The objectives of this research effort are the assessment, in vivo, and regionally of metabolic pathways in various organs, particularly the brain and the heart, by following the fate of radioactively-labeled metabolic substrates. The ultimate goals of this investigation are to develop and apply methods for the in vivo and regional measure of physiological processes which will be ultimately applied to the understanding of basic biological processes and to the understanding and diagnosis of pathology. The proposed approach consists of labeling selected metabolic substrates or other molecules of importance in physiological processes with a radioactive nuclide, the decay of which result inthe generation of high energy electromagnetic radiation. After the administration of the substrate to the subject under the study, the location of the nuclide, as a function of time, is followed by externally placed detectors, or more often, by positron emission tomography (PET), and the metabolic pathway under study is unraveled through the application of a suitable mathematical model. For this purpose, the labels must be with few exception, nuclide akin to those found in the chemical structure of living matter. We propose to use carbon-11, nitrogen-13, oxygen-15, and in some instances, in the labeling of substrate analogs, fluorine-18. These nuclides are prepared by a cyclotron located n our medical center. All of them decay with the emission of positrons, which, as they are absorbed, generate the annihilation radiation which is used in generating "functional images." The program is divided into three areas: (1) chemical investigations; (2) neurological studies; and (3) cardiovascular studies. The above three projects share the common CORE facilities and are extensively cross linked by the methodology used.