High resolution functional MRI of columnar structures

柱状结构的高分辨率功能 MRI

• 批准号: 6804046
• 负责人: RAVI S MENON
• 金额: $ 8.1万
• 依托单位: JOHN P. ROBARTS RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-27 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6804046
• 关键词: Macaca; bioimaging /biomedical imaging; blood volume; brain; brain circulation; brain electrical activity; cytochrome oxidase; electrodes; electrophysiology; fiber optics; functional magnetic resonance imaging; hemodynamics; infrared spectrometry; neurophysiology; oximetry; oxygen transport; ultrasound blood flow measurement

Revised Abstract: Functional magnetic resonance imaging (fMRI) has become the major tool for examining human brain function in sensory and cognitive neuroscience. Despite this enormous acceptance across many disciplines, fundamental aspects of the fMRI response remain poorly understood in large part because of difficulties in linking studies in animal models under the confounding effects of anesthesia with those done in awake humans. The studies proposed here are aimed at understanding the links between neural activity in the brain, the blood flow, blood volume and blood and tissue oxygenation changes that follow, and the fMRI signal. These experiments will be performed in an awake animal model. Awake animal models have the greatest relevance to human neuroscience, with the major advantage that they still allow minimally invasive multi-modality measurements of electrophysiology, oximetry and flow. Our previous NIH funded high-resolution fMRI data in humans has motivated us to develop a better understanding of the spatio-temporal characteristics of the fMRI signal. The techniques we will use to accomplish this are fMRI (BOLD and AST based), electrophysiology, fluorescence quenching, laser Doppler and near-infrared spectroscopy at high spatial and temporal resolution in a well-characterized animal model. Well-known modular functional organization of the primary visual cortex (V1) offers us a variety of opportunities to explore the source of the fMRI signal. Our fundamental hypothesis is that hemodynamic responses to neural activity are modulated at a sub-millimeter scale in this model brain system. A consequence of this hypothesis is that we would predict that fMRI signals should reflect functional specialization of neurons at the cortical columnar and lamellar level. In order to test our fundamental hypothesis, we propose 6 experiments with the following 3 Specific Aims. Specific Aim 1 will be to optimize fMRI parameters to obtain the highest spatial selectivity and sensitivity of BOLD and arterial spin tagging (AST) in-vivo. Specific Aim 2 will be to determine the spatial extent and temporal dependence of the fundamental underlying physiological quantities that the BOLD and AST signal depends on. Specific Aim 3 will be to use the responses of the quantities measured in Specific Aim 1 and 2 to generate a multi-parametric model that explains the BOLD effect in terms of its underlying physiological parameters. To quantify BOLD and AST resolution of functional domains in the horizontal direction in the cortex, we will examine the physiologic and fMRI responses in ocular dominance columns (ODCs). To quantify the BOLD resolution in the vertical direction (depth) in cortex, we will measure these responses as a function of cortical layer. Electrical activity will be measured using both local field potentials and unit activity using tungsten electrodes. The redox state of the mitochondrial enzyme cytochrome oxidase (Cyt-aa3) in the cells will be measured using a novel near-infrared (NIR) spectrometer of our own design. The partial pressure of oxygen in the tissue (pO2) will be measured using a commercial fluorescence-lifetime fiber optic technique (Oxylite, Oxford Optronix). The concentrations of oxyhemoglobin [HbO] and deoxyhemoglobin [Hbr] will also be measured using NIR spectroscopy (NIRS). Blood flow will be measured using a commercial fiber optic laser Doppler flow system (Oxyflow, Oxford Optronix).

修订摘要：功能磁共振成像（fMRI）已成为检查人脑功能在感觉和认知神经科学中的主要工具。尽管在许多学科中接受了这一巨大的接受，但fMRI反应的基本方面在很大程度上仍然很少了解，因为在麻醉的混杂作用与清醒人类的混杂作用下，动物模型的研究很难联系起来。此处提出的研究旨在了解大脑中神经活动，血液流量，血液体积和血液和组织氧合随后的变化与fMRI信号之间的联系。这些实验将在清醒的动物模型中进行。清醒的动物模型与人类神经科学具有最大的相关性，其主要优势是它们仍然允许对电生理学，血氧饱和度和流动的微创多模式测量。 我们以前的NIH资助了人类的高分辨率功能磁共振成像数据，激励了我们更好地了解fMRI信号的时空特征。我们将用来实现此目的的技术是fMRI（基于BOLD和AST），电生理学，荧光淬灭，激光多普勒和近红外光谱在高空间和时间分辨率下在良好的动物模型中。主要的视觉皮层（V1）的著名模块化功能组织为我们提供了探索fMRI信号来源的各种机会。我们的基本假设是，在该模型大脑系统中，对神经活动的血液动力学反应以亚毫米量表进行调节。该假设的结果是，我们将预测fMRI信号应反映在皮质柱和层状水平上神经元的功能专业化。为了检验我们的基本假设，我们提出了6个实验，其中3个特定目标。具体目标1将是优化fMRI参数，以获得大胆和动脉自旋标记（AST）的最高空间选择性和灵敏度。具体目标2将是确定大胆和AST信号所依赖的基本基本生理量的空间范围和时间依赖性。特定目的3将使用特定目标1和2中测量的数量的响应来生成多参数模型，该模型用其潜在的生理参数来解释大胆效应。为了量化皮质水平方向上功能域的粗体和AST分辨率，我们将检查眼部优势柱（ODC）中的生理和fMRI响应。 为了量化皮层垂直方向（深度）的粗体分辨率，我们将测量这些响应是皮层层的函数。电活动将使用局部电位和使用钨电极同时测量。线粒体酶细胞色素氧化酶（CYT-AA3）的氧化还原状态将使用我们自己设计的新型近红外（NIR）光谱仪进行测量。将使用商业荧光长期光纤技术（Oxylite，Oxylite，Oxford optronix）测量组织中氧的部分压力（PO2）。还将使用NIR光谱法（NIRS）测量氧气血红蛋白[HBO]和脱氧血红蛋白[HBR]的浓度。血流将使用商用光纤激光多普勒流动系统（Oxyflow，Oxford Optronix）进行测量。