Review Article | Breast Imaging

eISSN 2005-8330
https://doi.org/10.3348/kjr.2020.0093
Korean J Radiol 2021;22(1):9-22

Diffusion-Weighted Magnetic Resonance Imaging

of the Breast: Standardization of Image Acquisition
and Interpretation
Su Hyun Lee, MD, PhD1, Hee Jung Shin, MD, PhD2, Woo Kyung Moon, MD, PhD1
1
Department of Radiology, Seoul National University Hospital, Seoul, Korea; 2Department of Radiology, Asan Medical Center, University of Ulsan
College of Medicine, Seoul, Korea

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a rapid, unenhanced imaging technique that measures the
motion of water molecules within tissues and provides information regarding the cell density and tissue microstructure. DW
MRI has demonstrated the potential to improve the specificity of breast MRI, facilitate the evaluation of tumor response to
neoadjuvant chemotherapy and can be employed in unenhanced MRI screening. However, standardization of the acquisition
and interpretation of DW MRI is challenging. Recently, the European Society of Breast Radiology issued a consensus statement,
which described the acquisition parameters and interpretation of DW MRI. The current article describes the basic principles,
standardized acquisition protocols and interpretation guidelines, and the clinical applications of DW MRI in breast imaging.
Keywords: Diffusion-weighted MRI; Dense breast; Standardization; Supplemental screening; Cancer

INTRODUCTION of DCE MRI in breast cancer screening. Although abbreviated

breast MRI has solved some of the aforementioned
Dynamic contrast-enhanced (DCE) magnetic resonance problems, it still requires the use of contrast agents, which
imaging (MRI) is the standard protocol for the breast MRI, limits its use in population-based screening (9). Recently,
which evaluates the morphologic and kinetic features of there have been growing public concerns over the unknown
breast lesions. It is the most sensitive and accurate imaging health effects of gadolinium deposition in brain and
modality used for the detection and characterization of other tissues, as a consequence of repeated gadolinium
breast cancer. DCE MRI can detect breast cancers that were contrast agent injections (10, 11). Therefore, in the current
occult on mammography and ultrasound at an earlier stage clinical scenario, research involving the development of an
and consequently reduce the occurrence of interval cancers unenhanced, rapid and less expensive screening tool that
(1-8). However, high cost, long duration of examination and complements mammography and is potentially safer than
the use of contrast agents have limited the widespread use DCE MRI has become increasingly important.
Diffusion-weighted (DW) imaging is a functional MRI
Received: February 5, 2020 Revised: May 6, 2020 technique that can produce contrast in tissues without
Accepted: May 9, 2020
using gadolinium contrast medium injections and the
This study was supported by a grant from the National
R&D Program for Cancer Control, Ministry of Health and process of whole breast imaging can be completed within
Welfare, Republic of Korea (HA17C0056). a few minutes (12). Various useful clinical applications
Corresponding author: Woo Kyung Moon, MD, PhD, Department of DW MRI in breast imaging have been explored so
of Radiology, Seoul National University Hospital, 101 Daehak-ro,
Jongno-gu, Seoul 03080, Korea. far and a growing number of imaging centers are
• E-mail: moonwk@snu.ac.kr incorporating DW MRI into the routine clinical breast MRI
This is an Open Access article distributed under the terms of examination. However, DW MRI acquisition parameters
the Creative Commons Attribution Non-Commercial License
(https://creativecommons.org/licenses/by-nc/4.0) which permits
are not standardized and there is no uniform method of
unrestricted non-commercial use, distribution, and reproduction in interpretation; consequently, resulting in a large variability
any medium, provided the original work is properly cited. in image quality and diagnostic performance, which has

Copyright © 2021 The Korean Society of Radiology 9

 Lee et al.

