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Quantitative Transverse Relaxometry in Multiple Sclerosis

  • Author / Creator
    Uddin, Md Nasir
  • Quantitative transverse relaxometry is an MRI method that has shown promise for study of iron accumulation and demyelination in healthy brain and in associated neurological disorders. Multiple sclerosis (MS) is one such neurodegenerative disorder in which iron accumulation in deep grey matter (DGM), demyelination in white matter and brain atrophy have been observed. This thesis concerns the development and application of transverse relaxation mapping to evaluate iron sensitivity and track the disease progression in relapsing-remitting MS (RRMS) using high field (4.7 T) as well as standard clinical (1.5 T) MRI. A two-year longitudinal study was conducted to evaluate the changes in iron accumulation in MS DGM using spin echo based transverse relaxation rate (R2) mapping methods and atrophy measurements. Relative to controls, measurable differences in DGM structures using R2 mapping showed strong association with disease severity in patients with RRMS, particularly in the globus pallidus and the pulvinar. Atrophy of the globus pallidus over two years was related to R2 increase. At high fields such as 4.7 T, tissue heating is a major limitation of R2 mapping using a typical multi-echo spin echo sequence. This sequence typically uses 16-32 echoes. To overcome the tissue heating limitation reduced echo train lengths were evaluated. Stimulated echo compensation was used to account for the use of non-ideal refocusing pulses. Consistent R2 values were found with as few as 4 echoes compared to 20 echoes. Radiofrequency power savings through the use of reduced number of echoes enabled increased slice coverage without effects on R2 from incidental magnetization transfer. Quantitative transverse relaxometry methods can be used to evaluate iron accumulation in human brain. However, added iron specificity may be obtained by using subtractive measures. The benefits and limitations of within and between field difference transverse relaxometry methods (R2’= R2* - R2 and Field Dependent Relaxation Increase FDRI) for iron accumulation were compared in human brain and in an iron-doped agar phantom using 4.7 and 1.5 T. Using 4.7 T, R2’ was found to provide more specific iron measures due to its small intercept with estimated post-mortem iron concentration. However, in white matter, R2’ was highly sensitive to fiber orientation relative to B0 which increases with field strength, while FDRI was much less sensitive to this orientation. Overall for brain iron correlation, the transverse relaxation difference methods added little value over a single R2* measurement at highest available field, which was 4.7 T. Proton density (PD) and T2-weighted images have been part of clinical MRI protocols for MS for many years. From these images, quantitative T2 maps were obtained using indirect and stimulated echo compensation. After demonstrating feasibility in healthy controls, seven-year changes in T2 were examined retrospectively and correlated with disease severity and brain atrophy in MS brain. Changes in T2 in brain structures particularly in globus pallidus, caudate and posterior internal capsule showed significant correlations with disease severity in MS over 7 years. Given the wide use of PD and T2-weighted images in MS clinical trials, this retrospective T2 method may provide an additional measure of disease progression and state. Furthermore, the use of a dual echo PD and T2-weighted FSE would enable tracking of quantitative T2 in clinical exams.

  • Subjects / Keywords
  • Graduation date
    2016-06
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R35X25M6H
  • 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 H (Biomedical Engineering)
  • Examining committee members and their departments
    • Yahya, Atiyah (Oncology-Medical Physics)
    • Beaulieu, Christian (Biomedical Engineering)
    • Wachowicz, Keith (Oncology-Medical Physics)
    • Thompson, Richard (Biomedical Engineering)
    • Dunn, Jeff (Radiology, University of Calgary)