The utility of advanced quantitative MRI for assessment of spinal cord tissue damage in multiple sclerosis has not yet been established. In this work, we used T1-mapping as well as quantitative magnetization transfer saturation and echo-planar imaging to quantify the extent of pathologic changes in the cervical cord of multiple sclerosis patients. Our results point to extensive demyelination and axonal loss both in the normal-appearing and lesional cervical cord, as well as to and chronic inflammation of cSCWM lesions in secondary progressive multiple sclerosis. Hence, quantitative spinal cord MRI may provide valuable information about the pathologic substrate of this disease.

A new approach for estimating inner axon radii from intra-axonal T2 relaxation times was recently proposed. However, further validations are required before this technique can be used widely. The main aim of this study is to validate this T2-based pore size estimation technique in phantoms comprising co-electrospun hollow axon-mimicking fibres designed to have non-circular cross-sections and different radii distributions. For this purpose, a diffusion-relaxation MRI dataset was acquired with a 7T preclinical scanner, from which the intra-fibre T2 times and pore sizes were estimated. The resulting pore sizes were compared to those measured from Scanning Electron Microscope images.

In-vivo quantification of axon diameter is an attractive and debated topic in the MRI community. The possibility to resolve submicrometric axon diameters non-invasively yields the potential to push further the boundaries in research and clinics but yet, further work is needed to better explore and validate the existing approaches to estimate the inner axon diameter. Recently, the feasibility of estimating the axon diameter from the intra-axonal transverse relaxation time has been investigated combining a diffusion-relaxation protocol and histological data. In the present study, we apply this approach in a larger in vivo population to assess variability across participants.

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.

The decision process of artificial intelligence is elusive. We proposed a new method that by combining an attention-based convolutional neural network (GAMER-MRI) with the modified Layer-wise Relevance Propagation could reveal relevant regions on quantitative imaging maps in differentiating multiple sclerosis patients with mild-moderate and severe disabilities. The assessment of the relevant regions included the impact of inverting values within the regions and the heatmap on the MNI152 template. Our results show good network performance and identify brain regions relevant to the corticospinal tract. The proposed method might be useful to further explore patterns of brain microstructural alterations associated with disability.

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.