O-15 PET Assessment of Stroke Dynamics & Therapy in Rats

O-15 中风动力学 PET 评估

• 批准号: 6967642
• 负责人: PETER Thornton FOX
• 金额: $ 16.67万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967642
• 关键词: brain imaging /visualization /scanning; brain metabolism; hemodynamics; laboratory rat; method development; neurophysiology; nonhuman therapy evaluation; outcomes research; oxygen consumption; positron emission tomography; statistics /biometry; stroke therapy

DESCRIPTION (provided by applicant): The long-range goal of the research program initiated here is to develop 15O PET methods suitable for use in rats to investigate the temporal dynamics of experimentally induced stroke and the dynamics and mechanism of action of therapeutic interventions for stroke in quantitative and cost-efficient manner. In preliminary investigations to demonstrate feasibility, we have made significant progress in developing fully quantitative 15O PET methods for measuring blood flow (BF), metabolic rate of oxygen (MRO2) and oxygen extraction fraction (OEF) in the non-ischemic rat brain in vivo, without arterial sampling for arterial input function measurement; to our knowledge, we are the first laboratory in the world to do so. We now propose to complete the implementation and validation of these methods and to pioneer their application in the setting of experimentally induced stroke, including simple therapeutic interventions. The objective of this study, therefore, is to test the hypothesis that 0 PET measurements of BF, MRO? and OEF in rats can be utilized as an in vivo test module for the study of stroke and of therapeutic interventions in stroke. Our objective will be achieved via the following 3 specific aims. Aim 1: To develop methods for quantitative, PET measurements of BF, MRO2 and OEF in rat brain using bolus, intravenous administration of 15O tracers (H2 15O and O15O) and to validate these methods relative to intra-carotid injection of the same tracers in the setting of well-established physiological challenges. Aim 2: To apply methods for quantitative, PET measurements of BF, MRO2 and OEF in rat brain using bolus, intravenous administration of 15O tracers (H2 15O and O15O) in the setting of a stroke model. Aim 3: To apply methods for quantitative, PET measurements of BF, MRO2 and OEF in rat brain using bolus, intravenous administration of 15O tracers (H2 15O and O15O) in the setting of a therapeutic intervention applied in a model of acute stroke.

描述（由申请人提供）：此处启动的研究项目的长期目标是开发适用于大鼠的15 O PET方法，以定量和经济有效的方式研究实验诱导卒中的时间动力学以及卒中治疗干预的动力学和作用机制。在证明可行性的初步研究中，我们在开发用于测量体内非缺血大鼠脑中的血流量（BF）、氧代谢率（MRO 2）和氧提取分数（OEF）的完全定量15 O PET方法方面取得了重大进展，而无需动脉采样用于动脉输入功能测量;据我们所知，我们是世界上第一个这样做的实验室。我们现在建议完成这些方法的实施和验证，并在实验诱导的中风，包括简单的治疗干预的设置中开拓其应用。因此，本研究的目的是检验0 PET测量BF、MRO？和OEF可用作研究中风和中风治疗干预的体内测试模块。我们的目标将通过以下三个具体目标来实现。目标1：开发使用推注、静脉注射15 O示踪剂（H2 15 O和O 15 O）定量PET测量大鼠脑中BF、MRO 2和OEF的方法，并验证这些方法相对于在既定生理挑战环境中颈动脉内注射相同示踪剂的相关性。目标二：在脑卒中模型中，使用推注、静脉注射15 O示踪剂（H2 15 O和O 15 O），应用定量PET测量大鼠脑中BF、MRO 2和OEF的方法。目标3：在急性卒中模型中应用治疗干预的背景下，采用推注、静脉注射15 O示踪剂（H2 15 O和O 15 O），应用定量PET测量大鼠脑中BF、MRO 2和OEF的方法。