Lesion Heterogeneity on High-Field Susceptibility MRI Is Associated with Multiple Sclerosis Severity

BACKGROUND AND PURPOSE: Susceptibility MR imaging contrast variations reflect alterations in brain iron and myelin content, making this imaging tool relevant to studies of multiple sclerosis lesion heterogeneity. In this study, we aimed to characterize the relationship of high-field, susceptibility contrasts in multiple sclerosis lesions to clinical outcomes. MATERIALS AND METHODS: Twenty-four subjects with multiple sclerosis underwent 7T MR imaging of the brain, disability examinations, and a fatigue inventory. The inverse of T2* relaxation time (R2*), frequency, and relative susceptibility (from quantitative susceptibility mapping) were analyzed in 306 white matter lesions. RESULTS: Most lesions were hypointense on R2* (88% without a rim, 5% with). Lesions that were hyperintense on quantitative susceptibility mapping were more frequent in relapsing-remitting than in progressive multiple sclerosis (54% versus 35%, P = .018). Hyperintense lesion rims on quantitative susceptibility maps were more common in progressive multiple sclerosis and patients with higher levels of disability and fatigue. Mean lesion R2* was inversely related to disability and fatigue and significantly reduced in progressive multiple sclerosis. Relative susceptibility was lower in lesions in progressive multiple sclerosis (median, -0.018 ppm; range, -0.070 to 0.022) than in relapsing-remitting MS (median, -0.010 ppm; range, -0.062 to 0.052; P = .003). CONCLUSIONS: A progressive clinical phenotype and greater disability and fatigue were associated with lower R2* and relative susceptibility values (suggestive of low iron due to oligodendrocyte loss) and rimmed lesions (suggestive of chronic inflammation) in this multiple sclerosis cohort. Lesion heterogeneity on susceptibility MR imaging may help explain disability in multiple sclerosis and provide a window into the processes of demyelination, oligodendrocyte loss, and chronic lesion inflammation.