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Title: Investigation of multiple sclerosis spinal cord using high field MRI with multi-transmit technology
Author: Kearney, H.
ISNI:       0000 0004 5351 7484
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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This thesis explores abnormalities in the multiple sclerosis (MS) spinal cord and their relationship with physical disability through the use of conventional and quantitative magnetic resonance imaging (MRI). Firstly, an hypothesis was tested that spinal cord atrophy would be associated with disability, independently from brain atrophy and lesion load, in long disease duration MS. The results presented confirm that cord atrophy is significantly associated with higher levels of physical disability after more than twenty years of MS. Following this observation, the next experiment investigated whether a combination of an active surface model (ASM) and high resolution axial images, would provide a more reproducible measure of spinal cord cross-sectional area; compared to previously described methodologies. The results presented show the superior reproducibility of the ASM combined with axial images for the measurement of cord area in MS, which may be of relevance to future clinical trials utilising cord atrophy as an outcome measure. The pathology of MS in the spinal cord was also explored in several ways using MRI. Firstly, spinal cord lesion morphology was studied, to investigate whether focal lesions, that traversed two or more spinal cord columns and involved the grey matter, would be associated with progressive MS. The results presented confirm this association and also that diffuse abnormalities are more frequently seen in progressive disease. Secondly, spinal cord lesion load was measured quantitatively on axial images, to investigate if this measure would be associated with disability independently from cord atrophy. The functional importance of focal lesions in MS is highlighted by demonstrating an independent association between lesion load and disability. Thirdly, magnetisation transfer ratio (MTR) measures of the outer spinal cord were obtained, in an area expected to contain the pia mater and subpial tissue, to investigate whether outer cord abnormalities could be seen in MS compared to healthy controls and if such abnormalities would be associated with cord atrophy. The results presented show that significant decreases in MTR occur in the outer cord early in the disease course, prior to the development of cord atrophy and further decreases in MTR were seen in progressive MS. Furthermore, an independent association is presented between outer cord MTR and cord atrophy, suggesting that spinal cord meningeal inflammation may be associated with axonal loss in MS. Lastly, diffusion tensor imaging was used in the spinal cord grey matter, in order to investigate whether microstructural abnormalities in this structure would be associated with physical disability. The results of this study identified an association between grey matter radial diffusivity and disability, independently from cord atrophy, suggesting a significant contribution of spinal cord grey matter pathology to clinical dysfunction. In summary, this thesis shows that MS spinal cord abnormalities may be visualised and quantified using high field MRI, and are significantly associated with disability. The observations presented may of relevance to future MRI studies and clinical trials in MS that aim to understand and potentially prevent the pathological processes underlying irreversible physical disability.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available