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.
| Lee, Kihak; Fox, Peter T; Lancaster, Jack L et al. (2008) A positron-probe system for arterial input function quantification for positron emission tomography in humans. Rev Sci Instrum 79:064301 |
| Yee, Seong-Hwan; Lee, Kihak; Jerabek, Paul A et al. (2006) Quantitative measurement of oxygen metabolic rate in the rat brain using microPET imaging of briefly inhaled 15O-labelled oxygen gas. Nucl Med Commun 27:573-81 |
| Yee, Seong-Hwan; Jerabek, Paul A; Fox, Peter T (2005) Non-invasive quantification of cerebral blood flow for rats by microPET imaging of 15O labelled water: the application of a cardiac time-activity curve for the tracer arterial input function. Nucl Med Commun 26:903-11 |