prevented the incorporation of DW MRI findings into the DW MRI signal is proportional to the water mobility and is
Breast Imaging Reporting and Data System (BI-RADS). commonly described by the monoexponential equation:
Standardized acquisition protocols and interpretation SD = S0e–b*ADC, where SD is the signal intensity with
guidelines are required, in order to facilitate the clinical diffusion-weighting, S0 is the signal intensity without
application of DW MRI and to enable cross-institutional diffusion-weighting, b is the diffusion sensitization factor
comparisons. Recently, the European Society of Breast and ADC is the apparent diffusion coefficient. The b value
Radiology (EUSOBI) issued a consensus statement, which is a factor that reflects the degree of diffusion-weighting,
describes the acquisition parameters for standard breast DW which is determined by the amplitude and duration of the
MRI sequences (13). sensitizing gradients and the time interval between the
In the present article, the authors briefly review gradient pair (expressed in sec/mm2). ADC is defined as the
the basic principles, optimized image acquisition and average area occupied by a water molecule per unit time
standardized interpretation guidelines for DW MRI and (expressed in mm2/sec) and can be calculated using the
subsequently explain the clinical applications of DW MRI in image acquisitions at two or more different b values.
breast imaging. The extensions of DW MRI to characterize The standard DW MRI sequence produces two sets of
diffusion directionality and perfusion fractions within images (Fig. 1): T2-weighted reference images obtained
tissues, namely the diffusion tensor imaging (14, 15) without diffusion gradients (S0), and DW images obtained
and intravoxel incoherent motion imaging (16), are the with diffusion gradients (SD) that reflect the water mobility.
fields of active research that have the potential to provide The parametric ADC map is created to enable the diffusion
valuable information. However, the aforementioned imaging quantification without T2 shine-through effects. An area of
modalities are not routinely used in clinical breast imaging restricted diffusion, such as a breast cancer lesion, appears
and hence, they are not included in the current review. bright on the DW image and dark on the ADC map (Fig. 1)
(18).
Basics Physics of DW MRI
Image Acquisition
DW MRI involves the use of a specific sequence in
which the diffusion or random motion of water molecules Standardized Acquisition Parameters
in a tissue primarily contributes to image contrast. The The acquisition parameters can affect the quality of
sequence, originally proposed by Stejskal and Tanner (17), DW MRI and ADC values. Although different parameters
was based on a spin echo sequence that has symmetric may need to be used for DW MRI, depending on the MRI
diffusion sensitizing gradients, inserted before and after the machine, several acquisition parameters are suggested to
180° refocusing pulse. Paired pulsed gradients cause the ensure the quality of breast DW MRI. Recently, the EUSOBI
signal loss from diffusing water spins, but stationary water working group issued a consensus statement, which outlined
spins remain unaffected. The reduction in the intensity of the minimum set of acquisition parameters that should be

S0 SD ADC
b = 0 sec/mm2 b = 800 sec/mm2

A B C
Fig. 1. Standard DW image sets.
DW image sets consist of T2-weighted reference image obtained without diffusion gradients (A), DW images obtained with diffusion gradients
(b value of 800 sec/mm2) (B), and the parametric ADC map (C). An area of restricted diffusion with breast cancer (arrow) appears bright on the
DW image and dark on the ADC map. ADC = apparent diffusion coefficient, DW = diffusion-weighted, S0 = signal intensity with b = 0 s/mm2, SD =
signal intensity with b = 800 s/mm2

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Standardization of DW MRI Acquisition and Interpretation

met in clinical practice and proposed a guideline for the be generated.

standardized acquisition protocol (Table 1) (13). According
to the aforementioned guidelines, breast DW MRI should Choice of b Value
be performed in a closed bore magnet at field strength of The choice of b value is important because it determines
1.5T or higher with a maximum gradient strength of at least the ADC value and affects the signal-to-noise ratio of the
30 mT/m, using a dedicated breast coil with at least four image and the contrast-to-noise ratio of the lesion (20-
channels, and before the administration of the contrast 23). The ADC values decrease with the increase in b values,
agent when possible (19). In combination with the spin owing to the non-Gaussian nature of water diffusion in
echo, single-shot or multishot echo-planar imaging (EPI) tissues (13). Hence, using a common b value is important
should be used as the readout sequence in axial planes of for the purpose of standardization and comparison.
bilateral breasts with a minimum in-plane resolution of Recently, a high b value of 800 sec/mm2 and a low b value
2 x 2 mm2 and a section thickness of 4 mm or less. The of 0–50 sec/mm2 were chosen by the EUSOBI working
echo time should be minimized to the lowest possible group as a good compromise for the standardization and
value, in order to reduce susceptibility artifacts, and the accurate estimation of breast ADCs (13). However, in terms
repetition time should be 3000 msec or more. In practice, of qualitative lesion detection, DW MRI with a very high
all EPI sequences are fat-suppressed to prevent ghosting b value of 1200–1500 sec/mm2 may be optimal because
and the potential underestimation of ADC values. Among higher b values increase the visibility of the lesion and the
the different methods employed for the fat suppression, specificity of lesion detection, despite the lower signal-
spectral adiabatic inversion recovery is preferred over to-noise ratios and longer duration of imaging (Fig. 2)
the short tau inversion recovery. Parallel imaging with an (20, 22). Hence, when DW MRI is used for screening
acceleration factor of 2 is recommended, in order to reduce examinations, where both the lesion detection and
the distortion attributable to susceptibility artifacts. An accurate ADC quantitation are priorities, acquisition with
ADC map, calculated using at least two b values, needs to three different ranges of b values, i.e., 0–50 sec/mm2, 800

