Multiscale Dynamic Measurements and Modeling of Cerebrovascular Physiology

描述（由申请人提供）：功能磁共振成像（fMRI）正在推动脑科学的一场革命，为大脑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，越来越清楚的是，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有很大的差异，因为血流和氧合受到潜在的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能提供更直接的大脑活动测量，它的效用将得到改善。在这个方向上的一个重要努力是使用血液动力学测量来估计脑氧代谢率（cro2），这是一种代谢标志物，在健康和疾病中与大脑激活更直接相关。然而，这种估计依赖于血管对神经元和代谢信号的反应模型。脑激活的血流动力学反应主要是由活跃的小动脉扩张和氧气消耗驱动的，对此定性的生物物理模型在概念上是直接的，并且很容易用于估计cmor2。在分析功能磁共振成像和光学数据时，利用这种血管和氧转运反应的定性模型变得越来越普遍；然而，这种方法的准确性几乎没有得到证实。在先进的显微成像方法和详细的显微血管解剖网络（VAN）模型的指导下，我们将建立一个基于风管模型的定性模型来准确估计cmor2。我们的目标是建立方法的准确性，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的常规应用奠定基础。先进的光学显微镜方法通过其测量亚细胞分辨率的多种生理过程的能力，是脑生理学新发现的核心。需要基于这些可测量量的VAN模型来整合多个描述性实验的结果，并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模型与脑血管生理学的新型光学显微镜测量相结合，以了解与人类cmor2估计相关的参数，如不同血管段的顺应性，小动脉、毛细血管和小静脉壁的氧通透性，组织的氧外排和组织氧储备。然后，我们将利用该VAN模型来确定集总参数风帆模型的精度，该模型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.