Dynamics of oxygen metabolism in the human brain

人脑氧代谢动态

• 批准号: 8770674
• 负责人: RICHARD BRUCE BUXTON
• 金额: $ 23.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8770674
• 关键词: Accounting; Address; Agreement; Bayesian Modeling; Behavior; Blood Vessels; Blood Volume; Brain; Brain region; Calibration; Cerebrovascular Circulation; Cerebrum; Complex; Development; Disease; Dissociation; Functional Magnetic Resonance Imaging; Future; Goals; Health; Hemoglobin; Human; Hypercapnia; Hyperoxia; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Metabolism; Methodology; Methods; Modeling; Motivation; Organ; Oxygen; Pharmaceutical Preparations; Photic Stimulation; Physiological; Positron-Emission Tomography; Research; Resolution; Series; Signal Transduction; Spin Labels; Stimulus; Techniques; Testing; Theoretical model; Time; Uncertainty; Venous; Work; age effect; age group; area striata; base; blood flow measurement; blood oxygen level dependent; blood oxygenation level dependent response; deoxyhemoglobin; healthy aging; high risk; imaging modality; innovation; novel; novel strategies; public health relevance; relating to nervous system; research study; response; tool; visual stimulus

DESCRIPTION (provided by applicant): Our overall goal is to establish the basis for a new experimental paradigm for functional magnetic resonance imaging (fMRI) that makes possible quantitative measurement of the dynamics of the cerebral metabolic rate of oxygen metabolism (CMRO2) noninvasively in the human brain. Functional MRI methods based on blood oxygenation level dependent (BOLD) signal changes clearly have the potential to provide a window on CMRO2 dynamics, using simultaneous measurement of both the BOLD response to activation and the cerebral blood flow (CBF) response with a spiral dual-echo arterial spin labeling (ASL) technique. We and others have combined these tools in calibrated-BOLD studies to quantify changes in CMRO2, but these studies have focused on sustained changes in an approximate steady-state. The primary obstacle to extending these methods to measuring full CMRO2 dynamics is a physiological question: Do the dynamics of venous cerebral blood volume (CBVV) strongly differ from the dynamics of CBF? The key variable needed to estimate the dynamics of CMRO2 is the dynamics of the venous hemoglobin saturation, and the basic problem is that the BOLD effect depends primarily on changes in total deoxyhemoglobin, and thus also on the dynamics of venous blood volume. Dynamic measurements of CBF and BOLD signals provide sufficient information to estimate CMRO2 dynamics only if CBVV follows CBF. A primary example of this fundamental ambiguity of the BOLD signal is a long-standing issue in fMRI: is the post-stimulus undershoot of the BOLD signal a neural, vascular or metabolic effect? Despite considerable effort by many groups, there is still no clear answer, and the possibility of a dissociation of venous blood volume changes from CBF changes due to different dynamic time constants currently stands in the way of developing reliable tools for measuring CMRO2 dynamics. The motivation for this high risk/high gain proposal is that our recent studies of the effect of hyperoxia on the BOLD signal suggest a novel approach for addressing this primary physiological question, with a method that is specifically sensitive to CBVV. In addition, current models for the BOLD response and for analyzing the ASL experiment are essentially steady-state models, and these need to be expanded to include full dynamics. We will address these two basic limitations to measuring CMRO2 dynamics with two Aims. Aim 1: Extend our current modeling framework to include dynamics as well as potentially confounding physiologically variables, and use this to develop a Bayesian framework for estimating CMRO2 dynamics. Aim 2: Using the post- stimulus undershoot as a test case, use the hyperoxia approach to measure the dynamics of CBVV in human primary visual cortex in response to visual stimuli with varying duration and intensity. The endpoint will be a novel assessment of the dynamics of CBVV that will establish the feasibility of measuring the dynamics of CMRO2 for future applications in health and disease.

描述（由申请人提供）：我们的总体目标是为功能磁共振成像（fMRI）建立新的实验范式的基础，以使氧代谢性（CMRO2）在人脑中的大脑代谢速率（CMRO2）的动力学进行定量测量。基于血液氧化水平依赖性（BOLD）信号变化的功能性MRI方法显然有可能提供CMRO2动力学的窗口，同时测量对激活的大胆反应和脑血流（CBF）响应，并使用螺旋双回波动脉旋转旋转旋转（ASL）技术。我们和其他人将这些工具结合在校准的研究研究中，以量化CMRO2的变化，但是这些研究集中在近似稳态的持续变化上。将这些方法扩展到完整CMRO2动力学的主要障碍是一个生理问题：静脉脑血体积（CBVV）的动力学是否与CBF动力学有很大不同？估计CMRO2动力学所需的关键变量是静脉血红蛋白饱和度的动力学，基本问题是，大胆效应主要取决于总脱氧血红蛋白的变化，因此也取决于静脉血体积的动力学。 CBF和BOLD信号的动态测量可提供足够的信息来估计CMRO2动力学，只有CBVV遵循CBF。 BOLD信号的这种基本歧义的一个主要例子是fMRI中的一个长期存在的问题：大胆信号的刺激后刺激性是否存在神经，血管或代谢效应？尽管许多小组的努力巨大的努力，但仍然没有明确的答案，并且由于目前不同的动态时间常数而导致的CBF变化变化的可能性可能会开发出可靠的工具来测量CMRO2动力学。这一高风险/高收益建议的动机是，我们最近对高氧对大胆信号的影响的研究提出了一种解决这一主要生理问题的新方法，该方法对CBVV特别敏感。此外，目前的大胆响应模型和分析ASL实验的模型本质上是稳态模型，并且需要扩展这些模型，以包括完整的动态。我们将解决以两个目标测量CMRO2动态的这两个基本局限性。 AIM 1：将当前的建模框架扩展到包括动力学以及潜在地混淆生理变量，并使用它来开发贝叶斯框架来估计CMRO2动力学。 AIM 2：使用后刺激效力为测试案例，使用高氧方法来测量人类原发性视觉皮层中CBVV的动力学，以响应视觉刺激，并具有不同的持续时间和强度。终点将是对CBVV动力学的新评估，该评估将确定测量CMRO2在健康和疾病中应用的可行性。