? High intensity focused ultrasound (HIFU) is an exciting new therapeutic technology with numerous significant clinical applications. It is also one of the most promising modern interdisciplinary areas of physics and medicine. HIFU enables delivery of a relatively large amount of energy to a small region of tissue with little effect on the surrounding areas. The associated high acoustic pressure and heat deposition of HIFU results in tissue necrosis and blood coagulation. This ultrasound impact can be used to ablate tumors, pre-coagulate a region of an organ to be surgically resectioned, and obtain hemostasis in hemorrhaging parenchyma or damaged vessels. The tissue can be treated not only on the organ surface, but also noninvasively deep within the organ itself. The work in the parent grant has demonstrated the clinical applicability and engineering manifestation of HIFU in achieving rapid hemostasis in vivo, with models of organ and blood vessels injuries. The research team of bioengineers and surgeons from the Center of Industrial and Medical Ultrasound (CIMU) of the University of Washington has shown the efficacy of the treatment to stop bleeding in open liver and punctured vessels. The work has identified specific areas where lack of understanding and knowledge of physical mechanisms involved in ultrasound/tissue interaction inhibit application. These include better understanding thermal effects, cavitation, streaming, effect of acoustic nonlinearity that play important roles in arresting bleeding. Design and optimization of HIFU probes require characterization of transducers to predict ultrasound field, and its impact on blood and tissue. The objective of the proposed FIRCA grant is to address some of these areas, to provide insight into the physical mechanisms involved in HIFU hemostasis, and to provide numerical and experimental tools based on this knowledge for optimization, planning, and monitoring of treatment. Theoretical and numerical models for the nonlinear acoustic field produced by HIFU probes will be developed and coupled with the temperature model, bubble dynamics, and streaming. Experiments will be performed in tissue mimicking liquids and phantoms and compared with the theoretical results in order to reveal the importance of basic physical effects in halting the bleeding jet and accelerating hemostasis. This research will be done primarily in Russia at the Department of Acoustics, Physics Faculty of the Moscow State University in collaboration with Vera A. Khokhlova and her colleagues as an extension of the parent NIH grant # R01 EB 00292-03. ? ? ? ?