Table 1. Standardized Breast DW MRI Acquisition Parameters

Parameter Minimum Requirement* Requirement for Screening Examination†
Equipment
Magnet field strength ≥ 1.5T 3T
Type of coil Dedicated breast coil with ≥ 4 channels 16 or 18 channels
Timing of acquisition Before contrast injection, when possible Before contrast injection
Acquisition parameter
Type of sequence EPI based EPI based (single-shot or multishot)
Orientation Axial Axial
Both breasts with or without covering
Field of view Both breasts with covering the axillary region
the axillary region
In-plane resolution ≤ 2 x 2 mm2 ≤ 1.3 x 1.3 mm2
Slice thickness ≤ 4 mm ≤ 3 mm
Number of b values 2 3
Lowest b value 0 sec/mm (not exceeding 50 sec/mm2)
2
0 sec/mm2
2
800 sec/mm and additional acquisition of
High b value 800 sec/mm2
1200 sec/mm2
Fat saturation SPAIR SPAIR
TE Minimum possible Minimum possible
TR ≥ 3000 ms ≥ 7500 ms
Acceleration Parallel imaging (factor ≥ 2) Parallel imaging (factor ≥ 2)
Post-processing Generation of ADC maps Generation of ADC maps, additional generation of MIP
*Recommendation of the European Society of Breast Radiology (13), †Recommended in Korean multicenter screening DW MRI study. ADC =
apparent diffusion coefficient, DW = diffusion-weighted, EPI = echo-planar imaging, MIP = maximum intensity projection, MRI = magnetic
resonance imaging, SPAIR = spectral adiabatic inversion recovery, STIR = short tau inversion recovery, TE = echo time, TR = repetition time

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 Lee et al.

Acquired b = 0 sec/mm2 Computed b = 500 sec/mm2 Acquired b = 800 sec/mm2

A B C

Computed b = 1000 sec/mm2 Acquired b = 1200 sec/mm2 Computed b = 1500 sec/mm2

D E F

Computed b = 2000 sec/mm2 ADC map

Rt: 1.71 Lt: 0.90

(x 10-3 mm2/sec) (x 10-3 mm2/sec)
G H
Fig. 2. Effect of b value on the signal intensity of normal breast parenchyma and benign and malignant breast lesions.
As the b value increases (A-G), the signal intensity of normal breast parenchyma (background diffusion signal) and a biopsy-proven
fibroadenoma (arrowhead) decreases, whereas the signal intensity of an invasive ductal carcinoma (arrow) remains high, increasing the lesion
visibility and specificity for lesion detection, despite the lower signal-to-noise ratio. On the ADC map calculated using the b values of 0 sec/mm2
and 800 sec/mm2 (H), the breast cancer appears as dark signal intensity (ADC value, 0.90 x 10-3 mm2/sec), while the fibroadenoma appears as
high signal intensity (ADC value, 1.71 x 10-3 mm2/sec).

sec/mm2, and 1200–1500 sec/mm2, may be recommended of 2 x 2 mm2 and section thickness of 4 mm can result in a
(Table 1) (19). The diffusion-sensitizing gradients are significant partial volume effect. In order to facilitate the
usually applied in three orthogonal directions (x, y, or z use of DW MRI as an unenhanced screening method, its
axes) and the acquired images are automatically averaged ability to detect and characterize breast lesions, including
into a final combined image. subcentimeter lesions, should be enhanced.
Currently, advanced DW MRI techniques to improve the
Advanced Acquisition Technique image quality and achieve higher spatial resolution are
Conventional DW MRI is performed using a single-shot under research. Such techniques include the readout-
EPI, in which all k-space lines, which form the image, are segmented EPI, a multishot EPI approach in which k-space
acquired during a single excitation. Thus, EPI is a rapid MRI sampling occurs with a small number (three to six) of
technique, capable of acquiring individual MR slices within excitations (shots) and each shot divides the k-space into so
a time frame of 50–100 msec, consequently minimizing called segments. Multishot EPI reduces the required matrix
the effects of patient movement (24). However, EPI suffers size acquired per shot, thus, reducing the susceptibility
from susceptibility artifacts or distortions, low signal-to- artifacts and allowing for higher spatial resolution and
noise ratio and spatial blurring, particularly at higher field total image matrix size at the expense of the acquisition
strengths. Furthermore, in case of small lesions (< 1 cm in time (Fig. 3) (25-28). Currently, this sequence is marketed
size), the typical DW MRI axial in-plane spatial resolution by a vendor (Siemens Healthineers) under the trade name

