FreeSurfer-Based MRI Volumetry Reveals Thalamic and Hippocampal Atrophy as Significant Correlates of Disability in...

Background and Objectives: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease that progressively leads to brain atrophy and the accumulation of disability over time. In this study, we used FreeSurfer to compare subcortical volumes and cortical surface areas between patients with MS and healthy controls and to investigate how regional atrophy relates to both disease lasting and clinical disability. Materials and Methods: We included 80 participants in this study, 40 patients with clinically definite MS and 40 age- and sex-matched healthy controls, all imaged on a Philips Ingenia 3.0T MRI scanner. High-resolution 3D T1-weighted MPRAGE sequences of the brain were processed using FreeSurfer 7.3.3. MS patients were stratified by disease lasting into two subgroups: ≤5 years (n = 17) and >5 years (n = 23). Subcortical volumes were normalised to estimated total intracranial volume (eTIV). Between-group differences were assessed using Welch's t-test with Benjamini-Hochberg false discovery rate (FDR) correction. Multiple linear regression models controlled for age, sex, and the Expanded Disability Status Scale (EDSS). Results: We found statistically significant volume reductions in 48 of the 52 normalised regions examined. Thalamic volume showed the most severe reduction (mean-21.6% bilaterally) in MS patients. The corpus callosum, hippocampus, and amygdala were also prominently affected. Receiver operating characteristic (ROC) analysis of mean bilateral thalamic volume yielded an area under the curve (AUC) of 0.822 (95% CI: 0.731-0.913). Cortical surface area did not survive FDR correction in the primary comparison, though nominal reductions emerged in longer-lasting MS patients. EDSS correlated with both thalamic and hippocampal volumes in regression models. Conclusions: FreeSurfer-based volumetric analysis detected widespread grey and white matter volume differences in MS patients relative to matched controls, with changes already present in patients within the first five years of diagnosis. The high proportion of significant regions is consistent with a combined pattern of generalised and regionally accentuated atrophy. Among the regions examined, thalamic volume showed the strongest cross-sectional discrimination (AUC = 0.822; sensitivity 65%, specificity 90%) and the most consistent associations with EDSS; these findings support further evaluation of thalamic volume as a candidate imaging biomarker of neurodegeneration, although its diagnostic performance is moderate and requires external longitudinal validation before clinical deployment.