and/or aims): The overall objective of this research program is to clarify the mechanical and neurological processes involved in esophageal motor physiology through integration of biological data, mathematical modeling, computer simulation and basic principles of mechanics and controls. A second objective is to develop computer-graphics based diagnostic systems for interactive analysis of motility data concurrent with dynamic simulations and to introduce this system into the research and clinical environment. The applicant proposes to combine biological and mechanical analysis with specific objectives in four related categories. These include: (1) Development of a computer-graphics based system for analysis of concurrent manometric and videofluoroscopic data integrated by computer simulations for research in esophageal mechanics, (2) Application of these analysis techniques to the study of esophageal motility. (3) Development of a computer graphics based diagnostic system which combines manometric and radiographic data with mechanical analysis and mathematical models for use in a clinical setting. (4) Clinical application of this new diagnostic tool at the Medical College of Wisconsin and at the Johns Hopkins Medical institution. Specific objectives include: (a) Quantification of esophageal motor physiology by space-time variations in pressure, local power, and active and passive tension. This will be obtained by combining biological data, mathematical models and mechanical principles. (b) Detailed analysis of the transition zone between the striated and smooth muscle regions by careful analysis of resolved spatial and temporal variations in pressure, muscle tension and other mechanical variables. These will be obtained from enhanced concurrent manometric and videofluoroscopic data, by using """"""""pharmacological dissection"""""""" to separate smooth from striated muscle contraction in the region of transition, and by developing mathematical models for the transition from striated to smooth muscle. (c) Analysis and modeling of the role of local longitudinal muscle shortening in bolus transport and in the opening of the lower esophageal sphincter. (d) Analysis of the effect of a catheter on esophageal bolus transport and on intraluminal manometric recordings by combining mathematical models with biological protocols. Special emphasis is placed on the transition in peristaltic transport from the striated to smooth muscle segments, the difference between striated and smooth muscle contraction and analysis of active versus passive components of circular muscle tension and the development of useful computer based tools for use in motility research and in clinical procedures.
