Removing outliers from the normative database improves regional atrophy detection in single-subject voxel-based morphometry.

PURPOSE: Single-subject voxel-based morphometry (VBM) compares an individual T1-weighted MRI to a sample of normal MRI in a normative database (NDB) to detect regional atrophy. Outliers in the NDB might result in reduced sensitivity of VBM. The primary aim of the current study was to propose a method for outlier removal ("NDB cleaning") and to test its impact on the performance of VBM for detection of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). METHODS: T1-weighted MRI of 81 patients with biomarker-confirmed AD (n = 51) or FTLD (n = 30) and 37 healthy subjects with simultaneous FDG-PET/MRI were included as test dataset. Two different NDBs were used: a scanner-specific NDB (37 healthy controls from the test dataset) and a non-scanner-specific NDB comprising 164 normal T1-weighted MRI from 164 different MRI scanners. Three different quality metrics based on leave-one-out testing of the scans in the NDB were implemented. A scan was removed if it was an outlier with respect to one or more quality metrics. VBM maps generated with and without NDB cleaning were assessed visually for the presence of AD or FTLD. RESULTS: Specificity of visual interpretation of the VBM maps for detection of AD or FTLD was 100% in all settings. Sensitivity was increased by NDB cleaning with both NDBs. The effect was statistically significant for the multiple-scanner NDB (from 0.47 [95%-CI 0.36-0.58] to 0.61 [0.49-0.71]). CONCLUSION: NDB cleaning has the potential to improve the sensitivity of VBM for the detection of AD or FTLD without increasing the risk of false positive findings.

Asymmetry of thalamic hypometabolism on FDG-PET/CT in neurofibromatosis type 1: Association with peripheral tumor burden.

BACKGROUND AND PURPOSE: Thalamic hypometabolism is a consistent finding in brain PET with F-18 fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). However, the pathophysiology of this metabolic alteration is unknown. We hypothesized that it might be secondary to disturbance of peripheral input to the thalamus by NF1-characteristic peripheral nerve sheath tumors (PNSTs). To test this hypothesis, we investigated the relationship between thalamic FDG uptake and the number, volume, and localization of PNSTs. METHODS: This retrospective study included 22 adult NF1 patients (41% women, 36.2 ± 13.0 years) referred to whole-body FDG-PET/contrast-enhanced CT for suspected malignant transformation of PNSTs and 22 sex- and age-matched controls. Brain FDG uptake was scaled voxelwise to the individual median uptake in cerebellar gray matter. Bilateral mean and left-right asymmetry of thalamic FDG uptake were determined using a left-right symmetric anatomical thalamus mask. PNSTs were manually segmented in contrast-enhanced CT. RESULTS: Thalamic FDG uptake was reduced in NF1 patients by 2.0 standard deviations (p < .0005) compared to controls. Left-right asymmetry was increased by 1.3 standard deviations (p = .013). Thalamic hypometabolism was higher in NF1 patients with ≥3 PNSTs than in patients with ≤2 PNSTs (2.6 vs. 1.6 standard deviations, p = .032). The impact of the occurrence of paraspinal/paravertebral PNSTs and of the mean PNST volume on thalamic FDG uptake did not reach statistical significance (p = .098 and p = .189). Left-right asymmetry of thalamic FDG uptake was not associated with left-right asymmetry of PNST burden (p = .658). CONCLUSIONS: This study provides first evidence of left-right asymmetry of thalamic hypometabolism in NF1 and that it might be mediated by NF1-associated peripheral tumors.

DeePSC: A Deep Learning Model for Automated Diagnosis of Primary Sclerosing Cholangitis at Two-dimensional MR Cholangiopancreatography.

