Development of a burst wave lithotripsy system for noninvasive fragmentation of ureteroliths in pet cats

(2023) 19:141 Maxwell et al. BMC Veterinary Research https://doi.org/10.1186/s12917-023-03705-1 BMC Veterinary Research Open Access RESEARCH Development of a burst wave lithotripsy system for noninvasive fragmentation of ureteroliths in pet cats Adam D. Maxwell1,2, Ga Won Kim2, Eva Furrow3, Jody P. Lulich3, Marissa Torre3, Brian MacConaghy2, Elizabeth Lynch2, Daniel F. Leotta2, Yak‑Nam Wang2, Michael S. Borofsky4 and Michael R. Bailey1,2* Abstract Background Upper urinary tract stones are increasingly prevalent in pet cats and are difficult to manage. Surgi‑ cal procedures to address obstructing ureteroliths have short- and long-term complications, and medical therapies (e.g., fluid diuresis and smooth muscle relaxants) are infrequently effective. Burst wave lithotripsy is a non-invasive, ultrasound-guided, handheld focused ultrasound technology to disintegrate urinary stones, which is now undergoing human clinical trials in awake unanesthetized subjects. Results In this study, we designed and performed in vitro testing of a modified burst wave lithotripsy system to noninvasively fragment stones in cats. The design accounted for differences in anatomic scale, acoustic window, skin-to-stone depth, and stone size. Prototypes were fabricated and tested in a benchtop model using 35 natural calcium oxalate monohydrate stones from cats. In an initial experiment, burst wave lithotripsy was performed using peak ultrasound pressures of 7.3 (n = 10), 8.0 (n = 5), or 8.9 MPa (n = 10) for up to 30 min. Fourteen of 25 stones frag‑ mented to < 1 mm within the 30 min. In a second experiment, burst wave lithotripsy was performed using a second transducer and peak ultrasound pressure of 8.0 MPa (n = 10) for up to 50 min. In the second experiment, 9 of 10 stones fragmented to < 1 mm within the 50 min. Across both experiments, an average of 73–97% of stone mass could be reduced to fragments < 1 mm. A third experiment found negligible injury with in vivo exposure of kidneys and ureters in a porcine animal model. Conclusions These data support further evaluation of burst wave lithotripsy as a noninvasive intervention for obstructing ureteroliths in cats. *Correspondence: Michael R. Bailey 1 Department of Urology, University of Washington School of Medicine, Seattle, WA, USA 2 Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, WA, USA 3 Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN, USA 4 Department of Urology, University of Minnesota, Minneapolis, MN, USA Background Upper urinary tract stones in cats are a significant cause of morbidity and mortality [1, 2] The vast majority of these stones (87–98%) are calcium-based [3–5]. There is no protocol for medical stone dissolution of calciumbased stones, and medical management with intravenous fluid therapy and drugs to facilitate obstructing stone passage are effective in only a small proportion of patients (13%) [1, 6]. In the remaining cases, placement of a subcutaneous ureteral bypass (SUB) device or ureteral stent is recommended to relieve obstruction [7]. However, these procedures carry a 6–18% perioperative © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecom‑ mons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Maxwell et al. BMC Veterinary Research (2023) 19:141 mortality rate and a 29–56% risk of long-term complications such as device occlusion, urinary tract infection, and, in the case of stents, lower urinary tract signs without infection [4, 8–11]. The high costs and specialized techniques required for placement of SUB devices or stents also limit availability of these options. For these reasons, new minimally invasive techniques and procedures are sought to improve the efficacy, safety, and availability of treatments for feline ureteroliths. Minimally invasive techniques such as shock wave lithotripsy (SWL) [12] and endoscopic laser lithotripsy [13] are the primary interventions for stones in humans. These methods are not available for treating ureteroliths in cats, as feline calcium oxalate uroliths are relatively resistant to fragmentation by SWL and the feline ureter is too small for laser lithotripsy instrumentation [7, 14]. Burst wave lithotripsy (BWL) is a new noninvasive approach to fragment urinary tract stones based on focused ultrasound technology. This method uses a focused ultrasound transducer to apply short harmonic bursts of ultrasound to a stone to produce cyclic stressing that leads to fractures and fragmentation [15]. A BWL system consists of a small electronic pulser and therapy transducer that can be coupled to the skin of a patient by a thin layer of ultrasound gel. An ultrasound imaging probe incorporated with the therapy head allows detection and localization of a stone, using custom algorithms to enhance detection of calcifications [16, 17]. This technology has progressed from conception to human clinical trials over the last 8 years [18, 19]. BWL has been demonstrated to fragment a number of different stone compositions, including calcium oxalate stones, in preclinical and human studies [19, 20], without producing any significant injury or complications [20, 21]. In a preclinical study using calcium oxalate monohydrate stones (known to be resistant to SWL) implanted in the kidneys of pigs, stones were noninvasively fragmented by BWL, with 88% of the resulting fragments smaller than 2 mm [20]. No injury was found to the kidney parenchyma and only mild hemorrhagic injury to the collecting space lining. The fine control of acoustic parameters such as amplitude and frequency has been demonstrated to have a number of benefits, one of which is the control of the size of fragments generated from the stone during the procedure [19]. For instance, 170 kHz ultrasound bursts produce fragments in artificial stones up to 4 mm, while 800 kHz ultrasound produce fragments approximately 0.6 mm in size. While the normal luminal diameter of the feline ureter is (...truncated)