Atrophy in multiple sclerosis: Measurement and clinical implications

This thesis describes the development and application of new magnetic resonance imaging techniques to characterise and quantify underlying tissue changes in multiple sclerosis (MS) that are responsible for or associated with disability. Characterisation, measurement of such changes and their relationship to other quantitative parameters of disease activity or progression may yield important information on the pathophysiology of disability in MS. They would also be of considerable value in evaluating a putative treatment. The work described focuses on the measurement of spinal cord and cerebral atrophy. The development and evaluation of new highly reproducible quantitative techniques are described. The results of cross-sectional and longitudinal clinical studies presented. These demonstrate that the measurement of atrophy is a powerful way in which to monitor clinically relevant disease progression. The results also indicate that the development of atrophy in MS is common. The techniques are reviewed critically, compared to other current clinical and imaging measures of disease progression and shown to have high sensitivity to change and greater possible specificity to underlying pathology. The role of axonal loss in the development of atrophy and it's relationship to inflammatory activity are discussed. It is concluded that atrophy may develop independently of inflammation. Finally improved techniques to further investigate the nature and significance of atrophy are suggested