Ultrasonic propulsion is an investigational procedure for awake patients. Our purpose was to evaluate whether ultrasonic propulsion to facilitate residual kidney stone fragment clearance reduced relapse.

This multicenter, prospective, open-label, randomized, controlled trial used single block randomization (1:1) without masking. Adults with residual fragments (individually 5 mm or smaller) were enrolled. Primary outcome was relapse as measured by stone growth, a stone-related urgent medical visit, or surgery by 5 years or study end. Secondary outcomes were fragment passage within 3 weeks and adverse events within 90 days. Cumulative incidence of relapse was estimated using the Kaplan-Meier method. Log-rank test was used to compare the treatment (ultrasonic propulsion) and control (observation) groups.

The trial was conducted from May 9, 2015, through April 6, 2024. Median follow-up (interquartile range) was 3.0 (1.8–3.2) years. The treatment group (n = 40) had longer time to relapse than the control group (n = 42; P < .003). The restricted mean time-to-relapse was 52% longer in the treatment group than in the control group (1530 ± 92 days vs 1009 ± 118 days), and the risk of relapse was lower (hazard ratio 0.30, 95% CI 0.13–0.68) with 8 of 40 and 21 of 42 participants, respectively, experiencing relapse. Omitting 3 participants not asked about passage, 24 treatment (63%) and 2 control (5%) participants passed fragments within 3 weeks of treatment. Adverse events were mild, transient, and self-resolving, and were reported in 25 treated participants (63%) and 17 controls (40%).

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.

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.

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.

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.

Effective stone comminution during shock wave lithotripsy (SWL) is dependent on precise three-dimensional targeting of the shock wave. Respiratory motion, imprecise targeting or shock wave alignment, and stone movement may compromise treatment efficacy. The purpose of this study was to evaluate the accuracy of shock wave targeting during SWL treatment and the effect of motion due to respiration.

Methods: Ten patients underwent SWL for the treatment of 13 renal stones. Stones were targeted fluoroscopically using a Healthtronics Lithotron (5 cases) or Dornier Compact Delta II (5 cases) shock wave lithotripter. Shocks were delivered at a rate of 1-2Hz with ramping shock wave energy settings of 14-26kV or level 1-5. After the low energy pre-treatment and protective pause, a commercial diagnostic ultrasound imaging system was used to record images of the stone during active SWL treatment. Shock wave accuracy, defined as the proportion of shock waves that resulted in stone motion with shock wave delivery, and respiratory stone motion were determined by two independent observers who reviewed the ultrasound videos.

Results: Mean age was 51±15 years with 60% males and mean stone size was 10.5±3.7 mm (range 5-18 mm). A mean of 2675±303 shocks were delivered. Shock wave-induced stone motion was observed with every stone. Accurate targeting of the stone occurred in 60±15% of shock waves.

Conclusions: Ultrasound imaging during SWL revealed that 40% of shock waves miss the stone and contribute solely to tissue injury, primarily due to movement with respiration. These data support the need for a device to deliver shock waves only when the stone is in target. Ultrasound imaging provides real-time assessment of stone targeting and accuracy of shock wave delivery.

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.

The benefits of removing small (≤6 mm), asymptomatic kidney stones endoscopically is unknown. Current guidelines leave such decisions to the urologist and the patient. A prospective study involving older, nonendoscopic technology and some retrospective studies favor observation. However, published data indicate that about half of small renal stones left in place at the time that larger stones were removed caused other symptomatic events within 5 years after surgery.

The removal of small, asymptomatic kidney stones during surgery to remove ureteral or contralateral kidney stones resulted in a lower incidence of relapse than nonremoval and in a similar number of emergency department visits related to the surgery.

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.

The color Doppler ultrasound twinkling artifact has been found to improve detection of kidney stones with ultrasound; however, it appears on only ~60% of stones. Evidence from ex vivo kidney stones suggests twinkling arises from microbubbles stabilized in crevices on the stone surface. Yet it is unknown whether these bubbles are present on stones in humans. Here, we used a research ultrasound system to quantify twinkling in humans with kidney stones in a hyperbaric chamber. Eight human patients with non-obstructive kidney stones previously observed to twinkle were exposed to a maximum pressure of 4 atmospheres absolute (ATA) while breathing air, except during the 10-min pause at 1.6 ATA and while the pressure decreased to 1 ATA, during which patients breathed oxygen to minimize the risk of decompression sickness. A paired one-way t-test was used to compare the mean twinkle power at each pressure pause with baseline twinkling, with p < 0.05 considered to indicate significance. Results revealed that exposure to 3 and 4 ATA of pressure significantly reduced twinkle power by averages of 35% and 39%, respectively, in 7 patients (p = 0.04); data from the eighth patient were excluded because of corruption. This study supports the theory that microbubbles are present on kidney stones in humans.

A considerable publication record exists comparing sensitivity and specificity of radiological ultrasound (including point of care ultrasound) to computerized tomography for stone disease. However, the practical application of in-office ultrasound to support the growing number of kidney stone centers around the world represents a nuanced topic that is ripe for study and discussion. We provide a descriptive analysis of how in-office ultrasound is being used as an adjunct to clinical care based on our experience during 50 days in clinic at an institutionally affiliated, multidisciplinary kidney stone center. Clinic subjects gave consent and underwent ultrasound as part of research studies. Ultrasonograms were shared with and verified by the treating physician before the patient was discharged from care. We counted the number of times research imaging altered the care plan. Of the 60 patients enrolled the clinician used the information obtained from the studies in 20 (33%) to determine the course of clinical care that resulted in a change in treatment or process. Ultrasound has the potential to be a cost-effective and valuable tool that can provide more efficient workflow within a kidney stone center or urology clinic.

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.

Ultrasonic propulsion is an investigative modality to noninvasively image and reposition urinary stones. Our goals were to test safety and effectiveness of new acoustic exposure conditions from a new transducer, and to use simultaneous ureteroscopic and ultrasonic observation to quantify stone repositioning.

During operation, ultrasonic propulsion was applied transcutaneously, whereas stone targets were visualized ureteroscopically. Exposures were 350 kHz frequency, ≤200 W/cm² focal intensity, and ≤3-second bursts per push. Ureteroscope and ultrasound (US) videos were recorded. Video clips with and without stone motion were randomized and scored for motion ≥3 mm by independent reviewers blinded to the exposures. Subjects were followed with telephone calls, imaging, and chart review for adverse events.

The investigative treatment was used in 18 subjects and 19 kidneys. A total of 62 stone targets were treated ranging in size from a collection of "dust" to 15 mm. Subjects received an average of 17 ñ 14 propulsion bursts (per kidney) for a total average exposure time of 40 ñ 40 seconds. Independent reviewers scored at least one stone movement ≥3 mm in 18 of 19 kidneys (95%) from the ureteroscope videos and in 15 of 19 kidneys (79%) from the US videos. This difference was probably because of motion out of the US imaging plane. Treatment repositioned stones in two cases that would have otherwise required basket repositioning. No serious adverse events were observed with the device or procedure.

Ultrasonic propulsion was shown to be safe, and it effectively repositioned stones in 95% of kidneys despite positioning and access restrictions caused by working in an operating room on anesthetized subjects.

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.

Introduction: Studies suggest that the width of the acoustic shadow on ultrasound (US) more accurately reflects true stone size than the stone width in US images. We evaluated the need for training in the adoption of the acoustic shadow sizing technique by clinical providers.

Methods: Providers without shadow sizing experience were recruited and assigned in a stratified, alternating manner to receive a training tutorial ("trained") or no intervention ("control"). Each conducted a baseline assessment of 24 clinical US images; where present, shadow width was measured using custom calipers. The trained group subsequently completed a standardized training module on shadow sizing. All subjects repeated measurements after ~1 week. Group demographics were compared using Fisher's exact test. Measurements were compared to clinically reported stone sizes on corresponding CT and US using mixed-effects models. One millimeter concordance between shadow and CT size was compared using a generalized linear mixed-effects model.

