Methods, computing devices, and a computer-readable medium are described herein related to fragmenting or comminuting an object in a subject using a burst wave lithotripsy (BWL) waveform. A computing device, such a computing device coupled to a transducer, may carry out functions for producing a BWL waveform. The computing device may determine a burst frequency for a number of bursts in the BWL waveform, where the number of bursts includes a number of cycles. Further, the computing device may determine a cycle frequency for the number of cycles. Yet further, the computing device may determine a pressure amplitude for the BWL waveform, where the pressure amplitude is less than or equal to 8 MPa. In addition, the computing device may determine a time period for producing the BWL waveform.

Described herein are methods and apparatus for detecting stones by ultrasound, in which the ultrasound reflections from a stone are preferentially selected and accentuated relative to the ultrasound reflections from blood or tissue. Also described herein are methods and apparatus for applying pushing ultrasound to in vivo stones or other objects, to facilitate the removal of such in vivo objects.

Embodiments of the invention include improved radiofrequency (RF) pulse amplifier systems that incorporate an energy array comprising multiple capacitors connected in parallel. The energy array extends the maximum length of pulses and the maximum achievable peak power output of the amplifier when compared to similar systems. Embodiments also include systems comprising the amplifier configured to drive a load, wherein the load may include one or more ultrasound (e.g., piezoelectric) transducers Related methods of using the amplifier are also provided.

Purpose:
To evaluate if treating small asymptomatic renal stones with office-based burst wave lithotripsy (BWL) and ultrasonic propulsion (UP) prevents future stone growth, emergency department visits, and surgical procedures for stone care.

Methods:
Participants with 2–7 mm asymptomatic renal stones were treated with BWL to break stones and UP to facilitate clearance of fragments. The primary outcome measure was relapse, defined as stone growth, an urgent or emergent medical visit, or operation for the randomized stones of interest within 14 months of the procedure. These events would include visits caused by the treatment and the presence of residual stones. Relapse data from untreated control groups with small stones or fragments from three published contemporaneous studies with similar protocols and 1- to 5-year follow-up were pooled and inverse probability weighted for comparison. The cumulative incidence of relapse was estimated using the Kaplan–Meier method.

Results:
Between April 2023 and September 2024, 18 participants underwent treatment of 27 asymptomatic small stones; 7 (39%) participants underwent a second BWL procedure to complete treatment. The control group had significantly shorter time to relapse than the treatment group (p = 0.048 by weighted log-rank test). The hazard ratio for relapse in the treatment group, compared with the control group, was less than 0.01 (p < 0.001). There was no relapse in the treated group within 14 months. For comparison, the 1-year relapse rate was 26% in the control group.

Conclusions:
In a small feasibility study, no stone-related relapse events occurred within 14 months following treatment of small, asymptomatic renal stones with BWL and UP.

Ureteroliths are a major source of morbidity and mortality in cats, and limited non-surgical options are available for their treatment. Ultrasound-guided, burst wave lithotripsy (BWL) is approved by the Food and Drug Administration to fragment renal and ureteral calculi noninvasively in awake human patients. In this single-arm clinical trial, BWL was performed under general anesthesia in treatments less than 90 min. Outcomes included apparent fragmentation, ureterolith passage, decrease in pyelectasia or hydroureter, and decrease in serum creatinine concentration. Adverse events were characterized by severity and relationship to BWL. In total, 12 ureters with 17 ureteroliths were treated with BWL. Five ureters received 1 treatment, 6 received 2, and 1 received 3, resulting in 20 total treatments. Ureterolith fragmentation was apparent in 11 of 12 treated ureters. Of 10 ureters with follow-up imaging, 8 had ureterolith passage and an accompanying decrease in ureteral dilatation. For the cats with ureterolith passage, the median serum creatinine concentration change was –29% (range, –56% to 28%) at 1–3 weeks. One serious BWL-related adverse event of worsening obstruction from residual fragments occurred, but was solved with retreatment.

