Multi-nuclear magnetic resonance for characterizing human central nervous system tissue

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Magnetic resonance imaging (MRI) measures signal from different nuclei. Central nervous system (CNS) microstructure influences MR signal but conventional MRI is qualitative, with limited specificity (similar contrasts for different tissue changes) and limited sensitivity (small tissue changes are not detectable), posing significant shortcomings in MRI's ability to assess CNS tissue properties during development, aging and injury. My long-term goal is to understand how human CNS microstructure governs MR signal changes. In the next 5 years, my short-term goal is to develop, validate, and apply quantitative MR methods in the CNS to probe myelin and axons using a multi-nuclear approach. Hydrogen (1H) is by far the most common type of MR. T2 relaxation, inhomogeneous magnetization transfer (ihMT), diffusion and MR spectroscopy (MRS) can provide quantitative information about myelin and axons, but many questions remain about how these methods are related and influenced by microstructural changes. Trying to characterize complex multi-nuclei tissue using information from a single nuclei (1H) is limiting. Sodium (23Na) plays important roles in nerve signal transmission and axon composition. CNS studies show 23Na concentration (total, intra- and extracellular), cellular volume fractions and relaxation vary with tissue microstructure. Phosphorus (31P) enables quantification of chemicals related to phospholipid membrane metabolism. 23Na, 31P, and 1H provide complimentary information. Phospholipids are a major myelin component, thus 31P plus 1H T2-based myelin water and ihMT will give a more detailed view of myelin. 1H diffusion and MRS with 23Na can more completely characterize axonal integrity. However, CNS studies comparing 23Na and 1H, and 31P and 1H are limited. My program is framed around a series of human post-mortem and in vivo synergistic studies to characterize CNS tissue: 1H ihMT work will examine (a) variation in normal brain and spinal cord; (b) orientation effects; (c) changes with CNS damage; (d) combined ihMT-T2 experiments 23Na imaging efforts will target (a) 3T technical development; (b) 23Na comparison to 1H MRS and diffusion 31P MRS focuses on (a) 3T technical development; (b) 31P comparison to 1H ihMT and T2-myelin water Our access to human brain and spinal cord post-mortem tissue and established collaborations with experts in biology and CNS tissue microstructure places us in a unique position to examine factors that influence ihMT, an emerging myelin imaging approach. Expanding research to beyond 1H-MR enables a more comprehensive assessment of tissue composition, and permits comparison studies between 1H advanced MR and 23Na/31P. My research program will provide high-quality interdisciplinary training to 12 HQP, supporting the development of Canada's future scientific leaders in academia and industry. Recruitment and mentorship of women will help address the gender imbalance in physics.