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To understand the clinical significance of the tumor microenvironment (TME), it is essential to study the interactions between malignant and non-malignant cells in clinical specimens. Here, we established a computational framework for a multiplex imaging system to comprehensively characterize spatial contexts of the TME at multiple scales, including close and long-distance spatial interactions between cell type pairs. We applied this framework to a total of 1,393 multiplex imaging data newly generated from 88 primary central nervous system lymphomas with complete follow-up data and identified significant prognostic subgroups mainly shaped by the spatial context. A supervised analysis confirmed a significant contribution of spatial context in predicting patient survival. In particular, we found an opposite prognostic value of macrophage infiltration depending on its proximity to specific cell types. Altogether, we provide a comprehensive framework to analyze spatial cellular interaction that can be broadly applied to other technologies and tumor contexts., Competing Interests: The authors have no conflicts of interest., (© 2023 The Authors.)

Background: Car driving is a form of passive transport that is associated with an increase in physical inactivity, obesity, air pollution and noise. Built environment characteristics may influence transport mode choice, but comprehensive indices for built environment characteristics that drive car use are still lacking, while such an index could provide tangible policy entry points., Objective: We developed and validated a neighbourhood drivability index, capturing combined dimensions of the neighbourhood environment in the City of Toronto, and investigated its association with transportation choices (car, public transit or active transport), overall, by trip length, and combined for residential neighbourhood and workplace drivability., Methods: We used exploratory factor analysis to derive distinct factors (clusters of one or more environmental characteristics) that reflect the degree of car dependency in each neighbourhood, drawing from candidate variables that capture density, diversity, design, destination accessibility, distance to transit, and demand management. Area-level factor scores were then combined into a single composite score, reflecting neighbourhood drivability. Negative binomial generalized estimating equations were used to test the association between driveability quintiles (Q) and primary travel mode (>50% of trips by car, public transit, or walking/cycling) in a population-based sample of 63,766 Toronto residents enrolled in the Transportation Tomorrow Survey (TTS) wave 2016, adjusting for individual and household characteristics, and accounting for clustering of respondents within households., Results: The drivability index consisted of three factors: Urban sprawl, pedestrian facilities and parking availability. Relative to those living in the least drivable neighbourhoods (Q1), those in high drivability areas (Q5) had a significantly higher rate of car travel (adjusted Risk Ratio (RR): 1.80, 95%CI: 1.77-1.88), and lower rate of public transit use (RR: 0.90, 95%CI: 0.85-0.94) and walking/cycling (RR: 0.22, 95%CI: 0.19-0.25). Associations were strongest for short trips (<3 km) (RR: 2.72, 95%CI: 2.48-2.92), and in analyses where both residential and workplace drivability was considered (RR for car use in high/high vs. low/low residential/workplace drivability: 2.18, 95%CI: 2.08-2.29)., Conclusion: This novel neighbourhood drivability index predicted whether local residents drive or use active modes of transportation and can be used to investigate the association between drivability, physical activity, and chronic disease risk., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Positron emission tomography using [ 18 F]fluorodeoxyglucose (FDG PET) potentially underperforms for staging of patients with grade 1-2 estrogen receptor positive (ER+) breast cancer. The aim of this study was to retrospectively investigate the diagnostic accuracy of FDG PET in this patient population. Suspect tumor lesions detected on conventional imaging and FDG PET were confirmed with pathology or follow up. PET-positive lesions were (semi)quantified with standardized uptake values (SUV) and these were correlated with various pathological features, including the histological subtype. Pre-operative imaging detected 155 pathologically verified lesions (in 74 patients). A total of 115/155 (74.2%) lesions identified on FDG PET were classified as true positive, i.e., malignant (in 67 patients) and 17/155 (10.8%) lesions as false positive, i.e., benign (in 9 patients); 7/155 (4.5%) as false negative (in 7 patients) and 16/155 (10.3%) as true negative (in 14 patients). FDG PET incorrectly staged 16/70 (22.9%) patients. The FDG uptake correlated with histological subtype, showing higher uptake in ductal carcinoma, compared to lobular carcinoma ( p < 0.05). Conclusion: Within this study, FDG PET inadequately staged 22.9% of grade 1-2, ER + BC cases. Incorrect staging can lead to inappropriate treatment choices, potentially affecting survival and quality of life. Prospective studies investigating novel radiotracers are urgently needed.

