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Morris, Sarah Rosemary

University of British Columbia

Myelin, the lipid-rich sheath which wraps around axons, has complex and unique physical and chemical properties which can be used to produce magnetic resonance imaging (MRI) contrast. Developing MRI to measure myelin is vital for monitoring the brain and spinal cord in health and disease. This thesis explores four MRI techniques sensitive to myelin: myelin water imaging (MWI), magnetisation transfer (MT), inhomogeneous magnetisation transfer (ihMT) and diffusion imaging. First, these metrics were recorded in regions throughout the healthy adult and pediatric brain. Reproducibility, dynamic range and correlations between metrics were investigated. Healthy adult and pediatric atlases of the metrics were made publicly available for other neuroimaging researchers. Next, the orientation dependence of MWI, MT and ihMT was quantified. White matter is anisotropic, consisting of fiber bundles which vary in angle to the MRI main magnetic field. This can affect MRI metrics through the susceptibility of lipid-rich myelin, anisotropic vasculature, iron content, dipole-dipole and magic angle effects. We found that the orientation dependence curve for each metric varied between brain regions, suggesting that microstructural parameters other than fibre angle are affecting the orientation dependence. Then, we investigated the orientation dependence of ihMT in more detail, using a phospholipid bilayer sample rotated in a nuclear magnetic resonance (NMR) spectrometer to measure the variation with angle of the breadth of the lipid spectrum and dipolar order relaxation time. We found that the lipid linewidth had a greater effect on ihMT than the dipolar order relaxation time under our experimental conditions. Finally, ex vivo human spinal cord injury (SCI) tissue from the International SCI Biobank was scanned at 7 Tesla to obtain MWI, ihMT and diffusion metrics. This tissue then underwent histological staining for myelin lipids and inflammatory cells. We performed correlations between the MRI metrics and the digitised histological staining to validate the metrics’ specificity to myelin and sensitivity to inflammation processes. We measured the MRI metrics in motor and sensory white matter tracts along the cord, which provided a first glimpse into the possible utility of these techniques as biomarkers to assess the impact of SCI on myelin and axons in vivo.

Text

2023-04-24

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/84433

Physics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/