"Gradient and Spin Echo Magnetic Resonance Imaging for the Characterization of Myelin Health in Multiple Sclerosis"

Event Date:
2020-03-24T09:00:00
2020-03-24T11:00:00
Event Location:
Virtual Defence - UBC’s Virtual Meeting Room (VMR)
Speaker:
VANESSA WIGGERMANN
Related Upcoming Events:
Grad Theses
Intended Audience:
Public
Local Contact:

Physics and Astronomy

Event Information:

Final Doctoral Oral Examination

Abstract:
Multiple sclerosis (MS) is a pathologically complex, autoimmune disease that results in demyelination and neurodegeneration following an inflammatory-mediated event cascade. Magnetic resonance imaging (MRI) has been essential to study MS and is now a cornerstone of MS diagnosis and clinical decision making. However, typical clinical MRIs fail to capture the complexity of the disease, because they lack specificity to myelin and other pathological mechanisms influencing myelin health in MS.

In this thesis, I probed two quantitative MRI techniques for their potential to study myelin health in MS. First, myelin water imaging was tested for its specificity to myelin lipids, proteins and iron stored in myelin. I explored tissue class specific variations and demonstrated to-date unknown sensitivity of myelin water imaging to the presence of minimal myelin concentrations. In brain tissue samples, I identified MS lesion changes that are linked to late stage remyelination. Following this work, I investigated the accuracy of myelin water imaging and its potential application at ultra-high magnetic fields. Using signal simulations, I first described the dependence of the non-negative least squares signal analysis on processing and tissue parameters. The simulations showed that myelin underestimations due to B1+-inhomogeneities and noise can be minimized by adjusting the T2 range in accordance with the acquisition echo time. To translate myelin water imaging to 7T, I studied the T2 properties in seven healthy subjects in comparison to 3T data. I demonstrated the feasibility of myelin water imaging at 7T and discussed the challenges that need to be addressed to overcome current limitations in measuring short T2 signal at 7T.

The susceptibility-sensitive MR data that were explored in the next chapters provide greater sensitivity, albeit possibly less specificity to myelin, than myelin water imaging. Using the phase component of the susceptibility-sensitive data, I disproved that the contrast of MS lesions is driven by iron accumulation. In simulations and with post-mortem data, I demonstrated that the combined degree of iron and myelin loss determines the lesions’ MRI appearance. Following this histopathological validation, I studied new, acute lesions in eleven MS patients over five years in order to discern the pathological underpinnings of the signal changes and the techniques potential as a marker of tissue damage and repair. Current models and their shortcomings are discussed.

Finally, I discussed two technical developments to enhance current MS imaging methods. First a multi-dynamic, high-spatial resolution susceptibility-sensitive imaging approach is described for visualizing the central vein sign. Using phantom and in vivo data, I demonstrated the qualitative and quantitative agreement of the proposed approach with other imaging strategies. Secondly, FLAIR2 is introduced, a novel image contrast that was developed to provide improved contrast-to-noise, while shortening overall scan time. The potential of FLAIR2 to aid automated lesion segmentation was subsequently demonstrated on real-world multi-center clinical data.

Add to Calendar 2020-03-24T09:00:00 2020-03-24T11:00:00 "Gradient and Spin Echo Magnetic Resonance Imaging for the Characterization of Myelin Health in Multiple Sclerosis" Event Information: Final Doctoral Oral Examination Abstract: Multiple sclerosis (MS) is a pathologically complex, autoimmune disease that results in demyelination and neurodegeneration following an inflammatory-mediated event cascade. Magnetic resonance imaging (MRI) has been essential to study MS and is now a cornerstone of MS diagnosis and clinical decision making. However, typical clinical MRIs fail to capture the complexity of the disease, because they lack specificity to myelin and other pathological mechanisms influencing myelin health in MS. In this thesis, I probed two quantitative MRI techniques for their potential to study myelin health in MS. First, myelin water imaging was tested for its specificity to myelin lipids, proteins and iron stored in myelin. I explored tissue class specific variations and demonstrated to-date unknown sensitivity of myelin water imaging to the presence of minimal myelin concentrations. In brain tissue samples, I identified MS lesion changes that are linked to late stage remyelination. Following this work, I investigated the accuracy of myelin water imaging and its potential application at ultra-high magnetic fields. Using signal simulations, I first described the dependence of the non-negative least squares signal analysis on processing and tissue parameters. The simulations showed that myelin underestimations due to B1+-inhomogeneities and noise can be minimized by adjusting the T2 range in accordance with the acquisition echo time. To translate myelin water imaging to 7T, I studied the T2 properties in seven healthy subjects in comparison to 3T data. I demonstrated the feasibility of myelin water imaging at 7T and discussed the challenges that need to be addressed to overcome current limitations in measuring short T2 signal at 7T. The susceptibility-sensitive MR data that were explored in the next chapters provide greater sensitivity, albeit possibly less specificity to myelin, than myelin water imaging. Using the phase component of the susceptibility-sensitive data, I disproved that the contrast of MS lesions is driven by iron accumulation. In simulations and with post-mortem data, I demonstrated that the combined degree of iron and myelin loss determines the lesions’ MRI appearance. Following this histopathological validation, I studied new, acute lesions in eleven MS patients over five years in order to discern the pathological underpinnings of the signal changes and the techniques potential as a marker of tissue damage and repair. Current models and their shortcomings are discussed. Finally, I discussed two technical developments to enhance current MS imaging methods. First a multi-dynamic, high-spatial resolution susceptibility-sensitive imaging approach is described for visualizing the central vein sign. Using phantom and in vivo data, I demonstrated the qualitative and quantitative agreement of the proposed approach with other imaging strategies. Secondly, FLAIR2 is introduced, a novel image contrast that was developed to provide improved contrast-to-noise, while shortening overall scan time. The potential of FLAIR2 to aid automated lesion segmentation was subsequently demonstrated on real-world multi-center clinical data. Event Location: Virtual Defence - UBC’s Virtual Meeting Room (VMR)