Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: A system was built to detect cavitation in pig kidney during shock-wave lithotripsy (SWL) with a Dornier HM3 lithotripter. Active detection using echo on B-mode ultrasound, and passive cavitation detection using coincident signals on confocal orthogonal receivers, were used to interrogate the renal collecting system (urine) and the kidney parenchyma (tissue). Cavitation was detected in urine immediately upon shock-wave (SW) administration in urine or urine plus X-ray contrast agent but, in native tissue, cavitation required hundreds of SWs to initiate. Localization of cavitation was confirmed by fluoroscopy, sonography and by thermally marking the kidney using the passive cavitation detection receivers as high-intensity focused ultrasound sources. Cavitation collapse times in tissue and native urine were about the same, but less than in urine after injection of X-ray contrast agent. The finding that cavitation occurs in kidney tissue is a critical step toward determining the mechanisms of tissue injury in SWL. (E-mail: bailey@apl.washington.edu) [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: High-speed photomicrography was used to study the translational dynamics of single microbubbles in microvessels of ex vivo rat mesenteries. The microbubbles were insonated by a single 2 μs ultrasound pulse with a center frequency of 1 MHz and peak negative pressures spanning the range of 0.8–4 MPa. The microvessel diameters ranged from 10–80 μm. The high-speed image sequences show evidence of ultrasound-activated microbubble translation away from the nearest vessel wall; no microbubble showed a net translation toward the nearest vessel wall. Microbubble maximum translation displacements exceeded 20 μm. Microjets with the direction of the jets identifiable were also observed; all microjets appear to have been directed away from the nearest vessel wall. These observations appear to be characteristic of a strong coupling between ultrasound-driven microbubbles and compliant microvessels. Although limited to mesenteric tissues, these observations provide an important step in understanding the physical interactions between microbubbles and microvessels. [Copyright &y& Elsevier]

Our previous study showed that high-intensity focused ultrasound (HIFU) is capable of producing “primary acoustic hemostasis” in the form of ultrasound (US)-induced platelet activation, aggregation and adhesion to a collagen-coated surface. In the current study, 1.1 MHz continuous-wave HIFU was used to investigate the role of cavitation as a mechanism for platelet aggregation in samples of platelet-rich plasma. A 5 MHz passive cavitation detector was used to monitor cavitation activity and laser aggregometry was used to measure platelet aggregation. Using spatial average intensities from 0 to 3350 W/cm2, the effects of HIFU-induced cavitation on platelet aggregation were investigated by enhancing cavitation activity through use of US contrast agents and by limiting cavitation activity through use of an overpressure system. Our results show that increased cavitation activity lowers the intensity threshold to produce platelet aggregation and decreased cavitation activity in the overpressure system raises the intensity threshold for platelet aggregation. (E-mail: poliachi@u.washington.edu) [Copyright &y& Elsevier]