Ramani, Anita; (2003) Quantitative magnetisation transfer measurements in Multiple Sclerosis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Magnetic Resonance Imaging (MRI) is rapidly emerging as a powerful tool for evaluating white matter changes in Multiple Sclerosis (MS). MRI has conventionally used the T1 and T2 relaxation times and proton density of tissue water to produce contrast. Magnetisation Transfer Imaging (MTI) is a Magnetic Resonance (MR) technique that offers a new method for modifying tissue contrast and improving tissue characterisation. Biological tissues contain separate populations of hydrogen protons; a highly mobile (free) hydrogen pool, and an immobile (restricted motion, mostly macromolecules) hydrogen pool. Exchange of magnetisation between the free and restricted hydrogen protons is the basis of magnetisation transfer (MT); MT is an indirect process mediated by macromolecules. In this thesis, a new quantitative MT technique had been devised that allows in-vivo coverage of the whole brain and that precisely estimates the macromolecular proton fraction (f) and bound water T2 relaxation time (T2B). Both f and T2B were significantly different between MS lesions and normal control white matter. Compared with MTR (the Magnetisation Transfer Ratio, a simple, commonly used, parameter which can be calculated from a pair of differently MT weighted images), f and T2B have the potential advantage of relative independence from MT acquisition protocol while offering more pathologically specific information. In particular, f may provide a more direct indication of myelin content in white matter. MTR, however, is a composite measure that is derived from a number of more fundamental MR parameters. It is of interest to characterise these separately as they may offer greater pathological specificity. Quantification of these underlying parameters should also offer relative independence from scanner and acquisition parameters, making comparisons between studies more straightforward. MTR, as a measure, is dependent on the specific pulse sequence and scanner characteristics, making it difficult to compare results between centres. If MTI is to be used as a tool in multi-centre therapeutic trials, estimation of f and T2B, (which have the potential to be less dependent on acquisition parameters), may be of value. Furthermore, f may provide a more direct indication of white matter myelin content, as myelin protons are likely to make a major contribution to the overall macromolecular pool. Further studies are now needed to investigate the pathological basis of these fundamental parameters and to determine, in a large clinical cohort, their relationship to clinical subgroups and disability.

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