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Mike Bailey

Senior Principal Engineer

Assistant Professor, Mechanical Engineering and Adjunct Assistant Professor, Urology

Email

bailey@apl.washington.edu

Phone

206-685-8618

Research Interests

Medical Ultrasound, Acoustic Cavitation

Biosketch

Dr. Bailey's current research focuses on the role of cavitation in lithotripsy (kidney stone treatment) and ultrasound surgery. He is the lead APL-UW researcher on two collaborative programs among the Laboratory, Indiana University, Moscow State University, and the California Institute of Technology to optimize acoustic waves to exploit bioeffects due to cavitation. Previously, he was one of the designers of a shock wave lithotripter developed at APL-UW to concentrate cavitation and damage on the kidney stone and not on the kidney tissue. Dr. Bailey joined APL-UW in 1996.

Education

B.S. Mechanical Engineering, Yale University, 1991

M.S. Mechanical Engineering, The University of Texas at Austin, 1994

Ph.D. Mechanical Engineering, The University of Texas at Austin, 1997

Videos

Ultrasonic Detection and Propulsion of Kidney Stones

An ultrasound-based system assembled from commercial components and customized software control locates kidney stones, applies an acoustic radiative force, and repositions the stones so they are more likely to pass naturally. Watch urologist test the system.

2 May 2013

SonoMotion: A Budding Start-up Company

A research team has developed new technologies to treat kidney stone disease with an ultrasound-based system. Embraced by clinicians, their advances are now being taken to the next step: transition the prototype to an approved device that will roll into hospitals and clinics around the world.

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11 Feb 2013

At the Center for Industrial and Medical Ultrasound a team of scientists, engineers, and students has developed an ultrasound-based system that may provide an office procedure to speed the natural passage of kidney stones. The system uses commercial ultrasound components to locate stones in kidneys. It creates clear pictures of them and then applies an acoustic radiative force, repositioning stones in the kidney so they are more likely to pass naturally.

As a research team, considerable technical advancements have been made and valuable feedback and cooperation has been garnered from the user community – the clinicians. The scientists, engineers, urologists, and commercialization experts are now collaborating to take the next steps.

SonoMotion has partnered with a hardware manufacturing company and licensed the ultrasonic propulsion of kidney stones technology with the University of Washington. The next big step will be to transition the prototype system into one that will pass the rigors of FDA review and be ready to roll into hospitals and clinics around the world.

Center for Industrial and Medical Ultrasound - CIMU

CIMU is a group of scientists, engineers, and technicians dedicated to research across the field of bio-medical ultrasonics with the goal of developing technologies that will be used in a clinic to treat patients.

1 Nov 2010

Publications

2000-present and while at APL-UW

Fragmentation of urinary calculi in vitro by burst wave lithotripsy

Maxwell, A.D., B.W. Cunitz, W. Kreider, O.A. Sapozhnikov, R.S. Hsi, J.D. Harper, M.R. Bailey, and M.D. Sorensen, "Fragmentation of urinary calculi in vitro by burst wave lithotripsy," J. Urol., EOR, doi:10.1016/j.juro.2014.08.009, 2014.

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9 Aug 2014

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

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

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

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

Preclinical safety and effectiveness studies of ultrasonic propulsion of kidney stones

Harper, J.D., B. Dunmire, Y.-N. Wang, J.C. Simon, D. Liggitt, M. Paun, B.W. Cunitz, F. Starr, M.R. Bailey, K.L. Penniston, F.C. Lee, R.S. Hsi, and M.D. Sorensen, "Preclinical safety and effectiveness studies of ultrasonic propulsion of kidney stones," Urology, 84, 484-489, doi:10.1016/j.urology.2014.04.041, 2014.

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1 Aug 2014

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.

Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model

Khokhlova, T.D., Y.-N. Wang, J.C. Simon, B.W. Cunitz, F. Starr, M. Paun, L.A. Crum, M.R. Bailey, and V.A. Khokhlova, "Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model," P. Natl. Acad. Sci. USA, 111, 8161-8166, doi:10.1073/pnas.1318355111, 2014.

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3 Jun 2014

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.

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Pulsed focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: A study in a mouse model

Poliachik, S.L., T.D. Khokhlova, Y.-N. Wang, J.C. Simon, and M.R. Bailey, "Pulsed focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: A study in a mouse model," Ultrasound Med. Biol., EOR, doi:10.1016/j.ultrasmedbio.2014.02.027, 2014.

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21 May 2014

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.

Focused ultrasound to displace renal calculi: Threshold for tissue injury

Wang, Y.-N., J.C. Simon, B.W. Cunitz, F.L. Starr, M. Paun, D.H. Liggitt, A.P. Evan, J.A. McAteer, Z. Liu, B. Dunmire, and M.R. Bailey, "Focused ultrasound to displace renal calculi: Threshold for tissue injury," J. Therapeut. Ultrasound, 2, doi:10.1186/2050-5736-2-5, 2014.

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31 Mar 2014

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

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

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

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

Content and face validation of a curriculum for ultrasonic propulsion of calculi in a human renal model

Hsi, R.S., B. Dunmire, B.W. Cunitz, X. He, M.D. Sorensen, J.D. Harper, M.R. Bailey, and T.S. Lendvay, "Content and face validation of a curriculum for ultrasonic propulsion of calculi in a human renal model," J. Endourol., 28, 459-463, doi:10.1089/end.2013.0589, 2014.

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20 Mar 2014

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

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

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

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

Noninvasive ureterocele puncture using pulsed focused ultrasound: An in vitro study

Maxwell, A.D., R.S. Hsi, M.R. Bailey, P. Casale, and T.S. Lendvay, "Noninvasive ureterocele puncture using pulsed focused ultrasound: An in vitro study," J. Endourol., 28, 342-346, doi:10.1098/end.2013.0528, 2014.

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1 Mar 2014

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

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

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

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

Comparison of tissue injury from focused ultrasonic propulsion of kidney stones versus extracorporeal shock wave lithotripsy

Connors, B.A., A.P. Evan, P.M. Blomgren, R.S. Hsi, J.D. Harper, M.D. Sorensen, Y.-N. Wang, J.C. Simon, M. Paun, F. Starr, B.W. Cunitz, M.R. Bailey, and J.E. Lingeman, "Comparison of tissue injury from focused ultrasonic propulsion of kidney stones versus extracorporeal shock wave lithotripsy," J. Urol., 191, 235-241, doi:10.1016/j.juro.2013.07.087, 2014.

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1 Jan 2014

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.

Addressing nonlinear propagation effects in characterization of high intensity focused ultrasound fields and prediction of thermal and mechanical bioeffects in tissue

Khokhlova, V.A., P.V. Yuldashev, W. Kreider, O.A. Sapozhnikov, M.R. Vailey, T.D. Khokhlova, A.D. Maxwell, and L.A. Crum, "Addressing nonlinear propagation effects in characterization of high intensity focused ultrasound fields and prediction of thermal and mechanical bioeffects in tissue," J. Acoust. Soc. Am., 134, 4153, doi:10.1121/1.4831221, 2013.

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1 Nov 2013

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

An ultrasound system to identify and characterize kidney stones

Cunitz, B.W., B.L. Dunmire, M.D. Sorensen, R. Hsi, F. Lee, O.A. Sapozhnikov, J.D. Harper, and M. Bailey, "An ultrasound system to identify and characterize kidney stones," J. Acoust. Soc. Am., 134, 3976, doi:10.1121/1.4830485, 2013.

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1 Nov 2013

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

Fragmentation of kidney stones in vitro by focused ultrasound bursts without shock waves

Maxwell, A.D., B.W. Cunitz, W. Kreider, O.A. Sapozhnikov, R.S. Hsi, M.D. Sorensen, J. D. Harper, and M.R. Bailey, "Fragmentation of kidney stones in vitro by focused ultrasound bursts without shock waves," J. Acoust. Soc. Am., 134, 4183, doi:10.1121/1.4831340, 2013.

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1 Nov 2013

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

Kidney stone fracture by surface waves generated with focused ultrasound tone bursts

Sapozhnikov, O.A., A.D. Maxwell, W. Kreider, B.W. Cunitz, and M.R. Bailey, "Kidney stone fracture by surface waves generated with focused ultrasound tone bursts," J. Acoust. Soc. Am., 134, 4184, doi:10.1121/1.4831341, 2013.

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1 Nov 2013

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

Characterization of a multi-element clinical HIFU system using acoustic halography and nonlinear modeling

Kreider, W., P. Yuldashev, O.A. Sapozhnikov, N. Farr, A. Partanen, M. Bailey, and V.A. Khokhlova, "Characterization of a multi-element clinical HIFU system using acoustic halography and nonlinear modeling," IEEE Trans. Ultrason. Ferr. Freq. Control, 60, 1683-1698, doi:10.1109/TUFFC.2013.2750, 2013.

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1 Aug 2013

High-intensity focused ultrasound (HIFU) is a treatment modality that relies on the delivery of acoustic energy to remote tissue sites to induce thermal and/or mechanical tissue ablation. To ensure the safety and efficacy of this medical technology, standard approaches are needed for accurately characterizing the acoustic pressures generated by clinical ultrasound sources under operating conditions. Characterization of HIFU fields is complicated by nonlinear wave propagation and the complexity of phased-array transducers. Previous work has described aspects of an approach that combines measurements and modeling, and here we demonstrate this approach for a clinical phased-array transducer. First, low amplitude hydrophone measurements were performed in water over a scan plane between the array and the focus. Second, these measurements were used to holographically reconstruct the surface vibrations of the transducer and to set a boundary condition for a 3-D acoustic propagation model. Finally, nonlinear simulations of the acoustic field were carried out over a range of source power levels. Simulation results were compared with pressure waveforms measured directly by hydrophone at both low and high power levels, demonstrating that details of the acoustic field, including shock formation, are quantitatively predicted.

Ultrasound intensity to propel stones from the kidney is below the threshold for renal injury

Wang, Y.-N., J.C. Simon, B. Cunitz, F. Starr, M. Paun, D. Liggit, A. Evan, J. McAteer, J. Williams, Z. Liu, P. Kaczkowski, R. Hsi, M. Sorensen, J. Harper, and M.R. Bailey, "Ultrasound intensity to propel stones from the kidney is below the threshold for renal injury," Proc., Meetings on Acoustics., 19, 075066, doi:10.1121/1.4800361, 2013.

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3 Jun 2013

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

Rectified growth of histotripsy bubbles

Kreider, W., A.D. Maxwell, T. Khokhlova, J.C. Simon, V.A. Khokhlova, O. Sapzhnikov, and M.R. Bailey, "Rectified growth of histotripsy bubbles," Proc., Meetings on Acoustics, 19, 075035, doi:10.1121/1.4800326, 2013.

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2 Jun 2013

Histotripsy treatments use high-amplitude shock waves to fractionate tissue. Such treatments have been demonstrated using both cavitation bubbles excited with microsecond-long pulses and boiling bubbles excited for milliseconds. A common feature of both approaches is the need for bubble growth, where at 1 MHz cavitation bubbles reach maximum radii on the order of 100 microns and boiling bubbles grow to about 1 mm. To explore how histotripsy bubbles grow, a model of a single, spherical bubble that accounts for heat and mass transport was used to simulate the bubble dynamics. Results suggest that the asymmetry inherent in nonlinearly distorted waveforms can lead to rectified bubble growth, which is enhanced at elevated temperatures. Moreover, the rate of this growth is sensitive to the waveform shape, in particular the transition from the peak negative pressure to the shock front. Current efforts are focused on elucidating this behavior by obtaining an improved calibration of measured histotripsy waveforms with a fiber-optic hydrophone, using a nonlinear propagation model to assess the impact on the focal waveform of higher harmonics present at the source's surface, and photographically observing bubble growth rates.

Evidence for trapped surface bubbles as the cause for the twinkling artifact in ultrasound imaging

Lu, W., O.A. Sapozhnikov, M.R. Bailey, P.J. Kaczkowski, and L.A. Crum, "Evidence for trapped surface bubbles as the cause for the twinkling artifact in ultrasound imaging," Ultrasound Med. Biol., 39, 1026-1038, doi:10.1016/j.ultrasmedbio.2013.01.011, 2013.

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1 Jun 2013

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

Focused ultrasound to expel calculi from the kidney: Safety and efficacy of a clinical prototype device

Harper, J.D., M.D. Sorensen, B.W. Cunitz, Y.-N. Wang, J.C. Simon, F. Starr, M. Paun, B. Dunmire, H.D. Liggitt, A.P. Evan, J.A. McAteer, R.S. Hsi, and M.R. Bailey, "Focused ultrasound to expel calculi from the kidney: Safety and efficacy of a clinical prototype device," J. Urol., 190, 1090-1095, doi:10.1016/j.juro.2013.03.120, 2013.

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9 Apr 2013

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

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

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

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

Histological and biochemical analysis of mechanical and thermal bioeffects in boiling histotripsy lesions induced by high intensity focused ultrasound

Wang, Y.-N., T. Khokhlova, M. Bailey, J.H. Hwang, and V. Khokhlova, "Histological and biochemical analysis of mechanical and thermal bioeffects in boiling histotripsy lesions induced by high intensity focused ultrasound," Ultrasound Med. Biol., 39, 424-438, doi:10.1016/j.ultrasmedbio.2012.10.012, 2013.

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1 Mar 2013

Recent studies have shown that shockwave heating and millisecond boiling in high-intensity focused ultrasound fields can result in mechanical fractionation or emulsification of tissue, termed boiling histotripsy. Visual observations of the change in color and contents indicated that the degree of thermal damage in the emulsified lesions can be controlled by varying the parameters of the exposure. The goal of this work was to examine thermal and mechanical effects in boiling histotripsy lesions using histologic and biochemical analysis. The lesions were induced in ex vivo bovine heart and liver using a 2-MHz single-element transducer operating at duty factors of 0.005–0.01, pulse durations of 5–500 ms and in situ shock amplitude of 73 MPa. Mechanical and thermal damage to tissue was evaluated histologically using conventional staining techniques (hematoxylin and eosin, and nicotinamide adenine dinucleotide-diaphorase). Thermal effects were quantified by measuring denaturation of salt soluble proteins in the treated region. According to histologic analysis, the lesions that visually appeared as a liquid contained no cellular structures larger than a cell nucleus and had a sharp border of one to two cells. Both histologic and protein analysis showed that lesions obtained with short pulses (<10 ms) did not contain any thermal damage. Increasing the pulse duration resulted in an increase in thermal damage. However, both protein analysis and nicotinamide adenine dinucleotide-diaphorase staining showed less denaturation than visually observed as whitening of tissue. The number of high-intensity focused ultrasound pulses delivered per exposure did not change the lesion shape or the degree of thermal denaturation, whereas the size of the lesion showed a saturating behavior suggesting optimal exposure duration. This study confirmed that boiling histotripsy offers an effective, predictable way to non-invasively fractionate tissue into sub-cellular fragments with or without inducing thermal damage.

B-mode ultrasound versus color Doppler twinkling artifact in detecting kidney stones

Sorensen, M.D., J.D. Harper, R.S. Hsi, A.R. Shah, M.K. Dighe, S.J. Carter, M. Moshiri, M. Paun, W. Lu, and M.R. Bailey, "B-mode ultrasound versus color Doppler twinkling artifact in detecting kidney stones," J. Endourol., 27, 149-153, doi:10.1089/end.2012.0430, 2013.

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1 Feb 2013

Purpose:
To compare color Doppler twinkling artifact and B-mode ultrasonography in detecting kidney stones.

Patients and Methods:
Nine patients with recent CT scans prospectively underwent B-mode and twinkling artifact color Doppler ultrasonography on a commercial ultrasound machine. Video segments of the upper pole, interpolar area, and lower pole were created, randomized, and independently reviewed by three radiologists. Receiver operator characteristics were determined.

Results:
There were 32 stones in 18 kidneys with a mean stone size of 8.9 ± 7.5 mm. B-mode ultrasonography had 71% sensitivity, 48% specificity, 52% positive predictive value, and 68% negative predictive value, while twinkling artifact Doppler ultrasonography had 56% sensitivity, 74% specificity, 62% positive predictive value, and 68% negative predictive value.

Conclusions: When used alone, B-mode is more sensitive, but twinkling artifact is more specific in detecting kidney stones. This information may help users employ twinkling and B-mode to identify stones and developers to improve signal processing to harness the fundamental acoustic differences to ultimately improve stone detection.

Radiation force of an arbitrary acoustic beam on an elastic sphere in a fluid

Sapozhnikov, O., and M.R. Bailey, "Radiation force of an arbitrary acoustic beam on an elastic sphere in a fluid," J. Acoust. Soc. Am., 133, 661-676, doi:10.1121/1.4773924, 2013.

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1 Feb 2013

A theoretical approach is developed to calculate the radiation force of an arbitrary acoustic beam on an elastic sphere in a liquid or gas medium. First, the incident beam is described as a sum of plane waves by employing conventional angular spectrum decomposition. Then, the classical solution for the scattering of a plane wave from an elastic sphere is applied for each plane-wave component of the incident field. The net scattered field is expressed as a superposition of the scattered fields from all angular spectrum components of the incident beam. With this formulation, the incident and scattered waves are superposed in the far field to derive expressions for components of the radiation stress tensor. These expressions are then integrated over a spherical surface to analytically describe the radiation force on an elastic sphere. Limiting cases for particular types of incident beams are presented and are shown to agree with known results. Finally, the analytical expressions are used to calculate radiation forces associated with two specific focusing transducers.

Ultrasonic atomization of tissue and its role in tissue fractionation by high intensity focused ultrasound

Simon, J.C., O.A. Sapozhnikov, V.A. Khokhlova, Y.-N. Wang, L.A. Crum, and M.R. Bailey, "Ultrasonic atomization of tissue and its role in tissue fractionation by high intensity focused ultrasound," Phys. Med. Biol. 57, 8061-8078, doi:10.1088/0031-9155/57/23/8061, 2012.

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7 Dec 2012

Atomization and fountain formation is a well-known phenomenon that occurs when a focused ultrasound wave in liquid encounters an air interface. High intensity focused ultrasound (HIFU) has been shown to fractionate a tissue into submicron-sized fragments in a process termed boiling histotripsy, wherein the focused ultrasound wave superheats the tissue at the focus, producing a millimetre-sized boiling or vapour bubble in several milliseconds. Yet the question of how this millimetre-sized boiling bubble creates submicron-sized tissue fragments remains. The hypothesis of this work is that the tissue can behave as a liquid such that it atomizes and forms a fountain within the vapour bubble produced in boiling histotripsy. We describe an experiment, in which a 2 MHz HIFU transducer (maximum in situ intensity of 24,000 W cm-2) was aligned with an air–tissue interface meant to simulate the boiling bubble. Atomization and fountain formation was observed with high-speed photography and resulted in tissue erosion. Histological examination of the atomized tissue showed whole and fragmented cells and nuclei. Air–liquid interfaces were also filmed. Our conclusion was that HIFU can fountain and atomize tissue. Although this process does not entirely mimic what was observed in liquids, it does explain many aspects of tissue fractionation in boiling histotripsy.

Novel high-intensity focused ultrasound clamp — potential adjunct for laparoscopic partial nephrectomy

Harper, J.D., A. Shah, S.B. Mitchell, Y.N. Wang, F. Starr, M.R. Bailey, and L.A. Crum, "Novel high-intensity focused ultrasound clamp — potential adjunct for laparoscopic partial nephrectomy," J. Endourol., 26, 1494-1499, doi:10.1098/end.2012.0107, 2012.

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1 Nov 2012

BACKGROUND AND PURPOSE:
Partial nephrectomy (PN) can be technically challenging, especially if performed in a minimally invasive manner. Although ultrasound technology has been shown to have therapeutic capabilities, including tissue ablation and hemostasis, it has not gained clinical use in the PN setting. The purpose of this study is to evaluate the ability of a high-intensity ultrasound clamp to create an ablation plane in the kidney providing hemostasis that could potentially aid in laparoscopic PN.
METHODS:
A new instrument was created using a laparoscopic Padron endoscopic exposing retractor. Ultrasound elements were engineered on both sides of the retractor to administer high-intensity ultrasound energy between the two sides of the clamp. This high-intensity focused ultrasound (HIFU) clamp was placed 2 to 2.5 cm from the upper and lower poles of 10 porcine kidneys to evaluate its effectiveness at different levels and duration of energy delivery. PN transection was performed through the distal portion of the clamped margin. Kidneys postintervention and after PN were evaluated and blood loss estimated by weighing gauze placed at the defect. Histologic analysis was performed with hematoxylin and eosin and nicotinamide adenine dinucleotide staining to evaluate for tissue viability and thermal spread.
RESULTS:
Gross parenchymal changes were seen with obvious demarcation between treated and untreated tissue. Increased ultrasound exposure time (10 vs 5 and 2 min), even at lower power settings, was more effective in causing destruction and necrosis of tissue. Transmural ablation was achieved in three of four renal units after 10 minutes of exposure with significantly less blood loss (<2 g vs 30-100 g). Nonviable tissue was confirmed histologically. There was minimal thermal spread outside the clamped margin (1.2-3.2 mm).
CONCLUSION:
In this preliminary porcine evaluation, a novel HIFU clamp induced hemostasis and created an ablation plane in the kidney. This technology could serve as a useful adjunct to laparoscopic PN in the future and potentially obviate the need for renal hilar clamping.

Disintegration of tissue using high intensity focused ultrasound: Two approaches that utilize shock waves

Maxwell, A., O. Sapozhnikov, M. Bailey, L. Crum, Z. Xu, B. Fowlkes, C. Cain, and V. Khokhlova, "Disintegration of tissue using high intensity focused ultrasound: Two approaches that utilize shock waves," Acoust. Today, 8, 24-37, doi:10.1121/1.4788649, 2012.

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1 Oct 2012

Surgery is moving more and more toward minimally-invasive procedures — using laparoscopic approaches with instruments inserted through tiny incisions or catheters placed in blood vessels through puncture sites. These techniques minimize the risks to the patient such as bleeding complications or infection during surgery. Taken a step further, high-intensity focused ultrasound (HIFU) can provide a tool to accomplish many of the same procedures without any incision at all. This article discusses the acoustics of histotripsy — including the processes of generation and focusing of intense ultrasound, the formation of cavitation clouds and rapid boiling in tissue, and the interactions of ultrasound shock waves with bubbles leading to tissue disintegration.

Nonlinear modeling as a metrology tool to characterize high intensity focused ultrasound fields

Khokhlova, V., P. Yuldashev, W. Kreider, O. Sapozhnikov, M. Bailey, and L. Crum, "Nonlinear modeling as a metrology tool to characterize high intensity focused ultrasound fields," J. Acoust. Soc. Am., 132, 1919, doi:10.1121/1.2755042, 2012.