Purpose: To develop, train, and validate a multiview deep convolutional neural network (DeePSC) for the automated diagnosis of primary sclerosing cholangitis (PSC) on two-dimensional MR cholangiopancreatography (MRCP) images. Materials and Methods: This retrospective study included two-dimensional MRCP datasets of 342 patients (45 years ± 14 [SD]; 207 male patients) with confirmed diagnosis of PSC and 264 controls (51 years ± 16; 150 male patients). MRCP images were separated into 3-T (n = 361) and 1.5-T (n = 398) datasets, of which 39 samples each were randomly chosen as unseen test sets. Additionally, 37 MRCP images obtained with a 3-T MRI scanner from a different manufacturer were included for external testing. A multiview convolutional neural network was developed, specialized in simultaneously processing the seven images taken at different rotational angles per MRCP examination. The final model, DeePSC, derived its classification per patient from the instance expressing the highest confidence in an ensemble of 20 individually trained multiview convolutional neural networks. Predictive performance on both test sets was compared with that of four licensed radiologists using the Welch t test. Results: DeePSC achieved an accuracy of 80.5% ± 1.3 (sensitivity, 80.0% ± 1.9; specificity, 81.1% ± 2.7) on the 3-T and 82.6% ± 3.0 (sensitivity, 83.6% ± 1.8; specificity, 80.0% ± 8.9) on the 1.5-T test set and scored even higher on the external test set (accuracy, 92.4% ± 1.1; sensitivity, 100.0% ± 0.0; specificity, 83.5% ± 2.4). DeePSC outperformed radiologists in average prediction accuracy by 5.5 (P = .34, 3 T) and 10.1 (P = .13, 1.5 T) percentage points. Conclusion: Automated classification of PSC-compatible findings based on two-dimensional MRCP was achievable and demonstrated high accuracy on internal and external test sets.Keywords: Neural Networks, Deep Learning, Liver Disease, MRI, Primary Sclerosing Cholangitis, MR Cholangiopancreatography Supplemental material is available for this article. © RSNA, 2023.

Left ventricular myocardial strain responding to chronic pressure overload in patients with resistant hypertension evaluated by feature-tracking CMR.

OBJECTIVES: The study aimed to investigate the alterations of myocardial deformation responding to long-standing pressure overload and the effects of focal myocardial fibrosis using feature-tracking cardiac magnetic resonance (FT-CMR) in patients with resistant hypertension (RH). METHODS: Consecutive RH patients were prospectively recruited and underwent CMR at a single institution. FT-CMR analyses based on cine images were applied to measure left ventricular (LV) peak systolic global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). Functional and morphological CMR variables, and late gadolinium enhancement (LGE) imaging were also obtained. RESULTS: A total of 50 RH patients (63 ± 12 years, 32 men) and 18 normotensive controls (57 ± 8 years, 12 men) were studied. RH patients had a higher average systolic blood pressure than controls (166 ± 21 mmHg vs. 116 ± 8 mmHg, p < 0.001) with the intake of 5 ± 1 antihypertensive drugs. RH patients showed increased LV mass index (78 ± 15 g/m2 vs. 61 ± 9 g/m2, p < 0.001), decreased GLS (- 16 ± 3% vs. - 19 ± 2%, p = 0.001) and GRS (41 ± 12% vs. 48 ± 8%, p = 0.037), and GCS was reduced by trend (- 17 ± 4% vs. - 19 ± 4%, p = 0.078). Twenty-one (42%) RH patients demonstrated a LV focal myocardial fibrosis (LGE +). LGE + RH patients had higher LV mass index (85 ± 14 g/m2 vs. 73 ± 15 g/m2, p = 0.007) and attenuated GRS (37 ± 12% vs. 44 ± 12%, p = 0.048) compared to LGE - RH patients, whereas GLS (p = 0.146) and GCS (p = 0.961) were similar. CONCLUSION: Attenuation of LV GLS and GRS, and GCS decline by tendency, might be adaptative changes responding to chronic pressure overload. There is a high incidence of focal myocardial fibrosis in RH patients, which is associated with reduced LV GRS. CLINICAL RELEVANCE STATEMENT: Feature-tracking CMR-derived myocardial strain offers insights into the influence of long-standing pressure overload and of a myocardial fibrotic process on cardiac deformation in patients with resistant hypertension. KEY POINTS: • Variations of left ventricular strain are attributable to the degree of myocardial impairment in resistant hypertensive patients. • Focal myocardial fibrosis of the left ventricle is associated with attenuated global radial strain. • Feature-tracking CMR provides additional information on the attenuation of myocardial deformation responding to long-standing high blood pressure.

Accuracy of preoperative CT staging of acute colonic diverticulitis using the classification of diverticular disease (CDD) - Is there a beneficial impact of water enema and visceral obesity?

