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Quantitative Susceptibility Mapping in Human Brain: Methods Development and Applications Open Access


Other title
Magnetic Resonance Imaging
Quantitative Susceptibility Mapping
Type of item
Degree grantor
University of Alberta
Author or creator
Sun, Hongfu
Supervisor and department
Wilman, Alan H (Biomedical Engineering)
Examining committee member and department
De Zanche, Nicola (Oncology)
Yahya, Atiyah (Oncology)
Wilman, Alan H (Biomedical Engineering)
Wang, Yi (Biomedical Engineering, Cornell University)
Wachowicz, Keith (Oncology)
Thompson, Richard (Biomedical Engineering)
Department of Biomedical Engineering

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Quantitative susceptibility mapping (QSM) is an emerging magnetic resonance imaging (MRI) method that provides image contrast based on an important underlying brain tissue property. It is derived from the phase images from a gradient echo sequence, and overcomes the orientation dependency problem associated with phase imaging. However, QSM from gradient echo phase involves complicated image processing for reconstruction. This thesis explores technical challenges in QSM and provides advanced methods to solve them. Methods are introduced for background phase removal and fast QSM and then applied in three QSM applications: functional MRI studies, validation of QSM for deep grey matter iron in multiple sclerosis subjects and evaluation of QSM in patients with intracranial hemorrhage. One of the biggest challenges in QSM reconstruction is the removal of background phase. A novel method that makes use of the harmonic property of background field and Tikhonov regularization is presented in Chapter 2. The method is named RESHARP (Regularized Enabled Sophisticated Harmonic Artifact Reduction for Phase data). It is shown to be effective and robust in removal background phase while reserving local phase contrast. QSM has been proposed as a direct brain iron mapping technique for deep grey matter. However, most of the susceptibility to iron correlations are estimated using a brain iron study more than 50 years ago. A postmortem study is performed by measuring brain iron levels using Perls’ ferric iron staining and comparing with susceptibilities in multiple sclerosis brain, which is presented in Chapter 3. High linear correlations between Perls’ optical density and QSM were found in three subjects studied, leading to the conclusion that ferritin-iron is the main susceptibility source in deep GM which can be measured with QSM. Fast acquisition of QSM is also demonstrated in Chapter 4 using high resolution single-shot gradient echo-planar imaging (EPI). It reduces scan time from using regular gradient echo imaging of ~ 6mins to only 7 secs. Deep grey matter iron contrasts using EPI are found to be similar to traditional full scan. As an application of fast QSM with EPI, QSM extraction from regular fMRI studies is illustrated in Chapter 5, which also use gradient EPI. A single mean QSM from fMRI time series is derived for deep grey matter, which enables QSM application from any standard fMRI study. Heme-iron is highly concentrated in intracranial hemorrhage and changes its form with blood degradation, which makes it a perfect candidate for QSM application. However, gradient echo images in the clinic typically are obtained from a single echo with long echo time, which impedes QSM due to the fast signal decay within and around hemorrhage. A new method is presented in Chapter 6 that isolates the ICH dipole field followed by susceptibility superposition using multiple boundaries for background field removal. This method significantly reduces artifacts and makes susceptibility measurement of ICH feasible. In conclusion, this thesis has proposed methods to solve QSM reconstruction challenges, illustrated and validated its clinical value and power as a new contrast mechanism for MRI.
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. 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
Sun H, Wilman AH. Background field removal using spherical mean value filtering and Tikhonov regularization. Magn Reson Med 2013; 1157:1151–1157.Sun H, Walsh AJ, Lebel RM, Blevins G, Catz I, Lu J-Q, Johnson ES, Emery DJ, Warren KG, Wilman AH. Validation of quantitative susceptibility mapping with Perls’ iron staining for subcortical gray matter. Neuroimage 2014;105:486–492.Sun H, Wilman AH. Quantitative susceptibility mapping using single-shot echo-planar imaging. Magn. Reson. Med. 2015;73:1932–1938.Sun H, Kate M, Gioia LC, Emery DJ, Kenneth B, Wilman AH. Quantitative susceptibility mapping using a superposed dipole inversion method: application to intracranial hemorrhage. Magn. Reson. Med. 2015.

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