First Series Using Ultrasonic Propulsion and Burst Wave Lithotripsy to Treat Ureteral Stones.

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.

Improving Burst Wave Lithotripsy Effectiveness for Small Stones and Fragments by Increasing Frequency: Theoretical Modeling and Ex Vivo Study.

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.

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

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Characterization and Ex Vivo evaluation of an extracorporeal high-intensity focused ultrasound (HIFU) system.

BACKGROUND: High-intensity focused ultrasound (HIFU) has been in clinical use for a variety of solid tumors and cancers. Accurate and reliable calibration is in a great need for clinical applications. An extracorporeal clinical HIFU system applied for the investigational device exemption (IDE) to the Food and Drug Administration (FDA) so that evaluation of its characteristics, performance, and safety was required. METHODS: The acoustic pressure and power output was characterized by a fiber optic probe and a radiation force balance, respectively, with the electrical power up to 2000 W. An in situ acoustic energy was established as the clinical protocol at the electrical power up to 500 W. Temperature elevation inside the tissue sample was measured by a thermocouple array. Generated lesion volume at different in situ acoustic energies and pathological examination of the lesions was evaluated ex vivo. RESULTS: Acoustic pressure mapping showed the insignificant presence of side/grating lobes and pre- or post-focal peaks (≤-12 dB). Although distorted acoustic pressure waveform was found in the free field, the nonlinearity was reduced significantly after the beam propagating through tissue samples (i.e., the second harmonic of -11.8 dB at 500 W). Temperature elevation was <10°C at a distance of 10 mm away from a 20-mm target, which suggests the well-controlled HIFU energy deposition and no damage to the surrounding tissue. An acoustic energy in the range of 750-1250 J resulted in discrete lesions with an interval space of 5 mm between the treatment spots. Histology confirmed that the lesions represented a region of permanently damaged cells by heat fixation, without causing cell lysis by either cavitation or boiling. CONCLUSIONS: Our characterization and ex vivo evaluation protocol met the IDE requirement. The in-situ acoustic energy model will be used in clinical trials to deliver almost consistent energy to the various targets.

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

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

In-Office Ultrasound Facilitates Timely Clinical Care at a Multidisciplinary Kidney Stone Center.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evidence of Microbubbles on Kidney Stones in Humans.

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.

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

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.

Quantitative Assessment of Effectiveness of Ultrasonic Propulsion of Kidney Stones.

Purpose: 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. Materials and Methods: 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. Results: 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 ± 14 propulsion bursts (per kidney) for a total average exposure time of 40 ± 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. Conclusions: 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.

Measurement of Posterior Acoustic Stone Shadow on Ultrasound Is a Learnable Skill for Inexperienced Users to Improve Accuracy of Stone Sizing.

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.

Combined Burst Wave Lithotripsy and Ultrasonic Propulsion for Improved Urinary Stone Fragmentation.

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.

Retrospective comparison of measured stone size and posterior acoustic shadow width in clinical ultrasound images.

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.

Effect of Stone Size and Composition on Ultrasonic Propulsion Ex Vivo.

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 × 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.

Characterizing the Acoustic Output of an Ultrasonic Propulsion Device for Urinary Stones.

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.

Quantification of Renal Stone Contrast with Ultrasound in Human Subjects.

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.

Ultrasound-Induced Bubble Clusters in Tissue-Mimicking Agar Phantoms.

Therapeutic ultrasound can drive bubble activity that damages soft tissues. To study the potential mechanisms of such injury, transparent agar tissue-mimicking phantoms were subjected to multiple pressure wave bursts of the kind being considered specifically for burst wave lithotripsy. A high-speed camera recorded bubble activity during each pulse. Various agar concentrations were used to alter the phantom's mechanical properties, especially its stiffness, which was varied by a factor of 3.5. However, the maximum observed bubble radius was insensitive to stiffness. During 1000 wave bursts of a candidate burst wave lithotripsy treatment, bubbles appeared continuously in a region that expanded slowly, primarily toward the transducer. Denser bubble clouds are formed at higher pulse repetition frequency. The specific observations are used to inform the incorporation of damage mechanisms into cavitation models for soft materials.

Safety and Effectiveness of a Longer Focal Beam and Burst Duration in Ultrasonic Propulsion for Repositioning Urinary Stones and Fragments.

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 × 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.

Stone-Mode Ultrasound for Determining Renal Stone Size.

PURPOSE: The purpose of this study was to measure the accuracy of stone-specific algorithms (S-mode) and the posterior acoustic shadow for determining kidney stone size with ultrasound (US) in vivo. MATERIALS AND METHODS: Thirty-four subjects with 115 renal stones were prospectively recruited and scanned with S-mode on a research US system. S-mode is gray-scale US adjusted to enhanced stone contrast and resolution by minimizing compression and averaging, and increasing line density and frequency. Stone and shadow width were compared with a recent CT scan and, in 5 subjects with 18 stones, S-mode was compared with a clinical US system. RESULTS: Overall, 84% of stones identified on CT were detected on S-mode and 66% of these shadowed. Seventy-three percent of the stone measurements and 85% of the shadow measurements were within 2 mm of the size on CT. A posterior acoustic shadow was present in 89% of stones over 5 mm versus 53% of stones under 5 mm. S-mode visualized 78% of stones, versus 61% for the clinical system. S-mode stone and shadow measurements differed from CT by 1.6 ± 1.0 mm and 0.8 ± 0.6 mm, respectively, compared with 2.0 ± 1.5 mm and 1.6 ± 1.0 mm for the clinical system. CONCLUSIONS: S-mode offers improved visualization and sizing of renal stones. With S-mode, sizing of the stone itself and the posterior acoustic shadow were similarly accurate. Stones that do not shadow are most likely <5 mm and small enough to pass spontaneously.

First in Human Clinical Trial of Ultrasonic Propulsion of Kidney Stones.

PURPOSE: Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones. MATERIALS AND METHODS: Subjects underwent ultrasonic propulsion while awake without sedation in clinic, or during ureteroscopy while anesthetized. Ultrasound 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 less than 5 mm and 5 mm or greater. Adverse events were assessed weekly for 3 weeks. RESULTS: 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 greater than 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 more than 30 fragments passed by 4 of the 6 subjects who had previously undergone a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of a large stone at the ureteropelvic junction. In 4 subjects a seemingly large stone was determined to be a cluster of small passable stones after they were moved. CONCLUSIONS: Ultrasonic propulsion was able to successfully reposition stones and facilitate the passage of fragments in humans. No adverse events were associated with the investigational procedure.

Use of the Acoustic Shadow Width to Determine Kidney Stone Size with Ultrasound.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: Average error between the measured and true stone width was 1.4 ± 0.8 mm, 1.7 ± 0.9 mm, 0.9 ± 0.8 mm for ray line, spatial compound and harmonic imaging, respectively. Average error between the shadow width and true stone width was 0.2 ± 0.7 mm, 0.4 ± 0.7 mm and 0.0 ± 0.8 mm for ray line, spatial compound and harmonic imaging, respectively. Sizing error based on the stone width worsened with greater depth (p <0.001) while the sizing error based on the shadow width was independent of depth. CONCLUSIONS: 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.