We tested feasibility of burst wave lithotripsy (BWL) and ultrasonic propulsion to noninvasively fragment and expel small, asymptomatic renal stones in awake participants.

Adult patients suspected of having 2- to 7-mm stones were consented and screened for eligibility. BWL and ultrasonic propulsion were applied to up to 3 stones in 1 kidney of qualifying participants for a 30-minute total exposure. Participants completed a CT scan and the Wisconsin Stone Quality-of-Life (WISQOL) questionnaire within 90 days before and 120 days after the procedure. Participants were contacted weekly for 3 weeks after the procedure to assess adverse events (AEs). Outcomes included (1) no fragment > 2 mm, (2) unanticipated health care visits, (3) change in stone volume, (4) reported AEs, and (5) WISQOL score.

Forty-one participants were enrolled between April 2023 and October 2024. Twenty-one participants failed screening because no stones were seen, stones were too large or small, stone visibility was too deep or obstructed, or they declined to participate. Twenty participants with 31 stones received the research procedure with 7 undergoing a single repeat procedure. Twenty-two of 31 stones (71%) met the primary effectiveness outcome of no fragment > 2 mm, with 17 of 31 stones (55%) reported as stone free. Median stone volume reduction (IQR) was 100% (88%–100%). No participants returned unexpectedly for care related to the procedure. AEs were all Grade I by modified Clavien classification. WISQOL scores improved on 10 of 15 completed questionnaires.

Small, asymptomatic renal stones were effectively and safely removed in awake participants in a clinic setting.

Introduction: Current American Urological Association guidelines recommend that patients with acute obstructive kidney stone requiring continuous anticoagulation/antiplatelet therapy should not be treated by shockwave lithotripsy or percutaneous nephrolithotomy because of the risk of catastrophic renal hemorrhage possible with those techniques. Currently, ureteroscopy is the only recommended surgical treatment. We evaluated if burst wave lithotripsy (BWL) could be used in these cases by treating pigs with BWL while undergoing anticoagulation therapy.

Materials and Methods: Six pigs (31–37 kg) were given 200 units/kg porcine heparin, and then the right kidney of each animal was treated with a dose of BWL (18,000 ultrasound pulses at 10 Hz, 20 cycles/pulse, peak positive pressure of 12 MPa) known to fracture kidney stones. The contralateral kidney served as a control. Therapeutic anticoagulation was confirmed by evaluating activated partial thromboplastin time (aPTT). Microhematuria was checked by urine test strips. Kidneys were subsequently evaluated for hemorrhagic injury via MRI.

Results: aPTT was significantly elevated (>100 seconds) throughout the entire treatment period (p = <0.001) indicating therapeutic anticoagulation. Gross hematuria was not observed in any of the pigs. After BWL, microhematuria averaged 145.8 red blood cells (RBC)/μL in the BWL-treated kidney and 48 RBC/μL in the control kidneys, and there was no statistically significant difference noted in microhematuria rates between the two groups (p = 0.16). Hemorrhagic injury measured only 0.10±0.02% of the tissue in the BWL-treated kidneys and 0.12±0.04% in the control side, with a paired difference of –0.03±0.05%, showing no significant difference (p = 0.58).

Conclusions: A typical clinical dose of BWL causes no hemorrhagic injury to the kidney even during therapeutic anticoagulation therapy. This result suggests that BWL should be safe to use in patients with stone undergoing anticoagulation/antiplatelet therapy.

