US is particular important in patients with multiple le- representing 15-25% of these neoplasms [31]. While they
sions and MEN. arise from the alpha or beta cells of the pancreas, these
On MDCT and MRI, functioning NENs generally neoplasms are hormonally quiescent (probably very min-
show intense enhancement in the arterial phase with rapid imal secretion) and often present as a mass with or with-
washout in the portal venous phase. The most common out jaundice or gastric outlet obstruction. These tumors
NEN, the insulinoma, usually is small (≤2 cm in diame- are usually located in the pancreatic head and can mea-
ter) and seldom metastasizes (5-10% of cases). All other sure up to 20 cm in diameter. There may be solid and
NENs tend to be large and frequently have metastases necrotic components, with coarse calcifications present
(60-65% of cases). The appearance of liver metastases in in up to 25%. The mass is hypervascular with a late cap-
patients with functioning NEN is similar to that of the illary stain. The tumor does not encase vessels but in
primary tumor. 80-100% there is malignant transformation, with liver
The reported sensitivity of conventional CT for de- metastases and adenopathy. The cumulative 5-year sur-
tecting an insulinoma ranges from 28 to 79% with a vival is 52-58% [35]. The key features of non-function-
mean of 38%. It is slightly higher for gastrinomas, due ing NENs are their large size, hypervascularity, and the
primarily to their larger size. A dual-phase MDCT pro- absence of vascular encasement. Results with CT and
tocol with thin sections improves the detection rate to MRI are similar.
94% and reaches 100% if combined with EUS [32]. The
latter modality provides excellent results in the head of
the pancreas, but the results are less convincing for the Cystic Neoplasms of the Pancreas
tail of the pancreas because of its distance from the
stomach. EUS usually allows the detection of even small Serous and Mucinous Cystic Neoplasms of the Pancreas
NENs and their precise location. Ectopic gastrinomas
may be missed by EUS but combining this technique Cystic neoplasms of the pancreas are uncommon tumors
with somatostatin receptor scintigraphy (SSR or Octreo- and account for <5% of pancreatic neoplasms. Pancre-
scan) increases the overall sensitivity for gastrinomas atic cystic neoplasms are classified into two categories:
[33]. The sensitivity of transabdominal US for detecting (1) serous cystic (usually microcystic, occasionally
insulinomas is low (mean of 46%) and therefore should macrocystic: unilocular or oligocystic) neoplasms that
not be used for this purpose. are benign; and (2) mucinous cystic (macrocystic) neo-
Functioning NENs of the pancreas are of low signal in- plasms that are potentially malignant or already malig-
tensity on T1-weighted images and of high signal inten- nant at the time of diagnosis. The rare serous macro-
sity on T2-weighted images [5]. Occasionally, an insuli- cystic variant is benign and exhibits radiological fea-
noma is of dark signal intensity on T2-weighted se- tures similar to those of mucinous cystadenoma. Serous
quences due to a fibrous stroma. In our study, the MRI and mucinous cystic neoplasms, except for intraductal
sensitivity for detecting functioning NENs of ≤2 cm in papillary mucinous tumors (IPMT), do not communi-
diameter reached 85%, which is similar to the sensitivity cate with the pancreatic duct.
achieved by invasive procedures [5]. For gastrinomas, a Serous cystic neoplasms of the pancreas are observed
MRI sensitivity of up to 62% has been reported [34]. in middle-aged and elderly women. This type of tumor
With present techniques, MRI should detect lesions may not require surgical treatment whereas mucinous
>2 cm with a sensitivity of over 85%. Therefore, MRI cystic tumors should be resected because of their malig-
with state-of-the-art equipment and optimal imaging nant potential. Nevertheless, some surgeons prefer to re-
techniques appears to be a useful strategy for diagnosing sect the serous type as well. In general, the patient’s age,
small pancreatic NENs. Nevertheless, contrast-enhanced symptoms, and overall condition, the lesion’s location,
MDCT, with its superior spatial resolution and very thin and its growth over time are factors that help to decide
sections, currently surpasses MRI in diagnosing these whether surgery is needed [36]. Often, any cyst that in-
small neoplasms. creases in size over time, any symptomatic cyst, and cysts
SSR with various derivatives of long-acting somato- in older fit patients are selected for surgery. CT can ac-
statin analogues [22] can be used for small gastrinomas, complish pre-operative differentiation of the two types in
somatostatinoma, glucagonoma, carcinoid, and VIPoma, many cases. In serous cystic tumors, traditionally the di-
but insulinomas may be missed due to reduced receptor agnosis is made if the number of cysts within the tumor
expression [22, 33]. SSR with 111In-octreotide can is more than six and the diameters of the cysts <2 cm. A
newer nomenclature prefers to call cysts ≤1 cm definite- cysts of the pancreas, particularly if they are multiple.
ly serous, those >1-2 cm equivocal, and those >2 cm def- Both MRCP and MDCT with curved planar reconstruc-
initely mucinous. Grossly, these serous tumors appear ei- tion can demonstrate the absence of a connection to the
ther as solid tumors with innumerable tiny cysts or as main pancreatic duct.
honeycombed cystic tumors, depending on the amount of
connective tissue. They have a lobulated margin (Fig. 3).
At times, it is difficult to visualize the cystic areas. Cal- Intraductal Papillary Mucinous Neoplasm of the Pancreas
cifications in serous tumors are central in location. A cen-
tral enhancing scar may be present and is characteristic of A rare tumor that is considered a subtype of the mucinous
a serous tumor [28]. cystic neoplasms of the pancreas is the intraductal papil-
Mucinous cystic neoplasms of the pancreas (also lary mucinous tumor of the pancreas (IPMN, formerly al-
called cystadenomas and cystadenocarcinomas according so called ductectatic cystadenoma or ductectatic cystade-
to the old nomenclature) have six or fewer cysts, the di- nocarcinoma). IPMN can be classified as main duct,
ameters of the cysts measure >2 cm, a central enhancing branch duct (side-branch), or mixed type depending on
scar is rarely seen, and calcifications are peripheral [28]. the site and extent of involvement [39]. The cystic
The margins usually are smooth and metastatic disease changes always demonstrate a connection to the pancre-
may be present at the time of diagnosis. atic duct, which is a diagnostic feature that can be seen
Based on the above-mentioned criteria, a correct diag- on MDCT and MRI. The branch duct tumor consists of
nosis of a serous cystic pancreatic tumor can be made in cystic dilation of the side branches of the pancreatic duct,
62% of patients by CT, in 74% by sonography, and in usually in the uncinate process. These ducts are lined
84% using both modalities [37]. Overall, the results for with atypical, hyperplastic, or clearly malignant epitheli-
mucinous cystic tumors are inferior. Pancreatic pseudo- um. In the late stages, the tumor nodules of the ducts pro-
cysts and cystic forms of islet cell tumors, ductal carci- duce copious mucinous secretions that fill the entire duct.
nomas, solid and papillary tumors, and lymphangioma of Since extension into the parenchyma and beyond occurs
the pancreas can be indistinguishable on CT from cystic
relatively late in branch duct IPMN and overall malignant
neoplasms. Thus, EUS needle biopsies of the lesions of-
degeneration is rare, the overall prognosis is good. In 25-
ten are necessary [38].
44% of resected specimens of the other two types, ma-
Better definition of the internal architecture of these
lignancy is present. Resection is therefore the treatment
cystic neoplasms is frequently obtained with MRI rather
than CT. MRI also demonstrates the presence of mucin, of choice in these patients.
seen as an area of increased signal intensity within the CT shows markedly dilated ducts and cystic-appearing
cysts on T1-weighted sequences. Septa and wall thick- structures filled with mucinous material, which has a
ness of the lesions are well demonstrated by MRI but this slightly higher attenuation than that of water. MRI seems
is not always true for calcifications. MRI is of great help to have a slight advantage over CT because it can visu-
in distinguishing these cystic neoplasms from pseudo- alize mucin within the cysts as well as the internal
architecture of the lesion, including a solid mass and
mural nodules (which are signs of malignancy) slightly
better than CT. EUS also is well suited to detect mural
nodules.
Solid Pseudopapillary Epithelial Neoplasm of the Pancreas

Solid pseudopapillary epithelial neoplasms, previously
called solid and cystic tumors of the pancreas, are rare tu-
mors. They are seen almost exclusively in young women
and are located mostly in the tail of the pancreas. This
neoplasm is characterized by a solid peripheral area of tu-
mor and a central zone of degeneration consisting of he-
morrhage and cystic spaces filled with necrotic debris
that can be visualized by CT (Fig. 4) and MRI. On imag-
ing, these tumors appear as sharply defined, heteroge-
neous, large cystic pancreatic masses with solid compo-
nents. They usually are benign but in older women they
may be malignant [40]. Calcifications may be present in
Fig. 3. Thin-section (1.25 mm) axial MDCT of a serous cystic neo-
plasm of the pancreas in the pancreatic phase. A lobulated and sep-
the capsule or in the inner portion of the mass. EUS also
tated cystic mass is present in the tail of the pancreas (arrows). The can be helpful in visualizing the nodules and the internal
individual cysts are small and the septa barely perceptible architecture of these masses.
94 Ruedi F. Thoeni
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IDKD 2010-2013
Adrenal Imaging and Intervention

William W. Mayo-Smith1, Isaac R. Francis2
1 Department of Radiology, Warren Alpert School of Medicine Brown University, Rhode Island Hospital, Providence, RI, USA
2 Department of Radiology, University of Michigan, Ann Arbor, MI, USA
Introduction computed tomography (CT) study depending on the

suspected source of ACTH production. If pituitary and
The objectives of this chapter are: (1) to describe the dif- adrenal neoplasms are ruled out and an ectopic source of
ferent work-ups for adrenal masses, depending on clinical hormone secretion is suspected, then a chest and abdomi-
scenario, (2) define adrenal incidentaloma, (3) discuss the nal CT should be performed to search for it.
relative risk factors for benign and malignant adrenal Conn’s syndrome can result from either adrenal hyper-
masses, (4) describe the imaging techniques to differenti- plasia or an adrenal cortical tumor producing elevated
ate benign from malignant adrenal masses, and (5) discuss levels of aldosterone, leading to increased sodium reten-
the recommended medical work-up of an adrenal mass. tion, hypertension, and potassium wasting. The diagnosis
The adrenal gland is a complex organ that is made up is suspected in a hypertensive patient with low serum
of the catecholamine-producing medulla and the steroid- potassium and is confirmed by measuring the ratio of
producing cortex. It is a common site of primary tumors serum aldosterone to renin levels. When the diagnosis is
(functional and non-functional) and of metastases. The suspected based on biochemical assays, CT scans using
optimal work-up for an adrenal mass depends on the pa- 3-mm collimation targeted to the adrenals is useful to dif-
tient’s clinical scenario and whether detection or charac- ferentiate a small adrenal neoplasm from bilateral hyper-
terization is the primary concern. In general, it is useful plasia. If findings are equivocal on CT, then adrenal
to separate adrenal work-ups into one of three algorithms: venous sampling to localize and lateralize the site of
1. Detection of an adrenal tumor in a patient with a elevated aldosterone production should be performed.
known biochemical abnormality. Pheochromocytomas originate from the adrenal medul-
2. Staging of a patient with a known primary neoplasm. la and produce an excess of catecholamines, causing hy-
3. Characterization of an incidental adrenal mass detect- pertension. These tumors are solitary and occur sporadi-
ed on cross-sectional imaging. cally in 90% of cases. If the diagnosis is suspected, the
This is a relevant topic as there has been an over 20- most appropriate first-line test is the measurement of
fold increase in medical literature reports on this subject plasma metanephrines. If these are equivocal, urinary
in the past two decades. metanephrines can be measured. Once the diagnosis has
been established biochemically, the primary role of the ra-
diologist is to determine the site of origin of the pheo-
Detection of Biochemically Active Adrenal Tumor chromocytoma. Over 95% of pheochromocytomas origi-
nate in the adrenals; therefore, a non-contrast-enhanced
Biochemically active adrenal neoplasms originate in the CT examination of the adrenals is usually sufficient. MRI
adrenal cortex, in which case they produce an excess of of pheochromocytoma typically demonstrates a T2 hyper-
either glucocorticoids, aldosterone, or androgens, or in the intense mass, although the finding is non-specific, as
adrenal medulla, thus producing an excess of cate- pheochromocytomas can also have intermediate signal in-
cholamines. Cushing’s syndrome results from an over- tensity on T2-weighted images, thus simulating adrenal
production of cortisol by the adrenal cortex and approxi- cortical carcinoma; also, other adrenal lesions can be T2
mately 80% of these cases are due to stimulation of the hyperintense (adrenal cysts and lymphangiomas). MRI can
adrenal glands by a pituitary adenoma. A primary adren- also detect extra-adrenal paragangliomas along the sympa-
al cortical tumor is seen in 20% of patients with Cushing’s thetic chain. While metaiodobenzyl-guanidine (MIBG)
syndrome and <1% have ectopic production of ACTH by scintigraphy has high specificity (>95%) for the diagnosis
a non-pituitary neoplasm. The work-up of patients pre- of pheochromocytoma, its sensitivity is only 77-90%.
senting with Cushing’s syndrome involves a dexametha- Recent studies have suggested that MIBG scintigraphy
sone suppression test, pituitary magnetic resonance imag- should be used selectively and only in patients with famil-
ing (MRI) to look for a pituitary adenoma, and an adrenal ial or hereditary disorders, in the detection of metastatic
Adrenal Imaging and Intervention 97
disease, and in patients with biochemical evidence for (evaluating microscopic levels of lipid on a pixel by pixel
pheochromocytoma and negative CT or MRI. These stud- basis) is useful to differentiate adenomas from metastases
ies also concluded that MIBG scintigraphy does not offer on non-contrast- and contrast-enhanced CT [8]. Accord-
any added advantage in patients with biochemical evi- ing to their findings, if an adrenal mass has >10% nega-
dence for a pheochromocytoma, no hereditary or familial tive pixels, it is diagnostic of an adenoma (on either non-
diseases, and a unilateral adrenal mass detected on CT or contrast- or contrast-enhanced CT). However, due to dif-
MRI [1, 2]. fering results in more recent studies, this approach is still
The standard treatment of a biochemically active considered as “research” and its use in clinical practice re-
adrenal tumor is open or laparoscopic resection. More remains limited.
cently, non-invasive techniques have been described, in- The physiological difference in perfusion between ade-
cluding selective arterial embolization, percutaneous in- nomas and metastases can be used to differentiate these
jection of acetic acid, and radiofrequency ablation. entities. Adenomas enhance rapidly with intravenous
contrast (iodinated CT contrast or MR gadolinium
chelates) and also have rapid washout. Metastases also
Staging Patients with Known Carcinoma enhance vigorously with dynamic contrast but the
washout of contrast is more prolonged than in adenomas.
Evaluation of the adrenal gland in the oncology patient is This difference in contrast washout has been exploited to
complicated because the gland is a frequent site of metas- further differentiate benign from malignant adrenal le-
tases, but benign adrenal adenomas are also common (de- sions by comparing pre-contrast HU values with dynam-
tected in 2-5% of autopsy series). Thus, the presence of ic and 15-min delayed HU values [9, 10]. Absolute per-
an adrenal mass does not necessarily implicate metas- cent washout (APW) values are calculated by the formu-
tases. The role of cross-sectional imaging in the oncolo- la: (HU at dynamic CT – HU at 15-min delayed CT)/(HU
gy patient is to detect enlargement of the adrenal gland at dynamic CT – HU at non-contrast CT) × 100. A value
and characterize the enlargement as either benign or ma- ≥60% is diagnostic of an adenoma. Relative percent
lignant. More recently, PET imaging has facilitated the washout (RPW) is used when a non-contrast CT value is
staging of neoplasms because adrenal metastases tend to not available and the dynamic enhanced values are com-
demonstrate increased activity, having a greater uptake pared to 15-min delayed scans. RPW is calculated by the
relative to the liver, while most benign adenomas do not. formula: (HU dynamic CT – HU 15-min delayed
More recent studies have confirmed the high sensitivity CT)/HU dynamic CT × 100, and a value >40% is diag-
of PET/CT in detecting malignant lesions but the speci- nostic of adenoma.
ficity is lower (87-97%). This loss of specificity is attrib- Adenomas can be differentiated from metastases using
utable to a small number of adenomas and other benign CSMRI if the patient has a non-diagnostic CT, is allergic
lesions that mimic malignant lesions [3, 4]. to iodinated contrast, or in young patients, in whom radi-
Depending on the primary tumor, CT or PET/CT is a ation exposure is an issue [11, 12]. Most adrenal adeno-
useful first-line exam to stage a known neoplasm. If the pa- mas contain sufficient intracellular lipid and lose signal
tient demonstrates multiple sites of metastatic disease, then on the out-of-phase image compared to the spleen. Visu-
evaluation of an adrenal mass is not important. If the adrenal analysis is adequate in most cases to make this obser-
al mass is the only abnormality, further evaluation is re- vation, but quantitative methods, such as the signal in-
quired to differentiate an adenoma from a metastatic focus. tensity index, may also be useful [13, 14].
Currently, there are two main criteria (anatomical and If the CT, MRI, or PET findings are equivocal, adren-
physiological) used to differentiate benign adenomas from al biopsy using CT guidance should be performed, par-
malignant adrenal masses: (1) the intracellular lipid con- ticularly to stage a lung carcinoma in patient who has no
tent of the adrenal mass, which represents the anatomical other sites of metastatic disease, as this may determine
difference between adenomas and metastases, and (2) dif- whether surgical resection is a therapeutic option. The
ferences in vascular enhancement patterns, which repre- role of adrenal biopsy has evolved in the last few years;
sent the physiological difference. Approximately 80% of in addition to the above indication of an indeterminate
benign adenomas have abundant intracytoplasmic lipid in adrenal mass, adrenal biopsy can also be used to confirm
the adrenal cortex and thus are of low density on unen- metastatic disease to the adrenal glands in patients with
hanced CT or show signal drop-off on out-of-phase chem- suspected solitary adrenal metastasis. CT-guided biopsy
ical shift MRI (CSMRI). Conversely, most metastases has been shown to be safe, with a diagnostic yield of 83-
have little intracytoplasmic lipid and thus do not have a 96% and a 3% complication rate [15].
low density on non-contrast CT. At a threshold of 10 HU,
CT has a 71% sensitivity and 98% specificity for charac-
terizing adrenal adenomas. While a low HU is useful to Evaluation of an Incidentally Discovered Adrenal Mass
characterize lipid-rich adenomas, it is estimated that up to
20% of adenomas do not contain sufficient lipid to be of As the indications for abdominal imaging (particularly
low density on unenhanced CT [5-7]. More recently, Bae CT) continue to increase, so does the detection of the
et al. showed that a histogram analysis of adrenal masses incidental adrenal mass-given the high prevalence of
98 William W. Mayo-Smith, Isaac R. Francis
adenomas in the general population (3-7%) [16-18]. In References

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covered adrenal masses (incidentalomas) are benign in a tive iodine 123 metaiodobenzylguanidine scintigraphy rou-
patient with no known malignancy [19]. An adrenal inci- tinely necessary before initial adrenalectomy for pheochromo-
dentaloma is defined as “an unsuspected and asympto- cytoma? Surgery 134:918-923
2. Greenblatt DY, Shenker Y, Chen H (2008) The utility of
matic mass (≥1 cm) detected on imaging exams obtained metaiodobenzylguanidine (MIBG) scintigraphy in patients
for other purposes”. with pheochromocytoma. Ann Surg Oncol 15:900-905
Risk factors for an incidental adrenal mass being ma- 3. Boland GW, Blake MA, Holalkere NS, Hahn PF (2009)
lignant include lesion size, change in size, and their PET/CT for the characterization of adrenal masses in patients
with cancer: qualitative versus quantitative accuracy in 150
occurrence in a patient with a history of malignancy. consecutive patients. AJR Am J Roentgenol 192:956-962
For patients with no history of malignancy, most small 4. Groussin L, Bonardel G, Silvéra S et al (2009) 18F-Fluoro-
(<4 cm) incidentally discovered adrenal masses are be- deoxyglucose positron emission tomography for the diagnosis
nign, and an extensive and costly imaging workup is of adrenocortical tumors: a prospective study in 77 operated
patients. J Clin Endocrinol Metab 94:1713-1722
usually not justified. An additional biochemical workup 5. Lee MJ, Hahn PF, Papanicolaou N et al (1991) Benign and ma-
to exclude functioning adrenal cortical or medullary le- lignant adrenal masses: CT distinction with attenuation coeffi-
sions is recommended by endocrinologists; however, cients, size, and observer analysis. Radiology 179:415-418
these functioning lesions present very rarely as “inci- 6. Korobkin, M, Brodeur FJ, Francis IR et al (1998) CT time-at-
tenuation washout curves of adrenal adenomas and nonadeno-
dental” adrenal masses, such that this expensive workup mas. AJR Am J Roentgenol 170:747-752
is not done routinely [20]. 7. Boland GW, Lee MJ, Gazelle GS et al (1998) Characterization
If a mass of any size has the typical features of a be- of adrenal masses using unenhanced CT: an analysis of the CT
nign lesion, such as a cyst or myelolipoma, no additional literature. AJR Am J Roentgenol 171:201-204
8. Bae KT, Fuangtharnthip P, Prasad SR et al (2003) Adrenal
workup or follow-up imaging is needed. For adrenal masses: CT characterization with histogram analysis method.
lesions <4 cm with non-diagnostic imaging features, if Radiology 228:735-742
prior imaging is available and the lesion has been stable 9. Korobkin M, Giordano TJ, Brodeur FJ (1996) Adrenal adeno-
for at least 1 year, then it can be deemed benign and there mas: relationship between histologic lipid and CT and MR
findings. Radiology 200:743-747
is no need for additional imaging follow-up. But if the 10. Caoili EM, Korobkin M, Francis IR et al (2002) Adrenal
lesion is enlarging, then it may be prudent to proceed masses: characterization with combined unenhanced and de-
to adrenal biopsy or resection. If there are no prior com- layed enhanced CT. Radiology 222:629-633
parison CT or MRI exams and patient has no hystory of 11. Tsushima Y, Ishizaka H, Matsumoto M (1993) Adrenal mass-
es: differentiation with chemical shift, fast low-angle shot MR
malignancy, and if the lesion has benign imaging fea- imaging. Radiology 186:705
tures (homogeneous, smooth margins), a diagnosis of a 12. Israel GM, Korobkin M, Wang C et al (2004) Comparison of
benign lesion may be made and one can consider a unenhanced CT and chemical shift MRI in evaluating lipid-
follow-up with an unenhanced CT or CSMRI exam in rich adrenal adenomas. AJR Am J Roentgenol 183:215-219
13. Fujiyoshi F, Nakajo M, Fukukura Y, Tsuchimochi S (2003)
12 months. However, if there are suspicious imaging Characterization of adrenal tumors by chemical shift fast low-
features on contrast-enhanced CT, then one should angle shot MR imaging: comparison of four methods of quan-
proceed with an unenhanced CT or CSMRI; if these titative evaluation. AJR Am J Roentgenol 180:1649-1657
exams do not confirm that the lesion is a lipid-rich 14. Mayo-Smith WW, Lee MJ, McNicholas MM et al (1995) Char-
acterization of adrenal masses (5 cm) by use of chemical shift
adenoma, an adrenal protocol CT with washout calcula- MR imaging: observer performance versus quantitative mea-
tions is recommended. If the lesion does not have the sures. AJR Am J Roentgenol 165:91-95
imaging and washout features of a benign lesion, then a 15. Silverman SG, Mueller PR, Pinkney LP et al (1993) Predictive
biopsy may be appropriate. value of image-guided adrenal biopsy: analysis of results of
101 biopsies. Radiology 187:715-718
In patients with a prior history of cancer and an adren- 16. Grumbach MM, Biller BM, Braunstein GD et al (2003) Man-
al masses of any size, if imaging features on contrast- agement of the clinically inapparent adrenal mass (“inciden-
enhanced are not diagnostic for a benign lesion and there taloma”). Ann Intern Med 138:424-429
is no prior imaging, one can consider an unenhanced CT 17. Young WF (2007) Clinical practice. The incidentally discov-
ered adrenal mass. N Engl J Med 356:601-610
or CSMRI or PET imaging. If the lesion does not behave 18. Choyke PL (2006) ACR Appropriateness Criteria on inciden-
like a typical adenoma, then one should proceed to tally discovered adrenal mass. J Am Coll Radiol 3:498-504
adrenal CT with washout. If the lesion does not show 19. Song JH, Chaudhry FS, Mayo-Smith WW (2008) The inci-
either washout features of an adenoma or the findings of dental adrenal mass on CT: Prevalence of adrenal disease in
1049 consecutive adrenal masses in patients with no known
an adenoma on PET imaging, then a biopsy should be malignancy. AJR Am J Roentgenol 190:1163-1168
considered. 20. NIH state-of-the-science statement on management of the clin-
In patients with no history of cancer and an adrenal ically inapparent adrenal mass (“incidentaloma”) (2002) NIH
mass >4 cm in size, resection is an option; but if there is Consens State Sci Statements 19:1-25
21. Boland GW, Blake MA, Hahn PF, Mayo-Smith WW (2008)
a history of prior cancer, then a PET scan or a biopsy is Imaging characterization of adrenal incidentalomas: princi-
recommended [21]. ples, techniques and algorithms. Radiology 249:756-775
IDKD 2010-2013
Renal Tumors
Richard H. Cohan1, Ronald J. Zagoria2
1 University of Michigan, Ann Arbor, MI, USA
2 Wake Forest University, Winston-Salem, NC, USA
Introduction <1-1.5 cm in diameter. Given that small renal masses are

very common, further imaging assessment of all of these
This chapter reviews recent advances in the imaging of lesions is not feasible, even though a few will be cancers.
renal masses, primarily using computed tomography Recently, Patel and colleagues reported that the subjec-
(CT) and magnetic resonance imaging (MRI). The focus tive impressions of radiologists are frequently quite accu-
is on developments in the use of imaging to differentiate rate in identifying which small renal masses are cysts and
benign from malignant renal lesions and to assess pa- therefore which lesions may not require follow-up [4].
tients following treatment for a renal mass. Accordingly, we recommend that follow-up imaging of
small renal masses be performed in only a few circum-
stances: (a) when the imaging suggests to a radiologist
Ultrasonography that a lesion may not be a simple cyst (often due to lesion
heterogeneity), (b) when a lesion is detected in a young
Although non-contrast ultrasound evaluates the internal patient (<40 years), or (c) when a new small mass is seen
morphology of cystic lesions with more detail than CT, it in a patient at risk for renal malignancy (such as in pa-
is not as sensitive in detecting renal masses as CT or tients with von Hippel Lindau, hereditary papillary renal
MRI. Further, ultrasound is limited in its ability to char- cell cancer, or hereditary leiomyomatosis-renal cancer
acterize detected masses. Most investigators consider syndromes) [5]. In these instances, further evaluation
ultrasound to be diagnostically definitive only when it with immediate MRI can be performed. Often, long-term
identifies a renal mass as a simple cyst. The majority of follow-up (for up to 5 years) will be necessary. Follow-
radiologists recommend that complex cysts and solid up imaging can be performed safely in most patients and
masses detected on ultrasound be evaluated further with does not usually result in a change in tumor stage or prog-
CT or MRI. nosis, even if the mass being followed is later found to be
a small cancer. Most small renal cancers grow very slow-
ly, with a mean growth rate of 0.4-0.5 cm/year [6, 7].
CT and MRI Techniques Therefore, on a 6-month follow-up examination, the typical
growth of a renal cancer is near the range of CT measure-
Adequate CT evaluation of a patient with a known or sus- ment error (~2-3 mm). While the only generally known
pected renal mass requires that at least two series be ob- exceptions are the small aggressive renal type II papillary
tained: unenhanced and delayed-enhanced images, with cancers seen in patients with hereditary leiomyomatosis-
the latter obtained at least 100 s after initiation of contrast renal cancer syndrome [5], a recent study has demonstrated
material injection [1, 2]. Similarly, MRI examinations that some other small (<4 cm) renal cancers can invade the
should include T1-weighted sequences obtained before renal capsule or even metastasize distantly [8].
and after gadolinium administration [3]. Additional MRI
sequences or techniques that are often helpful include T2-
weighted, fat suppression, chemical shift, and diffusion- Cystic Renal Masses
weighted imaging.
In 1986, Bosniak presented a CT cyst classification system
[9] that categorized cysts based on their likelihood of their
Small Renal Masses being malignant. This system has undergone a number of
revisions, with the most recent version published in 2005
Most renal masses detected with CT and some masses [10]. According to Bosniak, lesions with no or minimal
detected with MRI cannot be characterized due to their complexity on CT, classified as category I or II lesions,
small size. For CT, this is felt to be true for renal masses are nearly always benign and do not require follow-up.
100 Richard H. Cohan, Ronald J. Zagoria
Only a tiny percentage of these contains malignant cells parenchymal defect [17, 18]. A mass that contains calci-
[11]. Category II lesions require imaging follow-up with fication is more likely to be a liposarcoma than an AML.
immediate MRI, and/or with surveillance imaging, since Some AMLs do not contain identifiable macroscopic
a few of these are malignant. When these follow-up fat, including up to one-third of such tumors in patients
studies are interpreted, it must be remembered that both with tuberous sclerosis. Although these tumors cannot be
benign and malignant lesions can enlarge over time [11]. differentiated from other renal neoplasms on gross in-
To further confuse the issue, some benign and malignant spection, a number of studies have assessed the ability of
lesions can decrease in size over time [7]. Therefore, it is imaging to differentiate minimal-fat-containing AMLs
important to assess cystic lesions for increasing com- from other solid renal masses.
plexity, such as the development of new wall thickening A few studies have attempted to identify small foci of
or nodularity on follow-up studies [11]. These features fat in minimal-fat-containing AMLs in the hope that this
are the best predictors of malignancy. More complex cat- will permit these lesions to be correctly identified. The
egory III and IV cysts should be treated (in appropriate authors of these series have studied unenhanced CT at-
candidates), since many of these are cancers and imaging tenuation [19], analyzed CT histograms [20], counted fat
distinction between benign and malignant category III attenuation pixels [21], and quantitatively assessed fat on
and IV lesions is not possible. MRI [22]. Unfortunately, the results have been mixed. In
When the Bosniak system is used with MRI, about some series, minimal-fat-containing AMLs have con-
80% of cystic masses demonstrate similar complexity as tained more measurable fat than renal cancers, while in
seen on CT, but one in five appears more complex, other studies this has not been confirmed. A series by
demonstrating additional septations, wall or septal thick- Catalano et al. [20] comparing AMLs to clear cell carci-
ening, or subtle enhancement [12]. This is due, in part, to nomas is particularly concerning. The authors found that
the ability of MRI to detect some internal cyst features many clear cell renal cancers actually contained more
not visible with CT, but also to the fact that MRI is more measurable fat than did minimal-fat-containing AMLs.
prone to artifacts. Additional MRI features independent of fat detection
have also been evaluated. It has been suggested that a di-
agnosis of minimal-fat-containing AML should be con-
Angiomyolipomas sidered, albeit not definitively, if a solid mass demon-
strates low signal intensity on T2-weighted sequences and
While nearly all angiomyolipomas (AMLs) are echogenic if it has only mild enhancement after gadolinium-based
on ultrasound examinations, so are many small renal can- contrast material injection. These MRI characteristics are
cers. In a few series, acoustic shadowing has been iden- not seen in the majority of renal cancers.
tified posterior to some AMLs but not posterior to renal
cancers; however, at many institutions this finding alone
is not accepted as conclusive evidence of an AML [13]. Differentiating Non-Fat-Containing Renal Tumors
Thus, echogenic masses generally are evaluated further
with CT or MRI to determine whether macroscopic fat is Renal masses that do not contain recognizable fat cannot be
present in the mass. If macroscopic fat is present, then the distinguished consistently from each other. In the past, this
mass can be diagnosed as an AML (with case reportable was not felt to be an important problem, as it was believed
exceptions, see [14]). Otherwise, the mass is highly likely that the vast majority of such lesions were renal cancers.
to be a renal cell carcinoma. Accordingly, all patients with non-fat-containing solid
On CT, the presence within a renal mass of even small renal masses were referred for treatment. It has become
areas measuring –10 HU or less is considered diagnostic apparent, however, that a sizeable minority of small solid
of macroscopic fat and of an AML [15]. On MRI, such renal masses are benign, a fact that has led some to
fat typically is of high T1 and T2 signal intensity and loses recommend pre-treatment biopsy for all small renal
signal with fat suppression. On opposed-phase chemical- tumors. Recent studies suggested that about one in five
shift imaging, there is a characteristic “India ink” artifact solid renal masses measuring <4 cm is benign [23, 24]. The
at fat-water interfaces within the AML and between the frequency of benign tumors is even greater for renal le-
AML and adjacent tissue [16]. sions measuring <1 cm, with nearly half being benign [24].
On occasion, AMLs can be very exophytic and diffi-
cult to differentiate from perinephric liposarcomas. This Differentiating Benign from Malignant Renal Neoplasms
is an important distinction, given the very different treat-
ments and prognoses for these two neoplasms. While per- Benign solid renal masses that are encountered routinely
cutaneous biopsy is often helpful in making the distinc- include the previously discussed minimal-fat-containing
tion, imaging features have also been identified that can AMLs and oncocytomas. While some oncocytomas con-
be used to facilitate differentiation. Fatty perinephric tain central scars that can be detected on imaging studies
masses are more likely to be exophytic AMLs if they con- and oncocytomas also may demonstrate a spoke-wheel
tain large vessels or vessels that can be seen to extend to vascular pattern at CT or MR arteriography, these fea-
the renal cortex, or if they are associated with a renal tures are not diagnostic. Necrosis in renal cancers and
Renal Tumors 101
scars in oncocytomas, when they are present, are indis- over 200 for 75 clear cell, but only 110 for 10 chromo-
tinguishable from one another. Furthermore, most onco- phobe, and 32 for 28 papillary cancers [32].
cytomas evaluated on CT do not contain identifiable cen- A number of investigators have used diffusion-weighted
tral scars [25]. Many renal cancers demonstrate a spoke- MRI in the evaluation of renal masses [33]. Preliminary
wheel arterial pattern and since renal cancer is much studies have demonstrated differences in diffusion for
more common, most tumors that have this appearance are different types of renal masses. Not surprisingly, dif-
malignant. fusion is least restricted in simple renal cysts and most
One cannot rely on an assessment of growth rate to restricted in the more cellular renal neoplasms (such as
distinguish oncocytomas from malignant renal neo- papillary cancers and angiomyolipomas) [33]. Diffusion-
plasms, because small renal cancers and many onco- weighted MRI may be able to play a role in renal mass
cytomas enlarge slowly and to a similar degree over time. characterization, particularly in patients who cannot re-
In a meta-analysis reported by Chawla et al., there was no ceive gadolinium-based contrast material [33]. However,
significant difference in the growth rates between these diffusion-weighted imaging has a number of problems.
two different neoplasms [26]. Firstly, there is overlap in the degree of restricted diffu-
Traditionally, percutaneous biopsy differentiation of sion identified in benign and malignant renal lesions.
oncocytomas from some renal cancers based upon histo- Secondly, there are many technical issues, with measured
logical appearance was difficult, if not impossible. How- apparent diffusion coefficients varying among scanner
ever, several stains have recently been used in conjunc- brands and protocols.
tion with an assessment of tumor morphology to facili-
tate this distinction, such as Hale colloidal iron, cyto-
keratin-7, and vimentin immunohistochemical stains. Pre-operative Imaging and Treatment of Renal Cancers
While several researchers have suggested that in many
cases these stains permit the distinction of these two CT and MRI are very accurate in their ability to localize
types of tumors [27, 28], the accuracy of biopsy for this and stage renal cancers prior to treatment. Pre-treatment
distinction remains controversial. imaging studies should be used to assess renal cancer
There are a variety of additional benign renal neo- size, location (with respect to the renal poles, renal sinus,
plasms that likewise have a non-specific appearance. and collecting system), evidence of gross perinephric
These include the common papillary adenomas and extension, involvement of the ipsilateral renal vein or
renomedullary interstitial cell tumors (generally measur- inferior vena cava (including a description of the extent
ing <1 cm and encountered in 40-50% of adults in autop- of involvement), the presence or absence of enlarged
sy series) as well as very rare lesions, such as metanephric lymph nodes, and of any distant metastases. Either tech-
neoplasms, hemangiomas and lymphangiomas, leio- nique can also be used for anatomical definition prior
myomas, juxtaglomerular tumors, mixed epithelial and to anticipated surgery (including location and number of
stromal tumors, and cystic nephromas [29]. renal vessels).
Treatment choice depends upon the pre-operative
Differentiating among Renal Cancer Subtypes imaging characteristics of each tumor and the patient’s
condition. Although percutaneous thermal ablation tech-
As is the case with benign versus malignant renal lesions, niques are being performed with increasing frequency,
one also cannot rely on differences in growth rates to dis- they are still most often reserved for patients who are not
tinguish among cell types of renal cancers. In a recent se- good operative candidates, who have renal insufficiency,
ries, neither the initial size of a detected renal cancer nor or who have multiple renal neoplasms. Based on early
the cell type of that cancer predicted the likelihood that the studies, the cure rate for percutaneous thermal ablation is
cancer would be more or less likely to grow quickly [7]. comparable to that for surgery, but studies evaluating
Nonetheless, there are some morphological differences long-term oncological efficacy have yet to be completed.
among the different types of renal cancers. Papillary tu- Masses most amenable to percutaneous ablation include
mors can often be differentiated from other renal cancer smaller lesions (<4 cm) and lesions for which there is no
cell types on MRI, as many papillary cancers demon- radiological evidence of advanced disease (N0, M0) [34].
strate characteristic T2 signal hypointensity [30, 31]. In Masses in almost any location in the kidney now can be
contrast, only a small minority of clear cell carcinomas treated with equal efficacy with ablation. Precautions to
are T2 hypointense [31]. Additionally, on contrast- protect adjacent organs, such as the bowel, should be
enhanced CT or MRI, both papillary subtypes, i.e., the used with ablation when the mass to be treated is closer
better-prognosis type 1 tumors and the more aggressive than 2 cm from these structures.
type II tumors, tend to demonstrate more well-defined Currently, many urologists have shifted away from use
margins, more homogeneity, and less enhancement than of open total and partial nephrectomy to laparoscopic
do other renal cancer cell types [30, 32]. In one recent procedures, because, as is the case with percutaneous
study, for example, the mean percent increase of T1 thermal ablation, laparoscopic nephrectomy is associated
signal intensity after gadolinium-based contrast material with considerably less patient perioperative morbidity
administration during the corticomedullary phase was and a shorter length of hospital stay [34].
102 Richard H. Cohan, Ronald J. Zagoria
Imaging after Renal Mass Treatment 8. Pahernik S, Ziegler S, Roos F et al (2007) Small renal tumors:
correlation of clinical and pathological features with tumor
size. J Urol 178:414-417
Both CT and MRI, often performed using unenhanced 9. Bosniak MA (1986) The current radiological approach to re-
arterial phase imaging, and delayed enhanced imaging, are nal cysts. Radiology 158:1-10
used widely to image patients after treatment of renal 10. Israel GM, Bosniak MA (2005) How I do it: evaluating renal
cancers. Recent studies have described the imaging ap- masses. Radiology 236:441-450
11. Gabr AH, Gdor Y, Roberts WW, Wolf JS (2008) Radiographic
pearance of masses treated with radiofrequency ablation surveillance of minimally and moderately complex renal cysts.
[35, 36]. It is important to be aware of the normal imaging Br J Urol Int 103:1116-1119
appearance of the ablated mass following successful abla- 12. Israel GM, Hindman N, Bosniak MA (2004) Evaluation of
tion in order to avoid confusion with tumor recurrence. cystic renal masses: comparison of CT and MR imaging by us-
After successful renal mass ablation, there is initial expan- ing the Bosniak classification system. Radiology 231:365-371
13. Farrelly C, Delaney H, McDermott R, Malone D (2008) Do all
sion of the ablation site. The ablation bed then typically non-calcified echogenic renal lesions found on ultrasound need
decreases in size, but rarely disappears entirely. Other typ- further evaluation with CT? Abdominal Imaging 33:44-47
ical “normal” findings include fat invagination between 14. Helenon O, Chretien Y, Paraf F et al (1993) Renal cell carcinoma
the ablation bed and normal renal parenchyma and a peri- containing fat: demonstration with CT. Radiology 188:429-430
lesional halo, such that the ablation cavity mimics an AML. 15. Simpson E, Patel U (2006) Diagnosis of angiomyolipoma us-
ing computed tomography-region of interest ≤10 HU or 4 ad-
Recurrent or residual tumor should be suspected when jacent pixels ≤10 HU are recommended as the diagnostic
the ablation bed increases in size or when areas of en- thresholds. Clin Radiol 61:410-416
hancement are identified. The latter are usually nodular 16. Israel GM, Hindman N, Hecht E, Krinsky G (2005) The use of
and crescentic and are often located at the interface be- opposed-phase chemical shift MRI in the diagnosis of renal
tween the ablation bed and adjacent renal parenchyma angiomyolipomas. AJR Am J Roentgenol 194:1868-1872
17 Israel GM, Bosniak MA, Slywotzky CM et al (2002) CT dif-
[37, 38]. Close-interval follow-up (for example, at 1, 3, ferentiation of large exophytic renal angiomyolipomas and
6, and 12 months) should be performed after ablation, perirenal liposarcomas. AJR Am J Roentgenol 179:769-773
since most tumor recurrences are detected within the first 18. Ellingson JJ, Coakley FV, Joe BN et al (2008) Computed to-
3 months of the procedure [38]. mographic distinction of perirenal liposarcoma from exophyt-
ic angiomyolipoma: a feature analysis study. J Comput Assist
The imaging appearance of patients treated with open Tomogr 32:548-552
and laparoscopic partial nephrectomy has also been de- 19. Jinzaki M, Silverman SG, Tanimoto A et al (2005) Angiomy-
scribed. Hemostatic devices such as Surgicel (Johnson & olipomas that do not contain fat attenuation at unenhanced CT.
Johnson, USA) and renal bolsters, when inserted after Radiology 234:311
partial nephrectomy, can be mistaken for areas of infection 20. Catalano OA, Samir AE, Sahani DV, Hahn PF (2008) Pixel dis-
tribution analysis: can it be used to distinguish clear cell car-
or recurrent tumor. While recurrent tumors often typically cinomas from angiomyolipomas with minimal fat? Radiology
occur in the surgical bed, in adjacent lymph nodes, or with 247:738-746
distant metastatic disease, patients treated laparoscopically 21. Simpfendorfer C, Herts BR, Motta-Ramirez GA et al (2009)
may demonstrate a different pattern of recurrence, with Angiomyolipoma with minimal fat on MDCT: can counts of
implants growing along the laparoscopic port sites or negative attenuation pixels aid diagnosis? AJR Am J Roentgenol
192:438-443
elsewhere in the mesentery or peritoneum [39]. 22. Kim JK, Kim HS, Jang YJ et al (2006) Renal angiomyolipoma
with minimal fat: differentiation from other neoplasms at dou-
ble-echo chemical shift FLASH MR imaging. Radiology
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IDKD 2010-2013
Urinary Tract Obstruction and Infection

Parvati Ramchandani1, Julia R. Fielding2
1 Department of Radiology, University of Pennsylvania Medical Center, Philadelphia, PA, USA
2 Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Urinary Tract Obstruction as discussed below; however, some controversy exists as

to which imaging studies are best for investigating sus-
Imaging plays an important role in the evaluation of pa- pected ureteral obstruction. Nonetheless, regardless of
tients with acute and chronic urinary tract obstruction. composition, virtually all ureteral stones will have high at-
The cause of obstruction varies greatly with the patient tenuation values, making them readily detectable with CT.
population and the geographic locale. In a series report- Non-mineralized matrix stones and some drug-related
ing on percutaneous nephrostomy drainage, urinary ob- stones (protease inhibitors) may not be visible on CT im-
struction was related to calculus disease in 26% of pa- ages but these are rarely encountered in routine clinical
tients and to malignancy in 61%. Carcinoma of the blad- practice. A history of protease inhibitor therapy use is
der, cervix, and colon were the most common primaries required to deduce that the drugs are the cause of acute
in patients with malignancies and urinary obstruction [1]. flank pain and of the imaging findings of obstruction [10].
Acute ureteral obstruction is usually secondary to
urolithiasis, and patients commonly present to an acute
care facility with flank pain or acute renal colic. Non- Table 1. CT findings in acute renal colic
contrast helical computed tomography (CT) is often the Hoppe Katz Ahmad
first study performed in suspected acute obstruction, as it (2006) [2] (2000) [3] (2003) [4]
is a safe and rapidly performed examination and the N 1500 1000 233
accuracy for detecting ureteral stones, the most common Urinary stone 69% 62% 68%
cause of ureteral obstruction, exceeds that of other imag- Additional or alternative 71% 10% 12%
ing studies. Other causes of acute abdominal pain, such as diagnosis
appendicitis, leaking aortic aneurysm, and diverticulitis, Alternate diagnosis only 24% 7.50% X
can also be readily diagnosed and occur in 13-19% of Normal 7% 28% X
cases (Table 1) [2-4]. Non-contrast helical CT has an over- Pyelonephritis 3% 1% 1%
all accuracy of 97% for diagnosing ureteral stone disease, Renal cell carcinoma/ 2% 0.40% 1%
with a reported sensitivity of 97-100% and specificity of renal mass
94-96% [5-9]. This far exceeds the accuracy of intra- Cholecystitis 0.30% 0.30% 0.40%
venous urography (IVU) or ultrasound (US) (Table 2), Adnexal mass X 2% 2%
Table 2. Diagnostic performance for CT, US, and IVU in detection of ureteral stones
Lead author Year of publication N Stone + Test Sensitivity Specificity
Catalano 2002 181 82 CT 0.92 0.96
US/plain radiography 0.77 0.96
Boulay 1999 51 49 CT 1.0 0.96
Sheley 1999 180 87 CT 0.86 0.91
Sourtzis 1999 36 36 CT 1.0 1.0
IVU 0.66 1.0
Yilmaz 1998 97 64 CT 0.94 0.97
US 0.19 0.97
IVU 0.52 0.94
Smith 1996 210 100 CT 0.97 0.96
N, number of patients; Stone +, number of patients with ureteral stone
Urinary Tract Obstruction and Infection 105
The proper technique for performing non-contrast he- presence of a tissue “rim” sign usually indicates that the
lical CT to detect ureteral stone disease using a helical calcification is a stone rather than a phlebolith. Alterna-
scanner is detailed below. Imaging should be performed tively, absence of the tissue rim sign or presence of a
from the top of the kidneys to the base of the bladder “comet tail” sign strongly suggests that the calcification
without intravenous or oral contrast material and scans is a phlebolith rather than a stone. In practice, the pres-
should be obtained during a single breath-hold. A 16- to ence of two or more secondary signs of obstruction even
64-slice MDCT with 1.5-mm collimation and a review of without clear visualization of a calcification within the
5-mm contiguous images is appropriate. To reduce the ra- ureter indicates obstruction. If there is no history of re-
diation dose, a variable mA is used for each slice based cent stone passage and the CT scan demonstrates find-
on beam attenuation. In a recent report, the artificial ad- ings suggestive of obstruction, a contrast-enhanced study
dition of noise to a renal colic CT was used to show that of the upper tracts may be needed to exclude a urothelial
tube current could be diminished 75% without changing neoplasm, with additional cystoscopy to optimally evalu-
the detection rate of stones >3 mm in diameter [11]. For ate the bladder.
the obese patient, a fixed mA equal to his/her weight in Intravenous urography is an alternative technique for
pounds will usually suffice. The expected dose is 30-40 the detection of urinary tract obstruction. It was once the
mSv. Review of the images in cine mode on a worksta- imaging modality of choice in a patient who presented
tion facilitates continuous identification of the ureter and with acute flank pain. However, the necessity for intra-
workflow. While 3D reconstructions are usually not nec- venous radiographic contrast administration and the
essary, they may be occasionally useful to distinguish delay in obtaining relevant information about the site of
intraureteral from extraurinary calcifications. obstruction makes IVU a less desirable study than unen-
Due to the accuracy of CT and greater familiarity with hanced CT in an acute pain setting. Extraurinary causes
the examination by referring physicians, especially with- of acute abdominal pain are not usually detectable with
in the emergency room, the number of renal colic CT IVU. The technique was also once considered to have a
scans has dramatically increased. This alone is not worri- role in the evaluation of pregnant patients with acute
some. More concerning is the number of patients who un- flank pain, when the results of an ultrasonographic ex-
dergo repeat CT scanning. In a study by Katz et al. pub- amination were negative or equivocal. However, even in
lished in 2004, 4% of patients were found to have under- this patient population, CT may be the modality of
gone three or more CT scans for renal stones during a choice, as it provides a definitive and rapid diagnosis.
6-year period [12]. However, other reports indicate that These advantages outweigh the slightly greater radiation
there has been no decrease in the rate of positive diagno- exposure [16, 17]. Acute colic in pregnant patients is dis-
sis of obstructing urinary stones on CT, validating the in- cussed below. It is safe to state that IVU in the evaluation
creased frequency with which CT scans are obtained in of acute colic has been relegated to historical significance
the setting of acute flank pain [13, 14]. The overall rate in most patients.
of stone positivity on CT scanning in patients with sus- Ultrasound, usually combined with an abdominal
pected renal colic was reported in several studies to be radiograph, is an alternative method for evaluating the
60-66% [13, 14]. Additionally, as discussed above, CT is obstructed or dilated urinary tract and is often the first
the diagnostic test of choice to evaluate many acute ab- imaging procedure in patients who should avoid radia-
dominal problems, and a decrease in the stone positivity tion, such as pregnant women and children. Renal calculi
rate may not necessarily reflect overuse of CT [15]. Nev- as small as 0.5 mm may be detectable under optimal
ertheless, it seems reasonable that a patient with known imaging conditions. For stones >5 mm in diameter, US
history of stones and the appropriate clinical findings can has been shown to have a sensitivity and specificity of
be treated conservatively and without imaging beyond an 96% and nearly 100%, respectively [18]. US is excellent
abdominal radiograph. for evaluation of the renal parenchyma and the collecting
In addition to direct visualization of the ureteral stone, system to the ureteropelvic junction but it is limited in its
secondary signs of ureteral obstruction on non-contrast evaluation of the ureter and of soft-tissue lesions within
CT scans include unilateral nephromegaly, perinephric the collecting system. The use of renal US in the evalua-
stranding, hydronephrosis, and periureteral stranding. tion of suspected acute ureteral obstruction is also re-
The combination of perinephric stranding and unilateral stricted because dilatation often does not develop for
hydronephrosis has a positive predictive value of 96% for hours or even days. In these cases, US findings are nor-
the presence of stone disease. The absence of both of mal in up to 50% of patients. US, either alone or com-
these signs has a negative predictive value of 93% for ex- bined with conventional radiography, has been compared
cluding stone disease. CT also gives information that de- with unenhanced CT. It has a much lower sensitivity:
termines therapy. Stones that are f5 mm in size, of 24-77% [19-22] vs. 92-96% for CT. In Sheafor’s study, in
smooth shape, and located within the distal one-third of which CT and US were compared [19], CT depicted 22
the ureter are likely to pass spontaneously [7]. of 23 ureteral calculi (sensitivity 96%) whereas US de-
The major pitfall in non-contrast helical CT evaluation picted 14 of 23 (sensitivity 61%). Differences in sensitiv-
of the urinary tract for stone disease is difficulty in dis- ity were statistically significant (p = 0.02). The specifici-
tinguishing pelvic phleboliths from ureteral calculi. The ty for each technique was 100%. CT can give a rapid and
106 Parvati Ramchandani, Julia R. Fielding
definitive diagnosis of urinary calculus disease as well as Table 4. Magnetic resonance urography protocol
other abdominal disorders with the same presentation. 250 mL IV saline: begin 15 min before imaging
US identification of ureteral jets within the urinary blad- Patient supine, give 10 mg IV furosemide
der lumen is helpful for assessing the presence of ob- Coronal HASTE/SSFSE scout
struction. One study showed an absent ureteral jet in 11 Axial abdomen HASTE/SSFSE
of 12 patients with high-grade obstruction and in 3 of 11 Axial IP/OOP gradient echo image
Coronal 3D TSE, HASTE or other fluid-bright sequence
patients with low-grade obstruction [23]. The identifica- If GFR <3.0 or serum Cr >3.0: STOP
tion of jets at the ureterovesical junctions indicates that If GFR >3.0 and suspicion for transitional cell carcinoma is high:
obstruction is incomplete, a finding that may be used to coronal 3D gradient echo image such as LAVA, VIBE with fat
guide therapy. saturation; 2-, and 5-min delay
In diuresis renography, radionuclides are injected to
evaluate the urinary tract for obstruction. Since consider-
ably less anatomical detail is available with this test than
with other radiographic examinations, it is less useful in acute flank pain that is similar to that of previous
the acute setting than for follow-up or the evaluation of episodes. In the absence of such a history, abdominal radio-
chronic urinary tract obstruction. Diuresis renography graphy may not be of value as an initial examination [9].
does have the advantage of yielding objective data re- If a ureteral calculus is present on CT but not clearly
garding the physiological significance of hydronephrosis identifiable on the CT scout view, a conventional abdom-
detected on imaging studies, and also allows evaluation inal radiograph may be useful – especially if the stone
of the function of each kidney. Administration of a di- is >4-5 mm in size and over 300 HU in density [28] – to
uretic, usually furosemide, augments the standard follow the progress of the stone for management purpos-
renogram and is useful in evaluating whether dilated uri- es. For radio-opaque calculi, confirmation of stone loca-
nary systems are functionally obstructed or not. tion during conservative therapy is best performed using
Magnetic resonance urography (MRU) using rapid plain films [29] (Table 4).
scanning techniques, such as half acquisition turbo spin In dealing with the pregnant patient with flank pain,
echo or single-shot fast spin echo and 3D gradient echo fetal age and estimated radiation dose are of paramount
contrast-enhanced sequences, is used for evaluation of importance. Right hydronephrosis is commonly encoun-
the urinary tract. Following the administration of 250 mL tered, as the enlarging uterus turns slightly to the right
of normal saline and 10 mg of furosemide, the kidneys thus compressing the ureter. When an obstructing stone
and dilated ureters are very bright on T2-weighted images is suspected in pregnant patients, US should be per-
and their stable position allows for clear imaging of the formed first. Based on clinical findings, some urologists
level of obstruction (Table 3). Unfortunately, stones ap- will place a stent in a pregnant patient with severe hydro-
pear as signal voids and can be difficult to identify and nephrosis. If more imaging information is needed from a
measure on MRU. Small calculi (which account for the patient in the first trimester, a limited IVU using a plain
majority of symptomatic stones) are also difficult to de- scout film followed by a 10-min post-infusion delayed
tect with this method. Also, urothelial lesions, blood film yields the least radiation. After 20-24 weeks, IVU
clots, and debris can mimic calculi. becomes difficult to interpret because of the enlarging
In patients with renal impairment due to ureteral ob- uterus and the developing fetal skeleton, such that CT
struction [24, 25], non-contrast CT was found to be the should be considered [17]. The expected fetal dose is ap-
best imaging modality to identify calculus causes of ob- proximately 16 mSv, well below that expected to cause
struction, while MRU was superior for identifying non- developmental anomalies.
calculus causes. In patients with normal renal function,
contrast-enhanced CT can identify the presence and
cause of hydronephrosis in nearly all cases [26]. MRU is Urinary Tract Infection
particularly helpful in delineating the anatomy in patients
with urinary diversion to bowel conduits [27]. Acute Pyelonephritis
An abdominal radiograph is a reasonable initial test in
patients who have a history of radiopaque calculi and This is usually an ascending infection from the bladder,
seen predominantly in females. Rarely, the source of in-
fection is hematogenous bacteremia. Diagnosis is usually
Table 3. Computed tomography urography protocol made on clinical grounds and with urine analysis. Imaging
may be needed to detect complications or the sequela of
No oral contrast, patient supine, 10 mg IV furosemide pyelonephritis. When clinical pyelonephritis persists for
Axial non-contrast enhanced abdomen
Inject intravenous contrast agent (100 mL of 350 mgI/mL) more than 3 days after suitable antibiotic therapy has been
Axial abdomen and pelvis at 75 s post-injection initiated, imaging is recommended. In such cases, CT is the
Axial abdomen and pelvis at 5 min post-injection imaging technique of choice to evaluate the kidneys for
Coronal reformatted images of 5-min delay exam possible complications of pyelonephritis, e.g., the develop-
Review using bone and soft tissue windows ment of an abscess. CT is also the most sensitive and
specific test for detecting the changes of acute pyelo- secondary, reactivation tuberculosis. Symptoms typical-
nephritis and its complications. Typical CT findings of ly include hematuria and sterile pyuria. The earliest
pyelonephritis include unilateral nephromegaly, renal stri- signs of renal tuberculosis are, among others, focal pap-
ations, wedge-shaped defects, and perinephric inflamma- illary necrosis and inflammation of the calyces. With
tory changes; detection of the latter usually requires con- progression, areas of fibrosis and calcification may de-
trast-enhanced images. Areas of liquefaction within the re- velop. Long-standing tuberculosis may result in numer-
nal parenchyma indicate the development of a renal ab- ous fibrotic strictures, ureteral wall thickening, hy-
scess. CT is more sensitive than US in detecting the de- dronephrosis, and autonephrectomy. Pyelonephritis re-
velopment of a renal abscess and in assessing its extent. lated to Bacillus-Calmette-Guerin (BCG) therapy for
In males with a urinary tract infection (UTI) and/or urothelial carcinoma has also been reported.
suspected pyelonephritis, clinical and imaging evaluation XGP, an inflammatory condition with a marked female
for causes of UTI, such as epididymitis, orchitis, and pro- predominance, is associated with recurrent UTIs caused
statitis, may be helpful in management. Patients with a by proteases or by E. coli infection. An infection-based
neurogenic bladder secondary to a spinal cord injury pose stone is seen in the majority of cases. The classic radio-
a difficult problem as the urine is usually colonized with graphic triad consists of reniform enlargement of the
bacteria. Development of systemic symptoms should kidney, a renal stone, and markedly decreased or absent
prompt rapid imaging as these patients may not be sen- renal function in the affected kidney. Localized XGP
sate to pain and a devastating abscess can develop quick- occurs in 20% of patients and can mimic renal neoplasms
ly [30]. Finally, in order to diminish radiation dose to on imaging studies.
pregnant patients, US with power Doppler may be at- Both malacoplakia and fungal infections have non-
tempted prior to CT to detect areas of aberrant blood specific appearances on imaging, with diagnosis only be-
flow. This approach also has been shown to be useful in ing established by histological examination to exclude
children [31, 32]. neoplasm. Malacoplakia constitutes congregations of his-
Vesicoureteral reflux in children can lead to reflux tiocytes and is more commonly seen in the bladder and
nephropathy, which may not be detected until they are ureter than in the kidney. The microscopic hallmark of
adults. The reflux of urine through the ducts of Bellini re- malacoplakia is the Michaelis-Gutman inclusion body,
sults in broad-based renal parenchymal scars that are cen- which is seen within the abnormal histiocytes. When
tered over clubbed and blunted calyces. Changes of reflux malacoplakia involves the ureter or bladder, multiple sub-
nephropathy occur preferentially in the poles of the kid- mucosal masses are usually identified. Imaging findings
neys, with the upper pole being affected most frequently. are non-specific and tissue is required for definitive di-
The interpolar regions are almost always spared of scar- agnosis. Fungal infections are usually seen in immuno-
ring in these patients. compromised patients, including diabetics. Debris, often
present within the renal collecting system, forms a
Emphysematous Pyelonephritis “hand-in-glove” filling defect of the contrast-opacified
calyces.
This life-threatening infection with a gas-producing or-
ganism may have a mortality of up to 90% without AIDS Nephropathy
prompt treatment, and nephrectomy is often required. In
diabetic patients, this infection is usually caused by a Autoimmune deficiency syndrome (HIV/AIDS) nephro-
strain of Escherichia coli. The diagnosis of emphysema- pathy comprises a variety of renal pathologies. Findings
tous pyelonephritis is made when gas is seen in the renal are generally non-specific but patients with HIV infection,
parenchyma. CT is the most accurate technique for diag- renal failure, and hyperechoic nephromegaly likely have
nosing emphysematous pyelonephritis and for differenti- AIDS nephropathy. These sonographic findings in an
ating this entity from emphysematous pyelitis or peri- AIDS patient usually indicate that the patient will develop
nephric emphysematous infections. CT is also the most irreversible renal failure.
accurate approach to differentiate localized gas-produc-
ing infections from diffuse emphysematous pyelonephri- BK Virus Nephropathy
tis; the former can be successfully treated with percuta-
neous drainage in combination with systemic antibiotic During the last decade, strong anti-rejection agents have
management. been used to improve renal allograft survival. The re-
sulting immunosuppression has allowed a generally be-
Granulomatous Renal Infections nign virus, known as BK, to become a deadly pathogen.
BK is present in the urine of 50% of transplant recipi-
Tuberculosis, xanthogranulomatous pyelonephritis ents 3 months post-operatively and may cause graft fail-
(XGP), malacoplakia, and fungal infections can all af- ure in 10%. The method of action of this small polyoma
fect the urinary tract. Renal tuberculosis is usually virus is unknown. Patients with transplanted kidneys
spread hematogenously from the lungs, seeding the who are BK-positive are treated with steroids. There is
kidneys. Symptomatic renal tuberculosis results from no known cure [33].
108 Parvati Ramchandani, Julia R. Fielding
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additional diagnoses on unenhanced helical computed tomo-
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IDKD 2010-2013
Benign Diseases of the Female Genital Tract

