The basic hypothesis of this Program is that structure-to-function interrelationships in the undisturbed, in situ, organs may differ significantly from that seen in isolated, or disturbed in situ, organs because of the mechanical interaction between the organ and its contiguous organs and/or neurohumoral integration with the body as a whole. The overall objective is to quantitate pathophysiological aspects of structure-to-function relationships in the in situ heart, lungs, thoracoabdominal wall and kidneys with increased accuracy and less invasion than is possible by conventional methods. The unique and central integrating feature of this program is the use of the Dynamic Spatial Reconstructor (DSR), a high speed x-ray CT scanner, which will enable us to make these quantitations with minimal invasion in experimental animals and in man. Four of the eight research projects in the program involve human subjects. In Project III we will study the role of the thoracoabdominal wall and body orientation on lung function in normal awake and anesthetized volunteers, in Project V we will quantitate coronary artery anatomy and in VI myocardial perfusion in patients with coronary artery disease. In Project I patients with peri and paracardial diseases will be studied so that the mechanical role of heart lung interaction in maintaining constant total heart volume can be quantitated. There are also six projects which involve study of dogs' coronary arterial anatomy (V), myocardial mechanical efficiency (IV), myocardial hypertrophy (VIII), heart lung interaction (I), thoracic wall to lung interaction (II) or renal perfusion (VII). These projects are supported by three cores, Core A supports the DSR scanner facility, Core B supports the computer based image data reconstruction and analysis needs and Core C provides the administrative support. The DSR will supply the desired data with: (1) Less invasion (less radiation, less contrast medium injected, no need to open the thoracic or abdominal cavity) than by conventional techniques providing comparable accuracy; (2) Greater accuracy and/or less ambiguity than occurs in conventional projection imaging techniques such as cine angiography or gamma camera imaging because it is a tomographic 3-D imaging technique; (3) A basis for comparison with other tomographic imaging techniques - specifically sector echocardiograms in Project VIII and Magnetic Resonance Images in Project I. The outcome of these projects could have direct impact on our understanding of the in situ pathophysiology of disease processes and the response to medical treatment.
