Magnetisation transfer imaging in the study of early relapsing-remitting multiple sclerosis
Multiple sclerosis is a common cause of neurological disability in the young adult, but, at present, disease modifying medication may have little, if any, effect upon long term clinical impairment. For this reason, there is a continuing need to understand the mechanisms that lead to long term disability and - in the context of clinical trials - to develop reliable surrogate markers of disease progression. It may be especially useful to describe the early evolution of abnormality within normal-appearing white matter (NAWM) and grey matter firstly because pathology in early MS may be a key determinant of later disability, and secondly because there is only a modest relationship between white matter lesion load and clinical impairment. This thesis presents a series of studies, investigating NAWM and grey matter abnormality in a cohort of patients with early relapsing-remitting MS. A key question was whether MRI measures were able to detect accumulating abnormality in NAWM and grey matter early in the clinical course. An initial investigation, using Ti relaxation time estimation, did not detect strong evidence for a net change over time. Attention was therefore turned to the magnetisation transfer ratio (MTR) and results from a series of studies, investigating NAWM, grey matter and thalamic MTR abnormalities in early relapsing-remitting MS are presented. Of note, a clinically relevant reduction in grey matter MTR was apparent, and there was evidence for increasing MTR abnormality in the grey matter, NAWM and the thalamus over a two year follow-up period. In part three of this thesis, a model for the MT effect is used to estimate two underlying MT parameters - the semi-solid proton fraction (/) and the semi-solid T2 (T2B) in sixty patients with clinically-definite MS. The aim was to assess the clinical relevance of these novel parameters.