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

用于表征人类中枢神经系统组织的多核磁共振

• 批准号: RGPIN-2022-04807
• 负责人: Laule, Cornelia
• 金额: $ 4.44万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=764458
• 关键词: Multi; nuclear; magnetic; resonance; characterizing

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.

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，具有有限的特异性（不同组织变化的相似对比）和有限的灵敏度（小组织变化无法检测），在MRI评估发育，衰老和损伤期间CNS组织特性的能力方面存在显著缺陷。我的长期目标是了解人类CNS微结构如何控制MR信号变化。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探测髓鞘和轴突。氢（1H）是迄今为止最常见的MR类型。T2弛豫、非均匀磁化传递（ihMT）、扩散和MR波谱（MRS）可以提供有关髓鞘和轴突的定量信息，但关于这些方法如何与微结构变化相关和受其影响仍存在许多问题。试图使用来自单个核（1H）的信息来表征复杂的多核组织是有限的。钠（23 Na）在神经信号传递和轴突组成中起重要作用。中枢神经系统的研究表明，23钠浓度（总，内和细胞外），细胞体积分数和松弛与组织的微观结构。磷（31 P）能够量化与磷脂膜代谢相关的化学物质。23 Na、31 P和1H提供免费信息。磷脂是主要的髓磷脂成分，因此基于31 P加上1H T2的髓磷脂水和ihMT将给出髓磷脂的更详细的视图。~ 1H扩散和~（23）Na MRS能更全面地表征轴突的完整性。然而，比较23 Na和1H以及31 P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，以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化;（B）方向效应;（c）中枢神经系统损伤的变化;（d）联合ihMT-T2实验23 Na成像工作将针对（a）3 T技术开发;（B）23 Na与1H MRS和扩散31 P MRS的比较侧重于（a）3 T技术开发;（B）31 P与1H ihMT和T2-髓磷脂水的比较尸体组织和与生物学和CNS组织微观结构专家建立的合作使我们处于独特的位置来检查影响ihMT的因素，一种新兴的髓鞘成像方法。将研究扩展到1H-MR以外，可以更全面地评估组织成分，并允许1H高级MR和23 Na/31 P之间的比较研究。我的研究项目将为12名HQP提供高质量的跨学科培训，支持加拿大未来在学术界和工业界的科学领导者的发展。招聘和指导妇女将有助于解决物理学领域的性别不平衡问题。