Multiscale modeling of cerebral blood flow and oxygen transport

脑血流和氧运输的多尺度建模

基本信息

批准号：
10231113
负责人：
Timothy W. Secomb
金额：
$ 39.79万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10231113
关键词：
Address Affect Alzheimer&apos s Disease Arizona Arteries Behavior Biological Process Blood Blood Vessels Blood capillaries Blood flow Brain Brain Injuries Brain imaging Caliber Cardiovascular system Cerebral cortex Cerebrovascular Circulation Cerebrum Chronic Computer Models Data Development Disease Erythrocytes Functional Magnetic Resonance Imaging Generations Goals Homeostasis Hypertension Hypotension Hypoxia Image Impairment Individual Lead Link Literature Maps Measures Mechanics Metabolic Methods Microcirculation Microscopic Modeling Multimodal Imaging Mus Neurodegenerative Disorders Normal Range Optical Coherence Tomography Oxygen Oxyhemoglobin Pathologic Perfusion Physiological Physiology Property Regulation Reporting Resistance Resolution Role Stimulus Striated Muscles Stroke Structure Testing Theoretical model Tissues Universities Validation Vascular System Vascular blood supply Work arteriole base blood perfusion brain tissue experimental group experimental study hemodynamics improved in vivo insight medical schools microscopic imaging model development multi-scale modeling nanoprobe neurovascular neurovascular coupling next generation oxygen transport parallel computer phosphorescence physical process predictive modeling relating to nervous system response simulation three dimensional structure tissue oxygenation two photon microscopy

项目摘要

The overall goal of this proposal is to gain quantitative understanding of the relationship between neural activation, blood flow and tissue oxygenation in the brain cortex, using multiscale theoretical models for blood flow, oxygen transport and flow regulation in networks of microvessels. Adequate blood flow to meet spatially and temporally varying demands of brain tissue is crucial, since lack of oxygen quickly leads to irreversible damage. The mechanisms by which blood flow is controlled are poorly understood. Multiple interactions between neural activity, metabolite levels, changes in vascular tone, network blood flow, and oxygen transport are difficult to unravel, and cannot be understood just by observing behavior of individual blood vessels. In the proposed work, the detailed structure of microvessel networks with thousands of segments in the mouse cerebral cortex will be imaged using two-photon microscopy. Observations using phosphorescence quenching nanoprobes will yield high resolution maps of tissue oxygen levels. Spectral domain optical coherence tomography will be used to measure blood flows. The multiscale modeling approach simulates biological and physical processes at the capillary diameter and cellular scale (~10 μm, including flow mechanics and active responses of vessel walls to hemodynamic, neural and metabolic stimuli), at the vessel scale (~100 μm, including segment flow resistance, oxygen loss and propagation of conducted responses along vessel walls) and at the network and tissue scale (~1000 μm, including entire network flows, perfusion, oxygen extraction and tissue hypoxic fraction). Specific Aim 1 is to develop predictive multiscale models for blood flow and oxygen transport in the mouse cerebral cortex, and validate these models using experimental data derived from multimodal imaging of the cortex microvasculature. The proposed studies will provide a model that will reconcile available data at the microscopic level with macroscopic level variables such as perfusion and oxygen extraction and will allow prediction of tissue oxygenation and occurrence of hypoxia for a range of blood perfusion and oxygen demand. Specific Aim 2 is to develop multiscale models for blood flow autoregulation and neurovascular coupling in the mouse cerebral cortex, and to test and refine these models using experimental data derived from multimodal imaging of the cortical microvasculature. The models will include effects of myogenic, metabolic, shear-dependent and conducted responses, as well as the possible role of capillary-level regulation. Models including or excluding these mechanisms will be tested for their ability to represent actual regulatory responses, as reported in the literature and as observed in multimodal imaging experiments under varying physiological conditions. Improved understanding of the mechanisms of flow regulation could lead to improved strategies for disorders related to neurovascular function, including stroke and neurodegenerative diseases, and for interpreting fMRI brain imaging.

该提案的总体目标是定量了解之间的关系使用多尺度理论，大脑皮层的神经激活、血流和组织氧合微血管网络中的血流、氧气运输和流量调节模型。满足脑组织在空间和时间上变化的需求的血流量至关重要，因为缺氧很快就会导致不可逆转的损伤。人们对控制血流的机制知之甚少。神经活动、代谢水平、血管张力变化、网络血流、和氧气的运输很难解开，并且不能仅通过观察个体的行为来理解在拟议的工作中，微血管网络的详细结构具有数千个。小鼠大脑皮层的各个部分将使用双光子显微镜进行观察成像。磷光猝灭纳米探针将产生组织氧水平的高分辨率图。域光学相干断层扫描将用于测量血流。模拟毛细管直径和细胞尺度（~10 μm，包括流量血管壁对血流动力学、神经和代谢刺激的力学和主动反应）规模（~100 μm，包括段流阻、氧损失和传导响应的传播沿着血管壁）以及网络和组织尺度（~1000 μm，包括整个网络流动、灌注、具体目标 1 是开发预测性多尺度模型用于小鼠大脑皮层的血流和氧气运输，并使用以下方法验证这些模型实验数据来自皮层微血管系统的多模态成像。研究将提供一个模型，将微观层面和宏观层面的现有数据进行协调诸如灌注和氧气提取等变量，将允许预测组织氧合和发生缺氧的血液灌注和需氧量的具体目标2是制定的。小鼠大脑血流自动调节和神经血管耦合的多尺度模型皮层，并使用来自多模态成像的实验数据来测试和完善这些模型该模型将包括肌源性、代谢性、剪切依赖性的影响。并进行了回应，以及毛细管水平调节的可能作用，包括或。排除这些机制将测试它们代表实际监管反应的能力，因为文献中报道以及在不同生理条件下的多模态成像实验中观察到更好地了解流量调节机制可能会导致改进策略。与神经血管功能相关的疾病，包括中风和神经退行性疾病，以及解释功能磁共振成像脑成像。