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1 Sep 2012

High intensity focused ultrasound (HIFU) is a rapidly growing medical technology with many clinical applications. The safety and efficacy of these applications require accurate characterization of ultrasound fields produced by HIFU systems. Current nonlinear numerical models based on the KZK and Westervelt wave equations have been shown to serve as quantitatively accurate tools for HIFU metrology. One of the critical parts of the modeling is to set a boundary condition at the source. In previous studies we proposed using measurements of low-amplitude fields to determine the source parameters. In this paper, two approaches of setting the boundary condition are reviewed: The acoustic holography method utilizes two-dimensional scanning of pressure amplitude and phase and numerical back-propagation to the transducer surface. An equivalent source method utilizes one-dimensional pressure measurements on the beam axis and in the focal plane. The dimensions and surface velocity of a uniformly vibrating transducer then are determined to match the one-dimensional measurements in the focal region. Nonlinear simulations are performed for increasing pressure levels at the source for both approaches. Several examples showing the accuracy and capabilities of the proposed methods are presented for typical HIFU transducers with different geometries.

Quantitative assessment of shock wave lithotripsy accuracy and the effect of respiratory motion

Sorensen, M.D., M.R. Bailey, A.R. Shah, R.S. Hsi, M. Paun, and J.D. Harper, "Quantitative assessment of shock wave lithotripsy accuracy and the effect of respiratory motion," J. Endourology, 26, 1070-1074, doi:10.1089/end.2012.0042, 2012.

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3 Apr 2012

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

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

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

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

Overview of therapeutic ultrasound applications and safety considerations

Miller, D.L., N.B. Smith, M.R. Bailey, G.J. Czarnota, K. Hynynen, I.R.S. Makin, and Bioeffects Committee of the American Institute of Ultrasound in Medicine, "Overview of therapeutic ultrasound applications and safety considerations," J. Ultrasound Med., 31, 623-634, 2012.

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1 Apr 2012

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 %u201Clithotripsy%u201D 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.

Focused ultrasound to expel calculi from the kidney

Shah, A., J.D. Harper, B.W. Cunitz, Y.-N. Wang, M. Paun, J.C. Simon, W. Lu, P.J. Kaczkowski, and M.R. Bailey, "Focused ultrasound to expel calculi from the kidney," J. Urol., 187, 739-743, doi:10.1016/j.juro.2011.09.144, 2012.

1 Feb 2012

Observations of translation and jetting of ultrasound-activated microbubbles in mesenteric microvessels

Chen, H., A.A. Brayman, W. Kreider, M.R. Bailey, and T.J. Matula, "Observations of translation and jetting of ultrasound-activated microbubbles in mesenteric microvessels," Ultrasound Med. Biol., 37, 2139-2148, doi:10.1016/j.ultrasmedbio.2011.09.013, 2011.

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1 Dec 2011

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 microsecond 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 micrometers. 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 micrometers. 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.

The dynamics of histotripsy bubbles

Kreider, W., M.R. Bailey, O.A. Sapozhnikov, V.A. Khokhlova, and L.A. Crum, "The dynamics of histotripsy bubbles," in Proc., 10th International Symposium on Therapeutic Ultrasound (ISTU 2010), 9-12 June, Tokyo, Japan, 427-430, doi:10.1063/1.3607944 (AIP Conf. Proc. 1359, 2011).

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9 Jun 2011

Histotripsy describes treatments in which high-amplitude acoustic pulses are used to excite bubbles and erode tissue. Though tissue erosion can be directly attributed to bubble activity, the genesis and dynamics of bubbles remain unclear. Histotripsy lesions that show no signs of thermal coagulative damage have been generated with two different acoustic protocols: relatively long acoustic pulses that produce local boiling within milliseconds and relatively short pulses that are higher in amplitude but likely do not produce boiling. While these two approaches are often distinguished as 'boiling' versus 'cavitation', such labels can obscure similarities. In both cases, a bubble undergoes large changes in radius and vapor is transported into and out of the bubble as it oscillates. Moreover, observations from both approaches suggest that bubbles grow to a size at which they cease to collapse violently. In order to better understand the dynamics of histotripsy bubbles, a single-bubble model has been developed that couples acoustically excited bubble motions to the thermodynamic state of the surrounding liquid. Using this model for bubbles exposed to histotripsy sound fields, simulations suggest that two mechanisms can act separately or in concert to lead to the typically observed bubble growth. First, nonlinear acoustic propagation leads to the evolution of shocks and an asymmetry in the positive and negative pressures that drive bubble motion. This asymmetry can have a rectifying effect on bubble oscillations whereby the bubble grows on average during each acoustic cycle. Second, vapor transport to/from the bubble tends to produce larger bubbles, especially at elevated temperatures. Vapor transport by itself can lead to rectified bubble growth when the ambient temperature exceeds 100C ('boiling') or local heating in the vicinity of the bubble leads to a superheated boundary layer.

Shock wave technology and application: An update.

Rassweiler, J.J., T. Knoll, J.A. McAteer, J.E. Lingeman, R.O. Cleveland, M.R. Bailey, and C. Chaussy, "Shock wave technology and application: An update." Eur. Urol., 59, 784-796, doi:10.1016:/ju.eururo.2011.02.033, 2011.

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1 May 2011

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

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

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

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

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

A method of mechanical emulsification in a bulk tissue using shock wave heating and millisecond boiling

Khokhlova, V.A., M.S. Canney, M.R. Bailey, J.H. Hwang, T.D. Khokhlova, W. Kreider, Y.N. Wang, J.C. Simon, Y. Zhou, O.A. Sapozhnikov, and L.A. Crum, "A method of mechanical emulsification in a bulk tissue using shock wave heating and millisecond boiling," J. Acoust. Soc. Am., 129, 2476, doi:10.1121/1.3588143, 2011.

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1 Apr 2011

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

Advantages and limitations of the fiber-optic probe hydrophone for characterization of shock waves in water

Pishchalnikov, Y.A., D.F. Gaitan, M.S. Einert, M.R. Bailey, O.A. Sapozhnikov, and J.A. McAteer, "Advantages and limitations of the fiber-optic probe hydrophone for characterization of shock waves in water," J. Acoust. Soc. Am., 129, 2677, doi:10.1121/1.3588972, 2011.

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1 Apr 2011

The fiber-optic probe hydrophone (FOPH) (RP Acoustics, Leutenbach, Germany) is the standard for shock wave measurement, as it is omnidirectional with a flat frequency response ranging from static pressure to several megahertz. The FOPH calibration is determined from the equation of state of water, the optical refractive index of the glass/water interface, and the dc level of reflected light. We tested the accuracy of this calibration by placing the sensitive tip of the FOPH under static pressure up to 140 MPa. The FOPH gave accurate readings of applied static pressures provided there were no defects in the fiber. Defects (cracks and chips) in the glass fiber were difficult to control and could occur during routine handling: stripping, cleaving, or mounting. Such defects led to spurious spikes in measured waveforms. Defects were also caused by cavitation damage to the fiber. In addition, cavitation bubbles on the fiber compressed the fiber and resulted in distorted waveform measurement. Thus, although the FOPH is omnidirectional and accurate from zero to tens of megahertz, it is also susceptible to minute defects in the fiber and to cavitation bubble collapse along the fiber.

Autoregressive ultrasound imaging method to enhance kidney stone twinkling and suppress blood flow

Kucewicz, J.C., B.W. Cunitz, B. Dunmire, M.R. Bailey, and L.A. Crum, "Autoregressive ultrasound imaging method to enhance kidney stone twinkling and suppress blood flow," J. Acoust. Soc. Am., 129, 2376, doi:10.1121/1.3587699, 2011.

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1 Apr 2011

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

Challenges of clinical high intensity focused ultrasound: The need for metrology

Hwang, J.H., V.A. Khokhlova, and M.R. Bailey, "Challenges of clinical high intensity focused ultrasound: The need for metrology," J. Acoust. Soc. Am., 129, 2403, doi:10.1121/1.3587823, 2011.

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1 Apr 2011

Metrology of high intensity focused ultrasound (HIFU) is critical to the advancement of clinical application of HIFU for safe and effective treatments in patients. Several methods for performing metrology of HIFU systems are available in the research laboratory setting; however, translation of these methods to the clinical setting remains in evolution. From our initial experience with clinical HIFU systems we have realized the importance of accurate acoustic characterization of HIFU systems in order to determine the parameters of the treatment protocol to result in safe and effective treatments. The acoustic parameters of the system, particularly at very high intensities, are very important to understand prior to delivering HIFU therapy to patients. Improved methods of HIFU metrology, especially to determine in situ exposure and dose, will result in a more rational approach to clinical HIFU therapy. Further advances in clinical HIFU therapy will require close cooperation between clinicians and scientists in order to make HIFU therapy safe and effective. Educating clinicians on the importance of metrology will also be important.

Characterization of nonlinearly distorted ultrasound waves in water using broadband laser vibrometry

Sapozhnikov, O.A., B.W. Cunitz, and M.R. Bailey, "Characterization of nonlinearly distorted ultrasound waves in water using broadband laser vibrometry," J. Acoust. Soc. Am., 129, 2678, doi:10.1121/1.3588977, 2011.

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1 Apr 2011

Laser vibrometry is a practical method to detect surface displacement. The method enables a direct measurement of acoustic field parameters such as acoustic particle displacement or acoustic particle velocity. Unlike other sensors, e.g., hydrophones, laser vibrometers are completely non-contact. Such devices are capable of measuring displacements from centimeters to sub nanometers at frequencies from near dc to 10 s of megahertz and have been proven to establish a primary standard for calibrating hydrophones [Bacon, IEEE Trans. UFFC, 35 (1988)]. In this technique, an ultrasonic transducer radiates an acoustic wave which is detected by a thin plastic membrane - a pellicle. The pellicle is effectively transparent to the acoustic beam so that the vibration of the pellicle follows the particle motion in the sound wave, but is reflective to the optical beam of the vibrometer allowing for a measurement. The present talk will report on measurements of nonlinearly distorted sawtooth waves in water performed with two commercial Polytec laser vibrometers: a scanning 24 MHz bandwidth system and a non-scanning 600 MHz bandwidth system. It is shown that appropriately chosen optical targets - pellicle or thick glass block with flat sides - allow resolution of both shock front and the smooth part of the waveform.

Clinical assessment of shockwave lithotripsy accuracy

Shah, A., J.D. Harper, J.L. Wright, M.D. Sorensen, M. Paun, and M.R. Bailey, "Clinical assessment of shockwave lithotripsy accuracy," J. Acoust. Soc. Am., 129, 2376, doi:10.1121/1.3587696, 2011.

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1 Apr 2011

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

Full-diffraction and parabolic axisymmetric numerical models to characterize nonlinear ultrasound fields of two-dimensional therapeutic arrays

Khokhlova, V.A., P.V.Yuldashev, M.V. Averiyanov, O.V. Bessanova, O.A. Sapozhnikov, and M.R. Bailey, "Full-diffraction and parabolic axisymmetric numerical models to characterize nonlinear ultrasound fields of two-dimensional therapeutic arrays," J. Acoust. Soc. Am., 129, 2404, doi:10.1121/1.3587828, 2011.

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1 Apr 2011

Numerical modeling has been shown to be an effective tool to characterize nonlinear pressure fields for single-element HIFU transducers, but it has not yet been applied for the much more complex three-dimensional (3-D) fields generated by therapeutic phased arrays. In this work, two approaches are presented to simulate nonlinear effects in the field of a 256-element focused array. A new full-diffraction approach includes rigorous 3-D simulations of the nonlinear wave equation with a boundary condition given at the elements of the array. A second simpler approach is based on the KZK model and a focused piston source as the boundary condition. The effective aperture and initial pressure of the piston source are set by matching linear simulations of the two models in the focal region. It is shown that as output power is increased, agreement in the focal waveforms of the two simulations, even when shocks were present, is maintained up to very high power outputs of the array. These results demonstrate the feasibility of using the simplified KZK model to evaluate the role of nonlinear effects in the fields of two-dimensional (2-D) phased arrays of clinical devices.

Histological and biochemical analysis of emulsified lesions in tissue induced by high intensity focused ultrasound

Wang, Y.N., T.D. Khokhlova, M.S. Canney, V.A. Khokhlova, L.A. Crum, and M.R. Bailey, "Histological and biochemical analysis of emulsified lesions in tissue induced by high intensity focused ultrasound," J. Acoust. Soc. Am., 129, 2477, doi:10.1121/1.3588148, 2011.

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1 Apr 2011

As recently shown, shock wave heating and millisecond boiling can be used to obtain mechanical emulsification of tissue with or without evident thermal damage, which can be controlled by varying the parameters of the high intensity focused ultrasound exposure. The goal of this work was to examine these bioeffects using histological and biochemical analysis. Lesions were created in ex vivo bovine heart and liver using a 2-MHz transducer and pulsing scheme with 71 MPa in situ shock amplitude, 0.01 duty factor, and 5-500 ms pulse duration. Mechanical tissue damage and viability of cells in the lesions were evaluated histologically using conventional staining techniques (H&E and NADH-diaphorase). Thermal effects were quantified by measuring denaturation of salt soluble proteins in the treated area and confirmed by histology. By visual observation, the liquefied lesions obtained with shorter pulses (< 15 ms) did not show any thermal damage that correlated well with the results of both histology and protein analysis. Increasing the pulse duration resulted in an increase in thermal damage; both protein analysis and NADH-diaphorase staining showed denaturation that was visually observed as whitening of the lesion content.

Holographic reconstruction of therapeutic ultrasound sources

Kreider, W., O.A. Sapozhnikov, M.R. Bailey, P.J. Kaczkowski, and V.A. Khokhlova, "Holographic reconstruction of therapeutic ultrasound sources," J. Acoust. Soc. Am. Vol. 129, 2403, doi: 10.1121/1.3587826, 2011.

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1 Apr 2011

Clinical therapeutic ultrasound systems rely on the delivery of known acoustic pressures to treatment sites. Assessing the safety and efficacy of these systems relies upon characterization of ultrasound sources in order to determine the acoustic fields they produce and to understand performance changes over time. While direct hydrophone measurements of intense acoustic fields are possible, data acquisition throughout a treatment volume can be time-consuming and is only applicable to the specific source conditions tested. Moreover, measuring intense acoustic fields poses challenges for the hydrophone. An alternate approach combines low-amplitude pressure measurements with modeling of the nonlinear pressure field at various transducer power levels. In this work, low-intensity measurements were acquired for several therapeutic transducers. Pressure amplitude and phase were measured on a plane near the test transducer; the Rayleigh integral was used to back-propagate the acoustic field and mathematically reconstruct relative vibrations of the transducer surface. Such holographic reconstructions identified the vibratory characteristics of different types of transducers, including a 256-element clinical array. These reconstructions can be used to define boundary conditions for modeling and to record characteristics of transducer performance.

In vivo tissue emulsification using millisecond boiling induced by high intensity focused ultrasound

Khokhlova, T.D., J.C. Simon, Y.-N. Wang, V.A. Khokhlova, M. Paun, F.L. Starr, P.J. Kaczkowski, L.A. Crum, J.H. Hwang, and M.R. Bailey, "In vivo tissue emulsification using millisecond boiling induced by high intensity focused ultrasound," J. Acoust. Soc. Am., 129, 2477, doi:10.1121/1.3588149, 2011.

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1 Apr 2011

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

Interrogating and imaging renal stones using vibro-acoustography

Illian, P.R., D. Gross, W. Lu, N.R. Owen, M.R. Bailey, and P.D. Mourad, "Interrogating and imaging renal stones using vibro-acoustography," J. Acoust. Soc. Am., 129, 2376, doi:10.1121/1.3587697, 2011.

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1 Apr 2011

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

Investigation of the effect of signal amplitude on twinkling artifact

Lu, W., B.W. Cunitz, O.A. Sapozhnikov, P.J. Kaczkowski, J.C. Kucewicz, N.R. Owen, M.R. Bailey, and L.A. Crum, "Investigation of the effect of signal amplitude on twinkling artifact," J. Acoust. Soc. Am., 129, 2376, doi: 10.1121/1.3587698, 2011.

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1 Apr 2011

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

Miniature acoustic fountain mechanism for tissue emulsification during millisecond boiling in high intensity focused ultrasound fields

Simon, J.C., O.A. Sapozhnikov, V.A. Khokhlova, T.D. Khokhlova, M.R. Bailey, and L.A. Crum, "Miniature acoustic fountain mechanism for tissue emulsification during millisecond boiling in high intensity focused ultrasound fields," J. Acoust. Soc. Am., 129, 2478, doi:10.1121/1.3588151, 2011.

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1 Apr 2011

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

Modeling of radiation force imparted to an elastic sphere from an ultrasound beam of arbitrary structure

Sapozhnikov, O.A. and M.R. Bailey, "Modeling of radiation force imparted to an elastic sphere from an ultrasound beam of arbitrary structure," J. Acoust. Soc. Am., 129, 2377, doi:10.1121/1.3587700, 2011.

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1 Apr 2011

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

Polyvinylidene flouride membrane hydrophone low-frequency response to medical shockwaves

Bailey, M.R., A.D. Maxwell, Y.A. Pishchalnikov, and O.A. Sapozhnikov, "Polyvinylidene flouride membrane hydrophone low-frequency response to medical shockwaves," J. Acoust. Soc. Am., 129, 2677, doi: 10.1121/1.3588971, 2011.

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1 Apr 2011

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

Prototype for expulsion of kidney stones with focused ultrasound

Shah, A., J.D. Harper, B.W. Cunitz, J.C. Kucewicz, Y.N. Wang, J.C. Simon, W. Lu, P.J. Kaczkowski, and M.R. Bailey, "Prototype for expulsion of kidney stones with focused ultrasound," J. Acoust. Soc. Am., 129, 2376, doi:10.1121/1.3587694, 2011.

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1 Apr 2011

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

Real-time tracking of renal calculi displaced by the radiation force of focused ultrasound

Illian, P.R., Jr., B.W. Cunitz, J.C. Kucewicz, M.R. Bailey, and P.J. Kaczkowski, "Real-time tracking of renal calculi displaced by the radiation force of focused ultrasound," J. Acoust. Soc. Am., 129, 2377, doi:10.1121/1.3587701, 2011.

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1 Apr 2011

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

Ultrasonic atomization on the tissue-bubble interface as a possible mechanism of tissue erosion in histotripsy

Sapozhnikov, O.A., V.A. Khokhlova, and M.R. Bailey, "Ultrasonic atomization on the tissue-bubble interface as a possible mechanism of tissue erosion in histotripsy," J. Acoust. Soc. Am., 129, 2478, doi:10.1121/1.3588152, 2011.

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1 Apr 2011

When an intense ultrasound beam is directed at a free surface of a liquid, an acoustic fountain is produced that is typically accompanied by ejection of tiny droplets, i.e., liquid atomization. This phenomenon is usually attributed to instability of cavitation-produced capillary waves on the surface. In addition to capillary effects, a process called spallation may also contribute. Although the acoustic fountain is typically observed at a flat liquid surface, nothing prohibits the atomization from occurring at a curved surface. This brings about the possibility to create an acoustic fountain and droplet emission at the surface of a gas cavity in liquid or, similarly, in the bulk of soft biological tissue. The appropriate condition occurs when high-intensity ultrasound is focused in tissue and creates large (0.1 - 1 mm in diameter) bubbles due to acoustic cavitation or rapid boiling. To test this hypothesis, acoustic pressure distribution and the corresponding radiation force on the empty spherical cavity were calculated using finite difference modeling and spherical harmonic expansion. It is shown that in histotripsy regimes appropriate conditions appear for the atomization, which may be considered as a possible mechanism of tissue erosion.

Blood vessel deformations on microsecond time scales by ultrasonic cavitation

Chen, H., W. Kreider, A.A. Brayman, M.R. Bailey, and T.J. Matula, "Blood vessel deformations on microsecond time scales by ultrasonic cavitation," Phys. Rev. Lett., 106, 034301, doi:10.1103/PhysRevLett.106.034301, 2011.

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18 Jan 2011

Transient interactions among ultrasound, microbubbles, and microvessels were studied using high-speed photomicrography. We observed liquid jets, vessel distention (motion outward against the surrounding tissue), and vessel invagination (motion inward toward the lumen). Contrary to current paradigms, liquid jets were directed away from the nearest vessel wall and invagination exceeded distention. These observations provide insight into the mechanics of bubble-vessel interactions, which appear to depend qualitatively upon the mechanical properties of biological tissues.

Novel ultrasound method to reposition kidney stones

Shah, A., N. Owen, W. Lu, B. Cunitz, P. Kaczkowski, J. Harper, M. Bailey, and L. Crum, "Novel ultrasound method to reposition kidney stones," Urol. Res., 38, 491-495, doi:10.1007/s00240-010-0319-9, 2010.

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1 Dec 2010

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

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

Blood vessel rupture by cavitation

Chen, H., A.A. Brayman, M.R. Bailey, and T.J. Matula, "Blood vessel rupture by cavitation," Urol. Res., 38, 321-326, doi:10.1007/s00240-010-0302-5, 2010.

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2 Aug 2010

Cavitation is thought to be one mechanism for vessel rupture during shock wave lithotripsy treatment. However, just how cavitation induces vessel rupture remains unknown. In this work, a high-speed photomicrography system was set up to directly observe the dynamics of bubbles inside blood vessels in ex vivo rat mesenteries. Vascular rupture correlating to observed bubble dynamics were examined by imaging bubble extravasation and dye leakage. The high-speed images show that bubble expansion can cause vessel distention, and bubble collapse can lead to vessel invagination. Liquid jets were also observed to form. Our results suggest that all three mechanisms, vessel distention, invagination and liquid jets, can contribute to vessel rupture.

Ureteroscopic ultrasound technology to size kidney stone fragments: Proof of principle using a miniaturized probe in a porcine model

Sorensen M.D., A.R. Shah, M.S. Canney, O.A. Sapozhnikov, J.M. Teichman, and M.R. Bailey, "Ureteroscopic ultrasound technology to size kidney stone fragments: Proof of principle using a miniaturized probe in a porcine model," J. Endourol., 24, 939-942, 2010.

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1 Jun 2010

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

Bandwidth limitations in characterizing of high intensity focused ultrasound fields in the presence of shocks

Khokhlova, V.A., O.V. Bessonova, J.E. Soneson, M.S. Canney, M.R. Bailey, and L.A. Crum, "Bandwidth limitations in characterizing of high intensity focused ultrasound fields in the presence of shocks," In Proceedings, Ninth International Symposium on Therapeutic Ultrasound, Aix-en-Provence, 24-26 September 2009, K. Hynynen and J. Souquet, eds., 363-366 (AIP, 2010).