Results: Twenty-six subjects were included. There was no significant difference between groups in demographics, clinical role, or US experience. Mean reported CT and US stone sizes were 6.8 ± 4.0 mm and 10.3 ± 4.1 mm, respectively. At baseline, there was no difference in shadow size measurements between groups (p = 0.18), and shadow size was no more accurate than US stone size (p = 0.28 trained; p = 0.81 control), compared to CT. After training, overestimation bias of shadow size in the trained group decreased to 1.6 ± 0.5 mm (p < 0.01), relative to CT. This was not significantly associated with clinical rank, US experience, or stone-measuring experience. One millimeter concordance with CT size significantly increased from 23% to 35% of stones after training (p = 0.01). No significant improvement occurred in the control group.

Conclusion: Acoustic shadow sizing was readily adopted by inexperienced providers, but was not more accurate than reported US stone sizes without training. Education on shadow sizing may be warranted before clinical adoption.

Multielement focused ultrasound phased arrays have been used in therapeutic applications to treat large tissue volumes by electronic steering of the focus, to target multiple simultaneous foci, and to correct aberration caused by inhomogeneous tissue pathways. There is an increasing interest in using arrays to generate more complex beam shapes and corresponding acoustic radiation force patterns for manipulation of particles such as kidney stones. Toward this end, experimental and computational tools are needed to enable accurate delivery of desired transducer vibrations and corresponding ultrasound fields. The purpose of this paper was to characterize the vibrations of a 256-element array at 1.5 MHz, implement strategies to compensate for variability, and test the ability to generate specified vortex beams that are relevant to particle manipulation. The characterization of the array output was performed in water using both element-by-element measurements at the focus of the array and holography measurements for which all the elements were excited simultaneously. Both methods were used to quantify each element’s output so that the power of each element could be equalized. Vortex beams generated using both compensation strategies were measured and compared to the Rayleigh integral simulations of fields generated by an idealized array based on the manufacturer’s specifications. Although both approaches improved beam axisymmetry, compensation based on holography measurements had half the error relative to the simulation results in comparison to the element-by-element method.

Purpose

Posterior acoustic shadow width has been proposed as a more accurate measure of kidney stone size compared to direct measurement of stone width on ultrasound (US). Published data in humans to date have been based on a research using US system. Herein, we compared these two measurements in clinical US images.

Methods

Thirty patient image sets where computed tomography (CT) and US images were captured less than 1 day apart were retrospectively reviewed. Five blinded reviewers independently assessed the largest stone in each image set for shadow presence and size. Shadow size was compared to US and CT stone sizes.

Results

Eighty percent of included stones demonstrated an acoustic shadow; 83% of stones without a shadow were ≤5 mm on CT. Average stone size was 6.5 ± 4.0 mm on CT, 10.3 ± 4.1 mm on US, and 7.5 ± 4.2 mm by shadow width. On average, US overestimated stone size by 3.8 ± 2.4 mm based on stone width (p < 0.001) and 1.0 ± 1.4 mm based on shadow width (p < 0.0098). Shadow measurements decreased misclassification of stones by 25% among three clinically relevant size categories (≤ 5, 5.1–10, > 10 mm), and by 50% for stones ≤ 5 mm.

Conclusions

US overestimates stone size compared to CT. Retrospective measurement of the acoustic shadow from the same clinical US images is a more accurate reflection of true stone size than direct stone measurement. Most stones without a posterior shadow are ≤ 5 mm.

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.

Maximizing the power of multi-element phased arrays is a critical factor for high intensity focused ultrasound (HIFU) applications such as histotripsy and transcostal sonications. This can be achieved by a tight packing of the array elements. Good electronic focusing capabilities are also required. Currently used quasi-random arrays with a relatively low filling factor of about 60% have this focusing ability. Here, a novel method of designing random HIFU arrays with the maximum possible filling factor (100% if no gaps between elements needed in practice are introduced) and polygonal elements of equal area and slightly different shape based on the capacity-constrained tessellation is described. The method is validated by comparing designs of two arrays with the same geometric and physical parameters: an existing 256-element array with a compact 16-spirals layout of circular elements and the proposed array with the maximum possible filling factor. Introduction of a 0.5 mm gap between the elements of the new array resulted in a reduction of its filling factor to 86% as compared with 61% for the spiral array. It is shown that for the same intensity at the elements, the proposed array provides two times higher total power while maintaining the same electronic focusing capabilities as compared to the spiral one. Furthermore, the surface of the capacity-constrained tessellation array, its boundary, and a central opening can have arbitrary shapes.

Kidney stones can exhibit a twinkling artifact under color-flow Doppler ultrasound. There has been much work that suggests the mechanism for this artifact is micron sized bubbles trapped in the cracks of the stone cavitating from the incident Doppler pulses. We hypothesize that the signal-to-clutter ratio (SCR) of stone-to-background in Doppler mode increases with the ultrasound mechanical index (MI), a metric of the likelihood of cavitation, and that a minimum MI is needed for visibility under Doppler.

Our results show the contrast ratio of the twinkling artifact on a kidney stone to background noise increases with the MI. This suggests that adjusting the system settings to increase the MI on the stone, such as lowering the frequency and increasing the amplitude, will improve stone contrast and the ability to detect a kidney stone. Additionally, ultrasound manufacturers can potentially implement a stone-specific imaging preset for Doppler that maximizes the MI of the output while remaining within the regulated safety limits.

The color Doppler ultrasound twinkling artifact, which highlights kidney stones with rapidly changing color, has the potential to improve stone detection; however, its inconsistent appearance has limited its clinical utility. Recently, it was proposed stable crevice bubbles on the kidney stone surface cause twinkling; however, the hypothesis is not fully accepted because the bubbles have not been directly observed. In this paper, the micron or submicron-sized bubbles predicted by the crevice bubble hypothesis are enlarged in kidney stones of five primary compositions by exposure to acoustic rarefaction pulses or hypobaric static pressures in order to simultaneously capture their appearance by high-speed photography and ultrasound imaging. On filming stones that twinkle, consecutive rarefaction pulses from a lithotripter caused some bubbles to reproducibly grow from specific locations on the stone surface, suggesting the presence of pre-existing crevice bubbles. Hyperbaric and hypobaric static pressures were found to modify the twinkling artifact; however, the simple expectation that hyperbaric exposures reduce and hypobaric pressures increase twinkling by shrinking and enlarging bubbles, respectively, largely held for rough-surfaced stones but was inadequate for smoother stones. Twinkling was found to increase or decrease in response to elevated static pressure on smooth stones, perhaps because of the compression of internal voids. These results support the crevice bubble hypothesis of twinkling and suggest the kidney stone crevices that give rise to the twinkling phenomenon may be internal as well as external.

Objective

To evaluate in more detail the effectiveness of a new designed more efficient ultrasonic propulsion for large stones and specific stone compositions in a tissue phantom model. In the first clinical trial of noninvasive ultrasonic propulsion, urinary stones of unknown compositions and sizes up to 10 mm were successfully repositioned.

Materials and Methods

The study included 8- to 12-mm stones of 4 different primary compositions (calcium oxalate monohydrate, ammonium acid urate, calcium phosphate, and struvite) and a renal calyx phantom consisting of a 12 mm x 30 mm well in a 10-cm block of tissue-mimicking material. Primary outcome was the number of times a stone was expelled over 10 attempts, with ultrasonic propulsion burst duration varying from 0.5 seconds to 5 seconds.

Results

Overall success rate at expelling stones was 95%. All calcium oxalate monohydrate and ammonium acid urate stones were expelled 100% of the time. The largest stone (12 mm) became lodged within the 12-mm phantom calyx 25% of the time regardless of the burst duration. With the 0.5-second burst, there was insufficient energy to expel the heaviest stone (0.88 g), but there was sufficient energy at the longer burst durations.

Conclusion

With a single burst, ultrasonic propulsion successfully moved most stones at least 3 cm and, regardless of size or composition, expelled them from the calyx. Ultrasonic propulsion is limited to the stones smaller than the calyceal space, and for each burst duration, related to maximum stone mass.

