Clinical correlates of R1 relaxometry and magnetic susceptibility changes in multiple sclerosis: a multi-parameter quantitative MRI study of brain iron and myelin

Objectives The clinical impact of brain microstructural abnormalities in multiple sclerosis (MS) remains elusive. We aimed to characterize the topography of longitudinal relaxation rate (R1) and quantitative susceptibility (chi) changes, as indices of iron and myelin, together with brain atrophy, and to clarify their contribution to cognitive and motor disability in MS. Methods In this cross-sectional study, voxel-based morphometry, and voxel-based quantification analyses of R1 and chi maps were conducted in gray matter (GM) and white matter (WM) of 117 MS patients and 53 healthy controls. Voxel-wise between-group differences were assessed with nonparametric permutation tests, while correlations between MRI metrics and clinical variables (global disability, cognitive and motor performance) were assessed both globally and voxel-wise within clusters emerging from the between-group comparisons. Results MS patients showed widespread R1 decrease associated with more limited modifications of chi, with atrophy mainly involving deep GM, posterior and infratentorial regions (p < 0.02). While R1 and chi showed a parallel reduction in several WM tracts (p < 0.001), reduced GM R1 values (p < 0.001) were associated with decreased thalamic chi (p < 0.001) and small clusters of increased chi in the caudate nucleus and prefrontal cortex (p < 0.02). In addition to the atrophy, chi values in the cingulum and corona radiata correlated with global disability and motor performance, while focal demyelination correlated with cognitive performance (p < 0.04). Conclusions We confirmed the presence of widespread R1 changes, involving both GM and WM, and atrophy in MS, with less extensive modifications of tissue chi. While atrophy and chi changes are related to global and motor disability, R1 changes are meaningful correlates of cognition.