This proposal is for the 17th through 21st years of the Simulation Resource for Circulatory Mass Transport and Exchanges at the University of Washington. Investigators from the University of Washington, Vanderbilt University, Michigan State University, University of Minnesota, Medical College of Wisconsin, the Mayo Clinic, McGill University, and Universities in the Netherlands, Italy, Hungary, and Germany collaborate in the development of computer models and/or the analysis of data from experimental studies. The modeling analysis efforts of about 25 investigators are focused on the kinetics of blood-tissue exchanges in well-perfused organs such as the normal heart, lung and brain, and on approaches to assessment of both physiologic and pathophysiologic states such as ischemia, injury, and abnormalities of function and metabolism. Particular emphasis is on the development and application of methods of interpreting data from positron emission tomography (PET) and multiple tracer indicator dilution studies. The proposed program has three sections. Section I concerns the development of analysis techniques for investigator-managed simulation analysis tools such as XSIM, a graphical simulation interface that funs under X-windows. Additional tools for fractal analysis and for functional imaging and visualization will be developed. Section II focuses on the development of models for mass transport and exchange. Section III contains 17 projects for which no funding is requested. These projects exemplify the application of the technology developed in the Resource to the analysis of experimental and clinical data. Included are projects on metabolic imaging of tumors and of regional cardiopulmonary metabolism and flows, heterogeneity of lung ventilation and perfusions, the metabolism of adenosine, amino acids and fatty acids in the heart, oxygen consumption in the heart, myocardial flow studies, and studies of brain microcirculation. The projects are supported by four Cores: computational facility; software development and maintenance, dissemination and training and administration.