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

描述(申请人提供)：在这里启动的研究计划的长期目标是开发适合在大鼠身上使用的15O PET方法，以定量和经济高效的方式研究实验诱导的中风的时间动力学以及中风治疗干预的动力学和作用机制。在论证可行性的初步研究中，我们在开发全定量15O PET方法方面取得了重大进展，可以在体内测量非缺血大鼠脑内的血流量(BF)、氧代谢率(MRO2)和氧摄取分数(OEF)，而不需要动脉采样来测量动脉输入功能；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，并开创它们在实验性卒中环境中的应用，包括简单的治疗干预。因此，本研究的目的是检验这样一种假设，即BF、MRO？大鼠的OEF可作为卒中研究和卒中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。目的1：建立静脉注射~(150)O示踪剂(H2~(150)O和~(150)O)对大鼠脑内BF、MRO2和OEF进行PET定量测定的方法，并与颈动脉内注射相同示踪剂的方法进行比较，以验证这些方法的有效性。目的：在建立卒中模型的基础上，应用PET定量测定大鼠脑内BF、MRO2和OEF的方法，包括静脉注射15O示踪剂(H2 15O和O150)。目的：在急性卒中模型治疗干预的背景下，应用PET定量测定大鼠脑BF、MRO2和OEF的方法，包括静脉注射15O示踪剂H2 15O和O15O。

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.