A noninvasive ultrasound (US) system to facilitate the passage of small kidney stones has been developed. The device incorporates a software-based US platform programmed with brightness mode and Doppler for visualizing stones, plus long duration focused pulses for repositioning stones using the same transducer. This paper characterizes the acoustic outputs of the ultrasonic propulsion device. Though the application and outputs are unique, measurements were performed based on the regulatory standards for both diagnostic US and extracorporeal lithotripters. The extended length of the pulse, time varying pressure output over the pulse, the use of focused targeting, and the need to regulate the output at shallow depths, however, required modifications to the traditional acoustic measurement methods. Output parameters included spatial-peak intensities, mechanical index (MI), thermal index, pulse energy, focal geometry, and target accuracy. The imaging and Doppler operating modes of the system meet the Food and Drug Administration acoustic power and intensity limits for diagnostic US device. Push mode operates at a maximum MI of 2.2, which is above the limit of 1.9 for diagnostic US, but well below any lithotripsy device and an ISPTA of 548 mW/cm², which is below the 720-mW/cm² limit for diagnostic US.

Multi-element ultrasound arrays are increasingly used in clinical practice for both imaging and therapy. In therapy, they allow electronic steering, aberration correction, and focusing. To avoid grating lobes, an important requirement for such an array is the absence of periodicity in the arrangement of the elements. A convenient solution is the arrangement of the elements along spirals. The objective of this work was to design, fabricate, and characterize an array for boiling histotripsy applications that is capable of generating shock waves in the focus of up to 100 MPa peak pressure while having a reasonable electronic steering range.

Hyperbaric pressures of 3–100 atmospheres absolute (ATA) have been shown to reduce the color Doppler ultrasound twinkling artifact on ex vivo human kidney stones, leading to the hypothesis that surface crevice microbubbles cause twinkling. Similarly supportive for the crevice bubble hypothesis is the suppression of kidney stone twinkling in animals breathing elevated levels of carbon dioxide. However, it is unclear whether stable microbubbles can exist on the surface of kidney stones in the human body. For the first time, we investigate the effect of hyperbaric pressure on in situ human kidney stones to determine whether stable microbubbles exist as measured by the color Doppler ultrasound twinkling artifact.

In the first-in-human trial of ultrasonic propulsion, subjects passed collections of residual stone fragments after repositioning with a C5-2 probe. Here, effectiveness and safety in moving multiple fragments is compared between the C5-2 and a custom SC-50 probe that produces a longer beam and burst duration.

Purpose: Greater visual contrast between calculi and tissue would improve ultrasound (US) imaging of urolithiasis and potentially expand clinical use. The color Doppler twinkling artifact has been suggested to provide enhanced contrast of stones compared with brightness mode (B-mode) imaging, but results are variable. This work provides the first quantitative measure of stone contrast in humans for B-mode and color Doppler mode, forming the basis to improve US for the detection of stones.

Materials and Methods: Using a research ultrasound system, B-mode imaging was tuned for detecting stones by applying a single transmit angle and reduced signal compression. Stone twinkling with color Doppler was tuned by using low-frequency transmit pulses, longer pulse durations, and a high-pulse repetition frequency. Data were captured from 32 subjects, with 297 B-mode and Doppler images analyzed from 21 subjects exhibiting twinkling signals. The signal to clutter ratio (i.e., stone to background tissue) (SCR) was used to compare the contrast of a stone on B-mode with color Doppler, and the contrast between stone twinkling and blood-flow signals within the kidney.

Results: The stone was the brightest object in only 54% of B-mode images and 100% of Doppler images containing stone twinkling. On average, stones were isoechoic with the tissue clutter on B-mode (SCR = 0 dB). Stone twinkling averaged 37 times greater contrast than B-mode (16 dB, p < 0.0001) and 3.5 times greater contrast than blood-flow signals (5.5 dB, p = 0.088).

Conclusions: This study provides the first quantitative measure of US stone to tissue contrast in humans. Stone twinkling contrast is significantly greater than the contrast of a stone on B-mode. There was also a trend of stone twinkling signals having greater contrast than blood-flow signals in the kidney. Dedicated optimization of B-mode and color Doppler stone imaging could improve US detection of stones.

Purpose: In the first-in-human trial of ultrasonic propulsion, subjects passed collections of residual stone fragments repositioned with a C5-2 probe. Here, effectiveness and safety in moving multiple fragments are compared between the C5-2 and a custom (SC-50) probe that produces a longer focal beam and burst duration.

Materials and Methods: Effectiveness was quantified by the number of stones expelled from a calyx phantom consisting of a 30-mm deep, water-filled well in a block of tissue mimicking material. Each probe was positioned below the phantom to move stones against gravity. Single propulsion bursts of 50 ms or 3 s duration were applied to three separate targets: 10 fragments of 2 different sizes (1–2 and 2–3 mm) and a single 4 x 7 mm human stone. Safety studies consisted of porcine kidneys exposed to an extreme dose of 10-minute burst duration, including a 7-day survival study and acute studies with surgically implanted stones.

Results: Although successful in the clinical trial, the shorter focal beam and maximum 50 ms burst duration of the C5-2 probe moved stones, but did not expel any stones from the phantom's 30-mm deep calyx. The results were similar with the SC-50 probe under the same 50 ms burst duration. Longer (3 s) bursts available with the SC-50 probe expelled all stones at both 4.5 and 9.5 cm "skin-to-stone" depths with lower probe heating compared to the C5-2. No abnormal behavior, urine chemistry, serum chemistry, or histological findings were observed within the kidney or surrounding tissues for the 10 min burst duration used in the animal studies.

Conclusions: A longer focal beam and burst duration improved expulsion of a stone and multiple stone fragments from a phantom over a broad range of clinically relevant penetration depths and did not cause kidney injury in animal studies.

Bone demineralization, dehydration and stasis put astronauts at increased risk of forming kidney stones in space. The color-Doppler ultrasound "twinkling artifact," which highlights kidney stones with color, can make stones readily detectable with ultrasound; however, our previous results suggest twinkling is caused by microbubbles on the stone surface which could be affected by the elevated levels of carbon dioxide found on space vehicles. Four pigs were implanted with kidney stones and imaged with ultrasound while the anesthetic carrier gas oscillated between oxygen and air containing 0.8% carbon dioxide. On exposure of the pigs to 0.8% carbon dioxide, twinkling was significantly reduced after 9–25 min and recovered when the carrier gas returned to oxygen. These trends repeated when pigs were again exposed to 0.8% carbon dioxide followed by oxygen. The reduction of twinkling caused by exposure to elevated carbon dioxide may make kidney stone detection with twinkling difficult in current space vehicles.

Bone demineralization, dehydration, and stasis put astronauts at an increased risk of forming kidney stones in space. The incidence of kidney stones and the potential for a mission-critical event are expected to rise as expeditions become longer and immediate transport to Earth becomes more problematic. At the University of Washington, we are developing an ultrasound-based stone management system to detect stones with S-mode^TM ultrasound imaging, break stones with burst wave lithotripsy (BWL^TM), and reposition stones with ultrasonic propulsion (UP^TM) on Earth and in space. This review discusses the development and current state of these technologies, as well as integration on the flexible ultrasound system sponsored by NASA and the National Space Biomedical Research Institute.

Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones.

Subjects underwent ultrasonic propulsion either awake without sedation in clinic or during ureteroscopy while anesthetized. Ultrasound imaging and a pain questionnaire were completed before, during, and after propulsion. The primary outcome was to reposition stones in the collecting system. Secondary outcomes included safety, controllable movement of stones, and movement of stones < 5 mm and ≥ 5 mm. Adverse events were assessed weekly for 3 weeks.

Kidney stones were repositioned in 14 of 15 subjects. Of the 43 targets, 28 (65%) showed some level of movement while 13 (30%) were displaced > 3 mm to a new location. Discomfort during the procedure was rare, mild, brief, and self-limited. Stones were moved in a controlled direction with over 30 fragments being passed by 4 of 6 subjects who previously had a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of a large stone at the UPJ. In 4 subjects a seemingly large stone was determined to be a cluster of small passable stones once moved.

Ultrasonic propulsion was able to successfully reposition stones and facilitate passage of fragments in humans with no adverse events associated with the investigational procedure.

Ultrasound is known to overestimate kidney stone size. We explored measuring the acoustic shadow behind kidney stones combined with different ultrasound imaging modalities to improve stone sizing accuracy. A total of 45 calcium oxalate monohydrate stones were imaged in vitro at 3 different depths with the 3 different ultrasound imaging modalities of conventional ray line, spatial compound and harmonic imaging. The width of the stone and the width of the acoustic shadow were measured by 4 operators blinded to the true size of the stone.

