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

CRCNS：美国法国大学：衰老脑微脉管系统的计算成像

• 批准号: 8646121
• 负责人: Bradley P Sutton
• 金额: $ 13.28万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8646121
• 关键词: Adult; Aerobic Exercise; Age; Aging; Animal Model; Animals; Appearance; Arteries; Atlases; Bioenergetics; Blood; Blood Vessels; Blood capillaries; Blood flow; Brain; Brain region; Caliber; Cardiovascular system; Cerebrovascular Circulation; Cerebrum; Characteristics; Chemicals; Code; Cognitive; Complex; Computer Simulation; Contrast Media; Coupled; Data; Diffusion weighted imaging; Disease; Education; Elderly; Europe; Evolution; Excision; Fibrosis; France; Goals; High Performance Computing; Histology; Human; Image; Impaired cognition; Individual; Intervention; Knowledge; Lead; Link; Liquid substance; Literature; Magnetic Resonance Imaging; Magnetism; Measures; Mechanics; Metabolic; Methods; Microcirculation; Microcirculatory Bed; Modeling; Modification; Monitor; Motion; Motivation; Neuroglia; Neurons; Nutrient; Outcome; Pathway interactions; Patients; Performance; Physics; Physiology; Play; Population; Principal Investigator; Property; Protocols documentation; Rattus; Research; Research Subjects; Resolution; Risk; Role; Scheme; Signal Transduction; Simulate; Stress; Structure; Techniques; Tissue Model; Tissues; Translating; Trees; Validation; Variant; age related; aging brain; aging population; arteriole; base; brain tissue; capillary; density; gray matter; healthy aging; hemodynamics; human data; image processing; in vivo; large scale simulation; neurophysiology; neuropsychological; normal aging; relating to nervous system; research study; simulation; venule; volunteer; wasting; web site; young adult

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.

描述（由申请人提供）：血液和组织之间的营养和废物的功能交换发生在微血管血管中，从小动脉从小动脉延伸到毛细血管并进入静脉。皮质微血管网络可以通过拓扑特征来描述：例如：相干途径中的微官的血管密度，分支和曲折的方向。曲折的曲折是在脑组织收缩时围绕微容器的围绕和循环，并在健康的衰老和病理状况下发生。微血管拓扑的这种变化对养分的递送以及从皮质中神经元和神经胶质细胞的废物清除具有重要意义。拟议的美国法国协作努力的主要目的是开发一种计算成像方法来量化脑脉管系统的微观结构，并预测其在衰老受试者中的演变。 目的和方法：研究团队开发了几种MRI方法，这些方法针对大脑中微血管流的不同特征，包括使用内部射流不相干运动（IVIM）技术使用扩散加权成像方案以及使用信号强度（FENSI）方法的血液的局部磁标记技术的局部磁标记。这些技术提供了多种信息和可调节的灵敏度，以研究微血管流动。结合对血管树的计算机模拟，可以使用这些措施提取微脉管系统的结构特征。将使用组织学调查衰老的动物模型，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，尤其是曲折的增加。该信息将用于对微血管流进行大规模模拟，以表征微血管拓扑特征和MRI信号之间的关系。将进行动物MRI实验，然后进行随后的组织学检查，以确认MRI无创提供的血管拓扑表征。然后，将使用与动物年龄相关的拓扑特征来预测与人类年龄相关的血管变化，并对人类血管网络进行大规模模拟，并进行MRI获取。对年轻和老年受试者的MRI获取将表征受试者特异性的血管拓扑结构和人类皮质中的解剖学特异性血管变化，这是非侵入性的。智力优点：对特定大脑区域拓扑的事先研究是通过侵入性的验尸方法进行的，并导致讨论整个年龄的平均大脑变化，而不是特定的人。提出的MRI方法将允许对人灰质中微血管拓扑的无创探测。这是由于（a）MRI序列提供的高空间分辨率，该分辨率可以在血管组织的空间尺度上解析皮层层，以及（b）复杂微血管网络上MRI信号的数值模拟。微血管拓扑的体内表征将提供对皮质区域变化的定量描述，这可能构成微血管拓扑结构的地图集。另外，它将以特定于主题和特定区域的方式为拓扑的破坏提供定量测量。更广泛的影响：衰老与脑血流的减少有关，血管反应的降低以补偿挑战或刺激，以及对大脑毛细血管微结构的修改。与这些变化相关的是认知表现的降低。随着美国和欧洲的年龄，必须确定老龄化人口如何维持长期，富有成效和独立的生活至关重要。我们的方法将对脉管系统中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（例如有氧运动）的影响。微血管拓扑的计算成像将引入大量研究，以研究衰老或疾病中脑神经元和神经胶质细胞代谢支持的变化。研究和教育的整合：从该项目中获得的知识将被传播，因为计算机模拟和数据与微血管流有关通过生理组织组织以及与研究团队开发的其他人类生理模拟代码相关的网站。该信息将由研究团队纳入本科和研究生课程，包括：建模人类生理学，建模人类生理学实验室，细胞生物能力以及其他流体力学和大规模运输课程。