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

描述（由申请人提供）：血液和组织之间的营养物质和废物的功能性交换发生在微血管中，从小动脉通过毛细血管延伸到小静脉。皮质微血管网络可以通过拓扑特征来描述，例如：血管密度、连贯通路中微血管的取向、分支和迂曲度。迂曲是脑组织收缩时微血管的卷曲和成环，发生在健康衰老和病理条件下。微血管拓扑结构的这种变化对皮层神经元和神经胶质细胞的营养输送和废物清除具有重要意义。拟议的美国-法国合作努力的主要目标是开发一种计算成像方法，以量化脑血管的微观结构，并预测其在老龄化受试者的演变。 目的和方法：该研究小组开发了几种针对大脑中微血管流动不同特征的MRI方法，包括使用具有体素内非相干运动（IVIM）技术的扩散加权成像方案，以及使用具有信号强度增强（FENSI）方法的血液局部磁标记。这些技术提供了多样化的信息和可调的灵敏度，以调查微血管流量。结合血管树的计算机模拟，可以使用这些措施提取微血管的结构特征。将采用组织学研究衰老动物模型，以确定大脑不同区域的血管拓扑结构，并确定与年龄相关的拓扑变化，特别是迂曲度增加。该信息将用于执行微血管流的大规模模拟，以表征微血管拓扑特征与MRI信号之间的关系。将进行动物MRI实验，随后进行组织学检查，以确认MRI无创提供的血管拓扑表征。然后，将使用动物年龄相关的拓扑特征来预测人类年龄相关的血管变化，并将进行人类血管网络和MRI采集的大规模模拟。年轻和老年成年受试者的MRI采集将以非侵入性方式表征人体皮质中受试者特定的血管拓扑结构和解剖学特定的血管变化。智力优势：先前对特定大脑区域的拓扑结构的研究是通过对死后组织的侵入性方法进行的，并导致对不同年龄的平均大脑变化的讨论，而不是特定于特定个体。所提出的MRI方法将允许非侵入性探测人类灰质中的微血管拓扑结构。这是可能的，因为（a）由MRI序列提供的高空间分辨率，其可以在血管组织的空间尺度上解析皮质层，以及（B）复杂微血管网络上的MRI信号的数值模拟。微血管拓扑结构的体内表征将提供皮质中区域变化的定量描述，这可以形成微血管拓扑结构图谱的基础。此外，它将提供定量措施的拓扑结构的破坏与年龄在特定主题和特定区域的方式。更广泛的影响：衰老与脑血流量减少、血管反应性降低以补偿挑战或刺激以及大脑中毛细血管微观结构的改变有关。与这些变化相关的是认知能力的下降。随着美国和欧洲人口的老龄化，确定老龄化人口如何保持长寿，生产力和独立生活至关重要。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，以确定对年龄相关变化或心血管干预（如有氧运动）影响的因果关系。微血管拓扑结构的计算成像将带来一系列研究，研究大脑神经元和神经胶质细胞在衰老或疾病中的代谢支持变化。研究和教育的一体化：从该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体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：人体生理学建模，人体生理学建模实验室，细胞生物能量学以及其他流体力学和质量运输课程。

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.