Multiscale Dynamic Measurements and Modeling of Cerebrovascular Physiology

描述（由申请人提供）：功能性磁共振成像（fMRI）正在推动脑科学的革命，为大脑的正常功能组织及其在疾病期间的变化提供新的见解。然而，越来越清楚的是，通过fMRI测量的血流动力学反应可以在受试者之间和受试者内具有很大的变化，因为血流和氧合受到除了潜在的神经元和代谢过程之外的因素的影响。因此，如果功能磁共振成像能提供更直接的大脑活动测量方法，那么它的实用性将会得到提高。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（CMRO2），这是一种与健康和疾病中的脑激活更直接相关的代谢标志物。然而，该估计依赖于对神经元和代谢信号的血管响应的模型。对脑激活的血液动力学响应主要由主动小动脉扩张和耗氧量驱动，对此，定性生物物理模型在概念上是直接的，并且易于用于估计CMRO2。利用这种定性模型的血管和氧气运输的反应，在分析功能磁共振成像和光学数据变得越来越普遍，但很少有确认的方法的准确性。通过先进的显微成像方法和详细的显微血管解剖网络（货车）模型直接测量小动脉扩张和耗氧量，我们将开发一个基于windkessel模型的定性模型，以准确估计CMRO2。我们的目标是建立该方法的准确性，为其在基础科学和临床护理中与fMRI和光学成像的常规使用奠定基础。先进的光学显微镜方法通过其测量具有亚细胞分辨率的多个生理过程的能力，对神经生理学的新发现至关重要。一个货车模型，基于这些可测量的量，需要整合多个描述性实验的结果，并使一个更严格的和可测试的检查脑血管生理学的尺度从微观到宏观。我们将推进我们的货车模型与脑血管生理学的新光学显微镜测量，以了解与人体CMRO2估计相关的参数，例如不同血管段的顺应性，小动脉，毛细血管和小静脉壁的氧渗透性，组织的氧流出量和组织氧储备。然后，我们将利用该货车模型来确定集总参数windkessel模型的准确性，这更有利于对人脑成像数据进行常规分析。

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.