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Feasibility of ultrasonic propulsion and burst wave lithotripsy (BWL) to noninvasively reposition distal ureteral stones to facilitate passage and relieve pain was tested. Patients presenting to the clinic or emergency department were recruited. Thirteen subjects underwent ultrasonic propulsion (lower amplitude, longer duration pulses) alone, and 10 subjects also received intermittent BWL (higher amplitude, shorter duration pulses). All participants were awake and underwent a pain assessment pre- and post-procedure. For analysis, subjects were sub-categorized based on whether their stone was acute or chronic (present for ≤10 days or >10 days from their initial ED or symptomatic presentation, respectively). Seventeen subjects were enrolled in the acute study population and 6 subjects were enrolled in the chronic population. Overall, 94% of acute stones passed in an average of 3.4 days post-procedure relative to 54% in 7.5 days in the American Urological Association guidelines. 67% of chronic cases passed stones or fragments, and two surgeries were cancelled. Pain reduction was statistically significant ( p = 0.0215). Adverse events were limited to hematuria on initial urination post-procedure (BWL only, n = 3) and a mild sensation, akin to a pinprick, associated with fewer than 10 of 620 propulsion bursts ( n = 3). [Work supported by NIH-P01-DK04331.]

It is hypothesized a 2.6-mm stone was too small to break with 390-kHz burst wave lithotripsy (BWL). In clinical trial NCT03873259, a 2.6-mm stone failed to break after 10 min of 390-kHz BWL and was removed intact. Ex vivo, the stone failed to break after another 30 min at 390 kHz but broke into four pieces in 4 min at 650 kHz. A linear elastic model was used to calculate the stress created inside stones of different sizes, shapes, and compositions by shock wave lithotripsy (SWL) and different BWL frequencies. The model predicts above a threshold frequency proportionate to wave speed over stone length, the maximum principal stress inside a stone increases to more than five times the acoustic pressure applied. Thus, smaller stones may fragment at higher but not lower frequency. Amplification remains with irregularly shaped stones but is not seen with an SWL waveform. Ex vivo, stones smaller than 3 mm broke fastest at 830 kHz while larger stones broke fastest with 390 kHz followed by 830 kHz. For small stones and fragments, increasing BWL frequency many produce, amplified stress in the stone causing the stone to break to smaller fragments to pass. [Work supported by NIH-P01-DK04331 and NIH-K01-DK104854.]

Burst Wave Lithotripsy (BWL) is a new stone treatment that utilizes ultrasound to fracture renal calculi. However, it is not known if BWL alters renal function, so we tested if a clinical dose of BWL impacts glomerular filtration rate (GFR) or kidney blood flow. Treatment consisted of placing each pig (32–42 kg) on its side, locating the lower pole of the right kidney, and treating that kidney with a BWL dose of 18,000 ultrasound pulses at 10Hz, 20 cycles/pulse and a peak negative pressure of −7 MPa (n = 6). Six additional pigs were used as sham controls. Inulin and para-aminohippuric acid (PAH) were infused into the pigs with blood and urine samples being collected both before and 1-h after BWL treatment. The concentrations of inulin and PAH were determined in the samples and used to calculate GFR and effective renal plasma flow (eRPF). For the BWL treated group, GFR and eRPF did not change after BWL exposure (−6.7 ± 7.2% for GFR, −10.9 ± 5.5% for eRPF), and this response was like the sham control group ( P = 0.23 for GFR, P = 0.08 for eRPF). A typical clinical dose of BWL caused no change in renal function. [Work supported by NIH, Grant P01 DK43881.]

The goal is to test effectiveness and safety of transcutaneous ultrasound pulses for facilitating clearance of residual urinary stone fragments in a randomized control trial (RCT). The study is conducted in a clinic setting with the control and treatment arms undergoing all the same activities with the exception of the ultrasonic propulsion procedure and associated pain questionnaire. Subjects are followed 90 days for assessment of adverse events and for up to 5 years for stone growth and symptomatic stone visits. Twenty-six of 33 subjects have been recruited in each arm The most recent treatment is reported. The subject received shock wave lithotripsy and did not pass any fragments for 17 months. The subject was randomized to the treatment arm. Fragments began moving with the third 3-s propulsion pulse at output 2 of 5 levels. Fifty-two percent of propulsion pulses (41 of 79) resulted in fragment movement. The subject reported no pain at the beginning or end of the procedure and telephoned within 2 h to report passing 9 fragments, no hematuria, and no adverse events. The treatment results of this RCT are compelling as an immediate and casual effect was measured. [Work supported by NIH-P01-DK043881 and VA Puget Sound resources.]

