CRCNS:US French Coll:Computational Imaging of the Aging Cerebral Microvasculature

描述(申请人提供)：血液和组织之间的营养和废物的功能性交换发生在微血管中，从小动脉延伸到毛细血管和小静脉。皮质微血管网络可以用拓扑特征来描述，如：血管密度、微血管在相关路径上的取向、分支和曲折。曲折是脑组织收缩时微血管的卷曲和环状，发生在健康衰老和病理条件下。这种微血管拓扑结构的变化对营养物质的输送和大脑皮层神经元和神经胶质细胞废物的清除具有重要意义。美法合作的主要目标是开发一种计算成像方法来量化脑血管的微结构，并预测其在老龄化受试者中的演变。 目的和方法：研究小组开发了几种针对脑内微血管血流不同特征的MRI方法，包括使用扩散加权成像方案和体素内非相干运动(IVIM)技术，以及使用血流增强信号强度(FENSI)方法对血液进行局部磁标记(FENSI)。这些技术提供了不同的信息和可调的灵敏度来研究微血管血流。结合维管树的计算机模拟，可以使用这些措施提取微血管的结构特征。将用组织学研究衰老的动物模型，以确定大脑不同区域的血管拓扑，并确定与年龄相关的拓扑变化，特别是曲折增加。这些信息将被用于对微血管流动进行大规模模拟，以表征微血管拓扑特征与MRI信号之间的关系。动物MRI实验将与随后的组织学检查一起进行，以确认MRI无创性提供的血管拓扑特征。然后，将使用动物与年龄相关的拓扑特征来预测人类与年龄相关的血管变化，并将进行大规模的人体血管网络模拟和MRI采集。年轻和老年成人受试者的MRI采集将非侵入性地表征受试者特定的血管拓扑结构和人体皮质的解剖特定的血管变化。智力价值：先前对特定大脑区域的拓扑结构的研究是通过对身体组织的侵入性方法进行的，并导致了关于大脑随年龄的平均变化的讨论，而不是特定于特定个人的变化。所提出的MRI方法将允许非侵入性地探测人类灰质中的微血管拓扑。这是由于(A)MRI序列提供的高空间分辨率可以在空间尺度上分辨血管组织的皮质层，以及(B)对复杂微血管网络上的MRI信号的数值模拟。微血管拓扑的活体表征将提供皮质区域差异的定量描述，这可能形成微血管拓扑图的基础。此外，它还将以特定主题和特定区域的方式提供拓扑随年龄变化的破坏程度的量化衡量标准。更广泛的影响：衰老与脑血流量减少、应对挑战或刺激的血管反应性降低以及大脑毛细血管微结构的改变有关。与这些变化相关的是认知能力的下降。随着美国和欧洲的人口老龄化，确定老龄化人口如何保持长寿、多产和独立的生活至关重要。我们的方法将能够对血管系统的微结构变化进行非侵入性评估，以确定与年龄相关的变化的因果效应或心血管干预措施的影响，如有氧运动。微血管拓扑的计算成像将迎来一系列研究，考察脑神经元和神经胶质细胞在衰老或疾病期间代谢支持的变化。研究与教育的结合：从这个项目中获得的知识将通过Physiome组织和与研究小组正在开发的其他人类生理学模拟代码相关的网站，以计算机模拟和与微血管流动有关的数据的形式传播。这些信息将被整合到研究团队提供的本科和研究生课程中，包括：建模人类生理学、建模人类生理学实验室、细胞生物能量学以及其他流体力学和质量传输课程。

DESCRIPTION (provided by applicant): The functional exchange of nutrients and wastes between blood and tissue occurs in the micro-vascular vessels, extending from the arterioles through the capillaries and into the venules. Cortical micro-vascular networks can be described by topological characteristics, such as: vascular density, orientation of the micro-vessels in coherent pathways, branching, and tortuosity. Tortuosity is coiling and looping of micro-vessels upon shrinking of the cerebral tissue and occurs during healthy aging and in pathological conditions. This change in micro-vascular topology has important implications on the delivery of nutrients and removal of wastes from neurons and glial cells in the cortex. The main objective of the proposed USA-France collaborative effort is to develop a computational imaging approach to quantify the microstructure of cerebral vasculature and predict its evolution in aging subjects. Objectives and Methods: The research team has developed several MRI methods that target different characteristics of micro-vascular flow in the brain, including using diffusion-weighted imaging schemes with the intravoxel incoherent motion (IVIM) technique and the use of localized magnetic tagging of blood with the Flow ENhancement of Signal Intensity (FENSI) method. These techniques provide diverse information and tunable sensitivity to investigate micro-vascular flow. Combined with a computer simulation of vascular trees, the structural characteristics of the microvasculature can be extracted using these measures. An animal model of aging will be investigated with histology to determine vascular topology in different regions of the brain and to determine age-related topological changes, especially increasing tortuosity. This information will be used to perform a large-scale simulation of micro-vascular flow to characterize the relationship between micro-vascular topological features and MRI signals. An animal MRI experiment will be conducted with subsequent histological examination to confirm the vascular topological characterization provided non-invasively by MRI. The animal age-related topological features will then be used to predict human age-related vascular changes and a large-scale simulation of human vascular networks and MRI acquisitions will be performed. MRI acquisitions on young and old adult subjects will characterize subject-specific vascular topology and anatomically-specific vascular changes in human cortex, non-invasively. Intellectual Merit: Prior studies of the topology of particular brain regions have been performed via invasive methods on post-mortem tissues and result in discussions of average brain changes across age, not specific to a particular individual. The proposed MRI methods will allow the non-invasive probing of the micro-vascular topology in the human gray matter. This is possible owing to (a) the high spatial resolution afforded by the MRI sequences which can resolve the cortical layer on the spatial scale of vascular organization, and (b) the numerical simulation of the MRI signal on complex micro-vascular networks. The in vivo characterization of micro-vascular topology will provide quantitative descriptions of regional variations in the cortex, which could form the basis of an atlas of micro-vascular topology. In addition it will provide quantitative measures of the disruption of the topology with age in a subject specific and region-specific manner. Broader Impacts: Aging is associated with reductions in cerebral blood flow, reductions in vascular reactivity to compensate for challenges or stimulation, and modifications to the microstructure of capillaries in the brain. Associated with these changes are reductions in cognitive performance. As the population in the US and Europe ages, it is critical to determine how the aging population can maintain long, productive, and independent lives. Our approach will enable non-invasive assessments of microstructural changes in the vasculature to determine causative effects on age-related changes or impacts of cardiovascular interventions, such as aerobic exercise. Computation-enabled imaging of the micro-vascular topology will usher in a continuum of research examining the variation of the metabolic support of brain neurons and glial cells in aging or disease. Integration of Research and Education: Knowledge gained from this project will be disseminated as computer simulations and data relating to micro-vascular flow through the Physiome organization and through web sites associated with other human physiology simulation codes being developed by the research team. This information will be integrated into undergraduate and graduate course offerings by the research team, including: Modeling Human Physiology, Modeling Human Physiology Lab, Cellular Bioenergetics, and other fluid mechanics and mass transport courses.