PURPOSE: We evaluated the accuracy of preoperative CT in staging colonic diverticulitis (ACD) by using the classification of diverticular disease (CDD) and investigated the diagnostic impact of water enema (WE) and visceral obesity. METHODS: In this retrospective study, the radiological and hospital information system was searched for patients who underwent CT for clinically suspected ACD prior to surgery between 2009 and 2019. From the initial population (n = 164), we included 155 patients (94.5 %) (85 women; mean age: 58 ±â€¯13 years) matching the following inclusion criteria: i.) clinically suspected ACD, ii.) i.v. contrast-enhanced CT, iii.) surgery for ACD within 1 week after CT, iv.) histopathological report that proved ACD. The remaining 9 patients (5.5 %) were excluded because histopathological reports were lacking (n = 3) or CT was performed without intravenous contrast agent (n = 6). WE (+ butylscopolamine i.v.) was performed in 93 patients (group A, 60 %). 62 patients (group B, 40 %) had no WE. Visceral-to-subcutaneous fat ratio (V/S) was determined for each patient. Two radiologists blinded for final diagnosis independently staged ACD according to CDD and assessed prevalence and confidence ratings of ACD-related CT-findings: pericolonic fat stranding, covered- and free-perforation, local and generalized peritonitis, abscess. Interobserver-agreement of CT-findings were assessed and effects of WE and V/S ratio on the diagnostic accuracy of CT with surgical and histopathological findings as reference were determined by calculating a logistic regression model. RESULTS: CT-staging showed high accuracy (94 %) and excellent interrater-correlation (ICC 0.96) for staging ACD. WE had no positive impact neither on diagnostic accuracy of staging, nor on confidence ratings of ACD-related CT-findings (all p > 0.5). Confidence ratings were significantly higher in examinations without WE for perforation, peritonitis as well as abscesses (all p < 0.5). Confidence ratings for the assessment of local peritonitis improved significantly with higher V/S (p = 0.049). The increase of V/S significantly correlated with the probability for correct CDD staging of ACD in CT (p = 0.023). CONCLUSION: Increase of visceral obesity significantly improves accuracy of CT in preoperative staging acute colonic diverticulitis. However, independently of the degree of visceral obesity, water enema has no diagnostic benefit and may therefore be omitted. Overall, CT proves high accuracy in preoperative staging ACD using the classification of diverticular disease. LEVEL OF EVIDENCE: Retrospective study, observational study.

Impairment of Everyday Spatial Navigation Abilities in Mild Cognitive Impairment Is Weakly Associated with Reduced Grey Matter Volume in the Medial Part of the Entorhinal Cortex.

BACKGROUND: Research in rodents identified specific neuron populations encoding information for spatial navigation with particularly high density in the medial part of the entorhinal cortex (ERC), which may be homologous with Brodmann area 34 (BA34) in the human brain. OBJECTIVE: The aim of this study was to test whether impaired spatial navigation frequently occurring in mild cognitive impairment (MCI) is specifically associated with neurodegeneration in BA34. METHODS: The study included baseline data of MCI patients enrolled in the Alzheimer's Disease Neuroimaging Initiative with high-resolution structural MRI, brain FDG PET, and complete visuospatial ability scores of the Everyday Cognition test (VS-ECog) within 30 days of PET. A standard mask of BA34 predefined in MNI space was mapped to individual native space to determine grey matter volume and metabolic activity in BA34 on MRI and on (partial volume corrected) FDG PET, respectively. The association of the VS-ECog sum score with grey matter volume and metabolic activity in BA34, APOE4 carrier status, age, education, and global cognition (ADAS-cog-13 score) was tested by linear regression. BA28, which constitutes the lateral part of the ERC, was used as control region. RESULTS: The eligibility criteria led to inclusion of 379 MCI subjects. The VS-ECog sum score was negatively correlated with grey matter volume in BA34 (ß= -0.229, p = 0.022) and age (ß= -0.124, p = 0.036), and was positively correlated with ADAS-cog-13 (ß= 0.175, p = 0.003). None of the other predictor variables contributed significantly. CONCLUSION: Impairment of spatial navigation in MCI is weakly associated with BA34 atrophy.

Dual-Energy Computed Tomography for Fat Quantification in the Liver and Bone Marrow: A Literature Review. / Dual-Energy-Computertomografie zur Fettquantifizierung in der Leber und im Knochenmark ­ ein Literatur-Review.