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9 Mar 2010

Nonlinear propagation effects result in the formation of weak shocks in high intensity focused ultrasound (HIFU) fields. When shocks are present, the wave spectrum consists of hundreds of harmonics. In practice, shock waves are modeled using a finite number of harmonics and measured with hydrophones that have limited bandwidths.

The goal of this work was to determine how many harmonics are necessary to model or measure peak pressures, intensity, and heat deposition rates of the HIFU fields. Numerical solutions of the Khokhlov-Zabolotskaya-Kuznetzov-type (KZK) nonlinear parabolic equation were obtained using two independent algorithms, compared, and analyzed for nonlinear propagation in water, in gel phantom, and in tissue. Measurements were performed in the focus of the HIFU field in the same media using fiber optic probe hydrophones of various bandwidths. Experimental data were compared to the simulation results.

Potential temperature limitations of bubble-enhanced heating during HIFU

Kreider, W., M.R. Bailey, O.A Sapozhnikov, and L.A. Crum, "Potential temperature limitations of bubble-enhanced heating during HIFU," In Proceedings, Ninth International Symposium on Therapeutic Ultrasound, Aix-en-Provence, 24-26 September 2009, K. Hynynen and J. Souquet, eds., 367-370 (AIP, 2010).

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9 Mar 2010

During high-intensity focused ultrasound (HIFU) treatments in the absence of bubbles, tissue is heated by absorption of the incident ultrasound. However, bubbles present at the focus can enhance the rate of heating. One mechanism for such enhanced heating involves inertial bubble collapses that transduce incident ultrasound to higher frequencies that are more readily absorbed. Previously, it has been reported that bubble-enhanced heating diminishes as treatments progress.

The objective of this effort is to quantify how inertial bubble collapses are affected as the focal temperature rises during treatment. A model of a single, spherical bubble has been developed to couple the thermodynamic state of a strongly driven spherical bubble with the temperature of the surrounding liquid. This model allows for the dynamic transport of heat, vapor, and non-condensable gases to/from the bubble and has been demonstrated to fit experimental data from the collapses and rebounds of millimeter-sized bubbles over a range of temperature conditions. The responses of micron-sized, air-vapor bubbles in water were simulated under exposure to MHz/MPa HIFU excitation at various surrounding liquid temperatures. Each bubble response was characterized by the power spectral density of its radiated pressure in order to emulate a hydrophone measurement. Simulations suggest that bubble collapses are significantly attenuated at temperatures above about 70 deg C. For instance, the acoustically radiated energy at 80 deg C is an order of magnitude less than that at 20 deg C. Simulations that fully include the effect of vapor on bubbles excited during HIFU suggest that the efficacy of bubble-enhanced heating may be limited to temperatures below 70 deg C.

Tissue erosion using shock wave heating and millisecond boiling in HIFU fields

Canney, M.S., T.D. Khokhlova, V.A. Khokhlova, M.R. Bailey, J.H. Hwang, and L.A. Crum, "Tissue erosion using shock wave heating and millisecond boiling in HIFU fields," In Proceedings, Ninth International Symposium on Therapeutic Ultrasound, Aix-en-Provence, 24-26 September 2009, K. Hynynen and J. Souquet, eds., 36-39 (AIP, 2010).

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9 Mar 2010

A wide variety of treatment protocols have been employed in high intensity focused ultrasound (HIFU) treatments, and the resulting bioeffects observed include both mechanical as well as thermal effects. In recent studies, there has been significant interest in generating purely mechanical damage using protocols with short, microsecond pulses. Tissue erosion effects have been attained by operating HIFU sources using short pulses of 10–20 cycles, low duty cycles (<1%), and pulse average intensities of greater than 20 kW/cm2.

The goal of this work was to use a modified pulsing protocol, consisting of longer, millisecond-long pulses of ultrasound and to demonstrate that heating and rapid millisecond boiling from shock wave formation can be harnessed to induce controlled mechanical destruction of soft tissue. Experiments were performed in excised bovine liver and heart tissue using a 2-MHz transducer. Boiling activity was monitored during exposures using a high voltage probe in parallel with the HIFU source. In situ acoustic fields and heating rates were determined for exposures using a novel derating approach for nonlinear HIFU fields. Several different exposure protocols were used and included varying the duty cycle, pulse length, and power to the source. After exposures, the tissue was sectioned, and the gross lesion morphology was observed. Different types of lesions were induced in experiments that ranged from purely thermal to purely mechanical depending on the pulsing protocol used. Therefore, shock wave heating and millisecond boiling may be an effective method for reliably generating significant tissue erosion effects.

Tissue erosion using millisecond boiling in high-intensity focused ultrasound fields

Canney, M.S., T.D. Khokhlova, Y.N. Wang, V.A. Khokhlova, M.R. Bailey, and L.A. Crum, "Tissue erosion using millisecond boiling in high-intensity focused ultrasound fields," J. Acoust. Soc. Am., 127, 1760, doi:10.1121/1.3383729, 2010.

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1 Mar 2010

High-intensity focused ultrasound (HIFU) transducers can be operated at high-pressure amplitudes of greater than 60 MPa and low-duty cycles of 1% or less to induce controlled bubble activity that fractionates tissue. The goal of this work was to investigate fractionation not from mechanically induced cavitation but from thermally induced boiling created by HIFU shock waves. Experiments were performed using a 2-MHz HIFU source. The focus was placed in ex vivo bovine heart and liver samples. Cavitation and boiling were monitored during exposures using a high-voltage probe in parallel with the HIFU source and with an ultrasound imaging system. Various exposure protocols were performed in which the time-averaged intensity and total energy delivered were maintained constant. The types of lesions induced in tissue ranged from purely thermal to purely mechanical depending on the pulsing protocol used. A pulsing protocol in which the pulse length was on the order of the time to boil (of only several milliseconds) and duty cycle was low (<1%) was found to be a highly repeatable method for inducing mechanical effects with little evidence of thermal damage, as confirmed by histology.

Shock-induced heating and millisecond boiling in gels and tissue due to high intensity focused ultrasound

Canney, M.S., V.A. Khokhlova, O.V. Bessonova, M.R. Bailey, and L.A. Crum, "Shock-induced heating and millisecond boiling in gels and tissue due to high intensity focused ultrasound," Ultrasound Med Biol., 36, 250-267, 2010.

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1 Feb 2010

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/cm2 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.

A derating method for therapeutic applications of high intensity focused ultrasound

Bessonova, O.V., V.A. Khokhlova, M.S. Canney, M.R. Bailey, and L.A. Crum, "A derating method for therapeutic applications of high intensity focused ultrasound," Acoust. Phys., 56, 354-363, 2010.

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1 Jan 2010

Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. In this work, a new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those simulated for propagation in water. Focal waveforms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue.

Therapeutic ultrasound: Recent trends and future perspectives

Crum, L., M. Bailey, J.H. Wang, V. Khokhlova, and O. Sapozhnikov, "Therapeutic ultrasound: Recent trends and future perspectives," In Physics Procedia, vol. 3 - International Congress on Ultrasonics, Santiago Chile, January 2009, Luis Gaete Garreton, ed., 25-34 (Elsevier, 2010).

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1 Jan 2010

Before ultrasound-imaging systems became widely available, ultrasound therapy devices showed great promise for general use in medicine. However, it is only in the last decade that ultrasound therapy has begun to obtain clinical acceptance. Recently, a variety of novel applications of therapeutic ultrasound have been developed that include sonothrombolysis, site-specific and ultrasound-mediated drug delivery, shock wave therapy, lithotripsy, tumor ablation, acoustic hemostasis and several others. This paper reviews a few selected applications of therapeutic ultrasound. It will address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. As a plenary presentation, its audience is intended for the ultrasound scientist or engineer, and thus is not presented at the level of the experienced medical ultrasound professional.

Ultra fast thermal effect of high intensity focused ultrasound (HIFU) and localized boiling in tissue due to exposure of shock waves

Khokhlova, V.A., M.S. Canney, M.R. Bailey, and L.A. Crum, "Ultra fast thermal effect of high intensity focused ultrasound (HIFU) and localized boiling in tissue due to exposure of shock waves," In Physics Procedia, vol. 3 - International Congress on Ultrasonics, Santiago, Chile, January 2009, Luis Gaete Garreton, ed. (Elsevier, 2010).

1 Jan 2010

Radiation pressure from ultrasound to help kidney stones pass

Lu, W., A. Shah, B.W. Cunitz, P.J. Kaczkowski, O.A. Sapozhnikov, and M.R. Bailey, "Radiation pressure from ultrasound to help kidney stones pass," J. Acoust. Soc. Am., 126, 2213, doi:10.1121/1.3248749, 2009.

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1 Oct 2009

Residual kidney stone fragments often remain months after treatment. These fragments may nucleate new stones and contribute to a 50% recurrence within 5 years. Here, a research focused ultrasound device was used to generate fragment motion with the goal of facilitating passage. Natural and artificial stones 1–8 mm in length were surgically placed in the urine space in pig kidneys. The ultrasound source was a 2.75-MHz, eight-element annular array with a 6-cm radius of curvature. At adjustable focal depths of 5–8 cm, the focal pressure beam width in water was about 2 mm, and peak pressure was about 4 MPa. Targeting was done by ultrasound using B-mode and twinkling artifact that stones produce in Doppler mode. The commercial imaging probe was placed within and oriented down the axis of the therapy probe. Ultrasound and fluoroscopy showed the stones moving in real-time under the influence of the focused ultrasound. Stones moved on the order of 1 cm/s away from the source and several stones moved several centimeters down the ureter. It appeared that stones were affected only when directly in the focal beam, perhaps indicating that radiation pressure not streaming caused the motion.

Toward a better understanding of high intensity focused ultrasound therapy using the Khokhlov-Zabolotskaya-Kuznetsov equation

Crum, L.A., M.S. Canney, M.R. Bailey, O.V. Bessonova, and V.A. Khokhlova, "Toward a better understanding of high intensity focused ultrasound therapy using the Khokhlov-Zabolotskaya-Kuznetsov equation," J. Acoust. Soc. Am., 126, 2201, 2009.

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1 Oct 2009

High intensity focused ultrasound (HIFU) therapy is an emerging medical technology in which acoustic pressure amplitudes of up to 100 MPa are used to induce tissue ablation, often in combination with real-time imaging. The ultrasound energy is typically focused into a millimeter-size volume and used to thermally coagulate the tissue of interest while ideally sparing surrounding tissue. Nonlinear effects are important in HIFU as in situ intensities for clinical applications of up to 30 000 W/cm2 have been reported. Since controlled experiments are often difficult to perform, especially in vivo, modeling can aid in understanding the physical phenomena involved in HIFU-induced tissue ablation. The Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation is applicable to HIFU because it includes all of the basic physical phenomena that are relevant to HIFU including acoustic beams, diffraction, focusing, nonlinear propagation, shock formation, and dissipation. In this paper, an overview of several recent advances in KZK modeling for HIFU applications are described. It is shown that shock-induced heating in tissue can cause localized boiling in milliseconds; furthermore, the bubbles associated with boiling can significantly alter HIFU treatments.

Nonlinear derating method for high intensity focused ultrasound (HIFU) fields

Bessonova, O.V., V.A. Khokhlova, M.S. Canney, M.R. Bailey, and L.A. Crum, "Nonlinear derating method for high intensity focused ultrasound (HIFU) fields," In Proceedings, IEEE International Ultrasonics Symposium, Rome, Italy, 20-23 September, 216-219, doi:10.1109/ULTSYM.2009.5441494 (IEEE, 2009).

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20 Sep 2009

In this work, a new derating method to extrapolate nonlinear ultrasound fields in water to biological tissue is proposed and tested for therapeutic medical systems. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those derated, using the proposed method, from the results of simulations in water. It is validated in modeling that for high gain sources, which are typically used for therapeutic medical applications, the focal field parameters in tissue can be obtained from the results obtained in water. The feasibility of the derating method is also demonstrated experimentally in water and excised bovine liver tissue using a 2 MHz HIFU source of 44 mm aperture and focal length.

Observations of bubble-vessel interaction in ultrasound fields

Chen, H., J. Kucewicz, W. Kreider, A. Brayman, M. Bailey, and T. Matula, "Observations of bubble-vessel interaction in ultrasound fields," Proceedings, IEEE International Ultrasonics Symposium, Rome, Italy, 20-23 September, 23-26, doi:10.1109/ULTSYM.2009.5441512 (IEEE, 2009).

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20 Sep 2009

Interactions between bubbles and nearby boundaries have been studied for some time; however, the direct interactions between bubbles and tissue boundaries, especially blood vessel walls, have not been studied to a large extent. In this work highspeed microscopy was used to study the dynamical interaction between microbubbles and microvessels of ex vivo rat mesentery subjected to a single pulse of ultrasound. Ultrasound contrast agent microbubbles were injected into the blood vessels of rat mesentery subsequent to having the blood flushed out. India ink was used to increase the contrast between microvessels and surrounding tissues. Tissue samples were aligned at the focus of both an ultrasound transducer with a center frequency of 1 MHz and an inverted microscope coupled to a high speed camera. Fourteen high-speed microphotographic images were acquired for each experiment using 50 ns shutter speeds. Observations of the coupled dynamics between bubbles and vessels ranging from 10 micrometer to 100 micrometer diameters under the exposure of ultrasound of peak negative pressure within the range of 1 MPa to 7.8 MPa suggest that the vessel wall dilates during bubble expansion, and invaginates during bubble contraction. A significant finding is that the ratio of invagination to distension is usually >1 and large circumferential strains can be imposed on the vessel wall during vessel invagination. In addition, the surrounding tissue response was also quantified. Based on these studies, we hypothesize that vessel invagination is the dominant mechanism for the initial induction of vascular damage via cavitation.

Potential mechanisms for vessel invagination caused by bubble oscillations

Kreider, W., H. Chen, M.R. Bailey, A.A. Brayman, and T.J. Matula, "Potential mechanisms for vessel invagination caused by bubble oscillations," In Proceedings, IEEE International Ultrasonics Symposium, Rome, Italy, 20-23 September, 353-356, doi:10.1109/ULTSYM.2009.5441744 (IEEE, 2009).

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20 Sep 2009

In medical ultrasound, acoustically excited bubbles are relevant to both imaging and therapeutic applications and have been implicated in causing vascular damage. A current paradigm for understanding interactions between bubbles and vessels considers the distention of small vessels and the impingement of bubble jets on vessel walls to be the most likely damage mechanisms. However, recent high-speed photographs suggest a type of interaction that is characterized by a prominent invagination of the vessel wall (i.e., an inward deflection toward the lumen) that appears to exceed any accompanying distention.

To elucidate mechanisms for such behavior, a confined flow geometry between an oscillating bubble and a nearby boundary is modeled and compared to fully spherical flow. From a Bernoulli-type equation for an incompressible and inviscid liquid, the pressure attributable to a bubble at a nearby boundary is found to become biased toward negative values as the flow becomes more confined and less spherical. Such negative values are consistent with invagination. Using radial bubble dynamics inferred from a high-speed photographic sequence of a bubble in a vessel, the aforementioned model was used to simulate the pressure radiated by the bubble at the vessel wall. At the 1 MHz acoustic frequency, the simulated negative pressure is 2.5 times the positive pressure; in turn, the observed vessel displacement inward was about 6 times the corresponding outward displacement.

The role of compressional pressure in the formation of dense bubble clouds in histotripsy

Maxwell, A.D., T.-Y. Wang, C.C. Cain, J.B. Fowlkes, Z. Xu, O.A. Sapozhnikov, and M.R. Bailey, "The role of compressional pressure in the formation of dense bubble clouds in histotripsy," In Proceedings, International Ultrasonics Symposium, Rome, 20-23 September, 81-84, doi:10.1109/ULTSYM.2009.5441398 (IEEE, 2009).

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20 Sep 2009

Histotripsy is a non-invasive ultrasound therapy which utilizes cavitation clouds to mechanically fractionate tissue. The mechanism by which bubble clouds form is important to understand the histotripsy process. We used high speed imaging with frame rates between 0.1-10 million fps to observe the progression of cloud formation. A 1 MHz spherically-focused transducer was used to apply single histotripsy pulses to optically-transparent gelatin tissue phantoms, with peak negative pressure of 19 MPa and 5-50 cycles. Dense bubble clouds were observed to first form at a distal position within the focus, and grow proximally towards the transducer, opposite the ultrasound propagation direction. Growth began from the site of single cavitation bubbles. Based on these observations, it was hypothesized that the shocked waveforms from histotripsy pulses scatter from single bubbles, which invert the shock and induce a large negative pressure in its vicinity. To test this hypothesis, the positive incident shock pressure was reduced without significantly affecting the negative pressure. When the peak positive pressure was lowered, the likelihood and size of bubble clouds initiating at the focus was greatly reduced. These results suggest that the positive pressure of the incident waveform is important for generating bubble clouds in histotripsy.

A proof of principle of a prototype ultrasound technology to size stone fragments during ureteroscopy

Sorensen, M.D., J.M.H. Teichman, and M.R. Bailey, "A proof of principle of a prototype ultrasound technology to size stone fragments during ureteroscopy," J. Endourol., 23, 1161-1164, 2009.

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1 Jul 2009

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

Pretreatment with low-energy shock waves induces renal vasoconstriction during standard SWL: A treatment protocol known to reduce lithotripsy-induced renal injury

Handa, R.K., M.R. Bailey, M. Paun, S. Gao, B.A. Connors, L.R. Willis, and A.P. Evan, "Pretreatment with low-energy shock waves induces renal vasoconstriction during standard SWL: A treatment protocol known to reduce lithotripsy-induced renal injury," Brit. J. Urol. Int., 103, doi:10.1111/j.1464-410X.2008.08277.x, 1270-1274, 2009.

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1 May 2009

The pretreatment protocol induces renal vasoconstriction during the period of SW application whereas the standard protocol shows vasoconstriction occurring after SWL. Thus, the earlier and greater rise in RI during the pretreatment protocol may be causally associated with a reduction in tissue injury.

A Schlieren system for optical visualization of ultrasonic fields

Kaczkowski, P.J., M.R. Bailey, V.A. Khokhlova, and O.A. Sapozhnikov, "A Schlieren system for optical visualization of ultrasonic fields," J. Acoust. Soc. Am., 125, 2742, 2009.

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1 Apr 2009

Ultrasonic field mapping is an essential component of transducer characterization and of beam forming verification. Such measurements are commonly performed by displacing a hydrophone over a range of points within the field; these procedures can be time consuming. A calibrated hydrophone can provide accurate measurements of the field, subject to limitations of bandwidth and aperture of the device. A rapid qualitative 2D measurement of the spatial acoustic field can be obtained by optical means, in which the change in optical index due to the presence of acoustic pressure is imaged using a Schlieren approach.

This technique illuminates a transparent refracting acoustic medium using a plane collimated source and then focuses the transmitted light using a lens or mirror. In the absence of acoustic field, all of the light focuses to a small spot; acoustically induced refractive index perturbations cause some of the light to focus elsewhere. Obscuring the primary focal spot of unperturbed light with a mask permits imaging only the perturbations in the acoustic medium. We will describe a mirror-based Schlieren system for imaging continuous as well as pulsed fields and with color corresponding qualitatively to the intensity of the field.

Direct observation of microbubble interactions with ex vivo microvessels

Chen, H., A.A. Brayman, M.R. Bailey, and T.J. Matula, "Direct observation of microbubble interactions with ex vivo microvessels," J. Acoust. Soc. Am., 125, 2680, 2009.

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1 Apr 2009

The interaction between microbubbles with tissue is poorly understood. Experimental evidence, supported by numerical simulations, suggests that bubble dynamics is highly constrained within blood vessels. To investigate this further, a high-speed microimaging system was set up to study the effects of acoustically activated microbubbles on microvessels in ex vivo rat mesentery tissues. The microbubble-perfused tissues were placed under a microscope and insonified with MHz ultrasound. A variety of interactions was observed by a high-speed camera: arterioles, venules, and capillaries were all recorded to dilate and invaginate by activated microbubbles.

For small diameter microvessels, dilation and invagination were nearly symmetric, and bubble-induced rupture of the vessel was observed at high pressure. For larger microvessels, the portion of the vessel nearest the bubble coupled the strongest to the bubble dynamics, and the extent of dilation was smaller than invagination. Tissue jetting toward the bubble was recorded in many cases. The interaction of multiple bubbles inside microvessels was also observed. Bubble oscillation, vessel wall velocity, and tissue jet velocity were quantitatively measured. Invagination of vessel walls, especially tissue jetting, may be the major mechanism for tissue injury by a bubble.

Focused ultrasound: Concept for automated transcutaneous control of hemorrhage in austere settings

Kucewicz, J.C., M.R. Bailey, P.J. Kaczkowski, and S.J. Carter, "Focused ultrasound: Concept for automated transcutaneous control of hemorrhage in austere settings," Aviat. Space Environ. Med., 80, 391-394, 2009.

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1 Apr 2009

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.

Impact of temperature on bubbles excited by high intensity focused ultrasound

Kreider, W., M.R. Bailey, O.A. Sapozhnikov, and L.A. Crum, "Impact of temperature on bubbles excited by high intensity focused ultrasound," J. Acoust. Soc. Am., 125, 2742, doi:10.1121/1.3050272, 2009.

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1 Apr 2009

Bubble-enhanced heating is a current topic of interest associated with high intensity focused ultrasound (HIFU). For HIFU treatments designed to utilize acoustic radiation from bubbles as a heating mechanism, it has been reported that useful bubble activity diminishes at elevated temperatures. To better understand and quantify this behavior, a model has been implemented that couples the thermodynamic state of a strongly driven spherical bubble with thermal conditions in the surrounding liquid. This model has been validated over a range of temperature conditions against experimental data from the collapses and rebounds of millimeter-sized bubbles.

With this model, the response of a micron-sized bubble was simulated under exposure to MHz/MPa HIFU excitation, while various surrounding liquid temperatures were considered. Characterizing the bubble response through the power spectral density of pressure radiated from the bubble, model calculations suggest that bubble collapses are significantly attenuated at temperatures above about 70°C. For instance, the acoustically radiated energy at 80°C is an order of magnitude less than that at 20°C. These results suggest that the efficacy of bubble-enhanced heating may be limited to temperatures below 70°C. Moreover, temperature will affect hydrophone measurements used to passively assess cavitation activity.

