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.

A scarce body of literature studies the Corpus Callosum (CC) normal-appearing white matter (NAWM) in Relapsing-Remitting Multiple Sclerosis (RRMS). This work aimed to characterize the degree of the alterations in different CC segments by assessing the extent of damage to myelin and axon, as measured with myelin volume fraction, axonal volume fraction, and g-ratio. These microstructural measures correlated with disease duration, EDSS, number, and volume of the lesions in other white matter regions. In sum, this work shows that CC pathology in RRMS patients is related to focal damage and/or diffuse neurodegeneration, which is clinically relevant.

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.