The objective of this Program Project Application is the application of positron emission tomography for the in vivo assessment of metabolic pathways in various organs, specifically the brain, heart and lung. The approach is to develop methods for the in vivo regional measurement of physiological parameters and to extend this knowledge to the understanding of basic biological processes in normal and diseased states. Compounds are labeled with the positron emitting radionuclides oxygen-15, carbon-11 and fluorine-18, produced by the cyclotrons located in the Washington University Medical Center. These radionuclides are then combined into radiopharmaceuticals which can either measure flow, metabolism or other physiological and pharmacological parameters. These radiopharmaceuticals are administered to animals or human subjects and used to measure in vivo function. The metabolic images obtained using PET are correlated with anatomical images obtained using magnetic resonance imaging. The Program Project Grant Application includes four research projects in distinct areas all of which utilize positron tomography. The three areas are: a) synthesis and evaluation of new radiopharmaceuticals, b) neurological studies, c) cardiovascular studies; and d) pulmonary. Synergism exists between the three projects: they all share the 3 Core functions; they are all aimed at measuring metabolism and other physiological parameters in humans and image manipulation is important in all projects. The 4 Projects share the 3 Cores which provide administration, radionuclides, radiopharmaceuticals and state-of-the-art imaging devices. The Departments involved in this Program Project includes the Department of Radiology, the Department of Internal Medicine, the Department of Neurology and Neurosurgery and the Institute of Biomedical Computing.