Marine mammals may develop kidney stones, which can be challenging to treat. We describe burst wave lithotripsy (BWL) and ultrasonic propulsion to treat ureteral calculi in a 48-year-old female bottlenose dolphin (Tursiops truncatus) and to reduce renal stone burden in a 23-year-old male harbor seal (Phoca vitulina). BWL and ultrasonic propulsion were delivered transcutaneously in sinusoidal ultrasound bursts to fragment and reposition stones. Targeting and monitoring were performed with real-time imaging integrated within the BWL system. Four dolphin stones were obtained and fragmented ex vivo. The dolphin case received a 10-min and a 20-min BWL treatment conducted approximately 24 h apart to treat two 8–10 mm partially obstructing right mid-ureteral stones, using oral sedation alone. For the harbor seal, while under general anesthesia, retrograde ureteroscopy attempts were unsuccessful because of ureteral tortuosity, and a 30-min BWL treatment was targeted on one 10-mm right kidney stone cluster. All 4 stones fragmented completely to < 2-mm fragments in < 20 min ex vivo. In the dolphin case, the ureteral stones appeared to fragment, spread apart, and move with ultrasonic propulsion. On post-treatment day 1, the ureteral calculi fragments shifted caudally reaching the ureteral orifice on day 9. On day 10, the calculi fragments passed, and the hydroureter resolved. In the harbor seal, the stone cluster was observed to fragment and was not visible on the post-operative computed tomography scan. The seal had gross hematuria and a day of behavior indicating stone passage but overall, an uneventful recovery. BWL and ultrasonic propulsion successfully relieved ureteral stone obstruction in a geriatric dolphin and reduced renal stone burden in a geriatric harbor seal.

Upper urinary tract stones are increasingly prevalent in pet cats and are difficult to manage. Surgical 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.

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 fragmented 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.

These data support further evaluation of burst wave lithotripsy as a noninvasive intervention for obstructing ureteroliths in cats.

Purpose:
Our goal was to test transcutaneous focused ultrasound in the form of ultrasonic propulsion and burst wave lithotripsy to reposition ureteral stones and facilitate passage in awake subjects.

Materials and Methods:
Adult subjects with a diagnosed proximal or distal ureteral stone were prospectively recruited. Ultrasonic propulsion alone or with burst wave lithotripsy was administered by a handheld transducer to awake, unanesthetized subjects. Efficacy outcomes included stone motion, stone passage, and pain relief. Safety outcome was the reporting of associated anticipated or adverse events.

Results:
Twenty-nine subjects received either ultrasonic propulsion alone (n = 16) or with burst wave lithotripsy bursts (n = 13), and stone motion was observed in 19 (66%). The stone passed in 18 (86%) of the 21 distal ureteral stone cases with at least 2 weeks follow‐up in an average of 3.9±4.9 days post-procedure. Fragmentation was observed in 7 of the burst wave lithotripsy cases. All subjects tolerated the procedure with average pain scores (0-10) dropping from 2.1±2.3 to 1.6±2.0 (P = .03). Anticipated events were limited to hematuria on initial urination post-procedure and mild pain. In total, 7 subjects had associated discomfort with only 2.2% (18 of 820) propulsion bursts.

Conclusions:
This study supports the efficacy and safety of using ultrasonic propulsion and burst wave lithotripsy in awake subjects to reposition and break ureteral stones to relieve pain and facilitate passage.

Introduction and Objective: In clinical trial NCT03873259, a 2.6-mm lower pole stone was treated transcutaneously and ex vivo with 390-kHz burst wave lithotripsy (BWL) for 40 minutes and failed to break. The stone was subsequently fragmented with 650-kHz BWL after a 4-minute exposure. This study investigated how to fragment small stones and why varying the BWL frequency may more effectively fragment stones to dust.

Methods: A linear elastic theoretical model was used to calculate the stress created inside stones from shock wave lithotripsy (SWL) and different BWL frequencies mimicking the stone's size, shape, lamellar structure, and composition. To test model predictions about the impact of BWL frequency, matched pairs of stones (1–5 mm) were treated at (1) 390 kHz, (2) 830 kHz, and (3) 390 kHz followed by 830 kHz. The mass of fragments > 1 and 2 mm was measured over 10 minutes of exposure.