Shadow width was a more accurate measure of true stone size than a direct measurement of the stone in the ultrasound image (p <0.0001). The ultrasound imaging modality also impacted the measurement accuracy. All methods performed similarly for shadow size while harmonic imaging was the most accurate stone size modality. Overall 78% of the shadow sizes were accurate to within 1 mm, which is similar to the resolution obtained with clinical computerized tomography.

In animal models, pretreatment with low-energy shock waves and a pause decreased renal injury from shockwave lithotripsy (SWL). This is associated with an increase in perioperative renal resistive index (RI). A perioperative rise is not seen without the protective protocol, which suggests that renal vasoconstriction during SWL plays a role in protecting the kidney from injury. The purpose of our study was to investigate whether there is an increase in renal RI during SWL in humans.

Subjects were prospectively recruited from two hospitals. All subjects received an initial 250 shocks at low setting, followed by a 2-minute pause. Treatment power was then increased. Measurements of the renal RI were taken before start of procedure, at 250, after 750, after 1500 shocks, and at the end of the procedure. A linear mixed-effects model was used to compare RIs at the different time points.

Fifteen patients were enrolled. Average treatment time was 46±8 minutes. Average RI at pretreatment, after 250, after 750, after 1500 shocks, and post-treatment was 0.67±0.06, 0.69±0.08, 0.71±0.07, 0.73±0.07, and 0.74±0.06, respectively. In adjusted analyses, RI was significantly increased after 750 shocks compared with pretreatment (p=0.05).

Renal RI increases early during SWL in humans with the protective protocol. Monitoring for a rise in RI during SWL is feasible and may provide real-time feedback as to when the kidney is protected.

Ultrasound (US) overestimates stone size when compared with CT. The purpose of this work was to evaluate the overestimation of stone size with US in an in vitro water bath model and investigate methods to reduce overestimation.

Ten human stones (3–12 mm) were measured using B-mode (brightness mode) US by a sonographer blinded to the true stone size. Images were captured and compared using both a commercial US machine and software-based research US device. Image gain was adjusted between moderate and high stone intensities, and the transducer-to-stone depth was varied from 6 to 10 cm. A computerized stone-sizing program was developed to outline the stone width based on a grayscale intensity threshold.

Overestimation with the commercial device increased with both gain and depth. Average overestimation at moderate and high gain was 1.9±0.8 and 2.1±0.9 mm, respectively (p=0.6). Overestimation increased an average of 22% with an every 2-cm increase in depth (p=0.02). Overestimation using the research device was 1.5±0.9 mm and did not vary with depth (p=0.28). Overestimation could be reduced to 0.02±1.1 mm (p<0.001) with the computerized stone-sizing program. However, a standardized threshold consistent across depth, system, or system settings could not be resolved.

Stone size is consistently overestimated with US. Overestimation increased with increasing depth and gain using the commercial machine. Overestimation was reduced and did not vary with depth, using the software-based US device. The computerized stone-sizing program shows the potential to reduce overestimation by implementing a grayscale intensity threshold for defining the stone size. More work is needed to standardize the approach, but if successful, such an approach could significantly improve stone-sizing accuracy and lead to automation of stone sizing.

Purpose
We have developed a new method of lithotripsy that uses short, broadly focused bursts of ultrasound rather than shock waves to fragment stones. This study investigated the characteristics of stone comminution by burst wave lithotripsy in vitro.

Materials and Methods
Artificial and natural stones (mean 8.2±3.0 mm, range 5–15 mm) were treated with ultrasound bursts using a focused transducer in a water bath. Stones were exposed to bursts with focal pressure amplitude 𕟮.5 MPa at 200 Hz burst repetition rate until completely fragmented. Ultrasound frequencies of 170 kHz, 285 kHz, and 800 kHz were applied using 3 different transducers. The time to achieve fragmentation for each stone type was recorded, and fragment size distribution was measured by sieving.

Results
Stones exposed to ultrasound bursts were fragmented at focal pressure amplitudes 𕟴.8 MPa at 170 kHz. Fractures appeared along the stone surface, resulting in fragments separating at the surface nearest to the transducer until the stone was disintegrated. All natural and artificial stones were fragmented at the highest focal pressure of 6.5 MPa with treatment durations between a mean of 36 seconds for uric acid to 14.7 minutes for cystine stones. At a frequency of 170 kHz, the largest artificial stone fragments were <4 mm. Exposures at 285 kHz produced only fragments <2 mm, and 800 kHz produced only fragments <1 mm.

Conclusions
Stone comminution with burst wave lithotripsy is feasible as a potential noninvasive treatment method for nephrolithiasis. Adjusting the fundamental ultrasound frequency allows control of stone fragment size.

Objective
To provide an update on a research device to ultrasonically reposition kidney stones transcutaneously. This article reports preclinical safety and effectiveness studies, survival data, modifications of the system, and testing in a stone-forming porcine model. These data formed the basis for regulatory approval to test the device in humans.

Materials and Methods
The ultrasound burst was shortened to 50 ms from previous investigations with 1-s bursts. Focused ultrasound was used to expel 2- to 5-mm calcium oxalate monohydrate stones placed ureteroscopically in 5 pigs. Additionally, de novo stones were imaged and repositioned in a stone-forming porcine model. Acute safety studies were performed targeting 2 kidneys (6 sites) and 3 pancreases (8 sites). Survival studies followed 10 animals for 1 week after simulated treatment. Serum and urine analyses were performed, and tissues were evaluated histologically.

Results
All ureteroscopically implanted stones (6/6) were repositioned out of the kidney in 14 ± 8 minutes with 13 ± 6 bursts. On average, 3 bursts moved a stone more than 4 mm and collectively accounted for the majority of relocation. Stones (3 mm) were detected and repositioned in the 200-kg stone-forming model. No injury was detected in the acute or survival studies.

Conclusion
Ultrasonic propulsion is safe and effective in the porcine model. Stones were expelled from the kidney. De novo stones formed in a large porcine model were repositioned. No adverse effects were identified with the acute studies directly targeting kidney or pancreatic tissue or during the survival studies indicating no evidence of delayed tissue injury.

The global prevalence and incidence of renal calculi is reported to be increasing. Of the patients that undergo surgical intervention, nearly half experience symptomatic complications associated with stone fragments that are not passed and require follow-up surgical intervention. In a clinical simulation using a clinical prototype, ultrasonic propulsion was proven effective at repositioning kidney stones in pigs. The use of ultrasound to reposition smaller stones or stone fragments to a location that facilitates spontaneous clearance could therefore improve stone-free rates. The goal of this study was to determine an injury threshold under which stones could be safely repositioned.

Kidneys of 28 domestic swine were treated with exposures that ranged in duty cycle from 0%–100% and spatial peak pulse average intensities up to 30 kW/cm² for a total duration of 10 min. The kidneys were processed for morphological analysis and evaluated for injury by experts blinded to the exposure conditions.

At a duty cycle of 3.3%, a spatial peak intensity threshold of 16,620 W/cm² was needed before a statistically significant portion of the samples showed injury. This is nearly seven times the 2,400-W/cm² maximum output of the clinical prototype used to move the stones effectively in pigs.

The data obtained from this study show that exposure of kidneys to ultrasonic propulsion for displacing renal calculi is well below the threshold for tissue injury.

Purpose: Ultrasonic propulsion to reposition urinary tract calculi requires knowledge about ultrasound image capture, device manipulation, and interpretation. The purpose of this study was to validate a cognitive and technical skills curriculum to teach urologists ultrasonic propulsion to reposition kidney stones in tissue phantoms.

Materials and Methods: Ten board-certified urologists recruited from a single institution underwent a didactic session on renal ultrasound imaging. Subjects completed technical skills modules in tissue phantoms, including kidney imaging, pushing a stone through a translucent maze, and repositioning a lower pole calyceal stone. Objective cognitive and technical performance metrics were recorded. Subjects completed a questionnaire to ascertain face and content validity on a five-point Likert scale.

Results: Eight urologists (80%) had never attended a previous ultrasound course, and nine (90%) performed renal ultrasounds less frequently than every 6 months. Mean cognitive skills scores improved from 55% to 91% (p<0.0001) on pre- and post-didactic tests. In the kidney phantom, 10 subjects (100%) repositioned the lower pole calyceal stone to at least the lower pole infundibulum, while 9 (90%) successfully repositioned the stone to the renal pelvis. A mean±SD (15.7±13.3) pushes were required to complete the task over an average of 4.6±2.2 minutes. Urologists rated the curriculum's effectiveness and realism as a training tool at a mean score of 4.6/5.0 and 4.1/5.0, respectively.

Conclusions: The curriculum for ultrasonic propulsion is effective and useful for training urologists with limited ultrasound proficiency in stone repositioning technique. Further studies in animate and human models will be required to assess predictive validity.

Purpose: To evaluate the feasibility of performing noninvasive puncture of pediatric ureteroceles with cavitation-based focused ultrasound (US) (histotripsy).

Materials and Methods: A model for the ureterocele wall was developed from an excised bovine bladder wall. The model was exposed to focused US pulses in a water bath under three different US parameter sets for up to 300 seconds to create localized perforations in the wall. B-mode US imaging was used to monitor the treatment and assess potential imaging guidance and feedback.

Results: Punctures were formed between 46–300 seconds, depending on the focused US exposure parameters and model wall thickness. Puncture diameter was controllable through choice of exposure parameters and could be varied between 0.8–2.8%u2009mm mean diameter. US-induced cavitation was visible on B-mode imaging, which provided targeting and treatment feedback.

Conclusions: Cavitation-based focused US can create punctures in a model that mimics the tissue properties of a ureterocele wall, under guidance from US imaging.

Focused ultrasonic propulsion is a new noninvasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, to our knowledge the extent of tissue injury associated with this technique is not known. We quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions and under conditions of higher power or continuous duty cycles. We compared those results to extracorporeal shock wave lithotripsy injury.

Nonlinear propagation effects are present in most fields generated by high intensity focused ultrasound (HIFU) sources. In some newer HIFU applications, these effects are strong enough to result in the formation of high amplitude shocks that actually determine the therapy and provide a means for imaging. However, there is no standard approach yet accepted to address these effects. Here, a set of combined measurement and modeling methods to characterize nonlinear HIFU fields in water and predict acoustic pressures in tissue is presented. A characterization method includes linear acoustic holography measurements to set a boundary condition to the model and nonlinear acoustic simulations in water for increasing pressure levels at the source. A derating method to determine nonlinear focal fields with shocks in situ is based on the scaling of the source pressure for data obtained in water to compensate for attenuation losses in tissue. The accuracy of the methods is verified by comparing the results with hydrophone and time-to-boil measurements. Major effects associated with the formation of shocks are overviewed. A set of metrics for determining thermal and mechanical bioeffects is introduced and application of the proposed tools to strongly nonlinear HIFU applications is discussed.

Ultrasound imaging has tissue and blood imaging modes. This report describes development of a kidney stone imaging mode. Two plane pulses generate a B-mode image. Overlaid in color are regions of high decorrelation between the pulses. Our previous data [UMB, 39, 1026-1038 (2013)] indicate the pulses excite bubbles on the stone surface, which causes the decorrelation. As such this mode automatically identifies stones in the image while scanning at a high frame rate. Further in a control box placed on the stone, highly focused beams are scanned across the stone and a harmonic B-mode image is produced to sharpen the lateral resolution. This mode is used to refine the size and shape of the stone. The first mode is used to aid visualization of stones. Our team is also using it to target and track stones that move with respiration during shock wave lithotripsy (SWL) and as an indicator of stone susceptibility to SWL since surface bubbles contribute to comminution. Improved stone sizing by the second mode aids treatment planning, and resolution of surface roughness is another indicator of stone fragility.

Shock wave lithotripsy (SWL) is the most common procedure for treatment of kidney stones. SWL noninvasively delivers high-energy focused shocks to fracture stones into passable fragments. We have recently observed that lower-amplitude, sinusoidal bursts of ultrasound can generate similar fracture of stones. This work investigated the characteristics of stone fragmentation for natural (uric acid, struvite, calcium oxalate, and cystine) and artificial stones treated by ultrasound bursts. Stones were fixed in position in a degassed water tank and exposed to 10-cycle bursts from a 200-kHz transducer with a pressure amplitude of p ≤ 6.5 MPa, delivered at a rate of 40–200 Hz. Exposures caused progressive fractures in the stone surface leading to fragments up to 3 mm. Treatment of artificial stones at different frequencies exhibited an inverse relationship between the resulting fragment sizes and ultrasound frequency. All artificial and natural types of stones tested could be fragmented, but the comminution rate varied significantly with stone composition over a range of 12–630 mg/min. These data suggest that stones can be controllably fragmented by sinusoidal ultrasound bursts, which may offer an alternative treatment strategy to SWL.

The use of projection methods is increasingly accepted as a standard way of characterizing the 3D fields generated by medical ultrasound sources. When combined with hydrophone measurements of pressure amplitude and phase over a surface transverse to the wave propagation, numerical projection can be used to reconstruct 3D fields that account for operational details and imperfections of the source. Here, we use holography measurements to characterize the fields generated by two array transducers with different geometries and modes of operation. First, a seven-element, high-power therapy transducer is characterized in the continuous-wave regime using holography measurements and nonlinear forward-projection calculations. Second, a C5-2 imaging probe (Philips Healthcare) with 128 elements is characterized in the transient regime using holography measurements and linear projection calculations. Results from the numerical projections for both sources are compared with independent hydrophone measurements of select waveforms, including shocked focal waveforms for the therapy transducer. Accurate 3D field representations have been confirmed, though a notable sensitivity to hydrophone calibrations is revealed. Uncertainties associated with this approach are discussed toward the development of holography measurements combined with numerical projections as a standard metrological tool.

Previous studies have provided insight into the physical mechanisms of stone fracture in shock wave lithotripsy. Broadly focused shocks efficiently generate shear waves in the stone leading to internal tensile stresses, which in concert with cavitation at the stone surface, cause cracks to form and propagate. Here, we propose a separate mechanism by which stones may fragment from sinusoidal ultrasound bursts without shocks. A numerical elastic wave model was used to simulate propagation of tone bursts through a cylindrical stone at a frequency between 0.15 and 2 MHz. Results suggest that bursts undergo mode conversion into surface waves on the stone that continually create significant stresses well after the exposure is terminated. Experimental exposures of artificial cylindrical stones to focused burst waves in vitro produced periodic fractures along the stone surface. The fracture spacing and resulting fragment sizes corresponded well with the spacing of stresses caused by surface waves in simulation at different frequencies. These results indicate surface waves may be an important factor in fragmentation of stones by focused tone bursts and suggest that the resulting stone fragment sizes may be controlled by ultrasound frequency.

Therapeutic ultrasound has an increasing number of applications in urology, including shockwave lithotripsy, stone propulsion, tissue ablation, and hemostasis. However, the threshold of renal injury using ultrasound is unknown. The goal of this study was to determine kidney injury thresholds for a range of intensities between diagnostic and ablative therapeutic ultrasound. A 2 MHz annular array generating spatial peak pulse average intensities (ISPPA) up to 28,000 W/cm² in water was placed on the surface of in vivo porcine kidneys and focused on the adjacent parenchyma. Treatments consisted of pulses of 100 μs duration triggered every 3 ms for 10 minutes at various intensities. The perfusion-fixed tissue was scored by 3 blinded independent experts. Above a threshold of 16,620 W/cm², the majority of injury observed included emulsification, necrosis and hemorrhage. Below this threshold, almost all injury presented as focal cell and tubular swelling and/or degeneration. These findings provide evidence for a wide range of potentially therapeutic ultrasound intensities that has a low probability of causing injury. While this study did not examine all combinations of treatment parameters of therapeutic ultrasound, tissue injury appears dose-dependent.