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Standardization of DW MRI Acquisition and Interpretation

RESOLVE (readout segmentation of long variable echo MRI by correcting the geometric distortions arising from
trains). Another advanced technique that aims to improve field inhomogeneities and other factors (32). However, a
the spatial resolution of DW MRI is the reduced field-of-view previous study reported that up to 10% of the breast DW
(rFOV). The rFOV technique permits high resolution DW MRI MRI scans showed spatial mismatch between the DW images
of the targeted volume by decreasing the required number of that could not be corrected by a registration algorithm,
k-space lines while reducing the distortion. The technique consequently emphasizing the importance of implementing
is commercially available from several vendors as FOCUS (GE techniques in minimizing the effects of eddy-currents and
Medical Systems), ZOOMit (Siemens Healthineers) and iZOOM patient movement at the time of acquisition (33). Other
(Philips Healthcare). Several studies have reported that DW postprocessing techniques, including maximum intensity
MRI with rFOV improved the lesion conspicuity, compared projections (MIPs), which select the matrix voxel with
to DW MRI with full FOV (Fig. 3) (29-31). However, the the highest signal intensity from the multiple sections to
absolute ADCs in DW MRI with rFOV were lower, compared produce a single image of the whole examination volume,
to DW MRI with full FOV (p < 0.001), which may render the or the fusion of high b value DW MRI to unenhanced T1-
previously published ADC cutoff values less useful in the weighted or T2-weighted images, improve the lesion
interpretation of DW MRI with rFOV (30, 31). detection and conspicuity on DW MRI by enhancing the
image display (26, 27, 34-36). Last of all, the computed DW
Postprocessing MRI is a technique used for obtaining high b value images
Postprocessing may also improve the image quality of DW from those acquired at lower b values. The aforementioned

A B

C D
Fig. 3. DW MRI acquired using different acquisition techniques at the b value of 1000 sec/mm2.
A. Single-shot EPI with in-plane resolution of 1.3 x 1.3 mm2. B. Readout-segmented EPI with in-plane resolution of 1.3 x 1.3 mm2. C. Reduced
field of view technique with in-plane resolution of 0.59 x 0.59 mm2. The T1-weighed dynamic contrast-enhanced MRI with in-plane resolution
of 0.9 x 0.9 mm2. D. Demonstrates two adjacent irregular enhancing masses. Core needle biopsy and conservation surgery revealed two adjacent
grade 2 invasive ductal carcinomas of size 2.4 cm and 0.5 cm. EPI = echo-planar imaging, MRI = magnetic resonance imaging

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 Lee et al.

technique can provide high b value images with good image normal breast parenchymal tissue exhibits a high signal
quality and high background suppression, while maintaining intensity on DW MRI with low b value, as the low b value
a short duration of imaging, and provide the flexibility image is primarily T2-weighted. As the b value increases,
for retrospective generation of images at any b value for the signal intensity of normal breast tissue gets suppressed
optimal interpretation (37, 38). (Fig. 2). The degree of background diffusion signal on high
b value DW MRI can vary among women and can be visually
Image Interpretation assessed according to the 4-point scale of minimum, mild,
moderate and marked (Fig. 4); similar to the background
Imaging Features of Normal Breast Parenchyma and parenchymal enhancement in DCE MRI (39). Several
Background Diffusion Signals previous studies have attempted to establish a normative
In order to develop standardized interpretation criteria, range of breast parenchymal ADC and the reported mean
it is necessary to understand the appearance and normative ADCs of normal breast tissue varies over a wide range from
range of ADCs in the breast parenchyma on DW MRI. The 1.51 x 10-3 to 2.09 x 10-3 mm2/sec (with the maximum b

A B

C D
Fig. 4. The degree of background diffusion signals on DW MRI.
MIP images of DW MRI acquired at the b value of 1200 sec/mm2 displaying minimal (A), mild (B), moderate (C), and marked (D) background
diffusion signals. MIP = maximum intensity projection

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Standardization of DW MRI Acquisition and Interpretation

