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Development and application of quantitative iron MRI in multiple sclerosis

  • Author / Creator
    Walsh, Andrew J
  • 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.

  • Subjects / Keywords
  • Graduation date
    2013-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3W950W9X
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Biomedical Engineering
  • Supervisor / co-supervisor and their department(s)
    • Wilman, Alan (Biomedical Engineering)
    • Emery, Derek (Radiology and Diagnostic Imaging)
  • Examining committee members and their departments
    • Blevins, Gregg (Medicine)
    • Beaulieu, Christian (Biomedical Engineering)
    • Thompson, Richard (Biomedical Engineering)
    • Rauscher, Alexander (Radiology)