Background In vanishing white matter (VWM), a form of leukodystrophy, earlier onset is associated with faster clinical progression. MRI typically shows rarefaction and cystic destruction of the cerebral white matter. Information on the evolution of VWM according to age at onset is lacking. Purpose To determine whether nature and progression of cerebral white matter abnormalities in VWM differ according to age at onset. Materials and Methods Patients with genetically confirmed VWM were stratified into six groups according to age at onset: younger than 1 year, 1 year to younger than 2 years, 2 years to younger than 4 years, 4 years to younger than 8 years, 8 years to younger than 18 years, and 18 years or older. With institutional review board approval, all available MRI scans obtained between 1985 and 2019 were retrospectively analyzed with three methods: (a) ratio of the width of the lateral ventricles over the skull (ventricle-to-skull ratio [VSR]) was measured to estimate brain atrophy; (b) cerebral white matter was visually scored as percentage normal, hyperintense, rarefied, or cystic on fluid-attenuated inversion recovery (FLAIR) images and converted into a white matter decay score; and (c) the intracranial volume was segmented into normal-appearing white and gray matter, abnormal but structurally present (FLAIR-hyperintense) and rarefied or cystic (FLAIR-hypointense) white matter, and ventricular and extracerebral cerebrospinal fluid (CSF). Multilevel regression analyses with patient as a clustering variable were performed to account for the nested data structure. Results A total of 461 examinations in 270 patients (median age, 7 years [interquartile range, 3-18 years]; 144 female patients) were evaluated; 112 patients had undergone serial imaging. Patients with later onset had higher VSR [F(5) = 8.42; P < .001] and CSF volume [F(5) = 21.7; P < .001] and lower white matter decay score [F(5) = 4.68; P < .001] and rarefied or cystic white matter volume [F(5) = 13.3; P < .001]. Rate of progression of white matter decay scores [b = -1.6, t(109) = -3.9; P < .001] and VSRs [b = -0.05, t (109) = -3.7; P < .001] were lower with later onset. Conclusion A radiologic spectrum based on age at onset exists in vanishing white matter. The earlier the onset, the faster and more cystic the white matter decay, whereas with later onset, white matter atrophy and gliosis predominate. © RSNA, 2021.

Background and Purpose: Achieving a specific diagnosis in leukodystrophies is often difficult due to clinical and genetic heterogeneity. Mitochondrial defects cause 5%-10% of leukodystrophies. Our objective was to define MR imaging features commonly shared by mitochondrial leukodystrophies and to distinguish MR imaging patterns related to specific genetic defects., Materials and Methods: One hundred thirty-two patients with a mitochondrial leukodystrophy with known genetic defects were identified in the data base of the Amsterdam Leukodystrophy Center. Numerous anatomic structures were systematically assessed on brain MR imaging. Additionally, lesion characteristics were scored. Statistical group analysis was performed for 57 MR imaging features by hierarchic testing on clustered genetic subgroups., Results: MR imaging features indicative of mitochondrial disease that were frequently found included white matter rarefaction ( n = 50 patients), well-delineated cysts ( n = 20 patients), T2 hyperintensity of the middle blade of the corpus callosum ( n = 85 patients), and symmetric abnormalities in deep gray matter structures ( n = 42 patients). Several disorders or clusters of disorders had characteristic features. The combination of T2 hyperintensity in the brain stem, middle cerebellar peduncles, and thalami was associated with complex 2 deficiency. Predominantly periventricular localization of T2 hyperintensities and cystic lesions with a distinct border was associated with defects in complexes 3 and 4. T2-hyperintense signal of the cerebellar cortex was specifically associated with variants in the gene NUBPL . T2 hyperintensities predominantly affecting the directly subcortical cerebral white matter, globus pallidus, and substantia nigra were associated with Kearns-Sayre syndrome., Conclusions: In a large group of patients with a mitochondrial leukodystrophy, general MR imaging features suggestive of mitochondrial disease were found. Additionally, we identified several MR imaging patterns correlating with specific genotypes. Recognition of these patterns facilitates the diagnosis in future patients., (© 2021 by American Journal of Neuroradiology.)