Caroline Reinhold1, Rahel A. Kubik-Huch2
1 McGill University Health Center, Montreal, Quebec, Canada
2 Institute of Radiology, Department of Medical Services, Kantonsspital Baden, Baden, Switzerland
Introduction
Endovaginal sonography (EVS) remains the procedure of
choice for the initial evaluation of benign diseases of the
female genital tract. When EVS findings are indetermi-
nate, further evaluation is typically performed with mag-
netic resonance imaging (MRI), due to its excellent soft-
tissue differentiation, multiplanar capabilities, and ab-
sence of ionizing radiation. MRI is thus well suited for
imaging women of reproductive age, particularly during
pregnancy. Accordingly, the technique has come to play
an increasing role in pelvimetry and, more recently, as an
adjunct to sonography for fetal imaging. MRI is used in
the pre-operative characterization of adnexal masses and
as a problem-solving tool in benign uterine disease (for
example, uterine malformations), adenomyosis, and to
select appropriate candidates for therapies such as myo-
mectomy and uterine embolization. The role of comput-
ed tomography (CT) is limited in the evaluation of benign
disease of the female pelvis and is usually employed in Fig. 1. Normal MR anatomy (sagittal T2-weighted image) of the
an emergency situation, such as in an acute abdomen uterus and cervix. Three zones are recognized in the uterus: the
caused by ovarian torsion or pelvic inflammatory disease. hyperintense endometrium, the hypointense junctional zone
(arrow), and the outer layer of the myometrium of intermediate
signal intensity. Four zones are distinguished in the cervix: the
hyperintense mucous within the endocervical canal, the cervical
Anatomy of the Female Genital Organs mucosa, the hypointense cervical stroma, and an additional layer of
smooth muscle. Scarring from C-section (arrowhead)
In women of reproductive age, the uterus is approxi-
mately 6-9 cm in length and varies in appearance ac-
cording to the menstrual cycle. The uterine zonal anato- 3. the hypointense cervical stroma surrounding the mucosa;
my is best depicted using sagittal T2-weighted images 4. an additional layer of intermediate signal intensity in
(Fig. 1). In the pre-menopausal woman, three distinct continuity with the uterine myometrium, representing
zones are recognized: smooth muscle.
1. the high-signal-intensity endometrium of varying In post-menopausal patients, the uterine corpus, but
thickness, depending on the menstrual cycle; not the cervix, regresses and decreases in size.
2. the hypointense junctional zone, anatomically corre- In pre-menopausal women, the mean ovarian volume is
sponding to the innermost layer of the myometrium; 10 ± 6 mL, with an upper limit of 22 mL [1]. In post-
3. the outer layer of the myometrium, which is of inter- menopausal women, the ovary atrophies and the follicles
mediate signal intensity. disappear over subsequent years. As a result of atrophy, the
Four zones are distinguished in the cervix by high- ovaries are reduced in volume (1-6 mL) and may be diffi-
resolution MRI: cult to visualize sonographically [1, 2]. An ovary is abnor-
1. the hyperintense mucous within the endocervical canal; mal if the volume is >8 mL or it is more than twice the vol-
2. the cervical mucosa of intermediate to high signal in- ume of the contralateral ovary. Small (<3 cm) anechoic
tensity; cysts can be seen in up to 15% of menopausal women [3].
Benign Diseases of the Female Genital Tract 111
Unlike sonography, MRI can detect the ovaries in almost that are in accordance with the long and short axes of the en-
100% of patients [3]. On T2-weighted images, the cortex dometrial cavity should be applied for the assessment of
and stroma of a pre-menopausal ovary is of low signal in- uterine and cervical pathologies. It is recommended that
tensity while the medulla is of higher signal intensity. In these oblique sequences are acquired under medical super-
pre-menopausal women, gadolinium enhancement of the vision, as the technician might not have sufficient anatomi-
ovaries is less than that of the myometrium while in post- cal knowledge to clearly identify the long axis of the uterine
menopausal women, it is equivalent [4, 5]. body. The short-axis coronal oblique sequence (perpendicu-
lar to the long-axis of the endometrial cavity) is particularly
valuable for assessing localized endometrial pathology as
Magnetic Resonance Imaging Technique well as the thickness of the junctional zone. It is also valu-
able for determining the extent of a uterine septum. A T2-
If possible, patients should be scheduled for MRI in the weighted sequence performed parallel to the long axis of the
second half of the menstrual cycle, since the thickness of endometrial cavity is critical to characterize the external
the endometrial stripe increases during the follicular and uterine contour in patients with mullerian duct anomalies.
secretory phases, allowing better appreciation of the nor- Since this series is so important in the classification of uter-
mal zonal anatomy of the uterus. ine anomalies, it is best performed early in the examination,
The objective of patient preparation is to obtain the best prior to filling of the bladder, which with increasing disten-
possible image quality, while making the examination as tion often displaces the uterus. If the fundal contour is in-
comfortable as possible for the patient. To minimize mo- adequately characterized on T2, then T1-weighted images
tion artifact induced by bowel peristalsis, patients are ad- parallel to the long axis can facilitate characterization of the
vised to fast for 6-8 h before the procedure. Unless con- external contour due to increased contrast between the
traindicated, the intravenous or intramuscular injection of myometrial fundal contour and the overlying fat.
peristaltic inhibitors, i.e., glucagon or butyl-scopolamine, The uterus should be imaged using the smallest possi-
is recommended to further decrease peristalsis artifacts. ble field of view (20-24 cm), with thin sections of 4-5 mm
An empty urinary bladder minimizes ghosting artifacts and the largest possible matrix size appropriate to each
from patient motion. In addition, it maintains the uterus in individual sequence. These imaging parameters provide
a more caudal position in the pelvis, away from small important anatomical detail, which becomes critical
bowel loops, and assures that the normally visible fat when uterine anomalies and endometrial pathology are
plane between the uterus and urinary bladder – an impor- imaged. In the imaging of large leiomyomas, the section
tant criteria to exclude tumor invasion of the bladder wall thickness and field-of-view (FOV) may need to be
in oncological patients – will not be obliterated. adjusted accordingly. However, when the myometrial ori-
Examinations are usually performed with the patient in gin of a subserosal leiomyoma must be established, thin
supine position and using a body-flex phased-array MRI sections at the level of the pedicle are frequently helpful.
surface coil; pregnant patients in the third trimester may We have recently added an axial echo-planar diffusion-
also be placed in an oblique or lateral decubitus position weighted MRI sequence of the small pelvis to our clini-
for greater comfort during imaging. cal routine protocol. Diffusion-weighted imaging (DWI),
Depending on the clinical questions to be answered, well established for intracranial imaging, is a functional
one or several fast sequences of the upper abdomen imaging technique whose contrast derives from the ran-
should be performed, e.g., a cine steady-state free pre- dom motion of water molecules within the extracellular
cession sequence (TrueFisp) in the coronal and axial tissue. DWI is useful in pelvic female tumors, i.e., in the
planes and a T1-weighted gradient echo sequence to differentiation of benign from malignant lesions, and has
exclude ascites, enlarged retroperitoneal lymph nodes, a high sensitivity in the detection of iliac lymph nodes.
hydronephrosis, or renal agenesis in patients with con- Gadolinium-enhanced imaging is not needed for most
genital uterine malformations. benign conditions but can be useful in selected patholo-
T1-weighted as well as axial STIR (short tau inversion gies. We routinely perform contrast-enhanced imaging in
recovery) sequences are standard techniques in the as- patients with symptomatic leiomyomas scheduled for la-
sessment of the small pelvis. The presence of a bright paroscopic surgery or uterine artery embolization, in the
mass on T1-weighted imaging requires an additional fat latter case with additional magnetic resonance angio-
suppressed T1-weighted sequence using chemical pre- graphy of the iliac arteries. Vascularity can help to pre-
saturation to distinguish fat (e.g., in a mature teratoma of dict response to treatment. In addition, the enhancement
the ovary, which shows signal loss) from blood, mucin, or pattern is one criterion that can be used to distinguish a
other proteinaceous material that remains of high signal benign fibroid from a malignant leiomyosarcoma.
intensity. A pre-contrast fat-saturated T2-weighted se-
quence in the axial or sagittal plane is also helpful to de-
tect small endometriosis implants, e.g., in the cul-de-sac. Congenital Uterine Anomalies
T2-weighted images are most important in the assess-
ment of the uterus, with sagittal sections best-suited to im- Buttram and Gibbons proposed a classification system in
age the uterus. Oblique coronal and axial slice orientations 1979 that was based on the degree of failure of normal de-
112 Caroline Reinhold, Rahel A. Kubik-Huch
I Hypoplasia/agenesis II Unicornuate III Didelphus
(a) Vaginal (b) Cervical (a) Communicating (b) Non

Communicating IV Bicornuate
(c) Fundal (d) Tubal (e) Combined (c) No cavity (d) No horn (a) Complete (b) Partial
V Septate VI Arcuate VII DES drug related
(a) Complete (b) Partial
Fig. 2. Classification system of mullerian duct anomalies according to the American Fertility Society [7]
velopment while taking into account similar clinical fea- communicating and communicating rudimentary horns
tures, reproductive outcomes, and management [6]. Mod- are usually surgically resected. Hematometra and en-
ified by the American Fertility Society (now the American dometriosis, as well as the potential for pregnancy with-
Society of Reproductive Medicine) in 1988, the classifi- in the hypoplastic horn, may complicate the patient’s
cation system is the most widely accepted framework of course in this setting. The appearance of the rudimentary
reporting uterovaginal anomalies [7] (Fig. 2). Uterine mal- horn is variable and depends on the presence of func-
formations can be associated with subfertility, pregnancy tioning endometrial tissue and whether or not the horn is
wastage, and menstrual disorders. obstructed (Fig. 3).
Class I: Mullerian agenesis and hypoplasia. In approxi- Class III: uterus didelphys. In uterus didelphys, two sep-
mately 10% of uterine congenital anomalies, there is arate uterine horns (often widely divergent) and two sep-
some degree of early failure to form the mullerian ducts arate cervices are visualized with MRI. The normal zon-
prior to fusion [8]. Complete vaginal agenesis, or Mayer- al anatomy is maintained within each hemiuterus, and the
Rokitansky-Kuster-Hauser (MRKH) syndrome, is the two horns remain symmetrical in size.
most common presentation of the class I anomalies. In
the group of patients with vaginal agenesis, 90% have as- Class IV: bicornuate uterus. In the bicornuate uterus, the
sociated uterine agenesis, while 10% present with a rudi- horns are symmetrical in size, with an intervening cleft
mentary uterus. The ovaries are normal in appearance and that extends to the internal cervical os in the “complete”
function, although they may be situated more cranially, bicornuate uterus and which terminates more proximally
outside of the pelvis. Vaginal agenesis is best diagnosed in the “incomplete” bicornuate uterus. The endocervical
in the transverse plane with fatty and connective tissue in canal may be solitary (bicornuate unicollis) or duplicated
the expected location of the vagina, between the urethra (bicornuate bicollis). Communication of the endometrial
and rectum. and/or endocervical segments must be present to diag-
nose this class of anomaly. Communication between the
Class II: unicornuate uterus. The unicornuate uterus ap- segments allows differentiation of a bicornuate bicollis
pears elongated, curved, and is typically deviated to one uterus from a uterus didelphys. The uterus didelphys has
side [8]. The endometrium frequently takes on a “ba- no communication between the endometrial segments. In
nana” or “bullet” shape. Unicornuate uteri without rudi- the bicornuate uterus, the fundal cleft on MRI is greater
mentary horns or those with non-cavitary rudimentary than 1.0 cm. This feature distinguishes the bicornuate
horns require no treatment. Those with both non- from the septate uterus [8-11].
a b
Fig. 3 a, b. Uterine malformation: a axial and

b coronal T2-weighted MR images. A uni-
cornuate uterus with a rudimentary left horn
(arrows) is seen
Class V: septate uterus. In the septate uterus, the external typically located in the anterolateral wall of the vagina,
uterine contour can be convex, flat, or minimally con- above the level of the symphysis pubis.
cave, with the fundal cleft always <1.0 cm [8-12]. The Endometrial polyps are among the most common patho-
fundal segment of the septum is isointense to myometri- logical lesions of the uterine corpus. Patients with post-
um in both partial and complete septa. In complete sep- menopausal bleeding and endometrial polyps usually un-
ta, the inferior segment of the septum is usually of low dergo endometrial sampling and polyp removal [13]. En-
signal intensity on T2-weighted images, corresponding to dometrial polyps have a variable appearance at EVS but are
the more fibrous component. This low-signal-intensity typically echogenic, with an intact overlying endometrium
band is frequently absent in partial septa, however, which or subendometrial halo. A vascular pedicle is usually iden-
tend to be uniformly isointense to myometrium. It is im- tified at color/power Doppler imaging. On T2-weighted im-
portant not to use the signal intensity of the septum to ages, polyps present as masses that are slightly hypointense
classify this anomaly since septal composition can over- or isointense relative to the normal endometrium. Large
lap between the septate and bicornuate uteri. polyps are frequently heterogeneous in signal intensity
[14, 15]. On T2-weighted sequences, the fibrous core is
seen as a hypointense area within the polyp. Endometrial
Benign Conditions of the Vagina, Cervix, and Uterus polyps show a variable degree of enhancement after
gadolinium administration, and the addition of gadolinium-
Bartholin’s cysts are caused by retained secretions within enhanced sequences significantly improves the detection
the vulvo-vaginal glands, mostly as a result of chronic in- rate of endometrial polyps. Small polyps enhance early and
flammation or trauma. They are located in the posterolat- are well delineated against the hypointense endometrial
eral parts of the lower vagina and vulva, whereas Naboth- complex on early dynamic scans. In addition, a vascular
ian cysts are retention cysts of the cervical glands and stalk can frequently be identified during the arterial phase.
clefts. Gartner duct cysts represent remnants of the Magnetic resonance imaging is useful for distinguishing
caudal end of the Wolffian or mesonephric ducts and are leiomyomas (Fig. 4) from other myometrial pathology and
a b
Fig. 4 a, b. Multiple uterine leiomyomas.

a Sagittal T2-weighted and b contrast-
enhanced T1-weighted images. The multiple
lesions are sharply demarcated and present
as hypointense lesions on the T2-weighted
sequence. Contrast-enhancement is less pro-
nounced than in the adjacent normal my-
ometrium. A signal void is indicative of cal-
cification (arrow)
solid pelvic masses, especially in patients with non- Leiomyomas must also be differentiated from uterine
diagnostic or equivocal ultrasound findings. A mass of adenomyosis (Fig. 6), although these conditions frequent-
intermediate signal intensity on T1-weighted images, low ly coexist. Differentiating the two entities may be critical
signal intensity on T2-weighted images, and splaying the because uterine-conserving therapy is established for
uterine serosa or myometrium allows the diagnosis of leiomyomas; whereas hysterectomy remains the definitive
leiomyoma to be made with confidence. The presence of treatment for debilitating adenomyosis. While MRI is ex-
feeding vessels originating in the myometrium further tremely accurate in making this distinction, especially in
supports the uterine origin of the mass (Fig. 5). Howev- patients with diffuse adenomyosis, the imaging features of
er, if a mass is adjacent to the uterus and is of intermedi- focal adenomyosis or adenomyomas can overlap with
ate or high signal intensity relative to the myometrium on those of leiomyomas [17-19]. Imaging characteristics that
T2-weighted images, the differential diagnosis includes favor the diagnosis of focal adenomyosis include:
degenerated leiomyoma and extrauterine tumors (benign 1. a lesion with poorly defined margins;
and malignant). In these patients, the diagnosis of 2. a lesion that is elliptical in shape extending along the
leiomyoma should be reserved only for cases in which the endometrium;
uterine origin of the mass is firmly established. Occa- 3. a lesion that has little mass effect upon the endometri-
sionally, it may be difficult to distinguish a pedunculated um relative to its size;
subserosal leiomyoma from an ovarian fibroma, since 4. a lesion with high signal intensity striations radiating
both lesions may be hypointense on T2-weighted images. from the endometrium into the myometrium [17-19].
This distinction is likely not significant as the latter is Cystic adenomyosis needs to be differentiated from a
rarely malignant [16]. Submucosal leiomyomas are usu- leiomyoma with central hemorrhagic degeneration or a bi-
ally distinguished from endometrial polyps by identifying cornuate uterus with an obstructed horn.
their myometrial origin and by their low signal intensity Another entity that may mimic a leiomyoma or adeno-
on T2-weighted images. myosis is a myometrial contraction. Myometrial contractions
a b
Fig. 5 a, b. Subserosal leiomyoma: a axial T2-

weighted and b sagittal contrast-enhanced
T1-weighted sequences. A large, relatively
hyperintense mass is seen adjacent to the
uterus. The presence of feeding vessels (ar-
row) originating in the myometrium supports
the uterine origin of the mass. A smaller
hypointense intramural leiomyoma is seen in
the uterine fundus
a b c
Fig. 6 a-c. Focal adenomyosis: a sagittal T2-weighted and b, c axial T2-weighted STIR im-
ages. Enlarged uterus with diffusely thickened junctional zone with multiple hyperintense
foci indicative of adenomyoma. A small leiomyoma is also present (arrow)
are transient and usually change or resolve over the fibrous strands, either from previous surgery or sec-
course of the exam. Contractions image as hypoechoic or ondary to pelvic inflammatory disease, endometriosis, or
low signal intensity lesions within the myometrium that trauma, the peritoneal fluid may not be reabsorbed; In-
deform the endometrium while sparing the outer uterine stead, it accumulates and entraps the ovary, forming a
contour. peritoneal inclusion cyst [21]. On imaging, peritoneal in-
Malignant degeneration of a leiomyoma is a rare occlusion cysts are multiloculated cystic adnexal masses.
currence. Unfortunately, echogenicity or signal charac- The diagnostic finding is the presence of an intact ovary
teristics do not reliably distinguish a benign leiomyoma amid septations and fluid.
from a leiomyosarcoma. However, if a leiomyoma sud- Hydrosalpinx is the result of obstruction of the fim-
denly enlarges, especially after menopause, and/or has an briated end of the fallopian tube and dilatation of its am-
irregular or indistinct border, the possibility of sarcoma- pullary and infundibular portions. The cause of obstruc-
tous transformation should be raised. tion includes pelvic inflammatory disease, endometriosis,
adjacent tumors, and adhesions from prior surgery. On
imaging, a hydrosalpinx appears as a fluid-filled tubular
Non-neoplastic Ovarian/Adnexal Masses structure with a somewhat folded configuration and well-
defined walls. It may contain folds that simulate an in-
Follicular cysts are the most common benign ovarian complete thick septum.
masses. Other non-neoplastic adnexal lesions include The prevalence of endometriosis in all women is esti-
hydrosalpinx, peritoneal inclusion cyst, endometrioma, mated to be 5-10%. It is defined as the presence of func-
adnexal torsion, and tubo-ovarian abscess. These non- tioning endometrial glands and stroma outside the
neoplastic masses should be distinguished from benign uterus. The most common sites of involvement, in order
and malignant ovarian neoplasms. of decreasing incidence, are: the ovaries, cul-de-sac, pos-
Paraovarian cysts, also known as paratubal cysts, terior uterine wall, uterosacral ligaments, anterior uterine
account for 10-20% of adnexal masses. They are found wall, and bladder dome. Other sites include the sigmoid
within the broad ligament or paraovarium and arise colon, fallopian tubes, and distal ureters. Endometrioma
from mesonephric (wolffian)/paramesonephric (mullerian) is usually a term reserved for ovarian involvement. On
structures or mesothelial inclusions.The hydatid cyst of EVS, endometriomas typically appear as well-defined
Morgani is the most common paramesonephric cyst and unilocular or multilocular cystic masses with diffuse, ho-
arises from the fimbrial end of the fallopian tube [20]. On mogeneously dispersed low-level internal echoes. A
imaging, paraovarian cysts have the typical appearance of fluid-fluid level and a thickened wall with calcifications
a cyst, although they can vary in size and contain com- are sometimes present. On MRI, due to their hemor-
plex contents secondary to hemorrhage. rhagic contents, endometriomas are typically high in sig-
In pre-menopausal women, peritoneal fluid is pro- nal intensity on T1-weighted images with and without fat
duced by normally functioning ovaries and is reabsorbed saturation. They demonstrate “shading” or a gradient of
by the mesothelial cells of the peritoneal cavity. In low signal intensity on T2-weighted images, reflecting
patients with adhesions composed of mesothelial and the shortening of T2 due to blood (Fig. 7). Based on the
a b c
Fig. 7 a-c. Endometrioma: axial T1-weighted image with (a) and without (b) fat saturation;
c sagittal T2-weighted image. There is a large lesion of the right ovary with bright signal on
T1-weighted images with and without fat saturation and low signal intensity on T2-weighted
imaging. Small hyperintense follicular cysts adjacent to this lesion are seen on the sagittal
image
criteria of multiple adnexal, masses of very high signal occurrence can cause chemical peritonitis. In 1-2% of pa-
intensity on T1-weighted images or any mass with very tients, usually in older women, there is malignant trans-
high signal intensity on T1-weighted images and low sig- formation to squamous carcinoma.
nal intensity (shading) on T2-weighted images, the over- On EVS, mature cystic teratomas can have variable ap-
all sensitivity, specificity, and accuracy for diagnosing pearances depending on the tumor contents; nonetheless,
endometriomas with MRI is 90, 98, and 96%, respec- several specific features have been described. A “der-
tively [22]. moid plug” or “Rokitansky” protuberance can be seen as
The MRI appearance of solid fibrotic endometriosis an echogenic mural nodule in a predominantly cystic
has also been described: masses of intermediate signal mass. It is composed of hair, teeth, and fat and causes
intensity studded with high-signal-intensity foci on acoustic shadowing. The “dermoid mesh” is another spe-
T1-weighted images, low-signal-intensity masses on cific sign; it refers to hair fibers that appear as linear
T2-weighted images, and enhancement following intra- hyperechogenic interfaces floating in the cyst [26]. On
venous contrast [23]. Some fibrotic solid masses have MRI, T1-weighted imaging with and without fat satura-
small foci of hyperintensity on T2-weighted images, re- tion techniques can establish the presence of fat in a cys-
flecting embedded endometrial glands. tic teratoma. The adipose tissue will have high signal in-
tensity on T1 without fat suppression and will show sig-
nal loss on fat-suppressed images, thus excluding the di-
Neoplastic Ovarian Masses agnosis of an endometrioma or hemorrhagic cyst (Fig. 8).
Chemical shift imaging using in- and out-of-phase imag-
Epithelial tumors are the most common histological type, ing is helpful in identifying tumors that have only a tiny
comprising 60% of all ovarian neoplasms and >85-90% amount of fat [27].
of ovarian malignancies. Serous tumors are the most Fibrothecomas account for only 1% of all ovarian
common ovarian epithelial tumors. On imaging, serous neoplasms; however, they are the most common solid be-
cystadenomas are unilocular, thin-walled, large cystic nign tumors affecting the ovary. They are derived from
masses that may contain thin septations and occasionally stromal cells; because the histological appearance of fi-
papillary projections [24]. Mucinous tumors are the sec- bromas and thecomas overlap, the term “fibrothecoma”
ond most common epithelial tumor. On imaging, muci- is often applied to this spectrum of tumors. Like granu-
nous cystadenomas typically present as large cystic mass- lose cell tumors, they are hormonally active. Pure theco-
es (up to 30 cm) with multiple thin septations and low- mas are composed predominantly of theca cells and are
level echoes/T1-T2 shortening in the dependent portions most common in peri-menopausal and post-menopausal
due to mucoid material. This results in the typical women. In 15% of patients, there is co-existing endome-
“stained glass” appearance on MRI [25]. Papillary pro- trial hyperplasia, and up to 30% of patients have en-
jections are less frequently seen than in serous cystade- dometrial carcinoma. In contrast, pure fibromas are
nomas. Rupture of the tumor capsule can result in composed predominantly of fibroblasts and are most
pseudomyxoma peritonei. common in women under age 50, most of whom are
Mature cystic teratomas contain derivatives of at least asymptomatic. Meigs syndrome, a combination of ovar-
two of the three germ layers; ectoderm, mesoderm, and ian fibroma, ascites, and right pleural effusion, is rare.
endoderm. Ectodermal elements, however, tend to pre- On EVS, fibrothecomas present as hypoechoic solid
dominate, thus the term “dermoid cyst” was adopted. In masses with marked posterior sound attenuation as a re-
10% of the cases, mature cystic teratomas are bilateral. sult of homogeneous fibrous tissue. The MRI appear-
They are usually asymptomatic except when complica- ance of fibromas and thecomas are similar: intermediate
tions, usually torsion, occur. Rupture is uncommon but its signal intensity on T1-weighted images and very low
a b c
Fig. 8 a-c. Ovarian dermoid: a axial T2-weighted, b T1-weighted, and c T1-weighted fat suppressed images. A right adnexal mass with a flu-
id center and a rim that is hyperintense on the T1-weighted image; the mass shows signal loss on the fat suppressed image, indicating the
presence of fat
a Table 1. Reference values for magnetic resonance pelvimetry based

on 100 women undergoing spontaneous vaginal delivery (from [30])
Reference values ± SD
(cm)
Obstetric conjugate 12.2 ± 0.9
Sagittal outlet 11.6 ± 1.0
Interspinous diameter 11.2 ± 0.8
Intertuberous diameter 12.1 ± 1.1
Transverse diameter 13.0 ± 0.9
work-up of colicky abdominal pain or suspected appen-

dicitis, or fetal reasons.
Magnetic resonance pelvimetry is indicated in preg-
nant women with a history of pelvic trauma, previous ce-
sarean section, or in women who desire a trial of labor
when the fetus is in breech presentation. The groundwork
in pelvimetry was conducted using conventional radio-
b graphy, with measurement of the various parameters on
lateral and anterior-posterior views using various tech-
niques to correct the distortion due to differing distances
from the film. In recent years, X-ray pelvimetry has been
steadily replaced by MRI, which offers the benefit of ac-
curate measurement of the maternal pelvic dimensions
without exposure of the patient to ionizing radiation.
Magnetic resonance pelvimetric reference values in a
large study population, stratified by delivery modality,
have been established by a member of the author’s own
group [29, 30]. The results are shown in Table 1. In addi-
Fig. 9 a, b. Ovarian fibrothecoma: a sagittal T2-weighted image and tion, it was demonstrated that the pelvimetric parameters
b macroscopic specimen. The hypointense adnexal mass ventral to associated with the largest intra- and interobserver error
the uterus was histologically confirmed as ovarian fibrothecoma. and intraindividual variability are the intertuberous dis-
A small submucosal and a larger subserosal leiomyoma are seen in
the uterus tance and the sagittal outlet – a finding that must be tak-
en into careful account by obstetric decision-makers.
In conclusion, technical advances in ultrafast MRI
have revolutionized our ability to image the fetus. MRI is
most likely to soon become an important tool for in-
signal intensity on T2-weighted images [28] (Fig. 9). trauterine fetal imaging as an operator-independent sup-
Due to these signal characteristics, fibrothecomas may plement to prenatal ultrasound [31, 32].
be difficult to distinguish from pedunculated fibroids or
Brenner tumors. Multiple imaging planes combined with
the observation of small follicular cysts surrounding the References
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IDKD 2010-2013
Malignant Diseases of the Female Genital Tract

Evis Sala1, Susan Ascher2
1 Department of Radiology, University of Cambridge and Addenbrookes Hospital, Hills Road, Cambridge, United Kingdom
2 Department of Radiology, Georgetown University Hospital, Washington, DC, USA
Introduction Patient Preparation, Positioning, and Coil Selection
Advances in cross-sectional imaging have led to an in- Patient preparation and positioning are very important
creasingly important role for radiology in the manage- to obtain optimal imaging results. Patients are usually
ment of malignant gynecological conditions. A number instructed to fast for 4-6 h before the MRI examination
of imaging modalities can be used to evaluate malignant in order to limit artifacts due to small-bowel peristalsis.
diseases of the female pelvis, including ultrasound (US), An anti-peristaltic agent (hyoscine butylbromide or
computed tomography (CT), magnetic resonance imag- glucagon) may be administered before imaging as an al-
ing (MRI), and positron emission tomography/computed ternative. Ideally, the patient is asked to empty the blad-
tomography (PET/CT). These modalities have different der prior to examination, as a full bladder may degrade
roles in screening, diagnosis, staging, treatment selection images due to ghosting and motion artifacts. Patients are
and follow-up. The aim of this chapter is to review the imaged in the supine position using a pelvic surface-
role of different techniques in the imaging of malignant array multichannel coil; a cardiac coil usually offers the
gynecological conditions. The emphasis is on the use of best image quality [2].
MRI in the staging of endometrial and cervical cancer
following the revised FIGO (International Federation of Choice of Sequences and Imaging Planes
Gynecology and Obstetrics) criteria, implemented begin-
ning June 1, 2009 [1]. The basic imaging protocol for gynecological MRI con-
sists of T1-weighted images in the axial plane and T2-
weighted images in the axial, sagittal, and coronal planes.
Ultrasound T1-weighted axial images with a large field of view to
evaluate the entire pelvis and upper abdomen for lymph-
The primary imaging modality in the initial assessment adenopathy as well as bone marrow changes are essential
of suspected gynecological pathology is US. It is used to in staging gynecological malignancies. High-resolution
evaluate a suspected pelvic mass, characterize adnexal le- axial oblique T2-weighted fast spin-echo (FSE) images
sions, and identify endometrial abnormalities in the post- taken parallel to the short axis of the uterine corpus are
menopausal patient. Transabdominal and transvaginal US favored for the evaluation of primary tumor and depth of
can assist in image-guided fine needle aspiration cytol- myometrial invasion [3] in endometrial carcinoma,
ogy or biopsy and can also be used to guide placement of whereas axial oblique T2-weighted FSE (parallel to the
brachytherapy seeds in the treatment of cervical and en- short axis of the cervix) is crucial in assessing parame-
dometrial cancer. trial invasion in patients with cervical cancer.
Dynamic multiphase contrast-enhanced 3D T1-weight-
ed sequences through the uterus in the sagittal and axial
Magnetic Resonance Imaging (parallel to the short axis of the uterine corpus) planes are
routinely used to improve staging accuracy in endometri-
This is the imaging modality of choice in the staging of al cancer [4, 5]. They are also useful for the evaluation of
uterine and cervical cancer and in the characterization of complex adnexal lesions, as they may help differentiate
adnexal lesions when the US findings are indeterminate. solid components or papillary projections from clots and
The advantages of MRI include superb spatial and tissue debris. Dynamic imaging is not necessary. Diffusion-
contrast resolution, the absence of ionizing radiation, its weighted imaging (DWI) may be useful in differentiating
multiplanar capability, and its fast techniques. However, benign from malignant endometrial lesions [6] and can
the optimization of MRI sequences and clinical proto- provide valuable information for pre-operative staging in
cols, as outlined below, is crucial to ensure best results. patient with endometrial and cervical carcinoma [7].
120 Evis Sala, Susan Ascher
DWI can help in the evaluation of tumor response to ra- Endometrial Carcinoma
diotherapy in patients with cervical cancer [8] and is use-
ful in the detection of peritoneal implants and metastatic On US, endometrial carcinoma is seen as a thickened en-
lymph nodes in patients with gynecological malignancies dometrium (>5 mm in post-menopausal patients). On
[9]. DWI is also useful in detecting peritoneal implants in sonohysterography, endometrial carcinoma may present
patients with gynecological malignancies [10]. Ultra- as an intrauterine polypoid mass or as an asymmetrical
small particles of iron oxide (USPIO) have been shown thickening of the endometrium. It is, however, impossible
to improve the detection of lymph node metastases inde- to distinguish between benign endometrial polyps, en-
pendent of node size in patients with endometrial and dometrial hyperplasia, and endometrial carcinoma con-
cervical cancer [10]. fined to the endometrium using US alone. Therefore, en-
dometrial carcinomas are typically diagnosed at endome-
trial biopsy or dilatation and curettage, with MRI being
Computed Tomography reserved to evaluate the extent of disease [11].
Imaging criteria for staging of endometrial cancer are
The role of CT in the imaging of malignant uterine based on the TNM/FIGO (International Federation of
conditions is limited due to its poor soft-tissue contrast. Obstetrics and Gynecology) classification. The overall
The main role of CT is in staging, treatment planning,
staging accuracy of MRI has been reported to be between
and follow-up of patients with ovarian cancer. However,
85 and 93% [4, 5, 12]. Routine use of dynamic intra-
CT is important in the evaluation of other gynecological
venous contrast enhancement is necessary for state-of-
malignancies by identifying enlarged lymph nodes and
the-art MRI evaluation of endometrial carcinoma [4, 5].
distant metastases and detecting recurrent pelvic tumors.
Stage IA tumors involve <50% of the myometrial thick-
ness (Fig. 1). The presence of low-signal-intensity tumor
Positron Emission Tomography/Computed Tomography (equilibrium and later phases of enhancement) within the
outer myometrium or beyond indicates deep myometrial
Patients with malignant gynecological conditions are in- invasion and thus stage IB disease. Erroneous MRI as-
creasingly being evaluated with PET/CT. This modality is sessment of the depth of myometrial invasion may occur
very valuable in the detection of metastatic lymph nodes due to an indistinct zonal anatomy, the presence of co-
as it has better sensitivity and specificity than MRI; it can existent benign pathology (leiomyomas, adenomyosis),
also differentiate tumor recurrence from radiation fibro- tumor extension into the uterine cornu, or a polypoid
sis. PET/CT is also very useful in evaluating recurrent tu- tumor distending the uterus so that rather than deep
mor prior to salvage therapy. Maximum standard uptake myometrial infiltration there is a thin rim of myometrium
values (SUV) at staging can predict survival in patients stretched over the tumor [2].
with cervical carcinoma. However, it must be remem- In stage II disease, the fibrocervical stroma is disrupt-
bered that in pre-menopausal patients physiological up- ed by high-signal-intensity tumor on T2-weighted im-
take can be seen in the uterus, ovarian follicles, and cor- ages, together with the disruption of normal enhancement
pus luteum cysts. The uptake of 2-deoxy-2-[fluorine- of the cervical mucosa by low-signal-intensity tumor on
18]fluoro-d-glucose (FDG) can also be seen in certain late dynamic contrast-enhanced MRI.
benign ovarian and uterine tumors as well as in inflam- In stage III disease, tumor extends outside the uterus
matory and infectious processes. but not outside the true pelvis. Stage IIIA is marked by
a b
Fig. 1 a, b. Stage IA endometrial carcinoma.

Sagittal T2-weighted fast spin echo (FSE) (a)
and sagittal gadolinium-enhanced 3D T1-
weighted gradient-recalled echo (GRE) (b)
images show an endometrial carcinoma in-
vading the inner half of the myometrium. The
depth of myometrial invasion is better appre-
ciated on the gadolinium-enhanced 3D T1-
weighted GRE MR image (arrow)
Malignant Diseases of the Female Genital Tract 121
parametrial involvement, in which there is disruption of 3. Examination under anesthesia (EUA), which includes
the serosa with direct tumor extension into the surround- a cystoscopy and proctoscopy, is now recommended
ing parametrial fat. In stage IIIB disease, tumor extends rather than mandatory, as previously stated. MRI has
into the vagina and there is segmental loss of the low- excellent imaging capabilities in assessing tumor in-
signal-intensity vaginal wall. In stage IIIC disease, volvement of the bladder and of the rectosigmoid,
lymphadenopathy is present. therefore avoiding an additional invasive, timely, and
Tumor that extends beyond the true pelvis or invades the costly EUA procedure. This is especially helpful in
bladder or rectum constitutes stage IV disease. A loss of the clinical stage I and II disease, when the potential for
low signal intensity of the bladder or rectal wall indicates invasion and hence upgrading of the tumor staging af-
stage IVA disease whereas stage IVB disease includes dis- ter EUA is low.
tant metastasis, malignant ascites, or peritoneal deposits. The most important issue in the staging of cervical
CT is valuable in detecting upper abdominal lymph- cancer is to distinguish early disease (stage IIA1 and be-
adenopathy and distant metastases in patients with low), which is treated with primary surgery, from ad-
advanced endometrial carcinoma. PET/CT is useful in vanced disease, which is treated with radiation, either
assessing nodal disease and distant metastases and has a alone or in combination with chemotherapy. The excep-
role in monitoring treatment response in these patients. tion is stage IB2, in which the lesion is >4 cm in diame-
ter and is treated as for advanced disease.
Stage IA and its subdivisions are defined as microinva-
Cervical Carcinoma sive tumors that cannot be reliably demonstrated on T2-
weighted images. However, dynamic contrast-enhanced
The main role for imaging is staging a biopsy-proven cer- MRI may detect microinvasive disease as a focally en-
vical carcinoma. MRI is the best single imaging investiga- hanced area seen in the early dynamic phase. In distin-
tion and can accurately determine tumor location (exophyt- guishing deep invasion (>3 mm) from superficial disease,
ic or endocervical) and size, the depth of stromal invasion, the accuracy of T2-weighted MRI, dynamic MRI, and con-
and extension into the lower uterine segment [13, 14]. On trast-enhanced T1-weighted imaging is 76, 98, and 63%,
T1-weighted images, tumors are usually isointense with the respectively [16]. Stage IB is defined as clinically visible
normal cervix and may not be visible. On T2-weighted lesions limited to the cervix uteri and is subdivided into
images, cervical cancer appears as a mass of intermediate stage IB1, in which lesions are <4 cm in their greatest di-
signal intensity and is easily distinguishable from the low mension, or stage IB2, in which lesions are >4 cm in their
signal intensity of the cervical stroma. MRI is recommend- greatest dimension. The carcinoma appears as a mass of
ed in evaluating cervical carcinoma patients with clinical high signal intensity in contrast to the low signal intensity
stage IB disease or greater when the primary lesion is of the cervical stroma on T2-weighted images.
>2 cm, because of the relatively high likelihood of parame- Young women with stage IA or small IB (<2 cm) tu-
trial invasion and/or lymph node metastases [13, 15]. The mors who wish to retain their fertility may be considered
staging accuracy of MRI ranges from 75 to 96%. The for trachelectomy, in which the cervix is excised but the
reported sensitivity of MRI in the evaluation of parametrial uterine body and hence fertility is preserved. MRI is
invasion is 69% and the specificity 93% [13, 15]. highly accurate in predicting myometrial invasion, with a
Although the FIGO system does not include radiology sensitivity and specificity of 100 and 99% respectively.
in the staging of cervical cancer, the revised FIGO stag- For internal os involvement, the sensitivity of MRI is
ing criteria for cervical carcinoma [1], implemented as of 90% and the specificity 98%.
June 1, 2009, encourage the use of imaging techniques, Stage IIA is defined as a tumor that invades the upper
if available, to assess important prognostic factors such as two-thirds of the vagina without parametrial invasion.
parametrial and pelvic side wall invasion, tumor size, and Segmental disruption of the hypointense vaginal wall is
lymph node metastases. Imaging is therefore complimen- demonstrated on T2-weighted images. When the tumor
tary to the clinical assessment. The FIGO committee extends beyond the uterus, with parametrial invasion,
made three changes that impact on radiology vs MRI of it is defined as stage IIB. Spiculated irregular tumor/
the pelvis. parametrial interface, soft-tissue extension into the parame-
1. The use of diagnostic imaging techniques to assess the tria, or encasement of the peri-uterine vessels is required
size of the primary tumor is now encouraged by FIGO to confidently diagnose parametrial invasion (Fig. 2).
but is still not mandatory. MRI is highly accurate in MRI has a specificity and negative predictive value of 97
measuring tumor size, which can affect prognosis and and 100%, respectively, in evaluating parametrial inva-
treatment. sion [3]. An important pitfall is the overestimation of
2. Stage IIA has been subdivided: Stage IIA1 consists of parametrial invasion on T2-weighted images of large
tumors without parametrial invasion that are ≤4 cm in tumors (accuracy of 70%) compared to smaller tumors
diameter and involve less than the upper two-thirds of (accuracy 96%). Large tumors can cause stromal edema
the vagina. Stage IIA2 tumors are without parametrial by tumor compression or inflammation – a fact that must
invasion, >4 cm in diameter, and involve less than the be considered when making treatment decisions in these
upper two-thirds of the vagina. patients.
a b
Fig. 2 a, b. a Stage IIB cervical carcinoma.

Sagittal T2-weighted image demonstrates an
intermediate signal intensity mass centred on
the posterior fornix (white arrow). b Axial
oblique T2-weighted image demonstrates
parametrial invasion with spiculated irregu-
lar tumor to parametrium interface on the
right (black arrows)
In stage IIIA, the tumor involves the lower third of the the site and size of peritoneal deposits, and the presence
vagina without extending to the pelvic side wall (>3 mm of enlarged lymph nodes and ascites (Fig. 3). This infor-
from pelvic side wall). When the tumor extends to the mation stratifies those patients with non-resectable dis-
pelvic side wall (pelvic musculature or iliac vessels) or ease, for whom neoadjuvant chemotherapy would be ben-
causes hydronephrosis, it is defined as stage IIIB. eficial, from those patients who should undergo primary
If the tumor invades the bladder or rectal mucosa it is cytoreductive surgery. The primary ovarian tumor may be
stage IVA. There is segmental disruption of the low sig- seen as mixed solid/cystic tumors, which are often bilat-
nal intensity of the bladder or rectal wall or segmental eral, or as multilocular cystic lesions with thick internal
thickening of the rectal wall. Prominent strands between septations and solid mural or septal components. Assess-
the tumor and the rectal wall may also indicate rectal in- ment can often be made as to whether the tumor invades
vasion. MRI can confidently exclude bladder or rectal in- the pelvic side wall or rectosigmoid colon or bladder, and
volvement, with a negative predictive value of 100% associated complications, such as hydronephrosis and
[17]. Distant metastases define stage IVB disease. Al- bowel obstruction, can be identified. Peritoneal deposits
though pelvic lymph node metastases do not change the can be clearly identified; they are usually seen as discrete
FIGO stage, para-aortic or inguinal lymph node metas- enhancing soft-tissue nodules. Liver, lung, and renal
tases are also defined as stage IVB. metastases and malignant pleural effusion indicate stage
CT has a limited role in staging cervical cancer due IV disease. PET/CT is of value in cases of suspected re-
to its low accuracy in the detection of early parametrial currence in which there is an increase in the level of the
extension [18]. However, CT has a diagnostic accuracy tumor marker CA-125 but indeterminate findings on CT
of approximately 90% in staging advanced cervical car- or MRI [20].
cinoma and is very useful in evaluating the presence of Currently, the main role of MRI is in the characteriza-
distant metastases [19]. PET/CT allows the identification tion of ovarian masses rather than the staging of histo-
of involved nodes when CT findings are negative, result- logically proven ovarian cancer. MRI is very sensitive
ing in a change in management in up to 25% of patients. (95%) in the detection of peritoneal metastases, which
In the detection of recurrent cervical cancer, it has a show delayed enhancement on contrast-enhanced MRI
reported sensitivity, specificity, and accuracy of 90.3, [21]. Gadolinium-enhanced MRI is comparable to la-
81.0, and 86.5, respectively. This is especially valuable to parotomy but superior to serum CA-125 levels in the de-
exclude the presence of distant disease prior to pelvic tection of residual or recurrent peritoneal and serosal im-
exenteresis [20]. plants in women who have been treated for ovarian can-
cer [21, 22]. MRI plays a crucial role in the detection of
recurrent disease. It is important to realize that second-
Ovarian Carcinoma look surgery is no longer routine and imaging diagnosis
of recurrence may obviate a second-look laparotomy
Ultrasound enables the detection and characterization of since secondary cytoreduction is only justified if resec-
adnexal masses but has no role in staging. It can guide tion is possible with no residual tumor. Imaging findings
biopsy of adnexal or peritoneal masses in patients that indicate non-resectable recurrent tumor are invasion
deemed unsuitable for primary surgery. CT is currently of the pelvic side wall, which should be suspected when
the modality of choice in staging ovarian cancer and can the primary tumor lies within 3 mm of the pelvic side
also be used to guide the biopsy of peritoneal or adnexal wall or when the iliac vessels are surrounded or distorted
disease. CT provides information on the primary tumor, by tumor.
Malignant Diseases of the Female Genital Tract 123
a b
c d
Fig. 3 a-d. Advanced ovarian carcinoma. Con-

trast-enhanced CT images show (a) a left
pleural effusion and a subcapsular liver de-
posit (arrow) and (b) peritoneal deposits along
the surface of the liver and gastrosplenic liga-
ment (arrows). There are also (c) a large omen-
tal cake and serosal deposits in the right para-
colic gutter (arrows), (d) bilateral solid cystic
ovarian masses and a large peritoneal deposit
in the Pouch of Douglas (arrows)
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105:103-104 nostic performance of nanoparticle-enhanced magnetic reso-
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IDKD 2010-2013
Magnetic Resonance Imaging of Prostate Cancer

Jelle O. Barentsz, Stijn W.T.P.J. Heijmink, Christina Hulsbergen-van der Kaa, Caroline Hoeks, Jurgen J. Futterer
Department of Radiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Introduction score) are important aspects. Additionally, however, mag-

netic resonance imaging (MRI) can play an important
With a total of 192,280 new cases predicted for 2009, role in detecting and localizing those areas most reflec-
prostate cancer (PC) now accounts for 25% of all new tive of the actual aggressiveness of the cancer. This di-
male cancers diagnosed in the USA [1]. Furthermore, in rectly influences patient assessment and may lead to im-
their lifetime, one in six men will be clinically diagnosed portant changes in treatment strategy, which can mean the
with PC, although many more will be found to have his- difference between treatment success and failure.
tological evidence of PC at autopsy [2-4]. Presently, ap- In the mid-1980s, the first prostate MRI examina-
proximately one in ten men will die of PC [5, 6]. The tions were performed. Since that time MRI has evolved
ever-aging population and more widespread use of the from a promising technique into a mature imaging
blood prostate-specific antigen (PSA) test [7, 8], as well modality for PC imaging [18, 19]. Beside anatomical in-
as the tendency to apply lower cut-off levels for this test formation, MRI provides functional tissue-characteristic
[9], will further increase the diagnosis of PC [10]. information. Multiparametric MRI consists of a combi-
An elevated PSA level, abnormal changes in PSA lev- nation of anatomical T2-weighted imaging and func-
el and dynamics (such as PSA velocity or doubling time), tional MRI techniques such as dynamic contrast-
or an abnormal digital rectal examination are biological enhanced MRI (DCE-MRI), diffusion-weighted imag-
indicators signaling an increased risk of PC. With the im- ing (DWI), and 1H MR-spectroscopic imaging (MRSI).
provement and wider range of curative therapies, the de- Within a multiparametric MRI examination the relative
tection and subsequent exact localization of PC have be- value of its component techniques differ. In addition to
come increasingly important because of their influence T2-weighted MRI, which mainly assesses anatomy,
on treatment strategy [11, 12], in particular, laparoscopic MRSI [20] can add specificity for PC detection, while
(robotic) radical prostatectomy and intensity-modulated DCE-MRI [21] and DWI [22] are both very sensitive
radiation therapy (IMRT) [13]. The urologist’s inability to and very specific.
palpate the operating field during laparoscopic surgery The clinical challenges in the work-up of patients with
makes it even more crucial to precisely localize the can- either suspected or proven PC include detection, local-
cer. Moreover, the urologist must determine whether the ization, TNM staging, determination of cancer aggres-
cancer is near a neurovascular bundle since this affects siveness, follow-up of patients in active surveillance pro-
the decision of whether or not to perform nerve-sparing tocols, and determination of the site and extent of cancer
prostatectomy [14]. IMRT also necessitates accurate PC recurrence after therapy.
localization. While the prostate receives a standard dose This chapter reviews the MRI anatomy of the prostate
of radiation, a higher (boost) dose can be given to domi- and the basic MRI techniques that can be applied in PC,
nant intraprostatic lesion(s) since it is those lesions that and discusses the clinical role of this imaging modality.
regularly appear to be the sites of recurrent disease [15]. At the end of this chapter, three clinically applicable pro-
Furthermore, precision radiation dosimetry will decrease tocols are provided.
radiation complications, particularly rectal wall toxicity
[16], thereby likely diminishing the development of post-
radiation rectal cancer [17]. Magnetic Resonance Imaging: Anatomy
In order to determine the optimal treatment for each
patient, it is necessary to thoroughly evaluate him and to In order to effectively apply the various MRI techniques,
determine the cancer’s characteristics. In this regard, lab- it is important to first understand the prostate’s normal
oratory values (PSA level and dynamics), the results of anatomy and its intrinsic age-related changes. The supe-
the digital rectal examination (clinical staging), and rior part of the prostate is called the base while its most
histopathological prostatic biopsy findings (Gleason caudal part is referred to as the apex, analogous to the
126 Jelle O. Barentsz, Stijn W.T.P.J. Heijmink, Christina Hulsbergen-van der Kaa, Caroline Hoeks, Jurgen J. Futterer
a b
c
d e
Coronal
Sagittal Axial
Fig. 1 a-e. Normal prostate with signs of benign prostatic hyperplasia (BPH) as seen on sagittal (a, d), coronal (b), and axial (c, e) high-
resolution T2-weighted images. The peripheral zone is white, BPH is blue, the urethra is yellow, and the seminal vesicles are green
anatomy of the heart. The prostate consists of three Magnetic Resonance Techniques and Their Role in
zones: (1) the peripheral zone, located posteriorly and Detection and Localization
caudally at its middle portion; (2) the transition zone, lo-
cated interiorly, around the urethra; and (3) the central For evaluation of the prostate, anatomical (high-resolu-
zone, which is posterior and superior to the transition tion) MRI can be combined with functional and meta-
zone. Ventral to the prostate is the anterior fibromuscular bolic information. DWI, dynamic MRI, and MRSI pro-
stroma. vide information about the motion of free water mole-
In aging, an important frequent change in prostate zon- cules and thus about cellular density (neo-)vasculariza-
al anatomy occurs, namely, the transition zone becomes tion and metabolism, respectively. These different types
hypertrophic (as in benign prostatic hyperplasia), thus of information can be combined into a multiparametric
compressing the central gland. Consequently, most men MRI examination.
who are imaged for prostate cancer have only two identi-
fiable compartments in the prostate, the hyperplastic tran- T2-Weighted Imaging
sition zone surrounded by the peripheral zone (Fig. 1).
Up to 70-80% of PCs are located in the peripheral Compared to CT computed tomography (CT) scanning,
zone [23], with an overall analysis of these cancers show- MRI has a high soft-tissue contrast resolution (Fig. 2).
ing that they are homogeneously distributed across the The use of a disposable endorectal coil combined with
entire zone [24]. Additionally, over half of the prostates other external coils at 1.5 Tesla (T) increases the soft-
examined contained two or more distinct cancer foci [25]. tissue contrast significantly and is now the accepted clin-
Nevertheless, while up to 20-52% of all PCs originate in ical standard for MRI of the prostate, when information
the transition zone, only a small percentage (3.6-25%) of about submillimeter extracapsular penetration is of clini-
these cancers occur solely in that zone [24, 26], and many cal importance [29]. A drawback is the extra time re-
such patients will have foci of concurrent peripheral-zone quired for inserting and checking the position of the
cancer [23, 27, 28]. Thus, a solitary transition zone can- endorectal coil as well as the substantial expense and
cer is rare in the general PC population. patient discomfort.
Magnetic Resonance Imaging of Prostate Cancer 127
a b
Fig. 2 a, b. A 60-year-old patient with a urinary

catheter, and stage 2b prostate cancer (PC) in
the left peripheral zone. a Axial MDCT does
not well-delineate the prostate and the tumor
is not visible. b T2-weighted axial MRI
shows good prostate delineation and tumor in
the left peripheral zone (arrow) without cap-
sular penetration
Fig. 3 a, b. a On axial T1-weighted MRI, the

post-biopsy hematoma (H (H) is white. b On the
T2-weighted image, both the hematoma (H (H),
benign prostatic hyperplasia ((B), and tumor
(*) are of low signal intensity
On MRI, PC typically appears as an area of low sig- incremental value from MRI [34]. In patients subjected to
nal intensity within the brighter, healthy peripheral multiple prior negative TRUS-guided biopsies, anatomi-
zone, as seen using a T2-dominated sequence [30-32] cal MRI by means of T2-dominated acquisition plays an
(Figs. 2b, 3). In the central gland, PC is not as clearly important role. In this patient population, a sensitivity of
discernible because the transition zone generally has 83% and positive predictive value of 50% for MRI have
lower signal intensity than the peripheral zone and is been established [35].
more inhomogeneous due to the architectural changes Post-biopsy hemorrhage causes areas of low signal in-
induced by benign prostatic hyperplasia, which may tensity on T2-dominated sequences, thereby making PC
mimic PC. A recent study showed that a homogeneous- detection more difficult. However, it was shown recently
ly low T2 signal intensity and lenticular shape were sig- that the amount of hemorrhage was significantly lower in
nificantly associated with the presence of transition- areas of cancer than in healthy tissue [36].
zone [4, 33]. It was reported that, relative to muscle,
cancers with higher Gleason scores had lower signal in- Diffusion-Weighted Imaging
tensities than cancers with low Gleason scores [32].
However, the number of patients in that study was lim- This non-invasive technique measures the fractional
ited. In a comparison of T2-weighted MRI with prosta- anisotropy of water molecules within the prostate, ex-
tectomy specimens, MRI attained 52-83% sensitivities pressed in apparent diffusion coefficient (ADC) map-
in PC localization, while specificities were somewhat ping. Thereby, the movement of water molecules in can-
lower (46-88%). cer tissue has been shown to be more restricted, thus pro-
A study that directly compared endorectal MRI with ducing lower ADC values [37, 38]. In a recent study of
digital rectal examination and transrectal ultrasound 38 patients who underwent DWI at 1.5 T with an en-
(TRUS)-guided biopsy localization revealed significant dorectal coil, the mean ADC values of regions of interest
Dynamic Contrast-Enhanced MRI
The use of intravenous contrast agents further enhances

the localization accuracy of MRI. Endorectal DCE-
MRI, in which the contrast agent concentration is fol-
lowed over time [46], discriminates between healthy
prostate tissue and PC [47]. Early contrast enhancement
and high (relative) peak enhancement are the most ac-
curate predictors of PC of the peripheral zone, while
fast washout of contrast agent and high permeability of
the blood vessels (Fig. 6) are most sensitive for transi-
tion-zone PC [48, 49]. A recent study showed that the
area under the receiver operating curve (AUC) for lo-
calizing PC increased significantly, from 0.68 with reg-
ular anatomical MRI to 0.91 with contrast-enhanced
MRI. However, the limitations associated with the use
of contrast agents are the lack of a uniform threshold,
Fig. 4. Axial T2-weighted image obtained from a 70-year-old male the low sensitivity for cancer, higher costs, and possible
with PSA = 35 and six negative TRUS biopsies shows a homo- adverse reactions, of which the most serious is nephro-
geneous area of low signal intensity in the right ventral prostate genic systemic fibrosis [50, 51].
(arrows)
1H Magnetic Resonance Spectroscopic Imaging
Additionally, MRSI (Fig. 7) can be added to the imag-

ing protocol to provide metabolic information based on
the tissue citrate, choline, and creatine concentrations,
and their relative ratios within the prostate. This is high-
ly informative since the ratio between choline and cit-
rate is markedly altered during the transformation from
healthy to malignant prostate cells [52, 53] and an in-
creasing choline+creatine/citrate ratio has been corre-
lated with higher Gleason scores [54]. Presently, three-
dimensional (3D) MRSI of the entire prostate can be
performed [55], thereby aiding in the diagnosis of
Fig. 5. Same patient as in Fig. 4. The ADC map (color coded) shows
restriction in the area suspicious for tumor on this T2-weighted im-
age (arrows)
within PC tissue were significantly lower than those with-

in healthy prostate tissue [39]. In preliminary studies, the
combination of this technique with MRSI [39] or T2-
weighted imaging [40] significantly improved localiza-
tion accuracy (Figs. 4, 5). This was confirmed in a more
recent study in 37 patients, in which sensitivity increased
from 51% for T2-weighted imaging to 71% when the lat-
ter was combined with DWI [41]. In a recent multipara-
metric analysis, DWI was the best-performing parameter Fig. 6. Same patient as in Fig. 4. Ktrans-map obtained with dynam-
in localization [42]. Preliminary studies at 3 T have ic contrast-enhanced MRI shows pathological enhancement in area
shown promising results [43-45]. suspicious for tumor on this T2-weighted image (arrows)
c
b
Fig. 7 a-c. Images obtained from a 65-year-old male with stage T3a PC in the left peripheral zone. The T2-weighted image (a) shows the tu-
mor. MRSI of the right peripheral zone (b) shows low the choline and high citrate peak, whereas tumor in the left peripheral zone (c) shows
high choline
central-gland PC (Fig. 7). The addition of 3D MRSI to sonable detection rates of 25-55% [62, 63]. Moreover, di-
MRI increases localization accuracy, by raising the rect MRI-GB within the MRI scanner is technically feasi-
specificity to as high as 91% [56]. However, a limitation ble and can be performed on a routine basis. In patients
of MRSI is its low spatial resolution and cumbersome with one previous negative TRUS biopsy, transrectal MRI-
post-processing. Compared to systematic biopsy, PC GB performed at 1.5 T has produced promising cancer de-
localization by means of MRI and MRSI was found to tection rates of 38-56% [64-66]. Lesions >10 mm can suc-
be more sensitive (67 and 76% vs. 50%) but less spe- cessfully be biopsied using this approach [66].
cific (69 and 57% vs. 82%) than systematic biopsy [57]. A multiparametric MRI approach consisting of T2-
With whole-mount-section histopathology as the stan- weighted MRI, DWI, and DCE-MRI performed at 3 T has
dard of reference, 3D MRSI had a significantly larger a median MRI-guided biopsy time of just 35 min and can
AUC (0.80) in localizing cancer than obtained with T2- generate an average of four biopsy cores per patient, as
weighted MRI (0.68) [58]. The combination of T2- recently reported by Hambrock et al. (Fig. 8) [67]. Those
weighted imaging and MRSI information to clinical da-
ta yielded the highest accuracy (AUC 0.85) in predict-
ing the probability that a patient has insignificant PC
[59], which was significantly higher than that obtained
with clinical nomograms. A recent multi-institutional
American College of Radiology Imaging Network study
raised doubts on the additive value of MRSI over T2-
weighted imaging alone [60]. However, potential factors
resulting in this conclusion were the selected prostatec-
tomy population, the small size of the average cancer
focus, and the inclusion of health centers without any
previous MRSI experience.
MRI-Guided Biopsies
Random systematic TRUS-guided biopsy has relatively

low detection rates and is prone to sampling error [61].
MRI-guided prostate biopsy (MRI-GB) has the potential
to increase PC detection, as multiparametric MRI can tar-
get biopsies towards regions previously determined to be Fig. 8. Same patients as in Fig. 4. MRI-guided biopsy of the tumor-
suspicious for cancer. Indeed, MRI findings have been suspicious region (red) showed PC with a Gleason score of 4+3.
used to direct biopsies under TRUS guidance, with rea- The biopsy needle is highlighted in white
authors showed that a cancer detection rate of 59% can score [75-77]. Preliminary results in the evaluation of
be achieved in a large cohort of patients with more than ADC as a marker of cancer aggressiveness are promis-
two previous negative TRUS biopsies [68]. In addition, ing; ADC values were found to negatively correlate
93% of the cancers found were clinically significant, thus (ρ = –0.497, p<0.0001) with peripheral-zone cancers and
not contributing to the over-diagnosis of insignificant Gleason scores. In another study, lesions in patients with
cancers. less aggressive cancers (PSA <10, T1 or T2a, Gleason
A limitation of MRI-GB is that multiparametric MRI score <6) had significantly higher ADC values than le-
for tumor localization and MRI-guided biopsy need to be sions in patients with intermediate- to high-risk cancers
performed in two different sessions, as image post- (PSA >10, T2b, Gleason score ≥7) (Fig. 9) [77-79].
processing and exact localization of the cancer demand
time. Another disadvantage is movement of the prostate Local (T) Staging
during the biopsy procedure [69]. A reduction of the
MRI-GB intervention time remains an important chal- The application of MRI to determine whether PC is lo-
lenge, perhaps solvable by robotics. In the future, MRI- cally advanced remains controversial due to varying re-
based guidance might also be used in the focal treatment sults across institutions. The most reliable MRI signs of
of PC, such as in the form of brachytherapy or cryotherapy. extracapsular extension are bulging of the prostate into
the periprostatic fat, obliteration of the recto-prostatic
angle, and asymmetry of the neurovascular bundles
Prediction of Prostate Cancer Aggressiveness (Fig. 10) [80]. Seminal vesicle invasion is usually easi-
ly detectable as areas of low signal intensity in the
Prostate cancer aggressiveness is pathologically graded brighter seminal fluid (Fig. 10).
by the Gleason score, which consists of a combination of Two meta-analyses on local staging by MRI at 1.5 T
the two most prevalent Gleason grades (range 1-5) based reported combined maximum sensitivities and specifici-
on the architectural characteristics of PC tissue [70]. ties of 71-74%, while sensitivity was 62-69% at a speci-
Biopsy specimens obtained from random TRUS guided- ficity of 80% [80-82]. Imaging in more than one plane as
biopsy are subject to sampling error in approximately well as the use of an endorectal coil resulted in a signif-
64% of the cases [71]; this results in incorrect Gleason icantly better staging performance. A large study of 336
scores and thus incorrect patient risk stratification, which patients conducted by Cornud et al. found an overall sen-
in turn leads to under- or overtreatment [72]. sitivity, specificity, and positive and negative predictive
Apart from a relationship between muscle-normalized values of 40, 95, 79, and 76%, respectively [83]. High-
signal intensity on T2-weighted MRI and cancer Gleason specificity MRI (in which only definite locally advanced
scores [73], a correlation between cancer visibility on cases are excluded from curative therapy) is now the
T2-weighted images and aggressiveness has been sug- optimal local staging method [84, 85].
gested, with low-grade cancers being detected in 43% The addition of MRI with an endorectal coil to clini-
and high-grade cancers in 79% of such cases [74]. More- cal data such as PSA, biopsy Gleason score, and Kattan
over, (choline+creatine)/citrate ratios, as determined by nomogram resulted in a significantly increased accuracy
MRSI, have been shown to correlate with the Gleason of predicting disease stage, extracapsular extension, and
a b c
Fig. 9 a-c. Images from a 62-year-old patient with PSA = 9 and PC with a Gleason score of 3 but with a local component with a score of 4.
a Axial T2-weighted MRI shows low signal in almost the entire peripheral zone. b On the ADC map, the tumor can be delineated based
on its lower value (uninterrupted line) and on the presence of local areas with very low value (stippled areas). c Prostatectomy confirmed
the lower signal to be a Gleason 3 tumor and the very low signal component to be Gleason 4
b d
Fig. 10 a-d. T2-weighted images from a 49-year-old male with stage T3B PC. a Coronal im-
age at basis shows seminal vesicle infiltration (*); b axial image at the mid-part shows
bulging (arrows); c axial image at the apex shows obliteration of the recto-prostatic angle
(arrow) and, for comparison, the normal recto-prostatic angle (drawn line); d schematic
drawing, as part of the structured report
seminal vesicle invasion [79, 86, 87]. Recently, it was Metastatic Disease (NM Staging)
shown that the presence and the degree of pre-radiation
therapy extracapsular extension predicted by MRI was a Nodes
predictor of post-therapy outcomes [88].
The addition of DWI to T2-weighted imaging was re- The prognosis of patients with PC is poorer if lymph
cently shown to be significantly better in establishing uri- node metastases are present. The risk of lymph node
nary bladder wall invasion as well as seminal vesicle in- metastasis is currently determined (albeit inaccurately)
vasion [89, 90]. Also, the addition of three-dimensional using nomograms [98, 99]. In patients with an elevated
MRSI to MRI improved staging accuracies, particularly risk for metastasis, additional examinations are required.
for less-experienced readers, and increased interobserver Today, the most commonly used imaging techniques for
agreement [91]. A drawback is the longer duration (by detecting lymph node metastasis are multi-detector CT
approximately 15 min) of the examination. scan (MDCT) and conventional MRI, with image inter-
Experience was found to be an important factor in dis- pretation essentially based on lymph node size and shape
ease staging [92]. However, the accuracy of a less-expe- criteria. Although the criteria vary slightly [100], lymph
rienced reader could be increased by contrast-enhanced nodes with a short-axis diameter >8 mm for round lymph
examinations [93]. Likewise, MRI interpretation using nodes and >10 mm for oval ones are generally considered
multiplanar cross-referencing significantly improved to be malignant [101, 102]. Both MDCT [103] and MRI
staging accuracy compared with interpretation without [104] have a low sensitivity (36 and 39%, respectively)
cross-referencing [94]. Interactive tutorials with direct for diagnosing PC lymph node metastases using these
feedback were also shown to significantly increase the size and shape criteria. In studies that have employed
accuracy of staging by less-experienced readers [95]. thresholds as small as 6 mm [105], the specificity was
Imaging at higher magnetic field strengths (e.g., 3 T) very high (95-100%) but the sensitivity was too low
can achieve better image resolution. Although not yet (0-25%) to be useful in regular clinical practice for the
widely available for clinical work, local staging at 3 T evaluation of metastatic lymph node disease [106]. Some
was shown in two studies to improve the sensitivities and authors advocate restricting the application of these tech-
specificities of experienced readers to 80-88% and 94- niques to high-risk patients (e.g., with PSA levels >20
100%, respectively [96, 97]. In the current PSA era, this ng/mL) in order for them to be cost-effective [107, 108].
higher resolution is mandatory as PC is detected at earli- Thus, supplementary, invasive diagnostic examinations in
er stages. Likewise, if extracapsular extension is present, the form of surgical pelvic lymph node dissection
it will most often be minimal. (PLND) are still commonly performed.
Magnetic resonance lymphography (MRL) using a findings on bone scintigraphy that have arisen due to
lymph-node-specific contrast agent (Combidex/Sinerem) conditions such as trauma, degenerative joint disease,
[109, 110] is an experimental technique that, compared to and other chronic diseases. However, conventional X-
PLND, has a high negative predictive value (>96%) for ray is too insensitive for the detection of metastatic bone
the detection of lymph node metastasis in extended areas. lesions. Lecouvet et al. evaluated the accuracy of bone
Importantly, its use can render PLND unnecessary in scintigraphy, targeted X-rays, and MRI in 66 patients
negative cases [111]. with prostate cancer, 41 of whom had bone metastases
(Fig. 11) [114]. Sensitivities were 46% for bone scinti-
Bone graphy alone, 63% for bone scintigraphy and targeted
X-rays, and 100% for MRI; the corresponding speciﬁcities
Most metastatic bone lesions are sclerotic [112]; a 50% were 32, 64, and 88%, respectively. Thus MRI was
change in bone mineral density is needed for metastat- significantly more sensitive than any other approach
ic bone lesions to be visible on X-ray images [113]. The ( <0.001); furthermore, MRI limited to the pelvis and
(p
most commonly used first-line diagnostic test to detect axial skeleton was shown to be sufficient, as the proba-
or exclude bone metastases is technetium-99m-diphos- bility of finding metastases outside these locations in
phonate bone scintigraphy. However, this approach the absence of metastases in the axial skeleton is negli-
lacks specificity, such that primary skeletal diseases gible. This is particularly the case in PC, which pre-
may generate false-positive findings. Conventional X- dominantly metastasizes to the spine and pelvis due to
ray examinations can be used to exclude false-positive the venous drainage routes [115, 116].
a b
Fig. 11 a-c. Patient with bone metastasis from

