Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7T imaging

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). Methods: In 41 MS subjects and 17 controls, using 3 and 7T imaging, we tested for (1) differences in thalamic volume and quantitative T-2* (q-T-2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. Results: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls (p<10(-2)); global q-T-2* was longer in secondary progressive multiple sclerosis (SPMS) only (p<10(-2)), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T-2* correlated with WM lesion volume (p<0.01). In relapsing-remitting MS, q-T-2* thalamic abnormalities were located next to the WM (p<0.01 (uncorrected), p=0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. Conclusion: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions.