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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., Competing Interests: Competing interest statement: A.D.M., B.W.C., and M.R.B. have equity and consult for SonoMotion, Inc. which has licensed technology related to this work from the University of Washington for commercialization.

Purpose of Review: 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., Recent Findings: 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., Summary: 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.

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/cm 2 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.

This article reviews new advances in ultrasound technology for urinary stone disease. Recent research to facilitate the diagnosis of nephrolithiasis, including use of the twinkling signal and posterior acoustic shadow, have helped to improve the use of ultrasound examination for detecting and sizing renal stones. New therapeutic applications of ultrasound technology for stone disease have emerged, including ultrasonic propulsion to reposition stones and burst wave lithotripsy to fragment stones noninvasively. The safety, efficacy, and evolution of these technologies in phantom, animal, and human studies are reviewed herein. New developments in these rapidly growing areas of ultrasound research are also highlighted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

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., (Published by Elsevier Inc.)

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/cm 2 , which is below the 720-mW/cm 2 limit for diagnostic US.

Newer imaging and therapeutic ultrasound technologies may benefit from in situ pressure levels higher than conventional diagnostic ultrasound. One example is the recently developed use of ultrasonic radiation force to move kidney stones and residual fragments out of the urinary collecting system. A commercial diagnostic 2.3 MHz C5-2 array probe has been used to deliver the acoustic pushing pulses. The probe is a curvilinear array comprising 128 elements equally spaced along a convex cylindrical surface. The effectiveness of the treatment can be increased by using higher transducer output to provide a stronger pushing force; however nonlinear acoustic saturation can be a limiting factor. In this work nonlinear propagation effects were analyzed for the C5-2 transducer using a combined measurement and modeling approach. Simulations were based on the three-dimensional Westervelt equation with the boundary condition set to match low power measurements of the acoustic pressure field. Nonlinear focal waveforms simulated for different numbers of operating elements of the array at several output power levels were compared to fiber-optic hydrophone measurements and were found to be in good agreement. It was shown that saturation effects do limit the acoustic pressure in the focal region of a diagnostic imaging probe.

Purpose of Review: Ultrasonic propulsion is a novel technique that uses short bursts of focused ultrasonic pulses to reposition stones transcutaneously within the renal collecting system and ureter. The purpose of this review is to discuss the initial testing of effectiveness and safety, directions for refinement of technique and technology, and opinions on clinical application., Recent Findings: Preclinical studies with a range of probes, interfaces, and outputs have demonstrated feasibility and consistent safety of ultrasonic propulsion with room for increased outputs and refinement toward specific applications. Ultrasonic propulsion was used painlessly and without adverse events to reposition stones in 14 of 15 human study participants without restrictions on patient size, stone size, or stone location. The initial feasibility study showed applicability in a range of clinically relevant situations, including facilitating passage of residual fragments following ureteroscopy or shock wave lithotripsy, moving a large stone at the ureteropelvic junction with relief of pain, and differentiating large stones from a collection of small fragments., Summary: Ultrasonic propulsion shows promise as an office-based system for transcutaneously repositioning kidney stones. Potential applications include facilitating expulsion of residual fragments following ureteroscopy or shock wave lithotripsy, repositioning stones prior to treatment, and repositioning obstructing ureteropelvic junction stones into the kidney to alleviate acute renal colic.

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., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Bone loss can result from bed rest, space flight, spinal cord injury or age-related hormonal changes. Current bone loss mitigation techniques include pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and whole body vibration. In this study, we attempted to mitigate paralysis-induced bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle. We employed a mouse model of disuse that uses onabotulinumtoxinA-induced paralysis, which causes rapid bone loss in 5 d. A focused 2 MHz transducer applied pulsed exposures with pulse repetition frequency mimicking that of motor neuron firing during walking (80 Hz), standing (20 Hz), or the standard pulsed ultrasound frequency used in fracture healing (1 kHz). Exposures were applied daily to calf muscle for 4 consecutive d. Trabecular bone changes were characterized using micro-computed tomography. Our results indicated that application of certain focused pulsed ultrasound parameters was able to mitigate some of the paralysis-induced bone loss., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has been recently gaining momentum. In HIFU, ultrasound energy from an extracorporeal source is focused within the body to ablate tissue at the focus while leaving the surrounding organs and tissues unaffected. Most HIFU therapies are designed to use heating effects resulting from the absorption of ultrasound by tissue to create a thermally coagulated treatment volume. Although this approach is often successful, it has its limitations, such as the heat sink effect caused by the presence of a large blood vessel near the treatment area or heating of the ribs in the transcostal applications. HIFU-induced bubbles provide an alternative means to destroy the target tissue by mechanical disruption or, at its extreme, local fractionation of tissue within the focal region. Here, we demonstrate the feasibility of a recently developed approach to HIFU-induced ultrasound-guided tissue fractionation in an in vivo pig model. In this approach, termed boiling histotripsy, a millimeter-sized boiling bubble is generated by ultrasound and further interacts with the ultrasound field to fractionate porcine liver tissue into subcellular debris without inducing further thermal effects. Tissue selectivity, demonstrated by boiling histotripsy, allows for the treatment of tissue immediately adjacent to major blood vessels and other connective tissue structures. Furthermore, boiling histotripsy would benefit the clinical applications, in which it is important to accelerate resorption or passage of the ablated tissue volume, diminish pressure on the surrounding organs that causes discomfort, or insert openings between tissues.

Purpose: 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., Materials and Methods: A human calcium oxalate monohydrate stone and/or nickel beads were implanted by ureteroscopy in 3 kidneys of live pigs weighing 45 to 55 kg and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to extracorporeal shock wave lithotripsy level pulse intensity or continuous ultrasound exposure 10 minutes in duration using an ultrasound probe transcutaneously or on the kidney. These kidneys were compared to 6 treated with an unmodified Dornier HM3 lithotripter (Dornier Medical Systems, Kennesaw, Georgia) using 2,400 shocks at 120 shock waves per minute and 24 kV. Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique according to the percent of functional renal volume., Results: Extracorporeal shock wave lithotripsy produced a mean ± SEM lesion of 1.56% ± 0.45% of functional renal volume. Ultrasonic propulsion produced no detectable lesion with simulated clinical treatment. A lesion of 0.46% ± 0.37% or 1.15% ± 0.49% of functional renal volume was produced when excessive treatment parameters were used with the ultrasound probe placed on the kidney., Conclusions: Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters but produced injury comparable in size to that of extracorporeal shock wave lithotripsy when using excessive treatment parameters., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Focused ultrasound has the potential to expel small stones or residual stone fragments from the kidney, or move obstructing stones to a nonobstructing location. We evaluated the efficacy and safety of ultrasonic propulsion in a live porcine model., Materials and Methods: Calcium oxalate monohydrate kidney stones and laboratory model stones (2 to 8 mm) were ureteroscopically implanted in the renal pelvicalyceal system of 12 kidneys in a total of 8 domestic swine. Transcutaneous ultrasonic propulsion was performed using an HDI C5-2 imaging transducer (ATL/Philips, Bothell, Washington) and the Verasonics® diagnostic ultrasound platform. Successful stone relocation was defined as stone movement from the calyx to the renal pelvis, ureteropelvic junction or proximal ureter. Efficacy and procedure time was determined. Three blinded experts evaluated histological injury to the kidney in the control, sham treatment and treatment arms., Results: All 26 stones were observed to move during treatment and 17 (65%) were relocated successfully to the renal pelvis (3), ureteropelvic junction (2) or ureter (12). Average ± SD successful procedure time was 14 ± 8 minutes and a mean of 23 ± 16 ultrasound bursts, each about 1 second in duration, were required. There was no evidence of gross or histological injury to the renal parenchyma in kidneys exposed to 20 bursts (1 second in duration at 33-second intervals) at the same output (2,400 W/cm(2)) used to push stones., Conclusions: Noninvasive transcutaneous ultrasonic propulsion is a safe, effective and time efficient means to relocate calyceal stones to the renal pelvis, ureteropelvic junction or ureter. This technology holds promise as a useful adjunct to surgical management for renal calculi., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Applications of ultrasound in medicine for therapeutic purposes have been accepted and beneficial uses of ultrasonic biological effects for many years. Low-power ultrasound of about 1 MHz has been widely applied since the 1950s for physical therapy in conditions such as tendinitis and bursitis. In the 1980s, high-pressure-amplitude shock waves came into use for mechanically resolving kidney stones, and "lithotripsy" rapidly replaced surgery as the most frequent treatment choice. The use of ultrasonic energy for therapy continues to expand, and approved applications now include uterine fibroid ablation, cataract removal (phacoemulsification), surgical tissue cutting and hemostasis, transdermal drug delivery, and bone fracture healing, among others. Undesirable bioeffects can occur, including burns from thermal-based therapies and severe hemorrhage from mechanical-based therapies (eg, lithotripsy). In all of these therapeutic applications of ultrasound bioeffects, standardization, ultrasound dosimetry, benefits assurance, and side-effect risk minimization must be carefully considered to ensure an optimal benefit to risk ratio for the patient. Therapeutic ultrasound typically has well-defined benefits and risks and therefore presents a manageable safety problem to the clinician. However, safety information can be scattered, confusing, or subject to commercial conflicts of interest. Of paramount importance for managing this problem is the communication of practical safety information by authoritative groups, such as the American Institute of Ultrasound in Medicine, to the medical ultrasound community. In this overview, the Bioeffects Committee of the American Institute of Ultrasound in Medicine outlines the wide range of therapeutic ultrasound methods, which are in clinical use or under study, and provides general guidance for ensuring therapeutic ultrasound safety.