BACKGROUND: With dual-energy computed tomography (DECT) it is possible to quantify certain elements and tissues by their specific attenuation, which is dependent on the X-ray spectrum. This systematic review provides an overview of the suitability of DECT for fat quantification in clinical diagnostics compared to established methods, such as histology, magnetic resonance imaging (MRI) and single-energy computed tomography (SECT). METHOD: Following a systematic literature search, studies which validated DECT fat quantification by other modalities were included. The methodological heterogeneity of all included studies was processed. The study results are presented and discussed according to the target organ and specifically for each modality of comparison. RESULTS: Heterogeneity of the study methodology was high. The DECT data was generated by sequential CT scans, fast-kVp-switching DECT, or dual-source DECT. All included studies focused on the suitability of DECT for the diagnosis of hepatic steatosis and for the determination of the bone marrow fat percentage and the influence of bone marrow fat on the measurement of bone mineral density. Fat quantification in the liver and bone marrow by DECT showed valid results compared to histology, MRI chemical shift relaxometry, magnetic resonance spectroscopy, and SECT. For determination of hepatic steatosis in contrast-enhanced CT images, DECT was clearly superior to SECT. The measurement of bone marrow fat percentage via DECT enabled the bone mineral density quantification more reliably. CONCLUSION: DECT is an overall valid method for fat quantification in the liver and bone marrow. In contrast to SECT, it is especially advantageous to diagnose hepatic steatosis in contrast-enhanced CT examinations. In the bone marrow DECT fat quantification allows more valid quantification of bone mineral density than conventional methods. Complementary studies concerning DECT fat quantification by split-filter DECT or dual-layer spectral CT and further studies on other organ systems should be conducted. KEY POINTS: · DECT fat quantification in the liver and bone marrow is reliable.. · DECT is clearly superior to SECT in contrast-enhanced CT images.. · DECT bone marrow fat quantification enables better bone mineral density determination.. · Complementary studies with split-filter DECT or dual-layer spectral CT as well as studies in other organ systems are recommended.. CITATION FORMAT: · Molwitz I, Leiderer M, Özden C et al. Dual-Energy Computed Tomography for Fat Quantification in the Liver and Bone Marrow: A Literature Review. Fortschr Röntgenstr 2020; 192: 1137 - 1152.

FDG Uptake in the Basal Forebrain as Measured by Digital High-Resolution PET Is a Promising Marker of Basal Forebrain Degeneration in the Lewy Body Disease Spectrum: A Pilot Study.

PURPOSE: Cognitive decline in diseases of the Lewy body spectrum (LBS) is linked to dysfunction/degeneration of the basal forebrain (BF). Assessment of glucose metabolism in the BF by FDG PET is hampered by the small size of the BF and limited spatial resolution of conventional PET. This pilot study tested the feasibility of assessing BF glucose metabolism by high-resolution digital PET (dPET). PATIENTS AND METHODS: The retrospective study included 12 LBS patients (61-86 years, 5 demented). Whole-brain stereotactic normalization to anatomical standard space was followed by local stereotactic normalization of a 7 × 7 × 7-cm box around the BF to a custom-made 1 × 1 × 1-mm FDG dPET template. FDG uptake was scaled voxelwise to mean FDG uptake in the pons. Scaled FDG uptake in the BF was compared between demented and nondemented LBS patients and tested for correlation with cortical FDG uptake. RESULTS: Scaled FDG uptake in the BF was significantly lower in demented compared with nondemented patients (1.14 ± 0.09 vs 1.25 ± 0.06, P = 0.031). Brain-wide voxel-based testing for correlations with scaled FDG uptake in the BF revealed a large cluster comprising medial and ventrolateral frontal cortex, anterior cingulate cortex, insular cortex, and striatum as well as smaller clusters in motor cortex and occipital cortex (P < 0.001, uncorrected). CONCLUSIONS: These results suggest that dementia-associated BF degeneration in LBS can be sensitively measured as reduced BF FDG uptake on dPET. More accurate delineation of the BF based on individual high-resolution MRI might be useful to make optimal use of improved spatial resolution of dPET and to correct for possible disease- and age-dependent partial volume effects.

5q21 deletion is often heterogeneous in prostate cancer.

