Measuring brain atrophy in multiple sclerosis with magnetic resonance imaging techniques: correlation with clinical outcomes and utility in clinical practice

Abstract

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system that affects both the white and grey matter of the brain and spinal cord. Magnetic resonance imaging (MRI) is routinely used to monitor the inflammatory aspects of the disease in conjunction with clinical assessment. Brain atrophy is considered a biomarker of neurodegeneration and MRI techniques to measure brain volumes and atrophy have been extensively researched and are currently used in MS clinical trials. In the research setting, MRI measured brain atrophy is associated with physical and cognitive disability at the group level, but there is a paucity of data with regard to MS clinical practice patients. In this thesis, cohorts of real-world MS patients have been investigated with regard to (i) examining the use of semi-automated and automated MRI techniques in measuring brain atrophy; (ii) assessing the associations between quantitative MRI brain atrophy measurements and clinical outcomes; and (iii) exploring the utility of quantitative MRI brain atrophy data in clinical practice. Currently there remains an unmet need for biomarkers of neurodegeneration and future disability in MS clinical practice. As outlined in this thesis, MRI measured brain atrophy holds great promise as a biomarker for this purpose. Continued optimisation of measurement techniques, and the development of approaches to address methodological limitations and confounding factors, will cement the role of MRI brain atrophy metrics in MS clinical practice.