First In-Human Burst Wave Lithotripsy for Kidney Stone Comminution: Initial Two Case Studies

Abstract

Purpose: To test the effectiveness (Participant A) and tolerability (Participant B) of urinary stone comminution in the first-in-human trial of a new technology, burst-wave lithotripsy (BWL). Materials and Methods: An investigational BWL and ultrasonic propulsion system was used to target a 7-mm kidney stone in the operating room before ureteroscopy (Participant A). The same system was used to target a 7.5 mm ureterovesical junction stone in clinic without anesthesia (Participant B). Results: For Participant A, a ureteroscope inserted after 9 minutes of BWL observed fragmentation of the stone to <2 mm fragments. Participant B tolerated the procedure without pain from BWL, required no anesthesia, and passed the stone on day 15. Conclusions: The first-in-human tests of BWL pulses were successful in that a renal stone was comminuted in <10 minutes, and BWL was also tolerated by an awake subject for a distal ureteral stone. Clinical Trial NCT03873259 and NCT02028559.

Keywords: burst wave lithotripsy; calculi; lithotripsy; physics; shock wave lithotripsy; ultrasound; urolithiasis.

FIG. 1.

Graphical illustration of the concepts of how SWL and BWL are believed to fragment stones which may then be repositioned to the ureter by ultrasonic propulsion. Traditional SWL (upper image sequence) fragments stones noninvasively through sequential shock waves that create localized stress, leading to a primary fracture point within the stone. Typically, stones treated with SWL break from larger fragments into proportionally smaller fragments with repeated shockwaves, analogous to a “fragmenting” strategy in laser lithotripsy.^, In contrast, BWL comminution of stones (lower image sequence) occurs through small pieces shedding off a single large stone, more analogous to a “dusting” strategy in laser lithotripsy.^, This action is achieved using focused sinusoidal bursts of US waves that repetitively stress multiple regions within the stone. BWL's lower pressure amplitude avoids cavitation clouds that can shield the stone from US energy and possibly cause tissue injury.^, Clinically, BWL is advantageous because a higher rate can be used compared with SWL (10–100 Hz vs 1–2 Hz) again because of lower amplitudes, which allows energy to be delivered more quickly.^,, (Image courtesy of Kim Reading of Applied Physics Laboratory.) BWL, burst-wave lithotripsy; SWL, shockwave lithotripsy.

FIG. 2.

(a) Custom handheld BWL and ultrasonic propulsion probe with a water-circulating coupling head. The therapy probe (black/silver, peripheral) is a single element annulus that supports coaxial alignment of a P4-2 imaging probe (red, central). The overall probe diameter (SC-60) is 6.5 cm. (b) User interface demonstrating real-time imaging. The upper right panel displays the B-mode image. The red oval represents the treatment focus, where a stone must be aligned for treatment to be effective. The upper left panel displays the customized “S-mode” image,^, utilizing color-flow Doppler to make the stone stand out in green. The bottom panel includes the system settings and system feedback parameters for monitoring operation. Pulses are triggered with a footswitch.

FIG. 3.

CT images of the targeted stones and SSD. Axial images of each subject shown in the top row. Coronal view of Participant A (lower left) and sagittal view of Participant B (lower right). SSD, skin-to-stone distances.

FIG. 4.

Participant A—Initial view of the fragments the 7-mm stone after 9 minutes of BWL (left) and the sizes measured on video using the laser fiber as scale (right). The four largest fragments in the image are (1.9, 1.6, 1.4, and 1.4 mm). Minimal bleeding, clotting, and discoloration of the tissue can be observed.

FIG. 5.

Ultrasonic propulsion of the stone fragments after BWL, visualized with the US Propulse 1 system (top) and by ureteroscopy (lower). The times (0, 0.5, and 1 second) show frames just before, in the middle of, and at the end of the 1-second ultrasonic propulsion pulse, which is traveling down in the US frames and out of the page in the ureteroscope frames. The red x and red lines in the US frames indicate the focus and focal region on the Propulse 1 display, and yellow arrows were added in postprocessing to show the one collection of fragments at 0 second spreading and moving downward in the frames at 0.5 and 1 second. This motion and US imaging revealed to the operator that the stone was no longer intact stone but was instead many fragments as has been observed in vitro. One ultrasonic propulsion pulse was observed to move the fragments out of the calix, and in ultimate clinical use, many pulses may move the stones out of the collecting system to facilitate clearance. (Supplementary Videos S1 and S2) are included.

FIG. 6.

Participant B—Two photographs of the passed stone on millimeter graph paper and a μCT slice of the stone with dimensions of μCT of 7.4 mm × 3.4 mm × 3.1 mm and the determined volume was 21.96 mm³. IR analysis identified the stone as calcium oxalate monohydrate, and the μCT analysis reported COM/COD/apatite 57%/37%/6% by volume. μCT, micro-CT.