Improved impulse response for hydrophone measurements in therapeutic ultrasound fields

Canney, M.S., V.A. Khokhlova, O.A. Sapozhnikov, Y.A. Pishchalnikov, A.D. Maxwell, M.R. Bailey, and L.A. Crum, "Improved impulse response for hydrophone measurements in therapeutic ultrasound fields," J. Acoust. Soc. Am., 125, 2740, 2009.

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1 Apr 2009

The accurate measurement of pressure waveforms in high intensity focused ultrasound (HIFU) fields is complicated by the fact that many devices operate at output levels where shock waves can form in the focal region. In tissue ablation applications, the accurate measurement of the shock amplitude is important for predicting tissue heating since the absorption at the shock is proportional to the shock amplitude cubed. To accurately measure shocked pressure waveforms, not only must a hydrophone with a broad bandwidth (>100 MHz) be used, but the frequency response of the hydrophone must be known and used to correct the measured waveform.

In this work, shocked pressure waveforms were measured using a fiber optic hydrophone and a frequency response for the hydrophone was determined by comparing measurements with numerical modeling using a KZK-type equation. The impulse response was separately determined by comparing a measured and an idealized shock pulse generated by an electromagnetic lithotripter. The frequency responses determined by the two methods were in good agreement. Calculations of heating using measured HIFU waveforms that had been deconvolved with the determined frequency response agreed well with measurements in tissue phantom.

Investigation of an ultrasound imaging technique to target kidney stones in lithotripsy

Shah, A., M. Paun, J. Kucewicz, O.A. Sapozhnikov, M. Dighe, H.A. McKay, M.D. Sorensen, and M.R. Bailey, "Investigation of an ultrasound imaging technique to target kidney stones in lithotripsy," J. Acoust. Soc. Am., 125, 2620, 2009.

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1 Apr 2009

Localization of kidney stones and targeting for lithotripsy can be challenges especially with ultrasound. However, twinkling artifact has been observed where Doppler ultrasound imagers assign color to the stone. We report a preliminary investigation from our observations in a porcine model and hypothesize why this artifact occurs. Glass beads, cement stones, and human stones were surgically placed into the renal collecting system through the ureter. The stones were imaged using several transducers and ultrasound imagers. In all cases, the twinkling artifact of the stone was observed, and its appearance and radiofrequency signature were unique from those of blood flow. Calcium oxalate monohydrate stones and smooth stones were not more difficult to image, contrary to previous reports. Increasing gain or placing the focal depth distal to the stone enhanced the artifact, but other user controls showed little effect. Twinkling started at the lateral edges of the stone and spread over the stone as gain was increased. The evidence supports the hypothesis that small motions induced by radiation force or elastic waves in the stone cause changes in received backscatter, particularly at imaging angles oblique to the stone surface.

Magnetic resonance imaging of boiling induced by high intensity focused ultrasound

Khokhlova, T.D., M.S. Canney, D. Lee, K.I. Marro, L.A. Crum, V.A. Khokhlova, and M.R. Bailey, "Magnetic resonance imaging of boiling induced by high intensity focused ultrasound," J. Acoust. Soc. Am., 125, 2420-2431, 2009.

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1 Apr 2009

Both mechanically induced acoustic cavitation and thermally induced boiling can occur during high intensity focused ultrasound (HIFU) medical therapy. The goal was to monitor the temperature as boiling was approached using magnetic resonance imaging (MRI). Tissue phantoms were heated for 20 s in a 4.7-T magnet using a 2-MHz HIFU source with an aperture and radius of curvature of 44 mm. The peak focal pressure was 27.5 MPa with corresponding beam width of 0.5 mm. The temperature measured in a single MRI voxel by water proton resonance frequency shift attained a maximum value of only 73 degrees C after 7 s of continuous HIFU exposure when boiling started. Boiling was detected by visual observation, by appearance on the MR images, and by a marked change in the HIFU source power. Nonlinear modeling of the acoustic field combined with a heat transfer equation predicted 100 degrees C after 7 s of exposure. Averaging of the calculated temperature field over the volume of the MRI voxel (0.3 x 0.5 x 2 mm(3)) yielded a maximum of 73 degrees C that agreed with the MR thermometry measurement. These results have implications for the use of MRI-determined temperature values to guide treatments with clinical HIFU systems.

Modeling weak shocks produced by high-intensity focused ultrasound

Khokhlova, V.A., O.V. Bessonova, M.S. Canney, M.R. Bailey, J.E. Soneson, and L.A. Crum, "Modeling weak shocks produced by high-intensity focused ultrasound," J. Acoust. Soc. Am., 125, 2600, 2009.

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1 Apr 2009

Both mechanically induced acoustic cavitation and thermally induced boiling can occur during high intensity focused ultrasound (HIFU) medical therapy. The goal was to monitor the temperature as boiling was approached using magnetic resonance imaging (MRI). Tissue phantoms were heated for 20 s in a 4.7-T magnet using a 2-MHz HIFU source with an aperture and radius of curvature of 44 mm. The peak focal pressure was 27.5 MPa with corresponding beam width of 0.5 mm.

The temperature measured in a single MRI voxel by water proton resonance frequency shift attained a maximum value of only 73 degrees C after 7 s of continuous HIFU exposure when boiling started. Boiling was detected by visual observation, by appearance on the MR images, and by a marked change in the HIFU source power. Nonlinear modeling of the acoustic field combined with a heat transfer equation predicted 100 degrees C after 7 s of exposure. Averaging of the calculated temperature field over the volume of the MRI voxel (0.3 x 0.5 x 2 mm(3)) yielded a maximum of 73 degrees C that agreed with the MR thermometry measurement. These results have implications for the use of MRI-determined temperature values to guide treatments with clinical HIFU systems.

Ureteroscopic ultrasound technology to size kidney stone fragments: Proof of principle using a miniaturized probe in a porcine model

Sorensen, M.D., A. Shah, M.S. Canney, O.A. Sapozhnikov, J.M.H. Teichman, and M.R. Bailey, "Ureteroscopic ultrasound technology to size kidney stone fragments: Proof of principle using a miniaturized probe in a porcine model," J. Acoust. Soc. Am., 125, 2622, 2009.

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1 Apr 2009

Background: the ability to measure stone fragment size could help prevent attempting to extract too large a stone fragment. We evaluated the ability of a 1.2 mm (3.6 French) ultrasound probe to measure stone fragments in a porcine kidney.

Methods: 15 human stones of three types (five each calcium oxalate, cystine, calcium phosphate) sized 3–7 mm were placed deep in a porcine kidney collecting system. The sound speed of each stone type was determined using a separate reference stone. A 2 MHz, 1.2 mm needle hydrophone was used to send and receive ultrasound pulses. Stone thickness was calculated as d=c*t/2 by determining the signal transit time through the stone and the stone sound speed. Calculated stone thicknesses were compared to digital caliper measurements.

Results: Stone size was determined for all 15 stones. Correlation between ultrasound-determined thickness and caliper measurements was excellent (r2=0.90, p<0.0001) with ultrasound performing well in all three stone types. All stone measurements were accurate within 1 mm, and ten (66%) stone measurements were accurate within 0.5 mm.

Conclusions: Ultrasound-based measurements are accurate and precise using a 3.6 French probe with stone fragments placed deep in a porcine kidney.

Beamwidth measurement of individual lithotripter shock waves

Kreider, W., M.R. Bailey, and J.A. Ketterling, "Beamwidth measurement of individual lithotripter shock waves," J. Acoust. Soc. Am., 125, 1240-1245, 2009.

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1 Feb 2009

New lithotripters with narrower foci and higher peak pressures than the original Dornier HM3 electrohydraulic lithotripter have proven to be less effective and less safe. Hence, accurate measurements of the focal characteristics of lithotripter shock waves are important. The current technique for measuring beamwidth requires a collection of single-point measurements over multiple shock waves, thereby introducing error as a result of any shock-to-shock variability.

This work reports on the construction of a hydrophone array sensor and on array measurements of individual lithotripter shock waves. Beamwidths for an electrohydraulic lithotripter with a broad-focus HM3-style reflector and a narrow-focus modified reflector were measured using both new and worn electrodes as well as two different electrical charging potentials. The array measured the waveform, beamwidth, and focal location of individual shock waves. The HM3-style reflector produced repeatable focal waveforms and beam profiles at an 18 kV charging potential with new and worn electrodes. Corresponding measurements suggest a narrower beamwidth than reported previously from averaged point measurements acquired under the same conditions. In addition, a lack of consistency in the measured beam profiles at 23 kV underscores the value of measuring individual shock waves.

Effect of elastic waves in the metal reflector on bubble dynamics at the focus of an electrohydraulic lithotripter

Sapozhnikov, O.A., W. Kreider, and M.R. Bailey, "Effect of elastic waves in the metal reflector on bubble dynamics at the focus of an electrohydraulic lithotripter," Nelineinyi mir (Nonlinear World), 7, 575-580, 2009 (in Russian).

1 Jan 2009

Focusing of high intensity ultrasound beams and ultimate values of shock wave parameters

Bessonova, O.V., V.A. Khokhlova, M.R. Bailey, M.S. Canney, and L.A. Crum, "Focusing of high intensity ultrasound beams and ultimate values of shock wave parameters," Acoust. Phys., 55, 463-473, 2009.

1 Jan 2009

Acoustic characterization of high intensity focused ultrasound fields: A combined measurement and modeling approach

Canney, M.S., M.R. Bailey, L.A. Crum, V.A. Khokhlova, and O.A. Sapozhnikov, "Acoustic characterization of high intensity focused ultrasound fields: A combined measurement and modeling approach," J. Acoust. Soc. Am., 124, 2406-2420, doi:10.1121/1.2967836, 2008.

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30 Oct 2008

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 24000 W/cm2. 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/cm2, 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.

Ultrasonic measurement of condensate film thickness

Kimball, J.T., M.R. Bailey, and J.C. Hermanson, "Ultrasonic measurement of condensate film thickness," J. Acoust. Soc. Am. EL, 124, 196-201, 2008.

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22 Sep 2008

The current work describes a modified time-of-flight ultrasound signal processing technique applied to the study of a distal liquid layer with a free surface. The technique simulates multiple reflections analytically and determines the film thickness by comparison to the measured pulse echo signal. The technique is applied with 20-MHz transducers to an n-pentane film condensing on a copper plate. The technique proved capable of measuring liquid thickness from approximately 8 µm, 1/6 the acoustic wavelength in pentane, to greater than 5 mm. Near the lower thickness limit, echoes from the liquid/vapor interface overlap each other and the significantly larger echoes from the metal/liquid interface.

Bubble proliferation in shock wave lithotripsy occurs during inertial collapse nonlinear acoustics

Pishchalnikov, Y.A., J.A. McAteer, I.V. Pishchalnikova, J.C. Williams Jr., M.R. Bailey, and O.A. Sapozhnikov, "Bubble proliferation in shock wave lithotripsy occurs during inertial collapse nonlinear acoustics," Nonlinear Acoustics: Fundamentals and Applications, edited by B.O. Enflo, C.M. Hedberg, and L. Kari, 460-463 doi:10.1063/1.2956259 (Amer. Inst. Phys., 2008).

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24 Jun 2008

In shock wave lithotripsy (SWL), firing shock pulses at slow pulse repetition frequency (0.5 Hz) is more effective at breaking kidney stones than firing shock waves (SWs) at fast rate (2 Hz). Since at fast rate the number of cavitation bubbles increases, it appears that bubble proliferation reduces the efficiency of SWL. The goal of this work was to determine the basis for bubble proliferation when SWs are delivered at fast rate. Bubbles were studied using a high-speed camera (Imacon 200). Experiments were conducted in a test tank filled with nondegassed tap water at room temperature. Acoustic pulses were generated with an electromagnetic lithotripter (DoLi-0). In the focus of the lithotripter the pulses consisted of a ~ 60 MPa positive-pressure spike followed by up to ~8 MPa negative-pressure tail, all with a total duration of about 7 µs. Nonlinear propagation steepened the shock front of the pulses to become sufficiently thin ( ~ 0.03 µm) to impose differential pressure across even microscopic bubbles.

High-speed camera movies showed that the SWs forced preexisting microbubbles to collapse, jet, and break up into daughter bubbles, which then grew rapidly under the negative-pressure phase of the pulse, but later coalesced to re-form a single bubble. Subsequent bubble growth was followed by inertial collapse and, usually, rebound. Most, if not all, cavitation bubbles emitted micro-jets during their first inertial collapse and re-growth. After jetting, these rebounding bubbles could regain a spherical shape before undergoing a second inertial collapse. However, either upon this second inertial collapse, or sometimes upon the first inertial collapse, the rebounding bubble emerged from the collapse as a cloud of smaller bubbles rather than a single bubble. These daughter bubbles could continue to rebound and collapse for a few cycles, but did not coalesce. These observations show that the positive-pressure phase of SWs fragments preexisting bubbles but this initial fragmentation does not yield bubble proliferation, as the daughter bubbles coalesce to reform a single bubble. Instead, bubble proliferation is the product of the subsequent inertial collapses.

Effect of elastic waves in the metal reflector on bubble dynamics at the focus of an electrohydraulic lithotripter

Sapozhnikov, O.A., W. Kreider, M.R. Bailey, V.A. Khokhlova, and F. Curra, "Effect of elastic waves in the metal reflector on bubble dynamics at the focus of an electrohydraulic lithotripter," J. Acoust. Soc. Am., 123, 3367-3368, 2008.

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1 May 2008

In extracorporeal electrohydraulic lithotripters, a hemi-ellipsoidal metal reflector is used to focus a spherical wave generated by an electrical discharge. The spark source is positioned at one of the ellipsoid foci (F1); this makes the reflected wave focused at the other focus (F2). Despite the common assumption that the reflector behaves as a rigid mirror, the true reflection phenomenon includes the generation and reverberation of elastic waves in the reflector, which reradiate to the medium. Although these waves are much lower in amplitude than the specularly reflected wave, they may influence cavitation at F2. To explore such effects, waves in water and a brass reflector were modeled in finite differences based on the linearized equations of elasticity. The bubble response was simulated based on a Rayleigh-type equation for the bubble radius. In addition, the role of acoustic nonlinearity was estimated by numerical modeling. It is shown that the elastic waves in the reflector give rise to a long "ringing" tail, which results in nonmonotonic behavior of the bubble radius during its inertial growth after shock wave passage. This numerical result is qualitatively confirmed by experimental observations of bubble behavior using high-speed photography.

Local heating by a bubble excited by high intensity focused ultrasound

Kreider, W., M.S. Canney, M.R. Bailey, V.A. Khokhlova, and L.A. Crum. "Local heating by a bubble excited by high intensity focused ultrasound," J. Acoust. Soc. Am., 123, 2997, 2008.

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1 May 2008

A current topic of interest for high intensity focused ultrasound (HIFU) treatments involves the relative roles of bubbles and nonlinear acoustic propagation as heating mechanisms. At high amplitudes, nonlinear propagation leads to the generation of boiling bubbles within milliseconds; at lower amplitudes, cavitation bubbles can enhance heating through viscous dissipation, acoustic radiation, and heat conduction. In this context, understanding the physics attendant to HIFU bubbles requires consideration of gas–vapor bubble dynamics, including thermal effects in the nearby liquid. To this end, recent experimental observations with high-speed photography suggest that bubbles undergo a brief period of growth after application of HIFU has stopped. To explain this observation, a model is implemented that couples the thermodynamic state of a strongly driven bubble with thermal conditions in the surrounding liquid. From model simulations, liquid heating in the vicinity of a HIFU bubble is estimated. Calculations suggest that thermal conduction and viscous dissipation can lead to the evolution of a nontrivial thermal boundary layer. Development of a boundary layer that reaches superheated temperatures would explain the aforementioned experimental observation. As such, cavitation bubbles and boiling bubbles share important characteristics during HIFU.

Simultaneous measurement of pressure and temperature in a focused ultrasound field with a fiber optic hydrophone

Canney, M.S., M.R. Bailey, V.A. Khokhlova, O.A. Sapozhnikov, and L.A. Crum, "Simultaneous measurement of pressure and temperature in a focused ultrasound field with a fiber optic hydrophone," J. Acoust. Soc. Am., 123, 3221, 2008.

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1 May 2008

The characterization of high intensity focused ultrasound (HIFU) fields is important for both clinical treatment planning as well as for regulation of HIFU medical devices. In previous work, we have used a 100-µm fiber optic probe hydrophone (FOPH) to measure pressure waveforms from a 2-MHz HIFU source with 42-mm aperture and 44-mm focal length. The formation of shock waves with peak positive pressure of up to 80 MPa were measured and modeled in transparent tissue-mimicking gel phantoms and boiling was achieved in milliseconds [Canney MS, et al., J. Acoust. Soc. Am., 120:3110 (2006)].

In this work, the FOPH was also used to measure temperature changes in tissue phantoms from HIFU at peak focal intensities of 5000–20,000 W cm2. Temperature measurements were obtained by first low-pass filtering the voltage signal measured from the FOPH to remove the acoustic part of the measurement. Then, calibration of voltage to temperature was performed using results from a separate calibration experiment. Experimental measurements were compared with numerical modeling using a KZK-type model for acoustic propagation coupled with a heat transfer model. In summary, temperatures of 100°C were measured at the HIFU focus in milliseconds, in agreement with modeling.

Magnetic resonance imaging of boiling induced by high intensity focused ultrasound

Khokhlova, T.D., M.R. Bailey, M.S. Canney, V.A. Khokhlova, D. Lee, and K.I. Marro, "Magnetic resonance imaging of boiling induced by high intensity focused ultrasound," J. Acoust. Soc. Am., 122, 3079, 2007.

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1 Nov 2007

Bubble activity in high intensity focused ultrasound (HIFU) medical therapy is commonly but not rigorously divided between mechanically induced cavitation (µ size gas bubbles) and thermally induced boiling (mm size vapor bubbles). Our goal was to confirm that boiling occurred at 100<th>°C. A 2 MHz focused transducer (42 mm aperture, 44 mm focal length) was used to heat tissue phantoms in a 4.7 Tesla magnet. Temperature was measured by magnetic resonance imaging (MRI) proton resonance frequency shift and calculated from acoustic absorption. The MRI voxel was 0.3x0.5x2 mm, and acquisition time was 1.3 s. Boiling was observed as a dark spot in MRI images and fluctuation in the transducer drive voltage. At 30 MPa peak pressure, boiling occurred in 7 s. Calculations yielded 100<th>circC in 7 s and a temperature half maximum width of 1 mm. Averaging the calculated temperature field over the MRI voxel yielded a maximum of 73<th>circC, which was the peak temperature measured in the last MRI slice before boiling. In conclusion, boiling appeared when the peak temperature reached 100<th>°C, and the results warn that MRI monitoring alone may underestimate the peak temperatures.

Stable cavitation in ultrasound image-guided high intensity focused ultrasound therapy

Vaezy, S., W. Luo, M. Bailey, L. Crum, B. Rabkin, and V. Zderic, "Stable cavitation in ultrasound image-guided high intensity focused ultrasound therapy," J. Acoust. Soc. Am., 122, 3077, 2007.

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1 Nov 2007

Microbubble activity is significantly involved in both diagnostic and therapeutic aspects of ultrasound image-guided HIFU therapy. Ultrasound interrogation techniques (A-, B-, M-mode, Doppler, harmonic and contrast imaging, and passive and active cavitation detection) were integrated with HIFU. Our results using HIFU devices of 1–5 MHz, and focal, derated intensities of 1,000–10,000 W/cm2, show the formation of microbubbles (about 100 bubbles/mm3, 5–100 microns in size) at the HIFU focus. Boiling, stable, and inertial acoustic cavitation activities were detected during therapy. The presence of bubbles allows the observation of the treatment spot as bright hyperechoic regions in ultrasound images, providing an effective method for guidance and monitoring of therapy. The stable cavitation of microbubbles may provide a mechanism for enhanced HIFU energy delivery, as well as induction of biological responses for stimulation and regulation of specific physiological events such as coagulum and thrombus formation for hemostasis applications, apoptotic activity in treating tumor margins, and stimulation of immune response. Stable cavitation of extrinsic bubbles (contrast agents) is used in detection and localization of internal occult bleeding, using harmonic imaging. There appears to be benefits in utilizing stable cavitation in both diagnostic and therapeutic objectives of ultrasound image-guided HIFU.

Calibration of PVDF hydrophones using a broad-focus electromagnetic lithotripter

Sapozhnikov, O.A., Y.A. Pishchalnikov, A.D. Maxwell, and M.R. Bailey, "Calibration of PVDF hydrophones using a broad-focus electromagnetic lithotripter," 2007 IEEE Ultrasonics Symposium, 28-31 October, New York, NY, 112-115 (IEEE: Piscataway, NJ, 2007).

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28 Oct 2007

Correct measurement of acoustic pressure is crucial in many applications, e.g., medical diagnostics and therapy, where the physical effect of ultrasound on tissue depends on specific parameters of the wave, such as positive and negative pressure, shock front thickness, and pulse duration. In our previous paper, we reported building a new low-cost PVDF hydrophone to detect broadband signals from lithotripters and high intensity focused ultrasound (HIFU) sources. The hydrophone was built to complement the fiber optic probe hydrophone (FOPH), which has become the de facto standard broadband hydrophone for high amplitude medical devices. Our PVDF membrane hydrophone is more sensitive than the FOPH, thereby making measurement possible when averaging is not an option. The goal of this research was to develop a reliable method of calibration by comparing the PVDF hydrophone to the FOPH in a repeatable broadband pressure field. The results showed that the PVDF membranes had similar, though not identical responses.

Identification of kidney stone fragmentation in shock wave lithotripsy

Owen, N.R., M.R. Bailey, L.A. Crum, and O.A. Sapozhnikov, "Identification of kidney stone fragmentation in shock wave lithotripsy," 2007 IEEE Ultrasonics Symposium, 28-31 October, New York, NY, 323-326 (IEEE: Piscataway, NJ, 2007).

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28 Oct 2007

Identification of stone fragmentation, or comminution, during shock wave lithotripsy (SWL) would aid a urologist in determining the treatment endpoint, but there is currently little feedback available to do so. Here we report the measurement and analysis of SW scattering by kidney stone models in water to study the inverse relationship between stone size and scatter frequency. Stones were exposed to 20 SWs, 120 SWS, or 220 SWs to measure scatter and cause different levels of comminution. Measured scatter signals were processed in frequency to study the effect of stone comminution on the distribution of spectral energy. Comminution was measured by normalizing the mass of stone fragments, separated by size, to the mass of an intact stone. Output from frequency analysis was compared with percent mass comminution, and the shift of spectral energy to higher frequencies was proportional to the percent mass of stone fragments smaller than 2 mm.