PC. a T1-weighted image shows a small, low
signal intensity lesion (arrow) with high inten-
sity on DWI (b), consistent with metastasis.
The bone scan (c) and plain film were negative
Recurrence therefore decreased, which makes the detection of recur-

rence more difficult. In one of the rare studies that used
Currently, a rise in PSA level is the only major indicator radical prostatectomy specimens after radiotherapy as the
for PC recurrence after radical prostatectomy or radio- standard of reference, retrospectively assessed endorectal
therapy [117, 118]. The recurrence of PC is indicated by MRI had a low to fair accuracy for the detection of local
PSA values >0.4 ng/mL following radical prostatectomy post-radiotherapy recurrence (AUC 0.61-0.75), the pre-
and by a PSA value 2 ng/mL above the nadir value (after diction of extracapsular extension (0.76-0.87), and evi-
the PSA bounce) following radiation therapy [119, 120]. dence of seminal vesicle invasion (0.70-0.76) [124].
Whenever such an elevation of PSA occurs, the main ob- Functional MRI techniques are of additional value in
jective is to determine whether it is due exclusively to re- the detection of disease recurrence following radiation
current or residual disease in or outside the prostate, therapy (Fig. 12). On MRSI, the presence of three or
since locally recurrent disease might still be cured with more suspicious voxels in a prostate half had a sensitivi-
adjuvant radiotherapy. ty of 89% and a specificity of 82% in the detection of lo-
The use of DRE and TRUS for recurrence detection is cal post-radiotherapy recurrence (n=23) [125]. Further-
compromised because of the difficulty in distinguishing more, post-radiotherapy DCE-MRI was shown to have a
between fibrotic changes and recurrent disease. TRUS- sensitivity of 70-74% and a specificity of 73-85% for re-
guided biopsy has a low sensitivity and specificity with currence detection [126, 127]. The addition of DWI to
respect to recurrence following prostatectomy or radio- T2-weighted imaging (AUC 0.61) also improved the de-
therapy [121, 122] whereas MRI can help in the detection tection of post-radiotherapy disease recurrence by 27%
of recurrent disease. One of the major advantages of MRI (AUC 0.88) [128].
is that it can be used to evaluate the recurrence of PC at In a retrospective study evaluating the value of anatom-
either local or distant sites. ical T2-weighted MRI in the detection of post-prostatec-
After external-beam radiation therapy, prostatic tissue tomy disease recurrence, the sensitivity was reported to be
demonstrates diffusely low signal intensity on T2-weighted 95% and the specificity 100% [129]. Thus, also in the
images, with indistinct zonal anatomy [123]. The contrast evaluation of post-prostatectomy disease recurrence func-
between benign, irradiated tissues and recurrent cancer is tional MRI techniques are of additional value (Fig. 13). In
a b
Fig. 12 a, b. A 69-year-old patient 2.5 years af-

ter external radiation beam therapy; his PSA
had risen to 2.1. a T2-weighted MRI shows
entirely low signal gland; no tumor can be
discriminated. b DCE-MRI shows enhance-
ment of the right half of the prostate (arrow).
Biopsy revealed Gleason 5+4 PC
a b
Fig. 13 a, b. Patient with PSA recurrence after

prostatectomy. a T1-weighted image shows
no lesion whereas (b) DWI shows enhance-
ment (red circle), which was due to recur-
rence of the tumor (Gleason 4+3)
this regard, DCE-MRI combined with anatomical T2- The highest b value should be 1000 if ADC is calcu-
weighted MRI was shown to improve sensitivity and lated, otherwise it should be 1400 (with adequate sig-
specificity [130, 131]. According to Sciarra et al. [132], nal to noise ratio).
DCE-MRI is even better when used in combination with 4. Contrast-enhanced imaging, axial: 4 mm at 1.5 and 3
MRSI, resulting in AUC values of 0.94-0.96 for the de- T. The resolution should be at least 1.0 × 1.0 mm at 1.5
tection of local recurrence compared to values of 0.81- T and 0.7 × 0.7 mm at 3 T. Quantitative or semi-quan-
0.94 for either DCE-MRI or MRSI alone. One of the titative DCE-MRI analysis does not comprise minimal
limitations in the reported studies was the use of TRUS- practice, but if available should be done as optimal
guided biopsies as the standard of reference [131]. practice. The maximum temporal resolution should be
10 s following a single dose of contrast, with an injec-
tion rate of 3 mL/s. For DCE-MRI, imaging acquisition
Protocols should be continued for 5 min to detect washout.
Imaging can adequately be performed at 1.5 T. A
The European Society of Urogenital Radiology and the pelvic coil should always be used; bowel relaxants (Bus-
Royal College of Surgeons (UK) are currently working copan, glucagon) provide optimal imaging with fewer
on a set of guidelines, with the first version to be pub- motion artifacts.
lished at the end of 2011 in European Radiology.
Currently, three protocols can be recommended: one Staging
for detection/localization and recurrence, one for staging,
and one for the assessment of nodal size and bone mar- This is a longer (45 min) protocol that allows determina-
row. Unfortunately, despite the enormous clinical poten- tion of (minimal) capsular penetration (Fig. 14). Prefer-
tial of Combidex/Sinerem has, due to the inability of the ably, this exam should be done with an endorectal coil.
pharmaceutical companies to provide convincing data to Minimum requirements should include images covering
the FDA and EMEA, this contrast agent was not ap- the entire prostate:
proved for nodal imaging and further development has 1. T1-weighted axial, to detect hematomas.
been discontinued. 2. T2-weighted axial and two other planes: 3 mm at 1.5
and 3 T. The resolution should be at least 0.3 × 0.3 mm -
Detection, Localization, Recurrence 0.7 × 0.7 mm at 1.5 T and 0.3 × 0.3 mm - 0.5 × 0.5 mm
at 3 T.
This is a fast (<30 min) protocol that does not involve the 3. DWI axial: 5 mm at 1.5 T, 4 mm at 3 T. The resolution
use of an endorectal coil. The minimum requirements should be at least 1.5 × 1.5 mm - 2.0 × 2.0 mm at 1.5 T
should include images covering the entire prostate: and 1.0 × 1.0 mm - 1.5 × 1.5 mm at 3 T, with a b0 im-
1. T1-weighted axial images, to detect post-biopsy age plus multiple b images allowing quantification.
hematomas. The highest b value should be 1000 if ADC is calcu-
2. T2-weighted axial images and images in one other lated, otherwise it should be 1400 (with adequate sig-
plane: 4 mm at 1.5 T, 3 mm at 3 T. The resolution nal to noise ratio).
should be at least 0.5 × 0.5 mm-0.7 × 0.7 mm at both 4. Contrast-enhanced imaging, axial: 3-4 mm at 1.5 T
1.5 and 3 T. and 3 mm at 3 T. The resolution should be at least
3. DWI axial: 5 mm at 1.5 T, 4 mm at 3 T. The resolution 1.0 × 1.0 mm at 1.5 T and 0.7 × 0.7 mm at 3 T. Quan-
should be at least 1.5 × 1.5 mm-2.0 × 2.0 mm at 1.5 T titative or semi-quantitative DCE-MRI analysis does
and 1.0 × 1.0 mm-1.5 × 1.5 mm at 3 T, with a b0 im- not comprise minimal practice, but if available should
age plus multiple b images allowing quantification. be done as optimal practice. The maximum temporal
a b c
Fig. 14 a-c. This 45-year-old patient requested erectile-function-preserving surgery. a High-resolution T2-weighted image obtained with an
endorectal coil (3T) shows minimal capsular penetration close to the neurovascular bundle (detail in b, arrows). Prostatectomy was done,
saving the right and sacrificing the left neurovascular bundle. c Histopathology revealed submillimeter capsular extension, but negative re-
section margins. T Tumor, ECE extracapsular extension
resolution should be 10 s following a single dose of Interpretation, Structured Reporting

contrast, with an injection rate of 3 mL/s. For DCE-
MRI, imaging acquisition should be continued for 5
min to detect washout. Due to a lack of standardization, the combined interpreta-
5. MRSI (optional). tion of anatomical and functional images is not possible.
Optimal results are obtained using an integrated comput-
Nodes and Bone er program that combines T2-weighted anatomical images
with DWI, DCE-MRI, and MRSI on one screen (Fig. 15).
This 30-min protocol is used to assess nodal size and Additionally, there is a dire need for a uniform scoring
bone marrow metastases. system; for example, in which every modality allows the as-
1. T1 (SE or f/T SE)-weighted coronal of the lower lum- signment of points on a 5-point scale regarding the impres-
bar spine plus pelvis: 3-mm slices. sion of a lesion’s malignancy, analogous to the BIRADS
2. 3D f/T SE T2-weighted coronal of the lower lumbar classification system in breast cancer imaging. Thus, a le-
spine plus pelvis; 1-mm isometric voxels. sion score of 20/20 or 15/15 definitely indicates an inter-
3. DWI (b value 0 plus 600) coronal of the lower lumbar mediate or highly aggressive tumor (Fig. 15). If the score
spine plus pelvis; 2.5-3 mm isometric voxels. is <10/15 or <14/20, there may be a non-aggressive tumor
4. T1 (SE or f/T SE)-weighted sagittal images of the cer- but other pathologies, such as prostatitis, are a possibility
vical and thoracic spine. (Fig. 16). This type of standardized scoring system allows
5. STIR or DWI sagittal images of the cervical and tho- the quantification of lesion development and reliable com-
racic spine. parison with a follow-up MRI examination (Fig. 16).
a b e
c d
Fig. 15 a-f. A 59-year-old patient with PSA = 12 and a Gleason 8 tumor of the right peripheral zone, stage T3a at prostatectomy. Screenshot
from computer monitor display. a DCE-MRI; b ADC-map (color coded); c choline image; d coronal T2-weighted image; e axial T2-weight-
ed image; f time concentration curve and H-spectrum of cursor. This patient’s score for all modalities was 5 points (20/20). Scale: 1 no tu-
mor, 5 definitely tumor
a b c
d e f
g
Fig. 16 a-g. This 55-year-old patient with PSA = 5, PC of stage T1 at digital rectal examina-
tion and Gleason 3+3 <5% on TRUS biopsy chose active surveillance. a T2-weighted im-
age shows no tumor: score 1/5; b DCE-MRI shows some asymmetrical enhancement with
curve 2: score 3/5; c ADC map shows only a small reduction: score 2/5. The total score of
6/15 argues for no or non-aggressive tumor. Follow-up MRI 1 year later: d T2-weighted im-
age at apex shows homogeneous, asymmetrical low signal: score 5/5; e DCE-MRI shows
pathological asymmetrical enhancement: score 5/5; f DWI shows an area with very low val-
ue: score 5/5. Based on these results, MRI-guided biopsy was performed. A Gleason 5+3
specimen was obtained on prostatectomy (g), which confirmed a Gleason 5+3 tumor
Conclusion cian in choosing the appropriate therapy based on PC

stage.
The use of MRI has led to improved localization of PC In case of a biochemical recurrence after radical treat-
compared to the results obtained with transrectal ultra- ment, MRI can detect disease location with greater accu-
sound. This has resulted in increased cancer detection racy than obtained with DRE and TRUS. Finally, MRI of-
by targeting biopsy under MRI guidance. Furthermore, fers advantages over bone scintigraphy.
radiotherapy planning and the guidance of minimally in- Nonetheless, among the different acquisition methods,
vasive local therapies have become possible as a result protocols, magnetic field strengths, and multimodality
of adequate PC localization with MRI. Multiparametric techniques that are used, a consensus is needed regarding
MRI using functional imaging has been shown to im- dedicated MRI protocols for different specific clinical in-
prove the prediction of tumor aggression. Also, com- dications. Implementation of protocols that on a larger
pared to staging nomograms, high-resolution (endorec- scale are highly similar if not identical will promote the
tal coil) MRI considerably improves the determination maturation of different multimodality techniques and im-
of local tumor extension, thereby supporting the clini- prove further development of supportive techniques such
as computer-aided diagnosis. Furthermore, the use of Hricak H, Dooms GC, McNeal et al (1987) MR imaging of the
consensus protocols enables larger studies, the aims of prostate gland 148:51-58
McNeal JE (1988) Normal histology of the prostate. Amer J Surg
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al anatomy of the prostate at 1.5T. JCAT 1096:983-989
Villiers G, De Meereleer GO (2007) MRI anatomy of the prostate
Take-Home Messages and application of MRI in radiotherapy planning. Eur J Radiol
63:361-368
• Currently, MRI is the most accurate imaging modality
Prostate Cancer
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• Prostate cancer in the central gland of the prostate is Futterer JJ, Heijmink SWTP, Scheenen TWJ et al (2006) Prostate
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• Multiparametric MRI comprises a combination of T2- Hambrock T, Somford DM, Hoeks C et al (2010) Magnetic reso-
weighted imaging, DWI, MRSI, and DCE-MRI. nance imaging guided prostate biopsy in men with repeat neg-
• The typical PC focus is of low signal intensity on T2- ative biopsies and increased prostate specific antigen. J Urol
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and high contrast agent permeability and fast washout. and lymph-node dissection in patients with prostate cancer: a
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190:1187-1192
IDKD 2010-2013
Imaging of the Male Pelvis: The Scrotum

Brent J. Wagner
Department of Radiology, The Reading Hospital and Medical Center, West Reading, PA, USA
Introduction
Although there are many potential ways one might com-
partmentalize the imaging of scrotal disease (including
pattern recognition, etiologies, and clinical presentation),
this chapter focuses on the requisite entities that, based
on their imaging and clinical features, constitute the core
knowledge needed for the radiologist when faced with an
abnormal scrotal sonogram. Hence, while not compre-
hensive, this review addresses diseases that are of inter-
est because of a distinctive combination of clinical rele-
vance and characteristic imaging features.
With the continued evolution of high-resolution linear
transducers over the past 15 years, clinicians, patients,
and imaging technicians are able to rely on ultrasound
as a tool with near 100% sensitivity for significant
intrascrotal pathology. Not only is the technique non-
invasive and relatively inexpensive, it is also highly
Fig. 1. Seminoma. A palpable nodule in a 33-year-old male. Sono-
effective in both the detection and the characterization of gram demonstrates a small, homogeneous, well-marginated intra-
a wide variety of disorders involving the scrotum. testicular mass
Intratesticular Disorders
seminomas is the most important distinguishing clinical
Neoplastic feature of the two groups of tumors (seminomatous vs.
non-seminomatous). This feature accounts for the previ-
Most neoplasms of the testis are germ cell tumors (GCTs), ous, widespread use of prophylactic retroperitoneal ra-
and the vast majority of these are malignant. Among the diotherapy for seminomas, even when imaging studies
various histological types, seminoma is the most common suggested that the lesion was confined to the testis. Over
to occur as a pure tumor, accounting for approximately the last decade, however, there has been a trend toward
40% of all testicular neoplasms. Most of the remainder are surveillance (using imaging and serum tumor markers) in
mixed tumors, containing two or more histological types. the 75% of patients with seminomas who are diagnosed
Lesions typically present as a palpable mass, although as having stage I disease [1, 2].
some aggressive tumors may present with metastatic foci For non-seminomatous tumors, computed tomography
to lung or bone or as nodal masses. (CT) is often used to determine whether patients require
The majority of GCTs are hypoechoic relative to the retroperitoneal lymph node dissection. Patients with
homogeneous medium-high echogenicity background of (1) nodal involvement (either enlarged on CT, or confirmed
the testis (Fig. 1). Calcifications are seen in at least one- on pathological assessment) and/or (2) hematogenous
third of cases, especially in non-seminomatous tumors, metastasis are generally treated with chemotherapy. The
which also tend to exhibit more heterogeneity. prognosis for patients with non-seminomatous tumors is
The management of GCTs nearly always involves or- more guarded than that for patients with seminoma, al-
chiectomy for the definitive diagnosis and treatment of though patients with stage I disease (limited to the scro-
the local disease. The well-established radiosensitivity of tum) have 5-year survival rates approaching 90%. While
Imaging of the Male Pelvis: The Scrotum 143
attempts have been made to use imaging to differentiate

GCTs [3], the initial management of both types is surgi-
cal (orchiectomy) and the exercise of pre-operatively dif-
ferentiating seminoma vs. non-seminoma is typically not
relevant [1].
Gonadal stromal tumors are less common (<10% of
lesions) and are often incidental findings. Both Leydig
cell and Sertoli tumors are occasionally the cause of gy-
necomastia. The vast majority of gonadal stromal tumors
are benign but they have gray-scale sonographic features
similar to the more sinister group of GCTs.
Patients with lymphoma of the testis are typically old-
er than those with GCTs. Lymphomas are rarely demon-
strated in patients without a known diagnosis of systemic
lymphoma. Hypoechoic, multifocal (or geographic), bi-
lateral lesions, which often have increased vascularity
compared with GCT’s, are characteristically seen [4].
While not strictly neoplastic, five entities deserve
brief discussion in the context of neoplastic intratesticu- Fig. 2. Tubular ectasia. The somewhat focal decreased echogenicity
lar tumors: resembles a mass but the non-spherical shape and the elongate
1. Simple cysts are typically peripheral, multiple, and con- anechoic channels are characteristic and do not suggest the need
tiguous with the tunica albuginea (more central cysts for tissue diagnosis
are usually a manifestation of tubular ectasia). These
have no malignant potential and are rarely of clinical
significance, although they may be palpable and clini- not have flow that can be detected sonographically.
cally mimic a GCT. Rarely, they may be complicated by Additionally, the onion-skin appearance is neither
hemorrhage; however, most cases are easily diagnosed sensitive (it is seen in approximately half the cases) nor
as simple cysts. Features that raise concern for malig- entirely specific (some neoplasms, including teratoma,
nancy (and indicate the need for prompt surgical re- may rarely have the same feature) [7].
moval) include solitary lesions complicated by internal 4. Congenital adrenal rest tumors are seen in patients
soft tissue, calcification, or a thick irregular wall. with poorly controlled congenital adrenal hyperplasia
2. Tubular ectasia represents a dilatation of the rete testis (CAH). Aberrant adrenal cortical cells migrate with
as it converges along the mediastinum testis. Patients gonadal tissue during fetal development and may
may have a history of prior epididymitis or vasectomy, hypertrophy at some point during the disease. The
but most have no specific symptoms. An ovoid or linear sonographic appearance is extremely variable but is
area of decreased echogenicity, contiguous with the epi- typically distinguished from that of malignant GCT by
didymis, can usually be differentiated from a neoplasm the multiplicity of the lesions, their eccentricity, and
based on the pattern of branching, anechoic channels their contiguity with the mediastinum testis. Treatment
(Fig. 2). In occasional cases that may mimic neoplasm, is glucocorticoid replacement or, rarely, surgery
T2-weighted magnetic resonance imaging will show a (partial orchiectomy) [8].
hyperintense focus (in contrast to the hypointensity that 5. Testicular microlithiasis (TML) describes the presence
is characteristic of most testicular neoplasms) [5]. of numerous small (1-2 mm) calcifications scattered
3. Epidermoid cyst is not considered to be a neoplasm by throughout the testicular parenchyma. This idiopathic
most authorities. Instead, it is an inclusion cyst, lined by condition is associated with oligospermia in a minori-
squamous epithelium and filled with keratinized debris. ty of patients but in most it is merely an incidental
Although it accounts for <10% of intratesticular mass- finding [5]. Several published reports concluded that
es, the differentiation of epidermoid cyst from germ cell there is a small but real increased risk of testicular
neoplasm is important in order to avoid radical surgery GCT in patients with TML (Fig. 3) [9]. This prompted
for this lesion, which can, instead, be effectively diag- multiple authors to suggest that patients should be
nosed and treated with a more limited procedure (enu- carefully screened for coexistent tumors and followed
cleation, sparing the testis) [5, 6]. Epidermoid cyst can sonographically at annual intervals for the develop-
be recognized in many instances by its “onion-skin” ment of malignancy. Recently, there has been a shift
appearance, i.e., alternating concentric rings of hypo- away from this recommendation, based on the high
and hyperechogenicity [5, 7]. A minority of cysts will cost of serial sonographic exams in a large number of
show wall calcification. The absence of Doppler flow men who have an increased but still very low risk of
may be of some help (the presence of central flow developing a germ cell tumor [9, 10]. Nonetheless, the
excludes the diagnosis), but one should remember that need for sonographic follow-up remains contentious
some malignant neoplasms, especially when small, will within the field.
144 Brent J. Wagner
paratesticular tissues may show reactive hyperemia, de-

spite the absence (or significant decrease) in Doppler
flow to the testis itself.
Traumatic injury to the testis is frequently an indica-
tion for sonography. The differentiation of testicular rup-
ture from a less serious injury (for example, merely a
hematoma with an intact tunica albuginea) generally rep-
resents the most important role of the imager. Findings of
a heterogeneous echo-texture within the testis, testicular
contour abnormality, and disruption of the tunica albug-
inea are considered very sensitive and specific for the di-
agnosis of testicular rupture [14].
Sarcoidosis is an unusual cause of a scrotal mass and
the scrotum may rarely be the presenting site of this dis-
ease in some patients. The pattern of multiple, hypo-
echoic, intratesticular masses associated with epididymal
enlargement and heterogeneity is characteristic, although
it may also be seen in lymphoma. A useful differentiating
Fig. 3. Mixed germ cell tumor arising in a background of testicular feature is the relative prominence of testicular disease in
microlithiasis
lymphoma (sarcoidosis tends to affect the epididymis
more than the testis, as discussed below) [5].
Non-neoplastic
Extratesticular Disorders
Infection typically begins in the epididymis. Epididymo-
orchitis is usually a clinical diagnosis, with sonography Neoplastic
sometimes used to rule out torsion or abscess. Sono-
graphic findings are often absent, although some patients In adults, malignant extratesticular neoplasms are rare and
will show a hydrocele (with or without complicating ele- have a non-specific appearance [15]. Mesothelioma is an
ments indicating pyocele). There may also be increased uncommon neoplasm that usually presents as a hydrocele,
Doppler flow to the epididymis. Progression to involve- with soft-tissue nodules of the tunica vaginalis. Alterna-
ment of the testis; which occurs in a minority of cases, tively, it may present as a large heterogeneous mass that
may result in abscess formation or infarction. may be difficult to separate from the testis. Mesothe-
Ischemia/infarction may result from torsion or, less com- liomas tend to occur in individuals who are decades older
monly, from a variety of other causes, including vasculitis, than those typically diagnosed with testicular GCTs.
diabetes, or orchitis, which may be segmental [11]. Patients Lymphoma may occasionally involve the epididymis,
with torsion typically have an acute clinical presentation although in the majority of patients this does not lead to
that includes severe unilateral scrotal pain, often follow- a diagnostic dilemma as: (1) the patient will be known to
ing minor trauma or physical exertion. The typical find- have lymphoma and (2) there will be coexistent involve-
ing of ischemia/infarction is an asymmetrical decrease in ment of the testis itself. Very rarely, solid tumors may
the color or amplitude (power) of the Doppler signal on metastasize to the epididymis. Affected patients almost
the symptomatic side. However, subtle variations of arte- always have advanced metastatic disease elsewhere
rial spectral Doppler waveforms may be seen early, in- throughout the body.
cluding the absence of the dicrotic notch and/or increased The most common extratesticular intrascrotal neo-
resistance (decreased or absent diastolic flow) [12]. The plasm is lipoma, which arises from the spermatic cord
latter finding may also be seen in the early stages of tor- and can often be diagnosed clinically based on palpation.
sion, when venous flow is altered but arterial flow is still Adenomatoid tumors are nearly as common as lipomas,
observed using color Doppler. Emergency surgery is accounting for about one-third of extratesticular masses.
indicated to detorse and save the testis; however, when These are benign, but may be surgically removed either
gray-scale findings are present, including heterogeneity to establish the diagnosis or because of local pain or ten-
and decreased echogenicity, the ischemia has almost derness. They are solid, well-marginated lesions that are
always progressed to infarction. At this point, testicular typically <20 mm in size. They most frequently arise
salvage is not possible [13]. from the epididymis.
Important pitfalls in Doppler evaluation must be rec- Papillary cystadenomas of the epididymis are seen in
ognized in order to avoid misdiagnosis. The examiner about one-quarter of patients with von Hippel-Lindau
must be careful not to alter the Doppler settings (gain, disease (the lesions are otherwise extremely rare). They
scale, etc.) when comparing normal (asymptomatic) are typically solid, measure between 1 and 5 cm, and may
testis to the painful side. One must also remember that be indistinguishable from adenomatoid tumors [15].
Imaging of the Male Pelvis: The Scrotum 145
Sarcoidosis is more likely to affect the epididymis 5. Woodward PJ, Sohaey R, O’Donoghue MJ, Green DE (2002)
than the testis. More than one-third of patients will Tumors and tumorlike lesions of the testis: radiologic-
pathologic correlation. Radiographics 22:189-216
have bilateral disease. Although discrete nodules are 6. Cho J-H, Chang J-C, Park B-H et al (2002) Sonographic and
occasionally seen, the appearance is more commonly MR imaging findings of testicular epidermoid cysts. AJR Am
one of heterogeneous enlargement. A diagnostic pattern J Roentgen 178:743-748
that may be of use in a previously undiagnosed patient 7. Maizlin ZV, Belenky A, Baniel J et al (2005) Epidermoid cyst
with hilar adenopathy – which could be either lym- and teratoma of the testis: sonographic and histologic similar-
ities. J Ultrasound Med 24:1403-1409
phoma or sarcoid – is to compare the testicular and the 8. Nagamine WH, Mehta SV, Vade A (2005) Testicular adrenal rest
epididymal involvement: in sarcoidosis, the degree of tumors in a patient with congenital adrenal hyperplasia: sono-
epididymal disease typically exceeds that of testis graphic and magnetic resonance imaging findings. J Ultrasound
involvement, whereas in lymphoma the converse is Med 24:1717-1720
expected. 9. Lam DL, Gerscovich EO, Kuo MC, McGahan JP (2007) Tes-
ticular microlithiasis: our experience of 10 years. J Ultrasound
Med 26:867-873
10. Costabile RA (2007) How worrisome is testicular microlithia-
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IDKD 2010-2013
Spread of Metastatic Disease in the Abdomen and Pelvis

James A. Brink1, Ali Shirkhoda2
1 Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA
2 Diagnostic Radiology, William Beaumont Hospital, Royal Oak, MI, USA
Introduction
Basic knowledge of the normal intra-abdominal anatomy
and of the anatomical variants is essential to understand-
ing the spread of pathology within the peritoneum. Of
special importance are constant landmarks, i.e., the
anatomical relationships maintained and bounded by
peritoneal and fascial attachments as well as by the ab-
dominal adipose tissue. The peritoneal and extraperi-
toneal spaces and their fascial planes create complex
three-dimensional structures with unique radiological
characteristics. Intraperitoneal and extraperitoneal adi-
pose tissue provides contrast interfaces between the or-
gans and visceral structures. The intra-abdominal adipose
also yields clues as to the spread and localization of many Fig. 1. The superior recess of the lesser sac is filled with ascetic flu-
pathological conditions. id and seen here as it extends superiorly (long arrow) to the lower
The four different pathways for the spread of neoplas- mediastinum, displacing the esophagus (short arrow) to the left side
tic diseases within the abdomen and pelvis are blood-
borne metastasis, lymphatic extension, direct invasion,
and intraperitoneal spread and seeding. Direct invasion
may occur from contiguous primary tumors and usually
implies that a locally aggressive tumor has broken
through fascial planes. Direct invasion from non-contigu-
ous primary tumors typically occurs via spread along the
peritoneal ligaments and mesenteries. Intraperitoneal
spread of malignancy occurs first by seeding of the peri-
toneal cavity with metastatic cells. Tumor spread occurs
via the natural flow of ascitic fluid within the peritoneal
spaces, which are defined by the peritoneal ligaments and
mesenteries [1].
The peritoneum is the largest and the most complexly
arranged serous membrane in the body. The potential
space between the parietal peritoneum lining the abdom-
inal wall and the visceral peritoneum enveloping the ab-
dominal organs is called the peritoneal cavity. It consists
of a main region, termed the greater sac, and a diverticu-
lum, called the omental bursa or lesser sac, situated be- Fig. 2. In this patient with a gastrostomy (PEG) tube, diluted water-
hind the stomach [2-4]. These two areas communicate via soluble contrast material was injected through the tube before an
the epiploic foramen (foramen of Winslow) and normal- abdominal CT scan. However, unbeknownst to the nurse, the tip of
ly contain only a small amount of fluid; therefore, they the tube was out of the stomach such that contrast was injected in-
to the peritoneal cavity. The CT scan reveals opacification of the
are normally not visible on cross-sectional imaging, ex- peritoneal cavity, with the exception of the bare area of the liver
cept when there is ascites (Fig. 1) or they are filled inad- (double arrows). The falciform ligament (single arrow) is outlined
vertently by contrast (Fig. 2). Fluid dynamics, respiratory by contrast material
Spread of Metastatic Disease in the Abdomen and Pelvis 147
motion, gravity, and anatomical barriers dictate the

spread of disease processes within the peritoneal cavity Coronary
and their appearance on cross-sectional imaging. Ligament
Tumors that arise within the abdominal cavity have the
propensity to spread (1) via the peritoneal ligaments and
mesenteries that suspend their organs of origin, either by
lymphatic extension or direct invasion, or (2) via seeding Transverse
of the peritoneal spaces in which they reside [5]. A work- Mesocolon
ing knowledge of the anatomy of the peritoneal liga-
ments, mesenteries, and spaces, although complex, per- Small Bowel
mits one to narrow the diagnostic possibilities when Mesentery
metastatic disease is recognized. Sigmoid
The peritoneal reflections in the abdomen comprise Mesocolon
four mesenteries, eight ligaments, and two omenta orga-
nized as follows:
1. four mesenteries: the small bowel mesentery, the trans-
verse mesocolon, the sigmoid mesocolon, and the
mesoappendix; Fig. 3. Posterior peritoneal reflections and recesses. Intraperitoneal
2. eight ligaments: right coronary, left coronary, falci- fluid flows naturally from the pelvis to the upper abdomen, prefer-
entially through the right rather than the left paracolic gutter ow-
form, hepatoduodenal, duodenocolic, gastrosplenic, ing to the broader diameter of the former. In addition, flow in the
splenorenal, and phrenicocolic ligaments; left paracolic gutter is cut off from reaching the left subphrenic
3. two omenta: lesser omentum and greater omentum. space by the phrenicocolic ligament. The transverse mesocolon di-
The peritoneal ligaments suspend and support the in- vides the abdomen into supra- and inframesocolic spaces. In the
traperitoneal organs and subdivide the peritoneal cavity right inframesocolic space, fluid is impeded from draining into the
pelvis via the small bowel mesentery. Owing to natural holdup of
into interconnected compartments that dictate the flow fluid at the root of the small bowel mesentery and sigmoid meso-
of fluid and location of disease (Figs. 3, 4) [2, 6]. These colon, these structures are naturally predisposed to involvement
reflections are generally recognizable on computed with serosal-based metastases in the setting of peritoneal carcino-
tomography (CT) scans as fat-containing structures, matosis (Reprinted with permission from [6])
either by their typical location and organ relationships
or by the landmarks provided by their major constituent
vessels. The ligaments can serve as conduits or as barriers
to the spread of disease [7].
Left lobe
Metastatic Spread via the Peritoneal Ligaments of liver
The major attachments of the upper abdomen include the Stomach

lesser omentum, the gastrosplenic ligament, and the
splenorenal ligament. The lesser omentum is subdivided
into the gastrohepatic ligament and the hepatoduodenal
GSL
ligament. In the embryo, the gastrosplenic ligament gives
rise to the gastrocolic ligament (also known as the greater
omentum) and the transverse mesocolon.
Gastrohepatic Ligament Lesser

P SAC
The gastrohepatic ligament can be recognized on CT
scans as a fatty plane that joins the lesser curvature of
the stomach to the liver. It extends from the fissure for
the ligamentum venosum to the porta hepatis and con- LK
tains the left gastric artery, coronary vein, and associat- Spleen
ed lymphatics. The size defining nodal enlargement in Splenic
this region is somewhat smaller than elsewhere in the artery
abdomen; nodes in the gastrohepatic ligament are gen-
erally considered abnormal when they exceed 8 mm in SRL
diameter [3]. On occasion, pathology in the gastro- Fig. 4. Peritoneal components in the left upper quadrant. The gas-
hepatic ligament may be mimicked by the absence of trosplenic ligament (GSL) and splenorenal ligament (SRL) are
opacification of the bowel loops, the pancreatic neck, or clearly seen (From [2])
148 James A. Brink, Ali Shirkhoda
Fig. 5. Intraperitoneal seeding of numerous hydatid cysts. This Fig. 6. Invasive pancreatic carcinoma arising from the pancreatic
patient had a hydatid cyst in the liver that ruptured during resec- tail, with numerous hematogenous metastases to the liver. A porto-
tion, resulting in extensive peritoneal implants, including in the caval lymph node at the base of the hepatoduodenal ligament (ar-
lesser omentum, which is seen here between the stomach, liver, row) is not enlarged according to size criteria but contains metasta-
and spleen tic disease, as evidenced by its central necrosis
the papillary process of the caudate lobe of the liver central necrosis suggests the presence of tumor within
projecting into the expected plane of the gastrohepatic these nodes (Fig. 6) [11, 12].
ligament [8, 9]. A broad range of tumors may spread via the hepato-
The gastrohepatic ligament provides an important con- duodenal ligament. Liver or biliary cancer, whether pri-
duit of disease from the stomach to the liver in that the mary or metastatic, may spread in an antegrade fashion
subperitoneal areolar tissue within the ligament is con- through lymphatics in the hepatoduodenal ligament to
tinuous with the Glisson capsule (the perivascular fibrous deposit in periduodenal or peripancreatic lymph nodes.
capsule within the liver). Thus, gastric malignancy can Similarly, malignant disease in the nodes about the su-
spread directly into the left lobe of the liver and vice ver- perior mesenteric artery (commonly involved in pan-
sa via this pathway. Neoplastic or infectious conditions creatic and colon cancer) can spread in a retrograde
that may spread throughout the entire peritoneum also in- fashion up the lymphatics in the hepatoduodenal liga-
volve this ligament. On CT, the abnormality is seen be- ment. Lymphoma can involve these nodes as well. Pri-
tween the stomach and the liver (Fig. 5). Common neo- mary gastric cancer arising in the lesser curvature of
plasms spreading via the gastrohepatic ligament include the stomach can directly spread through the gastro-
nodal metastases from gastric, esophageal, breast, pan- hepatic ligament to the hepatoduodenal ligament and
creatic, and lung cancer as well as nodal involvement of then to peripancreatic and periduodenal nodes. Vascular
lymphoma. Gastric and esophageal cancer can directly complications related to the portal vein and hepatic
invade the gastrohepatic ligament and spread into the left artery can result; portal venous thrombosis and hepatic
hepatic lobe [3]. arterial pseudoaneurysms may occur in advanced cases
owing to their coexistence in the hepatoduodenal liga-
Hepatoduodenal Ligament ment [2, 10].
The hepatoduodenal ligament is the free edge of the gas- Gastrosplenic and Splenorenal Ligaments
trohepatic ligament along its rightward aspect. It contains
important structures of the porta hepatis, including the In the embryo, the gastrosplenic ligament is a long liga-
common bile duct, hepatic artery, and portal vein. The mentous attachment between the stomach and the
hepatoduodenal ligament extends from the flexure be- retroperitoneum. It gives rise to the gastrocolic ligament
tween the first and second duodenum to the porta hepatis; (greater omentum) and the transverse mesocolon. In the
the foramen of Winslow is immediately posterior to this adult, the gastrosplenic ligament is a thin ligamentous at-
ligament, permitting communication between the greater tachment between the greater curvature of the stomach and
and lesser sacs [10]. The nodes of the foramen of the splenic hilus (Fig. 4). It contains the left gastroepiploic
Winslow, or portocaval space, have an unusual morphol- and short gastric vessels as well as associated lymphatics.
ogy such that their transverse dimension is greater than The gastrosplenic ligament is continuous with the gastro-
their anteroposterior dimension. Generally, the upper lim- colic ligament inferiorly and medially and with the
it of normal for the latter is 1.0-1.3 cm, whereas the for- splenorenal ligament posteriorly and medially [13, 14]. As
mer can be up to 2.0 cm in width. Size criteria are some- such, it provides an important pathway of communication
what less helpful than in other lymph nodes. In the ab- between the stomach, spleen, and retroperitoneum. Gastric
sence of frank enlargement, a more spherical shape or malignancies commonly spread through the gastrosplenic
a b
Fig. 7 a, b. Gastric adenocarcinoma invading

the spleen via the gastrosplenic ligament.
a Initial contrast-enhanced CT scan reveals
circumferential tumor involving the gastric
fundus. b A repeat CT scan 6 months later
shows invasion and dissection of the spleen
secondary to tumor spread via the gastro-
splenic ligament
ligament (Fig. 7), thereby involving the spleen and ulti- The gastrocolic ligament contains the gastroepiploic
mately resulting in disease about the tail of the pancreas. vessels and associated lymphatics. It provides an impor-
Conversely, pancreatic neoplasms may spread via the tant conduit of malignant disease from the greater curva-
splenorenal ligament to the gastrosplenic ligament and in- ture of the stomach to the transverse colon and vice ver-
volve the greater curvature of the stomach [2]. sa. When viewed in concert with the transverse meso-
colon, a conduit exists between the greater curvature of
Gastrocolic Ligament the stomach and the retroperitoneum. In addition to al-
lowing direct spread of disease between the stomach,
The gastrocolic ligament (or greater omentum) joins the transverse colon, and pancreas, the gastrocolic ligament
greater curvature of the stomach to the transverse colon. serves as an important nidus for peritoneal metastases –
On the left, it is continuous with the gastrosplenic liga- as commonly occur with ovarian, gastric, colon, and pan-
ment; on the right, it ends at the gastroduodenal junction, creatic cancers [16, 17]. Finally, dilated veins within this
near the hepatoduodenal ligament. Since, developmental- ligament may represent gastroepiploic collaterals result-
ly, it results from fusion of the anterior and posterior ing from splenic venous compromise, such as might oc-
leaves of the gastrosplenic ligament, it contains the four cur in the setting of invasive pancreatic tumors or in the
layers of peritoneum that invest the stomach and has a po- presence of intraperitoneal tumors, which spread to the
tential space within it (Fig. 8) [15]. retroperitoneum via the transverse mesocolon (Fig. 9).
Transverse Mesocolon
The transverse mesocolon serves as a broad conduit of

disease across the mid-abdomen; bare areas link the pan-
RPS creas to the transverse colon, spleen, and small bowel.
G On the right, the transverse mesocolon is continuous
P with the duodenocolic ligament; in the middle, it is
D
TC
GCL
Fig. 8. The gastrocolic ligament (GCL) joins the greater curvature

of the stomach (G) to the transverse colon (TC). In concert with the Fig. 9. A pancreatic islet-cell tumor arising in the pancreatic tail has
transverse mesocolon, a pathway of disease is formed between resulted in splenic vein thrombosis, with secondary short gastric
retroperitoneal structures, such as the pancreas (P) and the duode- venous collaterals in the gastrosplenic and splenorenal ligaments as
num (D), and the anterior aspect of the intraperitoneal cavity well as gastroepiploic venous collaterals (arrow) in the gastrocolic
(Modified from [15]) ligament
continuous with the small bowel mesentery; and on the the transverse colon and have the propensity to continue
left, it is continuous with the phrenicocolic and splenore- through the gastrocolic ligament to involve the stomach
nal ligaments (Fig. 10). It contains the middle colic ves- (Fig. 11). Alternatively, they may spread through the
sels and associated lymphatics. On CT, the transverse transverse mesocolon to involve the proximal jejunum,
mesocolon may be recognized as a fatty plane at the lev- just beyond the ligament of Treitz (Fig. 12). Like the
el of the uncinate process. Pancreatic tumors often gastrocolic ligament, a potential space exists within the
spread ventrally into the transverse mesocolon to involve transverse mesocolon due to embryological fusion of the
gastrosplenic ligament with the embryological trans-
verse mesocolon [13]. A less common but important
route of spread also exists between the right colon and
SRL the periduodenal and peripancreatic nodes via the right-
TM
ward aspect of the transverse mesocolon (duodenocolic
ligament). This is important because lymphadenopathy
PCL in the periduodenal and peripancreatic regions may her-
ald a right colon cancer when other, more common caus-
es of lymphadenopathy in this region are excluded [2].
Thus, three routes of spread between the intraperi-
toneal viscera and retroperitoneum are provided by three
pairs of ligaments. The gastrohepatic and hepatoduodenal
ligaments link the liver and lesser curvature of the stom-
SBM ach to the retroperitoneum; the gastrosplenic and spleno-
renal ligaments link the superior greater curvature of the
stomach and spleen to the retroperitoneum; and the
gastrocolic and transverse mesocolon link the inferior
Fig. 10. The transverse mesocolon (TM) provides an important con- greater curvature of the stomach and transverse colon to
duit for the spread of disease across the mid-abdomen. It is con- the retroperitoneum. The ligamentous pair in which
tinuous with the splenorenal ligament (SRL) and phrenicocolic lig-
ament (PCL) on the left and with the duodenocolic ligament on the
metastatic disease is recognized can therefore suggest the
right. In its mid-portion, it is continuous with the small bowel organ of origin and, in the case of gastric cancer, the
mesentery (SBM) (Reprinted with permission from [6]) location of the primary tumor within the stomach.
a b
Fig. 11 a, b. Invasive pancreatic carcinoma in-

vading the retroperitoneum, transverse meso-
colon, and greater omentum. Transaxial im-
age (a) and parasagittal reformation (b). M
mass, P normal pancreas, S stomach, TC
transverse colon. The transverse mesocolon
(black arrows) provides a pathway for the
spread of metastatic disease to the greater
omentum (white arrows). Also noted is en-
casement of the left renal artery and ovarian
vein (double arrows)
a b
Fig. 12 a, b. An incidental pancreatic adeno-

carcinoma involving the splenic vein (a) was
thought to be resectable owing to the lack of
extrapancreatic involvement. At surgery, up-
on elevation of the transverse colon, the tu-
mor was found to have penetrated the base of
the transverse mesocolon and involved the
proximal jejunum just beyond the ligament
of Treitz (seen in retrospect in b, arrows)
Metastatic Spread via the Peritoneal Spaces tovesical pouch in men), the lateral paravesical recesses,
and the medial and lateral inguinal fossae. Due to the
Diseases such as ovarian carcinoma (Fig. 13 a) and lym- deep and dependent nature of the pelvic peritoneal cavi-
phoma (Fig. 13 b) can diffusely extend through the peri- ty, many infections and half of all seeded metastases will
toneum, with propensity for involvement of the greater involve the pouch of Douglas. Fluid flows preferentially
omentum. However, the initiation and growth of seeded to the right lower quadrant and from there to the inferior
metastases on the peritoneal surfaces usually depend on portion of the small bowel mesentery and right paracolic
the natural flow of ascites through the peritoneal spaces. gutter.
Primary abdominal malignancies and secondary nodal
metastases can break through the visceral peritoneum and Left Peritoneal Space
shed cells into the peritoneal cavity (Fig. 13 c). Once in-
traperitoneal, such cells propagate through the peritoneal The left peritoneal space can be subdivided into four
spaces along predicable routes. A thorough understand- compartments. Although these freely communicate with
ing of the anatomy of the peritoneal spaces may help re- each other, the inflammatory nature of exudative fluid
fine differential diagnoses for the source of intra-abdom- collections within them favors the development of fi-
inal metastases [18, 19]. By recognizing that a process is brous adhesions, which may seal off one or more portions
intraperitoneal, one may better predict its organ of origin of the left peritoneal space from the others.
and likely routes of spread (Fig. 13). The left anterior perihepatic space is limited on the
The most dependent portion of the peritoneal cavity is right by the falciform ligament and on the left by the an-
in the pelvis. The cavity is anatomically continuous with terior wall of the stomach. It follows the posterior curve
the paracolic gutters and is subdivided into the midline of the diaphragm and is limited posteriorly by the left
pouch of Douglas (rectovaginal pouch in women, rec- coronary ligament (Fig. 14).
a b c
Fig. 13 a-c. Peritoneal malignancies. a Diffuse omental metastasis from a primary ovarian carcinoma associated with ascites. b Extensive
involvement of the greater omentum by Burkitt’s lymphoma. c Seeding of the inferior aspect of the peritoneum (cul de sac) by gastric
carcinoma (arrows)
a Left Left b
Subphrenic Coronary Rt. Coronary Lig.
Space Ligament Superior reflection
Fig. 14 a, b. The left (a) and
right (b) perihepatic spaces
are bounded posteriorly by Inferior reflection
the coronary ligaments.
The reflections of the coro- L A
LL
nary ligaments mark the Rt. Posterior
site of the non-peritoneal- Perihepatic Space
ized “bare area” of the Lesser (Morison’s Pouch)
liver. LL left lobe of the Omentum D K
liver, LK left kidney,
S stomach, TC transverse S Lesser
colon, P pancreas, D duo- LK Rt. Anterior
Sac C
denum, Lu lung, L liver P Perihepatic Space
(right lobe), A adrenal,
K kidney, C colon (Reprint- TC D
ed with permission from [6])
The left posterior perihepatic space (gastrohepatic The posterior left subphrenic (perisplenic) space is the
recess) is limited on the left by the lateral wall of the posterior continuation of the anterior subphrenic space
stomach. This space follows the posterior margin of the and generally surrounds the lateral and superior margins
left hepatic lobe deep into the fissure for the ligamentum of the spleen. The “bare areas” of the spleen are reliably
venosum to form the posterior margin of the left hepatic observed in perisplenic fluid collections [20-22]. Superi-
lobe. Thus, it is in close proximity to the lesser curve of orly, the perisplenic space is entirely subphrenic and sur-
the stomach, the anterior wall of the duodenal bulb, and rounds the top of the spleen (Fig. 16) [23].
the anterior wall of the gallbladder [13].
Although the gastrohepatic recess is close to the less- Right Peritoneal Space
er sac (divided from it by the lesser omentum), it is a por-
tion of the left peritoneal space, while the lesser sac is a There are three major subdivisions of the right peritoneal
portion of the right peritoneal space (Fig. 15). This dis- space: the right subphrenic space, the hepatorenal recess,
tinction is important in that lesser sac collections are very and the lesser sac (Figs. 14, 15). The right subphrenic
difficult to approach percutaneously whereas gastro- space occupies the smoothly contoured area between the
hepatic recess collections are usually accessible by guiding superolateral margin of the liver and the right hemi-
a catheter along the inferior margin of the left hepatic lobe. diaphragm. The medial extension of this compartment is
The anterior left subphrenic space is in direct conti- limited by the right coronary ligament, which is simply
nuity with the left anterior perihepatic space, which the right lateral margin of the liver’s bare area [24]. The
forms its right boundary. Far to the left, on the antero- hepatorenal recess (or Morison’s pouch) is the postero-
lateral surface of the stomach, this space is limited by the medial extension of the subphrenic space, inferior to the
greater omentum. This is a common site for fluid locula- coronary ligament. As its name implies, it extends be-
tion in the setting of malignant ascites (Fig. 16). tween the right hepatic lobe and the anterior border of the
right kidney.
The lesser sac has two major components [14, 25]: a
Caudate Lesser Fissure for small superior recess is immediately posterior to the
lobe omentum ligamentum venosum hepatoduodenal ligament. The caudate lobe of the liver is
enveloped by this peritoneal reflection (Fig. 15). The
larger inferior recess occupies the space behind the stom-
Liver ach, anterior to the transverse mesocolon and medial to
the gastrosplenic ligament. As both portions of the lesser
sac are surrounded by abdominal viscera, percutaneous
drainage of collections within this space is difficult. In-
IVC feriorly, the superior recess communicates with the right
perihepatic space through the foramen of Winslow. Cau-
Ao dally, behind the duodenum and pancreatic head, there
may be an extension that is responsible for peritoneal
fluid collections behind the pancreatic head [7].
Diaphragm Upper recess Esophagus
Fig. 15. The boundaries of the superior recess of the lesser sac may
be recognized when fluid engulfs the caudate lobe. The lesser References
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IDKD 2010-2013
Abdominal Vascular Disease: Diagnosis and Therapy

Johannes Lammer
Cardiovascular and Interventional Radiology, AKH-Universitätsklinik, Wien, Austria
Acute Arterial Occlusion Interventional treatment with a thrombectomy device

and/or local intra-arterial fibrinolysis with recombinant
If acute occlusion of the abdominal aorta or branch ves- tissue plasminogen activator (loading dose 10 mg, infu-
sels occurs, two causes have to be considered: (1) em- sion dose 5 mg/h) or urokinase (loading dose 250,000 IU,
bolization and (2) dissection. infusion dose 100,000 IU/h) together with a glycoprotein
IIb/IIIa antagonist (Aciximab: loading dose 0.25 mg/kg,
Embolization infusion dose 0.125 mg/kg/h) is one option. The other op-
tion is surgery, which may be faster, enables inspection,
Embolization is most common in elderly patients with and, if necessary, resection of the ischemic organs.
atrial fibrilation, a history of myocardial infarction, and
aortic aneurysm. Embolization from the heart or thoracic Dissection
aorta may cause acute subtotal or total occlusion of the
celiac artery, superior mesenteric artery (SMA), inferior Patients with chest trauma, chronic severe hypertension,
mesenteric artery (IMA), or the renal arteries. The most or a connective tissue disease such as Marfan syndrome
common causes of embolization are: or Ehlers-Danlos syndrome are vulnerable to aortic dis-
• atrial fibrillation; section. Acute type A and B aortic dissection may cause
• thoracic aortic aneurysm; dynamic compression of the true lumen of the aorta by
• myocardial infarction with mural thrombus formation; the pressurized false lumen. This can result in acute is-
• advanced aortic arteriosclerosis; chemia of the liver and spleen, the bowel, and one or both
• perforating arteriosclerotic ulcer; kidneys. The dissection plane may also run into one of
• hypercoagulability syndrome. the arteries perfusing the organ, thereby causing obstruc-
The symptoms of acute ischemia are dependent on the tion of the true lumen.
involved vascular territory. Embolization to the liver or There are several options in the interventional treat-
spleen may cause acute right or left upper abdominal ment of dissection. First, in case of dynamic compression
pain. Acute mesenteric ischemia typically causes severe of the true aortic lumen, occlusion of the proximal entry
abdominal pain and bowel paralysis. Embolization to the into the false lumen with an aortic stent graft will de-
kidney results in flank pain, hematuria, and hypertension. compress the false lumen and result in re-opening of both
In any case, severe elevation of serum lactate dehydroge- the true lumen of the aorta and the side branches (Fig. 1).
nase levels points to the ischemic nature of the acute Second, in case of static compression due to a side-
pain. In case of complete ischemia without a sufficient branch dissection, stent placement in the true lumen of
collateral circulation, the warm ischemic time tolerated the organ artery will reconstitute organ perfusion. Third,
by the abdominal organs is <6 h. Therefore acute diag- in case of organ perfusion through the false lumen, bal-
nosis and therapy are mandatory. loon fenestration of the intimal flap will re-establish flow
The primary diagnosis is made by CT with contrast en- into the malperfused territory.
hancement injected at a concentration of 300-400 mg io-
dine/mL and at an injection rate of 4 mL/s, with a total
bolus volume of 80-120 mL. A bolus care technique with Chronic Arterial Occlusive Disease
a delay of 20-40 s is used. The CT settings are 2-mm col-
limation, pitch = 2, with a reconstruction interval of 1 mm. In young patients, potential causes of chronic arterial oc-
In the arterial phase, the obstructing embolus and the is- clusion are fibromuscular disease, Takayasu arteritis, and
chemic territory can be visualized. In the delayed phase, Recklinghausen neurofibromatosis. In elderly patients,
residual perfusion through the collateral arteries may be the primary cause of chronic arterial occlusive disease is
demonstrated. arteriosclerosis.
Abdominal Vascular Disease: Diagnosis and Therapy 155
a b c
d e f
Fig. 1 a-f. Complicated type B aortic dissection. CT demonstrating (a) primary entry tear of type B aortic dissection and (b) compression of
true lumen of the aorta. c Aortic angiogram showing true and false lumen of type B dissection. d Aortography showing compression of the
true lumen, with malperfusion of the superior mesenteric and renal arteries (“floating visceral sign”). Aortography (e) after stentgraft im-
plantation and closure of primary entry tear, and (f) following stent graft implantation, which demonstrates spontaneous revascularization
of the visceral arteries
Mesenteric Artery Stenosis post-prandial cramps in 86%, weight loss in 74%,

abdominal bruit in 70%, and diarrhea.
Between the three large mesenteric arteries (celiac artery, The primary diagnosis is made by computed tomogra-
SMA, IMA) there are two main collateral pathways: phy angiography (CTA), magnetic resonance angiogra-
(1) the pancreatico-duodenal arteries and the arc of phy (MRA), or by intra-arterial catheter angiography of
Buehler, between the celiac artery and SMA; (2) the arc the abdominal aorta in a lateral projection. Intervention-
of Riolan and the marginal artery of Drummond, between al treatment consists of percutaneous transluminal angio-
the SMA and IMA. Therefore, an obstruction of at least plasty (PTA) with or without secondary stent placement
two mesenteric arteries is necessary to cause ischemic in at least one of the obstructed arteries.
symptoms. The typical clinical symptom is abdominal The causes and symptoms of chronic arterial occlusion
angina, with abdominal pain in 94% of patients, depend on the obstructed artery and its location. In
156 Johannes Lammer
celiac trunk stenosis, chronic obstruction may remain patients previously administered an ACE inhibitor (cap-
asymptomatic because of the collateral pathways through topril 25 mg) shows a delayed wash-out of the tracer
the gastroduodenal and pancreatic arteries from the within the post-stenotic kidney. In bilateral disease and in
SMA. The causes are an arteriosclerotic plaque, com- chronic ischemic nephropathy, however, lateralization of
pression by the arcuate ligament, or carcinoma of the the tracer is less evident. In a selected population at clin-
pancreas. Superior mesenteric artery stenosis will result ically high risk for renal artery stenosis, the sensitivity for
in post-prandial abdominal pain (abdominal angina) only detection of a unilateral stenosis >70% is 51-96% (mean
if two or all three gastrointestinal arteries are obstructed. 82%). Its positive predictive value for a renal artery
The causes for SMA obstruction are arteriosclerosis, fi- stenosis with improvement of hypertension after revascu-
bromuscular disease, Takayasu arteritis, pancreatic carci- larization is 51-100% (mean 85%). However, scintigra-
noma, or chronic pancreatitis. Inferior mesenteric artery phy is much less sensitive in unselected patients and in
stenosis, with obstruction of the IMA, is most common- those with bilateral disease, impaired renal function, uri-
ly observed in patients with advanced atheromatosis or a nary obstruction, and chronic ACE inhibitor intake.
partially thrombosed abdominal aortic aneurysm. Due to Newer tests are gadolinium-enhanced MRA and spiral
the collateral circulation through the arc of Riolan and CTA. For state-of-the-art MRA, high-field-strength sys-
the marginal artery, IMA obstruction normally remains tems with high performance gradients are necessary to
asymptomatic. obtain breath-hold 3D T1-weighted spoiled gradient-echo
imaging with short TR and TE. Intravenous administra-
Renal Artery Stenosis tion of gadolinium contrast material (0.1 mmol/kg; flow
rate 2 mL/s), a central k-space readout, and background
Hypertension and/or renal insufficiency are the most fre- subtraction are additional techniques to improve signal-
quent consequences of renal artery stenosis. Acute onset to-noise ratio and spatial resolution. The sensitivity of
of the clinical symptoms and repeated flash pulmonary MRA to detect a renal artery stenosis >50% is over 95%
edema are suggestive. The most common etiology in pa- (Fig. 2). The main limitations of renal MRA are its lack
tients over age 50 years is arteriosclerosis (65-75% of all of accuracy in the evaluation of small accessory renal ar-
patients), with males more often affected than females. In teries and branch vessels, artifacts due to the presence of
the majority of cases, the proximal 2 cm of the renal stents, and a tendency of the techniques to overestimate
artery are involved, accompanied by atherosclerotic moderate stenoses. In a double-blind randomized study,
changes in the aorta. In 30% of patients, the stenosis is contrast-enhanced MRA with the blood-pool contrast
bilateral. agent gadofosveset was not superior to gadobenate
In patients under the age of 50, renal artery stenosis is dimeglumine.
most often due to fibromuscular disease (20-30% of all The sensitivity of CTA to detect stenosis of the renal
patients). In this case, females are five times more likely artery and its accessory arteries is >95%. For high-
than males ratio to be affected. Most commonly, the mid- quality opacification of the renal arteries and to avoid
dle to distal renal artery, including its branches, is ob- renal vein overlap, correct bolus planning is mandatory:
structed, with bilateral involvement in 50-70% of pa- density measurement during bolus rise, flow 4 mL/s, total
tients. Imaging shows the typical “string of pearls” ap- volume 80-120 mL (multidetector scanners need less
pearance of the stenosis and, possibly, aneurysms and dis- contrast). A short breath-hold acquisition, 1- to 2-mm
sections. However, importantly, there is no aortic disease. collimation, pitch =1.5-6 (depending on single or multi-
Other causes of renal artery stenosis include Takayasu detector technology), and an overlap of reconstruction of
arteritis, mid-aortic syndrome, Recklinghausen neuro- 0.5-0.75 are important parameters to obtain good spatial
fibromatosis, and as a consequence of radiation therapy. resolution of the study. Curved planar reconstruction
However, an algorithm for the diagnosis of a renal artery (most useful for stents), volume rendering, and maximum
stenosis has yet to be established. intensity projection (MIP) are used for 3D imaging (Fig. 2).
Color duplex ultrasound is a non-invasive but complex Nonetheless, intra-arterial catheter arteriography together
examination that requires operator experience. The diag- with pressure gradient measurement is still the gold stan-
nostic criteria for renal artery stenosis are: increased peak dard for the evaluation of a renal artery stenosis.
systolic velocity >250 cm/s, a renal-to-aortic ratio of The revascularization technique of choice is renal PTA,
peak systolic velocity >3.5, intrastenotic turbulence, and without or with stent placement (Fig. 2). Aorto-renal by-
a flattened pulse wave in the periphery (pulsus tardus). pass surgery is indicated only if PTA fails. In a recently
The sensitivity of color duplex sonography for detection published meta-analysis, renal arterial stent placement
of a renal artery stenosis >70% is 72-92%. Color duplex proved to be technically superior and clinically compa-
ultrasound with an angiotensin-converting enzyme rable to renal PTA alone. The technical success rate of
(ACE) inhibitor provides a positive predictive value of stent vs. PTA was 98 vs. 77%, and the re-stenosis rate
67-95% for cure or improvement after revascularization. 17 vs. 26% (p <0.001). In hypertension, the cure rate of
A nuclear scan, specifically, renal scintigraphy with PTA vs. stent was 10 vs. 20%, the rate of improvement
technetium-99m mercaptoacetyltriglycine (MAG3) or 53 vs. 49 %. In renal insufficiency, the rate of improve-
Tc-99m diethylenetriaminepentaacetic acid (DTPA) in ment was 38 vs. 30%, that of stabilization 41 vs. 38%.
a b
c d
Fig. 2 a-d. Imaging and intervention in a pa-

tient with hypertension due to renal artery
stenosis. a MRA, b CTA, and c arteriography
show the stenosis of the right renal artery.
d Arteriography of right renal artery after
stent placement
The complication rate was 11-13% (95% CI 6-19%), the new, emerging technique that may replace open surgery
in-hospital mortality rate 1%. In a randomized study in the future. Since the first clinical implant of a tube
comparing stents vs. PTA in ostial stenoses, the techni- stent graft, in 1990, many different stent graft designs
cal success rate was 88 vs. 57%, and the 6-month pri- have been developed and tested in feasibility studies.
mary patency rate 75 vs. 29%. Surprisingly, randomized Most recently, randomized studies (EVAR 1, Dream)
trials comparing the effect of PTA and drug therapy on compared the results of open vs. endovascular repair. In
renal hypertension did not reveal a significant benefit of the EVAR trial, the 30-day mortality in the EVAR group
PTA and stenting over continuous drug therapy. Howev- was 1.7% (9/531) vs. 4.7% (24/516) in the open repair
er, in a Dutch study, PTA patients required only 2.1 group (p = 0.009). Four years after randomization, all-
vs. 3.2 daily drug doses (p <0.001), and 22 of 53 patients cause mortality was similar in the two groups (about
in the drug group had to be switched to the PTA group 28%; p = 0.46), although there was a persistent reduc-
because of persistent hypertension or deterioration of tion in aneurysm-related deaths in the EVAR group
renal function. (4 vs. 7%; p = 0.04).
Indications
Aneurysms
The indications for endovascular treatment of abdominal
Abdominal Aortic Aneurysm aortic aneurysm are currently the same as for open
surgery: (1) diameter of the aneurysm >5 cm (Fig. 3), (2)
The incidence of abdominal aortic aneurysm in European documented growth >0.5 mm/year, (3) symptomatic
adults 60 years and older is 2.5%. Up to 10% of patients aneurysm (i.e., embolization, pain, ureteral compres-
with symptomatic peripheral arterial disease die from sion), and (4) rupture. The specific clinical indications
rupture of the aneurysm. for the endovascular approach are typically: patients >75
Currently, the standard treatment is open surgery. years old, ASA class 3 and 4, “hostile abdomen”, and in-
However, endovascular implantation of stent grafts is a flammatory aneurysm or horse-shoe kidney.
158 Johannes Lammer
a b c
Fig. 3 a-c. Patient with abdominal aortic aneurysm and renal artery stenosis. a CTA with MIP reconstruction; aortography (b) before and
(c) after stent graft placement
The anatomic indications for stent graft treatment are: aneurysm sack through an endoleak. White and May pro-
• infrarenal neck >15 mm in length; posed a classification of primary (<30 days) and sec-
• infrarenal neck without thrombus or severe calcifica- ondary (>30 days) endoleaks. Type 1 endoleaks are char-
tion; acterized by direct perfusion through the proximal (in-
• angulation of the infrarenal neck <65°; frarenal) or distal (iliac) anastomosis. In type 2, there is
• patent celiac trunk and SMA; retrograde perfusion through branch vessels (lumbar ar-
• stent graft diameter 10% more than neck diameter; teries, IMA, accessory renal artery). Type 3 consists of
• iliac artery angulation <90°; mid-graft leak due to disintegration of the stent graft (dis-
• iliac artery without thrombus or severe calcification; connection of the second iliac limb, fabric erosion). In
• overlap of >15 mm within the iliac arteries. type 4, there is fabric porosity, while type 5 is character-
Endovascular implantation of stent grafts can be per- ized by endotension.
formed under general, epidural, or local anesthesia. The
use of epidural anesthesia is a major advantage in elder- Visceral Artery Aneurysm
ly and high-risk patients.
Aneurysms of the celiac trunk, splenic artery, hepatic
Stent Graft Designs artery, gastroduodenal artery, and SMA are caused by ar-
teriosclerosis, arteritis, periarterial inflammation (such as
Stent grafts have a self-expandable stent structure cov- pancreatitis), trauma, and soft-tissue diseases (such as
ered by an ultrathin polyester or ePTFE fabric. Current- Marfan and Ehlers-Danlos syndromes). An aneurysm
ly, only bifurcated stentgrafts are used for the treatment >2.5 cm in diameter should be considered for treatment
of abdominal aortic aneurysm. to prevent rupture. Meticulous imaging, including selec-
tive catheter angiography and 3D imaging with CTA or
Imaging before Stent Graft Implantation MRA, is necessary before surgery or endovascular treat-
ment. The endovascular options are embolization and ex-
Contrast-enhanced spiral CT with multiplanar recon- clusion with a stent graft.
struction (MPR) or MIP reconstruction is the most
important examination before stent graft implantation Renal Artery Aneurysm
(Fig. 3). The diameter of the landing zones (infrarenal
neck, iliac arteries), the maximum diameter of the The causes are arteriosclerosis, systemic vasculitis
aneurysm, the extent of the thrombus, and calcifications (such as polyarteritis nodosa or lupus erythematosus),
are well depicted on CT. fibromuscular disease, soft-tissue disorders, and trau-
ma. Arteriosclerotic and large aneurysms are usually
Complications calcified. The risk of rupture and chronic embolization
are indications for treatment. Bypass surgery, coil em-
The most frequent complication is incomplete exclusion bolization, and stent graft implantation are the thera-
of the aneurysm, with remaining pressurization of the peutic options.
Therapeutic Embolization of Gastrointestinal Bleeding during catheter angiography. Superselective catheteriza-

tion and bowel paralysis with Buscopan (Boehringer Ingel-
Bleedings in the upper gastrointestinal (GI) tract are heim, Germany) are mandatory for a bleeding angiogram.
usually treated by endoscopic coagulation therapy. The causes of lower GI bleeding are:
However, if endoscopic therapy fails or the bleeding • small bowel tumours (endocrine carcinomas, angio-
source is inaccessible to endoscopy, angiographic em- fibroma, melanoma metastasis, arteriovenous malfor-
bolization is indicated. Patients after gastric resection mation, etc.);
involving bilioenteric anastomoses and patients bleed- • Meckels diverticulum;
ing from hepatobiliary and pancreatic pathologies • large bowel diverticulum bleeding (most common
(pseudoaneurysms) should be treated primarily by an- cause in elderly patients);
giographic techniques. Due to the extensive collateral • hemangiomatosis and arteriovenous malformation of
circulation in the upper abdomen, a detailed angio- the colon;
graphic evaluation followed by embolization of all feed- • colon cancer (rectal bleeding due to hemorrhoidal dis-
ing arteries is required. ease has to be ruled out primarily).
The most common causes of upper GI bleeding are: GI bleedings are preferentially embolized by coils.
• gastroduodenal ulcer;
• proximal jejunal tumors (endocrine carcinomas, angio-
fibroma, melanoma metastasis, arteriovenous malfor- Treatment for Bleeding Complications after Surgery,
mation etc.); Trauma, and Post-partum
• pseudoaneurysm of the gastroduodenal, pancreatico-
duodenal, intrapancreatic, and splenic arteries after Bleeding in the abdomen may occur from iatrogenic
pancreatitis or trauma, bleeding through the Wirsung causes, particularly in the kidneys and the liver after per-
pancreatic duct; cutaneous interventions. It may also be due to trauma or
• pseudoaneurysm of the hepatic artery, bleeding tumor. Frequent and typical locations and causes are re-
through the common bile duct (triad of hemobilia: ab- nal arteriovenous fistulas due to nephrostomy (Fig. 4) or
dominal colic followed by jaundice and hematemesis biopsy, laceration of the hepatic arteries by percutaneous
or melena). manipulations, psoas and pelvic bleeding due to traumat-
In lower GI bleeding, diagnosis and treatment are ic arterial injury, and uterine artery bleeding post-partum.
preferentially done by colonoscopy. However, in select- Temporary occlusion of the uterine artery can be a valid
ed cases embolization is required. For the primary diag- alternative to emergency hysterectomy in patients with
nosis, a contrast-enhanced CT of the abdomen (400 mg intractable bleeding resulting from an atonic uterus. In
iodine/mL, flow 4 mL, volume 100 mL) in the arterial other anatomical locations, the type, source, and location
and delayed phases usually demonstrates the area of of the bleeding determine the method used to safely in-
bleeding nicely. This helps to find the bleeding source terrupt the extravasations.
a b c
Fig. 4 a-c. Hematuria and shock due to renal bleeding after nephrostomy. a CT showing large
perirenal hematoma and active bleeding. b Selective angiography demonstrates the bleeding
site. c Control angiography after selective coil embolization
160 Johannes Lammer
Therapeutic Embolization of Tumors higher efficacy in high-risk patients (defined by Child-

