During the first period of the MERIT Award, we have completed most of the studies described in the four specific aims of the original application. We have designed a new acoustic lens that significantly improves the performance and safety of the Siemens lens based on in vitro tests and animal experiments. We have demonstrated the feasibility of a steerable and non-axisymmetric acoustic field in treating stones in the ureter or under the influence of respiratory motion. We have built a prototype electromagnetic annual ring shock wave generator and assessed the benefit of microsecond tandem pulse technology in stone comminution. We have investigated the effects of gas concentration in the coupling water and pulse repetition frequency (PRF) on the transmission of the lithotripter shock waves into the patient and resultant stone fragmentation. We have identified optimal treatment strategy to maximize stone comminution while minimizing tissue injury. We have further devised methods to mitigate the influence of cavitation bubbles along the beam path of the lithotripter in the coupling medium so that the treatment can be performed successfully at higher PRF (thus reducing treatment time) without increasing the risk of tissue injury. In addition, we have determined that average peak pressure is a critical parameter for stone comminution. This important finding provides the physical basis for understanding the benefit of broad focal width/low peak pressure lithotripters, such as the Dornier HM3 in clinical treatment. This extensive body of work has been carried out through synergistic collaborations between engineers, mathematicians, and urologists with the technical and equipment support of Siemens - one of the leading lithotripter manufacturers. In the extension application of this MERIT Award, we will continue fundamental research in the area of surface wave-induced stone fracture, cavitation-produced injury at cellular level and in small blood vessels. We will further expand on technology development in the area of steerable beam formation and wet coupling device that can be readily integrated in contemporary shock wave lithotripters. This new line of research will be carried out through engineering design innovation, multiphysics model simulation and experimental validations both in laboratory systems and in animal models. The overarching goal of this MERIT Award is to combine synergistically fundamental studies with technology innovations and translational research to improve the clinical performance and safety profile of contemporary shock wave lithotripters.

Public Health Relevance

; Shock wave lithotripsy (SWL) is a non-invasive procedure and remains to be the first-line therapy for the treatment of kidney stone disease. We will continue the fruitful multidisciplinary collaboration to combine fundamental research with technology innovation that can be translationed to the next-generation shock wave lithotripters. This work will significantly improve the quality of clinical treatment for urolithiasis patients worldwide.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
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Kirkali, Ziya
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Duke University
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Fovargue, Daniel; Mitran, Sorin; Sankin, Georgy et al. (2018) An experimentally-calibrated damage mechanics model for stone fracture in shock wave lithotripsy. Int J Fract 211:203-216
Li, Fenfang; Yang, Chen; Yuan, Fang et al. (2018) Dynamics and mechanisms of intracellular calcium waves elicited by tandem bubble-induced jetting flow. Proc Natl Acad Sci U S A 115:E353-E362
Li, Fenfang; Yuan, Fang; Sankin, Georgy et al. (2017) A Microfluidic System with Surface Patterning for Investigating Cavitation Bubble(s)-Cell Interaction and the Resultant Bioeffects at the Single-cell Level. J Vis Exp :
Xing, Yifei; Chen, Tony T; Simmons, Walter N et al. (2017) Comparison of Broad vs Narrow Focal Width Lithotripter Fields. J Endourol 31:502-509
Yuan, Fang; Yang, Chen; Zhong, Pei (2015) Cell membrane deformation and bioeffects produced by tandem bubble-induced jetting flow. Proc Natl Acad Sci U S A 112:E7039-47
Neisius, Andreas; Smith, Nathan B; Sankin, Georgy et al. (2014) Improving the lens design and performance of a contemporary electromagnetic shock wave lithotripter. Proc Natl Acad Sci U S A 111:E1167-75
Hsiao, C-T; Choi, J-K; Singh, S et al. (2013) Modelling single- and tandem-bubble dynamics between two parallel plates for biomedical applications. J Fluid Mech 716:
Fovargue, Daniel E; Mitran, Sorin; Smith, Nathan B et al. (2013) Experimentally validated multiphysics computational model of focusing and shock wave formation in an electromagnetic lithotripter. J Acoust Soc Am 134:1598-609
Smith, Nathan B; Zhong, Pei (2013) A heuristic model of stone comminution in shock wave lithotripsy. J Acoust Soc Am 134:1548-58
Mancini, John G; Neisius, Andreas; Smith, Nathan et al. (2013) Assessment of a modified acoustic lens for electromagnetic shock wave lithotripters in a Swine model. J Urol 190:1096-101

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