
Jonathan Doucette
Doctor of Philosophy in Physics (PhD)
Research Topic
Probing Brain Tissue Microstructure with Magnetic Resonance Imaging through Bayesian Learning of Signal Dynamics
modelling of the MRI signal, quantitative susceptibility mapping, myelin water imaging, MRI physics, deep learning
Background in physics, electrical engineering, computer science or equivalent.
Please note that, while my main affiliation is the department of Pediatrics, I mainly supervise students in the department of Physics and Astronomy. I am also affiliated with the Physics department and the Radiology department.
Interest in biological systems
Programming skills depending on level (undergrad to PhD)
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Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
Multiple sclerosis (MS) is a complex, autoimmune disease that results in demyelination and neurodegeneration. Magnetic resonance imaging (MRI) is an essential cornerstone of MS diagnosis and clinical decision making, however, clinical MRIs lack specificity to the pathological mechanisms influencing myelin health.In this thesis, two quantitative MRI techniques were probed for their potential to study myelin health in MS. First, multi-echo spin-echo myelin water imaging (MWI) was tested for its specificity to myelin lipids, proteins and iron. We demonstrated to-date unknown sensitivity of MWI and identified MS lesion changes indicative of late-stage remyelination. Thereafter, the accuracy of MWI and its potential application at ultra-high magnetic fields were investigated. Using signal simulations, the dependence of the non-negative least-squares analysis on processing and tissue parameters was described. Myelin underestimations due to B⁺₁-inhomogeneities and noise were shown to be minimized by adjusting the T₂ range according to the echo time. To translate MWI to 7T, T₂ tissue properties in seven healthy subjects were studied in comparison to 3T. We demonstrated the feasibility of 7T-MWI and discussed current limitations in assessing short T₂ times.Secondly, susceptibility-sensitive MRI was explored, which provides greater sensitivity, albeit possibly lower specificity to myelin, than MWI. Using the phase component, we showed that the MS lesion contrast is typically not driven by iron accumulation. In simulations and with post-mortem data, it was demonstrated that iron and myelin loss in combination determine the lesions’ appearance. Thereafter, the potential of the technique to become a marker of tissue damage and repair was evaluated by studying the evolution and pathological underpinnings of acute MS lesions in eleven patients over five years. Current models and their shortcomings were discussed.Finally, two technical developments were introduced. First, a multi-dynamic, high-spatial resolution susceptibility-sensitive imaging approach was presented for visualizing the central vein sign. Using phantom and in vivo data, qualitative and quantitative agreement of the proposed approach with other imaging strategies was demonstrated. Secondly, FLAIR² was introduced, a novel contrast that improves contrast-to-noise, while shortening scan time. The potential of FLAIR² to aid automated lesion segmentation was demonstrated on real-world multi-centre clinical data.
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Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
In MRI the transverse relaxation rate, R₂=1/T₂, shows dependence on the orientation of ordered tissue relative to the main magnetic field. In previous studies, orientation effects of R₂ relaxation in the mature brain's white matter have been found to be described by a susceptibility-based model of diffusion through local magnetic field inhomogeneities created by the diamagnetic myelin sheaths. Orientation effects in human newborn white matter have not yet been investigated. The newborn brain is known to contain very little myelin and is therefore expected to exhibit a decrease in orientation dependence driven by susceptibility-based effects. We measured R₂ orientation dependence in the white matter of human newborns.R₂ data were acquired with a 3D Gradient and Spin Echo (GRASE) sequence and fibre orientation was mapped with diffusion tensor imaging (DTI). We found orientation dependence in newborn white matter that is not consistent with the susceptibility-based model and is best described by a model of residual dipolar coupling. In the near absence of myelin in the newborn brain, these findings suggest the presence of residual dipolar coupling between motionally restricted water molecules. This has important implications for quantitative imaging methods such as myelin water imaging, and suggests orientation dependence of R₂ as a potential marker in early brain development.
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