Pugh B cirrhosis, ECOG 1 tumor symptoms, bilobar and
Tumor embolization techniques range from palliative recurrent disease), a lower liver toxicity, but also systemic
embolization in bleeding genitoureteral tumors, to doxorubicin-related toxicity. Regional chemotherapy
chemoembolization techniques in hypervascularized he- with irinorecan drug-eluting beads in patients with col-
patic neoplasms, in particular hepatocellular carcinoma orectal liver metastases is under evaluation. Intrahepatic
(HCC), to the definitive treatment of benign lesions such radiation by radioactive β-emitting particles directly in-
as uterine fibroids. In the liver, tumor embolization is jected into the hepatic arteries is another treatment
mainly used in patients with inoperable HCC but pre- modality for primary and metastatic liver tumors.
served liver function (Child-Pugh A and B) and in those
with neuroendocrine tumor metastases. Classical treat-
ment is chemoembolization with doxorubicin mixed Venous Interventions
with Lipiodol (Guerbet, France), sometimes in combina-
tion with a temporary blockade of the hepatic artery by TIPS
Gelfoam or other embolization particles. In randomized
trials, chemoembolization of unresectable HCC has Transjugular intrahepatic portocaval shunt (TIPS) to de-
shown to be superior to supportive treatment only. New pressurize the portal venous system was introduced into
techniques include doxorubicin-loaded particles as an clinical medicine at the end of the 1980s. Since then, a
alternative embolization agent for HCC (Fig. 5). In the standardized technique has been developed that allows
Precision V trial, more than 200 patients were randomly safe implantation of this artificial connection between the
assigned to either transarterial chemoembolization portal and hepatic veins. The introduction of stent grafts
(TACE) with drug-eluting beads or to conventional instead of bare stents has also led to improved patency of
chemoembolization with Lipiodol and doxorubicin. The the shunt tract.
former group had a higher rate of objective response and TIPS is indicated in patients symptomatic from portal
disease control within 6 months of follow-up. In addition, hypertension with acute or chronic bleeding of esophageal
the use of drug-eluting beads resulted in a significantly or gastric varices and in those with intractable ascites.
a b
Fig. 5 a-d. Hepatocellular carcinoma before

and after transarterial chemoembolization
(TACE) with drug-eluting beads. a Contrast-
enhanced CT shows HCC in right hepatic
lobe. b Arteriography shows hypervascular
HCC. c Control arteriography after TACE of
HCC. d Contrast-enhanced CT shows com-
plete necrosis of the HCC
Endoscopic techniques to treat varices are competitive Kasirajan K, O’Hara PJ, Gray BH et al (2001) Chronic mesenteric
in bleeders whereas in some patients with ascites there ischemia: open surgery versus percutaneous angioplasty and
stenting. J Vasc Surg 33:63-71
are few alternatives. Randomized trials, meta-analyses, Khan S, Tudur Smith C, Williamson P, Sutton R (2005) Portosys-
and Cochrane data review analyses have shown that TIPS temic shunts versus endoscopic therapy for variceal rebleeding
is superior to endoscopic therapy in the prevention of re- in patients with cirrhosis. Cochrane Database Syst Rev
bleeding and is superior to paracenteses to remove as- 18:CD000553
cites. In patients with acute or subacute Budd-Chiari syn- Khuroo MS, Al-Suhabani H, Al-Sebayel M et al (2005) Budd-
Chiari syndrome: long-term effect on outcome with transjugu-
drome, TIPS can be a life-saving procedure and help to lar intrahepatic portosystemic shunt. J Gastroenterol Hepatol
overcome the acute phase, but the approach is burdened 20:1494-1502
by a relatively high re-thrombosis rate. The risks after Lammer J, Malagari K, Vogl T et al, on behalf of the PRECISION
TIPS procedure are liver failure from shunted blood vol- V investigators (2009) Prospective randomized study of doxo-
ume and encephalopathy. rubicin-eluting-bead embolization in the treatment of HCC:
results of the PRECISION V study. Cardiovasc Intervent
Radiol 12 [Epub ahead of print]
Embolization of the Portal Veins Leertouwer TC, Gussenhoven EJ, Bosch JL et al (2000) Stent
placement for renal artery stenosis: where do we stand? A
An intervention of increasing importance is pre-operative metaanalysis. Radiology 216:78-85
embolization of the right or left portal vein in order to in- Mann SJ, Pickering TG (1992) Detection of renovascular hyper-
tension: state of the art 1992. Ann Intern Med 117:845-853
duce hypertrophy of the contralateral hepatic lobe prior to Perler AB, Becker GJ (1998) Vascular intervention – a clinical ap-
extended hemi-hepatectomy. proach. Visceral vascular disease. Thieme, New York, Stuttgart,
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Prinssen M, Verhoeven EL, Buth J et al (2004) Dutch Randomized
Suggested Reading Endovascular Aneurysm Management (DREAM) Trial Group.
A randomized trial comparing conventional and endovascular
ASTRAL Investigators, Wheatley K, Ives N, Gray R et al (2001) repair of abdominal aortic aneurysms. N Engl J Med
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Bax L, Woittiez AJ, Kouwenberg HJ et al (2009) Stent placement chronic mesenteric ischemia: comparison of operative arterial
in patients with atherosclerotic renal artery stenosis and im- bypass grafting and percutaneous transluminal angioplasty. J
paired renal function: a randomized trial. Ann Intern Med Vasc Interv Radiol 6:339-349
150:840-848 Saab S, Nieto JM, Lewis SK, Runyon BA (2006) TIPS versus para-
Blankensteijn JD, de Jong SE, Prinssen M et al (2005) Dutch Ran- centesis for cirrhotic patients with refractory ascites. Cochrane
domized Endovascular Aneurysm Management (DREAM) Tri- Database Syst Rev 18:CD004889
al Group. Two-year outcomes after conventional or endovas- Salerno F, Cammà C, Enea M et al (2007) TIPS for refractory as-
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IDKD 2010-2013
Non-vascular Abdominal Disease: Diagnosis and Therapy

Carlo Bartolozzi, Valentina Battaglia, Elena Bozzi
Division of Diagnostic and Interventional Radiology, University of Pisa, Pisa, Italy
Introduction resolution of US enables the demonstration even of very

small lesions (<1 cm in maximum diameter). In nodules
Recent technological advances have given rise to a wide >1 cm in maximum diameter, the vascular supply should
range of diagnostic and interventional imaging-guided probe assessed as well. Moreover, the introduction of mi-
cedures for an increasing number of abdominal parenchy- crobubble contrast agents and the development of con-
mal diseases, such as those involving the kidneys, adren- trast-specific scanning techniques have expanded the
als, or pancreas. However, the liver, and the cirrhotic liver capabilities of US in examinations of the cirrhotic liver.
in particular, still represents the main field of application The advent of second-generation contrast agents and low-
of abdominal imaging modalities. Imaging plays a key role mechanical-index real-time scanning techniques has been
in the diagnostic work-up of the nodular lesion, especially fundamental in improving the ease and reproducibility of
in its initial detection and characterization. In addition, the US examinations [2]. Consequently, contrast-enhanced
results of imaging assessment guide the therapeutic op- US has been introduced into the diagnostic flow chart as
tions (surgical, interventional, or palliative) and provide the one of the imaging modalities able to demonstrate the
standard of reference in the evaluation of tumor response. vascular pattern of nodules >1 cm in diameter [3].
Dynamic multidetector computed tomography (MDCT)
and magnetic resonance imaging (MRI) are further imag-
Hepatocellular Carcinoma: Pathology ing modalities used to detect and characterize nodular
vascular changes. They provide a detailed view of the
The diagnosis of hepatocellular carcinoma (HCC) is hepatic parenchyma and allow a confident diagnosis of
based on imaging examinations in combination with clin- neoplasm. Importantly, these imaging evaluations are a
ical and laboratory findings. However, imaging of the cir- fundamental prerequisite for guiding the therapeutic
rhotic liver remains challenging since regenerative nod- approach. The added value of MRI over other cross-
ules and pre-neoplastic hepatocellular lesions, such as sectional imaging modalities is its ability to assess the
dysplastic nodules, can mimic small HCCs. New imaging components of a hepatic lesion in baseline image acqui-
technologies have improved investigations into the multi- sitions. The use of tissue-specific MRI contrast media
step process that takes place during carcinogenesis, from (hepatobiliary and reticuloendothelial agents) can reveal
regeneration towards dysplasia and full malignancy. metabolic disorders that occur as a result of cellular
The most important pathological alteration in the de- dedifferentiation. Current cross-sectional techniques
velopment of HCC is the derangement in the liver’s vascu- demonstrate the pathological changes associated with
lar supply due to progressive capillarization of the sinu- carcinogenesis, such that needle biopsy is no longer
soids, associated with the formation of an increasing considered as the standard reference procedure for the
number of unpaired arterioles. In addition, there are pro- definitive diagnosis of HCC [3].
gressive, intracellular histological changes, including loss
of the biliary polarization of hepatocytes, a derangement Pre-neoplastic Lesions: Regeneration
of their microscopic secretory structure, and the progres-
sive depletion of Kupffer cells within nodular lesions [1]. Regeneration is the result of the architectural rearrangement
Due to the wide spectrum of morphological changes of the hepatic parenchyma in response to chronic injury.
seen in cirrhotic parenchyma, all cross-sectional imaging Generally, regenerative nodules are small (around 1 cm) but
modalities should be applied in the detection and charac- in some cases may have a maximum diameter v3 cm.
terization of nodular lesions. Ultrasound (US) is the At US examination, a typical regenerative nodule may
modality most commonly applied in the surveillance of appear as a hypoechoic or hyperechoic small nodule that
cirrhotic patients and is thus considered as the first-line enhances relative to background because of its thin
approach in their diagnostic workup. The high spatial hyperechoic rim, which represents perinodular fibrous
Non-vascular Abdominal Disease: Diagnosis and Therapy 163
Arterial Late
a b
Fig. 1 a-c. a Baseline US examination shows the presence of a large (up to 3 cm) hyperechoic
nodule of the VI segment, partially exophytic, in a background of cirrhosis (arrow). b At
dynamic MRI study, the nodule does not show signs of hypervascularization (appearing as
hypointense on arterial phase); instead, the portal supply is still well evident, while the
nodule appears slightly isointense during the late phase. c On this baseline T2-weighted
image, the nodule appears as hypointense, due to its intranodular iron content, which
increases signal intensity compared to the surrounding parenchyma (arrow) c
tissue and which may mimic a pseudocapsule. Generally, HGDN are considered to be pre-malignant lesions, and
no further examination is required. In cases of larger nod- the subsequent development of HCC from a HGDN
ules, dynamic evaluation is required to exclude neoplas- within a period of years or even a few months has been
tic dedifferentiation (Fig. 1 a). documented [5]. Plain US and CT examinations are gen-
At dynamic contrast studies (contrast-enahnced US, erally useless in the characterization of dysplastic nod-
MDCT, or MRI), there is no evidence of a vascular sup- ules, due to the lack of specific imaging finding (Fig. 2 a).
ply different than that of the surrounding parenchyma, At dynamic study, the post-contrast enhancement pat-
due to the conspicuous and predominant feeding of these terns of HGDN may be highly variable. In fact, even if
nodules by portal vessels (Fig. 1 b) [4]. MRI can depict the main blood supply is still provided by branches of the
some peculiarities that may differentiate regenerative portal vein, the presence of a vascular supply on arterial
nodules from other focal lesions. On baseline examina- phase may be seen due to the development of sporadic
tion, regenerative nodules are isointense on T1- and T2- unpaired arteries. However, this finding is not associat-
weighted images due to the presence of normal liver ed with wash-out, which instead represents the diagnos-
cells. The frequent intranodular content of iron may de- tic finding for HCC (Fig. 2 b). Thus, in addition to dis-
crease the relaxation time on T2, thus reducing the signal playing the degree of vascular supply, MRI demonstrates
intensity of the nodules on these sequences (Fig. 1 c). parenchymal alterations, thereby playing an important
Nodular signal intensity after the administration of role in the differential diagnosis between pre-neoplastic
tissue-specific contrast agent (hepatobiliary or reticulo- and neoplastic lesions. In fact, at baseline MRI exami-
endothelial) is not modified due to the preserved meta- nation, dysplastic nodules typically show a characteristic
bolic activity of hepatocytes and Kupffer cells. hyperintensity on T1-weighted sequences due to the in-
tranodular presence of glycogen or lipids, while on T2-
Pre-neoplastic Lesions: Dysplasia weighted sequences they may be slightly hyperintense,
isointense, or even hypointense.
Dysplastic nodules are classified as low-grade (LGDN) In the hepatobiliary phase, after the administration of
and high grade (HGDN), depending on the degree of hepatospecific contrast agents, DNs are generally iso-
cellular atypia and on changes in architectural structure. intense or hyperintense compared to the surrounding liver
164 Carlo Bartolozzi, Valentina Battaglia, Elena Bozzi
Arterial Late
a b
Fig. 2 a-c. a At baseline US, it is possible to appreciate the presence of a suspected isoechoic nodule
surrounded by a thin hypoechoic rim. b The US post-contrast examination does not show any arte-
rial supply within the nodule, which remains hypoechoic in all post-contrast acquisitions. c On he-
patobiliary phase at MRI examination, the nodule is isointense with the surrounding parenchyma,
c due to the preserved biliary function
parenchyma, reflecting the maintenance of biliary func- signal intensities, appearing as either hyperintense or
tion but also cholestasis, which occurs in so-called green isointense. Hyperintensity, as in the case of HGDN, may
nodules (Fig. 2 c). be related to the intracellular presence of glycogen and
Sometimes, the progression from dysplasia to HCC is fat, which accumulate because of the loss of normal
detected in a very early phase, when it is possible to iden- cellular metabolic activity. On baseline T2-weighted
tify a focus of HCC within a pre-malignant lesion, known images, HCC usually shows mild signal hyperintensity,
as “a nodule within a nodule”. On T2-weighted images, while small and well-differentiated tumors may be
the typical appearance is a focus of high signal intensity isointense to the surrounding parenchyma. In a compar-
located within a low-signal-intensity nodule and also ison of histological data obtained from explanted
showing the post-contrast signal behavior of HCC. cirrhotic livers with the MRI signal intensity of corre-
sponding lesions, a relationship was found between
lesion malignancy and nodular intensity on T2-weighted
Hepatocellular Carcinoma: Imaging Findings images [6]. It also has been shown that nodular signal
intensity on T2-weighted images is significantly associ-
As noted above, one of the key pathological features di- ated with the intranodular blood supply; in fact, signal
agnostic of HCC is the vascular supply of the nodule. The intensity increases as the intranodular portal venous
progression from regeneration to overt HCC is character- blood supply decreases [7].
ized by neoangiogenesis, that is, the concomitant devel- Although their application has not yet been introduced
opment of feeding arteries and efficient arteriovenous into diagnostic guidelines, the use of tissue-specific con-
shunts. This pathological blood supply is well demon- trast medium may give additional information, such
strated on contrast-enhanced dynamic studies by the typ- as the atypical baseline or vascular pattern at dynamic
ical findings of wash-in during the arterial phase and sub- study, as in the case of borderline lesions (dysplastic
sequent wash-out (Fig. 3 a). However, a typical vascular nodules) or well-differentiated HCCs. Regarding hepato-
behavior may not be present at dynamic imaging. In these biliary contrast agents, the lack of contrast uptake is
cases, MRI both at baseline and following the adminis- strongly related to overt HCC, due to the loss of normal
tration of hepatospecific contrast media may lead to a de- metabolic function whereas the uptake is preserved in
finitive diagnosis of HCC. early HCCs, resembling that of HGDNs [8]. In daily
In addition, early or moderately differentiated HCC practice, the advantages of the most recent generation of
may show peculiar signal intensity on T1- and T2- MRI contrast media can be exploited, as they illustrate
weighted baseline acquisitions (Fig. 3 b). On baseline the nodule’s characteristic vascular and hepatospecific
T1-weighted images, HCC usually appears as a hypo- phases, i.e., neoangiogenesis and lack of hepatobiliary
intense nodule because of its increased cellularity, and function, respectively, which allow a highly confident
thus its higher amount of intracellular water; however, diagnosis of HCC (Fig. 3 c). Specifically, reticulo-
small, well-differentiated HCCs may show different endothelial system (RES) agents allow the carcinogenetic
Non-vascular Abdominal Disease: Diagnosis and Therapy 165
Fig. 3 a-c. a MR dynamic examination reveals

Arterial Late a nodule of the VIII segment that is hyper-
vascular on arterial phase and shows clear
cut washout in the late phase. b At baseline
MRI examination, the nodules has a typical
signal intensity, i.e., hypointense on T1-
weighted sequences and hyperintense on T2-
weighted sequences. c On hepatobiliary
phase, the nodule is hypointense to the sur-
rounding parenchyma, due to the complete
loss of biliary function
T1 w.i T2 w.i
b c
pathway to be followed; for example, the progressive in- visualization of the target allows continuous assessment
crease in sinusoid capillarization provides a hostile envi- of the ongoing changes that occur during the ablation
ronment for reticuloendothelial cells, such that their pro- procedure. In addition, the inclusion of periprocedural
gressive loss explains the very high signal intensity of contrast enhancement provides immediate evaluation of
HCC [9]. Nonetheless, due to the less consistent vascu- the presence of residual viable tumor, which may be re-
lar phases, the application of RES agents is strongly lim- treated during the same ablation session.
ited and has largely been discontinued. Contrast-enhanced CT and MRI play a major role in
follow-up, permitting assessment of the tumor’s response
Therapy and Follow-up in terms of necrosis or relapse as well as the detection
of new lesions in the surrounding parenchyma [3].
Nowadays, the therapeutic approach to HCC is based on MRI, when performed with hepatospecific contrast
surgical (transplantation and resection) and non-surgical agents, can provide additional information about post-
approaches, mini-invasive modalities (percutaneous and ablation tissue components. This may be useful in ques-
intra-arterial therapies), and palliative approaches. The tionable cases, in which periablation hyperemia (espe-
decision is based upon clinical and functional data as well cially after radiofrequency ablation) or arteriovenous
as on the imaging findings, i.e., number of lesions and shunts/thrombosis (especially after ethanol ablation)
their size, location, degree of vascularization, and rela- must be differentiated from tumoral persistence or re-
tionships with vascular and biliary structures. For exam- currence [10].
ple, a candidate for liver transplantation should fulfill
imaging criteria, which include the presence of a single
lesion measuring <5 cm or of up to three lesions, each Conclusions
with a greatest dimension f3 cm. Moreover, post-
processing of native images is fundamental in candidates In conclusion, HCC in a cirrhotic liver represents one of
for surgical or intra-arterial therapies, in order to provide the most important fields of application of imaging
an overall representation of the vascular anatomy or of modalities, based on their key role in the detection and
the feeding vessels of the lesions. characterization of nodular lesions. Moreover, any thera-
Imaging modalities are also very important as guid- peutic decision is strongly related to the imaging results,
ance for percutaneous ablation. In these cases, US repre- as they also guide the use of mini-invasive procedures
sents the most appropriate technique, as its real-time and allow evaluation of therapeutic success.
166 Carlo Bartolozzi, Valentina Battaglia, Elena Bozzi
References 6. Bartolozzi C, Cioni D, Donati F et al (2001) Focal liver

lesions: MR imaging-pathologic correlation. Eur Radiol 11:
1. International Consensus Group for Hepatocellular Neoplasia. 1374-1388
The International Consensus Group for Hepatocellular Neo- 7. Shinmura R, Matsui O, Kobayashi S et al (2006) Cirrhotic
plasia (2009) Pathologic diagnosis of early hepatocellular car- nodules: association between MR imaging signal intensity and
cinoma: a report of the international consensus group for he- intranodular blood supply. Radiology 237:512-519
patocellular neoplasia. Hepatology 49:658-664 8. Bartolozzi C, Crocetti L, Lencioni R et al (2007) Biliary and
2. Cosgrove D (2006) Ultrasound contrast agents. An overview. reticuloendhotelial impairment in hepatocarcinogenesis: the
Eur J Radiol 60:324-330 diagnostic role of tissue specific MR contrast media. Eur
3. Bruix J, Sherman M (2005) Practice Guidelines Committee, Radiol 17:2519-2530
American Association for the Study of Liver Diseases. Manage- 9. Chen RC, Lii JM, Chou CT et al (2008) T2-weighted and T1-
ment of hepatocellular carcinoma. Hepatology 42:1208-1236 weighted dynamic superparamagnetic iron oxide (ferucarbo-
4. Roncalli M, Roz E, Coggi G et al (1999) The vascular profile tran) enhanced MRI of hepatocellular carcinoma and hyper-
of regenerative and dysplastic nodules of the cirrhotic liver: plastic nodules. J Formos Med Assoc 107:798-805
implications for diagnosis and classification. Hepatology 10. Cioni D, Lencioni R, Bartolozzi C. (2001) Percutaneous abla-
30:1174-1178 tion of liver malignancies: imaging evaluation of treatment re-
5. Theise, Park YN, Kojiro M (2002) Dysplastic nodules and he- sponse. Eur J Ultrasound 13:73-93
patocarcinogenesis. Clin Liver Dis 6:497-512
IDKD 2010-2013
An Approach to Imaging the Acute Abdomen in the Pediatric Population

Alan Daneman1, Simon G. Robben2
1 Department of Radiology, University of Toronto and The Hospital for Sick Children, Toronto, Ontario, Canada
2 Department of Radiology, Maastricht University Medical Centre, Maastricht, The Netherlands
Introduction
The acute abdomen is a common and often challenging
emergency in the pediatric population. This chapter pro-
vides an approach to the imaging evaluation of children,
highlighting briefly the more common causes of abdom-
inal pain that may require surgery.
Causes of Acute Abdomen

There is a wide spectrum of pathologies that may give rise
to acute abdominal pain. These include congenital and ac-
quired lesions that may present in the immediate neonatal
period or in older infants and children. In neonates, the
acute abdomen is not an uncommon event in infants in
neonatal intensive care units and may be the result of sev-
eral causes, with congenital bowel obstruction, complica-
tions of mid-gut malrotation, and necrotizing enterocolitis
being the three most significant conditions. In older in-
fants and children, the common causes of acute abdomi- Fig. 1. A boy with right lower quadrant pain and fever. The abdom-
nal pain that may require surgery include acute appen- inal radiograph shows a triangular consolidation (arrows) in a basal
dicitis, complications of malrotation, intussusception, and segment of the right lower lobe: basal pneumonia. Dilated air-filled
Meckel diverticulum. Inflammatory bowel diseases may ascending colon was considered secondary to referred pain. Un-
eventful recovery after antibiotic therapy
also present with acute abdominal symptomatology.
Although the common, above-mentioned causes of
acute abdominal pain are due to lesions involving the
gastrointestinal tract, the acute abdomen may also be due cause abdominal pain out of proportion to the degree of
to abnormalities of other viscera, e.g., gynecological ab- trauma. Imaging in these children may reveal an underly-
normalities such as ovarian torsion, omental lesions such ing abnormality such as a neoplasm or an anomaly such
as omental infarcts, obstructions of the biliary and uri- as uretero-pelvic obstruction. Furthermore, one should
nary tracts due to stones and inflammatory processes consider non-accidental injury or abuse when certain
such as pancreatitis or hepatitis. traumatic lesions are found, especially when they appear
It has to be emphasized that abdominal pain may also in combination with hematomas of the left lobe of the liv-
be due to referred pain from extra-abdominal patholo- er and duodenum and pancreatitis.
gies, such as pneumonia or pleural effusion (Fig. 1).
Medical diseases, e.g., sickle cell disease, Henoch-
Schonlein purpura, and hemolytic uremic syndrome, may Modalities
also be the cause of significant acute abdominal pain.
Imaging of the child with acute abdominal pain should Ultrasonography (US) has come to play an ever-increasing
include a search for evidence of these other pathologies. role in the management of children with acute abdominal
Abdominal trauma may also be the cause of an acute pain and has replaced the plain abdominal radiograph as
abdomen. Occasionally, mild abdominal trauma may the modality of initial choice in many clinical situations.
168 Alan Daneman, Simon G. Robben
The major advantages of US are that it does not use ion- all the information required, e.g., appendicitis when
izing radiation, it is relatively inexpensive, and the ab- gas obscures the right lower quadrant, or in older, obese
dominal viscera, including the bowel, are well delineated children and those children with abscesses. CT without
in children. Therefore, many pathological entities can be contrast injection is also extremely helpful in delineating
easily confirmed or excluded. urinary stones when these are not well shown by US.
Plain abdominal radiograph (AXR) remains a standard Magnetic resonance imaging (MRI) has a very limited
method for evaluation of the acute abdomen in some clin- role in children with acute abdominal pain. However,
ical situations. It is essential when peritonitis is present it can depict the anatomy exceptionally well in certain
and perforation is suspected. All neonates with an acute conditions, in which case it may be used to complement
abdomen are evaluated with AXR. This modality is es- findings on US. These include biliary and pancreatic duct
sential for the detection of conditions such as necrotizing anomalies and gynecological disorders, such as complex
enterocolitis and congenital bowel obstruction. In the for- anomalies associated with hydrocolpos.
mer, AXR may be diagnostic; in the latter, the findings
guide the choice of subsequent contrast examinations of
the gastrointestinal tract. Views with a horizontal beam Acute Appendicitis
are essential to exclude the presence of free air due to
bowel perforation and can be performed with the neonate Acute appendicitis is a common clinical entity in pediatrics.
in the dorsal or lateral decubitus position. In older chil- In many patients, it is easy to make the diagnosis clinically
dren, the diagnosis of intestinal obstruction can often be with certainty and no imaging is required prior to appen-
made based on the supine film alone. A search for air- dicectomy. However, imaging is extremely important in
fluid levels on the upright view does not always add extra those children with non-specific symptoms or signs of
information and a search for free air in the abdomen is acute appendicitis. In such cases, we have used US as the
often more easily achieved with a lower radiation dose modality of initial choice, reserving CT for those patients
and a single upright view of the chest, which will also in whom the US examination is inconclusive or when
serve to exclude lung pathology. However, in both the abscesses are present in order to better define their extent
neonate and the older child, AXR findings are often non- prior to drainage by the interventional radiology team.
specific, which limits the role of this modality. The diagnosis of appendicitis is made on US when the
Contrast studies of the gastrointestinal (GI) tract are appendix is >6 mm in diameter and is non-compressible.
essential in certain conditions, such as suspected mid-gut These features should not be considered absolute and
malrotation and congenital bowel obstruction. In the lat- others should be taken into account, including edema of
ter situation, contrast enema may be important in some the mesentery, hyperemia of the wall of the appendix on
patients for diagnosis and in others for therapy as well. color or power Doppler examination, the presence of an
Computed tomography (CT) may be reserved for more appendicolith and local fluid collections, or abscess for-
complicated imaging situations, when US may not provide mation (Figs. 2, 3). There are other conditions that may
a b
Fig. 2 a, b. Abortive appendicitis in a 9-year-

old boy who had local peritoneal tenderness
for one day, exactly at the site of the appen-
dix, and normal temperature. a US shows
borderline appendix diameter (6 mm) and
slight edema of the apendiceal mesentery
(echogenic triangle, arrow) but no surround-
ing edema. b Color Doppler US demonstrat-
ed marked hyperemia. Complaints subsided
within 2 days without therapy
a b
Fig. 3 a, b. Rapidly progressing appendicitis in

an 8-year-old boy who had local peritoneal
tenderness exactly at the site of the appendix
for 1 day and low grade fever. a US shows
thickened appendix (8 mm) with edema of
the appendicular mesentery (echogenic trian-
gle, arrow) and extensive surrounding ede-
ma. b Color Doppler US demonstrated mod-
erate hyperemia. At surgery, an inflamed ap-
pendix was removed
An Approach to Imaging the Acute Abdomen in the Pediatric Population 169
cause the appendix to become thick-walled and dilated; intussusception promptly and accurately. The diagnosis
these include cystic fibrosis, Henoch-Schonlein purpura, can be made by US, AXR, or contrast studies of the colon.
and inflammatory bowel diseases. Ultrasonography has been shown in many series to be
100% accurate in depicting the presence or absence of
the common types of ileocolic or ileo-ileocolic intussus-
Malrotation ceptions in children. These lesions have a characteristic
sonographic appearance and are usually found just under
See the chapter “Malrotation: Techniques, Spectrum of the abdominal wall, most commonly on the right side of
Appearance, Pitfalls, and Management”, in the “Kangaroo” the abdomen (Fig. 4). Since it is a non-invasive procedure
section of this syllabus for a review of this important and because of its accuracy, sonography is the modality
cause of acute abdomen in the pediatric population. of choice for the evaluation of patients suspected of hav-
ing an intussusception. The sonographic appearance of
intussusception was excellently reviewed in a 1996 arti-
Intussusception cle by del-Pozo et al. (see “Suggested Reading”).
Some of the characteristic signs of an intussusception
Intussusception is not an uncommon phenomenon in can be seen on AXR, including the meniscus sign, target
children and is one of the commoner causes of the acute sign, and, less commonly, a soft-tissue mass (Fig. 5).
abdomen in those between 6 months and 5 years of age.
The vast majority of intussusceptions arise in the ileum
and are either ileocolic or ileo-ileocolic. They are thought
to occur because of hyperplasia of the lymphoid tissue
in the ileum, possibly as a result of a viral infection.
There are other types of intussusceptions that may re-
late to pathological lead points or gastro-jejunostomy
tubes, or that are seen in the post-operative period. These
are discussed separately at the end of this chapter. An-
other type of intussusception is the benign small bowel
intussusception. This is often an incidental finding and
does not present as an acute abdominal emergency. This
entity is discussed separately in the chapter “Pediatric
Intestinal Ultrasonography”, in the “Kangaroo” section of
this syllabus.
Ileocolic and Ileo-ileocolic Intussusceptions
Diagnosis
Children presenting with ileocolic or ileo-ileocolic intus-

susception commonly do not present with the classical
clinical triad of abdominal pain, red currant jelly stool, Fig. 5. Child with ileocolic intussusception that extended into the
transverse colon. Abdominal radiograph shows a gasless right up-
and a palpable abdominal mass. Instead, the presentation per abdomen due to the presence of the intussusception on the
may be non-specific. For this reason, the clinician often right. The arrows indicate a soft-tissue mass that represents the in-
has to rely on imaging procedures to diagnose or exclude tussusception, which is in the transverse colon
a b
Fig. 4 a, b. Sonograms of children with ileo-

colic intussusception. a Transverse scan
through an intussusception shows the typical
target sign, which can be easily detected just
deep to the abdominal wall anteriorly. The
characteristic of this target sign is multiple
concentric rings representing alternating mu-
cosal and muscular layers. b Transverse scan
through an intussusception shows the pres-
ence of a lymph node (arrow) within the
mesentery which has been drawn into the
intussusception between the layers of the
intussusceptum
However, in our institutions, we have relied on the plain

radiograph only in those instances in which there is a
clinical consideration of peritonitis. In this clinical set-
ting, AXR is essential to exclude perforation, which is the
major contraindication for attempted enema reduction.
Contrast enema represents a more invasive diagnostic
procedure, requiring radiation. Moreover, in a study by
Daneman and Navarro, in 2003, in which patients were
administered contrast enema for diagnosis, 50% of the
enemas were negative for intussusceptions (see “Suggest-
ed Reading”). Using sonography as the diagnostic modal-
ity enables one to avoid performing unnecessary contrast
enemas in those patients without intussusception.
Reduction
According to the many series in the recent literature, the

reduction rate of intussusception ranges from 80% to as Fig. 6. A 3-month-old child with an intussusception due to a dupli-
high as 95%. These series have used either fluoroscopic cation cyst. In the transverse scan, the duplication cyst (C) is eas-
or sonographic guidance for reducing the intussusception ily identified as a pathological lead point
and either hydrostatic (barium, water-soluble contrast,
saline) or pneumatic reduction. The fact that different
techniques have been used with similar success rates sug- However, it remains a diagnostic challenge as to how to
gests that it is not important which technique is used. search for pathological lead points in those patients in
Non-operative reduction of an intussusception should on- whom there is a high index of suspicion for this lesion and
ly be attempted after the surgical team has evaluated the in whom the sonogram is negative. In such cases, the choice
patient and the patient is clinically stable, well-hydrated, of which other imaging modalities to use will depend on the
has no evidence of peritonitis, and has an intravenous line clinical situation in each particular patient. We recommend
in place. The major contraindications to administering the attempted enema reduction in all patients with a lead point
enema are the clinical findings of peritonitis or shock or if there is no contraindication to non-operative reduction.
signs of perforation on an abdominal radiograph.
In order to improve the reduction rate, delayed, repeat- Postoperative Intussusception and Intussusception with
ed reduction attempts can be used as long as the intussus- Gastroenterostomy Tubes
ception moves in response to the initial attempted reduc-
tion and the child becomes asymptomatic and maintains Intussusception may occur as a complication in <1% of
stable vital signs. It has been shown that this approach is laparotomies. These are usually more difficult to diag-
safe and effective, with a good success rate. Navarro et al., nose on sonography than the usual ileocolic intussuscep-
in a study published in 2004 (see “Suggested Reading”), tions, as they are small bowel intussusceptions that are
used this approach in approximately 15% of patients with often surrounded by large, dilated loops of obstructed
intussusceptions, achieving successful reduction in 50% bowel. They frequently require surgical reduction.
of those intussusceptions not reduced on the first attempt. Intussusceptions may complicate the presence of a
There does not appear to be a fixed optimal timing be- gastrojejunostomy (GJ) tube. Most of the patients pre-
tween attempts, and delayed second or third attempts can senting with this complication are usually clinically sta-
be made several hours after the first. ble and do not require urgent reduction of the intussus-
ception. The majority can be managed by replacing the
Pathological Lead Points tube with a standard or a shortened GJ tube or with a gas-
trostomy tube. However, manipulation of the GJ tube and
Pathological lead points are found in about 5-7% of all flushing with air or saline may also be helpful. Surgery is
intussusceptions. The commonest are Meckel diverticu- rarely required for reduction.
lum, polyps, Henoch-Schonlein purpura, and cystic fi-
brosis. Less common causes are lymphoma, duplication
cyst, and various inflammatory lesions of the bowel. Necrotizing Enterocolitis
Management of these patients remains a challenge.
Contrast or air enema techniques are not always diag- Necrotizing enterocolitis (NEC) usually presents in
nostic in documenting the presence of a pathological lead infants in the neonatal intensive care unit, and more
point. Sonography is extremely useful in this regard as it commonly in premature neonates. The classical presenta-
may depict two-thirds of pathological lead points, providing tion includes abdominal distention and blood in the stool.
a specific diagnosis in one-third of these cases (Fig. 6). The radiologist plays an important role at the time of
a b
Fig. 7 a, b. a Necrotizing enterocolitis in a pre-

mature infant. Bowel loops show distention
with gas and thickened bowel walls. Large
bubbles of intramural air are seen at the de-
scending colon; a bubbly appearance in the
right flank also suggests the presence of in-
tramural air in the ascending colon and distal
ileal loops. b Detail shows the intramural gas
(arrow) to better advantage. Intramural gas is
most commonly seen in newborns with
necrotizing enterocolitis
diagnosis of NEC, during follow-up, and in the detection bowel (especially when the bowel wall is thinned) indicates
of later complications such as strictures. the presence of necrosis – a condition that may warrant
At the time of diagnosis, there are three abnormalities surgical intervention even if free air is not seen on AXR.
that may be seen on AXR: bowel dilatation, intramural Sonography comes to play a more major role in the
gas, and portal venous gas. Bowel dilatation is present in follow-up of both those patients who are not responding
almost 100% of the patients with NEC and the degree of to medical management and those who deteriorate clini-
distention of the bowel usually correlates well with the cally. In such cases, US may provide information that is
clinical severity. Follow-up AXR may show asymmetrical not depicted with AXR.
dilatation and fixed loops in those infants who deterio-
rate. Intramural gas is not present in 100% of patients and
the amount of intramural gas does not always correlate Meckel Diverticulum
well with the degree of clinical severity (Fig. 7). Portal
venous gas usually is present in those with severe NEC. Meckel diverticulum most commonly presents as pain-
Disappearance of the intramural gas and portal venous less rectal bleeding due to ulceration because of the pres-
gas does not necessarily correlate with clinical improve- ence of ectopic gastric mucosa. These patients are usual-
ment, as in either case the gas will eventually disappear ly adequately diagnosed and managed following a ra-
even in those children who deteriorate clinically. dionuclide scan.
Ultrasound is an extremely useful modality in the in- In <50% of the children presenting with Meckel di-
vestigation of patients with NEC as it can provide infor- verticulum, the clinical findings will be more complex,
mation regarding the presence of intraperitoneal fluid, with a combination of abdominal pain, vomiting, and, oc-
bowel wall thickness, and bowel perfusion (using color or casionally, rectal bleeding. In these children with acute
power Doppler sonography). US is much more accurate pain, the diagnosis is often difficult and non-specific. US
than AXR in documenting the presence of free and focal can be used successfully to document the presence of an
intra-peritoneal fluid and can also define the character of inflamed or hemorrhagic Meckel diverticulum, which in
this fluid. It is well known that not all patients with NEC this situation has a variable appearance and may simulate
will show free air on AXR following perforation; instead, the presence of an inflamed duplication cyst, appendici-
they may only present with free fluid. tis, or sometimes a small intussusception. The finding of
In the early phases of NEC, we have found that the bow- this somewhat atypical appearance on US is diagnosti-
el wall will be quite thickened; in patients who are more cally suggestive of a complicated Meckel diverticulum
severely affected, however, the mucosa and submucosa of rather than the other pathologies it simulates.
the bowel sloughs into the lumen of the bowel, leaving a
markedly thinned bowel wall, which is much more prone
to perforation. Thinning of the bowel wall can be docu- Congenital Bowel Obstruction in the Neonate
mented with sonography. In NEC, the bowel (particularly,
the thickened bowel) becomes markedly hyperemic, which Obstruction due to congenital lesions may occur at all
indicates the presence of viable bowel. However, the ab- levels of the GI tract and are, from a practical point of
sence of bowel perfusion in single or multiple loops of view, usefully divided into those lesions that are termed
might suggest each of the above conditions, the radio-

graphic findings in all of them are often non-specific.
Differentiation of these conditions will therefore depend
on other factors, such as the clinical history and the re-
sults of the physical examination. Invariably, to increase
diagnostic confidence, these conditions require the ad-
ministration of a water-soluble contrast enema to define
the distal colon and ileum. The contrast enema may also
prove therapeutic in patients with meconium ileus or
meconium plugging the colon.
Suggested Reading
Ang A, Chong NK, Daneman A (2001) Pediatric Emergency Care
17:334-340
Baldisserotto M, Marchiori E (2000) Accuracy of Noncompressive
Fig. 8. High gastrointestinal obstruction in a newborn with trisomy Sonography of Children with Appendicitis According to the
21 (Down syndrome). A double-bubble appearance is present due to Potential Positions of the Appendix. AJR Am J Roentgenol
distention of the stomach and duodenum by gas. This finding sug- 175:1387-1392
gests duodenal atresia. However, small amounts of gas are noted Bombelburg T, Von Lengerke HJ (1992) Sonographic findings in
distally, indicating a partial obstruction, such as a duodenal web, infants with suspected necrotizing enterocolitis. European J
duodenal stenosis, or malrotations with Ladd’s bands. In this pa- Radiol 15:149-153
tient, an annular pancreas was found at surgery. Patients with Down Buonomo C (1999) The radiology of necrotizing enterocolitis.
syndrome can have a variety of congenital duodenal abnormalities RCNA 37:1187-1198
Couture A, Baud C, Ferran JL et al (2008) Gastrointestinal tract
sonography in fetuses and children. 1st edn. Springer-Verlag,
Heidelberg Berlin New York
“high” and those that are termed “low”. High obstruc- Daneman A, Alton DJ, Ein S et al (1995) Perforation during at-
tions denote lesions of the esophagus, stomach, duode- tempted intussusception reduction in children – a comparison
num, and upper small bowel (Fig. 8). Low obstructions of perforation with barium and air. Pediatr Radiol 25:81-88
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The distribution of dilated bowel loops on plain radio- Daneman A, Lobo E, Alton DJ, Shuckett B (1998) The value of
graphs usually enables one to differentiate high from sonography, CT and air enema for detection of complicated
low obstruction relatively easily. This is simply done by Meckel diverticulum in children with nonspecific clinical pre-
evaluating the number of gas-filled loops that are visible. sentation. Pediatr Radiol 28:928-932
Daneman A, Myers M, Shuckett B, Alton DJ (1997) Sonographic
Fluid-filled loops may be difficult to visualize on AXR, appearances of inverted Meckel diverticulum with intussus-
possibly masquerading as free fluid or masses; thus, they ception. Pediatr Radiol 27:295-298
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IDKD 2010-2013
Imaging Uronephropathies in Children

Jeanne S. Chow1, Fred E. Avni2
1 Departments of Urology and Radiology, Children’s Hospital, Boston, MA, USA
2 Department of Radiology, University Clinics of Brussels, Erasme Hospital, Brussels, Belgium
Introduction and Techniques Management of In Utero Renal Pelvis Dilatation

The principle that guides imaging of the pediatric genito- Dilatation of the renal pelvis is a common finding on ob-
urinary tract is the same that guides imaging elsewhere in stetric US, with a frequency of around 1-4% of all preg-
the body of the child: judicious use of imaging while nancies. Yet, every dilatation does not have the same clini-
minimizing ionizing radiation exposure [1] and unneces- cal relevance; furthermore, the antenatal and postnatal evo-
sary sedation. Ultrasound (US) is the main imaging lution is variable. This has led to controversy in the litera-
modality of the genitourinary tract, providing excellent ture about the best work-up and follow-up after birth [6-8].
images of the kidneys and bladder. Also, at the level of
these organs, an abnormally dilated ureter is easily im- Definition
aged. Doppler provides additional information regarding
vascular flow and is especially helpful in evaluating the The best criterion for objectivating urinary tract (UT) di-
main renal artery and veins as well as the arcuate vessels. latation is the anteroposterior diameter of the renal pelvis,
US contrast agents are used to further evaluate the vas- which is measured on a transverse scan of the fetal ab-
cular flow of the kidneys, intrarenal masses, and vesico- domen. The upper limit for normal should be 4 mm in the
ureteral reflux [2]. The main limitation of US is that it second trimester and 7 mm in the third trimester.
provides little functional imaging, instead mainly reveal- Other US evidence of a UT abnormality includes the
ing the physical appearance of the urinary tract. visibility of the fetal ureter, dilatation of the renal ca-
If further imaging is necessary, contrast-enhanced com- lyces, abnormal echogenicity of the renal parenchyma,
puted tomography (CT) and magnetic resonance (MR) and the demonstration of an enlarged bladder (Table 1).
provide exquisite, detailed images of the urinary tract in
addition to more functional information. MR urography Findings on Obstetric US
has become very popular because it emits no ionizing ra-
diation and yields both anatomical and functional data. Abnormalities of the UT can be found at any time during
The latter includes uptake and excretion rates, which to- pregnancy. Once a dilatation has been detected in utero,
gether with relative function and indirect measurements of subsequent evaluations should address three issues: the
glomerular filtration rates provide more information than origin of the dilatation, the co-existence of associated
obtained from a MAG-3/Lasix renogram [3]. However, anomalies, and the prognosis.
because MR is a long procedure that often requires seda- The most common causes of dilatation in the fetus are
tion, Tc-99m(V) dimercaptosuccinic acid (DMSA) and related to obstructions of the ureteropelvic and uretero-
MAG-3 are more commonly used to provide functional vesical junctions and to complicated duplex kidneys. UT
imaging of the genitourinary tract. In addition, functional
information cannot be obtained without gadolinium, but
this approach places children with chronic renal failure Table 1. Characteristics suggesting an abnormality of the urinary
and end-stage renal disease at risk for developing nephro- tract on neonatal ultrasound
genic systemic fibrosis [4]. Although nephroureterolithia- Pelvic dilatation >7 mm
sis may be commonly studied by CT in adults, US is the Calyceal dilatation
first imaging modality in children [4, 5]. Parenchymal thinning
Lack of cortico-medullary differentiation
Small kidney
Key Point Thickening of the pelvic wall
Thickening of the ureteral wall
– Ultrasound is the main imaging modality of the geni- Ureteral dilatation >3 mm
tourinary tract in children. Enlarged bladder
Imaging Uronephropathies in Children 175
dilatation can also result from vesicoureteric reflux origin of the dilatation. Renal function is assessed
(VUR) and intravesical obstruction, especially in male fe- through isotopic studies, while complicated UT malfor-
tuses. In most cases, the US evaluation will be able to dif- mations are best evaluated by MR imaging. The latter is
ferentiate between etiologies. In some patients, especial- particularly helpful for the assessment of a very dilated
ly those with bilateral and complex uropathies, fetal MR UT and complicated duplex-kidney systems.
imaging will provide additional information. The type of treatment (conservative or surgical) will
Other organ malformations also can be associated with depend upon the diagnosis, renal function on follow-up,
UT dilatation; therefore, the US survey should be as and complications. Today, the trend is increasingly to-
meticulous and complete as possible. Chromosomal ward a conservative approach. The length of follow-up
analysis may be indicated in selected patients. must be adapted to the type of anomaly as well as to clin-
The prognosis of a uropathy will depend upon the type ical and imaging follow-up.
and extent of the anomalies. Amniotic fluid volume is im-
portant to the prognosis as well; oligohydramnios, Key Points
thought to be related to decreased urine production, is a
poor prognostic indicator. – Fetal renal dilatation is a common finding during ob-
It is of utmost importance that any relevant informa- stetric US.
tion is correctly transmitted to the postnatal team that will – Thresholds of 4 and 7 mm during the 2nd and 3rd
be in charge of caring for the newborn. trimester, respectively, are widely accepted.
– Postnatally, these patients must be further evaluated by
Postnatal Management of Fetal Pelvis Dilatation US; voiding cystourethrography is performed only if an
anomaly is found at birth or at the age of one month.
Certain conditions require immediate postnatal confir- – The trend is toward a more conservative approach to
mation and therapeutic maneuvers, such as obstructive treatment, based on clinical and imaging follow-up.
posterior urethral valves and prolapsed ectopic uretero-
cele into the urethra. In those cases, US and micturating
cystourethrography (MCU) should be performed directly Imaging Cystic Kidneys in Children
after birth. In all other cases, the work-up can be planned
without urgency. Patients with ureterovesical junction ob- Introduction
struction (UVJO) and complex uropathies should be put
on prophylactic chemotherapy at least until the final di- Renal cystic diseases may be discovered or suspected at
agnosis is made. any stage during fetal life or at any age in childhood.
An algorithm based on US examination is presently They encompass a large number of conditions that can be
applied by most teams (Fig. 1). Micturating voiding separated into those with or without hereditary transmis-
urethrography is only applied if US displays a significant sion. Imaging, mainly US, plays an important role in dif-
anomaly (Table 1). MCU is used to detect high-grade ferentiating between the various types of cystic diseases
VUR and urethral anomalies. If VUR is not present, com- as it shows the features of renal involvement as well as
plementary imaging is necessary to determine the precise associated anomalies.
US : 1st US around day 5
abnormal: pelvis ≥7 mm + dilated calices, or other anomalies normal
VCUG US at 1 mo
normal abnormal abnormal

pelvis ≥ 10 mm
other malformation,
US at 3 mo “extended criteria”
normal
pelvis ≥10 mm pelvis >10 (15) mm
Fig. 1. Algorithm in fetal hydronephrosis
(HN). Antenatal diagnosis of mild to moder-
further morphological & functional ate renal pelvis dilatation [6]. VCUG, Void-
Stop follow-up evaluation: scintigraphy, IVU, MRU … Stop follow-up ing Cystourethrography
176 Jeanne S. Chow, Fred E. Avni
Cystic Kidneys in the Fetus – Hyperechogenicity or cysts are cardinal findings.

– A familial history, detailed clinical inquiry, and asso-
In the fetus (and during the perinatal period), cystic renal ciated findings help in establishing the diagnosis.
disease should be suspected whenever bilateral hyperechoic
kidneys or cysts (uni- or bilateral) are discovered during an
obstetric US examination. The imaging approach to the di- Renal Ectopia and Duplications
agnosis should be based on a detailed sonographic analysis
that includes measurement of renal length, the presence or One of the most interesting areas of pediatric uroradiolo-
absence of cortico-medullary differentiation (CMD), and gy is studying and understanding the multitude of con-
the presence, number, size, and location of the cysts. This genital abnormalities of the urinary tract. During normal
evaluation should be completed through an analysis of the renal development, the kidneys ascend from the renal
entire fetus, looking for associated anomalies. pelvis while rotating medially. If the kidneys do not as-
The timing of detection and the amount of amniotic cend or ascend past their normal location in the renal fos-
fluid are the most important prognostic factors. Further- sae, they are ectopic. In some cases they are as low as the
more, a detailed clinical and familial inquiry is essential pelvis and in others as high as the thoracic cavity. If the
in disease evaluation. kidneys fuse during ascent, pelvic cake kidneys, midline
Autosomal recessive polycystic kidney disease (ARPKD) horseshoe kidneys, or left- or right-sided cross-fused ec-
is the main diagnosis to consider in case of bilateral, topic kidneys form. Since the embryological origin of the
markedly enlarged, hyperechoic kidneys without CMD. kidneys (metanephros) is separate from that of the ureters
The prognosis is usually poor if the amniotic fluid vol- (ureteric buds), the site of ureteral insertion is normal
ume is markedly decreased. even if the kidney is ectopic. However, the renal blood
In case of moderately enlarged hyperechoic kidneys, supply from the aorta will vary depending on the level of
three diagnoses have to be considered: ectopia.
1. nephropathy due to a mutation in the TCF2 gene, The ureteric bud must meet the metanephros in order
2. a milder form of ARPKD, and for the kidney to form. Without this interaction, kidney
3. autosomal dominant polycystic kidney disease (ADPKD). formation is not induced. If two ureteric buds meet at the
In TCF2-mediated nephropathy, CMD is absent or pre- metanephric blastema, then the kidney becomes “duplex”.
sent and whenever cysts are visible they are typically sub- Ureteral duplication may be complete or, more commonly,
cortical. In the milder form of ARPKD, cysts may be ob- incomplete.
served in the medullary area. The main sonographic fea- In incomplete ureteral duplication, a single ureteric
ture of ADPKD is a striking cortical hyperechogenicity bud bifurcates and meets the metanephros during ap-
associated with increased CMD. proximately the 5th to 6th week of gestation. The two
Whenever cysts are the main US finding in the fetal kid- branches of the ureter may join at the level of the renal
neys, their number and location are the main criteria for the pelvis (bifid pelvis) or at the proximal, mid-, or distal
differential diagnosis. The diagnosis of unilateral multiple ureter (bifid ureter) and terminate in a single distal
cysts suggests a multicystic dysplastic kidney. Bilateral ureter that inserts orthotopically into the bladder. Since
multiple cysts can be visualized in a large number of renal the two moieties of the kidney share a common distal
or syndromic diseases, the most common diagnoses being ureter, they behave similarly and usually appear normal.
bilateral multicystic dysplastic kidney, ADPKD, bilateral Rarely, one of the ureteral buds may be blind-ending and
obstructive dysplasia, and glomerulocystic kidneys. never appear to “reach” the kidney (blind-ending ureter-
al duplication). The associated kidney has a single col-
Renal Cystic Diseases in Children lecting system.
In complete ureteral duplication, two separate ureteric
In children, renal cystic diseases are usually discovered buds arise from the Wolffian duct. The lower-pole ureter
during US examination performed in the follow-up of a is considered the analogue to the normal single-system
known perinatally diagnosed disease, during the work-up ureter. Thus, the lower pole of the kidney has all of the
of syndromes diagnosed after birth, during screening in same abnormalities that can affect a single-system kid-
an at-risk family, or as an incidental finding. The US ap- ney, including VUR, ureteropelvic junction obstruction
proach is the same as that described for the fetus. The role (UPJO), and UVJO. The upper-pole ureter is “abnormal”
of imaging in the diagnosis and follow-up of renal in- and ectopic (Weigert-Meyer rule). The ectopic ureter in-
volvement is to search for complications such as hemor- serts medially and inferiorly to the normal ureteral ori-
rhage or urolithiasis. Specifically, an important role for fice, usually in the bladder. In girls, the ectopic ureter
US is the detection of hepatic-biliary complications. may insert below the bladder base, into the urethra or the
vagina. A vaginal ectopic ureter can cause constant uri-
Key Points nary dribbling in girls and incontinence [9]. In boys, ec-
topic ureters never terminate below the urinary sphincter
– Renal cystic diseases can be diagnosed in the perinatal and thus never result in incontinence; however, the ureter
period or in later childhood. can terminate in Wolffian duct derivatives, including the
seminal vesicals and vas deferens. Very rarely, three com- sent with intermittent pain from intermittent obstruction,
pletely or incompletely separated ureters form, resulting with hydronephrosis only evident during obstruction. To
in ureteral triplication [10]. be correctly diagnosed, these children must be imaged at
Ectopic ureters are often obstructed but rarely reflux. If the time of their painful episodes [13].
the ectopic ureter inserts into the urethra at the level of the The conundrum of UPJO is that we are still unable to
urinary sphincter, urinary flow is obstructed or refluxes predict whether the degree of obstruction and thus its
depending whether the sphincter is closed or open [11]. The eventual effects on renal function will improve or worsen
more distal the ureteral insertion, the more dysplastic and over time. US is routinely used to describe the degree of
dysfunctional the associated renal parenchyma. Ectopic obstruction and the appearance of the renal parenchyma.
ureters, and all the associated abnormalities, can also occur However, functional imaging studies, primarily MAG-3
in single-system kidneys (single ectopic ureter) [12]. studies with Lasix (MAG-3/Lasix renogram) and MR
A ureterocele is the dilated submucosal terminal urography, are used to help quantify the degree of ob-
segment of the ureter. It is associated with varying de- struction and the contributing function of each kidney.
grees of ureteral obstruction and subsequent dilatation An obstruction of the distal ureter as it enters into the
of the renal pelvis and calyces. In girls, ureteroceles are bladder results in UVJO. Most such cases are primary
most commonly seen in association with ectopic upper- and due to a ureteral obstruction, although secondary
pole ureters. In boys, they are most commonly associat- UVJO can occur with an abnormally thickened bladder.
ed with single-system kidneys and are orthotopic. The insertion of the obstructed ureter may be orthotopic
Although ureteroceles protrude into the bladder, when (primary mega-ureter) or ectopic. An orthotopic or ec-
the intravesical pressure equals that of the ureterocele, topic ureterocele may also be associated with obstruc-
the ureterocele can flatten and become imperceptible tion. Primary mega-ureter accounts for the majority of
(efface). When the intravesical pressure exceeds that of the cases of UVJO. In most patients with this condition,
the ureterocele, the latter everts or intussuscepts into its the degree of dilatation improves over time [14] such
ureter. Ectopic bladder-neck ureteroceles or large simple that surgical repair is required only for a minority of af-
ureteroceles can prolapse into the urethra and cause fected patients. Surgery is indicated if the degree of di-
bladder outlet obstruction. latation worsens, renal function is impaired, or the ob-
struction is thought to be contributing to stasis and UT
Key Points infections.
– Renal ectopia is due to abnormalities in the normal as- Key Points

cent of the kidney.
– Ureteral duplication may be incomplete (more com- – Ureteropelvic junction obstruction is the most com-
mon) or complete. mon cause of urinary tract obstruction.
– The Weigert-Meyer rule states that the upper-pole – Most cases of ureterovesical junction obstruction im-
ureter of a duplex kidney inserts ectopically, medially, prove with time.
and inferiorly to the orthotopic location.
– The lower-pole ureter is the analogue of the single-sys-
tem kidney. Voiding Abnormalities and Secondary Vesicoureteric
Reflux
Urinary Tract Obstruction Children with lower-spine abnormalities may have detrusor-
sphincter dysynergia, in which the bladder contracts but
Urinary tract obstructions occur at three main areas: the the urinary sphincter does not relax during voiding, re-
ureteropelvic junction, the ureterovesical junction, and sulting in chronic obstruction of the bladder outlet. The
the bladder outlet (i.e., the urethra). Rarely, the mid- uncoordinated voiding causes urinary retention, in-
ureter can be obstructed by webs, fibrosis, or compres- creased bladder pressures, secondary VUR, and sec-
sion from the inferior vena cava, or there may be ob- ondary UVJO. Similarly, children with voiding dysfunc-
struction at the level of the infundibula in the kidney. On tion without a neurogenic cause can also develop sec-
US, the normal hypoechoic medullary pyramids seen ondary reflux.
routinely in infancy and childhood should not be con- Urethral obstruction can occur in the posterior or an-
fused with dilated calyces or a sign of obstruction. terior urethra in boys whereas the urethra is rarely ob-
The most common congenital obstruction of the kid- structed in girls. Posterior urethral valve obstruction is
ney is UPJO, which is due to a stenosis at the junction of the most common congenital urethral obstruction and is
the renal pelvis and proximal ureter. Since most children caused by an obstructing membrane just below the level
are now diagnosed prenatally and followed postnatally, of the verumontanum. Anterior urethral obstruction is
they rarely present with symptoms and signs of obstruc- most commonly due to traumatic strictures and mostly lo-
tion, such as infection, pain, or renal stones. Some chil- cated in the bulbar urethra. Anterior urethral valves or di-
dren have UPJO due to a crossing renal artery and pre- verticula are rare. Depending on the severity of the ob-
struction, the portion of the urethra proximal to the ob- nephronia mimics a tumor in appearance and thus must
struction may be dilated, the bladder wall may be hyper- always be considered in the differential diagnosis of a re-
trophied, and secondary reflux and UVJO may occur. In nal mass.
circumcised boys, meatal stenosis is another cause of ure- If the renal mass is bilateral, the appearance and clin-
thral obstruction. Retrograde urethrogram under fluo- ical presentation are extremely helpful in predicting the
roscopy or ultrasound is the best way of studying the an- histology. If there are multiple large masses and the kid-
terior urethra whereas the posterior urethra can only be neys are also enlarged, bilateral nephrogenic rests due to
studied during voiding. nephroblastomatosis are most likely. Nephrogenic rests
are remnant fetal renal tissue that never fully matured. As
Key Points they have a high propensity to develop into Wilms’ tu-
mors, these masses need frequent surveillance. If the
– Voiding dysfunction can lead to vesicoureteral reflux. masses are partially echogenic, angiomyolipoma should
– Most obstructions of the bladder outlet in boys are be considered, especially if the patient has tuberous scle-
congenital (e.g., posterior and anterior urethral valves) rosis. Wilms’ tumors, lymphoma, and infections may al-
or post-traumatic (bulbar urethral stricture). so be bilateral.
Solitary simple cysts are much less commonly seen in
children than in adults. Calyceal diverticula may appear
Renal Masses in Children as simple cysts but they actually communicate with the
adjacent calyx and can become superinfected. Delayed
Once a mass is established to be intrarenal, its histology intravenous pyelogram, CT, or MR imaging, which show
can be predicted based on its appearance and on the pa- contrast within the cyst, is able to distinguish calyceal di-
tient’s age. Most intrarenal masses occurring in the new- verticula from simple cysts. If there are multiple simple
born period are benign. Although rare, the most common cysts, especially in enlarged kidneys, ADPKD should be
solid intrarenal mass seen in newborns is a mesoblastic considered.
nephroma [15]. These large, solid, enhancing masses are
benign, although the cellular subtype is the most aggres- Key Points
sive and can cause paraneoplastic syndromes. These must
be removed but the prognosis is excellent. – Most newborn renal masses are benign.
In the newborn, the most frequently occurring cystic – The most common renal malignancy in toddlers is
abnormality of the kidney is multicystic dysplasic kid- Wilms’ tumor.
ney, which can involve the entire kidney or be segmen- – Focal pyelonephritis mimics renal tumors.
tal. The condition is due to a congenital abnormality of
the kidney in which the collecting system forms as cysts,
and the renal parenchyma is dysplastic and non- Imaging Renal Failure in Children
functional. Multicystic dysplasic kidney is now com-
monly diagnosed in utero. Over time, the cyst fluid Introduction
resorbs and a tiny nub of tissue remains. These are typi-
cally treated non-surgically. Ultrasound plays a central role in pediatric imaging, par-
The most common renal mass in toddlers is Wilms’ tu- ticularly in pediatric nephrology, in which it helps to dif-
mor. Children with aniridia, WAGR (Wilms’ tumor, ferentiate between the etiologies of renal failure. For
aniridia, genitourinary abnormalities, and mental retarda- some diseases, the US pattern will be specific, while for
tion), Deny-Drash syndrome, Beckwith-Weidemann syn- others there will be little or no parenchymal changes. The
drome, hemihypertrophy, or nephroblastomatosis are pre- US evaluation should therefore be very meticulous and
disposed to developing this tumor. Wilms’ tumor is a sol- correlated to the biological and clinical data [18-20].
id, cystic, and often hemorrhagic mass and is far more
common but radiographically indistinguishable from ei- Sonographic Technique
ther clear cell sarcoma or malignant rhabdoid tumor.
However, if a tumor has a large subcapsular hematoma, Renal US has to be carried out with the highest-resolu-
and if there are brain metastases, malignant rhabdoid tu- tion transducers, depending on the patient’s size. The use
mor should be considered [16]. Centrally located multi- of both curved and linear transducers is essential. US
locular masses of the kidney may be a multilocular cys- studies include measurements of the kidneys and of any
tic nephroma, which is more common in boys in child- dilatation as well as the evaluation of renal echogenicity
hood and in women in adult life [17]. (cysts? calcifications?) and CMD. Doppler analysis also
In children over 11 years of age, renal cell carcinoma must be performed. In case of UT dilatation, the cause
becomes more common than Wilms’ tumor, although the and level of obstruction must be determined, including
likelihood of either tumor is extremely rare [18]. It is cru- the bladder, within the field of investigation. It might be
cial to confirm that the child has no clinical indicators of of interest in some patients to evaluate the liver, spleen,
UT infection, because focal pyelonephritis or lobar and biliary tract, too.
Acute Renal Failure after birth. The most common form of CNS is the Finnish
type. Proteinuria starts in utero and the placenta is thick-
Acute renal failure (ARF) is defined as urine production ened. On US, at birth, the kidneys are swollen and
<1 mg/kg/day. Its causes can be pre-renal, renal, or post- hyperechoic; CMD is present but the pyramids are
renal in origin. In the case of ARF of renal origin, US is irregular and within weeks they will “disappear”.
often diagnostic. Other causes of CNS include diffuse mesangial scle-
rosis (DMS), which can be part of the Drash syndrome
Hemolytic Uremic Syndrome (DMS, genital anomalies, and a risk for Wilms’ tumor).
In some patients, CNSs evolve toward end-stage renal
Hemolytic microangiopathic anemia, thrombocytopenia, disease and necessitate renal transplantation.
and ARF occurring together constitute hemolytic uremic
syndrome, which is the commonest cause of ARF in the Syndromes Affecting the Tubules and Metabolic Diseases
United States and in several European countries, espe-
cially in young infants. Renal diseases that include a primary and secondary
During the acute phase of the disease, the US appear- tubulopathy are numerous. Hypercalciuria is a constant
ance of the renal cortex is markedly hyperechoic, with in- finding and may lead to nephrocalcinosis, which is easi-
creased CMD. On Doppler analysis, there is no diastolic ly detected by US. For instance, type 1 primitive hyper-
flow, which correlates well with the lack of urine pro- oxaluria is seen as strikingly hyperechoic kidneys already
duction. The return of the diastolic wave indicates a re- at birth and results in urolithiasis.
turn to normal diuresis. Other organs may be involved as
well, including the gallbladder and digestive tract. Key Points
Medullary or Cortical Necrosis, Shock Kidneys – US is the key imaging examination in children with
acute or chronic renal failure.
Medullary and cortical necrosis in the neonate results – The etiologies of renal failure are numerous.
from a lack of renal perfusion. On US, the cortex in cor- – The US patterns will orient the diagnosis.
tical necrosis first appears hyperechoic, then shrinks, and
finally calcifies. In medullary necrosis, calcifications de-
velop within the medulla. Urinary Tract Infection
Renal Vein Thrombosis Introduction
While largely a neonatal disease, renal vein thrombosis Urinary tract infection is one of the commonest bacterial
may occur already in utero. When both renal veins are in- diseases in children: 5% of girls and 0.5% of boys will
volved, the condition is associated with ARF. On US, the suffer at least one episode. Despite numerous studies and
kidneys appear enlarged, CMD is absent, and hyper- publications, the role of imaging is controversial. The
echoic streaks are demonstrated in the interlobar areas. main challenges of imaging are to identify patients with
complicated UT infection, those with an underlying
Obstructive Uropathies cause, and those at risk for recurrence [21-23].
Imaging may be done at the time of diagnosis of an
Anuria and ARF may follow ureterocele prolapse within the acute episode, or during treatment, or in a late assess-
urethra, obstruction of a single renal system, tumoral en- ment. No single imaging technique allows complete eval-
trapment of the ureters, or bilateral obstructive urolithiasis. uation of the UT; instead, the use of each one must be op-
timized to obtain the maximum amount of information in
Chronic Renal Failure association with the lowest morbidity.
Chronic renal failure (CRF) is defined as a glomerular Imaging Acute Pyelonephritis

filtration rate <50 mL/min/1.73 m2/kidney. One of the
most common causes of CRF is renal hypodysplasia. On The main role of conventional US is to diagnose any as-
US, the kidneys are small, CMD absent, and small cysts sociated malformative uropathy and/or the complications
can be visualized. (abscess) of a UT infection. Color Doppler US may pro-
vide significant additional information regarding the de-
Renal Cystic Diseases (see above) gree of renal insult. The gold standard examination for
the diagnosis of renal lesions during an acute episode (as
Congenital Nephrotic Syndromes well as for the detection of scars) is DMSA scintigraphy.
CT scan with contrast enhancement is as efficient as a
Congenital nephrotic syndromes (CNSs) encompass dis- DMSA scan for the demonstration of acute renal lesions.
eases in which there is massive proteinuria occurring Its drawbacks are the radiation hazard and the need for
contrast injection. MR imaging has great potential to de- infection of the urine in a dilated urinary tract. Suspicion
tect renal inflammatory lesions and provides information of this diagnosis should prompt a diagnostic and thera-
on renal parenchyma status as well as on UT morpholo- peutic nephrostomy.
gy. In addition, it may clarify ultrasound findings. MCU
is an essential complementary examination for patients Late Complications of UT Infection
with UT infections, as there may be associated reflux in
as many as 40% of cases. Therefore, the technique is gen- The development of renal scars is the long-term risk of
erally advocated in case of UT infections to look for VUR untreated acute pyelonephritis. Patients with renal scars
and voiding dysfunction. However, MCU is an invasive are at risk for developing renal hypertension, complica-
technique and irradiation is a drawback. tions during pregnancy, and renal failure. Presently,
DMSA scintigraphy is the gold standard method for the
Proposed Work-Up diagnosis of scars, if performed at a time sufficiently
removed from the acute episode.
Based on these considerations, it is important to identify Xanthogranulomatous pyelonephritis is an atypical
among patients with clinical suspicion of acute chronic infectious renal lesion. It may appear as a tumor
pyelonephritis those who need an imaging work-up. or diffusely. CT is the best imaging modality.
Clearly, newborn boys and school-aged girls are groups
at risk. Still, it is impossible to define why certain pa- Key Points
tients will develop renal involvement and in which of
these patients the disease will recur. Therefore, every pa- – Imaging of UT infections is controversial.
tient with a UT infection should undergo imaging evalu- – The aim is to detect groups at risk, renal involvement,
ation albeit tailored and optimized to his/her condition. A and risks for recurrence.
work-up protocol is summarized in Fig. 2. – US Doppler, DMSA scintigraphy, and MCU form the
basis of the imaging work-up.
Complications of Acute Pyelonephritis
Renal abscess is the typical complication of delayed or Imaging Urolithiasis in Children

non-adapted treatment. Lesions are demonstrated by US,
although further, cross-sectional imaging (CT scan or Introduction
MR) is occasionally useful. Pyonephrosis corresponds to
Urolithiasis is less common in children than in adults
(1 child for every 20,000 adults). It is more frequent in
certain geographic areas. Hematuria and pain are the pre-
US + Doppler senting symptoms in about half of the patients whereas
the disease is asymptomatic and an incidental finding in
20% of patients. A familial history is frequent and ac-
counts for over 50% of patients. Metabolic disorders and
UT infections are common etiologies [24, 25].
Normal Abnormal The work-up of a patient with urolithiasis includes uri-
nalysis, blood tests, and genetic analysis, looking for fa-
voring diseases or infections. Imaging must be applied sys-
tematically, starting with US and using a tailored decision-
making process for additional imaging modalities [25].
DMSA APN
Imaging
Ultrasound, with its entire spectrum of optimized tech-

niques, is the ideal primary imaging modality in children
Normal Abnormal VCUG
(Fig. 3). It allows reliable demonstration of the kidneys
and urinary tract and is useful in diagnosis as well as in
post-therapeutic follow-up. On US, urolithiasis manifests
as either nephrocalcinosis or lithiasis. In nephrocalci-
nosis, echogenic deposits in the pyramids lead to a re-
Stop versed CMD. Nephrocalcinosis should be differentiated
from other causes of echogenic pyramids. Lithiasis is eas-
Fig. 2. Proposed imaging workflow for a child with a urinary tract
infection. US, Ultrasound; APN, Acute Pyelonephritis; DMSA, ily demonstrated within the dilated renal upper cavities
Tc-99m(V) Dimercaptosuccinic acid; VCUG, Voiding Cysto- and at the ureterovesical junction. It has the same ap-
urethrography pearance as in adults.
US (gray scale + DDS/CDS)
US inconclusive
negative + low negative + high
clinical suspicion or non-diagnostic
clinical suspicion positive mismatch US & clinics
only secondary signs

+ no stone visible,
or before intervention, if
therapeutically necessary
Fig. 3. Imaging algorithm for infants and chil- Stop
dren with suspected urolithiasis [7]. CDS,
Color Doppler Sonography (power Doppler); follow-up after/during treatment uro-CT x1
(ultra-)low dose + unenhanced x2
ce-VUS, contrast-enhanced Voiding Uroso- potentially + KUB for
nography; (uro-)CT, (urinary tract) CT; DD, confirmation, for treatment needs … + KUB (± IVU) before intervention / lithotripsy
Differential Diagnosis; DDS, Duplex
Doppler Sonography; KUB, Kidney-Ureter-
Bladder film; IVU, Intravenous Urography; x1
or KUB (+ adapted IVU, particularly if low-dose CT unavailable)
MRU, Magnetic Resonance Urography; US, x2
Ultrasound potentially contrast-enhanced CT-urography, if other DD or complication; MRU in selected cases
Some kidney diseases have a specific, characteristic 3. Grattan-Smith JD, Jones RA (2008) MR urography: technique
pattern, such as primary hyperoxaluria type 1. A plain and results for the evaluation of urinary obstruction in the
pediatric population, Magn Reson Imaging Clin N Am 16:
film of the abdomen may be necessary for the proper 643-660
demonstration of the stone prior to treatment. 4. Thomsen HS (2007) ESUR guideline: gadolinium-based con-
Tailored intravenous urography is still used by some trast media and nephrogenic systemic fibrosis Eur Radiol
clinicians to demonstrate the morphology of the UT, es- 17:692-2696
pecially if CT is not available. Furthermore, CT is much 5. Passerotti C, Chow JS, Silva A et al (2009) Ultrasound versus
computed tomography for evaluating urolithaisis. J Urol
less frequently used than in adults. It serves as a comple- 182:1829-1841
mentary tool in case of a non-diagnostic US examination 6. Riccabona M, Avni FE, Blickman JG et al (2008) Imaging
or prior to treatment. The radiation dose must be mini- recommandations in pediatric uroradiology (Part 1). Pediatr
mized and optimally adapted to the child’s size [5, 26]. Radiol 38:138-145
7. Riccabona M, Avni FE, Blickman JG et al (2009) Imaging rec-
ommendations in pediatric uroradiology (Part 2). Pediatr Ra-
Treatment diol 39:891-898
8. De Bruyn R, Marks SD (2008) Post-natal investigations of fe-
The treatment of urolithiasis should aim to avoid or cor- tal renal disease. Semin Fetal Neonatal Med 13:133-141
rect conditions that have led to the disease. If the lithia- 9. Carrico C, Lebowitz RL (1998) Incontinence due to an infra-
sphincteric ectopic ureter: why the delay in diagnosis and what
sis cannot be medically eliminated, more interventional the radiologist can do about it, Pediatric Radiology 28:942-949
treatments will be needed. For example, extracorporeal 10. Gill RD (1952) Triplication of the ureter and renal pelvis. J
lithotripsy, the primary treatment approach in adults, has Urol 140:147
been adapted to children as well. However, in selected 11. Wyly JB, Lebowitz RL (1984) Refluxing urethral ectopic
cases surgery will be unavoidable. ureters: recognition by the cyclic voidng cystourethrogram.
AJR 142:1263-1267
12. Prewitt LH, Lebowitz RL (1976) The single ectopic ureter.
Key Points AJR 127:941-948
13. Rooks VJ, Lebowitz RL (2001) Extrinsic ureteropelvic junc-
– Urolithiasis is less frequent in children. tion obstruction from a crossing renal vessel: demography and
– An etiology is more often detected than in adults. imaging. Pediatr Radiol 31:120-124
14. Shukla AR, Cooper J, Patel RP et al (2005) Prenatally detect-
– US is the main imaging modality. ed primary meagureter: a role for extended follow-up. J Urol
173:1353-1356
15. Chaudry G, Perez-Ataude AR, Ngan BY et al (2009) Imaging
References of congenital mesoblastic nephroma wath pathological corre-
lation. Pediatr Radiol 39:1080-1086
1. Brenner DJ, Elliston CD, Hall EJ, Berdon WE (2001) Estimat- 16. Eftekhari F, Erly WK, Jaffe N (1990) Malignant rhabdoid
ed risks of radiation-induced fatal cancer from pediatric CT. tumor of the kidney: imaging features in two cases. Pediatric
AJR Am J Roentgenol 176:289-296 Radiol 21:39-42
2. Ripolles T, Puig J (2009) Actualización del uso de contrastes 17. Boggs LK, Kimmelstiel P (1956) Benign multilocular cystic
en ecografía. Revisión de las guias clinicas de la Federación nephroma: report of two cases of so-called multilocular cyst of
Europea de Ecografía, Radiología 51:362-375 the kidney. J Urol 76:530-541
18. Estrada CR, Sthar AM, Eaton SH et al (2005) Renal cell car- 23. Lee M, Lin C, Huang F et al (2009) Screening young children
cinoma: Childrens Hospital Boston experience. Urology 66: with a first febrile UTI for high grade VUR with renal US
1296-1300 scanning and Technecium-99m-labelled DMSA. J Pediatr
19. Wedekin M, Ehrich JH, Offner G, Pape L (2008) Aetiology 154:797-802
and outcomes of acute and chronic renal failure in infants. 24. Ajdinovic B, Jaukovic L, Krstic Z, Dopuda M (2008) Impact
Nephrol Dial Transplant 23:1575-1580 of MCU and DMSA renal scintigraphy on the investigation
20. Ardissimo G, Dacco V, Testa S et al (2003) Epidemiology of CRF schema in children with UTI. Ann Nucl Med 22:661-665
in children: data of the Ital Kid Project. Pediatrics 111:382-387 25. Hoppe B, Kemper MJ (2008) Diagnostic examination of the
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J Roentgen 192:1197-1208 pediatric nephrourolithiasis. AJR 192:143-149
IDKD 2010-2013
Integrated Imaging in Genitourinary Oncology: PET/CT Imaging

Gerald Antoch
Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen,
University at Duisburg-Essen, Essen, Germany
Introduction mors to highly aggressive tumors with rapid growth and

distant metastases. Although different radionuclides have
Malignant tumors are the second most common cause of been proposed, none has evolved as “the” radionuclide
death in the western world [1]. Based on the assumption for the imaging of prostate cancer.
that patients’ prognoses can be improved by the adoption The uptake of one such agent, fluorodeoxyglucose
of stage-adapted therapy, accurate clinical and radiologi- (FDG), was shown in different studies to be increased in
cal tumor staging must be considered as essential when poorly differentiated prostate cancers associated with
assessing primary tumors and recurrent disease. In addi- high Gleason scores or high prostate-specific antigen
tion, different imaging procedures are used for therapy (PSA) levels. However, well-differentiated prostate can-
response assessment in patients undergoing treatment for cers frequently do not demonstrate an increase in gluco-
malignant disease. For both, tumor staging and therapy lysis, with negative FDG-PET scans as a consequence.
response assessment, morphological and functional Therefore, a positive FDG-PET scan may add relevant in-
imaging procedures are available; however, these have formation to morphology alone, when assessing the
well-known limitations in their diagnostic accuracy. pelvis for potential metastases, but a negative FDG-PET
Computed tomography (CT), magnetic resonance imag- scan has to be interpreted with caution. In addition, even
ing (MRI), and ultrasound (US) provide mainly morpho- in FDG-PET-positive tumors, urinary excretion of the ra-
logical information on the tumor and its potential metas- dionuclide may limit the diagnostic accuracy with regard
tases, but the lack of functional data has been shown to to assessment of the primary tumor and its potential
hamper accurate assessment of local lymph node in- infiltration into adjacent organs, such as the seminal
volvement [2, 3]. Therapy response assessment is mainly vesicles. Based on its high soft-tissue contrast MRI has
based on lesion size, which nonetheless has been shown become the modality of choice for imaging the primary
to be an insensitive indicator of response, at least in the tumor. Its use is further supported by the fact that poorly
initial phase of tumor treatment. The functional data pro- differentiated prostate cancers, benign hyperplasia, and
vided by positron emission tomography (PET) are known prostatitis show substantial overlap in FDG uptake.
to be more sensitive and specific than morphological da- The limitations of FDG in imaging prostate cancer
ta and to complement the latter in the assessment of lo- have led to the introduction of alternative radionuclides
cal lymph node involvement by malignant tumors [4-6]. for prostate imaging, shifting the focus away from glu-
Similarly, when PET and PET/CT are used to assess ther- colysis to cell-membrane turnover. Accordingly, choline
apy response, they have been found to offer earlier and has become the most commonly used radionuclide in
more reliable response assessment than achieved based prostate imaging. Choline is involved in transmembrane
on morphology alone. signaling and phospholipid synthesis in cell membranes.
This review summarizes the applications of PET and Different malignant tumors show substantial increases in
PET/CT imaging in different genitourinary tumors. The choline kinase activity, resulting in an increase in mem-
indications and diagnostic accuracies of integrated brane phospholipids. Thus, tracers such as 11C-choline or
18F-choline can estimate the proliferative potential of a
PET/CT are discussed and the different radionuclides
used in this type of imaging are addressed. tumor by detecting membrane lipid synthesis [8]. An
advantage of 18F-choline over 11C-choline is its longer
half-life and better image quality due to an increase in
Prostate Cancer spatial resolution, which is a consequence of the shorter
positron range of 18F. However, the urinary excretion of
18F-choline is higher than that of 11C-choline, which has
Prostate cancer is the most common malignancy in men
[7]. The disease is characterized by a widely variable bi- been attributed to incomplete tubular reabsorption of the
ological behavior which ranges from clinically silent tu- former. Regardless, compared with FDG, both tracers
184 Gerald Antoch
have the advantage of reduced urinary excretion with less endorectal coil [9]. However, its high soft-tissue contrast
interpretive issues caused by radioactive urine. There and the availability of MR-spectroscopy favor MRI as the
have been reports on the use of 11C-choline in primary tu- imaging method of choice for lesion localization within the
mor assessment and in localization of the primary tumor prostate gland. The main indication for 11C-choline or
within the prostate in patients with negative or unclear 18F-choline is detection of tumor recurrence in patients
findings on biopsy. Some studies have even reported a with rising PSA levels and negative findings on CT
higher accuracy for lesion localization than MRI using an or MRI after treatment of prostate cancer (Figs. 1, 2).
a b
Fig. 1 a-c. CT, 18F-choline-PET, and 18F-choline-PET/CT of a retroperitoneal lymph

node in a patient with an increase in the PSA after radical prostatectomy. Un-
remarkable lymph node on CT (a) diagnosed as metastasis on PET (b) and PET/CT
(c) based on increased choline uptake
a b c
Fig. 2 a-c. a CT, b 18F-choline-PET, and c 18F-

choline-PET/CT of a patient with prostate
cancer and a bone metastasis in the sacrum
Integrated Imaging in Genitourinary Oncology: PET/CT Imaging 185
In selected patients undergoing diagnosis of prostate can- Testicular Cancer

cer, both radionuclides may be used for initial tumor stag-
ing. For tumor recurrence, the detection rate of 11C-choline In testicular cancer, FDG-PET and FDG-PET/CT can be
is reportedly as high as 50% in patients with negative find- used for initial tumor staging, treatment monitoring, and
ings on morphological imaging procedures [10]. However, the detection of recurrent disease. The advantage of
many authors have reported that 11C-choline detection rates these modalities in tumor staging has been demonstrat-
depend upon the PSA level of the patient, with rising PSA ed in patients in whom CT alone indicated stage II dis-
levels paralleling an increase in tumor detection. Most in- ease (lymph node metastases) based on the detection of
stitutions schedule PET at PSA levels of at least >1 ng/mL. morphologically enlarged lymph nodes. Integration of
Other radionuclides include 11C-acetate, 18F-tes - FDG-PET into the staging algorithm may prevent false-
tosterone, and 11C-methionine. The mechanism of positive CT findings in this setting by demonstrating
11C-acetate uptake by malignant cells is lipid synthesis. PET-negativity within such lymph nodes [12]. Nonethe-
Thus, acetate accumulation has been attributed to an less, upstaging of not enlarged, CT-negative lymph
increase in fatty acid synthesis in prostate cancer cells. nodes based on FDG avidity within these nodes has
Like 11C-choline, acetate is not a tumor-specific radio- been discussed controversially. FDG-PET and PET/CT
nuclide, since uptake is increased also in benign hyper- have the potential to detect sub-centimeter metastases in
plasia and prostatitis. As with 11C-choline, 11C-acetate non-enlarged nodes, but the limited spatial resolution of
has been found to be of higher diagnostic accuracy than PET leads to a decrease in sensitivity with decreasing
FDG in the detection of prostate cancer foci [11]. lymph node size (Fig. 3). In addition, in some histo-
18F-dihydrotestosterone (18FHDT) and 11C-methionine pathological types of germ cell tumors, such as mature
are further tracers that have been used occasionally in teratoma, glycolysis is not increased. Accordingly,
imaging prostate cancer. 18FHDT has affinity for the FDG-PET and PET/CT are currently not recommended
androgen receptor and can be used to test for resistance for routine use in the staging of patients with testicular
to androgen ablation therapy. 11C-methionine is a non- cancer [13, 14].
specific radionuclide for amino acid transport and pro- While CT is recommended for treatment monitoring
tein synthesis; it has been used in prostate cancer imag- in germ cell tumors, the addition of FDG-PET or
ing only infrequently. PET/CT may be helpful in patients with residual lymph
a b
Fig. 3 a-c. Retroperitoneal lymph node metastasis in a patient with seminoma. Un-
clear finding on CT (a) but increased FDG-uptake on PET (b) and PET/CT (c) in-
dicates malignancy
186 Gerald Antoch
node enlargement after therapy. In a prospective trial in- recommended for therapy response assessment in pa-
volving a series of patients with seminoma, FDG-PET tients with non-seminomatous tumors, as mature differ-
was used to differentiate viable tumor tissue from entiated teratoma typically has no or only mild FDG up-
scar/fibrosis in patients with residual masses >1 cm af- take and thus may not be reliably differentiated from scar
ter chemotherapy [15]. There were no false-positives re- tissue or fibrosis [17]. Figure 4 shows the currently rec-
ported. All cases of residual disease seen on CT as masses ommended algorithm for the diagnosis and treatment of
>3 cm and 95% of those cases in which the residual testicular germ cell tumors.
masses were <3 cm were detected correctly with FDG- FDG-PET can be used in patients with suspected re-
PET. Based on these results, FDG-PET has been recom- current disease as determined by tumor markers but with
mended in seminoma patients to assess residual masses negative CT. In this population, FDG-PET or PET/CT
seen on CT for potential residual disease. It must be em- can detect otherwise occult recurrent tumor sites, as dis-
phasized, however, that other authors [16] have reported cussed by Hain et al. [18]. In that study, although FDG-
a substantial number of false-positive findings due to in- PET was able to identify tumor recurrence more reliably
flammation after chemotherapy of seminoma. In patients than CT, FDG-PET was falsely negative in some of the
undergoing radiotherapy, the issue of inflammatory patients later diagnosed with recurrence. Therefore, close
changes or tissue regeneration may take on additional imaging follow-up must be recommended in patients
importance. FDG-PET and PET/CT are currently not with clinical signs of recurrence but negative FDG-PET.
Fig. 4. Algorithm of diagnosis and treatment of testicular germ cell tumors modified according to the current recommendations. (From [13])
Ovarian Cancer ing in ovarian cancer has been the diagnosis of recur-
rent ovarian cancer. CT has been the imaging modality
Ovarian cancer is the second most common gynecolog- of choice to localize tumor recurrence in patients with
ical malignancy and is frequently detected at advanced rising tumor markers, but may be supported with func-
tumor stages, resulting in a poor patient prognosis. Even tional data in patients with equivocal findings on CT
those patients diagnosed in an operable stage have a alone (Fig. 5). Picchio et al. [20] reported an increase
high risk of tumor recurrence postoperatively, requiring in the sensitivity for detection of ovarian cancer recur-
close patient follow-up, including the measurement of rence from 70 to 83% and an increase in the specifici-
tumor markers (mainly 125Ca) and evaluation using dif- ty from 83 to 92% when FDG-PET was added to CT.
ferent imaging procedures. While FDG-PET and Similar sensitivities and specificities were reported by
PET/CT have been used to diagnose the primary tumor Bristow et al. [21]. Based on the available literature, the
and in the differential diagnosis of ovarian cancer from role of FDG-PET and PET/CT in patients with clini-
other ovarian lesions, both imaging modalities are limit- cally suspected ovarian cancer recurrence is currently
ed in menstruating women by false-positives due to fol- limited to those patients without tumor detection on CT.
licular cysts, cystadenomas, schwannomas, endometri-
omas, or inflammation. In addition, low-grade malig-
nancies and borderline tumors may be FDG-PET-nega- Cervical Cancer
tive, resulting in false-negative findings. Thus, the re-
ported sensitivities and specificities of up to 87% [19] Cervical cancer is the third most common malignancy
must be interpreted with caution. In post-menopausal in women [7]. These tumors manifest as an aggressive
women, however, the risk of false-positive findings is local growth, and the infiltration of adjacent organs is
lower and any FDG uptake must initiate further work-up not infrequent at the time of diagnosis. Metastases of
to exclude tumor growth. cervical cancer are primarily found in locoregional lymph
CT has been the standard of care in staging patients nodes while hematogenous metastases to the lungs, liver,
with ovarian cancer pre-operatively, whereas there are or bone will be found in rather later stages of the disease.
only limited data on a potential benefit of FDG- The role of FDG-PET or FDG-PET/CT in cervical can-
PET/CT in this clinical setting and no recommendation cer has yet to be defined clearly. Although both tech-
can currently be made. The main focus of hybrid imag- niques have been used to identify the primary tumor
a b
Fig. 5 a-c. a CT detected ascites, an indirect sign of peritoneal carcinomatosis, in this

patient with rising tumor markers after therapy for ovarian cancer. b FDG-PET and
c PET/CT show increased FDG uptake inter-intestinally, confirmed as peritoneal
carcinomatosis on further follow-up
188 Gerald Antoch
a b
Fig. 6 a-c. Detection of cervical cancer in a patient with an equivocal CT (a) with
FDG-PET (b) and FDG-PET/CT (c)
(Fig. 6), diagnosis of the primary is most frequently Endometrial Cancer

achieved by Papanicolaou (PAP) test. It is generally ac-
cepted that MRI is the imaging procedure of choice The diagnosis of endometrial cancer is established from
when assessing a potential invasion of the primary tumor biopsy. Even though these tumors are typically FDG-avid,
into adjacent organs. Thus, FDG-PET/CT has not been the role of FDG-PET and PET/CT in assessment of the
used frequently to assess primary cervical tumors. Tu- primary tumor is limited due to false-positives caused by
mor staging, however, has been considered an indication normal endometrial FDG uptake, which varies according
for FDG-PET and PET/CT in cervical cancer. The re- to the endometrial cycle. If potential local invasion of the
ported sensitivities and specificities vary widely. Sironi tumor into adjacent structures needs to be assessed pre-
et al. [22] obtained promising results: a sensitivity of operatively, this is typically done with MRI, because of its
72% in lymph nodes <5 mm and 100% in those >5 mm, superior soft-tissue contrast. Despite reports on the use of
both coupled with high specificities. Nevertheless, there FDG-PET and PET/CT for staging local lymph nodes and
are more data suggesting a rather low sensitivity for de- distant organs [26], CT currently remains the imaging
tection of lymph node metastases. For FDG-PET, Wright procedure of choice for N-staging and M-staging. Further
et al. [23] reported a sensitivity of 53% for pelvic nodes data are required to define the role of hybrid imaging pro-
and an even lower sensitivity for retroperitoneal/para- cedures in endometrial cancer.
aortic lymph nodes. Even though the addition of mor-
phological data with PET/CT may be considered helpful
over PET alone, Choi et al. [24] reported similar sensi- References
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Therefore, the role of FDG-PET and FDG-PET/CT in tics 2002. CA Cancer J Clin 52:23-47
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sen based on a conventional work-up in 24% of patients. modalities (CT MRI US) in lymph node staging of head and
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IDKD 2010-2013
Integrated Imaging in Gastrointestinal Oncology: PET/CT Imaging

Thomas F. Hany
Department of Radiology, Clinic and Policlinic of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland
Introduction their presence will preclude a curative approach. Inter-

estingly, extrahepatic metastasis of HCC occurs relative-
The basic principle of positron emission tomography ly late in the clinical course and therefore does not sig-
(PET) is the use of positron-emitting-isotope-labeled nificantly shorten the survival time. Whenever the stage
pharmaceuticals that are integrated into a metabolic path- of disease allows, surgical treatment should be pursued.
way. Positron-emitting isotopes are characterized by a be- Torizuka et al. evaluated patients with known HCC by
ta plus-decay, in which a positron is emitted. This using dynamic and static FDG-PET data acquisition [2].
positron collides with and annihilates any of the many High degrees of correlation were found between the his-
shell electrons in the neighboring atoms, thereby produc- tological grade and the kinetic rate constants as well as
ing two 511-keV gamma rays (photons) which are de- hexokinase activity. There have been only a few studies
tected in coincidence by the PET scanner. The additional involving PET/CT imaging. The largest of these, by Park
integration of a computed tomography scanner (PET/CT) et al., consisted of a prospective evaluation of FDG and
11C-acetate PET/CT in the detection of primary and
allows the acquisition of PET and CT images of the pa-
tient in the same imaging session. The clinically and most metastatic hepatocellular carcinoma [3]. In an analysis
widely evaluated positron-emitting isotope labeled phar- based on biopsied lesions, the sensitivity for primary HCC
maceutical is fluorine-18 fluoro-2-deoxy-D-glucose of FDG-PET/CT was 64.4% while that of 11C-acetate
(FDG). This glucose analogue is transported into the cell PET/CT was 84.4%. The overall sensitivities of FDG,
11C-acetate, and dual-tracer PET/CT for 35 metastatic
by specific transporters and phosphorylated by hexoki-
nase to FDG-6-phosphate. As FDG-6-phosphate is inert HCCs were 85.7, 77.0, and 85.7%, respectively. The addi-
to further metabolic processing or to transmembrane tion of 11C-acetate to FDG-PET/CT increased the overall
back-transport outside the cell, it accumulates within the sensitivity for the detection of primary HCC but not for the
cells. The physical half-life of FDG is around 110 min. detection of extrahepatic metastases. FDG, 11C-acetate,
The compound is used as a metabolic marker in oncolo- and dual-tracer PET/CT had a low sensitivity for the
gy, cardiology, neurology and inflammation imaging. detection of small primary HCC, but FDG-PET/CT had a
One of the most important advantages of this imaging relatively high sensitivity for the detection of extrahepatic
technique is the extensive anatomical coverage. Thus, im- metastases of HCC. Thus, only in selected cases, in which
ages from the head to the thighs are acquired routinely, there is known moderately to poorly differentiated HCC,
allowing evaluation of the entire body. All of the current- is FDG-PET/CT useful in a pre-therapy setting to detect
ly available data indicate that PET/CT is more sensitive additional intra- or extrahepatic lesions. The same holds
and specific than either of its constituent imaging meth- true for the evaluation of recurrent disease after therapy.
ods. With PET/CT, the most relevant additional effect is
that the CT data frequently add specificity to the FDG- Cholangiocarcinoma
PET data [1].
There is limited knowledge on the use of FDG-PET or
PET/CT in the evaluation of intrahepatic cholangiocarci-
Malignant Primary Liver Tumors noma. This type of hepatic cancer is associated with pri-
mary sclerosing cholangitis. In the study by Kluge et al.,
Hepatocellular Carcinoma both the sensitivity and the specificity of FDG-PET and
PET/CT in the detection of primary lesions were >90% [4];
Hepatocellular carcinoma (HCC) is frequently multifocal however, FDG-PET showed a poor performance in the
such that at the time of exploration multiple sites in both detection of locoregional metastases. In the study by
liver lobes are involved. Pre-operative assessment should Fritscher-Ravens et al., there were several false-negatives,
include the search for extrahepatic metastases, because especially in patients with mucinous adenocarcinoma.
Integrated Imaging in Gastrointestinal Oncology: PET/CT Imaging 191
Otherwise, the same results regarding locoregional and Pancreas

distant metastases were achieved with FDG-PET and
PET/CT [5]. In the study by Petrowsky et al. [6], 61 pa- Exocrine Pancreatic Carcinoma
tients with malignancies of the biliary tract, proven by his-
tology or cytology, were evaluated by FDG-PET/CT and The staging of pancreatic cancer includes a histological
contrast-enhanced CT. PET/CT detected all gallbladder workup and proof of the typical histological features of
cancers (n = 14). Overall, 45 of 61 tumors were correctly exocrine pancreatic cancers, mostly adenocarcinoma.
identified with PET/CT (sensitivity 74%) and 40 by However, T-staging essentially is only possible by evalua-
contrast-enhanced CT scan (sensitivity 66%). All 12 distant tion of the arterial vasculature, since tumors that show in-
metastases were detected by PET/CT, but only 3 out of vasion/encasement of the celiac trunk and superior mesen-
the 12 by CT (p <0.001) (Fig. 1). The detection of extra- teric artery are unresectable (T4). The most important in-
hepatic cholangiocarcinoma was significantly lower than formation from any imaging modality is, therefore, arter-
that of intrahepatic cholangiocarcinoma for both tech- ial vascular involvement of the primary tumor, the pres-
niques; also, regional lymph node metastases were detected ence of peritoneal carcinomatosis, and the detection of
by PET/CT in only 12% of the cases and by CT in only distant metastases. Regarding the performance of
24%. PET/CT findings resulted in a change of management PET/CT, the data are thus far rather sparse. In a study by
in 17% of patients with tumors deemed resectable after Farma et al., 82 patients with assumed resectable pancre-
the standard workup. Therefore, PET/CT seems particu- atic cancer underwent staging with non-contrast-enhanced
larly valuable in detecting unsuspected distant metastases, PET/CT and contrast-enhanced CT of the chest and ab-
which are not diagnosed by standard imaging. domen [7]. The sensitivity and specificity of PET/CT in
a b e
c f
Fig. 1 a-g. A 56-year-old male patient

with a histologically proven intrahep-
atic cholangiocarcinoma. a In the
maximum intensity projection image d g
of the FDG-PET/CT, the primary tu-
mor is well demarcated, with multiple
foci of pathological uptake. In the ax-
ial images at the level of the liver
(from top to bottom: b PET contrast-
enhanced, c CT, d fused image), the
intrahepatic tumor is highly FDG
avid. In the mid-thoracic region (from
top to bottom: e PET, f contrast-en-
hanced CT, g fused image), a medi-
astinal lymph node metastasis is eas-
ily demarcated paraesophageally
192 Thomas F. Hany
diagnosing pancreatic itself cancer were 89 and 88%, re- all, a significant rate of false-negative results – with sen-
spectively. The sensitivity of detecting metastases was sitivities ranging between 50 and 78% – in the detection
61% for PET/CT, 57% for contrast-enhanced CT, and of NET (depending on the localization) has been reported
87% for the two side by side. PET/CT findings influenced [10]. PET using the catecholamine precursor 6-(fluoride-
the clinical management of seven patients (11%), all of 18)-fluoro-dopa (18F-DOPA) has been proposed as a valu-
whom had distant metastases. As a major drawback of this able imaging option for NET [11]. This tracer highlights
study, the CT component of PET/CT was not performed the tumor’s intracellular decarboxylase activity and in the
using contrast-enhanced triple-phase CT. In a study by context of PET imaging provides higher spatial resolution
Strobel et al., 50 patients with biopsy-proven pancreatic than obtained with SRS. A major drawback of 18F-DOPA
cancer (adenocarcinoma) were evaluated by integrated is its physiological uptake by normal pancreas, which in
triple-phase contrast-enhanced PET/CT regarding re- certain cases obscures detection of the primary tumor. A
spectability and overall staging [8]. The criteria for irre- rather newly developed PET tracer uses the basic princi-
sectability were distant metastases, peritoneal carcino- ple of SRS, i.e., somatostatin labeling, but with 68Ga. In a
matosis, arterial infiltration, or infiltration of neighboring study by Ambrosini et al., 18F-DOPA and 68Ga were com-
organs other than the duodenum. Histology, intraoperative pared in a rather small group of 13 patients [12]. 68Ga-
findings, and follow-up CT together with the clinical find- DOTA-NOC (tetra-azycyclododecanetetra-acetic acid-[1-
ings were used as the standard of reference. Accordingly, Nal3]-octreotide) was found to be an accurate tracer for
27 patients had unresectable disease because of distant the assessment of NETs and was better than 18F-DOPA in
metastases (n = 17), peritoneal carcinomatosis (n = 5), or the detection of primary NETs – especially those of the
local infiltration (n = 5). In the assessment of resectability, pancreas – and metastases. The authors concluded that
PET alone had a sensitivity of 100%, a specificity of 44%, since the pancreas is the most frequent site of NETs, the
an accuracy of 70%, a positive predictive value of 61%, routine use of 68Ga-DOTA-NOC is more appropriate.
and a negative predictive value of 100%; unenhanced Here, larger, comparative studies that include morpholog-
PET/CT had respective values of 100, 56, 76, 66, and ical imaging modalities are needed to determine the role
100%; the corresponding values for enhanced PET/CT of PET/CT in NETs of the pancreas.
were 96, 82, 88, 82, and 96%. In five patients, unre-
sectability was missed by all imaging methods and was
only diagnosed intraoperatively. Enhanced PET/CT was Colorectal Carcinoma
significantly superior to PET alone (p = 0.035), with a
trend for the superiority of enhanced over unenhanced In the western world, colorectal carcinoma is the most
PET/CT (p = 0.070). Based on all of these data, it is clear important cause of death due to cancer, after bronchial
that non-contrast-enhanced PET/CT is able to detect dis- carcinoma [13]. About 70% of patients have curable re-
tant metastases but not local extent in a large proportion sectable tumor at initial diagnosis and are treated with cu-
of cases. Furthermore, in a rather considerable proportion rative intent. Approximately 50% of colon cancer patients
of patients, only intraoperative findings are able to reveal will present with hepatic metastases, either at the time of
surgery-precluding factors, such as deep retroperitoneal initial diagnosis or as a result of recurrence [14]. From a
infiltration, small liver metastases, and peritoneal involve- diagnostic perspective, colon cancer and rectal cancer are
ment. It seems that the most favorable approach consists often evaluated as a single group; however, especially
of the use of intravenous contrast-enhanced CT in the deep rectal cancer has a clearly different pathway of lo-
PET/CT protocol; however, this does not reflect clinical coregional and distant metastases (Fig. 2).
practice, since most patients with a suspected pancreatic
lesion rapidly undergo contrast-enhanced CT or magnetic Initial Staging
resonance imaging (MRI) evaluation.
Two studies using FDG-PET alone for initial staging
Endocrine Pancreatic Cancer demonstrated the high sensitivity of this modality in the
detection of both primary tumor (100 and 96%) and dis-
Neuroendocrine tumors (NETs) of the pancreas account tant metastases (87 and 78%) and confirmed its low sen-
for <5% of all malignant pancreatic tumors. PET imaging sitivity (29 and 29%) in lymph node staging [15, 16]. In a
using FDG has limited value, since these tumors are often study by Veit-Haibach et al., 47 patients underwent whole-
slow-growing, with an accordingly low metabolism [9]. In body PET/CT colonography one day after colonoscopy [17].
addition to morphological imaging modalities, including Compared with optimized abdominal CT staging alone,
contrast-enhanced CT and MRI, somatostatin receptor PET/CT colonography was significantly more accurate in
scintigraphy (SRS) is used to localize and characterize defining TNM stage (difference: 22%; 95% CI: 9-36%;
NETs in general and such tumors in the pancreas in par- p = 0.003), which was mainly based on a more accurate
ticular. Nonetheless, the interpretation of SRS findings definition of the T-stage. Differences were not detected
can be challenging due to the difficulty of distinguishing for defining N-stage between PET/CT colonography and
tumor from intestinal structures and to the variable densi- CT alone with a threshold of 0.7 cm for malignant nodes
ty of somatostatin receptors on the different tumors. Over- but were detected with a threshold of 1 cm. There were no
a b
c d
Fig. 2 a-d. A 63-year-old female patient with a
histologically proven deep rectal cancer. Ax-
ial FDG-PET/CT images at the level of the
primary tumor (a PET, b contrast-enhanced
CT, c fused images) reveal the FDG-avid pri-
mary tumor as well as enlarged and FDG-
avid bilateral inguinal lymph node metas-
tases. The lymph node spread is typical for
deep rectal cancer invading the anal canal.
d The same findings are seen in the contrast-
enhanced, T1-fat suppressed MRI images
differences in defining M-stage separately or when the lesion detection rate on contrast-enhanced CT images is
accuracy of PET/CT colonography was compared to high, evaluation solely by this approach can be challeng-
that of CT + PET. PET/CT colonography affected ing because of the likelihood of inconclusive results that
consecutive therapy decisions in four patients (9%; 95% require further diagnostic evaluation (56% of our patient
CI: 2.4-20.4%) compared with conventional staging population). The reason for this is predominantly related
(CT alone and colonoscopy). Therefore, the combination to the specificity of the structural abnormalities that may
of FDG PET/CT in conjunction with a dedicated contrast- be identified by this modality. Thus, nowadays, patients
enhanced CT protocol may be of interest as a possible with inconclusive contrast-enhanced CT findings are be-
single-step staging procedure. ing frequently referred for further evaluation with
18F-FDG PET/CT. More importantly, the study of Soyka
Recurrent Disease et al. showed that in 21% of the patients with apparently
conclusive findings on contrast-enhanced CT, the addition
The standard patient workup for the detection of recur- of non-contrast-enhanced PET/CT information led to ap-
rence and metastases in colorectal cancer includes regular propriate changes in therapy. In clinical routine, however,
clinical examinations, CT scans, colonoscopy, and usual- those patients in whom contrast-enhanced CT findings
ly the measurement of tumor markers such as CEA. How- were regarded as conclusive would not routinely be re-
ever, this approach lacks specificity and may result in di- ferred for further evaluation with FDG-PET/CT. If con-
agnostic and therapeutic delays due to several pitfalls: trast-enhanced PET/CT had served as the initial imaging
1. while serological tumor markers are useful, CEA lev- modality, 65% of these patients would have had a clear
els have only a 60-70% sensitivity for the detection of benefit, including changes in management as well as in
colorectal cancer recurrence [18]; diagnostic confidence. Therefore, it could be argued that
2. the morphology based information provided by CT contrast-enhanced PET/CT should be performed as the
does not permit distinction between post-surgical first-line diagnostic tool in the re-staging of colorectal
changes and tumor recurrence nor can it detect tumor cancer. Conversely, in 35% of the patients the associated
involvement of normal-sized lymph nodes [19]; radiation exposure would be futile, in addition to the need-
3. colonoscopy is only useful in the detection of local re- less expense of the procedure. However, this analysis
currence. holds true only if contrast-enhanced CT and non-contrast-
The suitability of FDG-PET in detecting recurrence enhanced PET/CT are performed within 2-4 weeks. In re-
and metastases has been shown in several studies. While ality, surgeons generally insist on contrast-enhanced CT
there is obviously a clear advantage of PET/CT over PET studies not older than 4 weeks before taking a patient in-
alone, a dedicated contrast-enhanced CT is required often to the operating room. Thus, another additional scan with
by clinicians. The study by Soyka et al. showed that con- contrast enhancement (CT or PET/CT) would be needed
trast-enhanced PET/CT, as a single-step examination, has in the majority of patients.
the same diagnostic confidence and impact as a sequen- Post-surgical and radiotherapy changes in the small
tial approach consisting of contrast-enhanced CT followed pelvis are the most challenging for morphological im-
by non-contrast-enhanced PET/CT [20]. Although the aging studies in recurrent rectal cancer, since tumor
194 Thomas F. Hany
recurrence cannot be differentiated from benign scar tissue. evaluated by FDG-PET/CT, there are no comprehensive
In a study by Even-Sapir et al., PET/CT was used to dis- data on the use of this modality.
tinguish benign and malignant pre-sacral abnormalities. Carcinoid tumors, as malignant tumors of non-epithe-
The sensitivity, specificity, positive predictive value, and lial origin, have a similar annual incidence as adeno-
negative predictive value were 100, 96, 88, and 100%, re- carcinomas (3.8 per million people). The different sub-
spectively. PET/CT findings were clinically relevant in types have a natural behavior ranging from benign to
47% of 62 patients [21]. However, there was no compar- high-grade malignancies. Similar to NETs of the pan-
ison to other, conventional imaging studies. In our own creas, the diagnostic workup consists of nuclear medicine
study, the diagnostic value of contrast-enhanced CT and studies including SRS combined with contrast-enhanced
non-enhanced PET/CT was prospectively evaluated and CT (SPECT/CT) or 68Ga-DOTA-NOC, since >80% of
compared in 76 patients referred for pre-operative evalu- carcinoid tumors express somatostatin receptors. The
ation for liver resection for metastatic colorectal cancer detection rates are therefore similar to those of NET of
[22]. Extrahepatic disease was missed by contrast- the pancreas [12].
enhanced CT in one-third of the cases (sensitivity 64%), Gastrointestinal stromal tumors (GIST) are mesenchy-
while PET/CT failed to detect extrahepatic lesions in mal tumors that in approximately 90% of patients origi-
only 11% (sensitivity 89%; p = 0.02). New findings on nate in the stomach and small intestine. Unlike contrast-
PET/CT resulted in a change in the therapeutic strategy enhanced CT, FDG-PET is able to show early effects in
in 21% of the patients. This study also demonstrated the patients undergoing treatment with imatinib mesylate
well known limitation in PET imaging’s spatial resolution (Glivec; Novartis, Switzerland) [24]. In two recent stud-
at ~4-6 mm, since small tumors (<5 mm) were often not ies, it was shown that patients without FDG uptake after
detected. Also, in patients who had received chemothera- the start of treatment had a better prognosis than patients
py within the month prior to PET/CT there was a high in- with residual activity not demonstrated with contrast-
cidence of false-negative results. This effect, however, enhanced CT [17, 25]. Furthermore, lesions were better
might be used as a predictor of success in neoadjuvant defined on PET/CT than by PET and CT performed side-
chemotherapy before resection. In summary, the above- by-side. This is relevant information for clinical decision-
described studies clearly illustrate the advantages of making.
PET/CT imaging in colorectal cancer.
Conclusions
Stomach and Small Bowel
In the work-up of several abdominal malignancies of the
Gastric Cancer gastrointestinal tract, FDG-PET/CT imaging is becoming
increasingly well established. Its main advantage lies in
In a review by Dassen et al. regarding the pre-operative the comprehensive evaluation of the patient, including all
diagnostic utility of FDG-PET/CT in gastric cancer, the body compartments, and therefore in the detection of piv-
authors concluded, that FDG-PET has no role in the pri- otal, therapy-deciding lesions. In the evaluation of prima-
mary detection of gastric cancer due to its low sensitivi- ry liver tumors (cholangiocarcinoma and poorly differen-
ty [23]. FDG-PET, however, is slightly better than CT in tiated HCC), FDG-PET/CT offers high sensitivity in the
the evaluation of lymph node metastases in gastric cancer detection of distant metastases. Secondary liver tumors,
and therefore might have a role in pre-operative staging. such as metastases from the gastrointestinal tract, are de-
Improvements in accuracy could be achieved by using tected by FDG-PET/CT at a high rate, making this imag-
PET/CT or PET tracers other than FDG, but these strate- ing technology a primary tool in the evaluation of patients
gies need further investigation. Nonetheless, FDG-PET is with suspicion of recurrent colon cancer. Further, full in-
able to adequately detect therapy responders at an early tegration of contrast-enhanced CT protocols improves di-
stage following neoadjuvant chemotherapy. agnostic confidence and reduces the sometimes cumber-
some diagnostic pathway for patients. New tracers such as
Small Bowel 68Ga-DOTA-TATE or 18F-DOPA will bring significantly
improved diagnostic confidence in the notoriously diffi-

Adenocarcinoma of the small bowel comprises a group of cult evaluation of patients with neuroendocrine tumors.
rare tumors, with an annual incidence of around 3.7 per
million people. The pathological (development from ade-
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33:1271-1274 PET, CT and in-line PET/CT in patients with gastrointestinal
14. Clarke MP, Kane RA, Steele G Jr et al (1989) Prospective com- stromal tumours: long-term outcome of treatment with ima-
parison of preoperative imaging and intraoperative ultrasono- tinib mesylate. Comparison of PET, CT, and dual-modality
graphy in the detection of liver tumors. Surgery 106:849-855 PET/CT imaging for monitoring of imatinib (STI571) therapy
15. Abdel-Nabi H, Doerr RJ, Lamonica DM et al (1998) Staging in patients with gastrointestinal stromal tumors. Eur J Nucl
of primary colorectal carcinomas with fluorine-18 fluoro- Med Mol Imaging 4:4
NUCLEAR MEDICINE SATELLITE COURSE
“DIAMOND”
IDKD 2010-2013
Lymphoma: Diagnostic and Therapeutic Applications

of Radiopharmaceuticals
Angelika Bischof Delaloye
Service de Médecine Nucléaire, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Introduction considered [5, 6]. Subtypes of MALT lymphomas in par-

ticular have different uptake patterns. Most patients with
Lymphoma is a heterogeneous family of diseases of the MALT in which there is plasmacytic differentiation show
lymphatic system. There are two main entities, Hodgkin’s FDG uptake whereas uptake is much less consistent in
disease (HD) and non-Hodgkin’s lymphoma (NHL), the typical MALT [7]. Besides histological subtype, location
latter emerging either from B cells or T cells. Positron is another factor that determines uptake patterns. Accord-
emission tomography (PET) with 18F-fluorodeoxyglu- ingly, the sensitivity of FDG-PET is lower in gastric
cose (FDG) assisted by in-line CT (PET/CT) plays a piv- (25-39%) than in non-gastric MALT (46-75%) [8, 9].
otal role in patient management. HD shows high FDG Gastric and extragastric MALT lymphomas frequently
uptake in close to 100% of the patients whereas FDG present as multifocal disease that is associated with chro-
avidity greatly varies among patients with NHL subtypes. mosomal translocations or trisomy 18. Dissemination be-
Aggressive lymphomas, such as diffuse large B cell lym- yond the gastrointestinal tract occurs in about 10% of pa-
phoma (DLBCL), the most current form of NHL, and tients with gastric MALT while significantly more pa-
mantle cell lymphomas (MCL) as well as Burkitt lym- tients (close to 50%) with extragastric MALT tend to pre-
phomas and even plasmocytomas take up FDG very avid- sent with involvement of other MALT organs [9].
ly. Follicular lymphomas (FL) also show high uptake in Involvement of the gastrointestinal tract occurs in
more than 90% of the cases whereas extranodal margin- 10-30% of patients with NHL. The affected sites, in de-
al zone lymphomas (MZL), such as splenic or mucosa- creasing order of frequency, are the stomach, small bow-
associated lymphoid tissue (MALT) MZL, are positive in el, large bowel, and esophagus. The appearance of these
only 67 and 54%, respectively [1]. tumors varies – from polypoidal masses to wall thicken-
It has been stipulated that the intensity of FDG uptake ing, diffuse or focal infiltrations, ulcerations, and some-
is an expression of disease aggressiveness [2-4]. This is times solitary or multiple nodules or extension from
probably true, at least partially, but is not really important mesenteric nodes – and therefore so do the FDG uptake
in clinical practice. In fact, a great number of FL, with no patterns [4, 5]. The occurrence of normally increased up-
signs of transformation, show high FDG uptake despite be- take in the gastrointestinal tract or of non-lymphomatous
ing considered indolent. The intensity of FDG uptake can pathological conditions further complicates the diagnosis
therefore not be reliably used for diagnosing transforma- with FDG-PET [5, 6, 10].
tion in FL. Due to possible inconsistencies of uptake in- Primary colorectal lymphomas are rare, representing
tensity versus aggressiveness and the great diversity of 10-20% of gastrointestinal lymphomas and 0.2-0.6% of
NHL, thorough histopathological characterization is nec- all large bowel malignancies. They are usually FDG-avid
essary to determine the most appropriate treatment B cell lymphomas, with the most common sites being the
scheme. This step cannot be replaced by FDG-PET studies. cecum and rectosigmoid [11].
Focal lesions in the liver are frequently observed in pa-
tients with NHL. Civardi et al. studied the prevalence, clin-
Particularities of Abdominal Lymphoma ical significance, and role of hepatitis C virus (HCV) in-
fection in a population of 414 consecutive patients with
Lymphomas of the abdomen and pelvis most often simply NHL [12] and 129 focal liver lesions, 76 detected at dis-
correspond to subdiaphragmatic nodal involvement by ease onset and 53 during follow-up. The prevalence of fo-
one of the most frequent lymphoma types (Hodgkin’s dis- cal liver involvement by NHL at disease onset was 7%.
ease, DLBCL, FL), usually characterized by high FDG Among the focal liver lesions detected at diagnosis,
uptake. However, in the abdomen other types, such as 30 (39%) were due to lymphoma. In addition, ten cases
nodal and extranodal MZL, including MALT lymphomas, of focal liver disease due to other malignancies were
with much less consistently increased uptake need to be found, seven hepatocellular carcinomas (HCC), and three
200 Angelika Bischof Delaloye
metastases of another tumor. Of the focal liver lesions, courses (chemo- or immunochemotherapy). There are a
58% were benign. Conversely, at follow-up, 74% of the consistent number of publications showing that early con-
liver lesions were due to NHL and 15% to another malig- version to a negative FDG-PET scan, irrespective of the
nancy. Focal liver lesions were more often the result of un- presence of residual masses on CT, indicates a much
derlying disease (26%) in patients with aggressive lym- more favorable outcome than in patients showing persis-
phoma than in those with indolent lymphoma (4%). The tent FDG uptake in their lymphomatous lesions [15-19].
incidence of focal lesions was similar in HCV-negative and This observation has led to the establishment of new re-
HCV-positive patients, whereas HCC only occurred in the sponse criteria (Table 1); these were originally meant to
latter group. be used as surrogate markers for clinical trials only but
Another particular form of abdominal lymphoma is are currently also applied in daily patient management
enteropathy-associated T cell lymphoma, which is seen in [20-22]. This classification not only eliminates the CRu
patients with refractory celiac disease. FDG-PET has (complete response unconfirmed) category but these
been shown to be superior to CT alone in detecting en- combined criteria provide a more accurate response clas-
teropathy-associated lymphoma as well as its distant sification than International Workshop Criteria (IWC)
spread [13]. Finally, post-transplant lymphoproliferative criteria alone. Indeed, in a multivariate analysis, it repre-
disorders (PTLD) need to be mentioned. Immuno- sented the only significant independent predictor of pro-
suppression is an important risk factor in the develop- gression free survival (PFS) [22]. Interestingly, the pre-
ment of PTLD. The WHO has classified PTLD into mor- dictive power of early FDG-PET (after 2-3 treatment
phological categories: early lesions, polymorphic PTLD, courses) is higher than that of end of treatment PET. This
or monomorphic PTLD (various types of B and T cell suggests that the early disappearance of FDG uptake is
lymphomas), Hodgkin’s lymphoma, and Hodgkin’s- related to the chemosensitivity of the tumor whereas end
lymphoma-like PTLD. The risk that a transplant patient of treatment FDG-PET more likely indicates the presence
will develop lymphoma over a 10-year period is 11.8 or absence of viable tumor cells [23]. Figure 1 shows two
times greater than in the general population. Early lesions FDG-PET scans (MIP, maximal intensity projection) of a
are most often seen in children and young adults and oc- patient with AIDS-related lymphoma; the first, acquired
cur within the first year of transplantation while the other after the patient had completed chemotherapy, shows
types appear later, post-transplantation [14]. PTLD is the residual uptake in the stomach and spleen. The patient was
most common malignancy observed in children after treated by more aggressive chemotherapy and splenectomy,
transplantation. Overall, it has been observed in up to neither of which could hinder the fulgurating progression
2.3% of kidney transplants, 2.8% of liver transplants, of the disease, as shown on the second scan.
6.3% of heart transplants, and 20% of small bowel trans- The IWC criteria include assessment by contrast-
plants. The clinical presentation is similar to that of nonenhanced CT, which is usually performed at diagnosis.
transplant-related lymphomas (lymphadenopathy, fever, The discussion about the necessity of a full diagnostic CT
weight loss, abdominal pain, splenomegaly). PTLD usu- at response assessment is not entirely closed. Most
ally involves extranodal sites, in particular the gastroin- authors tend to agree, however, that contrast-enhanced
testinal tract, and the allograft itself. Treatment consists CT is not necessary as a routine procedure but may be
of modifying the immunosuppression regimen, chemo- helpful in special cases, such as in the characterization of
therapy, and immunotherapy, alone or in combination. small nodes when FDG uptake is difficult to estimate
Adoptive T cell immunotherapy is under investigation. because of partial-volume effects [24, 25].
Indications of FDG-PET/CT Table 1. Response criteria based on International Workshop Criteria

(IWC) and FDG-PET
FDG-PET is indicated in the staging, response assess-
IWC+PET response Criteria
ment, and re-staging of lymphoma. At diagnosis, the as-
sessment of FDG avidity is probably more important than ACR CR, CRu, PR, or SD (IWC)
the mere staging that is usually performed based on con- PET negative
BM negative if positive prior therapy
trast enhanced CT. FDG-PET only occasionally leads to
upstaging, by revealing distant sites of involvement in pa- PR CR, CRu, or PR (IWC)
PET positive
tients with stage I or II Hodgkin’s lymphoma or NHL, and
SD SD (IWC)
therefore to management changes. In advanced disease, PET positive
upstaging is less relevant, as the same first-line treatment PD PD (IWC)
is usually administered in stage III and IV disease. PET positive corresponding to CT
abnormality
Response Assessment
PET, Positron emission tomography; CR, complete response; CRu,
complete response unconfirmed; PR, partial response; SD, sudden
The most important indication is assessment of the pa- death; BM, bone marrow; PD, progressive disease; CT, computed
tient’s response to therapy already after a few treatment tomography
Lymphoma: Diagnostic and Therapeutic Applications of Radiopharmaceuticals 201
a b IHP Criteria of Visual FDG-PET Interpretation
• PET is considered positive in case of focal or diffuse

