Abstract
BACKGROUND: In multiple sclerosis (MS), 7 Tesla (7T) MRI improves the visualization of cortical (CLs) and white matter (WM) lesions with a paramagnetic rim (PRLs), associated with smoldering inflammation. Spinal cord (SC) atrophy is a critical determinant of clinical disability in MS, but its importance relative to PRLs and CLs in predicting neurological disability remains unclear. PURPOSE: To identify the most relevant predictors for baseline neurological disability and 4-year disease progression independent of relapse activity (PIRA) in a heterogeneous MS cohort. MATERIALS AND METHODS: One-hundred-twelve MS patients (83 relapsing-remitting, 29 secondary progressive) were prospectively recruited between 2010 and 2024. 7T T2*-susceptibility-weighted imaging was acquired to segment CLs, PRLs, and non-rim WM lesions, and 3T T1-weighted brain MRI to estimate cortical thickness, brain WM volume, and the SC C2-C3 cross-sectional area (CSA) using FreeSurfer and Spinal Cord Toolbox. Expanded Disability Status Scale (EDSS) was assessed at baseline and longitudinally, in 97/112 MS patients, after a mean follow-up of 4.0 years. Associations between imaging metrics and clinical outcomes were evaluated using regression models. RESULTS: Baseline EDSS was associated with non-rim WM lesion volume (p=<0.001), CL volume (p=0.001), brain WM volume (p=0.017), and C2-C3 CSA (p=0.003). At follow-up, 23/97 patients showed PIRA. PIRA was associated with PRL volume (p=0.030), CL volume (p=0.011), and brain WM volume (p<0.001). A stepwise logistic regression identified CL volume as the strongest independent predictor of PIRA (Nagelkerke R (2) =0.200, OR=1.0006, p=0.005). Patients with a CL load > 403 mm (3) progressed in half of cases (70% sensitivity, 50% specificity) within 4 years. CONCLUSION: In MS, different imaging biomarkers are associated with either the current disability or PIRA. Spinal cord atrophy mainly explains the current EDSS, while brain WM atrophy and PRLs provide additional insights into future disability trajectory. Among all markers, CLs emerged as the main driver for PIRA.