Multiscale Dynamic Measurements and Modeling of Cerebrovascular Physiology

描述(申请人提供)：功能磁共振成像(FMRI)正在推动脑科学的革命，为了解大脑的正常功能组织及其在疾病期间的变化提供了新的见解。然而，越来越明显的是，通过fMRI测量的血流动力学反应在受试者之间和受试者内部可能会有很大的差异，因为血流和氧合受到潜在神经元和代谢过程以外的因素的影响。因此，如果功能磁共振成像提供了更直接的大脑激活测量方法，那么它的实用性将会提高。在这个方向上的一个重要努力是使用血液动力学指标来估计脑氧代谢率(CMRO2)，这是一种代谢标记物，在健康和疾病中与大脑激活更直接地联系在一起。然而，这一估计依赖于血管对神经元和代谢信号的反应模型。血流动力学对脑激活的反应主要是由活跃的小动脉扩张和氧气消耗驱动的，对于这一点，定性的生物物理模型在概念上是简单的，并且很容易用来估计CMRO2。在分析功能磁共振成像和光学数据时，利用血管和氧气运输反应的这种定性模型正变得越来越普遍；然而，对该方法的准确性几乎没有得到证实。在先进的显微成像方法直接测量小动脉扩张和耗氧量的指导下，结合详细的显微血管解剖网络(VAN)模型，我们将开发一个基于Windkesel模型的定性模型来准确估计CMRO2。我们的目标是建立方法学的准确性，为其在基础科学和临床护理中与功能磁共振成像和光学成像一起常规使用奠定基础。先进的光学显微镜方法是脑生理学新发现的核心，因为它们能够以亚细胞分辨率测量多个生理过程。基于这些可测量量的VAN模型需要集成来自多个描述性实验的结果，并能够对从微观到宏观的脑血管生理学进行更严格和可测试的检查。我们将把我们的VAN模型与新的脑血管生理学光学显微镜测量相结合，以了解与估计人类CMRO2相关的参数，如不同血管段的顺应性，小动脉、毛细血管和小静脉壁的氧气渗透性，组织的氧气外流，以及组织的氧气储备。然后，我们将利用这个VAN模型来确定集总参数Winkesel模型的准确性，这更有利于对人脑成像数据的常规分析。

DESCRIPTION (provided by applicant): Functional magnetic resonance imaging (fMRI) is driving a revolution in the brain sciences, providing new insights into the brain's normal functional organization and its alteration during disease. However, it is becoming clear that hemodynamic responses measured by fMRI can have a large variation between and within subjects as blood flow and oxygenation are influenced by factors other than the underlying neuronal and metabolic processes. Thus, the utility of fMRI would be improved if it provided more direct measures of brain activation. One important effort in this direction is using the hemodynamic measures to estimate the cerebral metabolic rate of oxygen (CMRO2), a metabolic marker that is more directly coupled to brain activation in health and disease. However, the estimation is dependent on a model of the vascular response to neuronal and metabolic signals. The hemodynamic response to brain activation is driven primarily by active arteriolar dilation and oxygen consumption, for which a qualitative biophysical model is conceptually straightforward and easily used to estimate CMRO2. Utilization of such qualitative models of the vascular and oxygen transport responses are becoming more common in analyzing fMRI and optical data; however there has been little confirmation of the accuracy of the methodology. Guided by direct measures of arteriole dilation and oxygen consumption by advanced microscopic imaging methods and a detailed microscopic vascular anatomical network (VAN) model, we will develop a qualitative model based on the windkessel model to accurately estimate CMRO2. Our goal is to establish the accuracy of the methodology to set the foundation for its routine use with fMRI and optical imaging in basic science and clinical care. Advanced optical microscopy methods are central to new discoveries in cerebrophysiology through their ability to measure multiple physiological processes with sub-cellular resolution. A VAN model, based on these measurable quantities, is required to integrate results from multiple descriptive experiments and to enable a more rigorous and testable examination of the cerebrovascular physiology that scales from the microscopic to the macroscopic. We will advance our VAN model in concert with novel optical microscopy measurements of the cerebrovascular physiology to learn about parameters relevant to the estimate of CMRO2 in humans such as the compliance of different vascular segments, the oxygen permeability of arteriole, capillary, and venules walls, the oxygen efflux from the tissue, and tissue oxygen reserve. We will then utilize this VAN model to determine the accuracy of the lumped parameter windkessel model, which is more conducive to routine analysis of human brain imaging data.