FDG uptake above background in a region where no
physiological uptake should occur.
• Mild and diffusely increased FDG uptake at the site of
a residual mass >2 cm in diameter regardless of local-
ization, with an intensity less than mediastinal blood
pool structures, is considered negative.
• With respect to partial volume effect, uptake above
surrounding background in residual masses <2 cm or
in normal lymph nodes should be considered positive.
• New lung nodules >1.5 cm in a patient with no evi-
dence of lymphoma before therapy should be consid-
ered positive for lymphoma only if their uptake ex-
ceeds that of mediastinal blood pool, except in patients
in whom a complete response is determined in all
known lymphoma sites. In such patients, these “new
lung lesions” most often correspond to infectious or
inflammatory changes.
Fig. 1 a, b. A 41-year-old patient after chemotherapy for AIDS-relat-
• Residual hepatic or splenic lesions >1.5 cm should be
ed diffuse large B cell lymphoma. a Partial response with residual considered positive if their uptake exceeds that of liv-
uptake in the stomach and splenomegaly. b Progression 4 months er or spleen, respectively, and negative if their uptake
later, after intensification of chemotherapy and splenectomy is equal or lower than that of the surrounding organ.
Diffusely increased splenic uptake (> normal liver) is
compatible with splenic involvement except <10 days
after treatment with cytokines, namely, granulocyte-
A main difficulty, however, remains: the definition of colony stimulating factors [29].
FDG-PET negativity. An independent nuclear medicine • Clearly increased (multi)focal bone marrow uptake
evaluation of the Eastern Cooperative Oncology Group should be considered positive for lymphoma but needs
(ECOG) revealed only moderate reproducibility of the in- to be compared to baseline PET (multifocal involve-
terpretation of interim FDG-PET scans [26]. Some faint ment?). Diffusely increased bone marrow uptake is usu-
diffuse uptake may persist in residual masses and is due ally due to bone marrow stimulation and should not be
merely to the presence of these masses, without neces- considered as indicating lymphoma.
sarily being indicative of viable tumors. It may, however, These criteria were essentially developed for patients
be difficult to call such a site FDG-negative. For this rea- with Hodgkin’s lymphoma or aggressive NHL, in which
son, Mikhaeel et al. proposed an intermediate category, a management change in patients who did not respond
minimal residual uptake (MRU) [17]. In a series of 121 or only partially responded to first-line therapy might
patients with aggressive lymphoma, a 5-year PFS of 89, improve outcome. Persistence of FDG-uptake in most
59, and 16% was observed for patients with no, minimal, cases points to therapy-resistant disease, with a high re-
and positive residual uptake, respectively, after therapy. currence rate and reduced PFS (10-50% at 1 year com-
However, this additional category is not widely used; in- pared with 79-100% in FDG-PET responders) [30, 31].
stead, in most reports the results have been designated as However, it remains uncertain whether more aggressive
negative or positive. An International Harmonization Pro- treatment administered at an earlier time point (after 2-3
ject (IHP) was convened to discuss the standardization of first-line treatment courses) will be able to improve out-
clinical-trial parameters in lymphoma based on consen- come to a greater extent than achieved when such treat-
sus recommendations derived from the published PET lit- ment is given at first clinical relapse or as consolidation
erature and the collective expertise of its members [27]. at the end of first-line therapy. Several trials are currently
These experts recommended visual assessment for deter- under way to study this essential question but no definite
mining PET positivity/negativity. Others could show that response is available so far. On the contrary, the absence
a reduction of the maximum SUV (standardized uptake of residual FDG uptake has a high negative predictive
value) by 65.7% allowed better separation of patients value in patients with aggressive NHL as well as in those
with improved event-free survival (EFS) (2-year EFS: 21 with Hodgkin’s disease [31, 32]. Therefore, it may well
vs. 79% in the groups with ≤65.7% >SUVmax decrease, be possible to reduce the number of treatment courses
respectively) than achieved with visual analysis (2-year and/or involved field irradiation in excellent responders
EFS: 51 vs. 79% in the PET-positive and PET-negative in order to avoid late side effects, such as other organ
groups, respectively), mainly by characterizing indeter- tumors (increased incidence of unilateral and bilateral
minate uptake as negative [28]. breast cancer in female patients previously treated for
mediastinal Hodgkin’s disease), or the increased inci- Pharma, Germany) to controls followed-up by watchful
dence of heart, mainly coronary artery disease. waiting, median PFS was 2 years longer in treated pa-
In patients with primary gastric lymphoma, DLBCL, tients [41]. Consequently, the indication of consolidation
or MALT MZL, persistent FDG uptake is not necessari- has been added by most medical regulatory agencies
ly a sign of residual lymphoma. In a study of 24 patients (FDA, EMEA, Swissmedic). Figure 2 shows the whole-
examined using FDG-PET and endoscopy at follow-up body scan obtained with 111In-ibritumomab tiuxetan
after treatment, 11 patients with ulcerative or mucosal le- (Zevalin) 3 days after injection in a patient who underwent
sions on endoscopy showed residual FDG uptake while first-line chemotherapy for FL and who was considered
no lymphoma cells were evidenced by histopathology [4]. to be in partial remission according to IWC criteria. Radio-
immunoscintigraphy clearly shows uptake in residual
tumor sites of the abdomen. After radioimmunotherapy,
Pitfalls in Interpretation this patient achieved CR, including molecular remission,
which has been ongoing for more than 6 years.
In addition, to those already mentioned above (faint up- It is also interesting that a significant dose-efficiency
take in residual masses, inflammatory changes in treated relationship between the dose delivered to the whole
lesions and lung infiltrates, bone marrow stimulation, body and bone marrow and PFS has been observed. This
normal stomach and bowel uptake, urinary tract activity) finding underlines the importance of further refining
all other well known pitfalls have to be considered dosimetry to improve the overall success of radionuclide
(brown adipose tissue uptake, thymic rebound, granulo- therapy [42]. Additional studies are necessary to evaluate
matous disease, muscle/bone uptake, contaminations, the respective roles of consolidation with Zevalin and
etc.). A noteworthy situation may be found in patients maintenance with non-labeled antibodies such as ritux-
treated with immuno-chemotherapy, in whom prolonged imab.
recruitment of inflammatory cells to the tumor may oc- Furthermore, available data suggest that radioimmuno-
cur. In vaccination trials, increased FDG uptake in re- therapy, associated with high-dose chemotherapy, can
sponding tumors was also observed and must be consid- be successfully used in conditioning before autologous
ered a favorable sign of response to treatment. stem cell transplantation (ASCT). The data reported
so far regarding reduced-intensity conditioning before al-
logeneic stem cell transplantation have also indicated
Radioimmunotherapy of Lymphomas
Radiolabeled antibodies directed against the surface anti-
gens CD20 (tositumomab, ibritumomab tiuxetan) and
CD22 (epratuzomab) of B cells have successfully been
used for the treatment of relapsing/resistant NHL, for first-
line treatment as well as for consolidation after first-line
chemotherapy [33-36]. In prior trials, the usual end point
was defined as response to treatment (complete, CR, or par-
tial, PR), with higher response rates, including CR, observed
with radiolabeled than with unlabeled antibodies [36].
Higher response rates were observed in patients with FL
but have also been reported for other, more aggressive
types of lymphoma, such as DLBCL and MCL, as well as
in transformed FL. Radioimmunotherapy is usually well Fig. 2. Anterior whole-body scan
tolerated, the only major side effects are related to bone obtained 3 days after injection
marrow depression, which appears later than with conven- of 111Indium-tositumomab tiux-
tional chemotherapy and is marked by a nadir 5-8 weeks etan (Zevalin) in a patient who
underwent first-line chemother-
after treatment. However bone marrow depression is most apy for follicular non-Hodgkin’s
often easily managed. The incidence of myelodysplastic lymphoma. According to the In-
syndrome/acute myeloid leukemia (MDS/AML) is compa- ternational Workshop Criteria
rable to that observed with conventional chemotherapies, classification, this patient was
in particular those containing anthracyclines. In patients in partial remission. The scan
clearly shows uptake of the la-
achieving CR, very long PFS times have been noted beled antibody in the residual
[37-39]. Thus, it can be expected that a subgroup of pa- abdominal mass. Consolidation
tients with advanced FL, a disease considered incurable with 90Yttrium-ibritumomab tiu-
today, might eventually be cured by a combined approach xetan (Zevalin) allowed her to
achieve complete remission, in-
of chemo(immuno)therapy and radioimmunotherapy [40]. cluding molecular remission,
In a recent randomized trial comparing consolidation which has been ongoing for
with 90Y-ibritumomab tiuxetan (Zevalin, Bayer Schering more than 6 years
Lymphoma: Diagnostic and Therapeutic Applications of Radiopharmaceuticals 203
positive results. There is also evidence that radioimmuno- 12. Civardi G, Vallisa D, Berte R et al (2002) Focal liver lesions in
therapy combined with ASCT can improve clinical out- non-Hodgkin’s lymphoma: investigation of their prevalence,
clinical significance and the role of Hepatitis C virus infection.
come (fewer relapses) without added toxicity; this thera- Eur J Cancer 38:2382-2387
peutic strategy therefore represents a very interesting 13. Hadithi M, Mallant M, Oudejans J et al (2006) 18F-FDG PET
treatment option for elderly patients, who account for the versus CT for the detection of enteropathy-associated T-cell lym-
majority of the NHL population [43]. phoma in refractory celiac disease. J Nucl Med 47:1622-1677
14. Zafar SY, Howell DN, Gockerman JP (2008) Malignancy after
solid organ transplantation: an overview. Oncologist 13:769-778
15. Hutchings M, Loft A, Hansen M et al (2006) FDG-PET after two
Conclusions cycles of chemotherapy predicts treatment failure and progres-
sion-free survival in Hodgkin’s lymphoma. Blood 107:52-59
Nuclear medicine plays a pivotal role in the management 16. Jerusalem G, Beguin Y, Fassotte MF et al (2000) Persistent tu-
mor 18F-FDG uptake after a few cycles of polychemotherapy
of patients with Hodgkin’s and NHL, particularly by al- is predictive of treatment failure in non-Hodgkin’s lymphoma.
lowing response assessment at an early stage of treatment Haematologica 85:613-618
(2-3 courses). The results have high prognostic implica- 17. Mikhaeel NG, Hutchings M, Fields PA et al (2005) FDG-PET
tions, with complete metabolic responders having a high- after two to three cycles of chemotherapy predicts progression-
ly significant better outcome than non-responders. free and overall survival in high-grade non-Hodgkin’s lym-
phoma. Ann Oncol 16:1514-1523
Radioimmunotherapy using labeled anti-CD20 anti- 18. Mikhaeel NG, Timothy AR, O’Doherty MJ et al (2000) 18-
bodies combined with chemo(immuno)therapy seems to FDG-PET as a prognostic indicator in the treatment of ag-
represent an efficient treatment option, allowing progressive Non-Hodgkin’s Lymphoma-comparison with CT.
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19. Spaepen K, Stroobants S, Dupont P et al (2002) Early restag-
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and indolent non-Hodgkin’s lymphoma: response assessment
by integrated international workshop criteria. Leuk Lymphoma
48:1522-1530
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20:2453-2463 Suppl 2:41-51
IDKD 2010-2013
Conventional Nuclear Medicine in the Evaluation of Gastrointestinal

and Genitourinary Tract Disorders
Ariane Boubaker
Service de Médecine Nucléaire, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Introduction of 150 to 200 MBq of Tc-99m pertechnetate with lemon

juice given at 15 min, allowing studying both the extrac-
Conventional nuclear medicine investigations of the tion and secretion phase. Quantitative parameters (capta-
gastrointestinal (GI) tract are not commonly performed in tion index, extraction ratio) are helpful to confirm low
routine clinical practice, although prevalence of disorders parenchymal extraction.
affecting the upper gastrointestinal tract is quite high
ranging from 15% to 40% in European countries. Most Esophageal Transit
diagnostic tests used to differentiate organic from nonor-
ganic cause are invasive (endoscopy, manometry, pH Esophageal transit scintigraphy is useful for the diagno-
monitoring) and may be not well tolerated by some sis and evaluation of response to treatment for achalasia,
patients. Radionuclide procedures are non-invasive and sclerodermia, esophageal spasm, or dysfunction due to
allow characterizing functional and motility abnormalities gastroesophageal reflux disease (GERD) [1-3]. The pa-
of the esophagus and stomach. They are easy to perform, tient can be examined in sitting or supine position: po-
widely available and deliver low radiation burden to the sition and gravity will affect the transit-time, the upright
patient at low cost. Despite the lack of standardization, position being more physiologic. Having the patient ly-
both esophageal transit studies and gastric emptying ing supine may increase the sensitivity of the procedure.
scintigraphy have shown excellent diagnostic results and The patient must have been fasting for at least 3 hours
are helpful complementary tools for the clinician at before examination. He should practice first with un-
diagnosis and/or follow-up after surgery or conservative labeled liquid to avoid false-positive abnormal transit by
management. moistening the esophageal mucosa, and get used to the
Conventional nuclear medicine investigations of the test. Esophageal motility varies with viscosity and volume
urinary system are part of the daily routine clinical prac- of the bolus: the ejection force of the pharynx is sufficient
tice and procedures are well established and standardized, to propel a liquid from mouth to stomach, whereas a
being a common investigation in children with congeni- semisolid bolus requires more peristalsis from the two
tal abnormalities and/or recurrent urinary tract infections. lower thirds of the esophagus, thus increasing the sensi-
In adults, dynamic renal scintigraphy with/without ACE tivity of the test. A large field of view cameras is used to
inhibitor is useful to detect haemodynamically significant image the entire esophagus including mouth and stom-
renal artery stenosis in patients with suspicion of reno- ach. If anterior and posterior projections cannot be ac-
vascular hypertension. Preoperative assessment of renal quired simultaneously, the anterior projection should be
function (hydronephrosis, live kidney donor, renal tumor) preferred. The typical procedure consists of a high-rate
and follow-up of renal transplanted patients are also dynamic acquisition (0.5 s/frame for 2 min) started just
common indications. before swallowing of 10-20 mL of orange juice contain-
ing 5-10 MBq of 99mTc-sulfur colloids, or any radio-
pharmaceutical not absorbed by the gastrointestinal
Gastrointestinal Tract tract. Both activity and volume have to be adjusted when
examining children. Qualitative evaluation should be
Salivary Glands done in cine mode to identify abnormal pattern such as
oral/pharyngeal retention, bolus fragmentation, tracheal
The main indication to perform salivary-gland scintigra- aspiration and gastroesophageal reflux. Esophageal
phy is xerostomia and suspicion of Sjögren disease. It transit time is quantified by drawing ROIs encompass-
may help the clinician in assessing parenchymal dys- ing the upper, middle and lower third of the esophagus
function due to inflammatory disease and/or fibrosis. A and the stomach. Normal transit time (>10% activity has
30-minute dynamic acquisition is started after injection cleared from esophagus) is <15 s.
206 Ariane Boubaker
Gastroesophageal Reflux Disease Once a standardized protocol has been defined, normal
results should be determined by each centre. Solid GES
Clinical presentation of GERD differs considerably in is generally affected first, being more sensitive for the di-
children when compared to adults [4-6]. In adults, the agnosis than the liquid GES. Liquid emptying is rapid,
main symptom is heartburn. Common manifestations of begins immediately after ingestion without any lag phase,
reflux in children include respiratory symptoms and and the normal clearance curve pattern is exponential
failure to thrive. Gastroesophageal reflux (GER) is (normal half-emptying <20 minutes). A normal solid
physiologic in infants and resolves spontaneously at 7- gastric emptying is characterized by an initial lag-phase
9 months of age, a clinically important reflux being gen- with no emptying (normal 5-25 minutes), during which
erally evident by 2 months of age. Serious complica- the solid material is converted into chime by acids and
tions of GERD may be esophagitis, bleeding, perfora- mechanical grinding, followed by a linear constant-rate
tion, Barrett’s esophagus, cancer, stricture or recurrent clearance. 99mTc-sulfur colloids are used because they are
pulmonary infections/asthma. The radionuclide method not absorbed in the gastrointestinal system. The meal
is the most sensitive non-invasive diagnostic test to de- should be labeled by cooking the radiopharmaceutical
tect GER. Because esophageal transit time is an impor- with proteins (i.e., egg albumin) to avoid elution from the
tant factor that may maintain or facilitate GER, the pro- solid to the liquid phase which would result in erro-
cedure should include an esophageal transit scintigra- neously shortened GE. After a fast of 4 hours, the patient
phy if possible. Half of the liquid (milk, water, or orange must eat the meal within 10-15 min and be positioned im-
juice) is labeled with 1 MBq 99mTc-sulfur colloids/kg mediately after the end of the meal. The use of simulta-
(minimum 3 MBq), the other half is used to wash radio- neous antero-posterior projections using a double-headed
activity from mouth and esophagus and to complete camera will allow correcting for movements and geomet-
the feeding. In case of dual phase study (liquid and sol- ric variations in counting. The total duration of the study
id), one third of the total activity to be administered is is 3 h. Images should be displayed to describe the pro-
used for the liquid, and two thirds to label the solid gression of the solid within the different portions of the
(eggs). The child/patient is placed supine with the cam- stomach and the time of activity appearance in the duo-
era in the back with stomach and mouth in the field of denum. Additional events like gastroesophageal reflux,
view. A 30- to 60-min dynamic acquisition at a rate of retention in esophagus/hiatal hernia should be described
5-10 sec/frame is recommended. A high sensitivity col- (Fig. 1). A time activity curve is generated using ROIs
limator should be used to increase the sensitivity of the and 50% emptying time is calculated.
test. In older children and adults, GER can be provoked
by an increased abdominal pressure (cough, Valsalva Gastrointestinal Bleeding
maneuver). Data should be analyzed in cine mode in or-
der to describe the importance and frequency of the re- Lower GI bleeding accounts for one third of all acute
flux. GER can be quantified as a fraction of total initial bleeding events, is more frequent in men, and increases in
gastric activity and/or an overall reflux index. The study incidence with age with a mortality of about 4% [12]. The
should be completed by 5-minute anteroposterior im- most common cause of acute lower bleeding is diverticu-
ages of the thorax to look for possible aspiration. If neg- losis, followed by angiodysplasia. Because GI bleeding is
ative, 10-15 min additional views of the thorax should often intermittent and possibly occurs at a slow rate,
be repeated at 2 and 24 h [7]. scintigraphy is particularly suitable for the accurate
diagnosis having the ability to detect bleeding flow rates
Gastric Emptying Scintigraphy <0.1 mL/min. 99mTc-sulfur colloids can be used to local-
ize the source of bleeding if it occurs during the first
Both rapid and delayed gastric emptying (GE) can cause minute after injection. Scintigraphy with 99mTc labeled
the same symptoms [8]. Causes of rapid GE are post- red blood cells (RBCs) is the best method in patients with
operative (pyloroplasty, hemigastrectomy), functional intermittent, low rate GI bleeding and has been proven to
dyspepsia, hyperthyroidism and Zollinger-Ellison syn- be superior to barium enema, angiography, computer
drome. Gastroparesis is defined as a delayed gastric emp- tomography (CT) scan and even colonic endoscopy in this
tying without mechanical outlet obstruction. The most clinical setting [13]. It is recommended to use the in vitro
common causes are diabetes, post-surgical and idiopathic. labeled RBC to minimize elution of 99mTc from the RBCs,
The true prevalence of gastroparesis is unknown (around thus avoiding false-positive results due to secretion of free
5%), women being affected more frequently (4:1, females: pertechnetate by the kidneys, and gastric and colonic mu-
males) [9]. Gastric emptying scintigraphy (GES) is con- cosa [14]. Scintigraphy gives the possibility to perform
sidered as the reference method as it is simple, largely successive acquisitions till 24 h after injection and contin-
available and non-invasive and provides reproducible uous monitoring if bleeding does not occur during the ini-
results of GE measurement [10]. Major efforts have been tial acquisition period. Single photon emission CT
made to standardize the procedure because the GE rate is (SPECT) or SPECT/CT may help to localize the bleeding
influenced by the volume and meal content, patient’s con- site. The diagnosis is made by detection of an extravasation
dition and position, as well as drug interference [11]. site of RBCs that increases with time. Both anterograde
Conventional Nuclear Medicine in the Evaluation of Gastrointestinal and Genitourinary Tract Disorders 207
a 6’ 7’ 8’ 9’ 10’
26’ 27’ 28’ 29’ 30’
Fig. 1 a-c. Solid gastric emp-

tying scintigraphy per- b
formed in a 69-year-old
woman presenting signs
and symptoms of gastro-
paresis (early satiety, bloat-
ing and post-prandial ab- 1h 1.5h 2h 3h
dominal fullness). a Con-
secutive 1-minute posterior
projections showing gastro-
esophageal reflux at 6-7
and 28-30 min. b Anterior
and posterior images at 1 h, c 100
1.5 h, 2 h and 3 h after in-
Gastric emptying (%)
gestion of the 99mTc la-

beled solid meal reveal re- 80
tention in the fundus and
body of the stomach. c The
time-activity curve correct- 60
ed for radioactive decay
confirms a delayed gastric 40
emptying with a dediffer-
entiation of the initial lag-
phase when compared to 20
normal values (dashed lines 60 120 180
representing ± 1 SD) Time (min)
and retrograde movements may occur in the intestinal lu- histamine type-2 (H2) receptor antagonists (cimetidine,
men (Fig. 2). Dynamic imaging is essential to correctly ranitidine) have been used to increase the sensitivity of the
identify the active source of bleeding. Colonic bleeding is test [16]. Pentagastrin is administered subcutaneous 15-20
seen at the periphery of the abdomen whereas bleeding in min prior to scintigraphy (6 μg/kg) to increase the uptake
the small intestine is more central with rapid visualisation 99mTcO – by the gastric mucosa; H receptor blockers in-
4 2
of curvilinear progression of the activity. crease the uptake in the mucosa by blocking the secretion
from the cells to the lumen; ranitidine (2 mg/kg in children,
Meckel’s Diverticulum and Heterotopic Gastric Mucosa 150 mg in adults) should be preferred to cimetidine be-
cause it has fewer side-effects. Glucagon relaxes the
99mTc pertechnetate (99mTcO4–) scintigraphy has been used smooth muscle of the gastrointestinal system and decreas-
since the 70s to diagnose heterotopic gastric mucosa es peristalsis (50-6 μg/kg intravenous 10 min after
[12-15]. Mucin-secreting cells of the stomach and proximal 99mTcO – injection). Omeprazole is a proton pump in-
4
small bowel are responsible for the uptake and secretion of hibitor which has been also reported to increase the sensi-
99mTcO – via the NIS (sodium iodide symporter system). tivity of the MD scintigraphy. Patient should be fasting for
4
Unexplained gastrointestinal bleeding and/or recurrent ab- 3-4 hours, and barium enema studies should not be
dominal pain are the main indication to perform 99mTcO4– performed during the 3-4 days prior to scintigraphy. The
scintigraphy to look for Meckel’s diverticulum (MD) or camera is positioned in anterior projection with stomach
heterotopic gastric mucosa (HGM). The prevalence of MD and bladder in the field of view. A 60×60 sec/frame
in the general population is estimated to be 1-4%, with dynamic acquisition is started after injection of 2 MBq/kg
HGM being present in about 50% of MD. Reported sensi- (10-150 MBq) of 99mTcO4– and additional static views
tivity of scintigraphy range from 50% to 92% and phar- (post void, erect, oblique, SPECT) are obtained. A bladder
macological preparation with pentagastrin, glucagon, or full of non-radioactive urine prior to injection of the
208 Ariane Boubaker
15” 30” 45” 1’ 1’15”
16’ 45’ 1h20’ 1h45’ 2h05’
Fig. 2 a, b. 99mTc labeled red blood cells (RBCs) bleeding scintigraphy performed in a 71-year-old woman presenting acute lower gastroin-
testinal bleeding. Colonic endoscopy performed two days before scintigraphy did not allow localizing the source of active bleeding. a Ini-
tial dynamic acquisition started immediately after injection of 920 MBq of 99mTc-RBCs shows a diffuse activity in the periphery of the ab-
domen (arrow) at 45 sec that increases with time. b Consecutive anterior static views show both anterograde and retrograde progression of
the activity in the transverse and sigmoid colon confirming the left descending colon to be the source of active bleeding
radiopharmaceutical may delay the renal excretion of derivatives, the most commonly used being mebrofenin
pertechnetate in the urinary tract and avoid false-positive (Bridatec, GE Healthcare, The Netherlands) [17, 18]. Af-
results during the dynamic acquisition. The diagnostic cri- ter intravenous injection, the radiopharmaceutical is
terion for HGM is the appearance of a focal uptake of rapidly extracted at the vascular pole of the hepatocyte
99mTcO – at the same time as the gastric mucosa (Fig. 3). and secreted at the biliary pole of the cell. Although not
4
MD is usually seen as a focal increased activity in the peri- frequently performed in clinical routine practice, HBS
toneal cavity most frequently in the right lower part of the may be useful in a variety of clinical situations. In neonates
abdomen. Pitfalls in interpretation and causes for false- past the age of 2 weeks with persistent jaundice and
positive and false-negative results are listed in Table 1. hyperbilirubinemia, HBS may be used to distinguish the
treatable causes of hepatitis (hypothyroidism, sepsis,
Protein-Losing Enteropathy panhypopituitarism, galactosemia) from extrahepatic
biliary atresia, as early surgery performed before the age
An excessive loss of protein in the gastrointestinal system of 2 months offers a better prognosis. The child has to fast
may be due to lymphatic obstruction (intestinal lym- for at least 2 hours before injection and should receive a
phangiectasia, cirrhosis), inflammatory bowel disease phenobarbital pre-treatment (5 mg/kg/day) 3 to 5 days
(Crohn’s disease, ulcerative colitis) gastrointestinal ma- before HBS in order to stimulate excretion of the radio-
lignancy (gastric cancer, lymphoma) and increased per- pharmaceutical and avoid false-negative results. A dynamic
meability (celiac disease, infections). Serial abdominal acquisition of 60×1 min/frame in anterior projection is
images acquired after intravenous injection of 99mTc la- started immediately after intravenous injection of 2-7
beled human serum albumin may show tracer extravasa- MBq 99mTc-mebrofenin/kg (minimal recommended
tion and accumulation in the intestine helping to localize activity 20 MBq), with consecutive static views per-
the site of excessive loss of protein. formed at 2, 4, 6 and 24 hours. A normal HBS includes
a rapid extraction in the liver with no significant cardiac
Hepatobiliary Scintigraphy blood-pool activity at 5-10 minutes post injection and
the visualization of activity in the small bowel at 60
Hepatobiliary scintigraphy (HBS) is an imaging tech- minutes. In the neonate the intrahepatic main bile ducts
nique performed using 99mTc labeled iminodiacetic acids are usually not seen. The diagnostic value of HBS relies
1’ 2’ 3’ 4’
Fig. 3 a, b. Meckel’s divertic- 5’ 6’ 7’ 8’

ulum scintigraphy perform-
ed in a 2-year-old child 24 b
hours after a first episode
of acute gastrointestinal
bleeding. a Initial dynamic
acquisition demonstrates a
focus of activity in the low-
er left quadrant of the ab-
domen that appears simul-
taneously to gastric mucosa
(arrows). b Left and right
lateral and antero-posterior
static views obtained 1 hour
after injection of 60 MBq of
99mTc-pertechnetate show
persistent focal uptake high-
ly suggestive of a Meckel’s
diverticulum containing
gastric mucosa as the
source of acute gastroin-
testinal bleeding
Table 1. Pitfalls and sources of error in the interpretation of Meckel’s on its high-negative predictive value in case of free
diverticulum scintigraphy excretion in the small bowel, whereas an absence of
False-negative results intestinal activity at 24 hours is not specific for biliary
1. Procedures atresia and may be due to other causes of hepatocellular
Barium studies (3-4 days prior to scintigraphy) dysfunction. Pitfalls in interpretation are mostly related
Administration of potassium perchlorate (thyroid blocade) to the urinary excretion of the tracer, posterior projec-
2. Anatomical causes
Ischemia, necrosis, ulceration tion or SPECT (SPECT/CT) being helpful to avoid
Lack of heteropic gastric mucosa false-positive results. Reported sensitivity and speci-
Obscured by urinary tract or full stomach ficity of HBS for the diagnosis of biliary atresia are 83
False-positive results to 100%, 33 to 100%, respectively [19]. The gold stan-
1. Procedures dard is liver biopsy with a sensitivity of 89-99% and a
Endoscopy
Laxative specificity of 83-98%. Common indications for HBS in
2. Anatomical causes adults are acute cholecystitis, biliary leak/extravasation
Urinary tract activity (hydronephrosis, ectopic kidney, bladder after surgery and follow-up after liver transplantation. A
diverticulum) normal HBS is characterized by a diffuse activity in the
Small bowel obstruction (intussusception, volvulus)
Neoplasm (carcinoid, lymphoma, colic adenocarcinoma)
liver beginning 6-8 s after spleen and kidneys (75% of
Inflammation (Crohn’s disease, appendicitis, peptic ulcer) blood supply to the liver supported by the portal vein),
Other site of heterotopic gastric mucosa (duplication, Barrett’s a rapid blood pool clearance (5-10 min), visualization of
esophagus) common bile duct and gallbladder 10-30 min after in-
Vascular abnormalities (angiodysplasia, hemangioma, aneurysm) jection. Transit from the biliary ducts to the small bowel
210 Ariane Boubaker
occurs within 30-45 min. Non-visualization of the gall- Unilateral hydronephrosis due to pelviureteric junction
bladder is a diagnostic criteria for acute cholecystitis, but stenosis is the most frequent congenital malformation. It
may be related to an insufficient (<2 h) or too long (>24 h) is a benign disease that will spontaneously regress in up
fasting period, bile duct obstruction and severe hepatocel- to 70% of the cases, and surgery should be done in se-
lular dysfunction. A partial biliary obstruction may be sus- lected children with renal function deterioration and/or
pected in case of delayed biliary to bowel transit beyond 60 complications (recurrent abdominal pain, infections)
min: other causes are opiates drugs, chronic cholecystitis, [21]. Diuretic renography using tubular tracers (99mTc-
dysfunction of the sphincter of Oddi. Some medications MAG3, 123I-hippuran) is up to now the only non-invasive
are known to decrease gallbladder contraction and should diagnostic modality that gives crucial information on re-
be interrupted before HBS: morphine, atropine, nifedipine, nal function and urinary flow during a single procedure,
indomethacin, benzodiazepine, octreotide. even in neonates and young infants. It is simple, repro-
ducible and there is no need to insert an intravenous can-
ula or a bladder catheter. In a well-hydrated child, the si-
Urinary Tract multaneous injection of radiotracer and furosemide
(1mg/kg) will enable to have the child voiding at least
Urinary Tract Dilation one time during the examination, which is mandatory in
assessing urinary flow (Fig. 4). The procedure is well
With the increased use of prenatal ultrasound, the num- standardized and can be used from 3-4 weeks of life, and
ber of neonates diagnosed with unilateral or bilateral repeated at 1-month interval during the first 6 months
mild to moderate pelvic dilation has tremendously in- when needed [22]. There is no consensus on the use of
creased during the past years. The recommendation al- camera-based methods to measure absolute renal func-
gorithm for post-natal examinations aimed first at con- tion, and the EANM recommendation is to use isotopic
firming the dilation with US performed at 2 and 7 days clearance methods to measure glomerular filtration rate
of life, and to exclude other renal abnormalities such (GFR) and/or effective renal plasma flow (ERPF) when
as urethral valves, vesicoureteric reflux, multicystic dys- absolute function has to be checked [23]. In adults, a
plasia, duplex kidney and primary mega-ureter [20]. unilateral hydronephrosis may be diagnosed by chance
1’ 2’ 5’ 10’ 20’
a
100 50
80 40
Count rate (Cts/s)
60 30
40 20
20 10
b c d
0 0
0 200 400 600 800 1000 1200 0 200 400 600 800 1000 1200
e f Time (s)
Fig. 4 a-f. 123I-hippuran F0 dynamic renography performed during follow-up in a 9 months old infant with congenital left pelviureteric junction
stenosis (PUJS) that was treated conservatively. a Consecutive 1-minute posterior views obtained 1, 2, 5, 10 and 20 minutes after injection of
9 MBq of 123I-hippuran and 1 mg/kg of furosemide show a normal right kidney and a preserved parenchymal extraction by the left dilated
kidney. Bladder activity is present at 5 minute. The clearance from the right kidney is normal, whereas there is clearly a delayed urinary out-
put from the left kidney. Delayed posterior static views obtained at 20 min (b), after micturition (c), and at 1 hour after injection (d) show a
progressive dilution of radioactive urine in the dilated renal pelvis that persists unchanged despite change of position and micturition. Left kid-
ney time-activity curve (e) is cumulative and confirms the preserved renal function of the parenchyma. The time-activity curve of the normal
contralateral kidney (f) demonstrates both rapid extraction and secretion of the radiotracer with a time-to-peak less than 3 minutes
on ultrasound or CT-scan performed for other reason and young infants (spontaneous resolution in 45-70% of cas-
diuretic renography is valuable to assess renal function es) or surgically. Voiding cystourethrography (VCUG) is
and urinary flow. the reference method for diagnosis and grading of VUR.
Direct radionuclide cystography delivers a lower radiation
Urinary Tract Infection and Vesicoureteric Reflux dose and is more sensitive than VCUG because of contin-
uous acquisition during filling and voiding phases [26].
Urinary tract infection (UTI) is an important routine clin- The disadvantages are the lack of anatomical information
ical problem in paediatrics: its prevalence in children with and the invasiveness and non physiologic condition due
fever ≥38.5 ranges from 1% to 20% depending mainly on to bladder catheterisation. Indirect radionuclide cysto-
sex and age, being more frequent in girls and in children graphy is performed after a dynamic renography with
aged less than 2 years [24]. Symptoms and signs are often 99mTc-MAG3 or 123I-hippuran [27]. It is less sensitive and
non specific, the major challenge being to differentiate specific than direct cystography, but is more physiologic
cystitis from acute pyelonephritis (APN). The risk for per- and non-invasive.
manent renal damage is related to the delay between the
onset of infection and treatment. 99mTc-DMSA scintigra- Acute Renal Failure
phy is the gold standard for cortical renal imaging. It is
easy to perform, does not require sedation or special pa- Dynamic renography may help the clinician in patients
tient preparation and has a sensitivity ranging from 80% presenting acute renal failure (ARF) by assessing the po-
to 100% to detect parenchymal defects due to infection, tential for renal function recovery. ARF due to acute
but does not allow to distinguish between APN and renal tubular necrosis (ATN) has an overall good prognosis
scars: a normal 99mTc-DMSA scintigraphy during the when compared to cortical necrosis or loss of nephronic
acute phase has a high negative predictive value for late mass due to recurrent cholesterol embolism for example. In
scarring, whereas an abnormal scan during the acute case of ATN, diuretic renography will demonstrate pro-
phase is not predictive of long-term outcome [25]. Vesico- gressive and symmetric tracer uptake in both kidney and
ureteric reflux (VUR) is a common cause of recurrent UTI delayed parenchymal retention (Fig. 5). Post-renal cause
and can be treated either conservatively in neonates and of ARF may be difficult to exclude in anuric patients,
a 1’ 2’ 5’ 10’ 20’
220
200
180
Count rate (Cts/s)
160
140
120
100
80
60
40
20
b c d
0
0 200 400 600 800 1000 1200
Time (s)
Fig. 5 a-d. Acute renal failure in a 46-year-old man after acute rhabdomyolisis. 123I-hippuran dynamic renography was performed to evalu-
ate the potential for renal functional recovery. a Consecutive 1-minute posterior views obtained 1, 2, 5, 10 and 20 minutes after injection
of 46 MBq of 123I-hippuran show a symmetric and heterogeneous renal parenchyma with increase of activity in the renal cortex despite
appearance of radioactive urine in the bladder at 5 min pi. There is no urine retention in the renal pelvis or ureters. Static views obtained
at 20 min (b) and 8 hours (c) after injection show persistent retention of the radiotracer in the renal parenchyma, typical of acute tubular
necrosis (ATN). Time-activity curves of both left and right kidneys (d) show preserved initial parenchymal extraction with delayed secre-
tion consistent with a good potential for renal function recovery
212 Ariane Boubaker
because ultrasound may not show significant dilation. In measurements or in patients with borderline renal func-
such patients, dynamic renography can be a sensitive tool tion [30]. Dynamic renography with tubular tracers is
by allowing delayed acquisition until 24 h pi and possi- useful to evaluate the renal parenchyma, to calculate rel-
bly demonstrate urinary retention in renal pelvis and/or ative renal function and to assess urinary flow. When
ureters even at very low rate of urine output. ultrasound and angio-CT do not reveal any significant
anatomical abnormality, the choice of the donated kid-
Renovascular Hypertension ney is usually based on the results of the renography: the
kidney with the best function will be left in the donor.
Although the prevalence of renovascular hypertension
(RVH) in non selected patients is less than 1%, 15-45% Evaluation of the Renal Graft
among patients referred to a specialty center, for refracto-
ry hypertension will have RVH. When a stenosis becomes The most common causes of early and late complications
hemodynamically significant, the glomerular filtration after renal transplantation are listed in Table 2. Dynamic
rate (GFR) of the affected kidney decreases and the renin- renography with tubular tracers can be performed during
angiotensin system is activated in order to maintain the the first 24 to 48 hours after transplantation and repeated
GFR by vasoconstriction (angiotensin II) of the efferent if necessary, as no contrast medium injection, potentially
arterioles. Giving an angiotensin converting enzyme in- nephrotoxic, is required. It allows verification of
hibitor (ACEI) will block the compensatory mechanism in parenchymal function: signs of acute tubular necrosis (cu-
the affected kidney, and provoke a decrease of GFR. The mulative curve due to parenchymal retention of the trac-
ACE-inhibitor dynamic renography will show typically a er) will be present in most patients. Renal function should
shift of the time-to-peak, a delayed production of urine be quantified either by concomitant plasma clearance
and parenchymal retention of the tracer [28]. Oral capto- (GFR, ERPF) or by quantification based on the renogram.
pril given 1 hour prior to renography has been used for The procedure should be standardized in order to allow
many years, but variable absorption may occur. Intra- comparison of the results during follow-up. Acute rejec-
venous enalapril (40 μg/kg, maximum 2.5 mg) infused tion may be difficult to distinguish from acute tubular
over 3-5 minutes is more reliable. The test accuracy can necrosis in the first days after operation: a worsening of
be improved by administration of 20 mg furosemide dur- the vascular phase, decrease of renal parenchymal extrac-
ing renography. A normal ACEI renography should be re- tion and worsening of parenchymal retention will be eas-
ported as low-probability for RVH disease, and a baseline ier to diagnose if a baseline study is available. Renogra-
study is not mandatory. An equivocal result should be re- phy is a very sensitive method to diagnose a urinary leak
ported when the baseline renography is abnormal and even at very low urine flow. If 99mTc-MAG3 is used, de-
there is no significant change under ACEI. A high proba- layed acquisitions may be difficult to interpret because of
bility study (significant change under ACEI when com- hepato-biliary excretion: bowel activity may mask urinary
pared to baseline) is a strong indicator of potential im- activity. Whereas arterial thrombosis is a rare complica-
provement after angioplasty or surgery. The accuracy of tion (<1%), renal artery stenosis (RAS) has been reported
the test is significantly decreased in patients with poor in up to 23% of renal allografts [1, 24]. ACE-inhibitor
renal function and/or a small shrunken kidney. scintigraphy is useful to determine if systemic hyperten-
sion is dependent on the renin-angiotensin system, thus
Renal Transplantation allowing proper clinical management (Fig. 6). When ob-
struction is suspected, the use of diuretic renography may
Live Kidney Donor help in a similar manner as in native kidneys.
Live kidney donation has become more frequent over the

last years to cover the increasing numbers of patients Table 2. Common complications after renal transplantation
waiting for renal graft. The first objective is not to harm
a previously healthy person, the preoperative assessment Early complications (delayed graft function or failure to improve)
of the potential donor is mandatory including psycho- Acute tubular necrosis
Acute rejection
logical and biological examinations [29]. Ablation of a Vascular occlusion
kidney will usually lead to a loss of about 25% of renal Urinary leak/urinoma
function if both kidneys are equally participating to the Hematoma
global function. The role of conventional nuclear medi- Drug toxicity
cine procedure in the live kidney donor is to assess renal Late complications (decrease of renal function)
function and to select the best functioning kidney to be Chronic allograft nephropathy (chronic rejection)
Drug toxicity
left in the donor. Isotopic clearance using 51Cr-EDTA for Renovascular hypertension (renal artery stenosis)
GFR and 99mTc-MAG3 or 123I-hippuran for tubular ex- Urinary tract infection
traction rate/effective renal plasma flow (ERPF) mea- Vesicoureteric reflux
surement have not been used extensively so far, but may Obstructive uropathy (intrinsic, lymphocoele)
be used in case of non conclusive creatinin clearance Bladder dysfunction (postvoiding residue, small bladder volume)
a
1’ 2’ 5’ 10’ 20’
b
120 500
100
400
Count rate (Cts/s)
80
300
60
200
40
100
20
0 0
0 200 400 600 800 1000 1200 0 200 400 600 800 1000 1200
c Time (s) Time (s)
280 280
240 240
Count rate (Cts/s)
200 200
160 160
120 120
80 80
40 40
0 0
0 200 400 600 800 1000 1200 0 200 400 600 800 1000 1200
d Time (s) Time (s)
Fig. 6 a-d. Baseline and ACE-inhibitor 123I-hippuran dynamic renography performed 3 weeks after renal transplantation in a 53-year-old
woman presenting a severe systemic hypertension and episodes of acute left cardiac failure. a At baseline, the renal transplant shows pre-
served parenchymal extraction (1 min pi) with prompt urine output (5 min) and rapid washout (10 and 20 min). b Under ACE-inhibitor
(2.5 mg of enalapril intravenously over 5 minutes) there is a clear delay in urinary output (faint bladder activity at 10 min) and significant
retention of the tracer in the renal cortex. c Time-activity curves obtained at baseline study show normal pattern of the transplanted kid-
ney (grey curve), and rapid bladder filling (dotted curve). d Under ACE-inhibitor, time-activity curve of the renal transplant is clearly ab-
normal with preserved initial extraction phase and clearly delay of secretion (no time-to-peak, lack of descending curve). The bladder time-
activity curve (dotted line) shows no significant activity till 10 min pi and low urine output. Renovascular hypertension was diagnosed and
surgery confirmed a narrowing of renal artery at the site of anastomosis
214 Ariane Boubaker
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IDKD 2010-2013
PET in Hepatobiliary-Pancreatic Tumors

Stefano Fanti, Anna Margherita Maffione, Vincenzo Allegri
Department of Nuclear Medicine, University of Bologna, Bologna, Italy
Overview Common laboratory findings in liver cancers are ane-

mia as well as elevated alkaline phosphatase and α-feto-
Primary liver cancer is a relatively uncommon entity, ac- protein (AFP); in particular, very high levels of AFP oc-
counting for only 1-2% of malignant tumors, while cur in 70% of patients with hepatocellular carcinoma.
cholangiocarcinoma is even rarer. However, in parts of Laboratory findings in pancreatic cancer are non-specific,
Africa and Asia these tumors may constitute up to 20- since prolonged biliary obstruction may alter liver en-
30% of all malignancies. Other benign and malignant zymes and cause abnormalities in vitamin-K-dependent
hepatobiliary-pancreatic tumors are very rare; they in- clotting factors (due to malabsorption of fat-soluble vita-
clude hepatoblastoma in infancy and early childhood, mins), while pancreatic duct obstruction may result in
hemangiomas (the most common benign tumors), and pancreatic atrophy and subsequent impaired glucose
angiosarcomas (vascular tumors). Hepatic adenomas, tolerance or frank diabetes. Carbohydrate antigen 19-9
although also rare, may occur particularly in women (CA 19-9) is the most commonly employed serological
taking oral contraceptives. In the USA, pancreatic can- marker in pancreatic cancer. Although it has a sensitivity
cer has an incidence of 12 per 100,000 men and women of 80%, serum levels are increased in many benign and
per year, and cancer of the pancreas is the third most malignant gastrointestinal conditions, such that the speci-
common malignancy of the gastrointestinal tract and the ficity for detecting pancreatic cancer is low.
fifth most common cause of cancer-related mortality.
Islet cell tumors constitute 5-10% of pancreatic tumors
and are usually referred to as neuroendocrine tumors of Current Role of Imaging
the pancreas.
It is noteworthy that metastatic malignant lesions of A number of imaging procedures are used to detect liver
the liver are common in clinical practice, with an inci- tumors, including ultrasound (US), computed tomography
dence at least 20 times greater than that of primary car- (CT), magnetic resonance imaging (MRI), and angiogra-
cinoma. By contrast, true cancers of the liver may escape phy. US has been suggested in the screening of high-risk
clinical recognition, as they often occur in patients with populations. It is widely available, reasonably accurate,
cirrhosis (60-75% of cases) and the symptoms may ini- and does not involve radiation exposure. It therefore
tially suggest a progression of the underlying liver dis- should be considered as the first imaging procedure to use
ease. The course of hepatocellular carcinoma and of when hepatocellular carcinoma or cholangiocarcinoma is
cholangiocarcinoma is fatal and usually rapid, with sur- suspected. Although the use of contrast-enhanced US is
gical resection offering the only chance of cure. Nonethe- recommended, and contrast enhancement is mandatory for
less, the 5-year survival is low and only very few patients CT, MRI is used with increasing frequency and is usually
have resectable tumors at the time of presentation. the most accurate diagnostic approach. All these imaging
Pancreatic carcinoma also has a very poor prognosis, modalities can be used for primary diagnosis, staging pur-
and early diagnosis is extremely difficult. The physical poses, and to identify tumor recurrence.
examination rarely confirms the presence of localized In pancreatic cancer, US, CT, and MRI are widely used
pancreatic cancer. The initial symptoms that prompt fur- as well, but they are supplemented by MR-cholangio-
ther investigations are painless jaundice (in case of bile pancreatography (MRCP) and endoscopic US (EUS).
duct obstruction) and weight loss, but they depend on the
site of the tumor within the pancreas and the degree of
organ involvement. In advanced disease, palpable lymph Positron Emission Tomography
nodes, hepatomegaly (due to metastasis), splenomegaly,
ascites, and peripheral edema (portal vein obstruction), or Positron emission tomography (PET) imaging allows the
an abdominal mass may be seen. in vivo study of tissue metabolism, and thus demonstrates
216 Stefano Fanti, Anna Margherita Maffione, Vincenzo Allegri
malignant tumors as hypermetabolic lesions based on curacy in detecting unsuspected distant metastases. Its
their increased tracer uptake. Nowadays, fluorine-18 role in detecting cancer recurrence, monitoring treatment
radiolabeled fluorodeoxyglucose (18F-FDG) is the tracer response, and predicting prognosis is still controversial.
compound of choice in clinical practice. FDG is initially
carried into the cell by glucose transporters (GLUT-1),
just as normal glucose, then is rapidly phosphorylated Role of Acetate PET in Liver Cancer
and trapped in the cells. Cancer cells are known to have
increased anaerobic glycolytic activity and to express 11C-acetate is used by cells as a precursor of membrane
higher numbers of glucose transporters. fatty acids but it can also be transformed into acetyl-CoA,
Despite the wide clinical application of FDG, not all tu- entering the tricarboxylic acid cycle. It is thus processed
mors show significantly increased metabolic activity on as an intermediate in glucose catabolism and in membrane
FDG-PET imaging. In particular, prostate cancer and neu- synthesis. The original application of 11C-acetate was not
roendocrine tumors may be difficult to study with FDG- in oncology but in cardiology, because accumulation of
PET, as the exam lacks sensitivity. Therefore, in addition the labeled compound in the myocardium is proportional
to FDG, several other tracers have been proposed, some of to the level of fatty acids oxidation and thus reflects car-
which are already used for clinical applications. For exam- diac energy metabolism. Initially, the oncological applica-
ple, 68Ga-DOTA-somatostatin analogues have been suc- tion of 11C-acetate was as a choline analogue for the de-
cessfully applied in the study of neuroendocrine tumors, tection of prostate cancer; later, its use was expanded to
both pancreatic and extra-pancreatic, while 11C-acetate has the evaluation of liver masses, together with 18F-FDG
been proposed for hepatocellular carcinoma PET. studies. Preliminary results showed that 11C-acetate has
In the past, the main limitation of PET imaging was its good sensitivity in the detection of low-grade but not
failure to provide anatomical data; however, with the high-grade hepatic cancer, while FDG has the opposite
introduction of a PET-CT hybrid system, morphological behavior. In our experience, acetate-based PET is the pre-
and metabolic imaging can be performed in a single ses- ferred approach to study most hepatocellular carcinomas,
sion, thereby reducing false-positive findings and incon- especially in the differential diagnosis of masses not iden-
clusive studies and increasing diagnostic accuracy. tified by conventional imaging and not suitable for biop-
sy, and for suspected recurrence of a hepatocellular carci-
noma that was previously treated surgically.
Role of FDG-PET in Liver Cancer
The success achieved with FDG-PET in studies of hepato- Role of PET with Other Tracers in Liver Cancer
cellular carcinoma has been limited by a false-negative
rate of 40-50%, with poor reliability especially in evalu- 11C-choline is another tracer suggested for studies of
ations of well-differentiated cancers. Of the few studies hepatocellular carcinoma; the results have been similar to
available in the literature, most are retrospective and all those achieved with acetate. As only a very few studies
of them report an inadequate sensitivity of FDG-PET in have been published, a role for 11C-choline remains to
the detection of primary hepatocellular carcinoma. The be confirmed, but as for acetate, it may be useful in the
true-positive rate of FDG was better in poorly differenti- evaluation of low-grade tumors. Finally, use of the tracer
ated tumors, with an increase in FDG uptake correlating 18F-fluorothymidine has been proposed to assess the
with lower survival. While FDG-PET might be useful in proliferation of hepatocellular carcinoma and cholangio-
the evaluation of extra-hepatic metastases, data support- carcinoma.
ing this possibility are limited. Instead, alternative tracers
have been proposed in conjunction with FDG; however,
the use of FDG alone may provide important prognostic Role of FDG-PET in Pancreatic Cancer
information, especially in patients who are candidates for
liver transplantation. Most of the literature describing the use of PET in pan-
FDG-PET has also been proposed for patients with creatic cancer refers to the tracer FDG. Normal pancreas
cholangiocarcinoma, mainly in disease diagnosis and tu- has low glucose utilization, whereas in pancreatic cancer
mor staging. In the former, PET seems to be helpful in GLUT-1 transporters are over-expressed compared with
discriminating between malignant and benign lesions. normal tissue; therefore, the tumor/background FDG up-
However, the accuracy of FDG-PET is dependent on the take ratio is high.
lesion’s anatomical location, growth pattern, and patho- The most important step in the initial approach to a
logical characteristics. For this reason, its application is patient suspected to have pancreatic carcinoma is to de-
limited to the detection of extra-hepatic, infiltrating, and cide whether the lesion is benign or malignant. The ma-
mucinous cholangiocarcinomas. Moreover, due to its low jor limitation of morphological imaging techniques is
sensitivity, PET provides complementary rather than con- their inability to confidently characterize small as well
firmative information in the diagnosis of regional lymph as cystic lesions. In this setting, PET/CT may be helpful
node metastasis. FDG-PET, however, has shown high ac- due to its high sensitivity (85-100%) and moderate
PET in Hepatobiliary-Pancreatic Tumors 217
specificity (67-90%). Several studies have reported that Regarding the use of FDG-PET for staging, about 40%
FDG-PET is more accurate than CT (the average sensi- of pancreatic cancers determined to be resectable by pre-
tivity and specificity for CT is 82 and 75%, respective- operative imaging turned out to be non-resectable at the
ly). Regarding characterization of the lesion, the princi- time of surgery. Therefore, correct staging is the princi-
pal cause of false-positive findings at PET is inflamma- pal aim of imaging in pancreatic malignancies, to deter-
tion due to chronic pancreatitis. However, the distribu- mine the appropriate management and the prognosis of
tion of areas of avid FDG uptake within the parenchyma the disease. For T staging, the poor spatial resolution of
can guide the diagnosis, as diffuse high uptake in the FDG-PET limits its utilization: anatomical imaging
whole pancreas is more often due to inflammation while modalities such as multidetector CT, EUS, and MRCP
focal uptake is a feature of pancreatic cancer. Unfortu- are better suited to demonstrate the relationship between
nately, morphological analysis is not specific because the tumor and the adjacent organs or vascular structures.
pancreatic cancer is sometimes accompanied by pancre- At present, there are no data to support the usefulness of
atitis, with FDG uptake in tumor tissue likely related to the hybrid-modality PET/CT in local T staging. Lymph
the presence of inflammatory cells. In such cases it is es- node metastasis is one of the most important aspects of
sentially impossible to clearly separate the two compo- clinical management, providing an independent prognos-
nents. Furthermore, cancer cells can diffusely infiltrate tic indicator for patients with pancreatic cancer. Un-
the entire pancreas, with pancreatic cancer manifesting fortunately, both CT and PET/CT are of low sensitivity
as diffuse, high FDG uptake throughout the organ. By (30-40%) for lymph node detection, perhaps due to the
contrast, benign lesions such as autoimmune pancreati- strong radioactive scatter from the main tumor to peri-
tis can assume a pattern of focal FDG uptake. Semi- pancreatic small lymph nodes and to the low number of
quantitative approaches are not very helpful due to the cancers cells in small metastatic lymph nodes. The prin-
wide overlap in standardized uptake values (SUVs) be- cipal cause of false-positive lymph nodes at FDG-PET is
tween inflammation and malignant pancreatic disease. the presence of reactive locoregional lymphadenopathies
False-positive findings can also occur due to recent following biliary instrumentation.
surgery or endoscopy, tissue inflammation after irradia- After the diagnosis of pancreatic cancer has been es-
tion, abscess, autoimmune pancreatitis, massive lympho- tablished and local resectability of the tumor confirmed,
cyte infiltration, retroperitoneal fibrosis, hemorrhage in the main objective of staging a pancreatic cancer is to
pancreatic pseudocysts, inflammatory pseudotumors, identify those patients with distant metastasis because
pancreatic tuberculosis, and focal high-grade dysplasia. this group is currently excluded from surgical treatment.
Most false-negative results occur in cases involving In this regard, the capability of whole-body scanning with
both tumors of small size and elevated serum glucose lev- a single examination at a single session is evidently an
els. It should be noted that many such patients suffer from advantage of FDG-PET over other imaging modalities.
pancreatic insufficiency and diabetes; consequently, the Whole-body FDG-PET detection of distant metastasis or
high serum glucose levels compete with FDG for glucose unexpected lesions changes patient management, is cost-
transporters sites, reducing the sensitivity of FDG-PET in saving, and improves the patient’s quality of life by avoid-
the detection of malignant lesions. Poor tumor cellulari- ing unnecessary surgery. Several studies have reported
ty, characteristic of scirrhous-type and cystic-type tumors better diagnostic accuracy in the detection of distant
as well as those featuring a desmoplastic reaction, is also metastasis using whole-body FDG-PET rather than other
an important cause of false-negative findings. The pauci- modalities, such as CT or US. The sensitivity of PET was
ty of cells in these not-rare forms of pancreatic cancer is between 80 and 90% and thus better than CT; the posi-
seen even in fairly large tumors. False-negatives on FDG- tive predictive value is very high for both modalities.
PET studies also arise from pancreatic tumors such as Regarding metastatic disease, liver is the commonest
mucinous or neuroendocrine tumors (NETs), which do organ to be affected, followed by the lungs and bone mar-
not have high glucose metabolism. row. Direct tumor spread into the peritoneum is also not
Regarding the detection accuracy of FDG-PET/CT, a uncommon and often missed on conventional anatomical
recent meta-analysis suggested that although the addition imaging. The accuracy of PET in detecting liver metasta-
of FDG-PET to the diagnostic work-up may enhance the sis is almost the same as obtained with conventional
diagnosis of pancreatic malignancy, the usefulness of this imaging (94 and 90%, respectively). False-positive find-
combined approach will vary depending upon the pre-test ings can occur due to intrahepathic cholestasis or in some
probability of the tumor, the results of CT, and the types of inflammation, such as abscess or intrahepatic
provider’s testing thresholds. Average sensitivity and bile duct infection, mainly due to percutaneous trans-
specificity shift from 92 and 68% after a positive CT re- hepatic cholangiodrainage. False-negative PET findings
port, to 73 and 86% after a negative CT report, and 100 may occur with lesions of small size but also because of
and 68% after an indeterminate CT report. the heterogeneity of hepatic parenchymal FDG uptake
In conclusion, the greatest benefit of PET in the dif- and respiratory motion artifacts.
ferentiation of benign from malignant lesions is the pos- PET has also been suggested in the evaluation of re-
sibility of excluding cancer without the need for biopsy sponse to therapy, and it may allow an earlier therapeutic
or surgery, either of which may increase morbidity. response assessment than is possible with conventional
218 Stefano Fanti, Anna Margherita Maffione, Vincenzo Allegri
imaging. However, only very preliminary data are avail- Dierckx R, Maes A, Peeters M, Van De Wiele C (2009) FDG PET
able, and larger prospective studies are necessary to con- for monitoring response to local and locoregional therapy in
HCC and liver metastases. Q J Nucl Med Mol Imaging
firm the role of PET in treatment response and to assess 53:336-342
the correct time between therapy and PET post-treatment Eckel F, Herrmann K, Schmidt S et al (2009) Imaging of prolifer-
examination. ation in hepatocellular carcinoma with the in vivo marker 18F-
With respect to recurrence, an elevated CA 19-9 has a fluorothymidine. J Nucl Med 50:1441-1447
positive predictive value of only 69% for pancreatobiliary Higashi T, Saga T, Nakamoto Y et al (2003) Diagnosis of pancre-
atic cancer using fluorine-18 fluorodeoxyglucose positron
malignancy. This means that >30% of patients with ele- emission tomography (FDG PET) – usefulness and limitations
vated CA 19-9 may have another tumor originating in an- in “clinical reality”. Ann Nucl Med 17:261-279
other organ, or they may have no tumor at all. False-pos- Kauhanen SP, Komar G, Seppänen MP et al (2009) A prospective
itive results have been associated with other pancreato- diagnostic accuracy study of 18F-fluorodeoxyglucose positron
biliary disorders, such as gallstones, pancreatitis, inflam- emission tomography/computed tomography, multidetector
row computed tomography, and magnetic resonance imaging
matory bowel disease, other liver disorders, pulmonary in primary diagnosis and staging of pancreatic cancer. Ann
diseases such as pneumonia, and hydronephrosis. There- Surg 250:957-963
fore, if CA 19-9 is elevated despite negative findings at Kornberg A, Küpper B, Thrum K et al (2009) Increased 18F-FDG
CT, then FDG-PET may have a role in detecting sites of uptake of hepatocellular carcinoma on positron emission to-
mography independently predicts tumor recurrence in liver
recurrence, either locally or as metastases in the liver, transplant patients. Transplant Proc 41:2561-2563
lungs, peritoneum, and distant lymph nodes. FDG-PET Lee TY, Kim MH, Park do H et al (2009) Utility of 18F-FDG
might also be appropriate for excluding the presence of PET/CT for differentiation of autoimmune pancreatitis with
recurrence in patients with indeterminate findings using atypical pancreatic imaging findings from pancreatic cancer.
other imaging modalities. Am J Roentgenol 193:343-348
Pakzad F, Groves AM, Ell PJ et al (2006) The role of positron emis-
sion tomography in the management of pancreatic cancer.
Semin Nucl Med 36:248-256
Suggested Reading Salem N, Kuang Y, Wang F et al (2009) PET imaging of hepato-
cellular carcinoma with 2-deoxy-2[18F]fluoro-D-glucose,
Bang S, Chung HW, Park SW et al (2006) The clinical usefulness 6-deoxy-6[18F] fluoro-D-glucose, [1-11C]-acetate and
of 18-fluorodeoxyglucose positron emission tomography in [N-methyl-11C]-choline. Q J Nucl Med Mol Imaging 53:
the differential diagnosis, staging, and response evaluation af- 144-156
ter concurrent chemoradiotherapy for pancreatic cancer. J Clin Seo S, Hatano E, Higashi T et al (2008) Fluorine-18 fluorodeoxy-
Gastroenterol 40:923-929 glucose positron emission tomography predicts lymph node
Breitenstein S, Apestegui C, Clavien PA (2008) Positron emission metastasis, P-glycoprotein expression, and recurrence after re-
tomography (PET) for cholangiocarcinoma. HPB (Oxford) section in mass-forming intrahepatic cholangiocarcinoma.
10:120-121 Surgery 143:769-777
IDKD 2010-2013
PET in Tumors of the Digestive Tract