Purpose: A persistent stone burden after renal stone treatment may result in future patient morbidity and potentially lead to additional surgery. This problem is particularly common after treatment of lower pole stones. We describe a potential noninvasive therapeutic option using ultrasound waves to create a force sufficient to aid in stone fragment expulsion., Materials and Methods: Human stones were implanted by retrograde ureteroscopy or antegrade percutaneous access in a live porcine model. The calibrated probe of a system containing ultrasound imaging and focused ultrasound was used to target stones and attempt displacement. To assess for injury an additional 6 kidneys were exposed for 2 minutes each directly to the output used for stone movement. Another 6 kidneys were exposed to more than twice the maximum output used to move stones. Renal tissue was analyzed histologically with hematoxylin and eosin, and nicotinamide adenine dinucleotide staining., Results: Stones were moved to the renal pelvis or ureteropelvic junction by less than 2 minutes of exposure. Stone velocity was approximately 1 cm per second. There was no tissue injury when tissue was exposed to the power level used to move stones. Localized thermal coagulation less than 1 cm long was observed in 6 of 7 renal units exposed to the level above that used for ultrasonic propulsion., Conclusions: Transcutaneous ultrasonic propulsion was used to expel calculi effectively and safely from the kidney using a live animal model. This study is the first step toward an office based system to clear residual fragments and toward use as a primary treatment modality in conjunction with medical expulsive therapy for small renal stones., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Cavitation often occurs in therapeutic applications of medical ultrasound such as shock-wave lithotripsy (SWL) and high-intensity focused ultrasound (HIFU). Because cavitation bubbles can affect an intended treatment, it is important to understand the dynamics of bubbles in this context. The relevant context includes very high acoustic pressures and frequencies as well as elevated temperatures. Relative to much of the prior research on cavitation and bubble dynamics, such conditions are unique. To address the relevant physics, a reduced-order model of a single, spherical bubble is proposed that incorporates phase change at the liquid-gas interface as well as heat and mass transport in both phases. Based on the energy lost during the inertial collapse and rebound of a millimeter-sized bubble, experimental observations were used to tune and test model predictions. In addition, benchmarks from the published literature were used to assess various aspects of model performance. Benchmark comparisons demonstrate that the model captures the basic physics of phase change and diffusive transport, while it is quantitatively sensitive to specific model assumptions and implementation details. Given its performance and numerical stability, the model can be used to explore bubble behaviors across a broad parameter space relevant to therapeutic ultrasound.