Results: The linear elastic model predicts that the maximum principal stress inside a stone increases to more than 5.5 times the pressure applied by the ultrasound wave as frequency is increased, regardless of the composition tested. The threshold frequency for stress amplification is proportionate to the wave speed divided by the stone diameter. Thus, smaller stones may be likely to fragment at a higher frequency, but not at a lower frequency below a limit. Unlike with SWL, this amplification in BWL occurs consistently with spherical and irregularly shaped stones. In water tank experiments, stones smaller than the threshold size broke fastest at high frequency (p = 0.0003), whereas larger stones broke equally well to submillimeter dust at high, low, or mixed frequencies.

Conclusions: For small stones and fragments, increasing frequency of BWL may produce amplified stress in the stone causing the stone to break. Using the strategies outlined here, stones of all sizes may be turned to dust efficiently with BWL.

We report stone comminution in the first 19 human subjects by burst wave lithotripsy (BWL), which is the transcutaneous application of focused, cyclic ultrasound pulses. This was a prospective multi-institutional feasibility study recruiting subjects undergoing clinical ureteroscopy (URS) for at least 1 stone ≤12 mm as measured on computerized tomography. During the planned URS, either before or after ureteroscope insertion, BWL was administered with a handheld transducer, and any stone fragmentation and tissue injury were observed. Up to 3 stones per subject were targeted, each for a maximum of 10 minutes. The primary effectiveness outcome was the volume percent comminution of the stone into fragments ≤2 mm. The primary safety outcome was the independent, blinded visual scoring of tissue injury from the URS video. Overall, median stone comminution was 90% (IQR 20, 100) of stone volume with 21 of 23 (91%) stones fragmented. Complete fragmentation (all fragments ≤2 mm) within 10 minutes of BWL occurred in 9 of 23 stones (39%). Of the 6 least comminuted stones, likely causative factors for decreased effectiveness included stones that were larger than the BWL beamwidth, smaller than the BWL wavelength or the introduction of air bubbles from the ureteroscope. Mild reddening of the papilla and hematuria emanating from the papilla were observed ureteroscopically. The first study of BWL in human subjects resulted in a median of 90% comminution of the total stone volume into fragments ≤2 mm within 10 minutes of BWL exposure with only mild tissue injury.

Unlike shock wave lithotripsy, burst wave lithotripsy (BWL) uses tone bursts, consisting of many periods of a sinusoidal wave. In this work, an analytical theoretical approach to modeling mechanical stresses in a spherical stone was developed to assess the dependence of frequency and stone size on stress generated in the stone. The analytical model for spherical stones is compared against a finite-difference model used to calculate stress in nonspherical stones. It is shown that at low frequencies, when the wavelength is much greater than the diameter of the stone, the maximum principal stress is approximately equal to the pressure amplitude of the incident wave. With increasing frequency, when the diameter of the stone begins to exceed about half the wavelength in the surrounding liquid (the exact condition depends on the material of the stone), the maximum stress increases and can be more than six times greater than the incident pressure. These results suggest that the BWL frequency should be elevated for small stones to improve the likelihood and rate of fragmentation.

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.

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.

In certain medical applications, transmitting an ultrasound beam through the skin to manipulate a solid object within the human body would be beneficial. Such applications include, for example, controlling an ingestible camera or expelling a kidney stone. In this paper, ultrasound beams of specific shapes were designed by numerical modeling and produced using a phased array. These beams were shown to levitate and electronically steer solid objects (3-mm-diameter glass spheres), along preprogrammed paths, in a water bath, and in the urinary bladders of live pigs. Deviation from the intended path was on average <10%. No injury was found on the bladder wall or intervening tissue.

