MRI of cerebral metabolic reactivity

脑代谢反应性MRI

• 批准号: 9036263
• 负责人: DAVID DUBOWITZ
• 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: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9036263
• 关键词: Address; Adopted; Altitude; Area; Attention; Basal Ganglia; Biological; Biological Preservation; Blood Vessels; Blood flow; Brain; Brain region; Carbon Dioxide; Cerebral Hypoxia; Cerebral Ischemia; Cerebrovascular Circulation; Cerebrovascular Insufficiency; Cerebrum; Consumption; Data; Disease; Equilibrium; Exhibits; Failure; Functional disorder; Future; Goals; Homeostasis; Human; Hypoxia; Image; Ischemia; Lead; Link; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Metabolism; Methodology; Methods; Modeling; Oxygen; Parietal; Physiological; Pilot Projects; Predisposition; Pulmonary Valve Insufficiency; Reproducibility; Resistance; Risk; Signal Transduction; Source; Stimulus; Stroke; Techniques; Testing; Tissue Viability; Tissues; Translating; Workplace; base; biophysical model; blood oxygen level dependent; cerebrovascular; cingulate cortex; hemodynamics; improved; innovation; insight; normal aging; novel; novel strategies; public health relevance; response; tissue oxygenation; tool

 DESCRIPTION (provided by applicant): The longterm goal of these studies is to understand the physiological consequences of cerebral hypoxia, and how failure of normal homeostatic mechanisms contributes to cerebral disease. Much attention has been devoted to understanding how cerebrovascular reserve impacts cerebral disease, however this tells only half the story; to understand tolerance to the effects of hypoxia, we also need to know the potential to limit cerebral metabolic activity. The central premise of the current proposal is that during hypoxia or ischemia cerebral tissue viability can maintained if the cerebral blood flow (CBF) can be increased or oxygen metabolism (CMRO2) can be reduced, both of which lead to preservation of local tissue oxygenation (PtiO2). An important determinant of oxygen homeostasis is local CO2; we recently discovered that during hypoxia the influence of CO2 on CMRO2 is increased. Thus CO2 provides a mechanism to both increase CBF (and O2 delivery) and decrease CMRO2 (and O2 consumption). We hypothesize that regional hypoxia tolerance in the brain is determined by the local strength of these hemodynamic and metabolic responses to CO2 in hypoxia (increasing CBF and decreasing CMRO2), which both act to preserve tissue oxygenation. The goals of this project are to determine if CBF and CMRO2 (and hence PtiO2) exhibit this expected difference in CO2 sensitivity during hypoxia in regions with know differences in hypoxia sensitivity. Our methodology allows measurement of regional CBF and CMRO2 responses, based on a novel multi-compartment model Blood Oxygenation Level-dependent (BOLD) signals. In Aim 1 we will test the reproducibility and sources of variance of our new MRI measurements of regional CMRO2 reactivity to CO2 / hypoxia. In Aim 2 we test our hypothesis that regions that are resistant to ischemic insults are better able to maximize local CBF and CMRO2 sensitivity to local CO2. This proposal presents a novel approach to address basic mechanistic questions in cerebral ischemic pathophysiology. The endpoint of this study will be a validated method to characterize CMRO2 reactivity in hypoxia, and a test of our hypothesis regarding regional hypoxia vulnerability in the human brain. These studies will also establish the basis and limitations for translating these novel MRI tools to evaluate ischemic vulnerability in cerebral disease.

 描述（由申请人提供）：这些研究的长期目标是了解脑缺氧的生理后果，以及正常稳态机制的失败如何导致脑疾病。人们一直致力于了解脑血管储备如何影响脑疾病，但这只说明了一半的故事;为了了解对缺氧影响的耐受性，我们还需要了解限制脑代谢活动的潜力。目前提案的核心前提是， 在缺氧或缺血期间，如果脑血流量（CBF）增加或氧代谢（CMRO 2）减少，则可维持脑组织的存活力，这两种情况均导致局部组织氧合（PtiO 2）的保持。氧稳态的一个重要决定因素是局部CO2;我们最近发现，在缺氧过程中，CO2对CMRO 2的影响增加。因此，CO2提供了一种既增加CBF（和O2输送）又减少CMRO 2（和O2消耗）的机制。我们假设，局部缺氧耐受性的大脑是由这些血流动力学和代谢反应的局部强度CO2缺氧（增加CBF和降低CMRO 2），这两个行动，以保持组织氧合。本项目的目标是确定CBF和CMRO 2（因此PtiO 2）是否在已知缺氧敏感性差异的区域缺氧期间表现出这种预期的CO2敏感性差异。我们的方法允许测量区域CBF和CMRO 2响应，基于一种新的多室模型血氧水平依赖性（BOLD）信号。在目标1中，我们将测试我们新的区域CMRO 2对CO2 /缺氧反应性的MRI测量的可重复性和方差来源。在目标2中，我们测试了我们的假设，即抵抗缺血性损伤的区域能够更好地使局部CBF和CMRO 2对局部CO2的敏感性最大化。这一建议提出了一种新的方法来解决脑缺血病理生理学的基本机制问题。本研究的终点将是一个验证的方法来表征CMRO 2在缺氧中的反应性，并测试我们的假设有关区域缺氧的脆弱性在人脑。这些研究还将建立基础和限制，翻译这些新的MRI工具，以评估缺血性脑疾病的脆弱性。