Progression independent of relapse activity (PIRA) has been described in patients with multiple sclerosis (MS) even in the earliest disease stages. Patients with PIRA show increased atrophy rates in multiple brain regions compared to stable patients. Here, we investigated whether patients with PIRA exhibit loss of integrity in WM tracts compared to stable patients. We studied 62 RRMS patients, 27 PIRA and 35 stable patients using a clinical DW-MRI protocol. Our results showed that PIRA patients present smaller FA values in areas of corpus callosum and along corticosprinal tract. These differences suggest neurodegeneration in major WM tracts of PIRA patients.

The presence of cortical lesions in multiple sclerosis patients has emerged as an important biomarker of the disease. They appear in the earliest stages of the illness and have been shown to correlate with the severity of clinical symptoms. However, cortical lesions are hardly visible in conventional magnetic resonance imaging (MRI) at 3T

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.

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.

Despite several large-scale genome-wide association studies (GWAS) have been performed in MS, to date no study explored the relationship between genetic risk factors for MS and the extent of myelin and axon damage in the brain of MS patients, as measured by advanced MRI techniques. Our results identify novel genetic loci that might be associated with myelin and axonal pathology in MS Patients.

The main limitation of current axon diameter mapping techniques is that the diffusion MRI (dMRI) signals from axons smaller than 2.0 μm are practically undistinguished from each other, even for the most advanced human scanners. Consequently, there is a resolution limit for the in vivo estimation of axon diameters from dMRI data. Therefore, it would be desirable to find another source of MRI contrast sensitive to the axonal calibre. This proof-of-concept study used a surface-based relaxation model to investigate whether the intra-axonal T2 estimated in a human brain is related to the inner axon radius measured from histological data.

The visualization and characterization of cortical MS lesions is challenging on conventional MRI. In the present study, we used a susceptibility source separation algorithm to divide the positive and negative susceptibility of quantitative susceptibility mapping (QSM) MRI, so that we could disentangle signal alterations due to myelin loss or iron accumulation. In 19 MS patient with 123 cortical lesions, we found that the major part of QSM susceptibility of cortical lesions is driven by myelin and iron loss, while only a small proportion of lesions (12/123, 9.8%) showed an increment of susceptibility that is caused by iron accumulation.