Project 2 plans a mechanistic approach to the development of practical treatment strategies that will Improve outcomes and reduce adverse effects in SWL. 1) We will advance understanding of the mechanisms of SW action in stone breakage and tissue injury using a fiberoptic hydrophone (FOPH) to determine the characteristics of SWs at their site of action in the renal pelvis and proximal ureter. 2) Poor acoustic coupling with dry-head lithotripters reduces the efficiency of treatment, leading to delivery of more SWs than are needed to break stones. We will find methods to eliminate coupling defects and develop imaging methods that allow urologists to monitor coupling throughout the treatment session. 3) Obese patients typically have poor outcomes with SWL and are often treated with excessive numbers of SWs at high pressures. We will detemiine the factors that limit successful treatment and explore ways to improve how SWs can be delivered when the patient's skin-to-stone distance predicts a poor result. 4) Urologists are increasingly aware that SWL can generate adverse effects but have little practical information to relate SW dose to the potential for injury. We will use an ultrasound-based system to determine the SW number threshold for cavitation-related injury in the kidney under routine treatment conditions and with protocols designed to protect against tissue damage. The goal is to monitor for conditions that are ripe for injury so that steps can be taken to minimize tissue damage. 5) A new generation of lithotripter has been introduced to clinical practice. These machines produce low acoustic pressures delivered to a wide focal zone. Preliminary studies suggest these machines may offer a significant advantage for improved stone breakage with minimal adverse effects, but a thorough independent assessment is needed to determine the advantages and limitations of this new technology. 6) Lithotripters break stones better at slow SW-rate than at fast rate. We have shown that SWs at fast rate are dramatically reduced in negative pressure and that cavitation is responsible for this effect. We now propose to use high-speed imaging and the FOPH to determine the mechanism of action of SW-rate on stone breakage. RELEVANCE (See instructions): Shock wave lithotripsy (SWL) is the most common treatment used to remove renal stones. However, SWL has been found to cause acute trauma to the kidney and sunrounding organs that is linked to potentially very serious chronic adverse effects. The proposed research will find ways to make SWL safer and more effective.