Motivation: Progression independent of relapse activity (PIRA) is the most frequent manifestation of disability accumulation in multiple sclerosis (MS), but the mechanisms leading to PIRA are currently unknown. Goal(s): To investigate the link between PIRA and white matter degeneration in people with MS. Approach: To compare the integrity of normal-appearing white matter (NAWM) between patients with MS who experienced PIRA versus stable patients using diffusion tensor imaging (DTI) measures from a clinical-compatible protocol. Results: Patients with PIRA exhibited significant differences in DTI-derived measures compared to stable patients: reduced fractional anisotropy and increased mean and radial diffusivity in NAWM. Impact: This study sheds light on the relationship between progression independent of relapse activity (PIRA) and white matter degeneration in people with multiple sclerosis. The results have important implications for understanding the mechanisms of disability progression in relapsing-remitting multiple sclerosis.

We have characterized the imaging correlates of subpial demyelination in the cerebral cortex of MS patients by exploiting multiparametric postmortem qMRI and histopathology. MTsat, qT1 and AD were the measures that best captured subpial lesions pathology. Additionally, we found that some subpial lesions exhibit a juxta-cortical rim of increased susceptibility and show lower MWF than the ones without rim.

Thalamus represents a pivotal structure to study MS-associated neurodegeneration. In this study we investigated the alterations in thalamic microstructure of MS patients by using magnetization transfer saturation (MTsat), T1-relaxometry, and myelin water fraction (MWF). Compared to healthy controls (HCs), MS patients presented significant modifications in the thalamic quantitative MRI metrics, suggesting ongoing microstructural and myelin loss. The thalamic quantitative MRI metrics explored showed variable degrees of association with MS lesion burden, brain atrophic changes, as well as with clinical and cognitive disability.