In Vitro Evaluation of Urinary Stone Comminution with a Clinical Burst Wave Lithotripsy System

Abstract

Objective: Our goals were to validate stone comminution with an investigational burst wave lithotripsy (BWL) system in patient-relevant conditions and to evaluate the use of ultrasonic propulsion to move a stone or fragments to aid in observing the treatment endpoint. Materials and Methods: The Propulse-1 system, used in clinical trials of ultrasonic propulsion and upgraded for BWL trials, was used to fragment 46 human stones (5-7 mm) in either a 15-mm or 4-mm diameter calix phantom in water at either 50% or 75% dissolved oxygen level. Stones were paired by size and composition, and exposed to 20-cycle, 390-kHz bursts at 6-MPa peak negative pressure (PNP) and 13-Hz pulse repetition frequency (PRF) or 7-MPa PNP and 6.5-Hz PRF. Stones were exposed in 5-minute increments and sieved, with fragments >2 mm weighed and returned for additional treatment. Effectiveness for pairs of conditions was compared statistically within a framework of survival data analysis for interval censored data. Three reviewers blinded to the experimental conditions scored ultrasound imaging videos for degree of fragmentation based on stone response to ultrasonic propulsion. Results: Overall, 89% (41/46) and 70% (32/46) of human stones were fully comminuted within 30 and 10 minutes, respectively. Fragments remained after 30 minutes in 4% (1/28) of calcium oxalate monohydrate stones and 40% (4/10) of brushite stones. There were no statistically significant differences in comminution time between the two output settings ( p = 0.44), the two dissolved oxygen levels ( p = 0.65), or the two calyx diameters ( p = 0.58). Inter-rater correlation on endpoint detection was substantial (Fleiss' kappa = 0.638, p < 0.0001), with individual reviewer sensitivities of 95%, 86%, and 100%. Conclusions: Eighty-nine percent of human stones were comminuted with a clinical BWL system within 30 minutes under conditions intended to reflect conditions in vivo. The results demonstrate the advantage of using ultrasonic propulsion to disperse fragments when making a visual determination of breakage endpoint from the real-time ultrasound image.

Editorial Comment on:“In VitroEvaluation of Urinary Stone Comminution with a Clinical Burst Wave Lithotripsy System” by Ramesh et al.

“…Compared with extracorpo-real shockwave lithotripsy (SWL), BWL may provide an officebased modality for stone management solely driven by ultrasonic (US) technologies to image, fragment, and reposition stones in the kidney. In this in vitro study, 3 the authors confirm that 5-7 mm kidney stones of various compositions can be comminuted within 30 minutes in tissue phantoms under clinically relevant test environments. Moreover, the potential of US…”

Fragmentation of Stones by Burst Wave Lithotripsy in the First 19 Humans

“…The system has previously been used to effectively comminute stones 3e7 mm in size ex vivo. 17 Table 1 shows the BWL exposure parameters. BWL was delivered at a frequency of 390 kHz to break stones consistently into 2 mm fragments.…”

Recent Advances in the Science of Burst Wave Lithotripsy and Ultrasonic Propulsion

“…This was used in the first clinical trial discussed below [20]. Following that trial, the device was refined to provide broader beams and longer duration exposures for ultrasonic propulsion and enabled BWL pulses with the same transducer [21][22][23][24]. The iteration of the hand held transducer used in most propulsion and BWL clinical trials to date uses a 350 kHz and 60 mm single element annular element for therapy (H209, Sonic Concepts, Bothell WA) and has within the aperture a phased array transducer (P4-2, Philips/ATL, Bothell, WA) for image guidance.…”

“…The authors concluded that real-time US may help to facilitate monitoring of BWL and prevent renal injury. Ramesh et al tested BWL on 46 human stones within a phantom model of the human kidney, finding that 89% of stones were comminuted within 30 minutes and 70% within 10 minutes of treatment [ 23 ]. Incorporating ultrasonic propulsion during a BWL treatment session is thought to provide benefit in determining the endpoint of fragmentation when small stone fragments are cleared from the treatment area.…”