The proposed research will provide the foundation for interpretating modes of renal injury induced by SWL in terms of the mechanical stress generated by shock waves focusing in tissue. The stress waves are directly to the strength and geometry of the shock waves, and, therefore, to the operation of lithotriptors. Thus, understanding the linkage between mechanical effects of shock waves and medical injury will permit new treatment guidelines to be formulated. The specific aim of this project are: 1. Measure the properties of mechanical stresses induced in mini-swine and cell-culture models in experiments at Indiana University (IU), and correlate with observations of renal injury. This phase of the study will test the hypothesis that a) measurable or calculable properties of the mechanical stress fields imposed by focusing shock waves can be correlated with observations of shock-wave-induced injury in SWL. 2. Determine if stress induced by shock interaction with tissues leads to differential motions, such as shear and tearing, which cause mechanical failure of biological structural elements. This work, is designed to test the hypothesis that b) interactions of SWL shock waves with acoustic inhomogeneities in tissues cause stresses and differential motions which lead to mechanical failure of biological structural elements. The mechanical stresses induced in the kidney of mini-swine during lithotripsy will be measured using newly tested methodology employing implantable thin-film pressure transducers. The transducers will measure the stresses imposed directly on the kidney and modifications to the stress waves as they propagate through the body. The stresses applied to living cells by SWL shock waves will also be measured using transducers installed directly into plastic vials containing cell cultures. Incorporating pressure transducers in both in vivo and in vitro tests makes it possible for the first time to tailor the conditions of the in vitro study to replicate the mechanical state experienced in the in vivo environment. Approximate theories of shock wave propagation will be used to develop numerical models of shock focusing in tissue. An important element of medical physics, previously not considered, concerns the mechanisms by which shock waves cause failure in weak structural elements, such as membranes and thin-walled liquid-filled vessels. An exploratory study of the mechanisms of shock-induced failure in simple mechanical models of biological structures will be undertaken using appropriate transparent materials and high-speed photographic flow- visualization techniques. Data from the mini-pig, cell-culture, and shock-failure experiments, taken both individually and as a whole, will be used in an iterative process to improve the design and interpretation of each type of experiment.