The primary goal of this application is to develop a highly controlled noninvasive ultrasound procedure to mechanically subdivide and remove tissue, primarily for cardiac applications. The method being developed can be thought of as analogous to lithotripsy for soft tissues. The Controlled Ultrasound Tissue Erosion (CUTE) process is fundamentally different from most soft tissue therapeutic ultrasound procedures in that tissue must be precisely removed instead of producing thermal necrosis in situ. The underlying mechanisms are different from those producing thermal necrosis and need to be fully elucidated so that the erosion process can be rationally optimized. This is the global aim of the proposal. Preliminary results suggest the following mechanistic hypotheses that form the basis of the experimental work proposed herein. 1. The CUTE process depends on co-operative interaction between an initiated """"""""bubble cloud"""""""" and the ultrasound insonation where acoustic parameters can be finely tuned (optimized) for the most efficient use of propagated energy, 2. The initiated bubble cloud must be maintained in an optimal state by appropriate adjustment of acoustic parameters, 3. The past history of exposure can predispose the process for optimal future exposure, 4. Pulsed ultrasound is the most effective way to organize the insonation to optimally maintain this complex set of co-operative phenomena. We propose to study these fascinating interactions of sound and bubble ensembles by, 1. Fully exploring acoustic parameter space seeking optimal parameters to maximize therapeutic effects of the propagated energy; and 2. Observing directly the """"""""bubble clouds"""""""" by sophisticated optical and acoustic techniques. If we can fully understand these co-operative processes, we will be ably to more effectively optimize the process for specific clinical application. Controlled Ultrasound Tissue Erosion promises to extend the therapeutic rationale of Lithotripsy to all (or most) soft tissues. The applications extend far beyond cardiology although specific cardiac applications are most promising.
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