Assessing Microstructural Changes in Multiple Sclerosis Using MTV, QSM, and Advanced Diffusion Metrics

Abstract

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterised by inflammation, demyelination, and neuro-axonal loss. Advanced Magnetic Resonance Imaging (MRI) techniques such as quantitative susceptibility mapping (QSM) and macromolecular tissue volume (MTV) allow in vivo quantification of iron accumulation and myelin content, respectively. Alongside these, advanced diffusion MRI metrics derived from Diffusion Tensor Imaging (DTI), Diffusion Kurtosis Imaging (DKI), and Neurite Orientation Dispersion and Density Imaging (NODDI) models provide complementary insights into microstructural damage. The purpose of the study was to evaluate the association between quantitative MRI (qMRI) and diffusion-derived measures in the characterisation of MS lesions and clinical disability prediction. Longitudinal data was obtained in an observational cohort of individuals with clinically isolated syndrome (CIS) and early MS, who were monitored for up to five years. Participants were subjected to multi-modal MRI, consisting of QSM, MTV, and diffusion sequences, as well as cognitive and clinical testing. Strict quality control measures were used, and lesion-level analysis was conducted in Stata to assess correlations between imaging variables and disability scores, including Expanded Disability Status Scale (EDSS). The findings indicated that diffusion changes at the lesion level were strongly correlated with lower MTV and higher QSM in chronic lesions, and certain metrics, including Fractional Anisotropy (FA), Mean Kurtosis (MK), and Neurite Density Index (NDI), were strongly correlated with clinical disability. The results provide evidence of the potential of integrated qMRI and advanced diffusion imaging as sensitive biomarkers to monitor disease in early MS.