PHYSIOLOGICAL BASIS OF FUNCTIONAL MRI

在过去的几年里，功能性磁共振成像（fMRI） 成为一个强大的和广泛使用的工具，调查工作， 人脑 由于血液引起的MR信号的微小变化 氧合依赖性（BOLD）效应伴随局部变化， 大脑代谢可以用来绘制大脑激活的模式， 执行各种感觉、运动和认知任务。 但 尽管功能磁共振成像技术的广泛使用，基本的生理 观察到的信号变化的生物物理机制是 仍然知之甚少。 拟议工作的总体目标是 回答两个基本问题：1）生理变化是什么 伴随着人类大脑的激活，（2）如何定量 从生理变化的角度解释观察到的MR效应？ 这 该项目汇集了两条研究路线， 我们的实验室在过去的几年里：1）理论数学 对激活期间发生的生理变化进行建模， 将这些变化定量转化为MR信号变化; 2）MRI实验技术的发展和评价 定量灌注测量。 基于理论 在建模过程中，我们围绕两个核心假设构建了这个项目： 1)脑氧代谢（CMRO 2）和脑血 脑血流（CBF）在大脑激活过程中紧密耦合，但在一个 非线性方式需要CBF的大变化来支持小的 由于从毛细管中提取的氧气有限，CMRO 2发生变化; 2）在fMRI中观察到的信号变化的时间轮廓 实验对血液的相对时间过程高度敏感， 在激活过程中流量和血容量发生变化。 这些假设将 使用最近开发的MRI技术进行测试，以测量 灌注和血容量的变化与传统的 fMRI信号对血氧敏感。 实验将测量 这些生理变量的变化，在性能的四个 刺激类型（感觉运动、视觉、听觉和认知）。 要进行的三组实验是：1）可变刺激 振幅以改变生理反应; 2.高时间 BOLD信号的时间过程的分辨率测量，血流 和血容量变化;以及3）持续激活以测试 CBF和CMRO 2的连续偶联。 此外，理论上 模型将进一步发展，包括粘弹性性能的 血管 这项工作的最终结果将是一个实验性的， 伴随的生理变化的理论表征 人类大脑激活。

In the last few years functional magnetic resonance imaging (fMRI) has become a powerful and widely used tool for investigating the working human brain. The small changes in the MR signal due to the Blood Oxygenation Dependent (BOLD) effect that accompany local changes in brain metabolism can be used to map patterns of brain activation during performance of a variety of sensory, motor and cognitive tasks. But despite the widespread use of fMRI techniques, the basic physiological and biophysical mechanisms underlying the observed signal changes are still poorly understood. The broad goal of the proposed work is to answer two basic questions: 1) What are the physiological changes accompanying human brain activation?, and 2) How can we quantitatively interpret observed MR effects in terms of physiological changes? This project brings together two lines of research that have developed in our laboratory over the last few years: 1) Theoretical mathematical modeling of the physiological changes occurring during activation and the quantitative translation of these changes into MR signal changes; and 2) Development and evaluation of MRI experimental techniques for quantitative perfusion measurements. Based on the theoretical modeling, we have framed this project around two central hypotheses: 1) The changes in cerebral oxygen metabolism (CMRO2) and cerebral blood flow (CBF) are tightly coupled during brain activation, but in a nonlinear fashion requiring large changes in CBF to support small changes in CMRO2 because of limited O2 extraction from the capillary; and 2) The temporal profile of signal changes observed in fMRI experiments is highly sensitive to the relative time courses for blood flow and blood volume changes during activation. These hypotheses will be tested using recently developed MRI techniques for measurement of perfusion and blood volume changes in combination with the conventional fMRI signal sensitive to blood oxygenation. Experiments will measure changes in these physiological variables during performance of four types of stimulation (sensorimotor, visual, auditory, and cognitive). The three sets of experiments to be performed are: 1) variable stimulus amplitude to vary the physiological response; 2. high temporal resolution measurements of the time course of BOLD signal, blood flow and blood volume changes; and 3) sustained activation to test the continued coupling of CBF and CMRO2. In addition, the theoretical models will be further developed to include viscoelastic properties of blood vessels. The end result of this work will be an experimental and theoretical characterization of the physiological changes accompanying human brain activation.