Burst wave lithotripsy (BWL) is a technology for comminuting urinary stones. A BWL transducer's requirements of high-pressure output, limited acoustic window, specific focal depth, and frequency to produce fragments of passable size constrain focal beamwidth. However, BWL is most effective with a beam wider than the stone. To produce a broad-beam, an iterative angular spectrum approach was used to calculate a phase screen that was realized with a rapid prototyped lens. The technique did not accurately replicate a target beam profile when an axisymmetric profile was chosen. Adding asymmetric weighting functions to the target profile achieved appropriate beamwidth. Lenses were designed to create a spherically focused narrow-beam (6 mm) and a broad-beam (11 mm) with a 350-kHz transducer and 84-mm focal depth. Both lenses were used to fragment artificial stones (11 mm long) in a water bath, and fragmentation rates were compared. The linearly simulated and measured broad beamwidths that were 12 mm and 11 mm, respectively, with a 2-mm-wide null at center. The broad-beam and the narrow-beam lenses fragmented 44 ±â€‰9% and 16 ±â€‰4% (p = 0.007, N = 3) of a stone by weight, respectively, in the same duration at the same peak negative pressure. The method broadened the focus and improved the BWL rate of fragmentation of large stones.

Theoretical and numerical models were developed to calculate the polariscopic integrated light intensity that forms a projection of the dynamic stress within an axisymmetric elastic object. Although the model is general, this paper addressed its application to measurements of stresses in model kidney stones from a burst wave lithotripter for stone fragmentation. The stress was calculated using linear elastic equations, and the light propagation was modeled in the instantaneous case by integrating over the volume of the stone. The numerical model was written in finite differences. The resulting images agreed well with measured images. The measured images corresponded to the maximum shear stress distribution, although other stresses were also plotted. Comparison of the modeled and observed polariscope images enabled refinement of the photoelastic constant by minimizing the error between the calculated and measured fields. These results enable quantification of the stress within the polariscope images, determination of material properties, and the modes and mechanisms of stress production within a kidney stone. Such a model may help in interpreting elastic waves in structures, such as stones, toward improving lithotripsy procedures.

Burst wave lithotripsy is a method to noninvasively fragment urinary stones by short pulses of focused ultrasound. In this study, physical mechanisms of stone fracture during burst wave lithotripsy were investigated. Photoelasticity imaging was used to visualize elastic wave propagation in model stones and compare results to numerical calculations. Epoxy and glass stone models were made into rectangular, cylindrical, or irregular geometries and exposed in a degassed water bath to focused ultrasound bursts at different frequencies. A high-speed camera was used to record images of the stone during exposure through a circular polariscope backlit by a monochromatic flash source. Imaging showed the development of periodic stresses in the stone body with a pattern dependent on frequency. These patterns were identified as guided wave modes in cylinders and plates, which formed standing waves upon reflection from the distal surfaces of the stone model, producing specific locations of stress concentration in the models. Measured phase velocities compared favorably to numerically calculated modes dependent on frequency and material. Artificial stones exposed to bursts produced cracks at positions anticipated by this mechanism. These results support guided wave generation and reflection as a mechanism of stone fracture in burst wave lithotripsy.

Burst wave lithotripsy and ultrasonic propulsion of kidney stones are novel, noninvasive emerging technologies to separately or synergistically fragment and reposition stones in an office setting. The purpose of this review is to discuss the latest refinements in technology, to update on testing of safety and efficacy, and to review future applications.

Burst wave lithotripsy produced consistent, small passable fragments through transcutaneous applications in a porcine model, while producing minimal injury and clinical trials are now underway. A more efficient ultrasonic propulsion design that can also deliver burst wave lithotripsy effectively repositioned 95% of stones in 18 human participants (18 of 19 kidneys) and clinical trials continue. Acoustic tractor beam technology is an emerging technology with promising clinical applications through the manipulation of macroscopic objects.

The goal of the reviewed work is an office-based system to image, fragment, and reposition urinary stones to facilitate their natural passage. The review highlights progress in establishing safety, effectiveness, and clinical benefit of these new technologies. The work is also anticipating challenges in clinical trials and developing the next generation of technology to improve on the technology as it is being commercialized today.

Burst wave lithotripsy is an experimental technology to noninvasively fragment kidney stones with focused bursts of ultrasound (US). This study evaluated the safety and effectiveness of specific lithotripsy parameters in a porcine model of nephrolithiasis.