values ranging from 600 to 1000 sec/mm2) (12). Although of high signal intensity that are distinct from background
hormonal fluctuations may influence the breast ADC values, signals, must be detected on high b value DW MRI (19).
a recent study reported that the ADC values of normal breast The use of MIP of DW MRI enables a quick overview of
parenchyma are not significantly affected by the menstrual the entire breast volume and shortens the reading time
cycle (40). Conversely, breast density can affect the ADC for lesion detection (Fig. 5); similar to the use of MIPs
values of the breast parenchyma and the ADC values tend for abbreviated contrast-enhanced MRI protocols (35). If
to be lower in fatty breasts than in dense breasts, which is lesions with high signal intensity are detected in the DW
most probably attributable to the intravoxel partial volume MRI, the location, size and morphology of the lesions can
averaging with fat (41). be assessed qualitatively. Morphology of the lesions on
DW images can be categorized as foci, masses, or non-
Lesion Detection and Qualitative Assessment on DW MRI mass lesions (Fig. 6). In case of the lesions categorized
In a multiparametric breast MRI protocol, lesion detection as masses, shape (round/oval, irregular) and internal
can primarily be based on the evaluation of contrast- signal pattern (homogeneous, heterogeneous, rim) can be
enhanced sequences (13). When DW MRI is employed as a reported, whereas in non-mass lesions, distribution (focal,
stand-alone screening tool, lesions, defined as unique areas regional, linear, segmental) and internal signal pattern

A B

C D
Fig. 5. Lesion detection and characterization on DW MRI.
Sagittal image from dynamic contrast-enhanced MRI (A) shows an irregular enhancing mass (arrow) in the left breast at the 1 o’clock position.
On reconstructed sagittal MIP of DW MRI obtained with a b value of 1200 sec/mm2 (B), a mass of high signal intensity (arrow) distinct from the
background diffusion signal is easily detectable. On the corresponding axial images of DW MRI obtained with a b value of 800 sec/mm2 (C) and
ADC map (D), an irregular mass of high signal intensity (arrow) with a low mean ADC of 0.97 x 10-3 mm2/sec is demonstrated. Core needle biopsy
and conservation surgery revealed a grade 2 invasive ductal carcinoma of size 1.5 cm.

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 Lee et al.

Unique area of high SI on b = 1200 DW image (axial/sagittal/coronal MIPs)

MASS/FOCUS† NONMASS

Irregular, rim, or Oval/round, and Segmental or linear Focal or regional

heterogeneous homogeneous

ADC ≤ 1.30* ADC > 1.30*

ADC ≤ 1.30* ADC > 1.30*

Biopsy 6 mo FU
Biopsy 6 mo FU

Low/iso SI on Low/iso SI on High SI on Low/iso SI on Low/iso SI on High SI on

b = 0 and b = 0 and ADC > 1.30* b = 0 and b = 0 and b = 0 and ADC > 1.30* b = 0 and
ADC ≤ 1.30* or high SI on b = 0 ADC > 1.3* ADC ≤ 1.30* or high SI on b = 0 ADC > 1.3*
and ADC ≤ 1.30* and ADC ≤ 1.30*

Biopsy 1 y FU Biopsy 1 y FU
6 mo FU 6 mo FU

Fig. 6. Interpretation guideline used in a prospective multicenter study (clinicaltrials.gov Identifier: NCT03835897) for 3T
screening DW MRI with b values of 0, 800, and 1200 sec/mm2. *ADC map is calculated from b = 0 and 800 sec/mm2 DW image, †Focus is
evaluated based on both SI on b = 0 sec/mm2 and ADC value (x 10-3 mm2/sec). FU = follow-up, SI = signal intensity

(homogeneous, heterogeneous) can be reported (13). weighted images, if available (12, 43). On the subject of
Qualitative evaluation of the lesion morphology might be of the size of the ROI to be used, two multicenter trials in the
assistance in avoiding the misclassification of false-positive United States employed the method of drawing the ROI for
benign lesions, such as complicated cysts or fibroadenomas, the entire lesion and measuring the average ADC across a
as well as to avoid misdiagnosis of false-negative malignant lesion (44, 45). However, according to a recently published
lesions, including mucinous carcinoma or invasive breast international expert agreement, the use of a small ROI
cancer with extensive necrosis (42). placed on the darkest part of the lesion on the ADC map
that represents the most suspicious area is suggested as
Quantitative Assessment on DW MRI the preferred method for measuring ADC values, in order to
Lesions detected on high b value DW MRI require cross- reduce the inter- and intra-reader variability and improve
correlation with the ADC map, in order to rule out “T2 the diagnostic performance of breast DW MRI (13). In any
shine-through” effects and the lesions with true restricted case, the type of ROI (whole lesion or focused) used for
diffusion should exhibit low ADCs. Quantitative ADC values ADC measurement should be reported.
(expressed in the units of 10-3 mm2/sec) are measured by In view of the fact that the ADC values are dependent
drawing a region of interest (ROI) on the lesion on the ADC on the b factor, a specific ADC threshold value, which can
map. The ROI should be drawn completely within the lesion, be used to differentiate between benign and malignant
consistent with the hyperintense areas on high b value DW lesions, has not been established. The EUSOBI proposed
MRI, while avoiding normal tissue and areas of necrosis, the use of ADC values measured at the high b value of
hemorrhage, or fat by cross referencing with the contrast- 800 sec/mm2 for the purpose of standardization and they
enhanced T1-weighted images or unenhanced T1- and T2- proposed the classification of diffusion level in lesions as

