Project 4

项目4

• 批准号: 10649652
• 负责人: ANDREAS A LINNINGER
• 金额: $ 60.39万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-16 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649652
• 关键词: 3-Dimensional; Address; Animals; Arteries; Biological; Biophysics; Blood; Blood Vessels; Blood capillaries; Blood flow; Brain; Cerebrovascular Circulation; Cerebrum; Collaborations; Coupled; Data; Diameter; Endothelial Cells; Equilibrium; Exercise; Face; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Gap Junctions; Goals; Human; Individual; Knowledge; Link; Liquid substance; Magnetic Resonance Imaging; Maps; Mathematics; Microcirculation; Modeling; Neurons; Oxygen; Pattern; Perfusion; Periodicity; Phase; Physics; Physiological; Property; Regulation; Resistance; Rest; Signal Transduction; Smooth Muscle; Smooth Muscle Myocytes; Specificity; Surface; Testing; Tissues; Vascular blood supply; Vasomotor; Work; arteriole; constriction; experimental study; hemodynamics; human subject; in vivo; mathematical model; neuroregulation; neurovascular; programs; reconstruction; response; simulation; spatiotemporal; theories; two-dimensional; vasomotion; venule

PROJECT SUMMARY/ABSTRACT – PROJECT 4 We propose to leverage our state-of-the-art expertise in theoretical biological physics and computational fluid dynamics to investigate fundamental aspects of the pial neurovascular circuit and its impact upon cortical blood supply and oxygenation. Project 4 will provide a quantitative path from in vivo responses in animal subjects (Projects 1 and 2) to the interpretation of fMRI data across human subjects (Project 3). This program will establish a link between observable neurovascular responses and the internal brain state. In particular, Project 4 will collaborate with Project 1 to integrate experimental knowledge of pial neurovascular circuit oscillations; it will collaborate with Project 2 to incorporate knowledge on the modulation of neuronal and vascular activity; finally, it will impact Project 3 by using blood oxygenation models to determine BOLD fMRI signals in response to pial neurovascular patterns. Project 4 features two specific aims: (ii) Capture the spatiotemporal neurovascular dynamics and the patterns of the pial vascular network, that is, the dilation and constriction of arterioles driven by their smooth muscle sheath; and (ii) Demonstrate the effects of the vasomotor dynamics onto the cortical blood supply and tissue pO2, thereby establishing a causal link between BOLD/CBV fMRI signals and neuronal activity patterns. For Aim 1, we shall rely on long standing experimental evidence for ultraslow, ~ 0.1 Hz oscillations of individual arteriole segments, as well as preliminary data of Project 1 on the pial neurovascular network. Their combination leads to our theoretical framework of brain arterioles forming a network of coupled oscillators that control the flow of blood throughout the entire brain. Our first goal is to develop coupled-oscillator-based mathematical models that capture the essence of the observed neurovascular and neuromodulatory dynamics across the cortical mantle and propose experimental tests. Our second goal is to demonstrate how the competition between modulatory drives and intrinsic oscillations of arterioles results in spatial parcellation and formation of the different constellations of temporally coherent regions, as observed in Projects 1 to 3. For Aim 2, we will use detailed hemodynamic simulations with an existing three dimensional reconstruction of the cortical microcirculation to gauge the regulatory effect of vasomotor actuation, modeled in the first aim and observed in experiments of Projects 1 and 2, on induced changes in cortical blood and oxygen supply. The effects of rhythmic changes in pial arteriole diameter upon the cerebral blood flow and dynamic resistance redistributions in microvessels will be specifically dissected to establish the feed forward regulation that vasomotor exercises upon cortical blood supply and tissue pO2. Vasomotor-modulated blood flow will be further used to compute spatiotemporal oxygenation maps throughout the depth of cortical layers and across the pial surface. Those maps will provide the link between the dynamics of oxygenation and the pial network, which will inform our inferences of the brain state and neuromodulatory inputs from BOLD fMRI signals.

项目摘要/摘要 - 项目4 我们建议利用理论生物物理学和计算的最先进的专业知识 流体动力学以研究皮尔神经血管回路的基本方面及其对皮质的影响 血液供应和氧合。项目4将提供来自动物体内反应的定量路径 对人类受试者fMRI数据解释的受试者（项目1和2）（项目3）。这个程序 将在可观察到的神经血管反应与内部大脑状态之间建立联系。尤其， 项目4将与项目1合作，以整合伴有伴石神经血管电路的实验知识 振荡；它将与项目2合作，以纳入有关神经元调节的知识和 血管活性；最后，它将通过使用血液氧合模型来确定大胆fMRI来影响项目3 响应于伴有脊髓神经血管模式的信号。 项目4具有两个具体目的：（ii）捕获时空神经血管动力学和 丘疹血管网络的模式，即由它们的平滑驱动的小动脉的扩散和收缩 肌肉鞘； （ii）证明血管舒缩动力学对皮质血液供应和 组织PO2，从而在BOLD/CBV FMRI信号和神经元活动模式之间建立因果关系。 对于AIM 1，我们将依靠长期的实验证据进行超声，〜0.1 Hz的振荡 单个动脉片段，以及PIAL神经血管网络上项目1的初步数据。他们的 组合导致我们的理论框架，形成了一个耦合振荡器网络，该网络 控制整个大脑的血液。我们的第一个目标是开发基于耦合振荡的人 捕获观察到的神经血管和神经调节动力学的本质的数学模型 跨皮质地幔和建议实验测试。我们的第二个目标是证明 调节驱动器与动脉固有振荡之间的竞争导致空间细胞和 如项目1至3所示，暂时相干区域的不同星座的形成。 对于AIM 2，我们将使用现有三维重建的详细血液动力学模拟 皮质微循环以衡量血管舒缩致动的调节作用，以第一个目的建模 并在项目1和2的实验中观察到有关皮质血液和氧气供应变化的变化。 丘疹动脉直径的节奏变化对脑血流和动态抗性的影响 将专门阐述微血管中的重新分配，以建立饲料的前备法规 皮质血液供应和组织PO2时进行血管舒缩运动。血管舒马调节的血流将是 进一步用于计算整个皮质层深度和跨越的时空氧合图 折面表面。这些地图将提供氧合动力学和pial网络之间的联系， 这将告知我们对大脑状态和来自大胆fMRI信号的神经调节输入的推论。