Cawley, NM; (2016) Developing new imaging biomarkers in multiple sclerosis. Doctoral thesis , UCL (University College London).

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Abstract

To date, there have been significant advances in the use of magnetic resonance imaging (MRI) in the initial diagnostic work-up of patients suspected of having MS and also in the monitoring of disease activity during active treatment. However, there is often a discrepancy between the clinical and conventional MRI findings which arises due to the complex heterogeneous features of MS pathology. The development of imaging biomarkers, which are directly linked to the pathological processes underlying progressive and relapsing forms of MS, are vital to developing a better understanding of the pathological mechanisms driving the disease. In order to address this, I performed clinical studies in both progressive and relapsing forms of MS with both innovative imaging techniques and with other more established imaging measures. After the introduction (where I review the main characteristics of MS (Chapter I) and of conventional and advanced MRI techniques employed in the studies presented in this thesis (Chapter II)), I present the following studies: (A)Pilot studies with innovative imaging techniques – this included a gammaaminobutyric acid (GABA) magnetic resonance spectroscopy study in patients with secondary progressive multiple sclerosis (SPMS) (Chapter III) and a novel diffusion study (neurite orientation dispersion and density imaging, NODDI) in the brain of patients with relapsing remitting multiple sclerosis (RRMS) (Chapter IV). The main results of these investigations are that GABA may be a marker of neurodegeneration and NODDI may better characterise microstructural changes in the brain than standard diffusion tensor imaging. (B) Clinical studies with more established imaging measures including an MRI follow-up spinal cord study in primary progressive multiple sclerosis (PPMS) (Chapter V) using 1H-Magnetic resonance spectroscopy (1HMRS), Q-space imaging (QSI) and spinal cord area. Another study looked at the development of spinal cord atrophy in a progressive MS cohort of patients over 1 year to determine the sample sizes required to demonstrate a reduction in spinal cord cross-sectional area as a primary outcome measure in clinical trials (Chapter VI). Both of these studies demonstrated spinal cord atrophy occurred over 1 year and it may be a useful outcome measure in phase II neuroprotective trials in early PPMS. In the final chapter (Chapter VII), I will summarise the results of the studies presented in the thesis and propose future directions for the research.

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