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.

Keywords: kidney stones; lithotripsy; ultrasound.

Conflict of interest statement

Maxwell, Cunitz, Dunmire, Bailey, and Sorensen have consulting agreements with and equity in SonoMotion, Inc., which has licensed this technology from the University of Washington.

Figures

FIG. 1.

Experimental arrangement. The stone was enclosed in a water-filled cavity within a tissue mimicking phantom submerged in a water bath. The BWL and ultrasonic propulsion ultrasound bursts were applied from a transducer positioned above the phantom. The real-time ultrasound image of the transducer was recorded to video. The “x” indicates the focus on the transducer. BWL = burst wave lithotripsy.

FIG. 2.

Comminution effectiveness of the two BWL output settings. On average the remaining stone mass >2 mm fell from 100% at the start to 21% at 10 minutes and 8% after 30 minutes. Seventy percent of stones were fully comminuted within 10 minutes, and 89% of stones were fully comminuted with 30 minutes. There was no statistical difference between the two settings (p = 0.44); both fragmented the stones effectively. The error bars represent the standard error. n = 23 for each setting.

FIG. 3.

BWL comminution effectiveness across different stone compositions. The majority of human stones, including apatite (n = 2), struvite (n = 6), and COM (n = 28), were fully comminuted within 10 minutes. Four of 10 brushite stones were more resistant to comminution. COM = calcium oxalate monohydrate.

FIG. 4.

BWL stone comminution effectiveness vs time for two different dissolved oxygen levels. No statistical difference was seen between the two different dissolved oxygen levels (p = 0.65). This comparison was conducted with brushite stones. The results are not changed when the two COM stones broken in the high gas content are included.

FIG. 5.

BWL stone comminution effectiveness vs time for two different containment (fluid) volumes. No statistical difference was seen between the two different containment volumes (p = 0.58). This comparison was conducted with COM stones.

FIG. 6.

Ultrasound images captured during ultrasonic propulsion of a minimally broken stone (upper frames) and a completely fragmented stone (lower frames). Both show frames captured from a video of stone motion during a single 3-second ultrasonic propulsion burst. The arrow points to the moving stone and/or fragments. The left frames are from before the ultrasonic propulsion application. Before propulsion, it is difficult to differentiate an unbroken stone from a pile of fragments. The right frames correspond to 1 second into the ultrasonic propulsion burst. Arrows point to echogenic stone or fragments. In the upper sequence, all three reviewers reported one large fragment. In the lower sequence, all three reviewers reported a collection of fragments all <2 mm. The reviewers viewed the entire movie not just the still images.