A 6- to 7-mm human kidney stone was surgically implanted in each kidney of three pigs. A burst wave lithotripsy US transducer with an inline US imager was coupled to the flank and the lithotripter focus was aligned with the stone. Each stone was exposed to burst wave lithotripsy at 6.5 to 7 MPa focal pressure for 30 minutes under real-time image guidance. After treatment, the kidneys were removed for gross, histologic, and MRI assessment. Stone fragments were retrieved from the kidney to determine the mass comminuted to pieces <2 mm.

On average, 87% of the stone mass was reduced to fragments <2 mm. In three of five treatments, stones were completely comminuted to <2-mm fragments. In two of five treatments, stones were partially disintegrated, but larger fragments remained. One stone was not treated because no suitable acoustic window was identified. No injury was detected through gross, histologic, or MRI examination in the parenchymal tissue, although petechial damage and surface erosion were identified on the urothelium of the collecting system limited to the area around the stone.

Burst wave lithotripsy can consistently produce stone fragments small enough to spontaneously pass by transcutaneous administration of US pulses. The data suggest that such exposures produce minimal injury to the kidney and urinary tract.

Objective: The goal was to test whether stone composition and kidney phantom configuration affected comminution in extracorporeal shockwave lithotripsy (SWL) laboratory tests. Confinement may enhance the accumulation of dust and associated cavitation bubbles in the fluid surrounding the stone. It is known that high shockwave delivery rates in SWL are less effective because bubbles generated by one shockwave do not have sufficient time to dissolve, thereby shielding the next shockwave.

Materials and Methods: Experiments were conducted with a lithotripter coupled to a water bath. The rate of comminution was measured by weighing fragments over 2 mm at 5-minute time points. First, plaster and crystal stones were broken in four phantoms: a nylon wire mesh, an open polyvinyl chloride (PVC) cup, a closed PVC cup, and an anatomical kidney model — the phantoms have decreasing fluid volumes around the stone. Second, the fluid volume in the kidney model was flushed with water at different rates (0, 7, and 86 mL/min) to remove dust.

Results: The efficiency of breakage of stones decreases for the dust emitting plaster stones (percentage of breakage in 5 minutes decreased from 92% ±â€‰2% [n = 3] in wire mesh to 19% ±â€‰3% [n = 3] in model calix) with increasing confinement, but not for the calcite crystal stones that produced little dust (percentage of breakage changed from 87% ±â€‰3% [n = 3] in wire mesh to 81% ±â€‰3% [n = 3] in kidney model). Flushing the kidney phantom at the fastest rate improved comminution of smaller plaster stones by 27%.

Conclusions: Phantoms restricting dispersion of dust were found to affect stone breakage in SWL and in vitro experiments should replicate kidney environments. The dust around the stone and potential cavitation may shield the stone from shockwaves and reduce efficacy of SWL. Understanding of stone composition and degree of hydronephrosis could be used to adapt patient-specific protocols.

Proceedings, 176th Meeting of the Acoustical Society of America, 5-9 November 2018, Victoria, BC, Canada.

Non-invasive kidney stone treatments such as shock wave lithotripsy (SWL) and burst wave lithotripsy (BWL) rely on the delivery of pressure waves through tissue to the stone. In both SWL and BWL, the potential to hinder comminution by exciting cavitation proximal to the stone has been reported. To elucidate how different stones alter prefocal cavitation in BWL, different natural and synthetic stones were treated in vitro using a therapy transducer operating at 350 kHz (peak negative pressure 7 MPa, pulse length 20 cycles, pulse repetition frequency 10 Hz). Stones were held in a confined volume of water designed to mimic the geometry of a kidney calyx, with the water filtered and degassed to maintain conditions for which the cavitation threshold (in the absence of a stone) matches that from in vivo observations. Stone targeting and cavitation monitoring were performed via ultrasound imaging using a diagnostic probe aligned coaxially with the therapy transducer. Quantitative differences in the extent and location of cavitation activity were observed for different stone types — e.g., stones (natural and synthetic) that are known to be porous produced larger prefocal cavitation clouds. Ongoing work will focus on correlation of such cavitation metrics with stone fragmentation.