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Standardization of DW MRI Acquisition and Interpretation

follows: very low (range of ADC, ≤ 0.9 x 10-3 mm2/sec); such as low cellularity or non-mass morphologic type, and
low (range of ADC, 0.9–1.3 x 10-3 mm2/sec); intermediate the limited resolution of the DW MRI technique, in addition
(range of ADC, 1.3–1.7 x 10-3 mm2/sec); high (range of ADC, to other technical issues including artifacts, inadequate
1.7–2.1 x 10-3 mm2/sec) and very high (range of ADC, > 2.1 fat suppression, or low signal-to-noise ratio. Mucinous
x 10-3 mm2/sec) (13). The authors also noted that when the carcinoma is a well-known cause of false-negative results,
ADC value is unrealistically high (> 3 x 10-3 mm2/sec) or owing to the low cellularity and high mucin content (47).
low (< 0.5 x 10-3 mm2/sec), repositioning the ROI may be Moreover, triple-negative cancer with extensive necrosis
required to eliminate the bias from adjacent noise regions, can present with high ADC values (48). Ductal carcinoma
such as voxels containing fat (13). The previously reported in situ (DCIS) and invasive lobular carcinoma are typically
ADC cutoff values to distinguish between benign and non-mass type carcinomas and are more likely to be missed
malignant lesions ranged from 1.1 x 10-3 to 1.6 x 10-3 mm2/ by DW MRI, compared to the invasive ductal carcinoma,
sec (46). The choice of ADC cutoff values to differentiate owing to the low conspicuity (49). Finally, considering the
between benign and malignant lesions can depend on typical in-plane spatial resolution (2 x 2 mm2) and section
the expectations from DW MRI (12). Higher cutoff values thickness (3–5 mm) of DW MRI, small cancers (1 cm or less
should be selected to increase the sensitivity and lower in size) are expected to be less detectable or incorrectly
cutoff values are desirable to improve the specificity. A characterized on account of the partial volume effects (50,
recent multicenter study, the American College of Radiology 51). Technical advances in breast DW MRI may improve the
Imaging Network 6702 trial, evaluated the ADC values of detection and characterization of smaller cancer foci and
undiagnosed breast lesions (BI-RADS 3, 4, or 5) identified non-mass lesions.
through DCE MRI and proposed 1.68 x 10-3 mm2/sec as Examples of false-positive findings on breast DW MRI
the cutoff value that can improve the specificity without include mastitis, abscesses and hematomas, complicated
affecting the sensitivity (45). An ongoing multicenter cysts, intramammary lymph nodes, intraductal papilloma,
prospective clinical trial (clinicaltrials.gov Identifier: atypical ductal hyperplasia and fibroadenomas with high
NCT03835897) in South Korea, which employs the DW MRI cellularity (33, 46, 47, 52, 53). According to previous
for primary breast cancer screening in high-risk women, uses reports, the diffusion of water molecules is not only
an interpretation algorithm that combines quantitative b restricted in the environments with high cellularity, but
value measurements with qualitative morphology evaluation also in the regions of intracellular and extracellular edema,
and uses an ADC cutoff value of 1.3 x 10-3 mm2/sec (Fig. 6). regions of high viscosity in abscesses and hematomas,
coagulated blood or proteinaceous debris within ducts and
False-Negative and False-Positive Findings cysts, and areas with a high degree of fibrosis (18, 54, 55).
The DW MRI signals and ADC values of various breast Furthermore, artifactual signal at the nipple, an area prone
lesions are summarized in Table 2. DW MRI cannot detect all to susceptibility-based distortion on DW MRI, can result in
the malignancies, which can be identified through DCE MRI. false-positive findings (49, 50).
False-negative findings on DW MRI can be caused by two
primary factors: the characteristics of the carcinoma itself,

Table 2. Signal Intensity on DW MRI and ADC Value for Various Breast Lesions
Signal Intensity Signal Intensity
ADC
Lesion Type Pathologic Condition on DW MRI with on DW MRI with
Value
High b value* Low b value
Cancer, intraductal papilloma, mastitis/
High cellularity, high viscosity fluid High Intermediate Decreased
abscess, hemorrhage
Medium cellularity, high water Fibroadenoma with increased cellularity, High to Intermediate Intermediate
content, proteinaceous fluid complicated cyst intermediate to high to high
Low cellularity, high water content Cyst, fibroadenoma, mucinous cancer Intermediate to low High Increased
Low cellularity, low water content Fibrous tissue, calcification Low Low Decreased
Signal intensity may differ depending on the imaging parameters. Higher b values result in overall lower signal from all tissues. *b =
800–1500 sec/mm2.