The mechanism of the twinkling artifact (TA) that occurs during Doppler ultrasound imaging of kidney stones was investigated. The TA expresses itself in Doppler images as time-varying color. To define the TA quantitatively, beam-forming and Doppler processing were performed on raw per channel radio-frequency data collected when imaging human kidney stones in vitro. Suppression of twinkling by an ensemble of computer-generated replicas of a single radio frequency signal demonstrated that the TA arises from variability among the acoustic signals and not from electronic signal capture or processing. This variability was found to be random, and its suppression by elevated static pressure and return when the pressure was released suggest that the presence of bubbles on the stone surface is the mechanism that gives rise to the TA.

Purpose
Focused ultrasound has the potential to expel small stones or residual stone fragments from the kidney, or move obstructing stones to a non-obstructing location. The purpose of this study was to evaluate the efficacy and safety of ultrasonic propulsion in a live porcine model.

Material and Methods
Calcium oxalate monohydrate kidney stones and laboratory model stones (2–8 mm) were ureteroscopically implanted within the renal pelvicalyceal system of 12 kidneys in eight domestic swine. Transcutaneous ultrasonic propulsion was performed using a Philips HDI C5-2 imaging transducer and Verasonics diagnostic ultrasound platform. Successful stone relocation was defined as stone movement from the calyx to the renal pelvis, ureteropelvic junction (UPJ) or proximal ureter. Efficacy and procedure time were determined. Three blinded experts evaluated for histologic injury to the kidney in control, sham, and treatment arms.

Results
All stones were observed to move during treatment, and 65% (17/26) were relocated successfully to the renal pelvis (3), UPJ (2), or ureter (12). Average successful procedure time was 14±8 min and required 23±16 ultrasound bursts of ~1 sec duration. There was no evidence of gross or histologic injury to the renal parenchyma in kidneys exposed to 20 bursts (1 sec duration, 33 sec intervals) at the same output (2400 W/cm²) used to push stones.

Conclusions
Non-invasive transcutaneous ultrasonic propulsion is a safe, effective, and time-efficient means to relocate calyceal stones to the renal pelvis, UPJ, or ureter. This technology holds promise as a useful adjunct to the surgical management of renal calculi.

Effective stone comminution during shock wave lithotripsy (SWL) is dependent on precise three-dimensional targeting of the shock wave. Respiratory motion, imprecise targeting or shock wave alignment, and stone movement may compromise treatment efficacy. The purpose of this study was to evaluate the accuracy of shock wave targeting during SWL treatment and the effect of motion due to respiration.

Methods: Ten patients underwent SWL for the treatment of 13 renal stones. Stones were targeted fluoroscopically using a Healthtronics Lithotron (5 cases) or Dornier Compact Delta II (5 cases) shock wave lithotripter. Shocks were delivered at a rate of 1-2Hz with ramping shock wave energy settings of 14-26kV or level 1-5. After the low energy pre-treatment and protective pause, a commercial diagnostic ultrasound imaging system was used to record images of the stone during active SWL treatment. Shock wave accuracy, defined as the proportion of shock waves that resulted in stone motion with shock wave delivery, and respiratory stone motion were determined by two independent observers who reviewed the ultrasound videos.

Results: Mean age was 51±15 years with 60% males and mean stone size was 10.5±3.7 mm (range 5-18 mm). A mean of 2675±303 shocks were delivered. Shock wave-induced stone motion was observed with every stone. Accurate targeting of the stone occurred in 60±15% of shock waves.

Conclusions: Ultrasound imaging during SWL revealed that 40% of shock waves miss the stone and contribute solely to tissue injury, primarily due to movement with respiration. These data support the need for a device to deliver shock waves only when the stone is in target. Ultrasound imaging provides real-time assessment of stone targeting and accuracy of shock wave delivery.

Context
The introduction of new lithotripters has increased problems associated with shock wave application. Recent studies concerning mechanisms of stone disintegration, shock wave focusing, coupling, and application have appeared that may address some of these problems.

Objective
To present a consensus with respect to the physics and techniques used by urologists, physicists, and representatives of European lithotripter companies.

Evidence acquisition
We reviewed recent literature (PubMed, Embase, Medline) that focused on the physics of shock waves, theories of stone disintegration, and studies on optimising shock wave application. In addition, we used relevant information from a consensus meeting of the German Society of Shock Wave Lithotripsy.

Evidence synthesis
Besides established mechanisms describing initial fragmentation (tear and shear forces, spallation, cavitation, quasi-static squeezing), the model of dynamic squeezing offers new insight in stone comminution. Manufacturers have modified sources to either enlarge the focal zone or offer different focal sizes. The efficacy of extracorporeal shock wave lithotripsy (ESWL) can be increased by lowering the pulse rate to 60-80 shock waves/min and by ramping the shock wave energy. With the water cushion, the quality of coupling has become a critical factor that depends on the amount, viscosity, and temperature of the gel. Fluoroscopy time can be reduced by automated localisation or the use of optical and acoustic tracking systems. There is a trend towards larger focal zones and lower shock wave pressures.

Conclusions
New theories for stone disintegration favour the use of shock wave sources with larger focal zones. Use of slower pulse rates, ramping strategies, and adequate coupling of the shock wave head can significantly increase the efficacy and safety of ESWL.

Recent studies in high intensity focused ultrasound (HIFU) have shown significant interest in generating purely mechanical damage of tissue without thermal coagulation. Here, an approach using millisecond bursts of ultrasound shock waves and repeated localized boiling is presented. In HIFU fields, nonlinear propagation effects lead to formation of shocks only in a small focal region. Significant enhancement of heating due to absorption at the shocks leads to boiling temperatures in tissue in milliseconds as calculated based on weak shock theory. The heated and potentially necrotized region of tissue is small compared to the volume occupied by the mm-sized boiling bubble it creates. If the HIFU pulse is only slightly longer than the time-to-boil, thermal injury is negligible compared to the mechanical injury caused by the exploding boiling bubble and its further interaction with shocks. Experiments performed in transparent gels and various ex vivo and in vivo tissues have confirmed the effectiveness of this emulsification method. In addition, since mm-sized boiling bubbles are highly echogenic, tissue emulsification can be easily monitored in real-time using B-mode ultrasound imaging.

"Twinkling" is a widely reported ultrasound artifact whereby kidney stones and other similar calcified, strongly reflective objects appear as turbulent, flowing blood in color and power Doppler. The twinkling artifact has been shown to improve kidney stone detection over B-mode imaging alone, but its use has several limitations. Principally, twinkling can be confused with blood flow, potentially leading to an incorrect diagnosis. Here a new method is reported for explicitly suppressing the display of color from blood flow to enhance and/or isolate the twinkle signal. The method applies an autoregressive model to standard Doppler pulses in order to differentiate tissue, blood flow, and twinkling. The algorithm was implemented on a software-based, open architecture ultrasound system and tested by a sonographer on phantoms and on stones implanted in a live porcine kidney. Stones of 3-10 mm were detected reproducibly while suppressing blood flow in the image. In conclusion, a new algorithm designed to specifically detect stones has been tested and has potential clinical utility especially as efforts are made to reduce radiation exposure on diagnosis and monitoring.

Kidney stone movement primarily due to patient respiration compromises shock wave lithotripsy (SWL) targeting and efficacy. The objective of this study is to describe the use of B-mode ultrasound to evaluate the accuracy of targeting during SWL. Patients undergoing electrohydraulic SWL were enrolled into this institutionally approved research study. A commercial diagnostic ultrasound imaging system, either Philips HDI 5000 or iU-22, was used to intermittently visualize and detect any shockwave-induced motion of the stone during 1-3 min periods. Four patients (mean age 52.7) underwent treatment of seven renal stones with mean individual stone size of 10.41 plus/minus 4.5 mm. A mean of 2937 shocks (range 2750-3000) were delivered at a rate of 1-2 Hz and charging voltage of 14-26 kV. Stone oscillation or jumping at the exact time of individual shock delivery was visualized with ultrasound: no stones completely failed to move. Accurate alignment, as interpreted by positive stone motion, occurred in a mean of 50 plus/minus 20.4% of shockwaves. Ultrasound imaging represents a method of real-time assessment of accuracy in SWL and may provide the basis for devices to control targeting so that shockwaves are only delivered when the stone is in focus.