Thomas F. Hany
Department of Radiology, Clinic and Policlinic of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland
Introduction cell carcinoma is associated with dietary factors whereas

adenocarcinoma is related to reflux. This distinction ex-
The basic principle of positron emission tomography plains why the former occurs more proximally in the
(PET) is the use of pharmaceuticals labeled with esophagus and the latter more distally. The major goals of
positron-emitting isotopes. These agents are such that the pre-operative evaluation of patients with esophageal
they can be integrated into one of the body’s metabolic cancers are to exclude distant metastases and to decide
pathways. Positron-emitting isotopes are characterized by whether complete resection of the primary tumor and
a beta plus-decay, in which a positron is emitted. This its lymphatic drainage (R0 resection) can be achieved
positron collides with any of the numerous shell electrons (Fig. 1). Evaluation of locoregional lymph nodes is
of neighboring atoms and the resulting annihilation pro- important in the determination of prognosis, since
duces two 511-keV gamma rays. These two photons are patients with peritumoral lymph node metastases have a
detected in coincidence by the PET scanner. Additional- significantly reduced overall survival, but the presence
ly, the use of an integrated PET/computed tomography of such lymph nodes has no influence on either tumor
(CT) machine allows PET and CT images of the patient resectability or therapeutic strategy [3].
to be acquired in the same imaging session. The clinical- Endoscopic ultrasonography (EUS) is considered the
ly and most widely evaluated of the labeled pharmaceu- most accurate modality for local staging of esophageal
ticals is fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). cancer. Most studies show that the accuracy of EUS is ap-
This glucose analogue is transported into the cell by spe- proximately 85% for T staging and 75% for N staging. CT
cific transporters and phosphorylated by hexokinase to and PET/CT scanning are not as accurate as EUS for local
18F-FDG-6 phosphate. The latter is inert to further meta- staging, because neither technique can assess the layers of
bolic processing or to transmembrane back-transport out- the esophageal wall, nor can small lymph nodes be reliably
side the cell and therefore accumulates intracellularly. distinguished from adjacent tumor. Further improvement
The long physical half-life of FDG, around 110 min, of locoregional staging is achieved by EUS used in com-
makes this compound amenable for use as a metabolic bination with fine-needle aspiration (EUS-FNA). EUS-
marker, with applications in oncology, cardiology, neu- FNA is reported to be more sensitive (83 vs. 29%;
rology, and inflammation imaging. One of the most im- p <0.001) and more accurate (87 vs. 51%; p <0.001) than
portant advantages of PET/CT imaging is its broad CT or EUS (87 vs. 74%; p=0.012) for nodal staging [4].
anatomical coverage, since images of the patient extend- For initial staging, a meta-analysis comparing EUS,
ing from the head to the thighs are acquired routinely. All CT, and FDG-PET demonstrated sensitivities for region-
of the currently available data indicate that PET/CT is al lymph node metastases of 80, 50, and 57%, respec-
more sensitive and specific than either of its constituent tively, and specificities of 70, 83, and 85%, respectively.
imaging methods. With PET/CT, the most relevant effect Interestingly, diagnostic performance did not differ sig-
is that the CT data frequently add specificity to the FDG- nificantly across these tests. For distant metastases, sen-
PET data [1]. sitivity and specificity were, respectively, 71 and 93% for
FDG-PET and 52 and 91% for CT. The diagnostic per-
formance of FDG-PET for distant metastases was shown
Esophagus, Stomach, and Small Bowel to be significantly higher than that of CT, which was not
significantly affected by study type and patient charac-
Esophagus teristics. For the detection of regional lymph node metas-
tases, EUS is the most sensitive modality, whereas CT
The incidence of esophageal cancer has been increasing and FDG-PET are more specific. For the evaluation of
worldwide, particularly for adenocarcinomas of the lower distant metastases, FDG-PET has probably a higher sen-
esophagus and gastroesophageal junction [2]. Squamous sitivity than CT [5].
220 Thomas F. Hany
a b
Fig. 1 a, b. Initial staging in a 49-year-old

patient with an advanced distal esophageal
cancer. In the maximum-intensity-projection
image (a), FDG uptake is seen in the distal
esophagus and in two sites in projection to
the right upper abdomen. These two lesions
can be localized easily to an enlarged celiac
trunk lymph node metastasis and an adrenal
metastasis (b)
Curative treatment can be achieved by radiochemo- authors concluded that the technique has no role in the
therapy and/or surgery. FDG-PET/CT has demonstrated a primary detection of gastric cancer due to its low sensi-
high negative predictive value. In a study by Lordick et tivity [7]. FDG-PET shows, however, slightly better re-
al., the effect of neo-adjuvant chemotherapy prior to sults than CT in the evaluation of lymph node metastases
surgery after 2 weeks of chemotherapy was compared to in gastric cancer and could therefore have a role in pre-
the initial scanning. An improved median survival in so- operative staging of the tumor. Improvements in the ac-
called metabolic responders compared to non-responders curacy of FDG-PET could be achieved by using PET/CT
was demonstrated, whereas response was defined as a or PET tracers other than FDG, but these approaches
≥35% decrease in standard uptake values (SUV). Re- need further investigation. The role of FDG-PET/CT is
markably, major histological remissions (<10% residual likewise limited in the detection of gastric cancer recur-
tumor) were noted in 58% of metabolic responders, but rence after curative tumor resection. In a study by Sim et
no histological response was seen in metabolic non- al., in which 52 patients underwent restaging by PET/CT
responders. Accordingly, FDG-PET has a relatively high and contrast-enhanced CT (ceCT), the sensitivity was
negative predictive value after treatment and vital tumor 68.4% (26/38) for PET/CT and 89.4% (34/38) for ceCT
tissue is very likely to be present in the unchanged FDG (p=0.057). The specificity was 71.4% (10/14) and 64.2%
uptake of the primary tumor [6]. These facts have found (9/14), respectively (p=1.0). Contrast-enhanced CT was
their way into the clinical practice guidelines of the more sensitive than PET/CT (p=0.039) in the detection of
National Comprehensive Cancer Network (NCCN), peritoneal seeding. Additional PET/CT combined with
which recommends PET/CT for initial staging and after ceCT showed no further increase of positive predictive
neo-adjuvant treatment. value regardless of tumor site. PET/CT was as sensitive
and specific as ceCT in detecting a recurrence of gastric
Stomach: Malignant Disease cancer, except in the case of peritoneal seeding. However,
additional PET/CT combined with ceCT did not increase
In a review by Dassen et al. regarding the pre-operative diagnostic accuracy in the detection of recurrent gastric
diagnostic utility of FDG-PET/CT in gastric cancer, the cancer [8]. Accordingly, further studies are warranted to
PET in Tumors of the Digestive Tract 221
validate the role of PET/CT in the detection of gastric were better defined on PET/CT than on either PET or CT,
cancer recurrence; however, this approach adequately de- when compared side-by-side. Normally, Response Evalu-
tects therapy responders at an early stage following neo- ation Criteria in Solid Tumors (RECIST) criteria are used
adjuvant chemotherapy. in the evaluation of therapeutic response, based on the
Regarding primary non-epithelial tumors, lymphoma change in tumor size. In a modified RECIST analysis,
is an important disease beside gastrointestinal stroma tu- carried out in time intervals of 2 months for up to 28
mors (discussed below). Primary gastric lymphoma months, Choi et al. used ceCT studies to evaluate changes
(PGL) is díagnostically challenging due to the physiolog- in tumor size and density [14]. When PET, RECIST, and
ical activity of FDG in the stomach and variability in the modified RECIST criteria were used in the analysis, a de-
degree of the tracer’s uptake in tumors of different histo- crease in tumor size >10% or a decrease in tumor density
logical subtypes [9]. In a study by Radan et al., PET/CT >15% on CT was demonstrated to have a sensitivity of
studies of 62 newly diagnosed PGLs were reviewed: 24 97% and a specificity of 100% in identifying PET re-
of low-grade mucosa-associated lymphoid tissue (MALT) sponders vs. 52 and 100% by RECIST. Good responders
type and 38 consisting of aggressive non-Hodgkin’s lym- on CT at 2 months had significantly longer time to pro-
phoma (AGNHL). FDG avidity was present in 89% of the gression than patients who did not respond (p = 0.01).
PGLs, including all AGNHL, but only in 71% of MALT- Therefore, the search for small changes in tumor size or
type lymphomas. Especially in AGNHL-PGL, FDG uptake density on CT may be a sensitive and specific method to
can be differentiated from physiological tracer activity by assess the response of GISTs.
its intensity but not by its pattern.
Small Bowel: Malignant Disease Colorectal Carcinoma

Adenocarcinomas of the small bowel are rare tumors, Colorectal carcinoma is the most important cause of
with an incidence of around 3.7 per million people each death due to cancer in the western world, after bronchial
year. The pathological (development from adenomatous carcinoma [15]. About 70% of patients have curable re-
polyps), genetic, and epidemiological features are very sectable tumor at initial diagnosis and are treated with cu-
similar to those of adenocarcinomas of the large bowel rative intent. Approximately 50% of colon cancer patients
but the prognosis is poor (reported 5-year-survival of will present with hepatic metastases, either at the time of
15-35%). Capsule endoscopy, CT enteroclysis, and initial diagnosis or as a result of recurrence [16]. From a
ceCT are mainly used in disease diagnosis and work-up. diagnostic perspective, colon cancer is often evaluated
These tumors do show clear FDG avidity and might be together with rectal cancer as a single group; however,
better evaluated by FDG-PET/CT, although no compre- especially deep rectal cancer has a clearly different path-
hensive date on the use of FDG-PET/CT are yet available. way of locoregional and distant metastases. In deep rectal
Carcinoid tumors, as malignant tumors of non- cancer without invasion of the anal canal, lung metastases
epithelial origin, have a similar incidence as adenocar- are more prevalent than metastases to the liver (Fig. 2).
cinomas (3.8 per million people each year). The different In very deep rectal cancer, lymphatic drainage is no
subtypes have a natural behavior ranging from benign to longer towards para-rectal/meso-rectal lymph node sta-
high-grade malignancies. Similar to neuroendocrine tions but to inguinal sites, analogous to anal squamous
tumors (NET) of the pancreas, the diagnostic work-up cancer. In these cases, the inguinal lymph nodes and
consists of nuclear medicine studies, including somato- possibly, the external iliac region have to be evaluated,
statin receptor scintigraphy combined with contrast- since clinical inspection, ultrasound, and fine-needle as-
enhanced CT (SPECT/CT) or Ga-68 octreotide (68Ga- piration cost-effectively lead to correct staging.
DOTA-NOC) labeling, since more than 80% of carcinoid
tumors express somatostatin receptors. Detection rates Initial Staging
are therefore similar to those of NET of the pancreas [10].
Two studies in which FDG-PET alone was used for ini-
tial staging demonstrated the high sensitivity of this ap-
Gastrointestinal Stromal Tumors proach in the detection of primary tumor (100 and 96%)
and distant metastases (87 and 78%) but a low sensitivi-
Gastrointestinal stromal tumors (GIST) are mesenchymal ty (29 and 29%) in lymph node staging [17,18]. In a study
tumors that in approximately 90% of patients originate in by Veit-Haibach et al., 47 patients underwent whole-body
the stomach and small intestine. FDG-PET is able to PET/CT colonography one day after colonoscopy [13].
show early effects in patients undergoing treatment with Compared with optimized abdominal CT staging alone,
imatinib mesylate (Glivec; Novartis, Switzerland) [11]. PET/CT colonography was significantly more accurate in
In two recent short-term follow-up studies, patients defining TNM stage (difference, 22%; 95% CI, 9-36%;
without FDG uptake after the start of treatment had a p = 0.003), mainly based on a more accurate definition of
better prognosis than those with residual activity not the T stage. Differences in defining N stage were not de-
demonstrated with ceCT [12, 13]. Furthermore, lesions tected between PET/CT colonography and CT alone
222 Thomas F. Hany
a b
Fig. 2 a, b. A 64-year-old male patient with a

histologically proven deep rectal cancer. In
the maximum-intensity-projection image (a),
focal uptake is seen just below the bladder.
Unexpectedly, additional uptake is seen is in
the right thorax. This lesion was identified as
a singular lung metastasis, typical for deep
rectal cancer without evidence of liver metas-
tases (b)
when the threshold for malignant nodes was 0.7 cm but phology-based information obtained with CT does not
were detected at a threshold of 1 cm. Differences were permit a distinction between post-surgical changes and
not detected in defining M stage separately or when the tumor recurrence, nor can it detect tumor involvement of
accuracies of PET/CT colonography were compared with normal-sized lymph nodes [20]. Colonoscopy is only use-
CT + PET. PET/CT colonography affected consecutive ful in the detection of local recurrence. The suitability of
therapy decisions in 4 patients (9%; 95% CI, 2.4-20.4%) FDG-PET in identifying recurrence and metastases has
compared with conventional staging (CT alone and been confirmed in several studies. Despite the obvious
colonoscopy). The combination of FDG-PET/CT in con- advantage of PET/CT over PET alone, a dedicated ceCT
junction with a dedicated ceCT protocol could be of in- is often requested by clinicians. Soyka et al. found that
terest as a single-step staging procedure. cePET/CT, as a single-step examination, has the same di-
agnostic confidence and impact as a sequential approach,
Recurrent Disease with ceCT first and non-cePET/CT afterward [21]. Al-
though the lesion detection rate on ceCT images is high,
Standard patient work-up for the detection of recurrence evaluation by ceCT alone can be challenging because of
and metastases in colorectal cancer includes regular clin- the possibility of inconclusive results that require further
ical examinations, CT scans, colonoscopy, and, usually, diagnostic evaluation (56% of our patient population).
the measurement of tumor markers such as CEA (Fig. 3). The reason for this is predominantly related to specifici-
However, this approach lacks specificity and may result ty issues regarding the structural abnormalities depicted
in diagnostic and therapeutic delays. Serological tumor by this modality. Consequently, patients with inconclu-
markers are useful, although it has been shown that the sive ceCT findings are now frequently referred for fur-
serum CEA level has only 60-70% sensitivity for the de- ther evaluation with 18F-FDG-PET/CT. More important-
tection of colorectal cancer recurrence [19]. The mor- ly, the same study showed that in 21% of the patients with
a b
Fig. 3 a, b. A 71-year-old male patient with a

history of colon cancer in whom an increase
in serum CEA was detected. In the maximum-
intensity-projection image (a), focal uptake is
seen in projection to the liver. The axial con-
trast-enhanced CT and fused PET/CT image
demonstrate a singular liver metastasis in the
right liver lobe, segment VII (b)
apparently conclusive findings on ceCT, the addition of comparison with other “conventional” imaging studies
non-cePET/CT information led to appropriate changes in was not performed. In our own study, by Seltzner et al.,
therapy. In clinical routine, in those cases in which ceCT the diagnostic value of ceCT and non-enhanced
was judged to be conclusive, the patient would not rou- PET/CT was prospectively evaluated and compared in
tinely be referred for further evaluation with 18F-FDG- 76 patients referred for pre-operative evaluation for liv-
PET/CT. However, if cePET/CT had been used as the ini- er resection for metastatic colorectal cancer [23]. Extra-
tial imaging modality, 65% of the patients would have hepatic disease was missed by ceCT in one-third of the
had a clear benefit, including changes in management patients (sensitivity 64%), while PET/CT failed to de-
and in diagnostic confidence. Therefore, one could argue tect extrahepatic lesions in only 11% (sensitivity 89%;
that cePET/CT should be the first-line diagnostic tool in p=0.02). New findings derived from PET/CT resulted
the restaging of colorectal cancer. Nonetheless, one could in a change in the therapeutic strategy in 21% of the pa-
also argue that in 35% of the patients both the radiation tients. This study also demonstrated the well known
exposure and the costs of the procedure would have been limitation in spatial resolution of around 4-6 mm of
futile. However, the former argument holds true only if PET imaging, since small tumours (e.g., <5 mm) were
ceCT and non-cePET/CT are performed within 2-4 often not detected. Also, patients who underwent
weeks. In general, surgeons insist on ceCT studies not chemotherapy within the month prior to PET/CT had a
older than 4 weeks before taking a patient into the oper- high incidence of false-negative results. Alternatively,
ating room. Thus, another, additional scan with contrast this effect might be used as a predictor of success
enhancement (ceCT or cePET/CT) would be needed in in neo-adjuvant chemotherapy before resection. The
the majority of patients. above-mentioned studies clearly demonstrate the ad-
Post-surgical and radiotherapy-induced changes in vantages of PET/CT imaging in colorectal cancer.
the small pelvis are the most challenging for morpho-
logical imaging studies in recurrent rectal cancer, since Therapy Response Assessment
tumor recurrence cannot be differentiated from benign
scar tissue. In a study by Even-Sapir et al., PET/CT was In general, a decrease or reduction to normal of FDG
used to distinguish benign from malignant pre-sacral uptake levels in tumor tissue is correlated with response
abnormalities. The sensitivity, specificity, positive pre- to treatment. Systematic reviews have only been per-
dictive value, and negative predictive value were 100, formed in patients with rectal cancer before and after
96, 88, and 100%, respectively, and PET/CT findings neo-adjuvant radio-chemotherapy. In a study by Kalff et
were clinically relevant in 47% of 62 patients [22]. A al., the prognostic information obtained from the degree
224 Thomas F. Hany
of change in tumor FDG uptake induced by chemoradi- 4. Vazquez-Sequeiros E, Wiersema MJ, Clain JE et al (2003) Im-
ation before radical curative surgery was evaluated in pact of lymph node staging on therapy of esophageal carcino-
ma. Gastroenterology 125:1626-1635
patients with T3/T4 rectal cancer. In 34 consecutive pa- 5. van Vliet EP, Heijenbrok-Kal MH, Hunink MG et al (2008)
tients with T3/T4 Nx M0 rectal cancer, FDG-PET was Staging investigations for oesophageal cancer: a meta-analy-
performed at baseline and after radiochemotherapy be- sis. Br J Cancer 98:547-557
fore planned curative surgery. The change in FDG up- 6. Lordick F, Ott K, Krause BJ et al (2007) PET to assess early
take was measured by SUV as well as by visual grading metabolic response and to guide treatment of adenocarcinoma
of the oesophagogastric junction: the MUNICON phase II tri-
as complete (CMR), partial (PMR), or no metabolic real. Lancet Oncol 8:797-805
sponse. Histopathological findings were available in 30 7. Dassen AE, Lips DJ, Hoekstra CJ et al (2009) FDG-PET has
patients. After an estimated median 3.1 years of follow- no definite role in preoperative imaging in gastric cancer. Eur
up, all 17 CMR patients were free of disease. The PET J Surg Oncol 35:449-455
8. Sim SH, Kim YJ, Oh DY et al (2009) The role of PET/CT in
response was highly significantly associated with over- detection of gastric cancer recurrence. BMC Cancer 9:73
all survival duration (p<0.0001) and time to progression 9. Radan L, Fischer D, Bar-Shalom R et al (2008) FDG avidity
(p<0.0001). Pathological complete response was the and PET/CT patterns in primary gastric lymphoma. Eur J Nucl
only other statistically significant prognostic factor Med Mol Imaging 35:1424-1430
(p<0.03). The percentage of maximum SUV change af- 10. Ambrosini V, Tomassetti P, Castellucci P et al (2008) Compar-
ison between 68Ga-DOTA-NOC and 18F-DOPA PET for the
ter chemoradiation was not predictive of survival in detection of gastro-entero-pancreatic and lung neuro-
PMR patients. Based on a simple qualitative assess- endocrine tumours. Eur J Nucl Med Mol Imaging 35:1431-
ment, post-chemoradiation 18F-FDG-PET provides 1438
good medium-term prognostic information in patients 11. Joensuu H, Roberts PJ, Sarlomo-Rikala M et al (2001) Effect
of the tyrosine kinase inhibitor STI571 in a patient with a
with advanced rectal cancer undergoing radical surgery metastatic gastrointestinal stromal tumor. N Engl J Med
with curative intent [24]. 344:1052-1056
12. Goerres GW, Stupp R, Barghouth G et al (2004) The value of
PET, CT and in-line PET/CT in patients with gastrointestinal
stromal tumours: long-term outcome of treatment with ima-
Conclusions tinib mesylate. Comparison of PET, CT, and dual-modality
PET/CT imaging for monitoring of imatinib (STI571) therapy
FDG-PET/CT imaging is becoming more established in in patients with gastrointestinal stromal tumors. Eur J Nucl
the work-up of several abdominal malignancies of the Med Mol Imaging 4:4
13. Veit-Haibach P, Kuehle CA, Beyer T et al (2006) Diagnostic
gastrointestinal tract. The main advantage lies in its com- accuracy of colorectal cancer staging with whole-body
prehensive evaluation of the patient, including all body PET/CT colonography. JAMA 296:2590-2600
compartments, and therefore the detection of pivotal, ther- 14. Choi H, Charnsangavej C, Faria SC et al (2007) Correlation of
apy-deciding lesions. The performance of FDG-PET/CT computed tomography and positron emission tomography in
in the evaluation of primary tumors of the gastrointestinal patients with metastatic gastrointestinal stromal tumor treated
at a single institution with imatinib mesylate: proposal of new
tract is characterized by a high sensitivity in the detection computed tomography response criteria. J Clin Oncol 25:
of distant metastases. Secondary liver tumors such as 1753-1759
gastrointestinal metastases are detected by FDG-PET/CT 15. Bade MA, Ohki T, Cynamon J, Veith FJ (2001) Hypogastric
at a high rate, making this imaging technology a primary artery aneurysm rupture after endovascular graft exclusion
with shrinkage of the aneurysm: significance of endotension
tool in the evaluation of patients with suspicion of recur- from a “virtual,” or thrombosed type II endoleak. J Vasc Surg
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18F-DOPA, will bring significantly improved diagnostic
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confidence in the notoriously difficult evaluation of pa- rodeoxyglucose whole-body PET: correlation with histopatho-
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18. Kantorova I, Lipska L, Belohlavek O et al (2003) Routine
(18)F-FDG PET preoperative staging of colorectal cancer:
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IDKD 2010-2013
Tumors of the Adrenergic System: Imaging and Therapy

Cornelis A. Hoefnagel
Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Targeting of Neuroendocrine Tumors Radiolabeled monoclonal antibodies target antigens on

the cell surface of some NET. Examples are the murine
Neuroendocrine tumors (NET) include pheochromocy- monoclonal antibodies 131I-UJ13A and 131I-3F8, used in
toma, neuroblastoma, carcinoid, paraganglioma, chemo- the 1980s, and, more recently, chimeric antibodies, such
dectoma, medullary thyroid carcinoma, islet cell tumors, as 131I-chCE7, in the treatment of neuroblastoma. Ra-
gastrinoma, small cell lung cancer, melanoma, and Merkel dioiodinated anti-CEA antibodies/fragments may target
cell tumor. NET vary considerably in their clinical presen- CEA-producing medullary thyroid carcinoma (MTC).
tation, location, and histology but share a common embry- More recently, bispecific anti-DTPA/anti-CEA immuno-
onic tissue origin, i.e., the neural crest. In addition, all of conjugates have been shown to improve tumor/non-tumor
these tumors express several unique characteristics that ratios and to prolong retention in MTC [4].
may be exploited in the targeting of radiopharmaceuticals Non-specific tumor-seeking agents, such as 67Ga-cit-
for diagnostic as well as therapeutic purposes [1]. The spe- rate, 201Tl-chloride, 99mTc-pentevalent DMSA, and
99mTc-sestamibi, are also used for diagnostic scintigra-
cific targeting of NET may be achieved via the metabolic
route (meta-iodo-benzylguanidine, MIBG), through recep- phy. Although these tracers may be sensitive, they lack
tor binding (peptides), or immunologically (antibodies). specificity and therefore cannot be used therapeutically.
In metabolic targeting, 123I- or 131I-MIBG and 111In- New specific tracers for positron emission tomogra-
pentetreotide are sensitive and highly specific tracers, phy (PET) imaging have recently been developed, for ex-
and therefore the most widely used. In addition, compar- ample, 124I-MIBG, 11C-hydroxyephedrin, 6-[18F]-fluo-
ative studies have demonstrated a complementary role for rodopamine, and 68Ga-octreotide (the latter from a gen-
these procedures [1]. An active uptake mechanism at the erator). These agents combine great sensitivity and
cell membrane and by neurosecretory storage granules in specificity with the high-quality hybrid imaging provid-
the cytoplasm of neural crest tumors is responsible for the ed by PET/computed tomography (CT). These tech-
uptake and retention of 123I- or 131I-MIBG, respectively. niques will significantly improve the quality and relia-
Although the radiopharmaceutical may be released from bility of diagnostic imaging of NET. While 18F-fluo-
the granules, its specific re-uptake maintains a prolonged rodeoxyglucose (18F-FDG) does not have this high de-
intracellular concentration; this is in contrast to non- gree of specificity, it may be used to detect dedifferenti-
adrenergic tissues, in which uptake relies on passive dif- ating, rapidly growing tumors [5].
fusion only. The high selective accumulation results in As the role of radiolabeled peptides for imaging is dis-
high tumor/non-tumor ratios. However, it should be kept cussed elsewhere in this volume, the remainder of this
in mind that a number of drugs may interfere with the up- chapter focuses on the diagnosis and therapy of NET us-
take and/or the retention of MIBG [2]. ing 123I-MIBG or 131I-MIBG.
Somatostatin analogs target peptide receptors on the
cell surface and therefore can be used in the diagnosis Techniques
and therapy not only of several NET but also in other tu-
mors in which peptide receptors have been demonstrated Currently, there are several nuclear medicine procedures
autoradiographically [3]. Unlike MIBG- and antibody- involving the use of MIBG in the diagnosis and therapy
based targeting, the peptides are not specific for neural of NET.
crest tumors. 111In-pentetreotide is mostly used for diag- Diagnostic scintigraphy of the whole body uses either
nostic scintigraphy, while 90Y-labeled octreotide or lan- 123I-MIBG (γ-emitter, t
1/2fys = 13 h, photon energy 159
reotide and 177Lu-labeled octreotate are administered for Kev) or 131I-MIBG (β/γ-emitter, t1/2fys = 8 days, photon
targeted therapy. Other peptides used for diagnostic energy 364 KeV). 123I-MIBG scintigrams are of better
scintigraphy include 111In-lanreotide, 99mTc-depreotide, quality and the results are more readily available, where-
and 123I-vasoactive intestinal peptide. as 131I-MIBG enables delayed imaging over several days.
Tumors of the Adrenergic System: Imaging and Therapy 227
Single photon emission tomography (SPECT) or SPECT/ rule out Wilms tumor, Ewing sarcoma, rhabdomyo-
CT using 123I-MIBG provides improved detection in ad- sarcoma, osteosarcoma, and malignant lymphoma [9].
dition to accurate localization of NET sites by hybrid (fu- A recent prospective trial of 123I-MIBG scintigraphy in
sion) imaging. Positron emission tomography (PET) or 100 neuroblastoma patients showed an overall sensitivity
PET/CT using novel, specific PET tracers (see above) is of 88%, which increased slightly, to 91%, by the addi-
currently the most accurate diagnostic modality for NET. tion of SPECT. In patients with a recent diagnosis of
Following re-injection of 123I-MIBG, an intraoperative neuroblastoma, the sensitivity of the procedure was 93%
gamma-probe can be used to guide the surgical resection and its specificity 92% [10]. At present, 123I/131I-MIBG
of NET. Finally, radionuclide therapy with high doses of scintigraphy has an established role in the staging of
131I-MIBG is an option for tumors retaining a high con- disease and as a parameter in the response criteria.
centration of the radiopharmaceutical for a prolonged Discrepant findings of MIBG and bone scintigrams have
period of time (as demonstrated on the diagnostic scinti- been described, in favor of either the former or the lat-
gram). The procedure can be monitored by post-therapy ter. Since a positive finding on an MIBG scintigram is
total-body scintigraphy with or without 131I-MIBG the more specific one, the initial use of 123I/131I-MIBG
SPECT/CT fusion imaging. is preferred, but complementary bone scintigraphy may be
indicated. Radioimmunoscintigraphy with 131I-3F8 [11]
and, more recently, radioiodinated chimeric antibodies
Diagnostic Imaging directed against neuroblastoma have yielded results com-
plementary to those obtained with MIBG imaging [12].
Pheochromocytoma
Carcinoid Tumors
The role of 123I/131I-MIBG-scintigraphy in the diagnosis of
pheochromocytoma is not as a screening test. Instead it is The cumulative sensitivity of 111In-pentetreotide scintig-
the best initial procedure in patients who, on the basis of a raphy in patients with carcinoid (86%) is higher than that
clinical or familial history, are suspected of having of 131I-MIBG scintigraphy (70%) [1], thus favoring use
pheochromocytoma and with high plasma levels or urinary of the former in the initial diagnosis. 131I-MIBG scintig-
excretion rates of catecholamines and catecholamine raphy should not be used as a screening test for the ini-
metabolites. The cumulative sensitivity of 123I/ 131I-MIBG tial diagnosis of carcinoid, nor can it be relied upon to ex-
scintigraphy in potential pheochromocytoma patients is 88% clude disease. However, the combined use of the two
[1]. Although CT and magnetic resonance imaging of adren- techniques are possibly of therapeutic interest. A positive
al masses provide the surgeon with better anatomical detail, 111In-pentetreotide scintigram may predict a response to
a positive 123I/131I-MIBG scan is a highly specific finding. palliative octreotide therapy and indicate the feasibility of
The scintigraphic technique is superior for localizing extra- 90Y-octreotide or 177Lu-octreotate therapy, whereas in the
adrenal, recurrent, multifocal, and malignant disease [6]. Al- work-up of patients with proven carcinoid 131I-MIBG
though cumulative results of 111In-pentetreotide scintigraphy scintigraphy allows the selection of those patients who
also show a sensitivity for this technique of 88% in may benefit from 131I-MIBG therapy.
pheochromocytoma, a disadvantage in the detection of an
adrenal tumor is the renal, hepatic, and splenic accumulation Other Neuroendocrine Tumors
of the tracer. A recent prospective multicenter evaluation of
123I-MIBG in 150 patients with confirmed or suspected In MTC, radioimmunoassays of serum calcitonin and
pheochromocytoma or paraganglioma demonstrated a sen- CEA levels are currently the most sensitive parameters in
sitivity of 82-88% and a specificity of 82-84%. In this se- diagnosis and follow up, but in recent years many nuclear
ries, the addition of SPECT hardly affected these values [7]. medicine procedures have emerged that allow the disease
to be localized. This is especially the case for the detec-
Neuroblastoma tion of liver metastases and adrenal pheochromocytomas.
Total-body scintigraphy with SPECT using 201Tl-chlo-
The cumulative findings of 131I-MIBG scintigraphy re- ride, 99mTc-pentavalent DMSA, and/or 99mTc-sestamibi
ported in the literature [1] indicate that 92% of neuro- and PET using 18F-FDG are best used initially. These are
blastomas concentrate MIBG. 123I/131I-MIBG imaging all relatively non-specific procedures, but their sensitivi-
allows the detection of primary tumors, residual or ties are in the range of 80-90%. 111In-pentetreotide and
recurrent disease, and metastases, regardless of localiza- radiolabeled anti-CEA antibodies, with sensitivities of
tion, in a single procedure. When used together with 60-70%, may have a complementary role. 131I-MIBG has
urinalysis for catecholamine metabolites, MIBG imaging the lowest sensitivity (35%) and thus should only be used
is the most sensitive and highly specific indicator of once MTC metastases have been confirmed, to evaluate
neuroblastoma [8]. The uptake of MIBG is so tissue- its potential therapeutic role [1,13].
specific that in a child presenting with a tumor of un- A comparison of the results of 131I-MIBG and 111In-
known origin 123I/131I-MIBG-scintigraphy can non- pentetreotide in a variety of other neural crest tumors [1]
invasively establish the diagnosis of neuroblastoma and showed highest sensitivities for 111In-pentetreotide in
228 Cornelis A. Hoefnagel
paraganglioma (97%), small cell lung cancer and, to a availability and feasibility of other treatment modalities
lesser degree, endocrine gastroenteropancreatic (GEP) as well as the patient’s condition determine the indication.
tumors, Merkel cell tumor, melanoma, and functioning The principle indications for 131I-MIBG therapy are ma-
pituitary tumors. 123I/131I-MIBG scintigraphy is useful lignant pheochromocytoma and paraganglioma, neuro-
for the detection of ganglioneuroma, paraganglioma, and blastoma stage III and IV, MTC, and symptomatic,
chemodectoma; it is of limited use in pancreatic islet cell metastatic carcinoid tumors [14].
tumors, retinoblastoma, schwannoma, and Merkel cell tu- Contraindications for radionuclide therapy in general
mors. It has no place in the diagnosis of small cell lung are: pregnancy, continued breast feeding, myelosuppres-
cancer and melanoma [1]. sion, and renal failure. In addition, relative contraindica-
Although high sensitivities for 111In-pentetreotide tions apply to those patients whose condition is unstable
scintigraphy have been reported in non-neural crest tu- or who fail to understand or cooperate with the radiation
mors, e.g., non-small cell lung cancer, brain tumors, and protection guidelines, or if isolation facilities are lacking.
lymphomas, as well as in granulomatous and auto-
immune diseases, 131I-MIBG scintigraphy, as a highly Malignant Pheochromocytoma and Paraganglioma
specific procedure for neural crest tumors, is virtually
always negative in non-neural crest tumors [1, 9]. The objective of 131I-MIBG therapy includes objective tu-
mor volume reduction (complete or partial response), tumor
arrest (stabilization of previously progressive disease), a re-
Rationale for Using MIBG and Somatostatin-Receptor duction of the tumor’s metabolic function (as the prognosis
Imaging Procedures in pheochromocytoma may depend on the long-term con-
sequences of catecholamine hypersecretion, this may
Scintigraphy using 111In-pentetreotide is the best initial actually prolong survival), and palliation of symptoms (e.g.,
procedure in patients with carcinoid, endocrine gastroen- hypertension, bone pain, sweating, constipation) [14].
teropancreatic tumors, and (benign) paraganglioma. In 1991, the results of 131I-MIBG therapy in 117 pa-
131I-MIBG can be reserved to evaluate the feasibility of tients with pheochromocytoma treated in 14 centers
therapy and for radionuclide treatment of these tumors. worldwide were pooled [15]. An objective response, de-
123I/131I-MIBG scintigraphy remains the best initial pro- fined as a >50% decrease in catecholamine excretion, a
cedure for pheochromocytoma, neuroblastoma, and ma- >50% reduction of tumor volume, or, if lesions could not
lignant paraganglioma, because of its high sensitivity/ be measured, significant scintigraphic improvement, was
specificity as well as its effective therapeutic application determined in 56% of the patients. The response of soft-
in these conditions. Both tracers play a modest role in tissue metastases was better than that of skeletal metas-
MTC, i.e., complementary to the more sensitive but tases. In addition, a subjective improvement of symp-
non-specific tracers and in the evaluation of the various toms, decrease in blood pressure, and pain relief were
therapeutic options. achieved in >60% of the patients. Long-lasting objective
responses have been reported also in malignant para-
ganglioma, in secreting and in non-secreting types [16].
Radionuclide Therapy These tumors may be treated either with 131I-MIBG or
90Y-/177Lu-labeled octreotide/octreotate.
Indications/Contraindications for Therapy At a European Association of Nuclear Medicine

(EANM) Radionuclide Therapy Committee workshop on
Any malignant neural crest tumor showing sufficient up- 131I-MIBG therapy, held in 1999, treatment results were
take and prolonged retention of 131I-MIBG on a diagnos- gathered for 534 patients with neural crest tumors, in-
tic tracer study (ideally >1% of the administered dose, cluding 77 patients with malignant pheochromocytoma
depending on tumor volume) is a candidate for radio- and 34 with paraganglioma (Table 1). The cumulative
nuclide therapy. Apart from tracer concentration, the objective response rates with respect to tumor volume
Table 1. Pooled results of 131I-MIBG therapy in neural crest tumors (EANM Radionuclide Therapy Committee Workshop, Barcelona,
October 1999)
Disease Patients (N) Objective response: Objective response: Subjective response:
tumor volume (%) biochemical (%) palliation (%)
Pheochromocytoma 77 51 68 68
Paraganglioma 34 48 51 70
Neuroblastoma 229 51 NA Most patients
Medullary thyroid carcinoma 29 23 60 60
Carcinoid 159 8 24 60
Other 6 2/6 NA NA
Total 534
Tumors of the Adrenergic System: Imaging and Therapy 229
were 51 and 48%, respectively; a >50% decrease in cat- toxicity and the early induction of drug resistance.
echolamine excretion was observed in 68 and 51%, re- Chemotherapy is reserved for the post-operative treat-
spectively, while symptomatic palliation occurred in 68% ment of minimal residual disease. Initial results have
of the patients. These results compare favorably with the demonstrated the feasibility and effectiveness of this ap-
best reported results of combination chemotherapy and proach, i.e., a higher objective response rate (>70%) and
were attained with a treatment that is non-invasive and as- considerably less toxicity than obtained with 131I-MIBG
sociated with minimal side effects. therapy after conventional treatment [22]. By 2001, re-
Recently published results in a group of 20 patients sults in 56 patients showed that 131I-MIBG is as effective
with malignant pheochromocytoma or paraganglioma as chemotherapy in attaining operable neuroblastoma:
who were treated with moderate administered doses 43 of 56 evaluable patients (77%) had complete or >95%
(7.4 GBq) at the Netherlands Cancer Institute (objective resection of the primary tumor or did not require surgery
response 47%, metabolic response 67%, subjective re- at all. At follow-up (13-144 months), 5-year survival was
sponse 89%) [17] compare well with those reported by 37%. Based upon these results, two new multicenter stud-
the group at Duke University (Durham, NC, USA), who ies have been initiated in which 131I-MIBG therapy is
treated 18 patients with moderate doses (7.4 GBq) and 15 integrated up-front in the treatment protocol of neuro-
with high doses (18.5 GBq). The objective response was blastoma. Patients with favorable parameters receive a
38%, metabolic response 60%, and subjective response less aggressive therapy than before, consisting of two
86% [18]. Moreover, both a metabolic response and a cycles of 131I-MIBG followed by surgery, whereas in
subjective response were suggested to have an important patients with unfavorable parameters (high-risk group)
influence on survival and quality of life, even in the ab- 131I-MIBG therapy is intensified and combined with the
sence of an objective volume response. topoisomerase I inhibitor Topotecan to enhance radiation-
induced cytotoxicity.
Neuroblastoma
Medullary Thyroid Carcinoma
Since 1984, therapeutic doses of 131I-MIBG have been
administered to children with metastatic or recurrent neu- In the abdomen, medullary thyroid carcinoma (MTC)
roblastoma that failed to respond to conventional treat- may present with liver metastases. Results of combina-
ment. In 1991, the pooled results of the major centers tion chemotherapy are disappointing whereas radio-
(273 patients) indicated an objective response rate of nuclide therapy using 131I-MIBG or 131I-anti CEA anti-
35% [15]; more recently, the response rate increased to bodies may provide both tumor regression and palliation.
51% (Table 1). Most of these patients had stage IV, pro- Pooled results in 29 patients with MTC treated with
gressive, and intensely pre-treated disease, and were ad- 131I-MIBG (Table 1) showed that an objective response
ministered 131I-MIBG only after other treatment modali- rate occurred in only 23% and tumor marker response in
ties had failed. Both 131I-MIBG therapy and isolation are 60%; nevertheless, palliative effects, which may be quite
generally well tolerated by children; however, hematolog- meaningful, were achieved in 60% of the patients. How-
ical side effects may occur. Apart from the objective re- ever, only a minority of patients demonstrated sufficient
sponse, the palliative effect was often impressive. Thus, uptake of 131I-MIBG.
for patients with recurrent and progressive disease after More patients may be amenable to radioimmuno-
conventional treatment 131I-MIBG therapy is probably the therapy. In a phase I/II study of treatment using bi-
best palliative treatment, as its invasiveness and toxicity specific anti-DTPA/anti-CEA immunoconjugates fol-
compare favorably with that of chemotherapy and exter- lowed by 131I-hapten in a two-step procedure, 26 MTC
nal beam radiotherapy [19]. patients showed mixed responses. Stabilization of dis-
Some groups have combined 131I-MIBG therapy with ease and palliation were attained with limited hemato-
chemotherapy and/or total-body irradiation, accepting logical toxicity, but a HAMA (human anti-mouse anti-
more toxicity, as well as with myeloablative chemotherapy body) response was reported in more than half of the
requiring autologous bone marrow or stem-cell rescue [20]. patients [23]. As patients may require several such
Voûte et al. [21] combined 131I-MIBG therapy with treatments, the use of chimeric or humanized immuno-
oxygen treatment under hyperbaric conditions. Their aim conjugates would be more appropriate.
was to improve survival in patients with recurrent stage
IV neuroblastoma by adding the toxic effect of hydroxyl Carcinoid Tumors
radicals to the radiation effect. Subsequently, high-dose
vitamin C therapy was added to this regimen. Palliative treatments for metastatic carcinoid tumors
More recently, 131I-MIBG therapy has been integrated include long-acting somatostatin analogs (Sandostatin),
in the treatment protocol as the initial therapy instead α-interferon, hepatic artery embolization, 131I-labeled and
of its use in pre-operative combination chemotherapy in unlabeled MIBG, and 90Y- or 177Lu-labeled octreotide
children presenting with advanced/inoperable neuro- therapy. The cumulative results of 131I-MIBG therapy in
blastoma. The objective is to reduce the tumor volume, 159 patients with symptomatic, metastatic disease showed
thereby enabling adequate surgical resection, and to avoid an objective response rate of only 8% and a >50% decrease
230 Cornelis A. Hoefnagel
in 5-hydroxyindoleacetic acid (5-HIAA) excretion in 24% 11. Yeh SDJ, Larson SM, Burch L et al (1991) Radioimmunode-
(Table 1). Despite the absence of an objective response, tection of neuroblastoma with Iodine-131-3F8: correlation
with biopsy, Iodine-131-Metaiodobenzylguanidine and stan-
palliation was achieved in 60% of patients and without dard diagnostic modalities. J Nucl Med 32:769-776
significant side effects [24]. In view of the often indolent 12. Hoefnagel CA, Rutgers M, Buitenhuis CKM et al (2001) A
character of this disease, the value of a prolonged sympto- comparison of targetting neuroblastoma with mIBG and anti
matic response should not be underestimated. In a study L1-CAM antibody mAB chCE7: therapeutic efficacy in a neu-
at Duke University Medical Center, 98 patients with roblastoma xenograft model and imaging of neuroblastoma pa-
tients. Eur J Nucl Med 28:359-368
metastatic carcinoid were treated with 131I-MIBG. In this 13. Hoefnagel CA, Delprat CC, Zanin D, van der Schoot JB
group, a subjective response was found to correlate with (1988) New radionuclide tracers for the diagnosis and therapy
prolonged survival [25]. of medullary thyroid carcinoma. Clin Nucl Med 13:159-165
In patients with carcinoid tumors not qualifying for 14. Hoefnagel CA and Lewington VJ (2004) MIBG therapy.
131I-MIBG therapy because of no or insufficient uptake In: Ell PJ and Gambhir SS (eds) Nuclear medicine in clinical
diagnosis and treatment, 3rd edn. Churchill Livingstone,
by the tumor, palliative treatment with high doses of un- Edinburgh, pp 445-457
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due to enhanced tumor/non-tumor ratios by pre-dosing 16. Baulieu J-L, Guilloteau D, Baulieu F et al (1988) Therapeutic
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combination of higher doses of 131I-MIBG and unlabeled ing paraganglioma. J Nucl Med 29:2008-2013
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131 metaiodobenzylguanidine as an effective treatment for
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IDKD 2010-2013
Neuroendocrine Tumors of the Abdomen: Imaging and Therapy

Dik J. Kwekkeboom
Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Introduction between a successful localizing study and a disappointing

one. For details of the scanning protocol, the reader is re-
The development of peptide receptor scintigraphy in ferred to the procedural guidelines for somatostatin re-
combination with radioiodinated somatostatin analogues ceptor scintigraphy with [111In-DTPA0]octreotide, pub-
allowed the in vivo demonstration of somatostatin-receptor- lished by the Society of Nuclear Medicine [2].
positive tumors in patients [1]. Later, other radiolabeled
somatostatin analogues were developed, two of which [111In-DTPA0]Octreotide Scintigraphy: Normal Scintigraphic
subsequently became commercially available. With the Findings and Artifacts
advent, over the past decade, of positron emission to-
mography (PET) tracers for somatostatin receptor imag- Normal scintigraphic features include visualization of the
ing, superior image quality and increased sensitivity in thyroid, spleen, liver, and kidneys, and in some patients the
tumor site detection have become possible, as confirmed pituitary gland (Fig. 1). In addition, the urinary bladder and
by several research groups. In the 1990’s, attempts at
treatment with radiolabeled somatostatin analogues were
undertaken in patients with inoperable and/or metasta-
sized neuroendocrine tumors. Improvements in the pep-
tides (higher receptor affinity) and the available radionu-
clides (β instead of γ emission), together with precautions
to limit the radiation dose to the kidneys and bone mar-
row, led to better results and a virtually negligible per-
centage of serious adverse events.
Somatostatin-Receptor-Based Radionuclide Imaging

The many drawbacks of [123I,Tyr3]octreotide, the radio-
iodinated somatostatin analogue first used for imaging in
patients, resulted in its replacement by the chelated and
111In-labeled somatostatin analogue [111In-DTPA0]oc-
treotide (OctreoScan, Covidien, Petten, The Netherlands),
which is commercially available and is now the most
commonly used agent for somatostatin receptor imaging
(SRI). The preferred dose of [111In-DTPA0]octreotide
(containing at least 10 mg of the peptide) is about
200 MBq. This dose is appropriate for single photon
emission computed tomography (SPECT), which shows
increased sensitivity in the detection of somatostatin-
receptor-positive tissues and provides better anatomical
delineation than planar views. The acquisition of suffi- Fig. 1. Normal distribution in somatostatin receptor imaging (SRI).
cient counts per view and the generation of spot images Variable visualization of the pituitary and thyroid (arrows, upper
panels). Faint breast uptake can sometimes be seen in women (right
with a sufficient counting time – as opposed to the low middle panel, arrow). Normal uptake in the liver, spleen, and kid-
count density of whole-body scans – are other important neys, and also some bowel activity is seen in the lower panel. Gall-
advantages of this approach and may make the difference bladder visualization in the lower right panel (arrow). Anterior views
232 Dik J. Kwekkeboom
Table 1. Pitfalls and causes of potential misinterpretation of positive density of somatostatin receptors. NETs comprise a
results with [111In-DTPA0]octreotide scintigraphy group of tumors that includes pituitary adenoma, pancre-
Radiation pneumonitis atic islet cell tumor, carcinoid, pheochromocytoma, para-
Accessory spleen ganglioma, medullary thyroid cancer, and small cell lung
Focal collection of stools carcinoma [4]. Tumors of the nervous system, including
Surgical scar tissue meningioma, neuroblastoma, and medulloblastoma, also
Gallbladder uptake
Nodular goiter very often express a high density of somatostatin recep-
Ventral hernia tors, as do tumors not classically originating from en-
Bacterial pneumonia docrine or neural cells, such as lymphoma, breast cancer,
Respiratory infections renal cell cancer, hepatocellular cancer, prostate cancer,
Common old (nasal uptake) sarcoma, and gastric cancer. In the majority of these tu-
Cerebrovascular accident
Concomitant granulomatous disease mors, somatostatin receptor (SR) subtype-2 is predomi-
Diffuse breast uptake nantly expressed, although low amounts of other SR sub-
Adrenal uptake types may be concomitantly present [5]. It should also be
Urine contamination emphasized that selected non-tumoral lesions may ex-
Concomitant second primary tumor press SRs. For instance, SRs are expressed on the epithe-
lioid cells of active granulomas in sarcoidosis and by in-
flamed joints in active rheumatoid arthritis, especially the
Table 2. Causes of potential misinterpretation of negative results proliferating synovial vessels [6]. Therefore, SR expres-
with [111In-DTPA0]octreotide scintigraphy sion is not specific for tumoral pathologies.
The most common indication for [111In-DTPA0]oc-
The presence of unlabeled somatostatin, because of octreotide treotide scintigraphy is the detection and localization of
therapy or due to the production of somatostatin by the tumor itself,
may lower tumor detectability gastroenteropancreatic neuroendocrine tumors (GEP-
Different somatostatin receptor subtypes have different affinities NETs) and their metastases, the staging of these patients,
for the radioligand; variable tumor differentiation and receptor the follow-up of patients with known disease, and, lastly,
expression also influences tumor detectability. This may be impor- the selection of patients with inoperable and/or metastat-
tant especially in patients with insulinomas and medullary thyroid ic tumors for peptide receptor radionuclide therapy
carcinomas (PRRT) [7-12].
Liver metastases of neuroendocrine tumors may appear isointense
because of a similar degree of tracer accumulation by the normal
liver. Correlation with anatomical imaging and/or SPECT imaging
Newer Ligands for Somatostatin Receptor Imaging
may be helpful
99mTc-depreotide (Neotect) is a commercially available so-
matostatin analogue that has been approved specifically for
use in the detection of lung cancer in patients with pul-
the bowel are usually visualized to variable degrees. Visu- monary nodules [13]. Due to the relatively high abdominal
alization of the pituitary, thyroid, and spleen is due to re- signal background and the impossibility to perform de-
ceptor binding whereas uptake in the kidneys is for the layed imaging because of the tracer’s short half-life, it is
most part due to re-absorption of the radiolabeled peptide less suited for the detection of abdominal NETs [14].
by the renal tubular cells after glomerular filtration. While Analogues that are used for PET or hybrid PET/CT
there is predominant renal clearance of the somatostatin imaging are of particular interest because of two advan-
analogue, hepatobiliary clearance via the bowel also oc- tages that they have over γ-emitting analogues. First, many
curs, thus necessitating the administration of laxatives in of them have a better affinity for SR subtype-2, the subtype
order to facilitate the interpretation of abdominal images. most commonly expressed by NETs; likewise, there are
False-positive results of SRI with [111In-DTPA0]oc- some analogues that better target other SR subtypes and are
treotide have been reported in virtually all cases; howev- therefore more appropriate for visualizing the respective tu-
er, the term “false-positive” is a misnomer because it in- mors. Second, PET and the combined anatomical and func-
cludes somatostatin-receptor-positive lesions unrelated to tional information obtained with PET/CT provide images
the pathology for which the investigation was performed with high spatial resolution, which results in a higher sen-
(see the review by Gibril et al. [3]). The most common of sitivity of this type of scanning. However, based on a re-
these are listed in Table 1. The potential causes of a false- view of the results obtained with these newer analogues,
negative study interpretation are given in Table 2. there are also causes for concern. Importantly, in many
studies these newer analogues were compared to [111In-
Imaging Results of [111In-DTPA0]Octreotide Scintigraphy DTPA0]octreotide scintigraphy using inadequate scanning
in Neuroendocrine and Other Tumors protocols or comparisons were made between two or
more new analogues such that a validated reference method
Somatostatin receptors have been identified in vitro in a was lacking. Also, the multitude of newly available PET
large number of human neoplasias, in particular, neu- analogues has led to a situation in which each center has to
roendocrine tumors (NETs) have a high incidence and accumulate its own results on the normal findings and
Neuroendocrine Tumors of the Abdomen: Imaging and Therapy 233
artifacts of their scanning methods. This hampers the ex- the GEPNETs are usually slow-growing. The treatment
change of data and their shared interpretation. It is, howev- of tumor metastases with somatostatin analogues results
er, likely that one of the new PET analogues, [68Ga-DOTA0, in reduced hormonal overproduction and symptomatic re-
Tyr3]octreotide or [68Ga-DOTA0, Tyr3]octreotate, will be- lief in most cases. Treatment with somatostatin analogues
come the new standard for SRI using PET. This is due to is, however, seldom successful in terms of tumor size re-
the fact that these somatostatin analogues have a high affin- duction [19].
ity for SR subtype-2, and 68Ga is a generator-produced A new treatment modality for patients with inoperable
rather than a cyclotron-produced product, such that label- or metastasized endocrine GEPNETs is the use of radio-
ing of the compound is simplified [15]. An additional rea- labeled somatostatin analogues. The majority of en-
son favoring the use of [68Ga-DOTA0,Tyr3]octreotide or docrine GEP tumors possess SRs and can therefore be vi-
[68Ga-DOTA0, Tyr3]octreotate as the standard analogue for sualized with SRI. A logical sequence to tumor visual-
PET imaging is that the 90Y or 177Lu-labeled counterparts ization in vivo is to then treat these patients with radiola-
of these compounds are administered for PRRT; thus, the beled somatostatin analogues. In the early phases of this
peptide used in diagnostic imaging closely mimics the one approach, virtually all patients considered as candidates
that is used for therapy. Other radionuclide-coupled ligands for PRRT had well-differentiated GEPNETs. At the time
that do not rely on the presence of SRs for tumor visual- of these early studies, in the mid- to late 1990s, no other
ization have also been tested in patients with GEPNETs. chelated somatostatin analogues labeled with β-emitting
The oldest of these, 123I-MIBG, performs poorly compared radionuclides were available, such that [111In-DTPA0]oc-
to [111In-DTPA0]octreotide scintigraphy [16]. treotide was used for PRRT. The results of these studies,
PET scanning with (18F)2-fluoro-2-deoxy-D-glucose in which high doses of the radionucleotide were admin-
18
( F-FDG) has gained importance for tumor staging and istered to patients with metastasized NETs, were encour-
the evaluation of treatment response for a number of tu- aging with regard to symptom relief but partial remis-
mor types. The method is based on glucose consumption sions (PRs) were exceptional [20, 21] (Table 3).
by the tumors, such that fast-growing tumors usually The next generation of SR-mediated radionuclide thera-
show high tracer uptake. However, 18F-FDG PET is less py was based on the use of the modified somatostatin ana-
suited for GEPNETs, because of the slow growing nature logue [Tyr3]octreotide, which has a higher affinity for SR
of these tumors. Therefore, the technique is recommend- subtype-2, and a different chelator, DOTA instead of DTPA,
ed only in patients with negative SRI findings [17], a sit- in order to ensure a more stable binding of the intended
uation that usually correlates with more aggressive tumor β-emitting radionuclide, 90Yttrium (90Y). The resulting
behavior and faster tumor growth. compound (90Y-DOTATOC; OctreoTher, Novartis, Switzer-
Newer PET radioligands that have been clinically land), was used in several phase-1 and phase-2 PRRT trials
tested in patients with GEPNETs include 18F-DOPA and [22-25] (Table 3) but renal insufficiency and myelodys-
11C-5-hydroxy-tryptophan [18]. PET with these ligands plastic syndrome were reported as serious adverse events
has been reported to be more sensitive than SRI with (SAEs). The incidence of these SAEs could, however, be
[111In-DTPA0]octreotide. These PET ligands, however, dramatically reduced through adequate renal protection,
have a short half-life and therefore have to be synthesized achieved by the co-infusion of amino acids. Consequently,
in the close vicinity of or in the hospital where they are SAEs have become relatively rare, occurring in <10% of
to be administered. Also, both 18F-DOPA and 11C-5- patients [26]. Despite differences in protocols, the rate of
hydroxy-tryptophan, unlike the radiolabeled somatostatin complete remission (CR) and PR reported by most of the
analogues used in PET, lack a sequel in PRRT. different studies with [90Y-DOTA0,Tyr3]octreotide are in the
same range, between 10 and 30%, which is better than the
rates obtained with [111In-DTPA0]octreotide.
Somatostatin-Receptor-Based Radionuclide Therapy Reubi et al. [27] reported a nine-fold increase in so-
matostatin receptor subtype-2 affinity for [DOTA0,
As noted above, the functioning and non-functioning en- Tyr3]octreotate vs. [DOTA0,Tyr3]octreotide, and a six to
docrine pancreatic tumors and carcinoids that make up seven-fold increase in the affinity for the Yttrium-loaded
Table 3. Tumor responses in patients with GEPNETs, treated with different radiolabeled somatostatin analogues
Center Tumor response ligand Patient Complete Partial Minimal Stable Progressive Complete
(reference) number remission remission response disease disease + partial
remissions
Rotterdam [20] [111In-DTPA0]octreotide 26 0 0 5 (19%) 11 (42%) 10 (38%) 0%
New Orleans [21] [111In-DTPA0]octreotide 26 0 2 (8%) NA 21 (81%) 3 (12%) 8%
Milan [22] [90Y-DOTA0,Tyr3]octreotide 21 0 6 (29%) NA 11 (52%) 4 (19%) 29%
Basel [23, 24] [90Y-DOTA0,Tyr3]octreotide 74 3 (4%) 15 (20%) NA 48 (65%) 8 (11%) 24%
Rotterdam [25] [90Y-DOTA0,Tyr3]octreotide 58 0 5 (9%) 7 (12%) 33 (61%) 10 (19%) 9%
Rotterdam [29] [177Lu-DOTA0,Tyr3]octreotate 310 5 (2%) 86 (28%) 51 (16%) 107 (35%) 61 (20%) 29%
counterparts of this compound. In addition, a comparison hormone-related crises [30]. All patients recovered after
carried out in patients showed that the uptake of radioac- adequate care. Subacute, hematological toxicity of WHO
tivity, expressed as percentage of the injected dose of toxicity grade 3 or 4 occurred 4-8 weeks after 3.6% of ad-
[177Lu-DOTA0,Tyr3]octreotate, was comparable to that ministrations, or, expressed in a patient-based manner, af-
after [111In-DTPA0]octreotide for kidneys, spleen, and ter at least one of several treatments in 9.5% of patients.
liver, but was 3- to 4-fold higher for four of five tumor Serious delayed toxicities were observed in 9 out of 504
types [28]. Therefore, [177Lu-DOTA0,Tyr3]octreotate po- patients. There were two cases of renal insufficiency,
tentially represents an important improvement because of both of which were probably unrelated to 177Lu-octreo-
the higher absorbed doses that can be achieved in most tate treatment. Three patients showed serious liver toxic-
tumors and the essentially equal doses to potentially ity, in two of these cases probably treatment-related. Last-
dose-limiting organs. Moreover, the lower tissue penetra- ly, myelodysplastic syndrome occurred in four patients
tion range of 177Lu vs. 90Y may be especially important and was probably treatment-related in three.
for small tumors. These findings support the use of Treatment responses according to tumor type at
177Lu-octreotate as the radiolabeled somatostatin ana- 3 months after the last therapy cycle were analyzed in
logue of choice in PRRT. 310 patients. The overall objective tumor response rate,
The side effects and treatment outcome of [177Lu- comprising CR, PR, and minimal response (MR), was
DOTA0,Tyr3]octreotate therapy have been analyzed by 46% (for an example, see Fig. 2). Prognostic factors pre-
our group in 504 and 310 patients with GEPNETs, re- dicting tumor remission, i.e., CR, PR, or MR, as treat-
spectively [29]. In the 504 patients, acute side effects oc- ment outcome were uptake on the OctreoScan (p <0.01)
curring within 24 h after administration of the radio- and Karnofsky performance score (KPS) >70 (p <0.05). A
pharmaceutical included nausea (following 25% of admin- small percentage of patients who had either stable disease
istrations), vomiting (10%), and abdominal discomfort or (SD) or MR at their first two evaluations after therapy
pain (10%). Six patients were hospitalized within 2 days had a further improvement in categorized tumor response
of administration of the radiopharmaceutical because of at 6 and 12 months follow-up, occurring in 4% and 5%
3-2007 5-2007 11-2007 2-2008 11-2008
CT
SRI
Post Tx 1 Post Tx 4
Fig. 2. Serial CT scans, SRI, and post peptide receptor radionuclide therapy (PPRT) scans in a patient with metastatic neuroendocrine tu-
mor with unknown primary. Month and year are indicated in the top row. Notice the ongoing tumor regression on CT, and also the im-
provement on SRI. The last post-therapy scan shows less tumor uptake than in the first; the difference is even more impressive if the same
scaling is used (but then, due to the impressive tumor uptake, in May 2007 the tumors would appear as one large hot spot occupying most
of the abdomen). This diminishing tumor uptake on subsequent post-therapy scans usually implies tumor shrinkage
Neuroendocrine Tumors of the Abdomen: Imaging and Therapy 235
of patients, respectively. Three of four patients with clin- cant weight loss, when waiting for formally assessed tu-
ically non-functioning neuroendocrine pancreatic tumors, mor progression would place these patients in an unfa-
that were judged inoperable before treatment with 177Lu- vorable starting position for treatment or would even
octreotate and who had PR, successfully underwent make them ineligible for treatment.
surgery 6-12 months after their last treatment; the fourth
patient died of postoperative complications. The median
time to progression was 40 months from the start of treat- Conclusions
ment. Median overall survival in our 310 GEP tumor
patients was 46 months (median follow-up 19 months; The use of [111In-DTPA0]octreotide in SRI has a proven
101 deaths). Median disease-related survival was >48 role in the diagnosis and staging of GEPNETs. Newer
months (median follow-up 18 months; 81 deaths). Median radiolabeled somatostatin analogues that can be used in
progression-free survival was 33 months. The most impor- PET imaging, and which have a higher SR affinity, espe-
tant factor predicting survival was treatment outcome. cially for subtype-2, have been developed. It would be de-
Low KPS and liver involvement were also very signifi- sirable, however, if one radiolabeled analogue became the
cant predictors. new standard for PET imaging, as the current application
of a multitude of analogues implies a fragmented knowl-
Comparison of Survival Data edge regarding image interpretation.
Treatment with radiolabeled somatostatin analogues
Since, in our study, treatment with [177Lu-DOTA0,Tyr3] is a promising new tool in the management of patients
octreotate is still open for new patients and the median with inoperable or metastasized NETs. The results thus
follow-up in relation to survival is still relatively short, far obtained with [ 90Y-DOTA 0,Tyr 3]octreotide and
we analyzed our local, Dutch patients separately, and [177Lu-DOTA0,Tyr3]octreotate have been very encour-
specifically those patients with longer follow-up. The re- aging in terms of tumor regression. Also, if kidney-
sults from these analyses suggest that both overall and protective agents are used, the side effects of this form
disease-specific survival times are consistently at or of therapy are few and mild, and the duration of the
above 48 months. These numbers compare favorably to therapy response for both radiopharmaceuticals may be
those reported in the literature. A comparison of survival longer than 30 months. Lastly, compared to historical
data for our patients, either from time of diagnosis or controls, there appears to be a benefit in overall sur-
from time of referral, with data from different epidemio- vival of several years from the time of diagnosis in pa-
logical studies or studies pertaining to a specific inter- tients treated with [ 177Lu-DOTA 0,Tyr 3]octreotate.
vention, and limiting our data to similar subgroups of pa- These data compare favorably with the limited number
tients, showed a benefit in overall survival for patients of alternative treatment approaches. If more wide-
treated with 177Lu-octreotate, which ranged from 40 to 72 spread use of PRRT can be guaranteed, it may well be-
months from the time of diagnosis [29]. We are aware come the therapy of choice in patients with metasta-
that comparisons with historical controls should be inter- sized or inoperable GEPNETs.
preted with caution, but we also think that this consistent
difference with many other reports in similar patient
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PEDIATRIC SATELLITE COURSE
“KANGAROO”
IDKD 2010-2013
Imaging Cystic Kidneys in Children

Fred E. Avni
Department of Radiology, University Clinics of Brussels, Erasme Hospital, Brussels, Belgium
Introduction associated anomalies. The timing of detection is impor-

tant as is the amount of amniotic fluid, since both are im-
Renal cystic diseases may be discovered or suspected at portant features for the final diagnosis and prognosis.
any gestational week during fetal life or at any age in A pre-existing familial history of any renal cystic dis-
childhood. They encompass a large number of conditions ease or of any syndrome with renal involvement in a fe-
that can be separated according to whether or not they are tus in which abnormal kidneys have been detected should
hereditarily transmitted (Table 1). Imaging, mainly ultra- raise strong suspicion. Finally, the evaluation should in-
sound (US), but also computed tomography (CT) and clude a detailed clinical inquiry, looking for toxic causes
magnetic resonance imaging (MRI) in selected indica- or maternal diseases that may influence fetal health.
tions, plays an important role in differentiating between
the various types of cystic diseases, by showing the char- Hyperechoic Kidneys in the Perinatal Period
acteristics of renal involvement as well as associated
anomalies [1-5]. This group includes many diseases that are genetically
transmitted or acquired during fetal life. Their evaluation
requires a step by step approach. Most will be discovered
Cystic Renal Diseases in the Fetus and in the Perinatal during the second and third trimester.
Period
Sonographic Criteria
In the fetus (and perinatal period), cystic renal disease
should be suspected whenever bilateral hyperechoic kid- Renal cortical hyperechogenicity is determined by com-
neys or cysts (uni- or bilateral) are discovered during an paring the renal cortex to the adjacent liver or to the spleen.
obstetrical ultrasound examination. The imaging ap- While hyperechogenicity is in most cases visually obvious,
proach for the diagnosis should be based on a detailed there are four objective criteria indicative of cystic disease:
sonographic analysis that includes measurement of renal 1. the renal cortex should not be hyperechoic compared
length, the presence or absence of corticomedullary dif- to the liver or spleen during the third trimester;
ferentiation (CMD), and the presence, number, size and 2. the appearance of the CMD, which can be normal, in-
location of the cysts. This evaluation should be complet- creased, absent or reversed (due to a hyperechoic
ed through an analysis of the entire fetus, looking for medulla);
Table 1. Classification of cystic diseases of the kidney in the fetus and in children
Genetic diseases Autosomal recessive polycystic kidney disease (ARPKD)
Autosomal dominant polycystic kidney disease (ADPKD)
Glomerulocystic kidney diseases (including TCF2 anomalies,
nephronophitisis/medullary sponge kidney complex)
Cystic dysplasia
Medullary cystic dysplasia associated with syndromes
Non-genetic diseases (congenital or acquired) Renal obstructive dysplasia (associated with urinary tract malformations)
Multicystic/dysplastic kidney (some cases with genetic transmission)
Localized cystic dysplasia
Simple cyst
Multilocular cyst
Cystic tumor
Cysts associated with chronic dialysis
240 Fred E. Avni
3. renal size: markedly increased (>+4 SD), moderately Table 2. Causes of moderately enlarged hyperechoic kidneys in the
increased (>+2 SD), or normal or small (<–2 SD) [6]; fetus
4. the presence of renal cysts. TCF2 mutation
Finally, any familial history or associated findings Autosomal recessive polycystic kidney disease
constitute important factors for the differential diagnosis Autosomal dominant polycystic kidney disease
[2, 6-9]. Maternally related diseases
Infection
Ischemia
Differential Diagnosis Metabolic diseases
Dysplasia
In case of markedly enlarged (>+4SD) hyperechoic kid- Nephrotic syndromes
neys diagnosed during the late first and early second “Transient”
trimesters, Meckel-Gruber syndrome should be consid-
ered first, especially if the medulla appears enlarged and
hypoechoic and if polydactyly and cerebral anomalies are Once these three diagnoses are excluded, there is a
associated. If the condition is detected during the second wide spectrum of other diseases that can lead to hyper-
and third trimesters, the main diagnosis to be added to the echoic kidneys; clinical inquiry may suggest the diagnosis
differential would be autosomal recessive polycystic kid- [14, 15]. Complementary examinations, such as chromo-
ney disease (ARPKD) and Bardet-Biedl syndrome somal analysis, are directed at searching for infectious,
(BBS). In ARPKD, CMD may be partially absent, com- toxic, maternally related, or ischemic causes and will help
pletely absent, or even reversed. A few visible cysts are to reach a diagnosis (Table 2).
rare but may be seen in utero. Oligohydramnios is a fre-
quent finding and is associated with pulmonary hypopla- Renal Cyst(s) Discovered in the Perinatal Period
sia, which confers a very poor prognosis [7-10].
In BBS, the kidneys are enlarged and hyperechoic and A unilocular, single renal cyst occurring in otherwise
there is post-axial polydactyly. The other symptoms of normal-appearing kidneys can be detected in utero or after
the disease will develop after birth. Cysts can be ob- birth. It should be differentiated, especially if the cyst is
served already in utero or appear after birth [7-12]. septated, from a cystic tumor, segmental cystic dysplasia,
In case of moderately enlarged hyperechoic kidneys a dysplastic upper-pole of a duplex kidney, or a urinoma.
(+2 SD), three diagnoses have to be considered first: Associated urinary tract malformation and dilatation may
1. TCF2 mutation associated nephropathy; help make the diagnosis. Noteworthy is the fact that
2. ARPKD; ADPKD may start asymmetrically (with a single cyst) [16].
3. autosomal dominant polycystic kidney disease (ADPKD). Whenever multiple cysts are detected, the first criteri-
An anomaly of TCF2 (leading to HNF-1β-related mor- on for the differential diagnosis is uni- or bilateral in-
phological anomalies) was recently shown to represent volvement. Multiple cysts detected in one kidney only
the main cause of fetal hyperechoic kidneys [11]. This most often correspond to a multicystic dysplastic kidney
mutation is associated with a wide spectrum of renal (MCDK), which usually has a straightforward US ap-
morphological and structural anomalies that histological- pearance: multiple cysts of various sizes without inter-
ly include glomerulocystic-type changes, cystic dyspla- connection, no recognizable normal renal parenchyma,
sia, and renal agenesis. Hepatic ductular plate anomalies and no central renal pelvis. MDCK should be differenti-
are commonly associated findings. In such kidneys, be- ated from obstructive dysplasia (associated with urinary
sides renal hyperechogenicity, CMD may or not be visi- tract obstructive malformation), in which the dilated uri-
ble. Cysts may be detected already in utero or, more of- nary tract is recognizable. The disease can also occur in
ten, after birth; they are located in the subcortical area. A the upper pole of a duplex kidney. MDCK evolves such
familial history of diabetes is a frequent finding. that in most cases the kidney will eventually shrink. This
The involvement and extent of the kidney lesions related can be followed by US [17, 18].
to ARPKD can vary from 10 to 90%, with the US appear- Bilateral multiple renal cysts can be visualized in a large
ances varying accordingly. In cases with mild involvement, number of isolated renal or syndromic diseases (Table 3)
the kidneys may be moderately enlarged, with a hyper- [3, 4] and may or may not be associated with global renal
echoic cortex and a few small cysts mainly within the pyra-
mids. After birth, cysts may also develop, throughout the Table 3. Bilateral multiple cysts in the perinatal period
medulla first and within the cortex thereafter. Fetuses with
mildly enlarged kidneys have a better prognosis for sur- Bilateral multicystic dysplastic kidney disease
vival than those with massive enlargement [9]. Bilateral obstructive dysplasia (+urinary tract dilatation)
Autosomal dominant polycystic kidney disease
Already in utero, ADPKD may be suspected based on a Autosomal recessive polycystic kidney disease
marked hyperechoic renal cortex that increases CMD. The Glomerulocystic disease (subcortical cysts)
kidneys are usually normal in size or slightly enlarged. Syndromes with cystic dysplasia, including (but not limited to)
Such finding should prompt familial inquiry. Cysts may be Ivemark syndrome, Zellweger syndrome, Meckel Gruber syn-
observed in utero but usually develop after birth [13]. drome, Bardet-Biedl syndrome, tuberous sclerosis complex
Imaging Cystic Kidneys in Children 241
Table 4. Bilateral macrocysts Conclusions

Tuberous sclerosis complex
Simpson-Golabi-Behmel The differential diagnosis of renal cystic disease is a dif-
TCF2 mutation syndrome ficult challenge. Cystic disease is suspected based on the
Bilateral multicystic dysplastic kidney disease discovery of hyperechoic kidney or/and cysts. It can be
identified by approaching the diagnosis in a step-by-step
manner that includes US analysis, familial history, and
clinical evaluation.
hyperechogenicity (see above). A step-by-step approach,
including detailed US analysis, familial history, and com-
plementary examinations, will lead to the diagnosis. Am- References
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olution US in the differential diagnosis of cystic diseases of the tic kidney diseases in children: changing sonographic patterns
kidney in infancy and childhood. J Ultrasound Med 16:235-240 through childhood. Pediatr Radiol 32:169-174
23. Traubici J, Daneman A (2005) High-resolution renal sonography 27. Turkbey B, Ocak I, Daryanani K et al (2009) ARPKD and con-
in children with ARPKD. AJR Am J Roentgenol 184:1630-1633 genital hepatic fibrosi. Pediatr Radiol 39:100-111
24. Lipschitz B, Berdon WE, Defelice AR, Levy J (1993) Associ- 28. Salomon R, Saunier S, Niaudet P (2009) Nephronophtisis. Pe-
ation of congenital hepatic fibrosis with ADPKD. Pediatr Ra- diatr Nephrol 24:2333-2344
diol 23:131-133 29. Blowey DL, Querfeld U, Geary D et al (1996) US findings in
25. Premkumar A, Berdon WE, Levy J et al (1988) Emergence of juvenile nephronophtisis. Pediatr Nephrol 10:22-24
hepatic fibrosis and portal HT in ARPKD. Pediatr Radiol
18:123-129
IDKD 2010-2013
Understanding Duplication Anomalies of the Kidney

Jeanne S. Chow
Departments of Urology and Radiology, Children’s Hospital, Boston, MA, USA
Introduction In incomplete ureteral duplication, a single ureteric

bud, which is derived from the the mesonephric (Wolffian)
Learning the basic rules governing duplication anomalies duct, bifurcates and meets the metanephros during
of the kidney is particularly rewarding because the fun- approximately week 5-6 of gestation. The two branches
damental rules can be applied reliably to the great variety of the ureter may join at the level of the renal pelvis (bifid
of cases and using all different imaging modalities. Al- pelvis) or the proximal, middle or distal ureter (bifid
though ultrasound is typically the starting point of imag- ureter) and terminate in a single distal ureter that inserts
ing of the urinary tract in infants and children, renal du- orthotopically into the bladder. Rarely, one of the ureter-
plex anomalies are also studied by micturating cysto- al buds may be blind-ending and never appear to “reach”
urethrography (MCU), also called voiding cystourethro- the kidney (blind ending-ureteric duplication). Since the
graphy (VCUG), intravenous pyelography (IVP), mag- upper and lower poles of the duplex kidney with a bifid
netic resonance urography (MRU), computed tomogra- ureter have a common distal ureter, the upper and lower
phy (CT), MAG-3 lasix renogram, and DMSA scan. poles typically appear similar (and normal). If there is
While more and more duplex anomalies are being dis- reflux or obstruction at the end of the common ureter,
covered in utero, most people with duplex anomalies are both the upper and the lower pole will be affected.
asymptomatic and thus may never be studied at all. In complete ureteral duplication, two separate ureteric
buds arise from the mesonephric duct to meet the
Embryology metanephric blastema. The lower-pole ureter is the ana-
logue of the normal single-system ureter and has a nor-
The ureteric bud must meet the metanephros in order for mally located ureteral orifice in the corner of the trigone
the kidney to form. Without this interaction, kidney forma- of the bladder. The upper-pole ureter is the “accessory
tion is not induced. If two ureteric buds meet the ureter” and inserts medially and inferiorly to the normal
metanephric blastema, then the kidney becomes duplex and ureteral orifice (Weigert-Meyer rule). Since the lower
the collecting system and ureter become duplicated (Fig. 1). pole of the duplex kidney is analogous to the normal
Ureteral duplication may be complete or incomplete. single-system kidney, abnormalities of the lower pole are
a Mesonephric Duct b
Accessory
Ureter
Fig. 1 a, b. Duplex Kidney: embryology of the ectopic pathway.

