Bodini, B; (2013) Exploring the relationship between white and grey matter damage in primary progressive multiple sclerosis with structural magnetic resonance imaging. Doctoral thesis (PhD), UCL (University College London).

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Abstract

In the first part of this thesis, an introduction of the main characteristics of the primary-progressive form of multiple sclerosis (PPMS) (Chapter I), and of the acquisition and post-processing of the conventional and quantitative magnetic resonance imaging techniques employed in the studies presented in this thesis (Chapter II), will be presented. In the second part of this thesis, several advanced imaging techniques will be employed to answer the following two key questions on PPMS: 1) Is there is a spatial and temporal link between the pathological processes occurring in the normal appearing white matter (WM) and in the grey matter (GM) of patients with PPMS?; 2) Which regions of WM and GM abnormalities significantly contribute to clinical progression and cognitive dysfunction over time in patients with PPMS? To answer the first question, I first used tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM), to explore the spatial relationship between the damage occurring in the normal-appearing WM and GM in patients with early PPMS (Chapter III). Then, I moved onto exploring the temporal relationship linking the pathological changes affecting the two compartments, employing magnetization transfer imaging (MTI) and diffusion-based tractography (Chapter IV). To answer the second question, I first looked at the prognostic role of WM lesion location in a study conducted on a large population of patients with well- established PPMS who were followed-up for ten years in five different European centres (Chapter V). Then, using a novel approach which combines MTI and TBSS, I explored the regions of short-term accrual of microstructural damage in patients with early PPMS (Chapter VI). Finally, I moved onto examining the relative contribution of WM and GM damage to long-term motor and cognitive disability in PPMS (Chapter VII). In the final Chapter, I will summarise the results of the studies presented in this thesis, provide an answer to the two key questions on PPMS, and propose future directions for research.

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