Jonathan Doucette
Doctor of Philosophy in Physics (PhD)
Research Topic
Probing Brain Tissue Microstructure with Magnetic Resonance Imaging through Bayesian Learning of Signal Dynamics
Alexander Rauscher
Associate Professor
Research Classification
Algorithms
Brain Metabolism
Imaging
Neurological Diseases
Modelization and Simulation
Research Interests
magnetic resonance imaging
physics
quantitative susceptibility mapping
myelin water imaging
brain
Relevant Degree Programs
Affiliations to Research Centres, Institutes & Clusters
Research Methodology
Magnetic Resonance Imaging
numerical simulations
Recruitment
Master's students
Doctoral students
Postdoctoral Fellows
MRI of multiple sclerosis, modelling of the MRI signal, quantitative susceptibility mapping, MRI physics
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Graduate Student Supervision
Doctoral Student Supervision (Jan 2008 - Nov 2019)
Gradient and spin echo magnetic resonance imaging for the characterization of myelin health in multiple sclerosis (2020)
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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Master's Student Supervision (2010 - 2018)
Frequency shift mapping in spinal cord models of white matter demyelination (2016)
The behavior of MR phase and frequency in demyelination and damage in central nervous tissue white matter arises not only from traditionally associated bulk susceptibility changes, but also from changes to its tissue microstructure. A recently proposed generalized Lorentzian model of microstructure-related magnetic susceptibility effects predicts an increase in MR frequency due to damage in myelin in MS lesions. The same model also predicts reduction in MR frequency due to axonal degeneration. Here, we investigate the effect of both myelin and axonal damage through transection of white matter fibers in the dorsal column of rat cervical spinal cord. This injury generates secondary damage consisting of neurodegeneration along nerve tracts bilateral to the transection site, producing cases of Wallerian and retrograde degeneration free of excessive hemorrhage and inflammation. High-resolution frequency maps of degenerating tracts were correlated with histopathology for axons, myelin, degenerated myelin, and macrophages. Damage to myelin sheaths is prominent in Wallerian degeneration, where we observe strong correlations with increasing frequency up to 8 weeks post-injury. Retrograde degeneration, which consists predominantly of axonal damage, produces decreased frequency shift over time. The MR frequency shifts are sensitive to the effects of macrophage in filtration and debris clearance, which vary with white matter fiber density and affect rates of degeneration. We demonstrate how MR frequency can successfully characterize injury in rat spinal cord white matter in a manner consistent with predictions outlined by the Generalized Lorentzian Approximation Model, and conclude that these results suggest potential applications of MR frequency to supplement or replace current clinical techniques, such as myelin water and diffusion weighted imaging, as a non-invasive and quantitative method of assessing white matter damage in CNS.
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Publications
- Myelin water imaging and R 2 * mapping in neonates: Investigating R 2 * dependence on myelin and fibre orientation in whole brain white matter (2020)
NMR in Biomedicine, 33 (3) - Myelin water imaging depends on white matter fiber orientation in the human brain (2020)
Magnetic Resonance in Medicine, - Non‐negative least squares computation for in vivo myelin mapping using simulated multi‐echo spin‐echo T 2 decay data (2020)
NMR in Biomedicine, - Quantitative Analysis of Punctate White Matter Lesions in Neonates Using Quantitative Susceptibility Mapping and R2* Relaxation (2019)
American Journal of Neuroradiology, 40 (7), 1221--1226 - Rapid myelin water imaging for the assessment of cervical spinal cord myelin damage (2019)
NeuroImage: Clinical, 23, 101896 - The role of diffusion and perivascular spaces in dynamic susceptibility contrast MRI (2019)
- The role of iron and myelin in orientation dependent R 2 * of white matter (2019)
NMR in Biomedicine, - What Have We Learned from Perfusion MRI in Multiple Sclerosis? (2018)
American Journal of Neuroradiology, - Cerebral Microbleeds: A Call for Standardized Advanced Neuroimaging (2017)
American Journal of Neuroradiology, 38 (11), E90--E91 - Cover Image, Volume 30, Issue 8 (2017)
NMR in Biomedicine, 30 (8), i--i - Susceptibility-sensitive MRI of multiple sclerosis lesions and the impact of normal-appearing white matter changes (2017)
NMR in Biomedicine, 30 (8), e3727 - A Prospective Pilot Investigation of Brain Volume, White Matter Hyperintensities, and Hemorrhagic Lesions after Mild Traumatic Brain Injury. (2016)
- Anisotropic cerebral vascular architecture causes orientation dependency in cerebral blood flow and volume measured with dynamic susceptibility contrast magnetic resonance imaging. (2016)
- Characterization of white matter integrity deficits in cocaine-dependent individuals with substance-induced psychosis compared with non-psychotic cocaine users. (2016)
- Corticospinal tract integrity measured using transcranial magnetic stimulation and magnetic resonance imaging in neuromyelitis optica and multiple sclerosis. (2016)
