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Background: Fatigue in multiple sclerosis (MS) has been inconsistently associated with disruption of specific brain circuitries. Temporal fluctuations of fatigue have not been considered. Objective: The aim of this study was to investigate the association of fatigue with brain diffusion abnormalities, using robust criteria for patient stratification based on longitudinal patterns of fatigue. Methods: Patient stratification: (1) sustained fatigue (SF, n = 26): latest two Modified Fatigue Impact Scale (MFIS) ⩾ 38; (2) reversible fatigue (RF, n = 25): latest MFIS < 38 and minimum one previous MFIS ⩾ 38; and (3) never fatigued (NF, n = 42): MFIS always < 38 (five assessments minimum). 3T brain magnetic resonance imaging (MRI) was used to perform voxel-wise comparison of fractional anisotropy (FA) between the groups controlling for age, sex, disease duration, physical disability, white matter lesion load (T2LV), and depression. Results: SF and, to a lesser extent, RF patients showed lower FA in multiple brain regions compared to NF patients, independent of age, sex, disease duration, and physical disability. In cingulo-postcommissural-striato-thalamic regions, the differences in FA between SF and NF (but not between RF and NF or SF) patients were independent of T2LV, and in ventromedial prefronto-precommissuro-striatal and temporo-insular areas, independent of T2LV and depression. Conclusion: Damage to ventromedial prefronto-precommissuro-striatal and temporo-insular pathways appears to be a specific substrate of SF in MS. [ABSTRACT FROM AUTHOR]

Background: Complement system activation products are present in areas of neuroinflammation, demyelination, and neurodegeneration in brains of patients with multiple sclerosis (MS). C3 is a central element in the activation of complement cascades. A common coding variant in the C3 gene (rs2230199, C3R102G) affects C3 activity. Objectives: To assess the effects of rs2230199 on MS severity using clinical, cognitive, and imaging measures. Methods: In total, 161 relapse-onset MS patients (Expanded Disability Status Scale (EDSS) ≤ 6) underwent physical assessments, cognitive tests (Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and California Verbal Learning Test (CVLT)), and magnetic resonance imaging (MRI). Lesion volumes were quantified semi-automatically. Voxel-wise analyses were performed to assess the effects of rs2230199 genotype on gray matter (GM) atrophy (n = 155), white matter (WM) fractional anisotropy (FA; n = 105), and WM magnetization transfer ratio (MTR; n = 90). Results: While rs2230199 minor-allele dosage (C3-102G) showed no significant effect on EDSS and Multiple Sclerosis Functional Composite (MSFC), it was associated with worse cognitive performance (p = 0.02), lower brain parenchymal fraction (p = 0.003), and higher lesion burden (p = 0.02). Moreover, voxel-wise analyses showed lower GM volume in subcortical structures and insula, and lower FA and MTR in several WM areas with higher copies of rs2230199 minor allele. Conclusion: C3-rs2230199 affects white and GM damage as well as cognitive impairment in MS patients. Our findings support a causal role for complement system activity in the pathophysiology of MS. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the repeatability of activated brown adipose tissue (BAT) radiomic features. To decipher radiomic features that may provide useful information on BAT, the impact of reconstruction methods and imaging modality choice was also evaluated. Methods: Twenty-seven healthy adults enrolled in this study. After a cooling procedure to activate BAT, volunteers underwent 18 F-FDG imaging. Participants underwent repeat imaging using the same imaging protocols and a similar 18 F-FDG dose within 14 d. Active BAT was segmented using the BARCIST 1.0 methods. Radiomic features were extracted from each region of interest on high-definition PET (HD PET), non-HD PET, and CT images. Lin's concordance correlation coefficient was used to estimate the repeatability of the extracted radiomic features. To determine whether BAT radiomic feature repeatability correlates with BAT SUV max repeatability, participants were stratified based on the relative difference in SUV max between sessions. Non-HD PET repeatable features were clustered together using hierarchical clustering, and the normalized dynamic range of each feature was computed to identify the most informative feature within each cluster. Results: Eighteen of the 27 volunteers had sufficient BAT activity for radiomic analysis. Sixty-six HD PET, 66 non-HD PET, and 6 CT features showed high repeatability (concordance correlation coefficient ≥ 0.80). Feature repeatability was significantly higher for PET than for CT, but there was no statistically significant difference between HD and non-HD PET in radiomic feature repeatability. The repeatability of radiomic features extracted from each modality and reconstruction method type followed the trend in SUV max , as participants with lower relative differences in SUV max between initial and repeated imaging sessions had higher radiomic feature repeatability. Hierarchical clustering of the high-repeatability PET features resulted in 10 highly correlated clusters ( R 2 ≥ 0.95). Seven features, including SUV max, did not cluster with any other features. Conclusion: Several clusters of highly repeatable BAT radiomic features derived from 18 F-FDG PET/CT appear to provide information regarding BAT activity distinct from SUV max These features might be explored as quantitative imaging biomarkers of BAT activity in future studies., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)