The Hemodynamic Response to Brain Activation

对大脑激活的血流动力学反应

• 批准号: 6668666
• 负责人: RICHARD BRUCE BUXTON
• 金额: $ 36.1万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668666
• 关键词: bioenergetics; biological signal transduction; brain circulation; brain electrical activity; clinical research; functional magnetic resonance imaging; hemodynamics; human subject; neural information processing; neuroanatomy; neurophysiology; oxygen; visual stimulus

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.

描述（由申请人提供）：功能性磁共振成像（fMRI）是许多基础神经科学研究的重要组成部分，为绘制工作人脑中的激活模式提供了强大的工具。然而，这些技术进入临床领域的速度很慢，这是因为当前技术缺乏敏感性，而且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）信号缺乏了解。对激活的反应。 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有力的探针。有三个问题阻碍了这些临床应用的发展：1）即使在健康受试者中，BOLD效应也是高度可变的，使得难以检测个体受试者之间的有意义的差异，2）BOLD响应中的非线性引入了对所使用的实验设计的强烈依赖，和3）在疾病人群中观察到的BOLD反应的改变的解释本质上是模糊的，因为BOLD效应取决于脑血流量（CBF）的组合变化，脑氧代谢率（CMRO 2）和脑血容量（CBV）。 该建议的基础是假设使用动脉自旋标记（ASL）技术同时测量CBF反应和BOLD反应，当用HR的动态模型分析时，将大大扩展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，来验证所提出的模型足以描述CBF和BOLD响应; 2）确定在对同一受试者的重复研究中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、CMRO 2变化和CBV变化的变化对BOLD响应的变异性的贡献程度，以及4）确定HR参数是否随着健康发育和衰老而存在显著变异。