Evaluation of a shock wave induced cavitation activity both in vitro and in vivo

Tu, J., T.J. Matula, M.R. Bailey, and L.A. Crum, "Evaluation of a shock wave induced cavitation activity both in vitro and in vivo," Phys. Med. Biol., 52, 5933-5944, 2007.

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1 Oct 2007

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.

Frequency analysis of shock wave scattering to identify kidney stone fragmentation in shock wave lithotripsy

Owen, N.R., M.R. Bailey, O.A. Sapozhnikov, and L.A. Crum, "Frequency analysis of shock wave scattering to identify kidney stone fragmentation in shock wave lithotripsy," Proceedings, 19th International Congress on Acoustics, 2-7 September, Madrid, Spain (2007).

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2 Sep 2007

Currently there is little feedback available in shock wave lithotripsy (SWL) to determine kidney stone fragmentation. The identification of fragmentation would aid a urologist in deciding to continue or stop treatment, and it could potentially reduce SW dose. Lithotripsy SWs strike stones with a broadband mechanical load. Reverberations excited within the stone are transmitted to surrounding fluid; a process termed resonant acoustic scatter (RAS). The frequency of RAS is inversely proportional to stone size. In experiment, variable SW treatments were applied to two types of stone models in vitro to produce different levels of fragmentation, which were measured by sieving dehydrated fragments and normalizing their mass to intact stone mass. RAS from selected SWs was measured with a broadband receiver and a new frequency analysis method was applied to display the redistribution of spectral energy. Mean percent mass for fragments smaller than 2 mm increased proportionally to the number of SWs applied. Amplitude of the frequency analysis output was directly proportional to fragmentation, and peak frequencies were inversely proportional to stone size. Results show promise that frequency analysis of RAS might provide feedback on fragmentation in SWL.

High-powered focused ultrasound fields in therapeutic medical applications: Modeling and measurements with a fiber optic hydrophone

Bailey, M.R., M.S. Canney, V.A. Kohkhlova, O.A. Sapozhnikov, and L.A. Crum, "High-powered focused ultrasound fields in therapeutic medical applications: Modeling and measurements with a fiber optic hydrophone," Proceedings, 19th International Congress on Acoustics, 2-7 September, Madrid, Spain (2007).

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2 Sep 2007

The goal of this work was to determine the acoustic waveform and beam width at the focus of a therapeutic ultrasound source both in water and in a tissue phantom. The source was a 2 MHz transducer of 45 mm focal length, 42 mm diameter, operating at 50 - 300 W acoustic power. Focal waveforms and beam widths calculated with a KZK-type model were in excellent agreement with values measured with a 100-µm, 100-MHz bandwidth fiber optic probe hydrophone (FOPH). Super focusing of the peak positive pressure and a proximal shift in the peak negative pressure were observed. Shocked distorted waveforms reached 70 MPa and - 15 MPa. Surface waves on the transducer were measured and included in the model but did not significantly affect the results obtained at focus. The change of the FOPH bandwidth to 30- MHz or the diameter of hydrophone to 500-µm resulted in 20% underestimation of the measured peak positive pressure but did not affect the measured negative peak pressure. Initiation of boiling was observed in tissue phantoms in milliseconds as predicted by weak shock theory due to absorption on the shocks. Work was supported by NIH DK43881, NSBRI SMS00402, and RFBR.

Use of scattering of ultrasound pulses and shock waves on kidney stones for imaging lithotripsy

Sapozhnikov, O.A., N.R. Owen, M.R. Bailey, A.I. Gromov, and L.A. Crum, "Use of scattering of ultrasound pulses and shock waves on kidney stones for imaging lithotripsy," Proceedings, 14th International Congress on Sound and Vibration, 9-12 July, Cairns, Australia (2007).

9 Jul 2007

Bubble proliferation in shock wave lithotripsy

Pishchalnikov, Y.A., J.A. McAteer, M.R. Bailey, J.C. Williams, Jr., and O.A. Sapozhnikov, "Bubble proliferation in shock wave lithotripsy," J. Acoust. Soc. Am., 121, 3081, 2007.

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1 May 2007

Stone breakage is less efficient when lithotripter shock waves (SWs) are delivered at 2 Hz compared to slower 0.5–1-Hz pulse repetition rates (PRFs). This correlates with increased number of transient cavitation bubbles observed along the SW path at fast PRF. The dynamics of this bubble proliferation throughout the bubble lifecycle is investigated in this report. Cavitation bubbles were studied in the free-field of a shock wave lithotripter using fine temporal and microscopic spatial resolution (high-speed camera Imacon-200). A typical cavitation bubble became visible (radius>10 μm) under the tensile phase of the lithotripter pulse, and at its first inertial collapse emitted a secondary SW and formed a micro-jet, which then could break up forming ~25 micro-bubbles. Subsequent rebound and collapse of the parent bubble appeared to produce a further 40–120 daughter bubbles visible following the rebound. Preexisting bubbles hit by the lithotripter SW also formed micro-jets and broke up into micro-bubbles that grew and coalesced, producing irregular-shaped bubbles that, in turn, broke into micro-bubbles upon subsequent inertial collapse. A conventional NTSC-rate camcorder was used to track cavitation bubbles from pulse-to-pulse, showing that a single bubble can give rise to a cavitation cloud verifying high-speed video results.

Formation of shock waveforms and millisecond boiling in an attenuative tissue phantom due to high-intensity focused ultrasound

Canney, M.S., M.R. Bailey, V.A. Khokhlova, and L.A. Crum, "Formation of shock waveforms and millisecond boiling in an attenuative tissue phantom due to high-intensity focused ultrasound," J. Acoust. Soc. Am., 121, 3082, 2007.

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1 May 2007

Nonlinear propagation effects during high-intensity focused ultrasound (HIFU) treatments can induce shocks in the acoustic waveform, dramatically accelerate heating rates, and result in rapid boiling of tissue at the focus. Localized boiling can be used for targeting and calibration of clinical HIFU treatments. In our previous work, millimeter size boiling bubbles were observed in several milliseconds in a weakly absorptive transparent tissue phantom, and temperature rise to 100<th>°C was calculated using weak shock theory from experimentally measured and numerically simulated focal waveforms. In this work, experiments are extended to an opaque phantom that has higher attenuation (0.5 dB/cm/MHz in the new phantom versus 0.15 dB/cm/MHz in the previous one) more similar to real tissue. Focal acoustic waveforms are measured using a fiber optic probe hydrophone and time to boil is monitored using a 20-MHz acoustic detector. Modeling of experimental conditions is performed with a KZK-type numerical model. Results demonstrate that although higher source amplitude is needed to attain the same focal amplitudes in the new, more attenuative phantom, similar amplitude shocks can be formed, resulting in equally fast heating rates.

Observations of cavitation and boiling in a tissue-mimicking phantom due to high intensity focused ultrasound

Canney, M.S., W. Kreider, M.R. Bailey, V.A. Khokhlova, and L.A. Crum, "Observations of cavitation and boiling in a tissue-mimicking phantom due to high intensity focused ultrasound," J. Acoust. Soc. Am., 122, 3079, 2007.

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1 May 2007

Bubbles generated by acoustic cavitation or boiling are often observed during high intensity focused ultrasound (HIFU) medical treatments. In this work, high-speed video imaging, a 20-MHz focused acoustic transducer, and the driving voltage to our 2-MHz HIFU source are used to distinguish between cavitation and boiling in a tissue-mimicking gel phantom at peak focal intensities up to 30,000 W/cm2. Bubble dynamics are modeled using a reduced order model that accounts for evaporation and condensation, heat and gas transfer across the interface, and temperature changes in the surrounding liquid. The model includes vapor trapping, whereby the noncondensable gas slows diffusion of vapor to the interface, thereby limiting condensation. At the transducer focus, evidence of cavitation is observed in the first millisecond before disappearing. Boiling is observed several milliseconds later, after sufficient heating of the focal volume to 100&$176;C. The disappearance of cavitation can be explained in part by the observed motion of bubbles away from the focal region due to radiation-pressure forces and in part by the softening of bubble collapses by vapor trapping. Thus, at clinical HIFU amplitudes, bubble dynamics and their impact on image-feedback and/or therapy change dramatically in only milliseconds.

A passive technique to identify stone comminution during shock wave lithotripsy

Owen, N.R., O.A. Sapozhnikov, M.R. Bailey, L. Trusov, and L.A. Crum, "A passive technique to identify stone comminution during shock wave lithotripsy," American Institute of Physics Proceedings, 900, 364-367, doi:10.1063/1.2723597, 2007.

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5 Apr 2007

The identification of comminution during shock wave lithotripsy can be difficult using fluoroscopy or other imaging modalities. However, correct interpretation is necessary to determine if a stone is breaking and to evaluate the endpoint of therapy. Reported here is a passive method to detect acoustic signals generated by shock wave (SW) impact on a model stone and to correlate the spectrum of the detected signals to stone size. Acoustic scatter from model stones in an electrohydraulic lithotripter was measured in water with a passive, focused receiver before and after the application of either 20 SWs or 50 SWs. The five stones used for each case were dehydrated after the experiment, separated with 3 mm, 2 mm, and 1 mm sequential sieves, and weighed to quantify comminution. The detection method was first successfully used to differentiate broken and unbroken stones. Then the system tracked the decreasing size of particles and clearly showed the presence of particles smaller than 2 mm, which was considered passable size. Thus, the detection system gives feedback on whether stones are breaking and when they may be considered fully comminuted.

Advantage of a broad focal zone in SWL: synergism between squeezing and shear

Sapozhnikov, O.A., M.R. Bailey, A.D. Maxwell, B. MacConaghy, R.O. Cleveland, J.A. McAteer, and L.A. Crum, "Advantage of a broad focal zone in SWL: synergism between squeezing and shear," American Institute of Physics Proceedings, 900, 351-355, doi:10.1063/1.2723594, 2007.

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5 Apr 2007

Objective: The focal zone width appears to be a critical factor in lithotripsy. Narrow focus machines have a higher occurrence of adverse effects, and arguably no greater comminution efficiency. Manufacturers have introduced new machines and upgrades to broaden the focus. Still, little data exists on how focal width plays a role in stone fracture. Thus, our aim was to determine if focal width interacts with established mechanisms known to contribute to stone fracture. Method: A series of experiments were undertaken with changes made to the stone in an effort to determine which is most important, the shock wave (SW) reflected from the back end of the stone (spallation), the SW ringing the stone (squeezing), the shear wave generated at surface of the stone and concentrated in the bulk of it (shear), or SWs generated from bubble collapse (cavitation). Shock waves were generated by a Dornier HM3-style lithotripter, and stones were made from U30 cement. Baffles were used to block specific waves that contribute to spallation, shear, or squeezing, and glycerol was used to suppress cavitation. Numerical simulation and high-speed imaging allowed for visualization of specific waves as they traveled within the stone. Results: For brevity, one result is explained. A reflective baffle was placed around the front edge of a cylindrical stone. The proximal baffle prevented squeezing by preventing the SW from traveling over the stone, but permitted the SW entering the stone through the proximal face and did not affect the other mechanisms. The distal baffle behaved the same as no baffle. The proximal baffle dramatically reduced the stress, and the stone did not break (stone broke after 45±10 SWs without the baffle and did not break after 400 SWs when the experiment stopped). The result implies that since removing squeezing halted comminution, squeezing is dominant. However, there is much more to the story. For example, if the cylindrical stone was pointed, it broke with the point on the distal end but not with the point on the proximal end. In both cases, squeezing was the same, so if squeezing were dominant, both stones should have broken. But the pointed front edge prevents the shear wave. The squeezing wave and its product — the shear wave — are both needed and work synergistically in a way explained by the model. Conclusions: A broad focus enhances the synergism of squeezing and shear waves without altering cavitation's effects, and thus accelerates stone fracture in SWL.

A mechanistic analysis of stone fracture in lithotripsy

Sapozhnikov, O.A., A.D. Maxwell, B. MacConaghy, and M.R. Bailey, "A mechanistic analysis of stone fracture in lithotripsy," J. Acoust. Soc. Am., 121, 1190-1202, 2007.

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1 Feb 2007

In vitro experiments and an elastic wave model were used to analyze how stress is induced in kidney stones by lithotripsy and to test the roles of individual mechanisms—spallation, squeezing, and cavitation. Cylindrical U30 cement stones were treated in an HM-3-style lithotripter. Baffles were used to block specific waves responsible for spallation or squeezing. Stones with and without surface cracks added to simulate cavitation damage were tested in glycerol (a cavitation suppressive medium). Each case was simulated using the elasticity equations for an isotropic medium. The calculated location of maximum stress compared well with the experimental observations of where stones fractured in two pieces. Higher calculated maximum tensile stress correlated with fewer shock waves required for fracture. The highest calculated tensile stresses resulted from shear waves initiated at the proximal corners and strengthened along the side surfaces of the stone by the liquid-borne lithotripter shock wave. Peak tensile stress was in the distal end of the stone where fracture occurred. Reflection of the longitudinal wave from the distal face of the stone—spallation—produced lower stresses. Surface cracks accelerated fragmentation when created near the location where the maximum stress was predicted.

The use of resonant scattering to identify stone fracture in shock wave lithotripsy

Owen, N.R., M.R. Bailey, L.A. Crum, O.A. Sapozhnikov, and L.A. Trusov, "The use of resonant scattering to identify stone fracture in shock wave lithotripsy," J. Acoust. Soc. Am., 121, EL41-EL47, doi:10.1121/1.2401266, 2007.

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1 Jan 2007

There is currently little feedback as to whether kidney stones have fractured during shock wave lithotripsy. Resonant scattering of the lithotripter shock wave was used here to differentiate intact and fractured stone models in water. Scattering, including reflection and radiation due to reverberation from within the stone, was calculated numerically with linear elasticity theory and agreed well with measurements made with a focused receiver. Identification of fracture was possible through frequency analysis, where scatter from fractured stones was characterized by higher energy in distinct bands. High-speed photography concurrent with measurement indicated the effect was not due to cavitation.

A sensitive, broadband polyvinylidine difluoride (PVDF) hydrophone for accurate characterization of shock waves

Maxwell, A.D., B.E. MacConaghy, O.A. Sapozhnikov, and M.R. Bailey, "A sensitive, broadband polyvinylidine difluoride (PVDF) hydrophone for accurate characterization of shock waves," J. Acoust. Soc. Am., 120, 3109-3110, 2006.

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1 Nov 2006

Few hydrophones are capable of measuring high-intensity fields such as shock waves accurately. One of the more reliable is the fiberoptic probe hydrophone. However, this system is expensive and insensitive. We created a new PVDF hydrophone and compared it with a fiberoptic system. The hydrophone consisted of a 25 µm thick PVDF membrane with a 0.5 mm active element and a preamplifier, which were each held in separate attached polycarbonate housings. The amplifier had adjustable gain and could account for membrane resonance to flatten the frequency response. A model of the frequency response for the system was developed, which agreed well with the measured response. Shock waves were measured in two Dornier HM-3 clones and an electromagnetic lithotripter. Measurements were also recorded using a 2 MHz focused piezoceramic source and a broadband PVDF source. Shock-wave measurements closely matched those recorded by the fiberoptic hydrophone and calculations made with a KZK-type model. Very little damage to the membrane was found after applying several thousand shock waves. This new membrane hydrophone is robust and sufficiently accurate to measure high-intensity fields, while greatly reducing cost, increasing sensitivity, and simplifying measurements of shock waves.

Bubble responses to lithotripsy shock waves

Kreider, W., M.R. Bailey, O.A. Sapozhnikov, and L.A. Crum, "Bubble responses to lithotripsy shock waves," J. Acoust. Soc. Am., 120, 3110, 2006.

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1 Nov 2006

The responses of bubbles subjected to a lithotripsy shock wave have been investigated numerically and experimentally to elucidate the role of heat and mass transfer in the underlying dynamics of strongly excited bubbles. Single spherical bubbles were modeled as gas–vapor bubbles by accounting for liquid compressibility, heat transfer, vapor transport, vapor trapping by noncondensable gases, diffusion of noncondensable gases, and heating of the liquid at the bubble wall. For shock-wave excitations, the model predicts bubble growth and collapse, followed by rebounds whose durations are significantly affected by vapor trapping. To experimentally test these predictions, bubble rebound durations were measured using passive cavitation detectors, while high-speed photographs were captured to evaluate the local cavitation field and to estimate radius–time curves for individual bubbles. Data were acquired for bubbles in water with varying temperature and dissolved gas content. Measurements verify that vapor trapping is an important mechanism that is sensitive to both temperature and dissolved gas content. While this work focuses primarily on individual bubbles, some bubble cloud effects were observed. Analysis with a simple multibubble model provides noteworthy insights.

Calculation and measurement of acoustic scatter to assess fragmentation in shock wave lithotripsy

Owen, N.R., O.A. Sapozhnikov, M.R. Bailey, and L.A. Crum, "Calculation and measurement of acoustic scatter to assess fragmentation in shock wave lithotripsy," J. Acoust. Soc. Am., 120, 3110, 2006., J. Acoust. Soc. Am., 120, 3110, 2006.

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1 Nov 2006

Shock wave lithotripsy (SWL) is currently conducted with little feedback on whether kidney stones are breaking. To determine if fragmentation could be assessed, acoustic scatter from intact and fractured stone models was calculated numerically and measured in vitro. Acoustic scatter from the stones, which were modeled with glass spheres, was calculated numerically using a linear elastic model, initialized with known elastic constants, and propagated from the stone model surface using the Helmholtz–Kirchhoff integral. Experimentally, shock waves were generated with a research lithotripter and scatter was measured with a broadband, spherically focused receiver. Calculated and measured results agreed well in the time domain. In frequency, power spectra were integrated to find energy and showed that scatter from the fractured stone model had higher energy in specific frequency bands that were related to the reverberation period. High-speed photography indicated that cavitation did not adversely affect the analysis of scatter. In this work it was possible to distinguish between the intact and fractured stone models. This method could be applied to stones that fragment gradually under the application of shock waves and potentially be used to estimate fragment size, and therefore the endpoint of therapy.

Measurement of reduced stress in model kidney stones with increased rate of shock wave delivery in lithotripsy

Ikeda, T., M.R. Bailey, B. MacConaghy, L.A. Crum, and Y. Matsumoto, "Measurement of reduced stress in model kidney stones with increased rate of shock wave delivery in lithotripsy," J. Acoust. Soc. Am., 120, 3065, 2006.

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1 Nov 2006

Slow clinical shock wave rates more effectively comminute stones. Higher rates create more cavitation bubbles along the focusing axis. Bubble clouds potentially reflect or attenuate the shock wave and also may collapse less energetically. Here, high-speed photo-elastography was used to visualize the dynamic stress distribution inside a transparent model stone. Photo-elastography records constant-stress lines, making quantification possible. PVDF sensors (4 mm diameter) measured force on the proximal face of the stones. The impulsive force of the shock wave and the cloud collapse at various clinical rates (single shocks, 1 Hz, 2 Hz, 3 Hz) in degassed and non-degassed water were calculated from the measurements. Impulse forces from the shock wave and cavitation collapse were comparable in the range 4–7 x 10-4 Ns. At clinical rates in gas-saturated water, the stress fringes of the tensile component of the shock wave were reduced; the observable maximum stress was decreased; and impulsive force from the shock and the cavitation were decreased over single shocks. The results are evidence of reduced stress in the stone at higher rates due to attenuation by bubbles and less so to softened cavitation collapse.

Millisecond initiation of boiling by high-intensity focused ultrasound in tissue-mimicking phantoms

Canney, M.S., M.R. Bailey, V.A. Khokhlova, and L.A. Crum, "Millisecond initiation of boiling by high-intensity focused ultrasound in tissue-mimicking phantoms," J. Acoust. Soc. Am., 120, 3110, 2006.

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1 Nov 2006

Nonlinear propagation effects leading to shock formation at the focus of hig-intensity focused ultrasound (HIFU) treatments can accelerate heating and cause rapid boiling in tissue. Boiling can be utilized for targeting the treatment with B-mode ultrasound and should be taken into account when planning the treatment, because bubbles reflect ultrasound and thereby displace and distort the lesion shape. In these experiments, an HIFU transducer of 2 MHz frequency, 4 cm aperture, and 4.5 cm focal length was used to investigate heating effects from shock formation in tissue-mimicking phantoms. The time required to attain 100<th>°C at the focus was calculated with weak shock theory from the peak amplitudes calculated with a KZK-type model, and time to boiling was measured by high-speed video and a 20-MHz passive cavitation detector (PCD) for different values of phantom absorption (both lower than tissue absorption) and HIFU power (100–200 W). Boiling was observed in 3 ms at the highest power level used by the observation of visible bubbles and by a significant change in the PCD time signal and spectrum.

Photo-elastic, high-speed images of stress induced in cylindrical model kidney stones by lithotripsy

MacConaghy, B.E., T. Ikeda, M.R. Bailey, A.D. Maxwell, and O.A. Sapozhnikov, "Photo-elastic, high-speed images of stress induced in cylindrical model kidney stones by lithotripsy," J. Acoust. Soc. Am., 120, 3066, 2006.

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1 Nov 2006

Recent experiments and calculations show that a focusing shear wave generated by the shock wave traveling along the length of a cylindrical stone creates the dominant stress and causes fracture of cylindrical model stones. A small disk placed on the proximal face of the stone suppressed the longitudinal wave responsible for spallation in calculations yet had little effect on the number of shock waves required to fracture the stone in experiment. However, a disk placed around the stone blocked the shock wave traveling along the stone in calculations and suppressed fracture in measurements. The conclusion was that so-called dynamic squeezing was a dominant mechanism to spallation. Here, photo-elastic, high-speed imaging was used to observe the suppression of various waves in cylindrical stones made of acrylic. Glycerol was used to avoid artifact from the curvature of the stone. Comparison was made to calculations using the elasticity equations for an isotropic medium. Agreement between measurement and calculation was excellent and supports dynamic squeezing. The results help validate the model, and the technique and modeling may help us understand where and how stress is created in other shock wave therapies.

Radiation force imparted on a kidney stone by a Doppler-mode diagnostic pulse

Sapozhnikov, O.A., L.A. Trusov, A.I. Gromov, N.R. Owen, M.R. Bailey, and L.A. Crum, "Radiation force imparted on a kidney stone by a Doppler-mode diagnostic pulse," J. Acoust. Soc. Am., 120, 3109, 2006.