Cancer heterogeneity represents a challenge for the analysis of prognostic molecular markers but can be used to study the evolution of molecular events in tumors. To assess the degree of heterogeneity of 5q21 deletions and their relationship with TMPRSS2:ERG status and 6q15 deletions in prostate cancer, a heterogeneity tissue microarray including 10 tissue spots from 10 different areas of 317 cancers was analyzed by fluorescence in situ hybridization for 5q21 deletion. Data on 6q and ERG were available from earlier studies. Deletions of 5q21 were found in 23% of 265 interpretable cancers and showed marked intratumoral heterogeneity. In the subset of 246 cancers with at least 3 interpretable spots, 23% had a 5q21 deletion. Heterogeneous 5q21 deletions were found in 71% and homogeneous in 29% of these cancers. The likelihood of 5q21 deletion was twice as high in ERG-negative (28%) than in ERG-positive cancers (16%, P = .024). In all 21 cases harboring both alterations, the tumor area containing a 5q21 deletion was smaller or equally large than the ERG-positive area but never larger. Deletions of 5q and 6q were significantly linked. However, the analysis of 32 tumors harboring both deletions did not suggest a specific order of appearance of these deletions. The 5q21 deletion preceded 6q15 in 10 tumors and 6q15 preceded 5q21 in 14 tumors. In summary, our study identifies 5q21 deletion as a highly heterogeneous aberration in prostate cancer that usually occurs late during cancer progression. This is a severe limitation for using 5q21 testing as a prognostic tool.

Upregulation of centromere protein F is linked to aggressive prostate cancers.

BACKGROUND: Centromere protein F (CENPF) is a key component of the kinetochore complex and plays a crucial role in chromosome segregation and cell cycle progression. Recent work suggests that CENPF upregulation is linked to aggressive tumor features in a variety of malignancies including prostate cancer. MATERIALS AND METHODS: Using a highly annotated tissue microarray, we analyzed CENPF protein expression from a cohort of 8,298 prostatectomized patients by immunohistochemistry to study its effect on prostate-specific antigen recurrence-free survival. RESULTS: CENPF overexpression was found in 53% of cancers, and was linked to higher Gleason grade, advanced pathological tumor stage, accelerated cell proliferation, and lymph node metastasis (p<0.0001, each). A comparison with other key molecular features accessible through the microarray revealed strong associations between CENPF overexpression and presence of erythroblast transformation-specific (ETS)-related gene (ERG) fusion as well as phosphatase and tensin homolog deletion (p<0.0001, each). CENPF overexpression was linked to early biochemical recurrence. A subset analysis revealed that this was driven by the ERG-negative subset (p<0.0001). This was independent of established preoperative and postoperative prognostic parameters in multivariate analyses. CONCLUSION: The results of our study identify CENPF overexpression as an important mechanism and a potential biomarker for prostate cancer aggressiveness.

p16 overexpression and 9p21 deletion are linked to unfavorable tumor phenotype in breast cancer.

Overexpression of the p16 tumor suppressor, but also deletion of its gene locus 9p21, is linked to unfavorable tumor phenotype and poor prognosis in breast cancer. To better understand these contradictory observations, and to clarify the prognostic impact of p16 expression and 9p21 deletion, a tissue microarray (TMA) with 2,197 breast cancers was analyzed by fluorescence in-situ hybridization and immunohistochemistry (FISH) for 9p21 deletion and p16 expression. p16 immunostaining was weak in 25.6%, moderate in 7.1%, and strong in 12.7% of 1,684 evaluable cancers. Strong p16 staining was linked to advanced tumor stage (p = 0.0003), high-grade (p < 0.0001), high tumor cell proliferation (p < 0.0001), negative hormone receptor (ER/PR) status (p < 0.0001 each), and shorter overall survival (p = 0.0038). 9p21 deletion was found in 15.3% of 1,089 analyzable breast cancers, including 1.7% homozygous and 13.6% heterozygous deletions. 9p21 deletion was linked to adverse tumor features, including high-grade (p < 0.0001) and nodal positive cancers (p = 0.0063), high cell proliferation (p < 0.0001), negative hormone receptor (ER/PR) status (p ≤ 0.0006), and HER2 amplification (p = 0.0078). Patient outcome was worse in 9p21 deleted than in undeleted cancers (p = 0.0720). p16 expression was absent in cancers harboring homozygous 9p21 deletions, but no difference in p16 expression was found between cancers with (59.2% p16 positive) and without heterozygous 9p21 deletion (51.3% p16 positive, p = 0.0256). In summary, p16 expression is unrelated to partial 9p21 deletion, but both alterations are linked to aggressive breast cancer phenotype. High-level p16 expression is a strong predictor of unfavorable disease course in breast cancer.

Targeting the Gremlin-VEGFR2 axis - a promising strategy for multiple diseases?

Published recently in the Journal of Pathology, Lavoz et al. show that Gremlin promotes renal inflammation directly via VEGFR2. As Gremlin has been implicated in many other diseases, such as heart, lung and liver fibrosis, osteogenesis, angiogenesis and cancer, the new findings provide a rationale for novel concepts to investigate and potentially treat several pathologies.