Histotripsy is a therapy that focuses short-duration, high-amplitude pulses of ultrasound to incite a localized cavitation cloud that mechanically breaks down tissue. To investigate the mechanism of cloud formation, high-speed photography was used to observe clouds generated during single histotripsy pulses. Pulses of 5-20 cycles duration were applied to a transparent tissue phantom by a 1-MHz spherically focused transducer. Clouds initiated from single cavitation bubbles that formed during the initial cycles of the pulse, and grew along the acoustic axis opposite the propagation direction. Based on these observations, we hypothesized that clouds form as a result of large negative pressure generated by the backscattering of shockwaves from a single bubble. The positive-pressure phase of the wave inverts upon scattering and superimposes on the incident negative-pressure phase to create this negative pressure and cavitation. The process repeats with each cycle of the incident wave, and the bubble cloud elongates toward the transducer. Finite-amplitude propagation distorts the incident wave such that the peak-positive pressure is much greater than the peak-negative pressure, which exaggerates the effect. The hypothesis was tested with two modified incident waves that maintained negative pressure but reduced the positive pressure amplitude. These waves suppressed cloud formation which supported the hypothesis., (© 2011 Acoustical Society of America)

Nonlinear propagation causes high-intensity ultrasound waves to distort and generate higher harmonics, which are more readily absorbed and converted to heat than the fundamental frequency. Although such nonlinear effects have been investigated previously and found to not significantly alter high-intensity focused ultrasound (HIFU) treatments, two results reported here change this paradigm. One is that at clinically relevant intensity levels, HIFU waves not only become distorted but form shock waves in tissue. The other is that the generated shock waves heat the tissue to boiling in much less time than predicted for undistorted or weakly distorted waves. In this study, a 2-MHz HIFU source operating at peak intensities up to 25,000 W/cm(2) was used to heat transparent tissue-mimicking phantoms and ex vivo bovine liver samples. Initiation of boiling was detected using high-speed photography, a 20-MHz passive cavitation detector and fluctuation of the drive voltage at the HIFU source. The time to boil obtained experimentally was used to quantify heating rates and was compared with calculations using weak shock theory and the shock amplitudes obtained from nonlinear modeling and measurements with a fiber optic hydrophone. As observed experimentally and predicted by calculations, shocked focal waveforms produced boiling in as little as 3 ms and the time to initiate boiling was sensitive to small changes in HIFU output. Nonlinear heating as a result of shock waves is therefore important to HIFU, and clinicians should be aware of the potential for very rapid boiling because it alters treatments., (2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: High intensity focused ultrasound (HIFU) is being developed for a range of clinical applications. Of particular interest to NASA and the military is the use of HIFU for traumatic injuries because HIFU has the unique ability to transcutaneously stop bleeding. Automation of this technology would make possible its use in remote, austere settings by personnel not specialized in medical ultrasound. Here a system to automatically detect and target bleeding is tested and reported., Methods: The system uses Doppler ultrasound images from a clinical ultrasound scanner for bleeding detection and hardware for HIFU therapy. The system was tested using a moving string to simulate blood flow and targeting was visualized by Schlieren imaging to show the focusing of the HIFU acoustic waves., Results: When instructed by the operator, a Doppler ultrasound image is acquired and processed to detect and localize the moving string, and the focus of the HIFU array is electronically adjusted to target the string. Precise and accurate targeting was verified in the Schlieren images., Conclusions: An automated system to detect and target simulated bleeding has been built and tested. The system could be combined with existing algorithms to detect, target, and treat clinical bleeding.

Acoustic characterization of high intensity focused ultrasound (HIFU) fields is important both for the accurate prediction of ultrasound induced bioeffects in tissues and for the development of regulatory standards for clinical HIFU devices. In this paper, a method to determine HIFU field parameters at and around the focus is proposed. Nonlinear pressure waveforms were measured and modeled in water and in a tissue-mimicking gel phantom for a 2 MHz transducer with an aperture and focal length of 4.4 cm. Measurements were performed with a fiber optic probe hydrophone at intensity levels up to 24,000 W/cm(2). The inputs to a Khokhlov-Zabolotskaya-Kuznetsov-type numerical model were determined based on experimental low amplitude beam plots. Strongly asymmetric waveforms with peak positive pressures up to 80 MPa and peak negative pressures up to 15 MPa were obtained both numerically and experimentally. Numerical simulations and experimental measurements agreed well; however, when steep shocks were present in the waveform at focal intensity levels higher than 6000 W/cm(2), lower values of the peak positive pressure were observed in the measured waveforms. This underrepresentation was attributed mainly to the limited hydrophone bandwidth of 100 MHz. It is shown that a combination of measurements and modeling is necessary to enable accurate characterization of HIFU fields.

