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

磁共振成像（MRI）测量来自不同核的信号。中枢神经系统（CNS）的微观结构影响MR信号，但传统的MRI是定性的，特异性有限（不同组织变化的对比相似），灵敏度有限（无法检测到小的组织变化），这在MRI评估中枢神经系统组织在发育、衰老和损伤过程中的特性方面存在重大缺陷。我的长期目标是了解人类中枢神经系统的微观结构如何控制磁共振信号的变化。在接下来的5年里，我的短期目标是开发、验证和应用定量MR方法在中枢神经系统中使用多核方法来探测髓磷脂和轴突。氢（1H）是迄今为止最常见的MR类型，T2弛豫、非均匀磁化转移（ihMT）、扩散和MR光谱（MRS）可以提供髓磷脂和轴突的定量信息，但关于这些方法如何与微观结构变化相关和影响许多问题仍然存在。试图利用单核（1H）的信息来表征复杂的多核组织是有限的。钠（23Na）在神经信号传递和轴突组成中起着重要作用。中枢神经系统研究表明，23Na浓度（总浓度、细胞内浓度和细胞外浓度）、细胞体积分数和松弛度随组织微观结构的变化而变化。磷（31P）可以量化与磷脂膜代谢相关的化学物质。23Na， 31P和1H提供互补信息。磷脂是髓磷脂的主要成分，因此31P + 1H T2-based髓磷脂水和ihMT将提供更详细的髓磷脂视图。1H扩散和23Na MRS能更完整地表征轴突完整性。然而，比较23Na和1H、31P和1H的CNS研究有限。我的计划是围绕一系列人类死后和体内协同研究来表征中枢神经系统组织：1H ihMT工作将检查(a)正常大脑和脊髓的变异；(b)取向效应；(c)随中枢神经系统损伤的变化；(d)结合hmt - t2实验，23Na成像工作将以(a) 3T技术发展为目标；(b) 23Na与1H MRS和扩散31P MRS的比较，重点是(a) 3T技术的发展；我们能够接触到人类大脑和脊髓死后组织，并与生物学和中枢神经系统组织微观结构方面的专家建立了合作关系，这使我们处于一个独特的位置，可以研究影响ihMT（一种新兴的髓鞘成像方法）的因素。将研究扩展到1H-MR之外，可以更全面地评估组织成分，并允许在1H高级MR和23Na/31P之间进行比较研究。我的研究项目将为12名HQP提供高质量的跨学科培训，支持加拿大未来学术界和工业界的科学领袖的发展。招募和指导女性将有助于解决物理学中的性别失衡问题。

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.