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Clinical Applications of DW MRI: Current accuracy by means of the changes in ADC, compared to the
Evidence and Possibilities changes on DCE MRI in some cases (44). However, in the
current literature, there is a wide variability in opinions
Lesion Characterization and Diagnosis regarding the utility of DW MRI to monitor and predict
The primary and most explored application of DW MRI in treatment response; probably due to the differences in study
breast imaging has been to use DW MRI as a supplement design, including patient characteristics, treatment regimens,
to DCE MRI in the differential diagnosis of benign and chemotherapy cycle and image timing, DW MRI acquisition
malignant lesions. Two meta-analyses, which evaluated parameters and methods of ADC measurement. In this
the diagnostic performance of quantitative breast DW scenario, further investigation is required, in order to validate
MRI, demonstrated that the overall specificity of DW ADC as a predictive biomarker for treatment response.
MRI is superior, compared to DCE MRI (56, 57). Several
studies, including one prospective multicenter trial, have Axillary Lymph Nodes
consistently reported that supplementing DCE MRI with DW DW MRI is a promising tool, which can be used to
MRI improves the specificity (75–84%), compared to the differentiate between metastatic and nonmetastatic axillary
specificity of DCE MRI alone (67–72%); thus, potentially lymph nodes in patients with breast cancer. According to
obviating unnecessary biopsies (33, 45, 58, 59). a meta-analysis, which included ten published studies, the
In addition to the differentiation between benign and mean ADC value of metastatic lymph nodes was significantly
malignant lesions, DW MRI has the potential to characterize lower, compared to that of nonmetastatic lymph nodes
malignancies in terms of tumor grade and hormone receptor and the pooled sensitivity and specificity of DW MRI were
status, and distinguish between invasive and noninvasive 89% and 83%, respectively (73). Another systematic review
diseases. It has been reported that high-grade invasive reported that DW MRI showed higher median sensitivity
cancers have lower ADC values, compared to intermediate- (84.2%) and negative predictive value (90.6%), compared
or low-grade cancers and DCIS (60-62). ADC values were to DCE MRI (60% and 80%); however, the sensitivity and
shown to be higher in estrogen receptor (ER)-negative negative predictive value was observed to be inferior to
tumors, compared to the ER-positive tumors; whereas the unenhanced T1-weighted/T2-weighted MRI (88.4% and
human epidermal growth factor receptor-enriched tumors 94.7%) (74). Scaranelo et al. (75) reported that axillary
exhibited the highest ADC values (48, 63-65). Considering lymph node evaluation with DW MRI is reproducible and
the whole scenario, further studies involving larger cohorts reliable, but the additional benefit over conventional T1-
from multiple institutions are required, in order to determine weighted/T2-weighted MRI is minimal. The use of dedicated
the association between ADC and tumor biomarkers. axillary protocols may improve the diagnostic performance
in nodal staging (76).
Monitoring and Prediction of Treatment Response
Neoadjuvant chemotherapy is increasingly being used for Unenhanced MRI for Breast Cancer Screening
breast cancer treatment. Cytotoxic effects of chemotherapy, DW MRI has the potential to be employed as a stand-
including cell lysis, apoptosis and necrosis, cause alterations alone tool for unenhanced MRI for breast cancer screening.
in the cell membrane integrity, which increases the water In a study involving 118 mammographically occult lesions
mobility in the extracellular space that occurs before the (91 benign, 27 malignant), DW MRI could detect 89% of
advent of morphologic changes. Multiple studies have the DCE MRI-detected malignancies, when the readers were
reported that the increase in tumor ADC, in response to not blinded to the images from DCE MRI (56). In another
treatment, is detectable earlier than the changes in size or nonblinded study involving 60 mammographically occult
vascularity, as measured by DCE MRI, which may denote an cancers, DW MRI detected more cancers, compared to the
early indication of the treatment efficacy (66-68). Moreover, MRI-guided focused ultrasound (78% and 63%, respectively,
some studies have found that the pretreatment tumor ADC p = 0.049) (77). In previous blinded reader studies in which
values are predictive of the pathological response; baseline the readers assessed only unenhanced MRI sequences,
ADC values were observed to be lower in clinical responders, including DW MRI with or without nonenhanced T1/T2-
compared to non-responders (69-72). Residual disease after weighted image, the sensitivity of DW MRI in various study
neoadjuvant chemotherapy may be predicted with greater designs ranged from 45% to 94% (27, 34, 49, 50, 78, 79).