This study evaluated the cavitation activity induced by shock wave (SW) pulses, both in vitro and in vivo, based on the area measurements of echogenic regions observed in B-mode ultrasound images. Residual cavitation bubble clouds induced by SW pulses were detected as echogenic regions in B-mode images. The temporal evolution of residual bubble clouds, generated by SWs with varying lithotripter charging voltage and pulse repetition frequency (PRF), was analyzed by measuring the time-varying behaviors of the echogenic region areas recorded in B-mode images. The results showed that (1) the area of SW-induced echogenic regions enlarged with increased SW pulse number; (2) echogenic regions in the B-mode images dissipated gradually after ceasing the SWs, which indicated the dissolution of the cavitation bubbles; and (3) larger echogenic regions were generated with higher charging voltage or PRF.

Study of coagulative lesion formation by high intensity focused ultrasound (HIFU) in tissue usually requires performing a sequence of experiments under different exposure conditions followed by tissue sectioning. This paper, inspired by the pioneering work of Frederic L. Lizzi, reports on the use of the bovine eye lens as a laboratory model to observe visually the development of HIFU-induced lesions. The first part of this work describes the measurement of the lens shape, density, sound speed and attenuation. The measured values were within the range of previously published values. In the second part, HIFU-induced lesion development was observed in real-time and compared with good agreement with theoretical simulation. Theoretical modeling included acoustic propagation, absorptive heating and thermal dose, as well as the experimentally measured lens characteristics. Thus, the transparent eye lens can be used as a laboratory phantom to facilitate the understanding of HIFU treatment in other tissues.

The importance of nonlinear acoustic wave propagation and ultrasound-induced cavitation in the acceleration of thermal lesion production by high intensity focused ultrasound was investigated experimentally and theoretically in a transparent protein-containing gel. A numerical model that accounted for nonlinear acoustic propagation was used to simulate experimental conditions. Various exposure regimes with equal total ultrasound energy but variable peak acoustic pressure were studied for single lesions and lesion stripes obtained by moving the transducer. Static overpressure was applied to suppress cavitation. Strong enhancement of lesion production was observed for high amplitude waves and was supported by modeling. Through overpressure experiments it was shown that both nonlinear propagation and cavitation mechanisms participate in accelerating lesion inception and growth. Using B-mode ultrasound, cavitation was observed at normal ambient pressure as weakly enhanced echogenicity in the focal region, but was not detected with overpressure. Formation of tadpole-shaped lesions, shifted toward the transducer, was always observed to be due to boiling. Boiling bubbles were visible in the gel and were evident as strongly echogenic regions in B-mode images. These experiments indicate that nonlinear propagation and cavitation accelerate heating, but no lesion displacement or distortion was observed in the absence of boiling.

Purpose We developed a new method of lithotripsy that uses short, broadly focused bursts of ultrasound rather than shock waves to fragment stones. We investigated the characteristics of stone comminution by burst wave lithotripsy in vitro. Materials and Methods Artificial and natural stones (mean ± SD size 8.2 ± 3.0 mm, range 5 to 15) were treated with ultrasound bursts using a focused transducer in a water bath. Stones were exposed to bursts with focal pressure amplitude of 6.5 MPa or less at a 200 Hz burst repetition rate until completely fragmented. Ultrasound frequencies of 170, 285 and 800 kHz were applied using 3 transducers, respectively. Time to 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 of 2.8 MPa or greater at 170 kHz. Fractures appeared along the stone surface, resulting in fragments that separated 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 a mean treatment duration of 36 seconds for uric acid stones to 14.7 minutes for cystine stones. At a frequency of 170 kHz the largest artificial stone fragments were less than 4 mm. Exposure at 285 and 800 kHz produced only fragments less than 2 mm and less than 1 mm, respectively. Conclusions Stone comminution with burst wave lithotripsy is feasible as a potential noninvasive treatment method for nephrolithiasis. Adjusting the fundamental ultrasound frequency allows for stone fragment size to be controlled. [ABSTRACT FROM AUTHOR]