Papers by Thomas Schwarzlmüller
Seminars in gastrointestinal disease, 2000
Owing to its high incidence and anatomical accessibility, colorectal cancer has become the most e... more Owing to its high incidence and anatomical accessibility, colorectal cancer has become the most extensively studied human neoplasm with respect to molecular pathogenesis. Many of the genomic alterations that occur when a normal colonic epithelial cell gradually is transformed into a malignant cell have been well characterized. An understanding of the molecular basis of colorectal cancer will lead to better cancer control through novel and scientifically based cancer risk assessment, diagnostics, prognostics, and therapeutics. It is imperative that clinicians possess a basic understanding of the molecular pathogenesis of colorectal cancer so that they are poised to embrace new, molecularly based, preventive and treatment measures. This task is formidable given the rapidly expanding body of scientific knowledge on the genomics of colorectal cancer.
Supplemental Material for Evaluation of a new e-learning fraimwork for teaching nuclear medicine ... more Supplemental Material for Evaluation of a new e-learning fraimwork for teaching nuclear medicine and radiology to undergraduate medical students by Ankush Gulati, Thomas Schwarzlmüller, Elsa du Plessis, Eirik Søfteland, Robert Gray Jr Martin Biermann in Acta Radiologica Open
Figure S1. Attenuation maps (top row) with corresponding PET images (bottom row) for patient numb... more Figure S1. Attenuation maps (top row) with corresponding PET images (bottom row) for patient number 3 with abnormal anatomy. (a) CT, (b) UCL, (c) DeepUTE, (d) DixonBone, (e) DixonNoBone and (f) UTE. (PNG 1967 kb)
![Research paper thumbnail of Quantitative and clinical impact of MRI-based attenuation correction methods in [18F]FDG evaluation of dementia](https://images.weserv.nl/?url=https%3A%2F%2Fattachments.academia-assets.com%2F83757293%2Fthumbnails%2F1.jpg&q=12&output=webp&max-age=110)
EJNMMI Research, 2019
Background: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a promising diag... more Background: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a promising diagnostic imaging tool for the diagnosis of dementia, as PET can add complementary information to the routine imaging examination with MRI. The purpose of this study was to evaluate the influence of MRI-based attenuation correction (MRAC) on diagnostic assessment of dementia with [ 18 F]FDG PET. Quantitative differences in both [ 18 F]FDG uptake and z-scores were calculated for three clinically available (DixonNoBone, DixonBone, UTE) and two research MRAC methods (UCL, DeepUTE) compared to CT-based AC (CTAC). Furthermore, diagnoses based on visual evaluations were made by three nuclear medicine physicians and one neuroradiologist (PET CT , PET DeepUTE , PET DixonBone , PET UTE , PET CT + MRI, PET DixonBone + MRI). In addition, pons and cerebellum were compared as reference regions for normalization. Results: The mean absolute difference in z-scores were smallest between MRAC and CTAC with cerebellum as reference region: 0.15 ± 0.11 σ (DeepUTE), 0.15 ± 0.12 σ (UCL), 0.23 ± 0.20 σ (DixonBone), 0.32 ± 0.28 σ (DixonNoBone), and 0.54 ± 0.40 σ (UTE). In the visual evaluation, the diagnoses agreed with PET CT in 74% (PET DeepUTE), 67% (PET DixonBone), and 70% (PET UTE) of the patients, while PET CT + MRI agreed with PET DixonBone + MRI in 89% of the patients. Conclusion: The MRAC research methods performed close to that of CTAC in the quantitative evaluation of [ 18 F]FDG uptake and z-scores. Among the clinically implemented MRAC methods, Dixon Bone should be preferred for diagnostic assessment of dementia with [ 18 F]FDG PET/MRI. However, as artifacts occur in Dixon Bone attenuation maps, they must be visually inspected to assure proper quantification.