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1 Nov 2006

Detection of kidney stones and estimation of their sizes is an important part of the lithotripsy treatment. Fluoroscopy is often used to target stones, but not every stone is radio-opaque and, in addition, fluoroscopy produces ionizing radiation. Acoustic waves offer an alternative way to visualize stones. The acoustic impedance of kidney stones typically differs significantly from that of surrounding tissue. A useful consequence of the impedance mismatch is the possibility to target stones with diagnostic mode ultrasound. Another consequence is that radiation force pushes the stone. Stone displacement may be responsible for the twinkling artifact that has been observed by several authors in color Doppler mode of ultrasound imaging. This effect can be used to detect not only renal and ureteral stones, but also calcifications in other organs (e.g., breast). In this paper we model the radiation force associated with the Doppler diagnostic pulse. The problem is divided into three parts: (1) acoustic scattering; it is solved in finite differences; (2) radiation force calculation; (3) stone velocity estimation supposing the stone sits in soft tissue.

Shock-wave energy deflection due to the presence of bone

Matula, T., J. Tu, M.Bailey, K. Fagnan, and R. LeVeque, "Shock-wave energy deflection due to the presence of bone," J. Acoust. Soc. Am., 120, 3109, 2006.

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1 Nov 2006

The physical interaction of shock waves with musculoskeletal tissues is inherently different from other high-pressure acoustic therapies. Whereas high-intensity focused ultrasound and lithotripsy focus their energy in regions of soft tissue, musculoskeletal shock-wave therapy (SWT) involves focusing shock waves (SWs) near or at bones. The presence of bones will cause reflection, refraction, and diffraction of acoustic energy. In our analysis of cavitation generated during clinical SWT treatment, we noticed that the cavitation was occurring away from the SW focus. We confirmed this by performing an in vitro experiment on a bone embedded in gel. We also quantified the deflection angle as a function position near a bone in water: A talus was manufactured using rapid prototyping. It was placed near the focus of an electrohydraulic SW device. To visualize the pressure field, a high-speed camera imaged the cavitation field generated around the focus. As the bone was moved closer to the focus, the cavitation field (and thus, the pressure field) deflected away from the bone. The deflection angle was measured as a function of relative distance between the bone and focus. Numerical simulations were performed to model the deflection of energy away from the bone.

Spatial distributions of acoustic parameters in high-frequency focused ultrasound fields

Khokhlova, V.A., O.S. Bessanova, M.S. Canney, M.R. Bailey, and L.A. Crum, "Spatial distributions of acoustic parameters in high-frequency focused ultrasound fields," J. Acoust. Soc. Am., 120, 3194, 2006.

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1 Nov 2006

Different peak and average acoustic parameters determine the efficiency of different physical mechanisms of high-intensity focused ultrasound (HIFU) interaction with biological tissue. Spatial distributions of these parameters are therefore important for transducer calibration and extrapolation of measurements in water to application in tissue. In the case of linear focusing, all parameters of the acoustic field can be obtained from the spatial distribution of the wave amplitude. However, in nonlinear focused beams, each parameter has its own characteristic spatial structure, which changes with the increase of the HIFU power level. This work compares the focal size and location calculated for the peak positive and peak negative pressure, mean intensity, and effective acoustic energy absorption in water and in tissue. Numerical solutions, obtained with the KZK-type model, are analyzed for various regimes of linear, quasilinear, and strongly nonlinear propagation which includes formation of shocks. The results of simulations are validated by comparison with measurements performed with a fiberoptic probe hydrophone in water and in a tissue mimicking phantom. The peak positive pressure and effective absorption are finely focused, whereas the negative pressure, responsible for cavitation, is broad and displaced towards the transducer.

Use of a bovine eye lens for observation of HIFU-induced lesions in real-time

Lafon, C., V.A. Khokhlova, O.A. Sapozhnikov, P.J. Kaczkowski, A.A. Brayman, M.R. Bailey, and L.A. Crum, "Use of a bovine eye lens for observation of HIFU-induced lesions in real-time," Ultrasound Med. Biol. 32, 1731-1741, 2006.

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1 Nov 2006

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.

A new PVDF membrane hydrophone for accurate measurement of medical shock waves

Maxwell, A.D., O.A. Sapozhnikov, and M.R. Bailey, "A new PVDF membrane hydrophone for accurate measurement of medical shock waves," Proceedings, IEEE International Ultrasonics Symposium, 2-6 October, Vancouver, Canada, 1608-1611 (IEEE, 2006).

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2 Oct 2006

Calibration of medical shock wave sources is critical and challenging. Aside from the fiber optic probe hydrophone, there are few if any commercially available hydrophones designed for measuring medical shock waves. We have developed a new PVDF membrane hydrophone and compared it to measurements with a fiber optic probe hydrophone (FOPH) in several lithotripters. One part of the hydrophone held the 5 cm times 5 cm times 25 µm PVDF film with geometrical element size 0.5 mm. The other part housed the preamplifier. By substitution comparison to FOPH and an NTR hydrophone, the sensitivity was found to be 0.035 MPa/mV at 2 MHz. Initial spot frequency comparisons showed the response to be fairly flat from 1-20 MHz but showed an elevated sensitivity at 15-20 MHz, and lithotripsy waveforms indicated some high-pass filtering. The impulse response of a 25 µm membrane was calculated and used to de-convolve the signal after which agreement with waveforms from the other hydrophones was excellent. The hydrophone is sufficiently robust to measure 1000 s of lithotripter shock waves. It is inexpensive, sensitive, and has a lower signal to noise ratio than the FOPH.

Characterization of high intensity focused ultrasound fields with a high spatio-temporal resolution

Canney, M.S., V.A. Khokhlova, M.R. Bailey, O.A. Sapozhnikov, and L.A. Crum, "Characterization of high intensity focused ultrasound fields with a high spatio-temporal resolution," Proceedings, 2006 IEEE International Ultrasonics Symposium, Vancouver, Canada, 856-859, doi:10.1109/ULTSYM.2006.231 (IEEE, 2006).

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2 Oct 2006

The accurate characterization of high intensity focused ultrasound (HIFU) fields is important for the prediction of thermal and mechanical bio-effects in tissue, as well as for the development of standards for therapeutic systems. At HIFU intensity levels, the combined effects of nonlinearity and diffraction result in the formation of asymmetric shocked waveforms and a corresponding distortion of the spatial distributions of various acoustic parameters that are responsible for different bio-effects. Acoustic probes that are capable of withstanding high pressures and that can measure waveforms with a high spatial and temporal resolution are required to capture the shock fronts and highly localized field structures that can arise at therapeutically relevant treatment regimes. An experimentally validated numerical model can also be an effective tool when direct measurements are not possible. In this work, acoustic measurements using force balance, acoustic holography, broadband fiber optic and PVDF hydrophones, were combined with simulations based on a KZK-type model to demonstrate an effective approach for the calibration of HIFU transducers in water and for derating these results to tissue.

Use of acoustic scattering to monitor kidney stone fragmentation during shock wave lithotripsy

Owen, N.R., O.A. Sapozhnikov, M.R. Bailey, and L.A. Crum, "Use of acoustic scattering to monitor kidney stone fragmentation during shock wave lithotripsy," Proceedings, IEEE International Ultrasonics Symposium, 2-6 October, Vancouver, Canada, 736-739 (IEEE, 2006).

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2 Oct 2006

It is currently difficult to assess whether a kidney stone has fractured during shock wave lithotripsy. Here we report the calculation and measurement of shock wave scattering by stone models in water. Calculations were based on linear elastic theory to find pressure in the fluid and stress in the stone models, and on scattering theory to find radiation from the stone models. Measurements were made with a spherical, broadband receiver. Calculation and measurement agree well in the time domain and through frequency analysis of detected acoustic scattering it was possible to distinguish between fractured and intact model stones. Cavitation was visualized with high speed photography and was not a dominant effect in the measurements.

Acoustic cavitation and medical ultrasound

Kreider, W., L. Crum, M. Bailey, T. Matula, V. Khokhlova, and O. Sapozhnikov, "Acoustic cavitation and medical ultrasound," Proceedings, Sixth International Conference on Cavitation, 11-15 September, Wageningen, The Netherlands (MARIN, The Netherlands, 2006)(CD-ROM).

11 Sep 2006

In vitro kidney stone erosion with dual frequency HIFU

Talor, R., M.R. Bailey, T.D. Khokhlova, T. Ikeda, Y. Matsumoto, and L.A. Crum, "In vitro kidney stone erosion with dual frequency HIFU," Proceedings, Sixth International Symposium on Therapeutic Ultrasound, 30 August - 1 September, Oxford, England (American Institute of Physics Conference Proceedings, Vol. 911, 2006).

30 Aug 2006

Use of acoustic holography for characterization of therapeutic transducers

Sapozhnikov, O.A., D. Cathignol, M.R. Bailey, A.V. Morozov, and Y.A. Pishchalnikov, "Use of acoustic holography for characterization of therapeutic transducers," Proceedings, Sixth International Symposium on Therapeutic Ultrasound, 30 August - 1 September, Oxford, England, 114 (American Institute of Physics, 2006).

30 Aug 2006

Interactions of cavitation bubbles observed by high-speed imaging in shock wave lithotripsy

Pishchalnikov, Y.A., O.A. Sapozhnikov, M.R. Bailey, J.A. McAteer, J.C. Williams Jr., A.P. Evan, R.O. Cleveland, and L.A. Crum, "Interactions of cavitation bubbles observed by high-speed imaging in shock wave lithotripsy," Proceedings, 17th International Symposium on Nonlinear Acoustics, edited by A.A. Atchley, V.W. Sparrow, and R.M. Keolian, 299-302 (American Institute of Physics Conference Proceedings Vol. 383, 2006).

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30 May 2006

A multi-frame high-speed photography was used to investigate the dynamics of cavitation bubbles induced by a passage of a lithotripter shock wave in a water tank. Solitary bubbles in the free field each radiated a shock wave upon collapse, and typically emitted a micro-jet on the rebound following initial collapse. For bubbles in clouds, emitted jets were directed toward neighboring bubbles and could break the spherical symmetry of the neighboring bubbles before they in turn collapsed. Bubbles at the periphery of a cluster underwent collapse before the bubbles at the center. Observations with high-speed imaging confirm previous predictions that bubbles in a cavitation cloud do not cycle independently of one another but instead interact as a dynamic bubble cluster.

Role of shear and longitudinal waves in stone comminution by lithotripter shock waves

Bailey, M.R., A.D. Maxwell, B. MacConaghy, O.A. Sapozhnikov, and L.A. Crum, "Role of shear and longitudinal waves in stone comminution by lithotripter shock waves," Proceedings, 17th International Symposium on Nonlinear Acoustics, edited by A.A. Atchley, V.W. Sparrow, and R.M. Keolian, AIP Conference Proceedings, 838, 323-326, doi:10.1063/1.2210370, 2006.

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30 May 2006

Mechanisms of stone fragmentation by lithotripter shock waves were studied. Numerically, an isotropic-medium, elastic-wave model was employed to isolate and assess the importance of individual mechanisms in stone comminution. Experimentally, cylindrical U-30 cement stones were treated in an HM-3-style research lithotripter. Baffles were used to block specific waves responsible for spallation, squeezing, or shear. Surface cracks were added to stones to simulate the effect of cavitation, and then tested in water and glycerol (a cavitation suppressive medium). The calculated location of maximum stress compared well with the experimental observations of where cracks naturally formed. Shear waves from the shock wave in the fluid traveling along the stone surface (a kind of dynamic squeezing) led to the largest stresses in the cylindrical stones and the fewest shock waves to fracture. Reflection of the longitudinal wave from the back of the stone — spallation — and bubble-jet impact on the proximal and distal faces of the stone produced lower stresses and required more shock waves to fracture stones, but cavitation stresses become comparable in small stone pieces. Surface cracks accelerated fragmentation when created near the location where the maximum stress was predicted.

Detecting fragmentation of kidney stones in lithotripsy by means of shock wave scattering

Sapozhnikov, O.A., L.A. Trusov, N.R. Owen, M.R. Bailey, and R.O. Cleveland, "Detecting fragmentation of kidney stones in lithotripsy by means of shock wave scattering," Procedings, Fifth International Symposium on Therapeutic Ultrasound, edited by G.T. Clement, N.J. McDannold, and K. Hynynen, 308-312(American Institute of Physics, 2006).

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8 May 2006

Although extracorporeal shock wave lithotripsy (a procedure of kidney stone comminution using focused shock waves) has been used clinically for many years, a proper monitoring of the stone fragmentation is still undeveloped. A method considered here is based on recording shock wave scattering signals with a focused receiver placed far from the stone, outside the patient body. When a fracture occurs in the stone or the stone becomes smaller, the elastic waves in the stone will propagate differently (e.g. shear waves will not cross a fracture) which, in turn, will change the scattered acoustic wave in the surrounding medium. Theoretical studies of the scattering phenomenon are based on a linear elastic model to predict shock wave scattering by a stone, with and without crack present in it. The elastic waves in the stone and the nearby liquid were modeled using a finite difference time domain approach. The subsequent acoustic propagation of the scattered waves into the far-field was calculated using the Helmholtz–Kirchhoff integral.

Experimental studies were conducted using a research electrohydraulic lithotripter that produced the same acoustic output as an unmodified Dornier HM3 clinical lithotripter. Artificial stones, made from Ultracal-30 gypsum and acrylic, were used as targets. The stones had cylindrical shape and were positioned co-axially with the lithotripter axis. The scattered wave was measured by focused broadband PVDF hydrophone. It was shown that the size of the stone noticeably changed the signature of the reflected wave.

New devices and old pitfalls in shock wave therapy

Bailey, M.R., T.J. Matula, O.A. Sapozhnikov, R.O. Cleveland, Yu A. Pishchalnikov, and J.A. McAteer, "New devices and old pitfalls in shock wave therapy," Proceedings, Fifth International Symposium on Therapeutic Ultrasound, edited by G.T. Clement, N.J. McDannold, and K. Hynynen, AIP Conference Proceedings, 829, 380-384, doi:10.1063/1.2205501, 2006.

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8 May 2006

Shock waves are now used to treat a variety of musculoskeletal indications and the worldwide demand for shock wave therapy (SWT) is growing rapidly. It is a concern that very little is known about the mechanisms of action of shock waves in SWT. The technology for SWT devices is little changed from that of shock wave lithotripters developed for the treatment of urinary stones. SWT devices are engineered on the same acoustics principles as lithotripters, but the targets of therapy for SWT and shock wave lithotripsy (SWL) are altogether different. For SWT to achieve its potential as a beneficial treatment modality it will be necessary to determine precisely how SWT shock waves interact with biological targets. In addition, for SWT to evolve, the future design of these devices should be approached with caution, and lithotripsy may serve as a useful model. Indeed, there is a great deal to be learned from the basic research that has guided the development of SWL.

Cavitation-induced saturation of the negative-pressure phase of lithotripter shock pulses

Pishchalnikov, Y.A., J.A. McAteer, M.R. Bailey, O.A. Sapozhnikov, I.V. Pishchalnikov, and J.C. Williams Jr., "Cavitation-induced saturation of the negative-pressure phase of lithotripter shock pulses," J. Acoust. Soc. Am., 119, 3407, 2006.

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1 May 2006

The tensile stress imposed by the negative-pressure phase of lithotripter shock pulses can cause cavitation. Bubbles continue to grow after the passage of the acoustic pulse; thus, some of the pulse energy is transformed to the kinetic and potential energy of the liquid surrounding the cavitation bubbles and, therefore, no longer belongs to the acoustic field. One might predict that this energy loss should be more pronounced for strong pulses that produce more cavitation. To investigate this, acoustic pulses were measured at the geometric focus of a Dornier HM-3 electrohydraulic lithotripter (water 39°C, dissolved gas ~8% saturation) using a fiber--optic probe hydrophone FOPH-500. Measurements showed that, while the amplitude and duration of the leading positive-pressure phase increased dramatically as charging potential was increased from 12 to 24 kV, the trailing negative-pressure phase of the pulse remained unchanged. This stabilization of the negative-pressure phase could be due to cavitation restricting the amplitude of the negative pressure that can be transmitted through the liquid, such that further increase of the amplitude at the source would not increase the negative amplitude at the target but would only result in stronger cavitation along the acoustic path.

Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom

Khokhlova, V.A., M.R. Bailey, J.A. Reed, B.W. Cunitz, P.J. Kaczkowski, and L.A. Crum, "Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom," J. Acoust. Soc. Am., 119, 1834-1848, 2006.

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1 May 2006

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.

Measurement and modeling of nonlinear waveforms in high-intensity focused ultrasound fields

Canney, M.S., M.R. Bailey, V.A. Khokhlova, M.A. Smagin, O.A. Sapozhnikov, and L.A. Crum, "Measurement and modeling of nonlinear waveforms in high-intensity focused ultrasound fields," J. Acoust. Soc. Am., 119, 3228, 2006.

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1 May 2006

Direct measurement of HIFU fields in situ is important for the accurate prediction of thermal and mechanical bioeffects, as well as for the development of standards for medical systems. An experimentally validated numerical model can be an effective tool in both laboratory and clinical settings when direct measurements are not possible. Calculations with a KZK-type model and measurements with a fiberoptic probe hydrophone were employed together to characterize HIFU fields in water and in a tissue-mimicking gel. To determine the boundary conditions for simulations, the normal velocity distribution on the transducer surface was reconstructed using acoustic holography and combined with acoustic power measurements. At the focus, highly nonlinear waveforms ( 700 and –150 bars peak pressures) were obtained both experimentally and numerically, which differed significantly from waveforms linearly extrapolated from low-amplitude results. Strongly distorted shock waveforms were localized in an axial region much smaller than the half-maximum beamwidth of the transducer excited at low level. At the highest excitation levels, the simulations predicted frequency content higher than was measurable in our configuration. Simulations also show that if these frequencies are not included, predicted heating rates are significantly lower.

Measurement of pressure produced at a solid surface by an acoustically driven cavitation bubble cloud

Ikeda, T., S. Yoshizawa, Y. Matsumoto, M.R. Bailey, L.A. Crum, and J.S. Allen, "Measurement of pressure produced at a solid surface by an acoustically driven cavitation bubble cloud," J. Acoust. Soc. Am., 119, 3408, 2006.

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1 May 2006

A cavitation bubble cloud typically acts as a strong acoustic scatterer; however, at certain frequencies and amplitudes waves transmitted by a cloud are amplified. A long-term goal is to break up kidney stones by using a two-frequency ultrasound forcing method with one frequency that generates the cloud followed by a lower second frequency that excites its violent collapse. The goal of this study is to determine the frequency and pressure amplitudes which produce the largest pressures as measured by a PVDF membrane on the stone surface. Reflection was also measured by a concave PVDF sensor placed 40 mm from the surface, and cloud sizes were determined by high-speed camera images. Transmission is quantified by the force. Reflection and transmission showed a reciprocal relation: peak in transmission corresponded to a minimum in reflection. The largest cloud observed created the largest reflection, whereas the smallest clouds created the largest transmitted signals. Forces generated by the small clouds were five times larger than the amplitude without a cloud. Thus, in using a two-frequency excitation combination, the pressures generated by the cloud cavitation might be optimized for lithotripsy applications.

Microbubble cavitation, boiling, and nonlinear acoustic propagation in high-intensity focused ultrasound therapy

Kaczkowski, P.J., M.R. Bailey, L.A. Crum, V.A. Khokhlova, and A. Anand, "Microbubble cavitation, boiling, and nonlinear acoustic propagation in high-intensity focused ultrasound therapy," J. Acoust. Soc. Am., 119, 3211, 2006.

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1 May 2006

The investigation of high-intensity focused ultrasound (HIFU) as a tool for noninvasive thermally ablative therapy has required deeper understanding of the relative roles of nonlinear mechanisms involved in heat deposition. Attempts at quantifying the dose response to particular exposure conditions in vitro are complicated by the interplay of several mechanisms. These include microbubble cavitation, nonlinear acoustic propagation and attenuation, dependence of tissue parameters on temperature and temperature history, and formation and evolution of vapor bubbles due to boiling. One immediately evident consequence of such effects is distortion of coagulative lesion shape and size, colloquially evolving from cigars to tadpoles. Developing a quantitative understanding of the relative roles of relevant nonlinear mechanisms is not straightforward, yet is desirable for design of algorithms for therapy planning and real-time monitoring using ultrasound. A historical perspective of research toward this end will be presented along with a recommendation for suitable terminology for the various physical acoustic regimes encountered in HIFU therapy.

Nonlinear mechanisms of heating by high-intensity focused ultrasound

Khokhlova, V.A., M.R. Bailey, M.S. Canney, P.J. Kaczkowski, and L.A. Crum, "Nonlinear mechanisms of heating by high-intensity focused ultrasound," J. Acoust. Soc. Am., 119, 3227, 2006.

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1 May 2006

Two major nonlinear mechanisms are known to influence HIFU heating: acoustic nonlinearity and cavitation. Heating may also result in formation of boiling vapor bubbles that grow much larger than the cavitation bubbles. The relevant role of these phenomena was investigated experimentally and numerically in a gel phantom. HIFU pressure thresholds for shock formation, cavitation, and boiling were measured using a fiber-optic probe hydrophone, passive cavitation detection, ultrasound and optical imaging, and thermocouples. The KZK and Bio-heat equations were employed to simulate experimental conditions. Elevated static pressure was applied to suppress bubbles and increase the boiling temperature, thus isolating the pure effect of acoustic nonlinearity in comparison of heating between short, high-amplitude and long, low-amplitude pulses of equal average intensity. The experimental results indicated that both nonlinear mechanisms accelerated lesion production with acoustic nonlinearity responsible for the greater effect. It was observed that lesion distortion and migration was due to boiling detected in as little as 40 ms within the center of the lesion, in agreement with nonlinear acoustic simulations. These data indicate that acoustic nonlinearity and the boiling play a significant role earlier in HIFU treatments than previously anticipated.

The role of cavitation in therapeutic ultrasound

Crum, L., M. Bailey, V. Khokhlova, O. Sapozhnikov, B. Rabkin, A. Evan, J. McAteer, Y. Pishchalnikov, J. Williams, and R. Cleveland, "The role of cavitation in therapeutic ultrasound," J. Acoust. Soc. Am., 119, 3405, 2006.

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1 May 2006

Ed Carstensen has made many contributions to biomedical ultrasound but among those that are becoming more and more relevant to current clinical practice are those that determine the conditions under which cavitation is induced in vivo. For many years, it was assumed that the medical ultrasound devices were unable to induce cavitation in living tissue because either the acoustic conditions were not sufficient or the nucleation sites that are required were too small. With the advent of lithotripters and high-intensity focused ultrasound (HIFU) devices, cavitation generation in vivo is commonplace. Our current research at the University of Washington has focused on the role that cavitation plays in stone comminution and tissue damage during lithotripsy, as well as the enhancement or reduction of desirable coagulative necrosis during HIFU application. During HIFU application, we find enhanced heating that results from nonlinear acoustic wave propagation (a key Carstensen contribution) leads to vapor bubble formation. This presentation will review our recent studies in this area.

