Khaleeli, Z.; (2010) Understanding progression in primary progressive multiple sclerosis: a longitudinal clinical and magnetic resonance imaging study. Doctoral thesis , UCL (University College London).

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Abstract

The work in this thesis applies magnetization transfer imaging (MTI) and conventional MRI measures (brain volume, T2 lesion load and enhancing lesions) to investigate the mechanisms underlying progression in primary progressive multiple sclerosis (PPMS), and identifies MR markers to predict and monitor progression. First, we demonstrated that MTI was sensitive to change in the normal appearing brain tissues over one year, and that clinical progression over this period was predicted by baseline normal appearing white matter (NAWM) MT ratio (MTR). However, our second study showed that over three years, grey matter MTR became a better predictor of progression than any other MRI measure. Grey matter MTR and T2 lesion load changes reflected concurrent progression during this study. To localize the baseline grey matter injury more precisely, we developed a voxelbased technique to identify areas of grey matter MTR reduction and volume loss in patients compared with controls. The regions of grey matter MTR reduction identified correlated with clinical function in anatomically related systems. Finally, because our studies showed that lesion load influenced progression, we used contrast enhanced T1-weighted imaging to examine active focal inflammation. We found that while lesion activity declined over five years, levels of activity at the start of the study could influence mobility five years later. The work presented in this thesis suggests that grey matter damage has a predilection for certain brain regions and is an important determinant of progression in early PPMS. In the white matter, changes in lesion volume and activity continue to influence progression, but NAWM injury may have a declining role. MTR is a sensitive and responsive tool for predicting, monitoring, and localizing clinically relevant brain injury in early PPMS.

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