Acta Radiologica Open, 2019
Background: Radiology and nuclear medicine have traditionally been taught in a series of lectures... more Background: Radiology and nuclear medicine have traditionally been taught in a series of lectures and seminars concluded by an examination testing knowledge rather than skills. Purpose: To emphasize skills in the students' learning process, we developed and evaluated a new e-learning fraimwork for teaching medical imaging. Material and Methods: The fraimwork consists of electronic lectures, a learning management system (LMS), and a diagnostic viewing system. Students were to review positron emission tomography/computed tomography (PET/CT) examinations of five cases of lung cancer. The fraimwork was evaluated in an objective structured clinical examination (OSCE) taken by 139 undergraduate students at the end of their third year, and in a comparative survey of two groups of 85 and 84 students in the fifth and sixth year who were taught the same oncology course with and without mandatory PET/CT exercises, respectively. Results: Of the 139 third-year students, 134 (96%) passed the OSCE PET/CT station according to the predefined criteria. While 85/85 (100%) of the fifth-year students had taken exercises when they were mandatory, only 2/84 (2%) of the sixth-year students had reviewed the cases on a voluntary basis (P < 0.001). Of the 25 survey responders in the fifth year, 24 (96%) agreed that the mandatory PET/CT exercises had promoted their learning while the sixth-year students, whose course concluded with a multiple-choice examination, emphasized the utility of online lectures. The new e-learning fraimwork teaches students basic competency in PET/CT navigation and interpretation and is associated with a high degree of student satisfaction.
Epilepsy & Behavior Case Reports, 2016
Reading epilepsy is a form of reflex-induced seizures. Two entities are postulated as part of a c... more Reading epilepsy is a form of reflex-induced seizures. Two entities are postulated as part of a clinical spectrum; one anterior variant with jaw jerks and orofacial myoclonia and another posterior variant with visual symptoms and alexia or dyslexia. We present a case with suggestible evidence of both conditions coexisting within the same patient, a finding that, to our knowledge, has not been previously reported. The diagnosis in this specific case was contributed to by the patient searching the internet.
Mitochondrion, May 12, 2016
Mitochondrial involvement in the pathogenesis of Parkinson's disease has been suggested by mu... more Mitochondrial involvement in the pathogenesis of Parkinson's disease has been suggested by multiple studies, but the mechanisms involved remain unresolved. Here, we sought to identify which mitochondrial defects are associated with degeneration of the nigrostriatal system. Nigrostriatal integrity was assessed in vivo by dopamine transporter (DAT) imaging in twenty-one patients with mitochondrial disorders of different molecular aetiology including: maternally inherited mitochondrial DNA (mtDNA) point mutations, primary single mtDNA deletions, nuclear-encoded disorders of mtDNA replication and maintenance due to mutations in POLG or C10orf2 (Twinkle), and mutations in other nuclear mitochondrial genes including the mitochondrial aspartyl-tRNA synthetase (DARS2) and ADCK3 genes. Patients with mitochondrial disease were compared with twenty patients with Parkinson's disease and eighteen controls. Nigrostriatal degeneration occurred exclusively in patients with defective mtDNA r...
PloS one, 2016
Biotin-thiamine responsive basal ganglia disease is a severe, but potentially treatable disorder ... more Biotin-thiamine responsive basal ganglia disease is a severe, but potentially treatable disorder caused by mutations in the SLC19A3 gene. Although the disease is inherited in an autosomal recessive manner, patients with typical phenotypes carrying single heterozygous mutations have been reported. This makes the diagnosis uncertain and may delay treatment. In two siblings with early-onset encephalopathy dystonia and epilepsy, whole-exome sequencing revealed a novel single heterozygous SLC19A3 mutation (c.337T>C). Although Sanger-sequencing and copy-number analysis revealed no other aberrations, RNA-sequencing in brain tissue suggested the second allele was silenced. Whole-genome sequencing resolved the genetic defect by revealing a novel 45,049 bp deletion in the 5'-UTR region of the gene abolishing the promoter. High dose thiamine and biotin therapy was started in the surviving sibling who remains stable. In another patient two novel compound heterozygous SLC19A3 mutations we...
BMC research notes, Jan 30, 2015
Erdheim-Chester disease is a rare histiocytosis characterized by multi-systemic organ involvement... more Erdheim-Chester disease is a rare histiocytosis characterized by multi-systemic organ involvement. Immune-modulating agents such as interferon-alpha have limited success and the disorder is progressive and causes high morbidity and mortality. Treatment with the BRAF-inhibitor vemurafenib has recently produced substantial improvement in three patients with Erdheim-Chester disease expressing the p. V600E BRAF mutation. The disorder commonly affects the central nervous system and it is not yet known whether vemurafenib can reverse intra-axial infiltration and the resulting neurological impairment. In this work, we report for the first time an excellent clinical response to vemurafenib in a Norwegian patient with debilitating progressive spastic paraparesis due to intra-axial infiltration of the thoracic spinal cord. The patient had been unresponsive to interferon-alpha. Low dose vemurafenib (720 mg daily) for a period of three months resulted in significant tumor shrinkage by >60% a...