What is boiling during high-intensity focused ultrasound

Kreider, W., M.R. Bailey, and L.A. Crum, "What is boiling during high-intensity focused ultrasound," J. Acoust. Soc. Am., 119, 3228, 2006.

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1 May 2006

For treatments that use high-intensity focused ultrasound (HIFU), it is important to understand the behavior of bubbles in the context of both large acoustic pressures and elevated temperatures in the surrounding medium. Based upon clinical and experimental observations, any preexisting cavitation nuclei in tissue or blood are likely to be less than 1 micron. For HIFU conditions characterized by megahertz frequencies and pressures on the order of megaPascals, gas bubbles less than a micron in radius can grow explosively. Calculations for a single, spherical bubble imply that the resulting bubble motions are significantly influenced by evaporation and condensation processes. Consequently, at both high and low ambient temperatures, HIFU-driven bubbles may best be described as gas-vapor bubbles that can exhibit rectified transfer of both heat and noncondensable gases. Moreover, increased vapor pressures associated with ambient temperatures at or above "boiling" may not lead to unbounded bubble growth as expected for a quasistatic bubble in a superheated medium. Instead, calculations suggest that growth of boiling bubbles can be confined.

Progress in lithotripsy research

Bailey, M.R., J.A. McAteer, Y.A. Pishchalnikov, M.F. Hamilton, and T. Colonius, "Progress in lithotripsy research," Acoustics Today, 3, 18-29, doi:10.1121/1.2961131, 2006.

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1 Apr 2006

Shock wave lithotripsy (SWL) for the non-invasive treatment of kidney stones was introduced in the United States in 1984. SWL virtually eliminated the need for open surgery to remove kidney stones, and it did not take long for physicians and patients to endorse this revolutionary technology. Early reports told of the efficient removal of even the most troublesome stones without apparent complications, and SWL quickly became the "treatment modality of choice." It was not long, however, before concerned physicians began to report the occurrence of adverse effects in SWL, particularly involving vascular trauma and including cases of severe hemorrhage in the kidney and acute renal failure — significant side effects of serious consequence. Researchers quickly recognized the challenge and opportunity to determine the mechanisms of shock wave action in lithotripsy, and in 1988, the Acoustical Society of America held the first in a series of popular sessions devoted to the topic of shock waves in medicine. The goal of the inaugural session was to improve the fundamental understanding of lithotripsy — to bring better devices and treatments to patients. The goal of this paper is to report on progress in this effort.

A Method to synchronize high-intensity, focused ultrasound with an arbitrary ultrasound imager

Owen, N.R., M.R. Bailey, J. Hossack, and L.A. Crum, "A Method to synchronize high-intensity, focused ultrasound with an arbitrary ultrasound imager," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 53, 645-650, 2006.

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1 Mar 2006

Ultrasound imaging is useful for monitoring high-intensity, focused ultrasound (HIFU) therapy; however, interference on the ultrasound image, caused by HIFU excitation, must be avoided. A method to synchronize HIFU excitation with ultrasound imaging is described here. Synchronization was tested with two unmodified, commercial imagers and two tissue phantoms.

Advantage of a broad focal zone in SWL: Synergism between squeezing and shear

Bailey, M.R., A.D. Maxwell, B. MacConaghy, L.A. Crum, J.A. McAteer, R.O. Cleveland, and C.A. Sapozhnikov, "Advantage of a broad focal zone in SWL: Synergism between squeezing and shear," J. Urol., 175, 538 (Suppl. S), 2006.

1 Mar 2006

Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom

Khokhlova, V.A., M.R. Bailey, J.A. Reed, B.W. Cunitz, P.J. Kaczkowski, and L.A. Crum, "Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom," J. Acoust. Soc. Am., 119, 1834-1848, doi:10.1121/1.2161440, 2006.

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1 Mar 2006

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.

Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom

Khokhlova, V.A., M.R. Bailey, J.A. Reed, B.W. Cunitz, P.J. Kaczkowski, and L.A. Crum, "Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom," J. Acoust. Soc. Am., 119, 1834, 2006.

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1 Mar 2006

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.

Strategies for improved shock wave lithotripsy

McAteer, J.A., J.C. Williams Jr., M.R. Bailey, R.O. Cleveland, and A.P. Evan, "Strategies for improved shock wave lithotripsy," Minerva Urologica E Neffrologica, 57, 271, 2005

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1 Dec 2005

Research in lithotripsy that started with the effort to characterize acute shock wave damage to the kidney has led to advances on several fronts, including discovery of strategies that have improved clinical treatment. It is appreciated now that shock wave trauma is primarily a vascular lesion, that injury is dose dependent, and that hemorrhage can be severe and can lead to a permanent loss of functional renal mass. Studies of the renal functional response to lithotripsy have shown that shock wave treatment triggers vasoconstriction in the kidney. This finding has been turned to advantage, and it is now known that when treatment is begun using low amplitude pulses, subsequent high amplitude shock waves are far less damaging. Thus, when shock waves are delivered judiciously, treatment can have a protective effect. The finding that cavitation is a key mechanism in vessel rupture has led to the development of novel experimental methods of shock wave delivery that can suppress bubble expansion and minimize tissue damage. Progress has also been made in understanding the physical mechanisms involved in stone comminution, and it is seen that the forces generated by cavitation, shear stress and circumferential squeezing act synergistically to fragment stones.

Recent work suggests that a broad focal zone may be an advantage, allowing stones to be broken with lower amplitude pulses. Cavitation has been shown to play a critical role in reducing stone fragments to a size that can be voided. Cavitation is also the factor that limits the rate at which treatment can be performed, as stones break significantly better at slow rate than at fast ratean observation from basic research that is now appreciated in clinical practice. The current environment in lithotripsy research is encouraging. There is great interest in developing new technology, and in finding ways to improve how lithotripsy is performed.

Cavitation selectively reduces the negative-pressure phase of lithotripter shock pulses

Pishchalnikov, Y.A., O.A. Sapozhnikov, M.R. Bailey, I.V. Pishchalnikov, J.C. Williams, and J.A. McAteer, "Cavitation selectively reduces the negative-pressure phase of lithotripter shock pulses," ARLO, 6, 280-286, 2005

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3 Nov 2005

Measurements using a fiber-optic probe hydrophone, high-speed camera, and B-mode ultrasound showed attenuation of the trailing negative-pressure phase of a lithotripter shock pulse under conditions that favor generation of cavitation bubbles, such as in water with a high content of dissolved gas or at high pulse repetition rate where more cavitation nuclei persisted between pulses. This cavitation-mediated attenuation of the acoustic pulse was also observed to increase with increasing amplitude of source discharge potential, such that the negative-pressure phase of the pulse can remain fixed in amplitude even with increasing source discharge potential.

HIFU echogenicity: Is it mechanical or thermal?

Crum, L., M. Bailey, B. Rabkin, S. Vaezy, and V. Khokhlova, "HIFU echogenicity: Is it mechanical or thermal?" Proceedings, Fifth International Symposium of Therapeutic Ultrasound, Boston (American Institute of Physics, 2005)

29 Oct 2005

Cavitation detection during shock-wave lithotripsy

Bailey, M.R., Y.A. Pishchalnikov, O.A. Sapozhnikov, R.O. Cleveland, J.A. McAteer, N.A. Miller, I.V. Pishchalnikov, B.A. Connors, L.A. Crum, and A.P. Evan, "Cavitation detection during shock-wave lithotripsy," Ultrasound in Med. Biol., 31, 1245-1256, doi:10.1016/j.ultrasmedbio.2005.02.017, 2005

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19 Sep 2005

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.

Hyperechogenicity during high intensity focused ultrasound (HIFU)

Crum, L., M. Bailey, B. Rabkin, V. Khokhlova, and S. Vaezy, "Hyperechogenicity during high intensity focused ultrasound (HIFU)," J. Acoust. Soc. Am., 118, 1911, 2005

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1 Sep 2005

Ultrasound guidance of HIFU therapy is attractive because of its portability, low cost, real-time image processing, simple integration with HIFU instruments, and the extensive availability of diagnostic ultrasound; however, the use of ultrasound visualization for the guidance and monitoring of HIFU therapy often relies on the appearance of a hyperechoic region in the ultrasound image. It is often assumed that the formation of a hyperechoic region at the HIFU treatment site results from bubble activity generated during HIFU exposure. However, it has been determined that this region can be generated with relatively short bursts of HIFU (on the order of 30 ms), bursts so short that negligible temperature elevations are expected to occur. In examining the histology associated with these hyperechoes, there is little evidence of traditional cavitation damage; rather, it appears as if there are many bubbles generated within the individuals cells, suggesting a thermal mechanism. Thermocouple measurements of the temperature elevation were inaccurate due to the short insonation period, but showed only a few-degree temperature rise. These anomalous results will be presented, along with additional data on HIFU hyperechogenicity, and a hypothesis given for the phenomenological origins of this effect.

Processing ultrasound backscatter to monitor high-intensity focused ultrasound (HIFU) therapy

Kaczkowski, P.J., A. Anand, and M.R. Bailey, "Processing ultrasound backscatter to monitor high-intensity focused ultrasound (HIFU) therapy," J. Acoust. Soc. Am., 118, 1876, 2005

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1 Sep 2005

The development of new noninvasive surgical methods such as HIFU for the treatment of cancer and internal bleeding requires simultaneous development of new sensing approaches to guide, monitor, and assess the therapy. Ultrasound imaging using echo amplitude has long been used to map tissue morphology for diagnostic interpretation by the clinician. New quantitative ultrasonic methods that rely on amplitude and phase processing for tissue characterization are being developed for monitoring of ablative therapy. We have been developing the use of full wave ultrasound backscattering for real-time temperature estimation, and to image changes in tissue backscatter spectrum as therapy progresses. Both approaches rely on differential processing of the backscatter signal in time, and precise measurement of phase differences. Noise and artifacts from motion and nonstationary speckle statistics are addressed by constraining inversions for tissue parameters with physical models. We present results of HIFU experiments with static point and scanned HIFU exposures in which temperature rise can be accurately mapped using a new heat transfer equation (HTE) model-constrained inverse approach. We also present results of a recently developed spectral imaging method that elucidates microbubble-mediated nonlinearity not visible as a change in backscatter amplitude.

Ultracal-30 gypsum artificial stones for research on the mechanisms of stone breakage in shock wave lithotripsy

McAteer, J.A., J.C. Williams, R.O. Cleveland, J. Van Cauwelaert, M.R. Bailey, D.A. Lifshitz, and A.P. Evan, "Ultracal-30 gypsum artificial stones for research on the mechanisms of stone breakage in shock wave lithotripsy," Urolog. Res., 33, 429-434, DOI: 10.1007/s00240-005-0503-5, 2005

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31 Aug 2005

Artificial stones are used in research on the mechanisms of stone breakage in shock wave lithotripsy (SWL) and in assessing lithotripter performance. We have adopted Ultracal-30 gypsum as a model, finding it suitable for SWL studies in vitro, acute animal experiments in which stones are implanted in the kidney, and as a target to compare the in vitro performance of intracorporeal lithotripters. Here we describe the preparation of U-30 stones, their material properties, shock wave (SW) breakage characteristics, and methods used for quantitation of stone fragmentation with this model. Ultracal-30 gypsum cement was mixed 1:1 with water, cast in plastic multi-well plates, then, the stones were liberated by dissolving the plastic with chloroform and stored under water. Stone breakage in SWL was assessed by several methods including measures of the increase in projected surface area of SW-treated stones. Breakage of hydrated stones showed a linear increase in fragment area with increased SW-number and SW-voltage. Stones stored in water for an extended time showed reduced fragility. Dried stones could be rehydrated so that breakage was not different from stones that had never been dry, but stones rehydrated for less than 96 h showed increased fragility to SWs. The physical properties of U-30 stones place them in the range reported for natural stones. U-30 stones in vitro and in vivo showed equivalent response to SW-rate, with ~200% greater fragmentation at 30 SW/min compared to 120 SW/min, suggesting that the mechanisms of SW action are similar under both conditions. U-30 stones provide a convenient, reproducible model for SWL research.

A suppressor to prevent direct wave-induced cavitation in shock wave therapy devices

Matula, T.J., P.R. Hilmo, and M.R. Bailey, "A suppressor to prevent direct wave-induced cavitation in shock wave therapy devices," J. Acoust. Soc. Am., 118, 178, 2005.

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1 Jul 2005

Cavitation plays a varied but important role in lithotripsy. Cavitation facilitates stone comminution, but can also form an acoustic barrier that may shield stones from subsequent shock waves. In addition, cavitation damages tissue. Spark-gap lithotripters generate cavitation with both a direct and a focused wave. The direct wave propagates as a spherically diverging wave, arriving at the focus ahead of the focused shock wave. It can be modeled with the same waveform (but lower amplitude) as the focused wave. We show with both simulations and experiments that bubbles are forced to grow in response to the direct wave, and that these bubbles can still be large when the focused shock wave arrives. A baffle or "suppressor" that blocks the propagation of the direct wave is shown to significantly reduce the direct wave pressure amplitude, as well as direct wave-induced bubble growth. These results are applicable to spark-gap lithotripters and extracorporeal shock wave therapy devices, where cavitation from the direct wave may interfere with treatment. A simple direct-wave suppressor might therefore be used to improve the therapeutic efficacy of these devices.

Monitoring bubble growth in supersaturated blood and tissue ex vivo and the relevance to marine mammal bioeffects

Crum, L.A., M.R. Bailey, J.F. Guan, P.R. Hilmo, S.G. Kargl, T.J. Matula, and O.A. Sapozhnikov, "Monitoring bubble growth in supersaturated blood and tissue ex vivo and the relevance to marine mammal bioeffects," ARLO, 6, 214-220, 2005

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24 Jun 2005

There have been several recent reports that active sonar systems can lead to serious bioeffects in marine mammals, particularly beaked whales, resulting in strandings, and in some cases, to their deaths. We have devised a series of experiments to determine the potential role of low-frequency acoustic sources as a means to induce bubble nucleation and growth in supersaturated ex vivo bovine liver and kidney tissues, and blood. Bubble detection was achieved with a diagnostic ultrasound scanner. Under the conditions of this experiment, supersaturated tissues and blood led to extensive bubble production when exposed to short pulses of low frequency sound.

Modeling of bubble oscillation induced by a lithotripter pulse

Kreider, W., M.R. Bailey, and L.A. Crum, "Modeling of bubble oscillation induced by a lithotripter pulse," Proceedings, 17th International Symposium on Nonlinear Acoustics, College Station, PA, 315-318 (American Institute of Physics, 2005)

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30 May 2005

In therapeutic applications of biomedical ultrasound, it is important to understand the behavior of cavitation bubbles. Herein, the dynamics of a single, spherical bubble in water are modeled using the Gilmore equation closed by an energy balance on bubble contents for calculation of pressures inside the bubble. Moreover, heat and mass transfer at the bubble wall are incorporated using the Eller–Flynn zeroth-order approximation for gas diffusion, an estimation of non-equilibrium phase change based on the kinetic theory of gases, and assumed shapes for the spatial temperature distribution in the surrounding liquid. Bubble oscillations predicted by this model are investigated in response to a lithotripter shock wave. Model results indicate that vapor trapped inside the bubble during collapse plays a significant role in the afterbounce behavior and is sensitively dependent upon the ambient liquid temperature. Initial experiments have been conducted to quantify the afterbounce behavior of a single bubble as a function of ambient temperature; however, the results imply that many bubbles are present and collectively determine the collapse characteristics.

Measurement and modeling of acoustic fields in a gel phantom at high intensities

Canney, M.S., M.R. Bailey, V.A. Khokhlova, and L.A. Crum, "Measurement and modeling of acoustic fields in a gel phantom at high intensities," Proceedings, International Symposium of Therapeutic Ultrasound, Boston, 107-111, doi:10.1063/1.2205447 (AIP, 2005)

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8 May 2005

The goal of this work was to compare measured and numerically predicted HIFU pressure waveforms in water and a tissue-mimicking phantom. Waveforms were measured at the focus of a 2-MHz HIFU transducer with a fiber optic hydrophone. The transducer was operated with acoustic powers ranging from 2W to 300W. A KZK-type equation was used for modeling the experimental conditions. Strongly asymmetric nonlinear waves with peak positive pressure up to 80 MPa and peak negative pressure up to 20 MPa were measured in water, while waves up to 50 MPa peak positive pressure and 15 MPa peak negative pressure were measured in tissue phantoms. The values of peak negative pressure corresponded well with numerical simulations and were significantly smaller than predicted by linear extrapolation from low-level measurements. The values of peak positive pressures differed only at high levels of excitation where bandwidth limitations of the hydrophone failed to fully capture the predicted sharp shock fronts.

A mechanistic analysis of stone comminution in lithotripsy

Maxwell, A.D., O.A. Sapozhnikov, M.R. Bailey, B. MacConaghy, and L.A. Crum, "A mechanistic analysis of stone comminution in lithotripsy," J. Acoust. Soc. Am., 117, 2385, 2005

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2 Apr 2005

In vitro experiments and an elastic wave model were employed to isolate and assess the importance of individual mechanisms in stone comminution in lithotripsy. Cylindrical U-30 cement stones were treated in an HM-3-style research lithotripter. Baffles were used to block specific waves responsible for spallation, squeezing, or shear. Surface cracks were added to stones to simulate the effect of cavitation, then tested in water and glycerol (a cavitation suppressive medium). Each case was simulated using the elasticity equations for an isotropic medium. The calculated location of maximum stress compared well with the experimental observations of where cracks naturally formed. Shear waves from the shock wave in the fluid traveling along the stone surface (a kind of dynamic squeezing) led to the largest stresses in the cylindrical stones and the fewest SWs to fracture. Reflection of the longitudinal wave from the back of the stone — spallation — and bubble-jet impact on the proximal and distal faces of the stone produced lower stresses and required more SWs to break stones. Surface cracks accelerated fragmentation when created near the location where the maximum stress was predicted.

Detecting cavitation in vivo from shock-wave therapy devices

Matula, T.J., J. Yu, and M.R. Bailey, "Detecting cavitation in vivo from shock-wave therapy devices," J. Acoust. Soc. Am., 117, 2371, 2005

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2 Apr 2005

Extracorporeal shock-wave therapy (ESWT) has been used as a treatment for plantar faciitis, lateral epicondylitis, shoulder tendonitis, non-unions, and other indications where conservative treatments have been unsuccessful. However, in many areas, the efficacy of SW treatment has not been well established, and the mechanism of action, particularly the role of cavitation, is not well understood. Research indicates cavitation plays an important role in other ultrasound therapies, such as lithotripsy and focused ultrasound surgery, and in some instances, cavitation has been used as a means to monitor or detect a biological effect. Although ESWT can generate cavitation easily in vitro, it is unknown whether or not cavitation is a significant factor in vivo. The purpose of this investigation is to use diagnostic ultrasound to detect and monitor cavitation generated by ESWT devices in vivo. Diagnostic images are collected at various times during and after treatment. The images are then post-processed with image-processing algorithms to enhance the contrast between bubbles and surrounding tissue. The ultimate goal of this research is to utilize cavitation as a means for optimizing shock wave parameters such as amplitude and pulse repetition frequency.

Modeling of initial bubble growth rates during high-intensity focused ultrasound

Kreider, W., M.R. Bailey, and L.A. Crum, "Modeling of initial bubble growth rates during high-intensity focused ultrasound," J. Acoust. Soc. Am., 117, 2474, 2005

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2 Apr 2005

In therapeutic applications of biomedical ultrasound, it is important to understand the behavior of cavitation bubbles. For applications that use high-intensity focused ultrasound (HIFU), both large negative acoustic pressures and heating can independently lead to bubble formation. Although neglected previously, heating during HIFU is expected to affect the growth and dissolution of bubbles by both raising the vapor pressure and promoting outgassing from gas-saturated tissues. Herein, the dynamics of a single, spherical bubble in water have been modeled using the Gilmore equation closed with an energy balance on bubble contents for calculation of pressures inside the bubble. Moreover, heat and mass transfer at the bubble wall are incorporated using the Eller–Flynn zeroth-order approximation for gas diffusion, an estimation of non-equilibrium phase change based on the kinetic theory of gases, and assumed shapes for the spatial temperature distribution in the surrounding liquid [Yasui, J. Phys. Soc. Jpn. 65, 2830-2840 (1996)]. This model allows explicit coupling of the ambient heating during HIFU to the thermodynamic state of an oscillating bubble and is currently being used to explore the growth rates of initially small, undetectable bubbles exposed to various HIFU treatment protocols.

Nonlinear enhancement and saturation phenomena in focused ultrasound beams of various geometry

Khokhlova, V.A., M.S. Basova, M.R. Bailey, and L.A. Crum, "Nonlinear enhancement and saturation phenomena in focused ultrasound beams of various geometry," J. Acoust. Soc. Am., 117, 2595, 2005

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2 Apr 2005

The effects of nonlinear enhancement of focusing gain and saturation are studied and compared for high-intensity focused ultrasound sources with an initial Gaussian shading and uniform amplitude distribution. Simulations are performed using the Khokhlov Zabolotskaya (KZ) nonlinear parabolic equation for weakly dissipative medium in a wide range of source linear focusing gains and source pressure amplitudes, including the strongly nonlinear regime with shocks. An artificial absorption proportional to the fourth power of frequency or an asymptotic frequency-domain approach is employed in the algorithm in order to reduce the number of harmonics for accurate modeling of strongly distorted waveforms with shocks. The effect of focusing gain and amplitude shading of the source on nonlinear enhancement of acoustic energy concentration and saturation levels at the focus is discussed. It is shown that nonlinear enhancement of focusing gain is different for different values of linear gain, different spatial distributions of the source amplitude, and different parameters of acoustic field. The levels of nonlinear saturation at the focus are obtained for very high source amplitudes. The results of simulations give lower enhancement and higher saturation levels compared to the known approximate analytic predictions.

Characterization of a vibro-acoustography system designed to detect kidney stones during lithotripsy

Owen, N.R., M.R. Bailey, and L.A. Crum, "Characterization of a vibro-acoustography system designed to detect kidney stones during lithotripsy," J. Acoust. Soc. Am., 117, 2588, 2005.

