The Hemodynamic Response to Brain Activation

描述（由申请人提供）：功能磁共振成像（fMRI）是许多基础神经科学研究的重要组成部分，为绘制工作中的人脑激活模式提供了强大的工具。然而，由于当前技术缺乏敏感性，而且缺乏对局部血流动力学反应的性质和变异性以及相关的血氧水平依赖性（BOLD）信号激活反应的了解，这些技术进入临床领域的速度很慢。 由于血流动力学反应 (HR) 是大脑中将神经活动与血流和能量代谢联系起来的关键生理过程，因此对 HR 的详细表征有可能为疾病的早期评估和相关病理生理学的研究提供强大的探针。阻碍这些临床应用开发进展的三个问题是：1) 即使在健康受试者中，BOLD 效应也存在很大差异，因此很难检测个体受试者之间有意义的差异，2) BOLD 响应中的非线性引入了对所用实验设计的强烈依赖性，以及 3) 在疾病人群中观察到的 BOLD 响应变化的解释本质上是不明确的，因为 BOLD 效应取决于脑血流量 (CBF)、脑氧代谢率 (CMRO2) 和脑血的综合变化体积（CBV）。 该提议的基础是这样的假设：使用动脉自旋标记 (ASL) 技术同时测量 CBF 响应和 BOLD 响应，当使用 HR 动态模型进行分析时，将极大地扩展 HR 测量的特异性和可靠性。为了验证这种方法的可行性，我们将：1）通过测试使用一个实验设计计算的模型参数是否允许准确预测不同实验设计的响应，验证所提出的模型是否足以描述 CBF 和 BOLD 响应； 2) 确定同一受试者重复研究中HR参数测量的再现性，并评估年轻健康成人中参数的变异性； 3) 确定静息 CBF、CMRO2 变化和 CBV 变化对 BOLD 反应变异性的影响程度，以及 4) 确定 HR 参数在健康发育和衰老过程中是否存在显着变化。

DESCRIPTION (provided by applicant): Functional magnetic resonance imaging (fMRI) is an essential part of many basic neuroscience studies, providing a powerful tool for mapping patterns of activation in the working human brain. However, these techniques have been slow to move into the clinical realm, due both to a lack of sensitivity of current techniques and also to a lack of understanding of the nature and variability of the local hemodynamic response and the associated Blood Oxygenation Level Dependent (BOLD) signal response to activation. Because the hemodynamic response (HR) is the key physiological process in the brain linking neural activity with blood flow and energy metabolism, a detailed characterization of the HR has the potential to provide a powerful probe for early assessment of disease and for investigations of the pathophysiology involved. There are three problems blocking progress in the development of these clinical applications: 1) The BOLD effect is highly variable even in healthy subjects, making it difficult to detect meaningful differences between individual subjects, 2) Nonlinearities in the BOLD response introduce a strong dependence on the experimental design used, and 3) The interpretation of alterations in the BOLD response observed in a disease population is intrinsically ambiguous because the BOLD effect depends on combined changes in cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and cerebral blood volume (CBV). The basis for this proposal is the hypothesis that simultaneous measurement of the CBF response and the BOLD response using arterial spin labeling (ASL) techniques, when analyzed with a dynamic model for the HR, will greatly expand the specificity and reliability of HR measurements. To validate the feasibility of this approach we will: 1) verify that the proposed model is adequate for describing the CBF and BOLD responses by testing whether the model parameters calculated with one experimental design allow accurate prediction of the responses with a different experimental design; 2) determine the reproducibility of the HR parameter measurements in repeated studies on the same subject, and assess the variability of the parameters in young healthy adults; 3) determine the degree to which variations in resting CBF, CMRO2 changes and CBV changes contribute to the variability of the BOLD response, and 4) determine whether there is a significant variation in the HR parameters with healthy development and aging.