Shock-wave heating and millisecond boiling in high intensity focused ultrasound fields have been shown to result in mechanical emulsification of ex-vivo tissue. In this work, the same in situ exposures were applied in vivo in pig liver and in mice bearing 5-7 mm subcutaneous tumors (B16 melanoma) on the hind limb. Lesions were produced using a 2-MHz annular array in the case of pig liver (shock amplitudes up to 98 MPa) and a 3.4-MHz single-element transducer in the case of mouse tumors (shock amplitude of 67 MPa). The parameters of the pulsing protocol (1-500 ms pulse durations and 0.01-0.1 duty factor) were varied depending on the extent of desired thermal effect. All exposures were monitored using B-mode ultrasound. Mechanical and thermal tissue damage in the lesions was evaluated histologically using H&E and NADH-diphorase staining. The size and shape of emulsified lesions obtained in-vivo agreed well with those obtained in ex-vivo tissue samples using the same exposure parameters. The lesions were successfully produced both in bulk liver tissue at depths of 1-2 cm and in superficial tumors at depths less than 1 mm without damaging the skin.

Vibro-acoustography (VA) is an ultrasound interrogation and imaging technique with a variety of applications. Here it was used to identify optimal parameters for detecting and imaging kidney stones in phantoms. The parameters varied included the difference frequency and the position in time of the analysis window used for image construction. Experiments in a water tank were conducted using a focused PVDF membrane hydrophone (receiver) placed in a central opening of an annular, dual element transducer (source), itself mounted on a translation stage. Our source consisted of 90-ms pulses with a center frequency of 2.0 MHz and difference frequencies between 50 and 350 kHz, applied both on and off stone. Variations in the amplitude of the measured ultrasound backscatter and acoustic emissions as a function of difference frequency, between signals from stone and phantom, guided the choice of imaging parameters. The results were detailed images of renal stones measuring 10 dB above the background tissue. These findings suggest that spectral information from the scattering and reverberation of VA induced ultrasound can be used to guide the interrogation and imaging of kidney stones.

Twinkling artifact on color Doppler ultrasound is the color labeling of hard objects, such as kidney stones, in the image. The origin of the artifact is unknown, but clinical studies have shown that twinkling artifact can improve the sensitivity of detection of stones by ultrasound. Although Doppler detection normally correlates changes in phase with moving blood, here the effect of amplitude on the artifact is investigated. Radio-frequency and in-phase and quadrature (IQ) data were recorded by pulse-echo ensembles using a software-programmable ultrasound system. Various hard targets in water and in tissue were insonified with a linear probe, and rectilinear pixel-based imaging was used to minimize beam-forming complexity. In addition, synthesized radio-frequency signals were sent directly into the ultrasound system to separate acoustic and signal processing effects. Artifact was observed both in onscreen and post-processed images, and as high statistical variance within the ensemble IQ data. Results showed that twinkling artifact could be obtained from most solid objects by changing the Doppler gain, yet signal amplitude did not have to be sufficiently high to saturate the receive circuits. In addition, low signal but high time gain compensation created the largest variance.

Feasibility of soft tissue emulsification using shock wave heating and millisecond boiling induced by high intensity focused ultrasound was demonstrated recently. However, the mechanism by which the bubbles emulsify tissue is not well understood. High-speed photography of such exposures in transparent gel phantoms shows a milimeter-sized boiling bubble, and histological analysis in tissue samples reveals sub-micron-sized fragments. Here, a novel mechanism of tissue emulsification by the formation of a miniature acoustic fountain within the boiling bubble is tested experimentally using a 2 MHz transducer generating up to 70 MPa positive and 15 MPa negative peak pressures at the focus. The focus was positioned at or 1-2 mm off the plane interface between air and various materials including degassed water, transparent gel, thin sliced muscle tissue phantom, and ex-vivo tissue. Pulsing schemes with duty factors 0.001-0.1, and pulse durations 0.05-500 ms were used. Violent removal of micron-sized fragments and substantial displacement of the phantom surface were observed through high-speed filming. At the end of each exposure, the resulting erosion of the phantom surface and subsurface area was photographed and related to the exposure parameters.

The radiation force created by an acoustic wave incident on an elastic sphere is studied theoretically. Elastic spheres with properties similar to kidney stones are considered. An acoustic wave is taken in the form of a high-intensity focused ultrasound beam of megahertz frequency, which is typical for transducers proposed for stone therapy. To study radiation force of beams with arbitrary structure, the source excitation is modeled as a sum of plane waves of various inclinations (angular spectrum representation). First, a plane acoustic wave scattering at the stone is modeled using the known solution in the form of a spherical harmonics series. Then superposition of such solutions is used to calculate the scattered field from a focused beam. Once the acoustic field is known, the radiation stress tensor is calculated on a surface surrounding the sphere. Finally, the net force acting on the sphere is calculated by integrating the radiation stress along the surface. Numerical calculations show that the direction and value of the radiation force acting on the sphere depend on the pressure field structure in the region where the scatterer is positioned.

Lithotripsy shockwaves are particularly difficult to measure because of their wide signal bandwidth and large pressures. A polyvinylidene fluoride (PVDF) membrane hydrophone and preamplifier were built and tested. A broad-focus electromagnetic lithotripter was used to calibrate the PVDF hydrophone. A fiber optic probe hydrophone (FOPH) with known impulse response was used as a measurement standard for secondary calibration. A low-frequency circuit model for the PVDF membrane electrodes in an infinite conductive medium was developed. The model response was compared with signals recorded by the FOPH and PVDF hydrophone at different levels of water conductivity ranging from 1 to 1300 microseconds/cm. Measured waveforms were distorted by high-pass filtering effects of the water conductivity. The model results showed good agreement with the measured waveforms and provided a correction for the system. When the input impedance was altered appropriately or the hydrophone was submerged in a nonconductive fluid, the PVDF and FOPH waveforms appeared nearly identical. The PVDF hydrophone is capable of measuring lithotripsy shockwaves accurately when the low-frequency response is properly taken into account.

Residual fragments remain in over 50% of treatments for lower pole kidney stones. A second-generation device based on a diagnostic ultrasound system and scanhead has been developed with a unique algorithm for stone detection and the capability to focus ultrasound to expel residual fragments. Focused ultrasound was applied to a bead on string in a water tank as well as to human stones (<5 mm) implanted in the lower pole of a live porcine model via retrograde ureteroscopy. Histological samples were collected and scored in a blinded fashion for therapeutic exposures and for super-therapeutic levels. The in-vitro bead was visually observed to move under focused ultrasound. Even with progressive manual displacement of the bead, the system continuously tracked and caused bead movement in real time. In the live porcine model, stones were expelled from the lower pole to the ureteropelvic junction in seconds to minutes using pulses at a duty factor of 0.02 and 8 W total acoustic power. Injury was observed no more frequently than in controls. Occurrence of injury rose slightly above control at a duty factor of 0.02 and 80 W and at a duty factor of 1 and 8 W.

An area of active research involves using the radiation force of ultrasound to expel small kidney stones or fragments from the kidney. The goal of this work is real-time motion tracking for visual feedback to the user and automated adaptive pushing as the stone moves. Algorithms have been designed to track stone movement during patient respiration but the challenge here is to track the stone motion relative to tissue. A new algorithm was written in MATLAB and implemented on an open-architecture, software-based ultrasound system. The algorithm was first trained then implemented in real-time on B-mode IQ data recorded from phantom experiments and animal studies. The tracking algorithm uses an ensemble of image processing techniques (2-D cross-correlation, phase correlation, and feature-edge detection) to overlay color on the stone in the real-time images and to assign a color to indicate the confidence in the identification of the stone. Camera images as well as ultrasound images showed that the system was able to locate a moving stone, re-target, and apply a new focused push pulse at that location.

The success of surgical management of lower pole stones is principally dependent on stone fragmentation and residual stone clearance. Choice of surgical method depends on stone size, yet all methods are subjected to post-surgical complications resulting from residual stone fragments. Here we present a novel method and device to reposition kidney stones using ultrasound radiation force delivered by focused ultrasound and guided by ultrasound imaging. The device couples a commercial imaging array with a focused annular array transducer.

