The role of 7 T MRI to assess atrophy of the subcortical deep gray matter in relapsing-remitting multiple sclerosis.

BACKGROUND: Deep gray matter (DGM) atrophy and lesions are found in multiple sclerosis (MS). OBJECTIVE: To optimize automated segmentation for 7 T DGM volumetrics and assess sensitivity to atrophy and relationship to DGM lesions and disability in relapsing-remitting (RR) MS. METHODS: 30 RRMS subjects [mean age 44.0 years, median Expanded Disability Status Scale (EDSS) score 2] and 14 healthy controls underwent 7 T MRI with 3D magnetization-prepared 2 rapid gradient-echoes (MP2RAGE) and fluid-attenuated inversion recovery. Customizing an automated pipeline to assess DGM structure volumes required pre-processing combining two MP2RAGE inversion times and uniform T1 images, and noise-suppressed reconstruction. DGM volumes were normalized. Brain DGM lesions and white matter T2 lesion volume (T2LV) were expert-quantified. Spearman correlations and Wilcoxon rank-sum tests were assessed. RESULTS: DGM lesions were found in 77% (n = 23) of MS subjects and no controls, with thalamic lesions most prevalent (73%). An average of 3.6 DGM lesions was found per person with MS. Total DGM volumes were lower in MS vs. controls (p = 0.034), varying by region, most pronounced in the caudate (p = 0.008). DGM volumes inversely correlated with EDSS (total DGM: r = - 0.45, p = 0.014; globus pallidus: r =  - 0.42, p = 0.023; putamen: r = - 0.44, p = 0.016; caudate: r = - 0.37, p = 0.047) and T2LV (total DGM: r = - 0.53, p = 0.003; putamen: r = - 0.40, p = 0.030; thalamus: r = - 0.63, p < 0.001). DGM atrophy was most closely linked to disability among all MRI measures. Thalamic lesion volume correlated inversely with thalamic volume (r = - 0.38, p = 0.045). CONCLUSION: 7 T MRI shows a link between DGM atrophy and both white matter lesions and physical disability in RRMS. Thalamic lesions are associated with thalamic atrophy.

Pooled analysis of multiple sclerosis findings on multisite 7 Tesla MRI: Protocol and initial observations.

Although 7 T MRI research has contributed much to our understanding of multiple sclerosis (MS) pathology, most prior data has come from small, single-center studies with varying methods. In order to truly know if such findings have widespread applicability, multicenter methods and studies are needed. To address this, members of the North American Imaging in MS (NAIMS) Cooperative worked together to create a multicenter collaborative study of 7 T MRI in MS. In this manuscript, we describe the methods we have developed for the purpose of pooling together a large, retrospective dataset of 7 T MRIs acquired in multiple MS studies at five institutions. To date, this group has contributed five-hundred and twenty-eight 7 T MRI scans from 350 individuals with MS to a common data repository, with plans to continue to increase this sample size in the coming years. We have developed unified methods for image processing for data harmonization and lesion identification/segmentation. We report here our initial observations on intersite differences in acquisition, which includes site/device differences in brain coverage and image quality. We also report on the development of our methods and training of image evaluators, which resulted in median Dice Similarity Coefficients for trained raters' annotation of cortical and deep gray matter lesions, paramagnetic rim lesions, and meningeal enhancement between 0.73 and 0.82 compared to final consensus masks. We expect this publication to act as a resource for other investigators aiming to combine multicenter 7 T MRI datasets for the study of MS, in addition to providing a methodological reference for all future analysis projects to stem from the development of this dataset.

Glial Activity Load on PET Reveals Persistent "Smoldering" Inflammation in MS Despite Disease-Modifying Treatment: 18 F-PBR06 Study.

PURPOSE OF THE REPORT: 18 F-PBR06-PET targeting 18-kDa translocator protein can detect abnormal microglial activation (MA) in multiple sclerosis (MS). The objectives of this study are to develop individualized mapping of MA using 18 F-PBR06, to determine the effect of disease-modifying treatment (DMT) efficacy on reducing MA, and to determine its clinical, radiological, and serological correlates in MS patients. PATIENTS AND METHODS: Thirty 18 F-PBR06-PET scans were performed in 22 MS patients (mean age, 46 ± 13 years; 16 females) and 8 healthy controls (HCs). Logarithmically transformed "glial activity load on PET" scores (calculated as the sum of voxel-by-voxel z -scores ≥4), "lnGALP," were compared between MS and HC and between MS subjects on high-efficacy DMTs (H-DMT, n = 13) and those on no or lower-efficacy treatment, and correlated with clinical measures, serum biomarkers, and cortical thickness. RESULTS: Cortical gray matter (CoGM) and white matter (WM) lnGALP scores were higher in MS versus HC (+33% and +48%, P < 0.001). In H-DMT group, CoGM and WM lnGALP scores were significantly lower than lower-efficacy treatment ( P < 0.01) but remained abnormally higher than in HC group ( P = 0.006). Within H-DMT patients, CoGM lnGALP scores correlated positively with physical disability, fatigue and serum glial fibrillary acid protein levels ( r = 0.65-0.79, all P 's < 0.05), and inversely with cortical thickness ( r = -0.66, P < 0.05). CONCLUSIONS: High-efficacy DMTs decrease, but do not normalize, CoGM and WM MA in MS patients. Such "residual" MA in CoGM is associated with clinical disability, serum biomarkers, and cortical degeneration. Individualized mapping of translocator protein PET using 18 F-PBR06 is clinically feasible and can potentially serve as an imaging biomarker for evaluating "smoldering" inflammation in MS patients.