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

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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.