Feasibility of repositioning stones was investigated by implanting artificial and human stones into a kidney-mimicking phantom that simulated a lower pole and collecting system. During experiment, stones were located by ultrasound imaging and repositioned by delivering short bursts of focused ultrasound. Stone motion was concurrently monitored by fluoroscopy, ultrasound imaging, and video photography, from which displacement and velocity were estimated. Stones were seen to move immediately after delivering focused ultrasound and successfully repositioned from the lower pole to the collecting system. Estimated velocities were on the order of 1 cm/s. This in vitro study demonstrates a promising modality to facilitate spontaneous clearance of kidney stones and increased clearance of residual stone fragments after surgical management.

A prototype ultrasound-based probe for use in ureteroscopy was used for in vitro measurements of stone fragments in a porcine kidney. Fifteen human stones consisting of three different compositions were placed deep in the collecting system of a porcine kidney. A 2 MHz, 1.2 mm (3.6F) needle hydrophone was used to send and receive ultrasound pulses for stone sizing. Calculated stone thicknesses were compared with caliper measurements. Correlation between ultrasound-determined thickness and caliper measurements was excellent in all three stone types (r(2) = 0.90, p < 0.0001). All 15 ultrasound measurements were accurate to within 1 mm, and 10 measurements were accurate within 0.5 mm. A 3.6F ultrasound probe can be used to accurately size stone fragments to within 1 mm in a porcine kidney.

PURPOSE: Proof-of-principle in vitro experiments evaluated a prototype ultrasound technology to size kidney stone fragments.
MATERIALS AND METHODS: Nineteen human stones were measured using manual calipers. A 10-MHz, 1/8'' (10F) ultrasound transducer probe pinged each stone on a kidney tissue phantom submerged in water using two methods. In Method 1, the instrument was aligned such that the ultrasound pulse traveled through the stone. In Method 2, the instrument was aligned partially over the stone such that the ultrasound pulse traveled through water.
RESULTS: For Method 1, the correlation between caliper- and ultrasound-determined stone size was r(2) = 0.71 (P < 0.0001). All but two stone measurements were accurate and precise to within 1 mm. For Method 2, the correlation was r(2) = 0.99 (P < 0.0001), and measurements were accurate and precise to within 0.25 mm.
CONCLUSIONS: The prototype technology and either method measured stone size with good accuracy and precision. This technology may be possible to incorporate into ureteroscopy.

Nonlinear propagation effects are present in most fields generated by high intensity focused ultrasound (HIFU) sources. In some newer HIFU applications, these effects are strong enough to result in the formation of high amplitude shocks that actually determine the therapy and provide a means for imaging. However, there is no standard approach yet accepted to address these effects. Here, a set of combined measurement and modeling methods to characterize nonlinear HIFU fields in water and predict acoustic pressures in tissue is presented. A characterization method includes linear acoustic holography measurements to set a boundary condition to the model and nonlinear acoustic simulations in water for increasing pressure levels at the source. A derating method to determine nonlinear focal fields with shocks in situ is based on the scaling of the source pressure for data obtained in water to compensate for attenuation losses in tissue. The accuracy of the methods is verified by comparing the results with hydrophone and time-to-boil measurements. Major effects associated with the formation of shocks are overviewed. A set of metrics for determining thermal and mechanical bioeffects is introduced and application of the proposed tools to strongly nonlinear HIFU applications is discussed.

Ultrasound imaging has tissue and blood imaging modes. This report describes development of a kidney stone imaging mode. Two plane pulses generate a B-mode image. Overlaid in color are regions of high decorrelation between the pulses. Our previous data [UMB, 39, 1026-1038 (2013)] indicate the pulses excite bubbles on the stone surface, which causes the decorrelation. As such this mode automatically identifies stones in the image while scanning at a high frame rate. Further in a control box placed on the stone, highly focused beams are scanned across the stone and a harmonic B-mode image is produced to sharpen the lateral resolution. This mode is used to refine the size and shape of the stone. The first mode is used to aid visualization of stones. Our team is also using it to target and track stones that move with respiration during shock wave lithotripsy (SWL) and as an indicator of stone susceptibility to SWL since surface bubbles contribute to comminution. Improved stone sizing by the second mode aids treatment planning, and resolution of surface roughness is another indicator of stone fragility.

Shock wave lithotripsy (SWL) is the most common procedure for treatment of kidney stones. SWL noninvasively delivers high-energy focused shocks to fracture stones into passable fragments. We have recently observed that lower-amplitude, sinusoidal bursts of ultrasound can generate similar fracture of stones. This work investigated the characteristics of stone fragmentation for natural (uric acid, struvite, calcium oxalate, and cystine) and artificial stones treated by ultrasound bursts. Stones were fixed in position in a degassed water tank and exposed to 10-cycle bursts from a 200-kHz transducer with a pressure amplitude of p ≤ 6.5 MPa, delivered at a rate of 40–200 Hz. Exposures caused progressive fractures in the stone surface leading to fragments up to 3 mm. Treatment of artificial stones at different frequencies exhibited an inverse relationship between the resulting fragment sizes and ultrasound frequency. All artificial and natural types of stones tested could be fragmented, but the comminution rate varied significantly with stone composition over a range of 12–630 mg/min. These data suggest that stones can be controllably fragmented by sinusoidal ultrasound bursts, which may offer an alternative treatment strategy to SWL.

The use of projection methods is increasingly accepted as a standard way of characterizing the 3D fields generated by medical ultrasound sources. When combined with hydrophone measurements of pressure amplitude and phase over a surface transverse to the wave propagation, numerical projection can be used to reconstruct 3D fields that account for operational details and imperfections of the source. Here, we use holography measurements to characterize the fields generated by two array transducers with different geometries and modes of operation. First, a seven-element, high-power therapy transducer is characterized in the continuous-wave regime using holography measurements and nonlinear forward-projection calculations. Second, a C5-2 imaging probe (Philips Healthcare) with 128 elements is characterized in the transient regime using holography measurements and linear projection calculations. Results from the numerical projections for both sources are compared with independent hydrophone measurements of select waveforms, including shocked focal waveforms for the therapy transducer. Accurate 3D field representations have been confirmed, though a notable sensitivity to hydrophone calibrations is revealed. Uncertainties associated with this approach are discussed toward the development of holography measurements combined with numerical projections as a standard metrological tool.

Previous studies have provided insight into the physical mechanisms of stone fracture in shock wave lithotripsy. Broadly focused shocks efficiently generate shear waves in the stone leading to internal tensile stresses, which in concert with cavitation at the stone surface, cause cracks to form and propagate. Here, we propose a separate mechanism by which stones may fragment from sinusoidal ultrasound bursts without shocks. A numerical elastic wave model was used to simulate propagation of tone bursts through a cylindrical stone at a frequency between 0.15 and 2 MHz. Results suggest that bursts undergo mode conversion into surface waves on the stone that continually create significant stresses well after the exposure is terminated. Experimental exposures of artificial cylindrical stones to focused burst waves in vitro produced periodic fractures along the stone surface. The fracture spacing and resulting fragment sizes corresponded well with the spacing of stresses caused by surface waves in simulation at different frequencies. These results indicate surface waves may be an important factor in fragmentation of stones by focused tone bursts and suggest that the resulting stone fragment sizes may be controlled by ultrasound frequency.

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.

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.

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.

A transducer is used to send an ultrasound pulse toward a stone and to receive ultrasound reflections from the stone. The recorded time between a pulse that is reflected from the proximal surface and a pulse that is reflected either from the distal surface of the stone or from a surface supporting the stone is used to calculate the stone size. The size of the stone is a function of the time between the two pulses and the speed of sound through the stone (or through the surrounding fluid if the second pulse was reflected by the surface supporting the stone). This technique is equally applicable to measure the size of other in vivo objects, including soft tissue masses, cysts, uterine fibroids, tumors, and polyps.

During shock wave therapy, a determination is made that a kidney stone has begun to fracture, and then a progress of its fragmentation is assessed. This determination can reduce the number of shock waves used to disintegrate kidney stones, and thereby reduce dose-dependent tissue damage. The identification of fracture is possible through the detection and analysis of resonant acoustic scattering, which is the radiation caused by reverberations within a stone particle that is struck by a shock wave. The scattering frequency can provide both an indication that the kidney stone has fragmented, and an indication of the relative sizes of the fragments. Such techniques can be combined with vibro-acoustography based gating that better targets the stone.