Mechanisms of Progressive Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with features of progressive neurodegeneration. The mechanisms of progressive neurodegenerative disease are incompletely understood but include inflammatory and non-inflammatory processes that lead to focal and diffuse axonal loss. Magnetic resonance imaging (MRI) is an indispensable technique that has been used to develop numerous biomarkers of inflammatory disease in MS. These biomarkers are used for diagnosis, monitoring disease activity and clinical trial outcomes. MRI biomarkers of the neurodegenerative components of MS have also been developed but lack the same level of sensitivity as inflammatory biomarkers, which has limited their uptake into clinical use and clinical trials.

This thesis explores techniques using diffusion-based MRI in order to characterise mechanisms underlying progressive MS. Refined methods of assessing microstructural damage and structural network disruption are described and evaluated. Several potential biomarkers are proposed to describe and predict progression in MS.