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）的新实验范例奠定基础，使无创地定量测量人脑中氧代谢的大脑代谢率（CMRO2）的动态成为可能。基于血氧水平依赖性 (BOLD) 信号变化的功能性 MRI 方法显然有可能为 CMRO2 动态提供一个窗口，通过螺旋双回波动脉自旋标记 (ASL) 技术同时测量 BOLD 对激活的反应和脑血流 (CBF) 反应。我们和其他人在校准 BOLD 研究中结合了这些工具来量化 CMRO2 的变化，但这些研究重点关注近似稳态下的持续变化。将这些方法扩展到测量完整 CMRO2 动态的主要障碍是一个生理问题：静脉脑血量 (CBVV) 的动态与 CBF 的动态有很大不同吗？估计 CMRO2 动态所需的关键变量是静脉血红蛋白饱和度的动态，基本问题是 BOLD 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容量的动态。仅当 CBVV 跟随 CBF 时，CBF 和 BOLD 信号的动态测量才能提供足够的信息来估计 CMRO2 动态。 BOLD 信号这种基本模糊性的一个主要例子是功能磁共振成像中长期存在的问题：BOLD 信号的刺激后下冲是否是神经、血管或代谢效应？尽管许多小组付出了相当大的努力，但仍然没有明确的答案，并且由于不同的动态时间常数而导致静脉血量变化与 CBF 变化分离的可能性目前阻碍了开发用于测量 CMRO2 动态的可靠工具。这一高风险/高增益提议的动机是，我们最近对高氧对 BOLD 信号影响的研究提出了一种解决这一主要生理问题的新方法，即一种对 CBVV 特别敏感的方法。此外，当前用于 BOLD 响应和分析 ASL 实验的模型本质上是稳态模型，需要扩展以包括完整的动力学。我们将通过两个目标解决测量 CMRO2 动态的两个基本限制。目标 1：扩展我们当前的建模框架，以包括动力学以及可能混淆的生理变量，并使用它来开发用于估计 CMRO2 动力学的贝叶斯框架。目标 2：使用刺激后下冲作为测试用例，使用高氧方法测量人类初级视觉皮层中 CBVV 响应不同持续时间和强度的视觉刺激的动态。终点将是对 CBVV 动力学的新颖评估，这将建立测量 CMRO2 动力学的可行性，以供未来在健康和疾病方面的应用。