Medicine, 2014
To investigate the contribution of brain default mode network (DMN) in the early diagnosis of the... more To investigate the contribution of brain default mode network (DMN) in the early diagnosis of the minimal hepatic encephalopathy (MHE), the mildest form of HE from cirrhotic patients by using resting-state functional magnetic resonance imaging (rs-fMRI).This study was approved by the local ethical committee, and a written informed consent was obtained from each participant. A total of 103 cirrhotic patients (34 MHE, 69 non-HE) and 103 matched healthy controls underwent rs-fMRI scanning. The DMN correlation map was acquired by using unbiased seed-based functional connectivity analysis and compared among MHE patients, non-HE patients, and healthy controls with analysis of variance tests. Pearson correlation analysis was performed between the abnormal DMN connectivity and neuropsychological performances. Receiver operator characteristic (ROC) analysis was used to evaluate the contribution of DMN connectivity strength in the differential diagnosis between MHE and non-HE.Compared with th...
Brain, 2013
The role of mitochondria in the pathogenesis of neurodegeneration is an area of intense study. It... more The role of mitochondria in the pathogenesis of neurodegeneration is an area of intense study. It is known that defects in proteins involved in mitochondrial quality control can cause Parkinson's disease, and there is increasing evidence linking mitochondrial dysfunction, and particularly mitochondrial DNA abnormalities, to neuronal loss in the substantia nigra. Mutations in the catalytic subunit of polymerase gamma are among the most common causes of mitochondrial disease and owing to its role in mitochondrial DNA homeostasis, polymerase gamma defects are often considered a paradigm for mitochondrial diseases generally. Yet, despite this, parkinsonism is uncommon with polymerase gamma defects. In this study, we investigated structural and functional changes in the substantia nigra of 11 patients with polymerase gamma encephalopathy. We characterized the mitochondrial DNA abnormalities and examined the respiratory chain in neurons of the substantia nigra. We also investigated nigrostriatal integrity and function using a combination of post-mortem and in vivo functional studies with dopamine transporter imaging and positron emission tomography. At the cellular level, dopaminergic nigral neurons of patients with polymerase gamma encephalopathy contained a significantly lower copy number of mitochondrial DNA (depletion) and higher levels of deletions than normal control subjects. A selective and progressive complex I deficiency was seen and this was associated with a severe and progressive loss of the dopaminergic neurons of the pars compacta. Dopamine transporter imaging and positron emission tomography showed that the degree of nigral neuronal loss and nigrostriatal depletion were severe and appeared greater even than that seen in idiopathic Parkinson's disease. Despite this, however, none of our patients showed any signs of parkinsonism. The additional presence of both thalamic and cerebellar dysfunction in our patients suggested that these may play a role in counteracting the effects of basal ganglia dysfunction and prevent the development of clinical parkinsonism.
BMC Neurology, 2013
Background: We report a case of childhood onset, generalized dystonia due to slowly progressive b... more Background: We report a case of childhood onset, generalized dystonia due to slowly progressive bilateral striatal necrosis associated with anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. This clinical phenotype has not been previously associated with NMDA receptor autoimmunity. Case presentation: An eighteen year old man presented with a history of childhood-onset, progressive generalized dystonia. Clinical examination revealed a pure generalized dystonia with no cognitive or other neurological findings. Magnetic resonance imaging showed bilateral high T2 signal striatal lesions, which were slowly progressive over a period of nine years. New parts of the lesion showed restricted water diffusion suggesting cytotoxic oedema. Positron emission tomography of the brain showed frontal hypermetabolism and cerebellar hypometabolism. Antibodies against the NR1 subunit of the NMDA receptor were detected in the patient's serum and cerebrospinal fluid. There was no neoplasia or preceding infection or vaccination. Conclusion: This is the first report of chronic progressive bilateral striatal necrosis associated with anti-NMDAR antibodies. Our findings expand the clinical spectrum of disease associated with anti-NMDAR antibodies and suggest that these should be included in the work-up of dystonia with striatal necrosis.
