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（由适用提供）：这些研究的长期目标是了解脑缺氧的身体后果，以及正常稳态机制的失败如何导致脑病。已经大量关注的是了解脑部储备如何影响大脑疾病，但是这仅讲述了一半的故事。要了解对缺氧影响的耐受性，我们还需要知道限制脑代谢活性的潜力。当前提议的中心前提是 如果可以增加脑血流（CBF）或可以降低氧代谢（CMRO2），则可以保持低氧或缺血性脑组织生存能力，这两者都会导致保存局部组织氧合（PTIO2）。氧气稳态的重要决定因素是局部二氧化碳。我们最近发现，在缺氧期间，二氧化碳对CMRO2的影响增加了。该二氧化碳提供了增加CBF（和O2递送）并减少CMRO2（和O2消耗）​​的机制。我们假设大脑中的区域缺氧耐受性取决于这些血流动力学和代谢反应对二氧化碳的局部强度（增加CBF并降低CMRO2），这两个反应都可以保留组织氧合作用。该项目的目标是确定CBF和CMRO2（以及PTIO2）是否在缺氧敏感性差异的区域中表现出这种二氧化碳灵敏度的预期差异。我们的方法允许根据一种新型的多室模型血液氧合水平依赖性（BOLD）信号来测量区域CBF和CMRO2响应。在AIM 1中，我们将测试区域CMRO2对CO2 /缺氧的新MRI测量值的可重复性和差异。在AIM 2中，我们测试了我们的假设，即对缺血性侮辱具有抗性的区域可以更好地最大程度地提高局部CBF和CMRO2对局部CO2的敏感性。该建议提出了一种新的方法，可以解决脑缺血性病理生理学中的基本机理问题。这项研究的终点将是一种表征缺氧中CMRO2反应性的验证方法，以及我们关于人脑区域缺氧脆弱性的假设的检验。这些研究还将建立转换这些新型MRI工具以评估脑疾病中缺血性脆弱性的基础和局限性。