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Seventy-seven patients with MS and 44 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, diffusion tensor imaging, perfusion weighted imaging, and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures. In the relapsing-remitting MS group, WM lesion burden proved to be the main contributor to volume loss for all deep gray matter structures.