18 https://doi.org/10.3348/kjr.2020.0093 kjronline.org
Standardization of DW MRI Acquisition and Interpretation

The limitations of DW MRI for breast cancer screening HM, Obdeijn IM, et al. Efficacy of MRI and mammography for
include the lack of evidence from larger prospective studies breast-cancer screening in women with a familial or genetic
predisposition. N Engl J Med 2004;351:427-437
and the difficulty of targeting the lesions in vacuum
2. Warner E, Plewes DB, Hill KA, Causer PA, Zubovits JT, Jong
assisted MRI-guided biopsy of the lesions detected only
RA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers
through DW MRI, particularly in the case of small lesions with magnetic resonance imaging, ultrasound, mammography,
(less than 1 cm in size) (80). Currently, ongoing prospective and clinical breast examination. JAMA 2004;292:1317-1325
clinical trials are investigating the role of DW MRI in 3. Kuhl CK, Schrading S, Leutner CC, Morakkabati-Spitz N,
screening high-risk women (NCT03835897) or women Wardelmann E, Fimmers R, et al. Mammography, breast
ultrasound, and magnetic resonance imaging for surveillance
with dense breasts (NCT03607552), using standardized
of women at high familial risk for breast cancer. J Clin Oncol
and optimized DW MRI protocols. Further evidence from
2005;23:8469-8476
the prospective multicenter clinical studies and technical 4. Leach MO, Boggis CR, Dixon AK, Easton DF, Eeles RA, Evans
advances in DW MRI will facilitate the use of DW MRI in DG, et al. Screening with magnetic resonance imaging and
unenhanced breast cancer screening. mammography of a UK population at high familial risk
of breast cancer: a prospective multicentre cohort study
(MARIBS). Lancet 2005;365:1769-1778
CONCLUSION 5. Lehman CD, Blume JD, Thickman D, Bluemke DA, Pisano
E, Kuhl C, et al. Added cancer yield of MRI in screening
In summary, DW MRI is a rapid, unenhanced technique, the contralateral breast of women recently diagnosed with
which shows the potential to be employed in breast cancer breast cancer: results from the International Breast Magnetic
screening and can be used in the accurate differential Resonance Consortium (IBMC) trial. J Surg Oncol 2005;92:9-
diagnosis of the breast lesions found in DCE MRI and the 15; discussion 15-16
6. Warner E, Hill K, Causer P, Plewes D, Jong R, Yaffe M, et
monitoring of breast cancer response to neoadjuvant
al. Prospective study of breast cancer incidence in women
chemotherapy. Standardized acquisition and interpretation
with a BRCA1 or BRCA2 mutation under surveillance with
protocols can improve the image quality of DW MRI and and without magnetic resonance imaging. J Clin Oncol
reduce the variability in results. High resolution DW MRI 2011;29:1664-1669
using advanced acquisition techniques and postprocessing 7. Berg WA, Zhang Z, Lehrer D, Jong RA, Pisano ED, Barr
will facilitate better detection and characterization of RG, et al. Detection of breast cancer with addition of
annual screening ultrasound or a single screening MRI to
subcentimeter cancers and reduce the false-negative and
mammography in women with elevated breast cancer risk.
false-positive findings. The results from ongoing prospective
JAMA 2012;307:1394-1404
clinical studies using standardized and optimized protocols 8. Passaperuma K, Warner E, Causer PA, Hill KA, Messner S,
will facilitate the use of DW MRI in unenhanced breast Wong JW, et al. Long-term results of screening with magnetic
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Cancer 2012;107:24-30
9. Kuhl CK, Schrading S, Strobel K, Schild HH, Hilgers RD, Bieling
Conflicts of Interest
HB. Abbreviated breast magnetic resonance imaging (MRI):
The authors have no potential conflicts of interest to
first postcontrast subtracted images and maximum-intensity
disclose. projection-a novel approach to breast cancer screening with
MRI. J Clin Oncol 2014;32:2304-2310
ORCID iDs 10. Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku
Su Hyun Lee J, et al. Gadolinium-based contrast agent accumulates in
the brain even in subjects without severe renal dysfunction:
https://orcid.org/0000-0002-0171-8060
evaluation of autopsy brain specimens with inductively
Hee Jung Shin
coupled plasma mass spectroscopy. Radiology 2015;276:228-
https://orcid.org/0000-0002-3398-1074 232
Woo Kyung Moon 11. McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray
https://orcid.org/0000-0001-8931-3772 DL, Thielen KR, et al. Intracranial gadolinium deposition after
contrast-enhanced MR imaging. Radiology 2015;275:772-782
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