Inhomogeneous magnetization transfer (ihMT) imaging reveals variable recovery profiles of active MS lesions according to size and localization

Abstract

Abstract This work aims at exploiting the unique myelin specificity of the inhomogeneous magnetization transfer (ihMT) technique to characterize the recovery dynamics of active multiple sclerosis (MS) lesions. IhMT and three other myelin-sensitive techniques, conventional MT, T1-weighted, and diffusion tensor imaging, were applied in a 12-month longitudinal study performed on relapsing-remitting MS patients. An exponential recovery model was used to fit the variations over time of the metrics derived from each MR technique within new active lesions. A principal component analysis was performed on the model parameters obtained for all MR myelin-sensitive techniques across all active lesions of all patients to identify specific recovery profiles. The results show that the recovery profiles of myelin-sensitive MR metrics in active MS lesions vary according to the localization and size of lesions. The distance of lesions from the ventricles is positively associated with the recovery rates of ihMTR and T1w-MPRAGE: the further the lesion is from the ventricles, the higher the recovery rate of these metrics. Lesion size is positively associated with initial loss and negatively associated with final recovery of ihMTR and other MR metrics: small lesions have lower initial loss and greater final recovery of MR metrics than large lesions. Thanks to the specificity of the ihMT technique for myelin, these features can be interpreted in terms of remyelination. This study thus provides longitudinal in vivo support for the pathological observations of higher remyelination in small lesions compared with large ones and faster remyelination in lesions away from the ventricles. These results support the use of ihMT and other measures for quantifying remyelination rates in clinical studies of remyelination therapies.