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Development and application of quantitative iron MRI in multiple sclerosis Open Access


Other title
Multiple Sclerosis
Magnetic Resonance Imaging
Type of item
Degree grantor
University of Alberta
Author or creator
Walsh, Andrew J
Supervisor and department
Emery, Derek (Radiology and Diagnostic Imaging)
Wilman, Alan (Biomedical Engineering)
Examining committee member and department
Beaulieu, Christian (Biomedical Engineering)
Rauscher, Alexander (Radiology)
Thompson, Richard (Biomedical Engineering)
Blevins, Gregg (Medicine)
Department of Biomedical Engineering

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Magnetic resonance imaging (MRI) is a valuable imaging modality and is commonplace in diagnosing, evaluating, and understanding the pathobiology of many neurological disorders. Current methods are helpful in the diagnosis of multiple sclerosis (MS) but fail to provide useful longitudinal information. Furthermore, current clinical MRI methods are limited in the research setting for evaluating the breadth of pathophysiology and focus on classical inflammation, demyelination, and gliosis. Techniques that are sensitive to iron have the potential to uncover new features including iron involvement in lesions, neurodegeneration, or altered metabolism. This thesis explores technical aspects of phase imaging and R2* mapping using high field MRI and their utility in evaluating brain iron in MS. MR phase images are generated through post-processing of gradient echo MRI acquisitions. Measurements from phase images using a standard high pass method could be used to locally quantify iron which is of interest in MS. However measurements in deep grey matter can be influenced by several factors including filter strength, structure shape, and location of background measurement. These factors were assessed in simulation and in control subjects and the best parameters are suggested. A new phase processing method is presented which uses the derivative of the spatial gradient to locally correct background phase. The contrast from lesions in MS patients was improved and less filtering effects were apparent in deep grey matter and in simulation. The contribution from tissue iron to quantitative MRI measurements is unclear, especially in neurological disorders. The relationship between iron staining and MRI relaxation and phase measurements in postmortem subjects is evaluated where R2* mapping demonstrated the highest correlation to iron compared to R2 mapping, fast spin echo imaging, and phase imaging. Furthermore, a single MRI method could not consistently demonstrate the iron status of MS lesions. A wide variation in normal brain iron content presents difficulties in establishing pathological iron changes in individual MS patients therefore longitudinal analysis of iron sensitive MRI was assessed. Changes relative to controls were found in several deep grey matter regions which strongly correlate to physical disability.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Walsh AJ, Wilman AH. Susceptibility phase imaging with comparison to R2 mapping of iron-rich deep grey matter. Neuroimage 2011;57(2):452–61.Walsh AJ, Eissa A, Blevins G, Wilman AH. Susceptibility phase imaging with improved image contrast using moving window phase gradient fitting and min- imal filtering. Journal of magnetic resonance imaging 2012;36(6):1460–9.Walsh A, Lebel R, Eissa A, Blevins G, Catz I, Lu J, Resch L, Johnson E, Emery D, Warren K, Wilman A. Multiple Sclerosis: Validation of MR Imaging for Quantification and Detection of Iron. Radiology 2013;267(2):531-42.

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