Tissue water content has been observed to influence ultrasonic atomization efficiency, which raises questions regarding ex vivo tissue storage time and viability. Here, we investigate the influence of tissue preservation solutions on acoustic properties and atomization efficiency. Samples from ten bovine livers were immediately submerged in phosphate-buffered saline (PBSaline), phosphate-buffered sucrose (PBSucrose), phosphate-buffered raffinose (PBRaffinose), or ViaSpan® clinical organ transplantation solution; no solution was also tested. Acoustic attenuation, sound speed, water content, and atomization efficiency were evaluated on either day 1 or day 2. For atomization efficiency, samples were partially submerged in water with the liver-air interface aligned with a 2-MHz focused transducer operating with 10-ms pulses at 1 Hz and peak pressures of 65/-16 MPa. Overall, no difference in atomization efficiency was observed. Water content in tissue was 66–78%, with PBSaline showing a significant increase between days (p = 0.0013). Only tissues in no solution showed a significant difference between days in acoustic attenuation (p = 0.0003). Sound speed measurements had more variation with only ViaSpan and PBSucrose showing no significant differences. As ViaSpan and PBSurcrose showed the most similarities in the tested acoustic properties, PBSurcose may be a low-cost alternative to the clinical ViaSpan solution for preserving ex vivo tissues. [Work supported by NIH DK043881 and EB017857.]Tissue water content has been observed to influence ultrasonic atomization efficiency, which raises questions regarding ex vivo tissue storage time and viability. Here, we investigate the influence of tissue preservation solutions on acoustic properties and atomization efficiency. Samples from ten bovine livers were immediately submerged in phosphate-buffered saline (PBSaline), phosphate-buffered sucrose (PBSucrose), phosphate-buffered raffinose (PBRaffinose), or ViaSpan® clinical organ transplantation solution; no solution was also tested. Acoustic attenuation, sound speed, water content, and atomization efficiency were evaluated on either day 1 or day 2. For atomization efficiency, samples were partially submerged in water with the liver-air interface aligned with a 2-MHz focused transducer operating with 10-ms pulses at 1 Hz and peak pressures of 65/-16 MPa. Overall, no difference in atomization efficiency was observed. Water content in tissue was 66–78%, with PBSaline showing a significant increase be...

Our goal is an office-based, handheld ultrasound system to target, detach, break, and/or expel stones and stone fragments from the urinary space 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 14 of 15 kidneys (93%). 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 4 of 4 stones on post mortem dissection. All clinical pathology, hematology, and urinalysis for a 1-week survival study with the BWL exposures in 10 specific pathogen free pigs were within normal limits. These results demonstrate that repositioning of stones with ultrasonic propulsion and breaking of stones with BWL are safe and effective. [Work supported by NIH P01 DK043881, K01 DK104854, and R44 DK109779.]

Ultrasound, not x-ray, is preferred for imaging kidney stones in children; however, stone size determination is less accurate with ultrasound. In vitro we found stone sizing was improved by measuring the width of the acoustic shadow behind the stone. We sought to determine the prevalence and accuracy of the acoustic shadow in pediatric patients. A retrospective analysis was performed of all initial stone events at a children’s hospital over the last 10 years. Included subjects had a computed tomography (CT) scan and renal ultrasound within 3 months of each other. The width of the stone and acoustic shadow were measured on ultrasound and compared to the stone size as determined by CT. Thirty-seven patients with 49 kidney stones were included. An acoustic shadow was seen in 85% of stones evaluated. Stone width resulted in an average overestimation of 1.2 ± 2.2 mm while shadow width resulted in an underestimation of 0.5 ± 1.7 mm (p < 0.001). A posterior acoustic shadow was seen in the majority of stones and was a more accurate measure of stone size. This would provide valuable information for stone management. [Work supported by NIH DK43881 and DK092197, and NSBRI through NASA NCC 9-58.]

A pause early in shock wave lithotripsy (SWL) increased vasoconstriction as measured by resistive index (RI) during treatment and mitigated renal injury in an animal model. The purpose of our study was to investigate whether RI rose during SWL in humans. Prospectively recruited patients underwent SWL of renal stones with a Dornier Compact S lithotripter. The renal protective protocol consisted of treatment at 1 Hz and slow power ramping for the initial 250 shocks followed by a 2 min pause. RI was measured using ultrasound prior to treatment, after 250 shocks, after 750 shocks, after 1500 shocks, and after SWL. A linear mixed-effects model was used to compare RI at the different time points and to account for additional covariates in fifteen patients. RI was significantly higher than baseline for all time points 250 shocks and after. Age, gender, body mass index, and treatment side were not significantly associated with RI. Monitoring for a rise in RI during SWL is possible and may provide real-time feedback as to when the kidney is protected. [Work supported by NIH DK043881, NSBRI through NASA NCC 9-58, and resources from the VA Puget Sound Health Care System.]

A pilot study was conducted to assess whether extracorporeal shock wave lithotripsy (SWL) treatment of the kidney influences the onset and severity of metabolic syndrome (MetS)—a cluster of conditions that includes central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension. Methods: Three-month-old juvenile female Ossabaw miniature pigs were treated with either SWL (2000 SWs, 24 kV, 120 SWs/min using the HM3 lithotripter; n = 2) or sham-SWL (no SWs; n = 2). SWs were targeted to the upper pole of the left kidney so as to model treatment that would also expose the pancreas—an organ involved in blood glucose homeostasis—to SWs. The pigs were then instrumented for direct measurement of arterial blood pressure via implanted radiotelemetry devices, and later fed a hypercaloric atherogenic diet for ~7 months to induce MetS. The development of MetS was assessed from intravenous glucose tolerance tests. Results: The progression and severity of MetS were similar in the sham-trea...

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 30,000 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 min at various intensities. The perfusion-fixed tissue was scored by three blinded independent experts. Above a threshold of 20,000 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. [Work supported by NIH DK43881, DK092197, and NSBRI through NASA NCC 9-58.]