Metanephros
a Embryology of a complete ureteral duplication showing that
the accessory ureter joins the upper pole of the metanephros. Ureter
b As the kidney continues to develop, the bladder insertion of
the lower-pole ureter ascends to the normal (orthotopic) posi-
tion in the bladder trigone. The upper-pole ureter descends so
that its orifice in the bladder is medial and inferior to the lower-
pole ureter
244 Jeanne S. Chow
Fig. 2. Comparison of the calyceal axes
b
similar to those of a single (non-duplex) collecting sys-
tem, such as vesicoureteral reflux and obstruction at the
ureteropelvic or ureterovesical junction.
Reflux into the lower-pole ureter and intrarenal col-
lecting system can be easily distinguished from reflux in-
to a single (non-duplex) system kidney by carefully not-
ing the axis of the calyces (Fig. 2). Normally, the axis of
the calyces (the line drawn from the lowest to the highest
calyx) of a single-system kidney is toward the contralat-
eral shoulder. Since only the lower calyces are opacified
in lower-pole reflux, the axis of the visualized calyces is
altered and lies toward the ipsilateral shoulder [1].
Ureteral obstruction of the lower pole ureter can occur
at the level of either the renal pelvis or the insertion of
the ureter into the bladder. Ureteropelvic junction ob-
struction (UPJO) of the lower pole of the kidney is visu-
alized by ultrasound [2]. Occasionally, when the upper Fig. 3 a, b. The ectopic pathway in boys (a) shows that the ectopic
pole is dysplastic, lower-pole UPJO can be mistaken for ureter may insert from just below the trigone of the bladder, to the
posterior wall of the uretha as low as the veromontanum, and the
obstruction of a single collecting system. Ureterovesical ejaculatory duct and its branches. The ectopic pathway in the girl
junction obstruction (UVJO) can occur due to primary (b) shows that the ectopic ureter may insert from just below the
mega-ureter, or it may be secondary to the effect of a di- trigone of the bladder down to the posterior wall of the urethra,
lated obstructed upper-pole ureter. In these cases, when to the vulva and vagina
the upper-pole ureter is decompressed, the lower pole ob-
struction also resolves.
The upper pole ureter inserts ectopically, medially, and
inferiorly, to the normal ureteral orifice into any
mesonephric duct derivative. In addition to forming the Ectopic ureters are often obstructed, usually at the
ureter, the Wolffian (mesonephric) duct contributes to the level of the ureterovesical junction, but rarely reflux.
formation of the trigone of the bladder, the urethra, and If the ectopic ureter inserts into the urethra at the level of
the vagina in females, and the posterior urethra and gen- the urinary sphincter, it is both obstructed and refluxes,
ital ducts in males. The “ectopic pathway” follows the depending on whether the sphincter is closed or open, the
pathway created by the Wolffian duct (Fig. 3). so-called sphinteric ectopic ureter (Fig. 5) [4]. The more
Girls with an ectopic ureter inserting into the vagina distal the ureteral insertion, the more dysplastic and
or perineum may present with constant urinary drib- dysfunctional is the associated renal parenchyma that
bling [3] (Fig. 4). In boys, the ureter can terminate in it drains.
Wolffian duct derivatives, including the seminal vesi- A ureterocele is the dilated submucosal terminal seg-
cles and vas deferens. However, ectopic ureters in boys ment of the ureter. It is associated with the upper-pole
never terminate below the urinary sphincter and thus ureter of a double collecting system in girls. In boys,
never cause incontinence. ureteroceles are rare, but when they do occur they are
Understanding Duplication Anomalies of the Kidney 245
Prolapse
Fig. 7. Prolapsing ectopic ureterocele
Fig. 4. Vaginal ectopic ureter
Sphincter closed Sphincter open

a b
(Voiding)
Fig. 5. Sphincteric ectopic ureter Fig. 8 a, b. Ureterocele disproportion. a A typical ectopic, obstruct-
ed, left upper pole ureter ending in ureterocele. b Ureterocele dis-
proportion
a b
imperceptible (efface) (Fig. 6a). When the intravesical

pressure exceeds that of the ureterocele, the ureterocele
everts or intussuscepts into its ureter (Fig. 6b). Everting
Effacement of ureterocele ureteroceles are often confused for periureteral diverticula.
Ectopic ureteroceles involving the bladder neck can
“Intussusception” prolapse into the urethra and cause obstruction of the
of bladder outlet (Fig. 7).
ureterocele Typically, ureteroceles of upper pole ureters are asso-
Fig. 6 a, b. Effacing (a) and everting (b) ureterocele ciated with hydroureteronephrosis. Rarely, the upper
pole is diminutive and dysplastic, and the ureterocele is
relatively large. This combination is described as urete-
rocele disproportion (Fig. 8). The condition can be mis-
most commonly associated with single-system kidneys taken for single ectopic ureters [5]. Ureteroceles can al-
and their orifices are orthotopic. These are associated so be associated with multicystic dysplastic kidneys. As
with varying degrees of ureteral obstruction and pelvi- the fluid in the multiple cysts resolves, these develop the
calyceal dilatation. appearance of ureterocele disproportion. Very rarely,
Although ureteroceles protrude into the lumen of the three complete ureters or three incompletely separated
bladder, when the intravesical pressure equals that of ureters form, resulting in complete or incomplete in
the ureterocele, the ureterocele can flatten and become ureteral triplication [6].
246 Jeanne S. Chow
In paired organs, such as the kidney, when there is a 8. Ureteroceles associated with duplex kidneys and ec-
congenital anomaly in one and there is something wrong topic upper-pole ureters are more common in girls
with the other, it is almost always the same anomaly, but than in boys. In boys, ureteroceles are usually associ-
often different in degree. Thus, if one kidney is duplex, ated with single (non-duplex) kidneys.
the other is more likely to be duplex as well. 9. Ureteroceles are dynamic.
Conclusions References
These are the fundamental principles to remember: 1. Claudon M, Ben-Sira L, Lebowitz RL (1999) Lower pole re-
1. The ureters are duplicated but the kidney is called “du- flux in children: uroradiologic appearance and pitfalls. AJR
plex”. 172:795-801
2. Ureteral duplication may be incomplete or complete. 2. Fernbach SK, Zawin JK, Lebowitz RL (1995) Complete du-
plication of the ureter with ureteropelvic junction obstruction
3. The Weigert-Meyer rule applies to complete ureteral of the lower pole of the kidney: imaging findings. AJR 164:
duplication and states that the upper-pole ureteral ori- 701-704
fice is ectopic. When the ectopia is slight, the upper 3. Carrico C, Lebowitz RL (1998) Incontinence due to an in-
pole is normal. When the ectopia is moderate or se- frasphincteric ectopic ureter: why the delay in diagnosis and
what the radiologist can do about it. Pediatric Radiology
vere, the upper pole is abnormal. 28:942-949
4. The lower pole is the analogue of a single-system kidney. 4. Wyly JB, Lebowitz RL (1984) Refluxing urethral ectopic
5. Lower-pole reflux can be distinguished from reflux in- ureters: recognition by the cyclic voidng cystourethrogram.
to a single-system kidney by the axis of the calyces. AJR 142:1263-1267
6. Ectopic ureters terminate along the ectopic pathway 5. Share JC, Lebowitz RL (1989) Ectopic ureterocele without
ureteral and calyceal dilatation (ureterocele disproportion):
and can cause incontinence in girls, but never in boys. findings on urography and sonography. AJR 152:567-571
7. Ureteroceles are caused by obstruction; they do not 6. Gill RD (1952) Triplication of the ureter and renal pelvis. J
cause obstruction. Urol 68:140-147
IDKD 2010-2013
Malrotation: Techniques, Spectrum of Appearances, Pitfalls,

and Management
Alan Daneman
Department of Radiology, University of Toronto and The Hospital for Sick Children, Toronto, Ontario, Canada
Introduction loop. Initially, the duodenum rotates to the right, then

posteriorly, and finally to the left of the SMA, thereby
The midgut is that part of the bowel supplied by the su- completing the normal duodenal loop. The third part of
perior mesenteric artery (SMA) and it extends from the the duodenum crosses the midline from right to left in the
mid-portion of the second part of the duodenum to the angle between the SMA (anterior to the duodenum) and
distal third of the transverse colon. The term “malrota- the aorta (posterior). The fourth part of the duodenum as-
tion” is broadly used to describe the spectrum of devel- cends to the left of the spine to reach the duodeno-jeju-
opmental abnormalities of the midgut that are associated nal flexure (D-J flexure) at the ligament of Treitz. The po-
with abnormal rotation and/or fixation [1-3]. Malrotation sition of the D-J flexure has been traditionally used as a
may occur as an isolated entity. However, it is also asso- landmark for documenting normal rotation of the midgut
ciated with congenital defects in the development of the on contrast examinations of the upper gastrointestinal
abdominal wall (e.g., omphalocele and gastroschisis) or (GI) tract. The other landmark used is the position of the
diaphragm (e.g., congenital diaphragmatic hernia). Fur- cecum in the right iliac fossa. When the D-J flexure and
thermore, it may also be associated with abnormalities of cecum are in their normal positions, the small bowel
visceral situs and with certain syndromes. mesentery has a long base extending from the left upper
quadrant (D-J flexure) obliquely down to the right lower
quadrant (cecum). This long mesenteric base protects
Embryology against the development of volvulus.
Abnormalities due to the arrest of rotation and/or fix-
During embryological development, the midgut under- ation can occur at any phase of the above-described
goes a complicated process of growth and lengthening, process and may involve only a part or all of the midgut.
herniation, rotation, reduction, and fixation [1]. Growth This leads to many variations of malrotation and/or mal-
and lengthening of the midgut result in its herniation in- fixation and accounts for the spectrum of clinical pre-
to the umbilical cord along the axis of the SMA, such that sentations and radiological appearances.
the apex of the herniated midgut is located at the level of
the omphalomesenteric duct. This herniated bowel under-
goes a 270° counterclockwise rotation, with subsequent Causes of Symptoms
reduction of the midgut back into the abdomen before the
end of the first trimester. The proximal loop of herniated The majority of these variations of malrotation and /or
bowel (including the small bowel up to the level of the malfixation are associated with clinical symptoms that
omphalomesenteric duct) is the first to reduce, followed usually present within the first few months of life and can
by reduction of the distal loop (including the distal small be life-threatening [1, 2]. Others may be associated with
bowel and colon to the level of the distal third of the few or no symptoms, with the latter type often found on-
transverse colon). The final phase involves fixation of the ly incidentally.
bowel into its final anatomical position. The cecum, how- Abnormalities of rotation and/or fixation usually lead
ever, is usually initially reduced into the upper abdomen to a situation in which the cecum and duodenum lie clos-
on the right. This precedes elongation of the proximal er to each other than normal, such that the base of the
colon until the cecum finally reaches the right lower small bowel mesentery is much shorter than normal. The
quadrant. The latter process may only be finally achieved obstruction occurs primarily in the duodenum (Figs. 1, 2)
during early infancy. and is most often due to peritoneal (Ladd) bands that an-
This complicated sequence is essential for the midgut chor the cecum to the retroperitoneum across the duode-
to assume its normal position in the abdomen. One im- num in the right upper quadrant. However, even more im-
portant aspect is the development of the normal duodenal portantly, obstruction may also be due to volvulus as a re-
248 Alan Daneman
Fig. 1. Series of anteroposterior fluoroscopic images from a contrast examination of the upper GI tract in a young infant with malrotation.
In the initial image (top left), before contrast was injected into the nasogastric tube, there is a non-specific bowel gas pattern with dimin-
ished gas in the mid and right abdomen. Contrast administration is followed by intermittent dilatation of the second and proximal third
parts of the duodenum; initially, no dilatation is visible but subsequent images show varying degrees of dilatation. The dilated third part of
the duodenum reaches only to the level of the right pedicles and does not cross the midline. The distal duodenum is on the right. The nor-
mal D-J flexure is absent. The findings are diagnostic of midgut malrotation with obstruction of the duodenum by Ladds bands and sug-
gest a volvulus, which was confirmed at surgery. This case illustrates the potential non-specificity of the abdominal radiograph in the pres-
ence of duodenal obstruction and the intermittent nature of the duodenal dilatation
sult of the narrow base of the small bowel mesentery

(Fig. 2). Much less commonly, there may be an associat-
ed internal hernia (Fig. 3). The clinical picture and imag-
ing appearance depend on the nature and degree of the
obstruction (which may be intermittent) as well as on the
presence or absence of vascular compromise.
Imaging Modalities
As the clinical findings are often non-specific, pediatri-
cians and surgeons rely on the radiologist to confirm or
exclude the diagnosis [1-3]. The radiologist thus plays an
exceptionally important role in the diagnosis of a malro-
tation and must be able to recognize the spectrum of ap-
pearances of its many variations, as depicted by any imag-
Fig. 2. Lateral fluoroscopic view of contrast examination of the up-
ing modality (Figs. 1-5). Failure to do so may lead to a
per GI tract in a neonate with malrotation and volvulus. The prox- delay in treatment and thus potentially to bowel necrosis
imal duodenum is dilated and ends in a beak that leads into a (which may require extensive resection) and even death.
corkscrew pattern of non-dilated small bowel. The beak and On a plain abdominal radiograph, malrotations may
corkscrew pattern are typical of obstruction due to volvulus, which show a wide spectrum of appearances [3]. In contrast to
was confirmed at surgery. The lateral view is often better than the
anteroposterior view shown in Fig. 1 in demonstrating the volvu- what might be expected, the finding of duodenal disten-
lus but the latter view remains essential to depict the position of tion with gas as a typical component of duodenal ob-
the of D-J flexure struction is often absent. If the duodenum is fluid-filled or
Malrotation: Techniques, Spectrum of Appearances, Pitfalls, and Management 249
Fig. 3. Anteroposterior abdominal radiograph from an upper GI se-

ries and follow-through contrast examination in a young teenager
with midgut malrotation and an internal hernia. Contrast outlines
the stomach and duodenal cap and then leads into a very well de-
fined, rounded collection of small bowel loops on the right, repre-
senting a paraduodenal internal hernia. This appearance of con-
tained, well defined small bowel is typical of an internal hernia
Fig. 5 a, b. Transverse sonograms of the upper abdomen in a neonate

with malrotation and volvulus proven at surgery. The volvulus
appears as a characteristic whirlpool in gray-scale (a) imaging and
on color Doppler evaluation (b). The small bowel and mesenteric
veins are coiled around the superior mesenteric artery
distention (with air fluid levels) of the entire small bowel,

resembling a low bowel obstruction or ileus. The appear-
ances of malrotation are indeed often non-specific (Fig. 1)
and may be normal even in the presence of volvulus.
Fig. 4. Contrast enema in a young infant with malrotation proven at Due to this wide variation of appearances on plain ra-
surgery. Note that the proximal colon turns back towards the left in diographs, the clinician should never rely on plain film
the right upper quadrant, and the cecum and appendix lie in the up-
per abdomen close to the position of the duodenum. As a result of findings to exclude malrotation. Any child in whom there
the proximity of the duodenum and cecum, the small bowel mesen- is a clinical suspicion of malrotation should be studied
tery is much shorter than normal, thus predisposing to develop- with modalities that will directly depict the position of the
ment of a volvulus bowel and/or the nature of the obstruction. These include
following modalities:
1. Contrast examinations of the gastrointestinal (GI) tract:
collapsed, it may not be visible and gaseous distension of An upper GI series (alone or in combination with a fol-
the stomach alone may suggest gastric obstruction. A low-through series) and/or a contrast enema (Figs. 1-4)
volvulus may lead to the presence of a soft-tissue mass [4-8]. The most important features of the GI tract to
due to the fluid-filled bowel, or the abdomen may be al- define are the position of the D-J flexure (which re-
most completely gasless. In children with severe vascular quires a straight A-P view on the upper GI series)
compromise due to volvulus, there is often gaseous and/or the position of the cecum and proximal colon.
250 Alan Daneman
2. Cross-sectional imaging of the abdomen, particularly colon may be easily displaced into positions that simu-
with sonography (but also with computed tomogra- late malrotation by adjacent markedly dilated loops of
phy and magnetic resonance) [9-15]. These modali- small bowel. This is seen particularly in neonates with
ties may depict a dilated duodenum, malposition of congenital obstruction involving the distal small bowel.
the D-J flexure, the whirlpool sign indicative of In such patients, the presence of a microcolon usually
volvulus (Fig. 5), an internal hernia, or abnormalities excludes malrotation, as this combination is rare. In old-
of the relationship of the SMA and superior mesten- er children, especially if the clinical setting is not acute,
teric vein. contrast from the original upper GI series can be fol-
Meticulous attention to technique is critical with each lowed with serial plain radiographs to determine the ce-
of these modalities in order to delineate the relevant cal position. This approach may take much longer than
structures accurately. However, even when a technically performing a contrast enema and is usually less fruitful
perfect examination is performed, none of the above fea- in the neonate and young infant, since in this age group
tures are 100% accurate in allowing the confirmation or it is not always possible to clearly depict the position of
exclusion of malrotation. Accordingly, there has been the cecum.
much debate over the years as to which modality should In recent years, signs of malrotation have been visu-
be used first and what protocol of subsequent modalities alized using sonography and other cross-sectional imag-
may be required in order to enable the radiologist to ing modalities, but they are still not used as the modali-
rapidly make an accurate diagnosis. Independent of ty of choice by most radiologists [9-15]. It is true, how-
which modality is chosen first, the radiologist should ever, that sonography is being used much more fre-
never hesitate to ask for or perform other types of exam- quently than suggested in the literature. Direct visualiza-
inations aimed at obtaining more information that may tion of a volvulus (whirlpool sign) (Fig. 5) may obviate
increase confidence in the diagnosis – whether malrota- the necessity for contrast examination of the GI tract; but
tion is present or not. As information from the various ex- this sign is not present in those children without volvu-
aminations is accumulated, the balance of evidence from lus but who are symptomatic because of obstruction due
all the examinations should be weighed together so that to bands. Furthermore, the sign may be difficult to ap-
the correct diagnosis can be determined. preciate in children with volvulus and a large amount of
Most institutions still use the upper GI series as the dilated, gas-filled bowel. Inversion of the superior
modality of choice in children in whom malrotation is mesenteric artery and vein relationship may be present
suspected clinically [4-8]. This examination is relative- in normal rotation, and a normal relationship may be
ly non-invasive, easy to perform, and the position of the present in children with malrotation. Therefore, a normal
D-J flexure is highly accurate in predicting malrotation sonogram does not exclude malrotation and, to date,
(Fig. 1). Indeed, the presence or absence of malrotation sonography has not been used as a screening procedure
can be readily made in most children using this modal- for this condition. Nevertheless, it is essential that radio-
ity alone. However, there will remain a group of chil- logists be able to recognize these abnormal signs when
dren in whom the diagnosis of malrotation will be dif- they are detected as an incidental or unexpected finding
ficult based on the upper GI series alone, either because on cross-sectional imaging.
of technical difficulties in some patients or because of Yousefzadeh [15] has drawn attention to the sono-
difficulties in differentiating normal variations in duo- graphic depiction of the third part of the duodenum (D3)
denal anatomy from true abnormalities of rotation. It is in the angle between the SMA and the aorta, and has sug-
in these children that the radiologist must not be reluc- gested that documentation of the presence of the D3 in
tant to extend the GI contrast examination or to perform this normal position excludes the presence of malrota-
another type of examination that will generate further tion. This is an extremely interesting approach because, if
diagnostic information. shown to be accurate, then the sonographic depiction of
For this purpose, the next most commonly evaluated D3 in this position would obviate the necessity for doing
factor to determine on contrast examinations of the GI a fluoroscopic, contrast examination of the upper GI tract
tract is the position of the cecum [4, 5]. In the acute clin- in those children suspected of having this condition.
ical situation, particularly in neonates and young infants, However, to date, there are no data to substantiate this
the quickest way to achieve this is by performing an im- suggestion.
mediate contrast enema (Fig. 4), i.e., before too much Filling the duodenum with fluid administered orally or
contrast from the prior upper GI series fills the small through a feeding tube may facilitate delineation of the
bowel. The advantage of the contrast enema is that it rel- position of the duodenum and D-J flexure on sonography.
atively quickly provides information on the position of This approach has been advocated by some as the tech-
the entire large bowel. However, interpretation of the ce- nique of choice, and some groups have used it quite ex-
cal position may be difficult. It must be remembered that tensively but have yet to publish their data. Gent and
the position of the cecum and proximal small bowel has LeQuesne presented their experience with this technique,
a wide range of normality, particularly in neonates and based on over 100 cases, at the World Federation of Ul-
young infants, and may well be normal even in patients trasound in Medicine and Biology Meeting in Sydney in
with malrotation. Furthermore, the cecum and proximal 2009. These authors illustrated their technique, which
Malrotation: Techniques, Spectrum of Appearances, Pitfalls, and Management 251
delineates the anatomy of the duodenum exquisitely. They References

have been able to easily confirm the diagnosis of mal-
1. Strouse PJ (2000) Disorders of intestinal rotation and fixation
rotation in the vast majority of patients, with no false- (“malrotation”). Pediatr Radiol 34:837-851
negatives. In a few patients in whom the diagnosis was 2. Lampl B, Levin TL, Berdon WE, Cowles RA (2009) Malrota-
unsure, an upper GI series was required for confirmation. tion and midgut volvulus: a historical review and current con-
To the best of this author’s knowledge, there has, to date, troversies in diagnosis and management. Pediatr Radiol
been no large single series comparing the accuracy of this 39:359-366
3. Daneman A (2009) Malrotation: the balance of evidence. Pe-
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Color Doppler sonographic assessment of bowel per- 4. Long FR, Kramer SS, Markowitz RI et al (1996) Intestinal
fusion may be useful in patients in whom bowel perfusion malrotation in children: Tutorial on radiographic diagnosis in
is in doubt. However, its role is limited as poor perfusion difficult cases. Radiology 198:775-780
is usually seen in sicker patients and surgeons are keen to 5. Long FR, Kramer SS, Markowitz RI, Taylor GE (1996) Radio-
graphic Patterns of Intestinal Malrotation in Children. Radio-
get these children to the operating room as soon as pos- Graphics 16:547-556
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7. Donnolly LF, Rencken IO, de Lorimier AA, Gooding CA (1996)
Left paraduodenal hernia leading to ileal obstruction. Pediatr
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8. Manji R, Warnock GL (2000) Left paraduodenal hernia: an un-
Accurate diagnosis of malrotation requires (i) a high in- usual cause of small-bowel obstruction. Can J Surg 44:455-457
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GI contrast examinations or cross-sectional imaging. Ultrasound Med 19:371-376
Although the diagnosis of malrotation can be accu- 11. Shimanuki Y, Aihara T, Takano H et al (1996) Clockwise
whirlpool sign at color Doppler US: an objective and definite
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when attempting to confirm or exclude malrotation in 13:200-203
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mesenteric vascular relationship in malrotation. Pediatr Radiol
various diagnostic examinations, the balance of evidence 19:173-175
derived from all of them should be weighed together to 14. Weinberger E, Winters WD, Liddell RM et al (1992) Sono-
determine the correct diagnosis. If uncertainty remains graphic diagnosis of intestinal malrotation in infants: impor-
after all imaging avenues have been exhausted, as does tance of the relative positions of the superior mesenteric vein
and artery. AJR Am J Roentgenol 159:825-828
happen (though uncommonly), then the decision whether 15. Yousefzadeh DK (2009) The position of the duodenojejunal
to perform laparoscopy or to operate should be left to the junction: the wrong horse to back on in diagnosing or exclud-
surgeon. ing malrotation. Pediatr Radiol 39:S172-S177
IDKD 2010-2013
Pediatric Intestinal Ultrasonography

Simon G. Robben
Department of Radiology, Maastricht University Medical Centre, Maastricht, The Netherlands
Introduction However, increased knowledge, improved technique

(e.g., graded compression), improved hardware (high-
Ultrasonography (US) is the imaging modality of choice frequency transducers), and improved software (adaptive
for the initial evaluation of diseases in children for imaging, compound imaging) have resolved the limita-
many reasons. First, it is relatively inexpensive and pa- tions to US use. Nowadays it is impossible to imagine
tient friendly. Second, it lacks radiation and motion ar- US without intestinal US, especially in pediatrics! The
tifacts. Third, the small size of the child compensates for hallmark of intestinal US is the “gut signature”, i.e.,
the limited penetration of sound waves and facilitates the characteristic appearance of the layers of the gut
the use of high-frequency transducers. Fourth, flow (Table 1 and Fig. 1).
studies are possible using the Doppler mode, while real-
time imaging allows the visualization of movements
such as peristalsis. Moreover, US involves direct contact
with the patient, thus offering a unique opportunity to
ask specific questions and to perform additional physi-
cal examinations, emphasizing the role of the radiolo- Table 1. Gut signature, characterized by alternating hyper- and
gist as a clinician. Accordingly, ultrasonography has be- hypoechoic layers
come the most important imaging technique in children
Layer Echogenicity
and can be considered as the workhorse of pediatric
radiology. Mucosal surface Hyperechoic
Initially, US of the stomach and intestines was not Mucosa Hypoechoic
popular for obvious reasons: bowel gas has the annoying Submucosa Hyperechoic
characteristic of reflecting all sound waves or creating Muscularis propria Hypoechoic
artifacts because of its abnormally low acoustic impedance. Serosal surface Hyperechoic
a b c
Fig. 1 a-c. Gut signature in a stomach, b ileum, and c appendix (between arrows)
Pediatric Intestinal Ultrasonography 253
Gastroesophageal Junction palpation is accurate but not always successful as it de-

pends on factors such as the experience of the examiner,
The gastroesophageal junction (Fig. 2) can be visualized the presence of gastric distension, and the cooperation of
with US in 87-95% of children with suspected gastro- the infant.
esophageal reflux disease (GERD), and reflux of gastric In virtually all patients, US is very accurate in facili-
content into the esophagus can be demonstrated ultra- tating the diagnosis and therefore plays a key role in the
sonographically [1, 2]. A threshold of three reflux periods initial care of these infants. It is important that the radio-
within 10 min corresponds to a sensitivity of 82% and a logist understands the anatomical changes of the pyloric
specificity of 85% for GERD [1]. Farina et al. increased channel in affected infants, as demonstrated by US. Py-
the sensitivity to 98% using color Doppler US [3]. How- loric muscle hypertrophy is shown to a variable degree
ever, in premature infants the results differ: the sensi- during the US examination. In addition, a certain amount
tivity is 38% and the specificity is 100% compared to of thickening of the mucosa is present (Fig. 3). A muscle
24-hour pH-metry [4]. thickness that is consistently v3 mm is considered to be
US studies have also shown that there is a positive cor- diagnostic of IHPS, although some clinicians have stated
relation between GERD and the length of the abdominal that the overall morphological and dynamic impression,
esophagus, protrusion of the gastric mucosa, and an in- including length of the pyloric canal as well as relaxation
creased gastroesophageal angle (angle of His). Therefore, and peristalsis, are just as important. The US examination
US can be the initial imaging technique in children sus- can be performed in a very short time with an accuracy
pected of having GERD. Moreover, it can evaluate the approaching 100%.
post-operative situation after a fundoplication and gastric
emptying, another important contributing factor to the
pathogenesis of GERD.
Stomach
Gastric emptying in vomiting patients can be evaluated
with US, which depicts dynamic and anatomical abnor-
malities.
Infantile hypertrophic pyloric stenosis (IHPS) [5] is a

condition of unknown etiology that affects young infants
ages 2-8 weeks and with a male-to-female ratio of ap-
proximately 4:1. In IHPS, the antropyloric portion of the
stomach becomes abnormally thickened and manifests as
an obstruction to gastric emptying. Typically, infants with
IHPS are clinically normal at birth but during the first
few weeks of postnatal life, they develop non-bilious
“projectile” vomiting that leads to weight loss, dehydra-
tion and hypochloremic alkalosis, and eventually death. Fig. 3. Hypertrophic pyloric stenosis (between large arrows). Mus-
Surgical treatment is curative. The clinical diagnosis re- cle thickening is indicated by small arrows. A Antrum of stomach
lies on palpation of the thickened pylorus. Abdominal with retained fluid
a b
Fig. 2 a, b. Sagittal slice of a

normal gastroesophageal
junction (arrows) in a 3-
month-old boy. b Same
slice during transit of air.
During real-time ultra-
sonography, the direction
of transit can easily be
appreciated. S Stomach,
L liver
254 Simon G. Robben
Foveolar hyperplasia consists of a polypoid thickening of Contents: The small bowel is either empty or filled with
the mucosal layer. It may be seen after long-standing liquid contents but little air, whereas the colon is gener-
prostaglandin therapy, hypertrophic gastropathy, or cow’s ally filled with gas-filled bulky stools.
milk allergy, but it may also be idiopathic. While the con-
dition may simulate pyloric hypertrophy, on closer US Folds: The folds in the jejunum are more numerous,
examination the obstruction will appear to be caused by longer, thinner, and closer together than the ileal folds. In
thickened mucosa instead of thickened muscle. the terminal ileum, the mucosa may be thickened due to
Rare causes of gastric outlet obstruction include hyperplasia of lymphoid tissue. The colon is recognized
pylorospasm, (eosinophilic) gastritis, food allergy, by its haustrations.
chronic granulomatous disease, hyperlipidemia, du-
plication cysts, ectopic pancreas, benign and malignant Peristalsis: The small bowel moves continuously due to
tumors, and bezoars. persistaltic waves whereas the colon shows sparse move-
ments.
Baud proposed a systematic US approach for identify-
Small Bowel ing small bowel disease, based on wall thickening [6].
1. Determine wall thickening: normal (f3 mm), mild (3-
Conventional radiography and US are the initial imag- 6 mm), moderate (6-9 mm), or severe (>9 mm).
ing modalities in children with abdominal pain or ob- 2. Determine location (proximal or distal) and extent (fo-
struction. The most important additional value of US cal 5 cm, segmental 6-40 cm, or diffuse >40 cm).
over conventional abdominal radiographs in these chil- 3. Determine stratification. The bowel wall is stratified
dren is its capability to visualize peristalsis, vascularity, when the hyperechogenicity of the submucosa is pre-
bowel wall characteristics, dilatation of fluid-filled served and the mucosa, submucosa, and muscularis
loops, and extra-intestinal abnormalities, e.g., ascites propria are visible as separate layers. Non-stratifica-
and other fluids. tion implies the absence of distinction between mucosa
The jejunum and ileum can be distinguished from the and submucosa or between all three layers (Fig. 4).
colon based on anatomical location, caliber, contents, 4. Determine the valvular fold pattern: normal, thick-
folds, and peristalsis. ened, thumb-printing, and hyperplastic valvular folds.
In general, thickened small bowel loops show de-
Anatomical location: The colon has a peripheral location creased peristalsis and contain little air. They are there-
in which the ascending and descending colon lie dorsal- fore easily visualized and measured. At least three pat-
ly in both flanks and the transverse colon is located ven- terns can be distinguished.
trally in the upper abdomen. The sigmoid colon traverses
the left psoas muscle and courses into the pelvis whereas Stratified thickening of the small bowel is found in infec-
the small bowel has a more central position. tious ileitis, advanced appendicitis, early Crohn’s disease,
and graft versus host disease.
Caliber: The diameter of the small bowel is small while,
as its name indicates, the diameter of the large bowel is Non-stratified thickening occurs in Henoch-Schönlein
relatively large. purpura, advanced Crohn’s disease, tuberculous ileitis,
a b
Fig. 4 a, b. Difference be-

tween a stratified wall
thickening in early Crohn’s
disease and b non-strati-
fied wall thickening in ad-
vanced Crohn’s disease
3. Determine stratification, which is best seen on trans-

verse images. The bowel wall is stratified when the
hyperechogenicity of the submucosa is preserved and
the mucosa, submucosa, and muscularis propria are
visible as separate layers. Non-stratification implies
an absence of distinction between the mucosa and
submucosa or between all three layers.
4. Determine the haustral pattern, which is best seen on
longitudinal images; also, confirm the absence or pres-
ence of the haustral folds and their length (normal or
shortened) and aspect.
These criteria distinguish three patterns.
Stratified thickening is found in infectious colitis, ad-

Fig. 5. Two benign small bowel intussusceptions in a patient with a
malabsorption syndrome vanced appendicitis, and inflammatory bowel disease (ul-
cerative colitis and Crohn’s disease).
Non-stratified thickening with loss of haustral folds is

protein-losing enteropathy, hereditary angioedema, is- found in early hemolytic uremic syndrome (HUS) and
chemia, celiac disease, Burkitt’s lymphoma, Kawasaki’s advanced Crohn’s disease.
disease, and viral enteritis.
Non-stratified thickening with preservation of normal
Non-stratified thickening with hyperplastic valvular folds haustral fold length is found in pseudomembranous coli-
can be seen in viral (and sometimes bacterial) lymphoid tis and neutropenic colitis (typhlitis).
hyperplasia and Yersinia ileitis.
Malrotation and midgut volvulus are discussed in the Rectum

chapter by Daneman.
In several studies, US was used to measure the trans-
Benign small bowel intussusception (BSBI) is a recently verse diameter of the rectum. This seems to be a reliable
described entity. It differs from the classical symptomatic approach to identifying rectal impaction and may replace
ileocolic intussusception in that it occurs predominantly digital rectal examination. All children with rectal im-
in the right lower quadrant or periumbilical region, has a paction on digital examination were ultrasonographical-
smaller diameter (mean diameter 1.4 vs. 2.5 cm), a thin- ly shown to have had a rectal diameter >30 mm [9].
ner outer rim, and does not contain mesenteric lymph Moreover, several studies reported that in children with
nodes (Fig. 5) [7]. Moreover, peristalsis in the intussus- constipation the mean diameter of the rectum is signifi-
cepted loop persists, in contrast with ileocolic intussus- cantly larger than in normal children. In a series of 225
ception. Often, BSBI is an incidental finding but it occurs children, the mean rectal diameter in normal children
with increased frequency and number in celiac disease. In was 32 mm (SD 8.2) and in children with constipation
general, BSBI does not need immediate reduction be- 43 mm (SD 9.7) [10]. To overcome the problem of age-
cause of its spontaneously resolving nature. dependency of the rectal diameter in normal children,
Bijos et al. proposed the rectopelvic ratio, defined as the
Appendicitis, Meckels diverticulum, necrotizing entero- ratio of the rectal diameter (as determined with US) to
colitis, and ileocolic intussusception are discussed else- the distance between the anterior superior iliac spines
where in this volume. [10]. A rectopelvic ratio >0.189 corresponds to a sensi-
tivity for rectal impaction of 88% compared to procto-
scopy. The rectal diameter can also be used to monitor
Large Bowel therapy.
The differences between the normal small and large bow-

el were described above. In addition to the systematic ap- Anus
proach to the small bowel, Baud proposed an analogous
approach to the colon [8]. Anal atresia is a relatively frequent congenital abnor-
1. Determine wall thickening: normal (f3 mm), mild (3- mality in which the anus is absent and a rectoperineal,
6 mm), moderate (6-9 mm), or severe (>9 mm). rectovestibular, rectovaginal, rectourethral, or rectovesi-
2. Determine the extent and location of disease: diffuse, cal fistula may be identified in almost all cases. Since
cecum, ascending colon, proximal and distal trans- the fistula demonstrates an internal sphincter, some clin-
verse colon, descending colon, or rectosigmoid. icians instead prefer the term “ectopic anus” or “anorectal
256 Simon G. Robben
malformation”. During pre-operative evaluation, it is im- When a cystic mass is found on US examination, it
portant to assess the type of anal atresia, which may be should be evaluated for its size, shape, location, relation
high (distal rectal pouch above the puborectal sling), in- to organs, and contents and wall characteristics. In the
termediate (at the sling), or low (through the sling). majority of cases, US can provide a specific diagnosis or
Transperineal US is a good diagnostic modality for offer a narrow differential diagnosis [18].
defining the type of anal atresia as it can be used to mea-
sure the distance between the rectal pouch and the per- Hydrops of the gallbladder is a rare cause of a right up-
ineum (P-P distance). A P-P threshold value of 15 mm per quadrant mass in children. It has been described in
discriminates the low type of atresia from the intermedi- the absence of stones, infections, or congenital abnor-
ate and high types with a sensitivity of 100% and a malities, in which case it is probably caused by transient
specificity of 86% [11]. Moreover, internal fistula can be obstruction of the cystic duct or increased mucus secre-
correctly identified in 82% of the patients with the high tion with ineffective emptying. It has also frequently been
type of anal atresia [12]. associated with Kawasaki’s disease. Rarely, it is associat-
Transperineal sonography is also a useful method for ed with childhood infections, Henoch-Schönlein purpura,
differentiating between an anteriorly displaced anus, Cryptosporidium infection in immunocompromised chil-
which is a normal anatomical variant, and a low-type im- dren, Epstein-Barr virus infections, and typhoid fever. US
perforate anus with perineal fistula, which is a patholog- examination reveals a dilated anechoic elliptical gallblad-
ical developmental abnormality requiring surgical repair der without wall thickening. The bile ducts are not dilat-
[13]. In adults, transperineal ultrasonography is a simple, ed and no stones are seen [17, 19].
painless, cost-effective and real-time method to detect
and classify perianal fluid collections, abscesses, fistulas, Choledochal cysts are actually focal cystic dilatations of
and sinus tracts [14-16]. These data can probably be ex- the biliary tree. Most patients present in the first decade
trapolated to the pediatric population, e.g., children with of life with symptoms of episodic abdominal pain, mass,
Crohn’s disease. and jaundice. US is the best initial method of evaluating
dilatation of the bile ducts. On US, the choledochal cyst
is located in the porta hepatis, separate from the gall-
Cystic Intestinal Masses bladder, with bile duct(s) leading into or out of it. The en-
tire biliary tree should be evaluated but intrahepatic bile
Cystic intra-abdominal masses originating from the ali- duct dilatation may be absent. Surgical resection is nec-
mentary canal are increasingly recognized because of the essary to prevent the development of ascending cholan-
advent of routine prenatal US. These masses can be di- gitis, stones, or malignant degeneration [17, 18, 20].
vided into cysts originating from solid organs (mes-
enchymal hamartoma, congenital splenic cyst, pancreatic Mesenteric cysts are cystic lymphangiomas that are most
pseudocyst, pancreatic cystadenoma, hydronephrosis, often found in the small bowel mesentery, especially the
multicystic dysplastic kidney, multilocular cystic nephro- ileal mesentery but also in the greater and lesser omen-
ma, adrenal hemorrhage, ovarian cysts and cystic neo- tum and occasionally in the mesenteric root and retroperi-
plasms, hematocolpos, urachal cysts, abdominal and toneum. About one-third occur in children younger than
sacrococcygeal teratoma, and cerebrospinal fluid pseudo- 15 years. Newborns present with abdominal distention
cyst) and those originating from the alimentary canal and and a palpable mass whereas children are much more
its appendages (hydrops of the gallbladder, choledochal likely to present with pain, anorexia, vomiting, or fever.
cyst, mesenteric and omental cysts, gastrointestinal du- US can characterize the mass as a typical thin-walled uni-
plication cyst, meconium pseudocyst, and appendiceal or multilocular cyst that displaces adjacent structures to
abscess) [17] (Table 2). the periphery of the abdomen (Fig. 6). Calcification of
Table 2. Cystic masses of the gut and gut-related structures

Biliary system
Choledochal cyst
Hydrops of gallbladder
Gastrointestinal tract
Mesenteric cyst/lymphangioma
Enteric/duplication cyst
Omental cyst
Meconium pseudocyst
Miscellaneous
Abscess
Teratoma
Sacrococcygeal teratoma
Fig. 6. Multilocular cystic lymphangioma
the wall is rare in children. The cyst content is anechoic a

but if hemorrhage has occurred then debris may be seen.
Lymphangiomas may be so large that they are difficult to
distinguish from severe ascites. However, ascites sepa-
rates individual bowel loops and fills the perihepatic and
perisplenic spaces [17, 18].
Gastrointestinal duplication cysts are spherical or tubular

masses adherent to the gastrointestinal (GI) tract and
sometimes communicating with it [17, 18, 21]. These
cysts are lined with intestinal epithelium and contain
smooth muscle within their walls. They may occur any-
where along the alimentary tract but the most common
location is the ileum, followed by the stomach. Most pa-
tients present within the first year of life; their symptoms
include GI obstruction and, less commonly, a palpable
mass, intussusception, and abdominal distension.
The cystic nature of duplication cysts can be easily ap-
preciated on US. The content of the cyst is often anechoic
but there may be debris after hemorrhage or due to mu-
coid material. Rarely, the cyst appears completely hyper-
echoic after hemorrhage. Two signs are virtually diag-
nostic of duplication cysts:
1. a double-layered wall consisting of echogenic mucosa
and hypoechoic muscularis propria (Fig. 7);
2. peristalsis in the cyst. b
In 15-20% of cases, the cyst contains gastric mucosa,
which accounts for the above-mentioned hemorrhages.
Meconium pseudocyst is a manifestation of the cystic

type of meconium peritonitis that results from in utero
bowel perforation. Bowel perforation may be secondary
to intestinal obstruction (meconium ileus, atresia, or
volvulus) or idiopathic. The spilled meconium is encap-
sulated and forms a large meconium-filled (hyperechoic)
cyst that is lined by a thick inflammatory and fibrotic
membrane, often containing calcifications. The perfora-
tion may still communicate with the cyst postnatally. Di-
lated fluid-filled bowel loops may be seen next to the cyst
if obstruction is still present. Distant peritoneal or scrotal
calcifications are additional evidence for meconium peri-
tonitis and may also be demonstrated with US or con-
ventional radiographs [17, 18, 22]. Fig. 7 a, b. Duplication cyst. a Large right-sided cyst on prenatal
magnetic resonance imaging shows no typical features. b Postnatal
Intra-abdominal abscesses often are complications of ap- ultrasound demonstrates gut signature in the wall of the cyst
pendicitis, inflammatory bowel disease, or intra-abdomi- suggestive of duplication cyst
nal surgery. However, they can also occur in patients on
immunosuppressive therapy or in those with AIDS or
chronic granulomatous disease. The typical presentation is Abdominal teratomas usually arise from the retroperi-
intermittent fever, increased white blood cell count or toneum, presacral region, or the ovary, whereas mesen-
C-reactive protein, and abdominal tenderness. US shows teric and gastric teratomas are rare. These tumors occur
an ill-defined, fluid-filled mass with a thickened wall and mainly in children, and 80% are benign. Mature, imma-
irregular inner surface. The fluid (pus) demonstrates sep- ture, and malignant types have been described. Most chil-
tations, debris, or debris-fluid levels. The presence of gas dren present with a palpable abdominal mass that on US
bubbles in the pus often makes differentiation from bow- is seen to be either (multi)cystic or solid. Teratomas typ-
el loops difficult; the presence of peristalsis rules out an ically contain calcifications and fat. The latter is difficult
abscess. If feasible, ultrasonographically guided aspiration to appreciate with US but highly echogenic tissue is sug-
and/or drainage can be performed, if necessary in the ICU. gestive of fatty tissue.
258 Simon G. Robben
Sacrococcygeal teratomas usually present as a large ex- ileum. The bowel wall thickening is extensive, asymmet-
ternal cystic tumor located at the coccyx but in some rical, and poorly stratified whereas the mesenteric in-
cases consist of a large cystic intra-abdominal mass volvement is bulky and lobulated and appears to be in
without any external mass. These pre-sacral tumors ob- continuity with the bowel wall. Despite the extensive bow-
struct the rectum and bladder. A pre-sacral extension of el wall thickening, the lumen may remain wide. Burkitt’s
an intra-abdominal cyst provides a clue to the diagno- lymphoma can lead to intestinal obstruction and intussus-
sis of sacrococcygeal teratoma. Cystic tumors carry a ception. It can also involve the liver, spleen, kidneys and
better prognosis than do solid, hypervascular tumors pancreas. Extensive involvement of the omentum and
[17, 18]. peritoneum is rare [25, 26].
Cerebrospinal fluid pseudocyst (liquor cyst) is a compli- Intra-abdominal lipomatous tumors (lipoma, lipoblastoma,
cation resulting from ventriculoperitoneal shunt, with a and the rare liposarcoma) predominantly involve the
frequency of approximately 3%. Risk factors for pseudo- mesentery and omentum [27-29]. They show hypo- or
cyst formation are related to inflammatory processes and hyperechoic textures and are finely lobulated, homo-
CNS tumors. Pseudocysts tend to occur within 6 months geneous, or with fibrovascular septa. In most cases,
of the last abdominal surgical procedure. Children pre- magnetic resonance imaging is necessary for further
sent with abdominal pain, distention, or mass. US will evaluation.
demonstrate a sonolucent, well-defined mass in non-
infected cysts, whereas infected cysts show septa, inter- Inflammatory myofibroblastic tumor (inflammatory
nal debris, and fluid-fluid levels. There is no statistically pseudotumor) most commonly occurs in the mesentery of
significant correlation between pseudocyst size and the children or young adults [29, 30]. The typical complaints
presence of infection. It is important to identify the tip of are of fever, malaise, weight loss, or abdominal pain. The
the shunt within the cyst, producing the characteristic US characteristics of inflammatory pseudotumor are non-
“railroad sign” [17, 23, 24]. specific: solid, well-defined (sometimes lobulated), with
mixed echo-texture and frequent calcifications. Infiltra-
tion of the adjacent bowel may occur. Prominent vascu-
Solid Intestinal Masses larity may be shown with Doppler US.
The many types of solid masses (often of neoplastic ori- Fibromatosis or abdominal desmoid is part of the clini-
gin) that can be found during US examination are sum- cal-pathological spectrum of deep fibromatoses [29, 30].
marized in Table 3. The latter encompass a group of benign fibroproliferative
processes that are locally aggressive and have the capac-
Burkitt’s lymphoma is a fast-growing and aggressive ma- ity to infiltrate or recur but not to metastasize. Mesenteric
lignant neoplasm predominantly affecting children and structures are the most common sites of origin of intra-
that may be associated with immunodeficiency. US will abdominal fibromatosis. Other locations are the abdomi-
demonstrate bowel wall thickening combined with a nal wall, pelvis, and retroperitoneum. Thirteen percent of
mesenteric mass, predominantly of the cecum and distal patients with mesenteric fibromatosis have familial ade-
nomatous polyposis (FAP), specifically, the Gardner syn-
drome variant. In these patients, prior abdominal surgery
is an important risk factor for the development of mesen-
Table 3. Solid masses of the gut and gut-related structures
teric fibromatosis. The US appearance is a solid, well-
Lymphoma circumscribed mass of variable echo-texture and homo-
Burkitt’s lymphoma geneity. Locally aggressive fibromatosis infiltrates the
Non-Hodgkin’s lymphoma mesenteric fat.
Peritoneal, mesenteric, and omental
Lipoma, lipoblastoma, and liposarcoma Neurofibromatous tumors are associated with neurofibro-
Inflammatory myofibroblastic tumor matosis type 1 (NF1). Abdominal involvement is found
Fibromatosis (= desmoids) in 10-25% of patients with NF1, regardless of their age.
Neurofibromas (NF1-associated) Intra-abdominal neurofibromas present as hypoechoic
Rhabdomyosarcoma heterogeneous masses or as multiple rounded, hypo-
Metastasis echoic, well-circumscribed, variably sized mesenteric
Mesenteric lymphadenitis nodules.
Small and large bowel
Juvenile colonic polyps Rhabdomyosarcomas are rare intra-abdominal pediatric
Hamartomatous small bowel polyps tumors involving the mesentery, peritoneum, or omen-
Polyposis tum, often associated with ascites. Leung et al. described
Carcinoid an omental embryonal rhabdomyosarcoma consisting of
Vascular malformations lobulated round masses surrounded by tissue with a
cerebriform pattern [31]. Rhabdomyosarcomas may also a

occur in the biliary tree, and are actually the most common
pediatric tumor of the biliary tree. US findings are non-
specific but if a solid tumor in the biliary tree is detected,
it is highly suggestive of rhabdomyosarcoma [32].
Intestinal polyps in the small bowel are usually hamar-

tomatous polyps in patients with Peutz-Jeghers syn-
drome. These polyps occur more often in the jejunum
than in the ileum. US is only able to detect polyps >15
mm and is therefore not a screening tool for the detection
of uncomplicated polyps. However, it is valuable in diag-
nosing complications associated with polyps of the small
bowel, e.g., intussusceptions.
b
Juvenile polyps are the most common neoplasms of the
large bowel in children. The sigmoid and rectum are pref-
erential locations. The presenting symptom is rectal bleed-
ing in over 90% of patients. Occasionally, a colo-colic in-
tussusception is the first manifestation of a juvenile polyp.
US demonstrates a pedunculated spherical nodule 10-25
mm in diameter and containing multiple 2- to 3-mm cysts.
Administration of fluid within the bowel lumen will great-
ly improve the visualization of these polyps; however, the
assessment of rectal polyps is unreliable.
Mesenteric lymphadenitis. Abdominal lymph nodes vary-

ing from 0 to 10 mm in diameter are detected in almost
all asymptomatic children (Fig. 8a). Approximately half
of these lymph nodes (43-54%) are >5 mm in their short
axis, with the number and shape of the nodes being Fig. 8 a, b. Enlarged mesenteric lymph nodes. a Asymptomatic
age-independent [33, 34]. There is a gender dependency child shows lymph nodes with normal texture and ellipsoid shape;
in that boys are more affected than girls [33, 35]. In chil- the largest node has a short axis of 8 mm. b Tuberculous mesen-
dren with recurrent or acute abdominal pain without teric lymph node shows indistinct margins, round shape, and het-
erogeneous texture with hypoechoic areas of necrosis and a diam-
known cause, the lymph nodes are significantly larger eter of 20 mm
than in asymptomatic children, but there is considerable
overlap between the two groups. Children with abdomi-
nal pain and abdominal lymph nodes >10 mm in their
short axis may be considered as having primary mesen-
teric lymphadenitis, if no other acute inflammatory Atresias are congenital interruptions of the lumen of the
process is identified [34, 36]. There are few US criteria alimentary canal caused by a failure of canalization dur-
that are typical for a specific causative agent. The pres- ing organogenesis. The result is dilatation proximal to the
ence of calcifications and necrosis suggests tuberculous atresia and complete collapse distal to the atretic segment.
lymphadenitis (Fig. 8b). While the clinical and radiographic presentation is typical,
US may be used to demonstrate accompanying pathology:
1. exclusion of associated malrotation in cases of high
Neonatal Bowel Obstruction obstruction;
2. evaluation of the colon and rectum in cases of high ob-
Many neonatal bowel obstructions are caused by diseases struction; single atresias are associated with a normal-
discussed in other chapters, e.g., duplication cysts, mal- sized colon, multiple atresias, with microcolon;
rotation or volvulus, meconium peritonitis, necrotizing 3. evaluation of associated malformations of the heart,
enterocolitis, anal atresia, and pyloric hypertrophy. Addi- kidneys, and biliary tree;
tional causes of neonatal obstruction include various 4. demonstration of extrinsic duodenal compression in
types of atresia, annular pancreas, meconium ileus, cases of high obstruction, e.g., duplication cysts, pre-
Hirschsprung’s disease, and meconium plug syndrome. duodenal portal vein, annular pancreas; and
These diseases are diagnosed by conventional abdominal 5. demonstration of signs of prenatal meconium peritoni-
radiographs and/or conventional contrast studies but US tis as a cause of small bowel atresia (meconium cysts,
may be of additional value [37]. subtle peritoneal or scrotal calcifications).
260 Simon G. Robben
Meconium ileus is a small bowel occlusion caused by in- 8. Baud C (2008) Infectious and inflammatory colitis. In: Cou-
spissated, abnormally tenacious, meconium in the distal ture A, Baud C, Ferran J et al (eds) Gastrointestinal tract
sonography in fetuses and children. 1st edn. Springer-Verlag,
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colon in a neonate with distal occlusion suggests in Crohn's disease. Am J Gastroenterol 102:2214-2219
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Meconium plug syndrome can be considered as neonatal AJR Am J Roentgenol 177:627-632
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mental bowel-wall thickening on abdominal ultrasonography:
an additional diagnostic sign in Kawasaki disease. Pediatr Ra-
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sonographic features of gastrointestinal duplications. J Ultra-
their ultrasonographic manifestations. sound Med 13:863-870
22. Yang WT, Ho SS, Metreweli C (1997) Case report: antenatal
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Diseases of the Abdomen and Pelvis 2010-2013

Diagnostic Imaging and Interventional Techniques

DISEASES OF THE ABDOMEN

42nd International Diagnostic Course

Pediatric Satellite Course “Kangaroo”

presented by the Foundation for the

J. HODLER G. K. VON SCHULTHESS

ISBN 978-88-470-1636-1 e-ISBN 978-88-470-1637-8

Springer Dordrecht Heidelberg London Milan New York

Library of Congress Control Number: 2010922809

© Springer Verlag Italia 2010

Cover design: Simona Colombo, Milan, Italy

Springer-Verlag Italia S.r.l., Via Decembrio 28, 20137 Milan

The International Diagnostic Course in Davos (IDKD) offers a unique learning

Trauma of the Abdomen and Pelvis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Diseases of the Esophagus and Stomach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Small-Bowel Imaging: Pitfalls in Computed Tomography Enterography/Enteroclysis 28

Diseases of the Small Bowel, Including the Duodenum – MRI . . . . . . . . . . . . . . . . . . . . . . 32

Imaging of the Colon and Rectum: Inflammatory and Infectious Diseases . . . . . . . . . . 37

Imaging of Diffuse and Inflammatory Liver Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

Focal Liver Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

Imaging Diseases of the Gallbladder and Bile Ducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Diseases of the Pancreas, I: Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

Diseases of the Pancreas, II: Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

Adrenal Imaging and Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96

Urinary Tract Obstruction and Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

Benign Diseases of the Female Genital Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

Malignant Diseases of the Female Genital Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

Magnetic Resonance Imaging of Prostate Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

Imaging of the Male Pelvis: The Scrotum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

Spread of Metastatic Disease in the Abdomen and Pelvis . . . . . . . . . . . . . . . . . . . . . . . . . . . 146

Abdominal Vascular Disease: Diagnosis and Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154

Non-vascular Abdominal Disease: Diagnosis and Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . 162

An Approach to Imaging the Acute Abdomen in the Pediatric Population . . . . . . . . . . . 167

Imaging Uronephropathies in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

Integrated Imaging in Genitourinary Oncology: PET/CT Imaging . . . . . . . . . . . . . . . . . . . . 183

Integrated Imaging in Gastrointestinal Oncology: PET/CT Imaging . . . . . . . . . . . . . . . . . 190

Nuclear Medicine Satellite Course “Diamond”

Conventional Nuclear Medicine in the Evaluation of Gastrointestinal

PET in Hepatobiliary-Pancreatic Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215

PET in Tumors of the Digestive Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219

Tumors of the Adrenergic System: Imaging and Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . 226

Neuroendocrine Tumors of the Abdomen: Imaging and Therapy . . . . . . . . . . . . . . . . . . . . 231

Pediatric Satellite Course “Kangaroo”

Understanding Duplication Anomalies of the Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243

Malrotation: Techniques, Spectrum of Appearances, Pitfalls, and Management . . . . . 247

Pediatric Intestinal Ultrasonography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252

Allegri V., 215 Hoefnagel C.A., 226

Emergency Radiology of the Abdomen: The Acute Abdomen

Introduction 1. The multidetector CT (MDCT) image data volume

Fig. 2 a-c. Acute appendicitis. Axial (a, b)

Fig. 3 a-c. Ultrasonography of acute appen-

Left Lower Quadrant flammatory changes, such as fat stranding, inflammatory

exquisite lower abdominal pain. It is diagnosed with CT (or

Fig. 5 a, b. Perforated sigmoid diverticulitis. a CT demonstrates tiny

bowel obstruction is the delineation of a transition zone Ischemic Bowel Disease

Fig. 7 a, b. Cecal volvulus. Trans-

Fig. 8 a-c. Strangulating small bowel ob-

Fig. 9 a-c. Right-sided urinary colic. Axial

Fig. 10 a-c. Severe acute pancreatitis. Axial