OBJECTIVES: Susceptibility source-separation (χ-separation) MRI provides in-vivo proxy of myelin (diamagnetic susceptibility, χ METHODS: Fifty participants with MS (pwMS) were followed annually over a mean period of 3.3 years (SD = 1.8 years) with MRI, including χ-separation, and clinical assessments. To monitor lesions from their early stage (lesion age <
1 year), we identified newly-noted lesions (NNLs) and contrast-enhancing lesions (CELs), and tracked their longitudinal changes in χ RESULTS: Twenty-three pwMS were detected with NNLs and/or CELs (38 NNLs, 31 CELs
7 overlapped). Among these lesions (62 lesions in total), 27 exhibited χ CONCLUSION: The presence of HPS is associated with impaired remyelination capacity and a lack of disease improvement in pwMS. Identifying HPS may help demarcate lesions more amenable to myelin repair therapies.