Advanced Quantitative Magnetic Properties Mapping of Tissue Microstructure

动机 * 超高场（UHF > 3特斯拉）MRI技术的出现，包括硬件和MRI序列物理学，引入了以前所未有的准确度可视化人体组织结构中的体内变化的可能性。因此，MRI体素级微结构的超高分辨率映射对于提供对神经发育、脑可塑性和细胞老化的更细致的理解将是非常有影响力的 * 该提议旨在扩展基于定量磁化率和弛豫测量的脑组织微结构MRI模型，以基于7特斯拉（T）MRI数据创建中间分辨率微结构图。具体而言，通过使用目前可通过7 T动物MRI实现的50 - 150 μm各向同性体素尺寸的中间分辨率，拟议的工作将寻求创建髓鞘双层，轴突和神经胶质细胞磁化率特性的可重复评估。通过使用成像体素内的真实细胞几何形状和髓磷脂体积分数的计算模型，MRI测量将与潜在的生物学特征相关。** 总体目标 * 本提案旨在制定一种可重复的定量显微结构MRI方法，以测量髓鞘体积分数和小鼠脑神经胶质细胞中储存的铁蛋白铁的量。MRI方法将使用铜腙（CPZ）喂养小鼠的7 T MRI作为高度可控的生物系统进行开发和验证，用于估计髓鞘体积分数和脑白色物质中的铁蛋白铁量。**影响：* 虽然传统的MRI对比可以可靠地描述人脑组织中的对比度，但它们缺乏定量特异性。这对于基础和发育神经科学中的基础脑神经解剖学的MRI研究特别相关。非侵入性的，空间分辨定量的关键微结构特征在大脑中将显着增强MRI作为一种工具，神经发育，神经科学和脑老化的研究。同样重要的是，拟议的计划将为高素质的人员提供极好的培训机会，并为增加对小鼠脑组织微观结构组织的理解奠定基础，最终目标是将这些发现/方法转化为人类成像。

Motivation***The advent of ultra high field (UHF > 3 Tesla) MRI technologies, both hardware and MRI sequence physics, has introduced the possibility of visualizing in vivo changes in human tissue structure with an unprecedented level of accuracy. Accordingly, an ultra-high resolution mapping of MRI voxel-level microstructure would be highly impactful for providing a more nuanced understanding of neurodevelopment, brain plasticity and cellular aging***This proposal aims to extend quantitative magnetic susceptibility and relaxometry-based MRI models of brain tissue microstructure to create intermediate resolution microstructure maps, based on 7 Tesla (T) MRI data. Specifically, by using an intermediate resolution of 50 – 150 μm isotropic voxel sizes, presently achievable with 7 T animal MRI, the proposed work will seek to create reproducible assessments of myelin bilayer, axon and neuroglia magnetic susceptibility properties. MRI measurements will be related to underlying biological features by using computational models of realistic cell geometries and myelin volume fraction within an imaging voxel. ******Overall Objective***This proposal aims to formulate a reproducible, quantitative microstructure MRI method to measure both myelin volume fraction and the amount of ferritin iron stored in neuroglial cells in mouse brain. The MRI method will be developed and validated using 7 T MRI of cuprizone (CPZ)-fed mice as a highly controllable biological system for estimating myelin volume fraction and the amount ferritin iron in brain white matter.******Impact: ***While traditional MRI contrasts can reliably depict contrast in human brain tissue, they lack quantitative specificity. This is particularly relevant for MRI studies of fundamental brain neuroanatomy in basic and developmental neuroscience. A non-invasive, spatially resolved quantification of critical microstructural features in the brain would significantly enhance MRI as a tool for neurodevelopmental, neuroscience and brain aging research. Equally important, the proposed program will provide excellent training opportunities for highly qualified personnel, as well as set the basis for increased understanding of the microstructural organization of mouse brain tissue, with the ultimate goal of translating these findings/methods to human imaging.*****