We explored the value of multiple longitudinal quantitative MRI (qMRI) measures in detecting microstructural changes occurring in normal-appearing tissue of patients with multiple sclerosis (PwMS). While no differences in qMRI longitudinal changes were measured between PwMS and healthy controls, progressive PwMS showed accelerated T1-relaxometry increase in normal-appearing tissue with respect to both healthy controls and relapsing-remitting PwMS, reflecting increased micro/macrostructural damage. In PwMS the rates of qMRI changes during follow-up were associated with the severity of clinical disability, with higher neurological impairment being associated with qMRI changes reflecting accelerated micro/macrostructural damage, demyelination, and axon/dendrite loss.

We performed an extensive assessment of the clinical relevance of a method that we had previously developed, which provides personalized quantitative MRI abnormality maps of individual multiple sclerosis (MS) patients. Specifically, we assessed the relationships between quantitative T1 (qT1), myelin water fraction (MWF), neurite density index (NDI), magnetization transfer saturation (MTsat) abnormality maps and clinical disability in a cohort of 102 MS patients and 98 healthy subjects. We found that qT1 and NDI alterations in white matter lesions were strongly related to patients' clinical disability, supporting the use of those personalized maps for patient stratification and follow-up in clinical practice.

Damage to the myelin sheath and the neuroaxonal unit are features of multiple sclerosis, as well as reparative processes for both. However, a detailed characterization of the dynamics of those in vivo is challenging. In this longitudinal study, we applied a multi-contrast quantitative MRI approach to disentangle lesion progression in vivo in patients with MS. The microstructural measures were compared between multiple sclerosis groups (55 relapsing-remitting, 24 progressive) and 34 healthy controls. Our results indicate changes in microstructural MRI measures in white matter lesions and normal appearing tissue related to myelin and axonal integrity in RRMS and PMS.

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.

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.

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.

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.

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.

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