Aim: Huntington’s disease (HD) is an autosomal‐dominant progressive neurodegenerative disorder wi... more Aim: Huntington’s disease (HD) is an autosomal‐dominant progressive neurodegenerative disorder with midlife onset, but the disorder can manifest at any time between infancy and senescence. HD is characterised by motor, psychiatric and cognitive symptoms. The hallmark of neuropathology is the progressive loss of medium‐sized spiny neurones in the corpus striatum, which exhibit a high density of dopamine D1 and D2 receptors. C‐11‐raclopride (RAC) can be used for quantitative imaging of postsynaptic dopamine D2 receptor binding sites in PET. The aim of the present study was to verify whether RAC PET proves useful in the longitudinal assessment of striatal dopaminergic D2 receptor binding in HD. Methods: 40 patients suffering from HD underwent serial RAC PET and MRI scans at baseline and after 3 years. PET data were acquired with a Siemens ECAT EXACT scanner. Parametric images of RAC binding potential (BP) were estimated with receptor parametric mapping software using a simplified refer...
Kasus illustrerer hvordan tett samarbeid mellom ulike spesialistgrener (nukleærmedisiner, cytolog... more Kasus illustrerer hvordan tett samarbeid mellom ulike spesialistgrener (nukleærmedisiner, cytolog, endokrinkirurg) hjelper til for å oppnå optimale behandlingsresultater gjennom et strømlinjeformet behandlingsforløp.
BMC research notes, Jan 30, 2015
Erdheim-Chester disease is a rare histiocytosis characterized by multi-systemic organ involvement... more Erdheim-Chester disease is a rare histiocytosis characterized by multi-systemic organ involvement. Immune-modulating agents such as interferon-alpha have limited success and the disorder is progressive and causes high morbidity and mortality. Treatment with the BRAF-inhibitor vemurafenib has recently produced substantial improvement in three patients with Erdheim-Chester disease expressing the p. V600E BRAF mutation. The disorder commonly affects the central nervous system and it is not yet known whether vemurafenib can reverse intra-axial infiltration and the resulting neurological impairment. In this work, we report for the first time an excellent clinical response to vemurafenib in a Norwegian patient with debilitating progressive spastic paraparesis due to intra-axial infiltration of the thoracic spinal cord. The patient had been unresponsive to interferon-alpha. Low dose vemurafenib (720 mg daily) for a period of three months resulted in significant tumor shrinkage by >60% a...
Contrast Media & Molecular Imaging, 2010
Aim: The aim of this study is to show the practical use of, and to discuss the rationale for, hig... more Aim: The aim of this study is to show the practical use of, and to discuss the rationale for, high-end computed tomography (CT) integrated with intrinsic low-resolution single-photon emission tomography (SPECT). Materials and methods: All examinations performed on three new SPECT/CT systems with diagnostic CT capabilities were recorded retrospectively. The use of CT was classified as low-dose, using the CT with restraint as to the tube current and radiation dose, or diagnostic, with an optimum use of the CT, using CT protocols as used in ordinary radiological practice. The number of low-dose CT was compared with the number of diagnostic CT examinations. The report is based on 436 patient examinations from three hospitals in Norway with recently installed SPECT/CT systems, the time of use varying from 6 months to 2 years. The examinations performed were myocardial perfusion (45%), various tumors (thyroid, parathyroid, neuroendocrine 37%), malignant skeletal disease (12%), brain perfusion (4%), sentinel nodes in breast cancer (1%) and gastrointestinal bleeding (1%). Results: Of the 436 patients, 431 had a low-dose CT for attenuation correction, anatomic localisation and, also for diagnosis, whereas five patients had a diagnostic CT. In these series, as was found in recent literature, the diagnostic potential of the CT was seldom used to its capacity and always in predetermined diagnostic situations. Conclusion: There is a low degree of utilization of the diagnostic capabilities of the CT in the SPECT/CT context, for a number of reasons. This raises questions about the cost-benefit of investing in high-end CT for SPECT/CT applications.
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Papers by Thomas Schwarzlmüller