The quest for a myelin specific magnetic resonance marker of multiple sclerosis pathology: Myelin water imaging

Magnetic resonance imaging (MRI) has been an invaluable tool for the visualization of MS abnormalities in brain. In this thesis, patients with multiple sclerosis were compared to healthy controls using two non-conventional MR techniques believed to be related to myelin content.; First, a model for the evolution of magnetization transfer (MT) abnormalities in patients with MS was proposed based on data collected from a relatively small sample size. The MT ratio (MTR) of normal appearing white matter (NAWM) in brain is normal at clinical onset and then slowly decreases over time, correlating strongly with disease duration. This suggests that the gradual progression in disease seen in patients with MS may be due not only to new lesion formation, but also due to global changes in NAWM. In the immediate months before lesion appearance on conventional MRI there is an abrupt decrease in MTR. Lesion recovery is variable, with some lesions showing good recovery of MTR and others showing no recovery or worsening. The early behaviour of lesions may be predictive of future recovery. Chronic stable lesions have a constant and low MTR.; Next, MT and myelin water imaging were compared in lesions and white matter for both an MS patient group, as well as a control group. The myelin water fraction of some white matter structures were found to correlate with MTR, while in others they did not. This regional dependence of the correlation between MTR and myelin water fraction is unexpected and has not been observed elsewhere. Myelin water imaging and MT imaging do however indeed probe different properties of brain tissue: myelin water imaging specifically measures the amount of water trapped between the myelin bilayer based on a given T 2 relaxation time range (typically 0--50ms), while MT probes the interaction between all of the semi-solid protons with all of the aqueous protons. The previously observed dissociation between MTR and myelin water fraction is reasonable as while myelin water imaging is a specific marker for myelin content, MT is influenced by many factors which are unrelated to myelin content including exchange rates between the semi-solid and aqueous proton pools, pH and distribution of galactocerebrosides. A change in the size of either the semi-solid or aqueous pool would also effect the measured MT ratio, for example: accumulation of cells such as astrocytes and macrophages which would serve to increase the size of the semi-solid pool, thereby increasing MTR without any increase in myelin content. Likewise, an increase in the aqueous proton pool due to oedema would decrease MTR without any reduction in myelin content. (Abstract shortened by UMI.)...