176th Meeting of the Acoustical Society of America, 5-9 November 2018, Victoria, BC, Canada.

Modeling and numerical simulation of bubble clouds induced by intense ultrasound waves are conducted to quantify the effect of cloud cavitation on burst wave lithotripsy, a proposed non-invasive alternative to shock wave lithotripsy that uses pulses of ultrasound with an amplitude of O(1) MPa and a frequency of O(100) kHz. A unidirectional acoustic source model and an Eulerian-Lagrangian method are developed for simulation of ultrasound generation from a multi-element array transducer and cavitation bubbles, respectively. Parametric simulations of the spherical bubble cloud dynamics reveal a new scaling parameter that dictates both the structure of the bubble cloud and the amplitude of the far-field, bubble-scattered acoustics. The simulation further shows that a thin layer of bubble clouds nucleated near a kidney stone model can shield up to 90% of the incoming wave energy, indicating a potential loss of efficacy during the treatment due to cavitation. Strong correlations are identified between the far-field, bubble-scattered acoustics and the magnitude of the shielding, which could be used for ultrasound monitoring of cavitation during treatments. The simulations are validated by companion experiments in vitro.

176th Meeting of the Acoustical Society of America 5-9 November 2018, Victoria, BC, Canada.

Our goal is an office-based, handheld ultrasound system to target, detach, break, and/or expel stones and stone fragments from the urinary collecting system to facilitate natural clearance. Repositioning of stones in humans (maximum 2.5 MPa, and 3-second bursts) and breaking of stones in a porcine model (maximum 50 cycles, 20 Hz repetition, 30 minutes, and 7 MPa peak negative pressure) have been demonstrated using the same 350-kHz probe. Repositioning in humans was conducted during surgery with a ureteroscope in the kidney to film stone movement. Independent video review confirmed stone movements (≥ 3 mm) in 15 of 16 kidneys (94%). No serious or unanticipated adverse events were reported. Experiments of burst wave lithotripsy (BWL) effectiveness on breaking human stones implanted in the porcine bladder and kidney demonstrated fragmentation of 7 of 7 stones on post mortem dissection. A 1-week survival study with the BWL exposures and 10 specific pathogen-free pigs, showed all findings were within normal limits on clinical pathology, hematology, and urinalysis. These results demonstrate that repositioning of stones with ultrasonic propulsion and breaking of stones with BWL are safe and effective.

Proceedings, 176th Meeting of the Acoustical Society of America, 5-9 November 2018, Victoria, BC, Canada.

Burst wave lithotripsy (BWL) is a new non-invasive method for stone comminution using bursts of sub-megahertz ultrasound. A porcine model of urolithiasis and techniques to implement BWL treatment has been developed to evaluate its effectiveness and acute safety. Six human calcium oxalate monohydrate stones (6–7 mm) were hydrated, weighed, and surgically implanted into the kidneys of three pigs. Transcutaneous stone treatments were performed with a BWL transducer coupled to the skin via an external water bath. Stone targeting and treatment monitoring were performed with a co-aligned ultrasound imaging probe. Treatment exposures were applied in three 10-minute intervals for each stone. If sustained cavitation in the parenchyma was observed by ultrasound imaging feedback, treatment was paused and the pressure amplitude was decreased for the remaining time. Peak negative focal pressures between 6.5 and 7 MPa were applied for all treatments. After treatment, stone fragments were removed from the kidneys. At least 50% of each stone was reduced to <2 mm fragments. 100% of four stones were reduced to <4 mm fragments. Magnetic resonance imaging showed minimal injury to the functional renal volume. This study demonstrated that BWL could be used to effectively fragment kidney stones with minimal injury.

Proceedings, 176th Meeting of the Acoustical Society of America, 5-9 November 2018, Victoria, BC, Canada.

