Rashid, W; (2005) The investigation of pathogenesis in multiple sclerosis using quantitative magnetic resonance parameters. Doctoral thesis , UCL (University College London).

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Abstract

This thesis studies the use of several quantitative MR techniques to investigate further the pathophysiology of multiple sclerosis (MS) and to evaluate the sensitivity of quantitative MRI parameters in early disease both for prognostic purposes and as potential outcome measures in treatment monitoring trials. Presented are investigations using multiple MR techniques into clinically early relapsing-remitting MS and also a non-invasive MR technique (Continuous Arterial Spin Labelling CASL ) to determine cerebral perfusion in patients with a wide spectrum of MS severity. Presented are cross-sectional and longitudinal investigations of several MR parameters - enhancing lesions, diffusion tensor imaging and cord area - acquired from a cohort of relapsing-remitting MS patients recruited within three years of first symptom onset to assess the clinical and pathological evolution of the disease from its earliest clinical stages. Results from the presented studies include: (i) a high degree of gadolinium enhancement which relates to relapse frequency but not clinical impairment or disability in the medium term (ii) evidence of progressive loss of cervical cord area and (iii) subtle diffusion changes in normal appearing brain tissue but no definitive longitudinal changes in comparison to healthy controls. Also presented is the first application of non-invasive cerebral perfusion measurement using a MR technique which models for blood brain barrier permeability (CASL with two-compartment methodology). The most significant finding was a consistent decrease in perfusion in patients with progressive disease in comparison to controls particularly in the deep grey matter, probably reflecting neuronal loss or dysfunction and increased perfusion in white matter in patients with relapse onset MS which may reflect underlying inflammation. Overall, promising and novel results using several quantitative MR parameters investigating specific MS cohorts have been detailed in this thesis and provide useful insights for further work in MS.

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