- FLAIR2: A Combination of FLAIR and T2 for Improved MS Lesion Detection. (2016)
- Microbleeds in Alzheimer’s Disease: A Neuropsychological Overview and Meta-Analysis (2016)
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 43 (06), 753--759 - Motor Skill Acquisition Promotes Human Brain Myelin Plasticity. (2016)
- Myelin Water Fraction Is Transiently Reduced after a Single Mild Traumatic Brain Injury--A Prospective Cohort Study in Collegiate Hockey Players. (2016)
- Operationalizing Neuroimaging for Disorders of Consciousness: The Canadian Context. (2016)
- Prevalence of Brain Microbleeds in Alzheimer Disease: A Systematic Review and Meta-Analysis on the Influence of Neuroimaging Techniques. (2016)
- Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica (2016)
NeuroImage: Clinical, 11, 743--750 - RE: Elucidating Pretreatment Cognitive Impairment in Breast Cancer Patients: The Impact of Cancer-Related Post-traumatic Stress. (2016)
- Reduced Myelin Water in the White Matter Tracts of Patients with Niemann-Pick Disease Type C. (2016)
- Subcortical grey matter alterations in cocaine dependent individuals with substance-induced psychosis compared to non-psychotic cocaine users. (2016)
- Changes in cerebral vascular reactivity and structure following prolonged exposure to high altitude in humans. (2015)
- Mortality from treatable illnesses in marginally housed adults: a prospective cohort study. (2015)
- Orientation Dependent MR Signal Decay Differentiates between People with MS, Their Asymptomatic Siblings and Unrelated Healthy Controls. (2015)
- Trajectories of subcortical iron accumulation in MS. (2015)
- A prospective study of the influence of acute alcohol intoxication versus chronic alcohol consumption on outcome following traumatic brain injury. (2014)
- Increased spinal cord movements in cervical spondylotic myelopathy (2014)
The Spine Journal, - Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study. (2014)
- To exclude or not to exclude: further examination of the influence of white matter hyperintensities in diffusion tensor imaging research. (2014)
- Evaluation of white matter myelin water fraction in chronic stroke. (2013)
- Magnetic resonance frequency shifts during acute MS lesion formation. (2013)
- A prospective study of physician-observed concussion during a varsity university hockey season: white matter integrity in ice hockey players. Part 3 of 4. (2012)
- Rapid whole cerebrum myelin water imaging using a 3D GRASE sequence. (2012)
- Bilateral filtering of magnetic resonance phase images. (2011)
- The influence of white matter fibre orientation on MR signal phase and decay. (2011)
- Susceptibility weighted imaging with multiple echoes. (2010)
- Localization of the subthalamic nucleus: optimization with susceptibility-weighted phase MR imaging. (2009)
- MR relaxation in multiple sclerosis. (2009)
- Phase unwrapping of MR images using Phi UN--a fast and robust region growing algorithm. (2009)
- Quantification of modulated blood oxygenation levels in single cerebral veins by investigating their MR signal decay. (2009)
- ToF-SWI: simultaneous time of flight and fully flow compensated susceptibility weighted imaging. (2009)
- Improved elimination of phase effects from background field inhomogeneities for susceptibility weighted imaging at high magnetic field strengths. (2008)
- Informatics in Radiology: GUIBOLD: a graphical user interface for image reconstruction and data analysis in susceptibility-weighted MR imaging. (2008)
- Investigation of the influence of carbon dioxide concentrations on cerebral physiology by susceptibility-weighted magnetic resonance imaging (SWI). (2008)
- Investigations on the effect of caffeine on cerebral venous vessel contrast by using susceptibility-weighted imaging (SWI) at 1.5, 3 and 7 T. (2008)
- Susceptibility weighted imaging at ultra high magnetic field strengths: theoretical considerations and experimental results. (2008)
- Detection of multiple intracranial hemorrhages in a child with acute lymphocytic leukemia (ALL) by susceptibility weighted imaging (SWI). (2007)
- Obtaining blood oxygenation levels from MR signal behavior in the presence of single venous vessels. (2007)
- Contrast-enhanced, high-resolution, susceptibility-weighted magnetic resonance imaging of the brain: dose-dependent optimization at 3 tesla and 1.5 tesla in healthy volunteers. (2006)
- Demonstration of paramagnetic and diamagnetic cerebral lesions by using susceptibility weighted phase imaging (SWI). (2006)
- Susceptibility weighted imaging: data acquisition, image reconstruction and clinical applications. (2006)
- Application of an exogenous hyperoxic contrast agent in MR mammography: initial results. (2005)
- High resolution susceptibility weighted MR-imaging of brain tumors during the application of a gaseous agent. (2005)
- Magnetic susceptibility-weighted MR phase imaging of the human brain. (2005)
- Nonnvasive assessment of vascular architecture and function during modulated blood oxygenation using susceptibility weighted magnetic resonance imaging. (2005)
- Subtraction of in-phase and opposed-phase images in dynamic MR mammography. (2005)
- Optimized 3 T EPI of the amygdalae. (2004)
- Robust field map generation using a triple-echo acquisition. (2004)
- Automated unwrapping of MR phase images applied to BOLD MR-venography at 3 Tesla. (2003)
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