Burst wave lithotripsy (BWL) is a potential noninvasive treatment for breaking kidney stones. BWL requirements of high-pressure output, limited aperture for acoustic window, and specific focal length and frequency constrain the focal beam width. However, BWL is most effective only on stones smaller than the beam width. We tested a porous piezoelectric material (PZ36) to increase the output power and designed acoustic lenses that broaden the beam. A weighted iterative angular spectrum approach was used to calculate the source phase distribution needed to generate desired cross sectional focal beam profiles each of 12 mm width. The phase calculations were then 3D printed as holographic lenses placed over a circular aperture of 80-mm diameter, 350 kHz PZ36 to produce the desired beam at 85 mm depth. The difference in simulated beam width and that measured by hydrophone was <1 mm, and the structural–similarity index value was greater than 0.65. The differences in structures were due not to shape and size of the 6-dB contours but to amplitude distribution within the contour. In conclusion, this design approach combined with 3D printing provides a way to tailor focal beam profiles for lithotripsy transducers.

Combined laboratory experiment and numerical simulation are conducted on bubble clouds nucleated on the surface of a model kidney stone to quantify the energy shielding of the stone caused by cavitation during burst wave lithotripsy (BWL). In the experiment, the bubble clouds are visualized and bubble-scattered acoustics are measured. In the simulation, a compressible, multi-component flow solver is used to capture complex interactions among cavitation bubbles, the stone, and the burst wave. Quantitative agreement is confirmed between results of the experiment and the simulation. In the simulation, a significant shielding of incident wave energy by the bubble clouds is quantified. The magnitude of shielding can reach up to 90% of the energy of the incoming burst wave that otherwise would be transmitted into the stone, suggesting a potential loss of efficacy of stone comminution. There is a strong correlation between the magnitude of the energy shielding and the amplitude of the bubble-scattered acoustics, independent of the initial size and the void fraction of the bubble cloud within a range addressed in the simulation. This correlation could provide for real-time monitoring of cavitation activity in BWL.

Purpose

Burst wave lithotripsy (BWL) is a new technology in development to fragment urinary stones. Ultrasonic propulsion (UP) is a separate technology under investigation for displacing stones. We measure the effect of propulsion pulses on stone fragmentation from BWL.

Materials and Methods

Two artificial stone models (crystalline calcite, BegoStone plaster) and human calcium oxalate monohydrate (COM) stones measuring 5 to 8 mm were subjected to ultrasound exposures in a polyvinyl chloride tissue phantom within a water bath. Stones were exposed to BWL with and without propulsion pulses interleaved for set time intervals depending on stone type. Fragmentation was measured as a fraction of the initial stone mass fragmented to pieces smaller than 2 mm.

Results

BegoStone model comminution improved from 6% to 35% (p < 0.001) between BWL and BWL with interleaved propulsion in a 10-minute exposure. Propulsion alone did not fragment stones, whereas addition of propulsion after BWL slightly improved BegoStone model comminution from 6% to 11% (p < 0.001). BegoStone model fragmentation increased with rate of propulsion pulses. Calcite stone fragmentation improved from 24% to 39% in 5 minutes (p = 0.047) and COM stones improved from 17% to 36% (p = 0.01) with interleaved propulsion.

Conclusions

BWL with UP improved stone fragmentation compared with BWL alone in vitro. The improvement was greatest when propulsion pulses are interleaved with BWL treatment and when propulsion pulses are applied at a higher rate. Thus, UP may be a useful adjunct to enhance fragmentation in lithotripsy in vivo.

Burst wave lithotripsy (BWL) is an experimental method to noninvasively fragment urinary calculi using low-frequency focused bursts of ultrasound. To optimize many of the acoustic parameters for this technology, it is necessary to understand the physical interactions between ultrasound bursts and stones. In this study, the interaction of elastic waves with model stones was simulated and experimentally visualized by photoelastography, a technique using polarized light to spatially and temporally visualize stress patterns.