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1 Apr 2005

Acoustic properties of a vibro-acoustography system designed to detect kidney stones were measured. Our system was formed with two spherical transducers (10 cm diameter, 20 cm curvature) in degassed water that were confocal and separated by an angle of 30 degrees. They were driven at 1.1 MHz and 1.125 MHz to generate a difference frequency of 25 kHz. The acoustic field was characterized by scattering from a known target, the curved surface of a steel cylinder with 6.4 mm diameter. Waveforms of both the low and high frequency scattered signals were measured for different target locations, different hydrophone locations encircling the target, and different acoustic pressures. Focal dimensions of the –6 db pressure profile measured at 25 kHz and the fundamental were both 3 x 10 mm, in an elliptical shape, which is highly localized. Scatter amplitude was rather insensitive to hydrophone position when the target was in the focus, quite sensitive to hydrophone position when the target was out of the focus, and increased linearly with the sum of the sources. It is hoped that this characterization will help improve the understanding of the mechanisms of the targeting technique.

Observation of cavitation during shock wave lithotripsy

Bailey, M.R., L.A. Crum, Y.A. Pishchalnikov, J.A. McAteer, I.V. Pishchalnikova, A.P. Evan, O.A. Sapozhnikov, and R.O. Cleveland, "Observation of cavitation during shock wave lithotripsy," J. Acoust. Soc. Am., 117, 2371, 2005.

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1 Apr 2005

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 (PCD), using coincident signals on confocal, orthogonal receivers, were equally sensitive and were used to interrogate the renal collecting system (urine) and the kidney parenchyma (tissue). Cavitation was detected in urine immediately upon SW administration in urine or urine plus X-ray contrast agent, but in tissue, cavitation required hundreds of SWs to initiate. Localization of cavitation was confirmed by fluoroscopy, sonography, and by thermally marking the kidney using the PCD 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. Cavitation, especially in the urine space, was observed to evolve from a sparse field to a dense field with strong acoustic collapse emissions to a very dense field that no longer produced detectable collapse. The finding that cavitation occurs in kidney tissue is a critical step toward determining the mechanisms of tissue injury in SWL.

Acoustic nonlinearity in the derating problem for HIFU sources

Khokhlova, V.A., M.R. Bailey, and L.A. Crum, "Acoustic nonlinearity in the derating problem for HIFU sources," Proceedings, Fourth International Symposium on Therapeutic Ultrasound, 18-20 September, Kyoto, Japan, 164-166, doi:10.1063/1.1901619 (Springer, 2005).

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28 Mar 2005

Numerical simulations of focused acoustic beams are performed in water over a wide range of linear gains and source amplitudes, in order to demonstrate the combined effect of acoustic nonlinearity, diffraction, and focusing on extrapolation (derating) of the main parameters of high intensity acoustic fields at the focus from the linear theory. It is shown that nonlinear corrections to the focusing gain are different for different parameters of the acoustic field and for different values of the linear gain. Nonlinear enhancement of the focusing gain is found to be more pronounced for the peak positive pressure and for higher linear gains. The levels of nonlinear saturation for various parameters of the field at the focus are obtained for very high source amplitudes. The results of simulations give higher saturation levels compared to the approximate analytic predictions.

Assessing the mechanism of kidney stone comminution by a lithotripter shock pulse

Sapozhnikov, O.A., M.R. Bailey, A.D. Maxwell, B. MacConaghy, R.O. Cleveland, and L.A. Crum, "Assessing the mechanism of kidney stone comminution by a lithotripter shock pulse," Proceedings, American Institute of Physics Conference, number 754, 164-166, doi:10.1063/1.1901627, (2005).

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28 Mar 2005

Comminution of axisymmetric stones by a lithotripter shock wave was studied experimentally and theoretically. In experiments, shock waves were generated by a research electrohydraulic lithotripter modeled after the Dornier HM-3, and stones were made from U-30 cement. Cylindrical stones of various length to diameter ratios, stones of conical shape, and stones with artificial cracks were studied. In other cases, baffles to block specific waves that contribute to spallation or squeezing were used, and glycerol was used to suppress cavitation. The theory was based on the elasticity equations for an isotropic medium. The equations were written in finite differences and integrated numerically. Maximum compression, tensile and shear stresses were predicted depending on the stone shape and side-surface condition in order to investigate the importance of the stone geometry. It is shown that the theoretical model used explains the observed position of a crack in a stone. The theory also predicts the efficiency of stone fragmentation depending on its shape and size, as well as on the presence of cracks on the stone surface and baffles near the stone.

Shock wave physics of lithotripsy: Mechanisms of shock wave action and progress toward improved SWL

Evan, A.P., J.A McAteer, J.C. Williams, L.R. Willis, M.R. Bailey, L.A. Crum, J.E. Lingeman, and R.O. Cleveland, "Shock wave physics of lithotripsy: Mechanisms of shock wave action and progress toward improved SWL," in Textbook of Minimally Invasive Urology, edited by R. Moore, J.T. Bishoff, S. Loening, and S.G. Docimo, 425-438 (London, Martin Dunitz Limited, 2004).

15 Dec 2004

A portable ultrasound-guided high intensity focused ultrasound therapy system for hemostasis and tissue necrosis

Owen, N.R., M.R. Bailey, S.J. Carter, and L.A. Crum, "A portable ultrasound-guided high intensity focused ultrasound therapy system for hemostasis and tissue necrosis," Proceedings of the 55th International Astronautical Congress, 4-8 October, Vancouver, British Columbia (International Astronautical Federation, 2004).

4 Oct 2004

Image-guided high intensity focused ultrasound for mission critical care

Crum, L.A., and M.R. Bailey, "Image-guided high intensity focused ultrasound for mission critical care," Proceedings, 55th International Astronautical Congress, 4-8 October, Vancouver, British Columbia (International Astronautical Federation, 2004).

4 Oct 2004

Cavitation detection and suppression in HIFU

Bailey, M.R., J. Reed, A. Anand, P. Kaczkowski, W. Kreider, S. Vaezy, L.A. Crum, R. Seip, J. Tavakkoli, and N.T. Sanghvi, "Cavitation detection and suppression in HIFU," Proceedings of the 3rd International Symposium on Therapeutic Ultrasound, edited by J.Y. Chapelon and C. Lafon, 42-48 (Lyon, France, INSERM, 2004).

15 Sep 2004

Modeling of stresses generated by lithotripter shock wave in cylindrical kidney stone

Sapozhnikov, O.A., R.O. Cleveland, M.R. Bailey, and L.A. Crum, "Modeling of stresses generated by lithotripter shock wave in cylindrical kidney stone," Proceedings of the 3rd International Symposium on Therapeutic Ultrasound, edited by J.Y. Chapelon and C. Lafon, 323-328 (Lyon, France, INSERM, 2004).

15 Sep 2004

Nonlinear effects in HIFU lesion production in tissue-mimicking phantom

Khokhlova, V., P.J. Kaczkowski, B.W. Cunitz, M.R. Bailey, J.A. Reed, M. Nakazawa, and L.A. Crum, "Nonlinear effects in HIFU lesion production in tissue-mimicking phantom," Proceedings of the 3rd International Symposium on Therapeutic Ultrasound, edited by J.Y. Chapelon and C. Lafon, 275-280 (Lyon, France, INSERM, 2004).

15 Sep 2004

The relation between cavitation and platelet aggregation during exposure to high-intensity focused ultrasound

Poliachik, S.L., W.L. Chandler, R.J. Ollos, M.R. Bailey, and L.A. Crum, "The relation between cavitation and platelet aggregation during exposure to high-intensity focused ultrasound," Ultrasound Med. Biol., 30, 261-269, 2004.

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1 Feb 2004

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.

Cavitation in shock wave lithotripsy: the critical role of bubble activity in stone breakage and kidney trauma

Bailey, M.R., R.O. Cleveland, T. Colonius, L.A. Crum, A.P. Evan, J.E. Lingeman, J.A. McAteer, O.A. Sapozhnikov, and J.C. Williams, "Cavitation in shock wave lithotripsy: the critical role of bubble activity in stone breakage and kidney trauma," Ultrason. Symp. Proc., 1, 724-727, 10.1109/ULTSYM.2003.1293503, 2003.

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8 Oct 2003

Shock wave lithotripsy (SWL) is the use of shock waves to fragment kidney stones. We have undertaken a study of the physical mechanisms responsible for stone comminution and tissue injury in SWL. SWL was originally developed on the premise that stone fragmentation could be induced by a short duration, high amplitude positive pressure pulse. Even though the SWL waveform carries a prominent tensile component, it has long been thought that SW damage to stones could be explained entirely on the basis of mechanisms such as spallation, pressure gradients, and compressive fracture. We contend that not only is cavitation also involved in SWL, bubble activity plays a critical role in stone breakage and is a key mechanism in tissue damage.

Our evidence is based upon a series of experiments in which we have suppressed or minimized cavitation, and discovered that both stone comminution and tissue injury is similarly suppressed or minimized. Some examples of these experiments are: (1) application of overpressure, (2) time reversal of acoustic waveform, (3) acoustically-transparent, cavitation-absorbing films, and (4) dual pulses. In addition, using passive and active ultrasound, we have observed the existence of cavitation, in vivo, and at the site of tissue injury.

Numerical and experimental results showed mitigation of bubble collapse intensity by time-reversing the lithotripsy pulse and in vivo treatment showed a corresponding drop from 6.1% ± 1.7% to 0.0% in the hemorrhagic lesion. The time-reversed wave did not break stones. Stone comminution and hemolysis were reduced to levels very near sham levels with the application of hydrostatic pressure greater than the near 10-MPa amplitude of the negative pressure of the lithotripter shock wave. A Mylar sheet 3-mm from the stone surface did not inhibit erosion and internal cracking, but a sheet in contact with the stone did. In water, mass lost from stones in a dual pulse lithotripter is 8 times greater than with a single lithotripter, but in glycerol, which reduces the pressures generated in bubble implosion, the enhancement is lost.

This cavitation-inclusive mechanistic understanding of SWL is gaining acceptance and has had clinical impact. Treatment at slower SW rate give- s cavitation bubble clusters time to dissolve between pulses and increases comminution. Some SWL centers now treat patients at slower SW rate to take advantage of this effect. An elegant cavitation-aware strategy to reduce renal trauma in SWL is being tested in experimental animals. Starting treatment at low amplitude causes vessels to constrict and this interferes with cavitation-mediated vascular injury. Acceptance of the role of cavitation in SWL is beginning to be embraced by the lithotripter industry, as new dual-pulse lithotripters—based on the concept of cavitation control—have now been introduced.

Separating nonlinear propagation and cavitation effects in HIFU

Reed, J.A., M.R. Bailey, M. Nakazawa, L.A. Crum, and V.A. Khokhlova, "Separating nonlinear propagation and cavitation effects in HIFU," Ultrason. Symp. Proc., 1, 728-731, DOI: 10.1109/ULTSYM.2003.1293504, 2003.

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8 Oct 2003

High intensity focused ultrasound (HIFU) can destroy tumors or stop internal bleeding. The primary physical mechanism in HIFU is the conversion of acoustic energy to heat, which as HIFU amplitude increases is enhanced by nonlinear acoustic propagation and nonlinear scattering from bubbles. The goal of this work is to study and separate the effects of nonlinear propagation and cavitation during HIFU heating of tissue. Transparent polyacrylamide gel was used as a tissue-mimicking phantom to visualize HIFU lesion growth. Lesion size was also measured in excised turkey breast. Lesions were produced by the same time-averaged intensity, but with different peak acoustic pressure amplitudes compensated by different duty cycles. In order to separate cavitation and nonlinear wave effects, experiments were performed under static pressure (10.34MPa) greater than the peak negative pressure amplitude of the sound waves (8.96MPa). Suppression of cavitation by overpressure was measured by reduced acoustic scattering and transmission loss in the treatment region. We found that, with the same time-averaged intensity, a shorter, higher amplitude wave created a larger lesion than a longer, lower amplitude wave with or without overpressure.

Acoustic hemostasis

Crum, L., M. Andrew, M. Bailey, K. Beach, A. Brayman, F. Curra, P. Kaczkowski, S. Kargl, R. Martin, and S. Vaezy, "Acoustic hemostasis," J. Acoust. Soc. Am., 113, 2280, 2003.

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1 Oct 2003

Over the past several years, the Center for Industrial and Medical Ultrasound (CIMU) at the Applied Physics Laboratory in the University of Washington has undertaken a broad research program in the general area of High Intensity Focused Ultrasound (HIFU). Our principal emphasis has been on the use of HIFU to induce hemostasis; in particular, CIMU has sought to develop a small, lightweight, portable device that would use ultrasound for both imaging and therapy. Such a technology is needed because nearly 50% of combat casualty mortality results from exsanguinations, or uncontrolled bleeding. A similar percentage occurs for civilian death due to trauma. In this general review, a presentation of the general problem will be given, as well as our recent approaches to the development of an image-guided, transcutaneous, acoustic hemostasis device.

Cavitation bubble cluster activity in the breakage of kidney stones by lithotripter shockwaves

Pishchalnikov, Y.A., O.A. Sapozhnikov, M.R. Bailey, J.C. Williams, R.O. Cleveland, T. Colonius, L.A. Crum, A.P. Evan, and J.A. McAteer, "Cavitation bubble cluster activity in the breakage of kidney stones by lithotripter shockwaves," J. Endourology, 17 (7), 435-446, doi: 10.1089/089277903769013568, 2003.

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1 Sep 2003

High-speed photography was used to analyze cavitation bubble activity at the surface of artificial and natural kidney stones during exposure to lithotripter shock waves in vitro. Numerous individual bubbles formed at the surface of stones, but these bubbles did not remain independent and combined with one another to form bubble clusters. Bubble clusters formed at the proximal end, the distal end, and at the sides of stones. Each cluster collapsed to a narrow point of impact. Collapse of the proximal cluster caused erosion at the leading face of the stone and the collapse of clusters at the sides of stones appeared to contribute to the growth of cracks. Collapse of the distal cluster caused minimal damage. We conclude that cavitation-mediated damage to stones was due not to the action of solitary bubbles, but to the growth and collapse of bubble clusters.

Tissue ablation using high-intensity focused ultrasound in the fetal sheep model: Potential for fetal treatment

Paek, B.W., S. Vaezy, V. Fujimoto, M.R. Bailey, C.T. Albanese, M.R. Harrison, D.L. Farmer, "Tissue ablation using high-intensity focused ultrasound in the fetal sheep model: Potential for fetal treatment," Am. J. Obstet. Gynecol., 189, 702-705, doi:10.1067/S0002-9378(03)00664-1, 2003.

1 Sep 2003

Dual-pulse lithotripter accelerates stone fragmentation and reduces cell lysis in vitro

Sokolov, D.L., M.R. Bailey, and L.A. Crum, "Dual-pulse lithotripter accelerates stone fragmentation and reduces cell lysis in vitro," Ultrasound Med. Biol., 29 (7), 1045-1052, doi:10.1016/S0301-5629(03)00887-1, 2003.

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17 Jul 2003

Lithotripsy is a common effective treatment for kidney stones. However, focal volumes are often larger than stones, and surrounding tissue is often injured. Our goal was to test in vitro a new lithotripter consisting of two opposing, confocal and simultaneously triggered electrohydraulic sources. The pulses superimpose at the common focus, resulting in pressure doubling and enhanced cavitation growth in a localized, ~ 1-cm wide volume. Model gypsum stones and human erythrocytes were exposed to dual pulses or single pulses. At the focus, model stones treated with 100 dual pulses at a charging voltage of 15 kV broke into 8 times the number of fragments as stones treated with 200 single pulses at 18 kV. At axial positions 2 and 4 cm away from the focus, lysis of erythrocytes was reduced or equivalent for dual pulses vs. single pulses. Hence, in half the time, dual pulses increased comminution at the focus without increasing injury in surrounding regions.

Mechanisms of cell and tissue damage in shock wave lithotripsy

McAteer, J.A., J.C. Williams, A.P. Evan, L.R.Willis, M.R. Bailey, R.O. Cleveland, and L.A. Crum, "Mechanisms of cell and tissue damage in shock wave lithotripsy," in Therapeutic Ultrasound, Proceedings of the 2nd International symposium, M.A. Andrew, L.A. Crum, and S. Vaezy, eds., 491-500 (American Institute of Physics Press, 2003).

1 Jun 2003

Physical mechanisms of the therapeutic effect of ultrasound

Bailey, M.R., V.A. Khokhlova, O.A. Sapozhnikov, S.G. Kargl, and L.A. Crum, "Physical mechanisms of the therapeutic effect of ultrasound," Acoust. Phys., 49, 369-388, DOI: 10.1134/1.1591291, 2003

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30 Jan 2003

Therapeutic ultrasound is an emerging field with many medical applications. High intensity focused ultrasound (HIFU) provides the ability to localize the deposition of acoustic energy within the body, which can cause tissue necrosis and hemostasis. Similarly, shock waves from a lithotripter penetrate the body to comminute kidney stones, and transcutaneous ultrasound enhances the transport of chemotherapy agents. New medical applications have required advances in transducer design and advances in numerical and experimental studies of the interaction of sound with biological tissues and fluids. The primary physical mechanism in HIFU is the conversion of acoustic energy into heat, which is often enhanced by nonlinear acoustic propagation and nonlinear scattering from bubbles. Other mechanical effects from ultrasound appear to stimulate an immune response, and bubble dynamics play an important role in lithotripsy and ultrasound-enhanced drug delivery. A dramatic shift to understand and exploit these nonlinear and mechanical mechanisms has occurred over the last few years. Specific challenges remain, such as treatment protocol planning and real-time treatment monitoring. An improved understanding of the physical mechanisms is essential to meet these challenges and to further advance therapeutic ultrasound.

A gypsum-based artificial stone for shock wave lithotripsy research

McAteer, J.A., J.C. Williams, Jr., A.P. Evan, R.O. Cleveland, M.R. Bailey, and L.A. Crum, "A gypsum-based artificial stone for shock wave lithotripsy research," J. Acoust. Soc. Am., 112, 2315, 2002.

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1 Oct 2002

Natural kidney stones are heterogeneous in structure, composition, material properties and fragility, and as such are problematic for use in determining the mechanisms of SW-action in SWL. A variety of model stones have been developed. We have adopted Ultracal-30 gypsum [Dahake and Gracewski, J. Acoust. Soc. Am. 102, 2138 (1997)] for in vitro and in vivo studies. U-30 stones (7.5x6.5 mm) cast in polystyrene molds were liberated with chloroform and stored in water. Drop-impact testing of dry stones showed a linear relationship between increase in surface area of fragments and energy applied. Breakage of hydrated stones in a research-electrohydraulic lithotripter, likewise showed a linear increase in fragment area with increased SW number and SW voltage. The density (1800 kg/m3) and transverse (1520 m/s) and longitudinal (3100 m/s) wave speeds of U-30 stones place them in the range determined for natural stones. U-30 stones implanted in pig kidneys exhibited cavitation erosion and spall fracture similar to stones in vitro, and U-30 stones in vitro and in vivo showed equivalent response to SW rate (200% higher fragmentation at 0.5 Hz compared to 2 Hz). U-30 stones softened with prolonged exposure to water and degraded during long-term implantation in vivo. With these caveats U-30 stones provide a useful model for SWL research.

Cavitation bubble cluster activity in the breakage of stones by shock wave lithotripsy

Pishchalnikov, Y.A., O.A. Sapozhnikov, J.C. Williams, Jr., A.P. Evan, J.A. McAteer, R.O. Cleveland, T. Colonius, M.R. Bailey, and L.A. Crum, "Cavitation bubble cluster activity in the breakage of stones by shock wave lithotripsy," J. Acoust. Soc. Am., 111, 2461, 2002.

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1 Oct 2002

High-speed photography was used to investigate cavitation at the surface of artificial and natural kidney stones during exposure to lithotripter shock pulses in vitro. It was observed that numerous individual bubbles formed over virtually the entire surface of the stone, but these bubbles did not remain independent and combined with one another to form larger bubbles and bubble clusters. The movement of bubble boundaries across the surface left portions of the stone bubble free. The biggest cluster grew to envelop the proximal end of the stone (6.5 mm diameter artificial stone) then collapsed to a small spot that over multiple shots formed a crater in that face of the stone. The bubble clusters that developed at the sides of stones tended to align along fractures and to collapse into these cracks. High-speed camera images demonstrated that cavitation mediated damage to stones was due not to the action of solitary, individual bubbles, but to the forceful collapse of dynamic clusters of bubbles.

Dual-pulse lithotripter accelerates stone comminution and reduces cell injury in vitro

Sokolov, D.L., M.R. Bailey, and L.A. Crum, "Dual-pulse lithotripter accelerates stone comminution and reduces cell injury in vitro," J. Acoust. Soc. Am., 112, 2290, 2002.

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1 Oct 2002

Peak acoustic pressures and cavitation generated in shock wave lithotripsy (SWL) appear to contribute to both desired stone comminution and undesired injury to surrounding renal tissue. Our dual pulse system, comprised of two opposing, confocal lithotripters and generating simultaneous, converging shock pulses, localizes and intensifies the peak pressures and cavitation. Comparison of cavitation damage to aluminum foil shows an 8-cm stripe of pits produced by a single pulse lithotripter and a 1-cm stripe of deep pits produced by the dual pulse lithotripter. 100 dual pulses generated at 15 kV comminuted gypsum stones placed at the geometric focus F2 into 8 times as many fragments and significantly reduced hemolysis in dilute blood 2 and 4 cm off F2 when compared to 200 single pulses generated at 18 kV. Thus the dual pulse lithotripter enhanced comminution and reduced injury while cutting treatment time in half. Additionally, when cavitation was suppressed by placing the stones in glycerol, the improvement in comminution was reduced to only a twofold increase. This result indicates that the localized and intensified cavitation is the dominant mechanism in the accelerated comminution produced by the dual pulse lithotripter.

Effect of overpressure and pulse repetition frequency on cavitation in shock wave lithotripsy

Sapozhnikov, O.A., V.A. Khokhlova, M.R. Bailey, J.C. Williams Jr., M.A. McAteer, R.O. Cleveland, and L.A. Crum, "Effect of overpressure and pulse repetition frequency on cavitation in shock wave lithotripsy," J. Acoust. Soc. Am., 112, 1183-1195, doi:10.1121/1.1500754, 2002.

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1 Oct 2002

Cavitation appears to contribute to tissue injury in lithotripsy. Reports have shown that increasing pulse repetition frequency [(PRF) 0.5–100 Hz] increases tissue damage and increasing static pressure (1–3 bar) reduces cell damage without decreasing stone comminution. Our hypothesis is that overpressure or slow PRF causes unstabilized bubbles produced by one shock pulse to dissolve before they nucleate cavitation by subsequent shock pulses. The effects of PRF and overpressure on bubble dynamics and lifetimes were studied experimentally with passive cavitation detection, high-speed photography, and B-mode ultrasound and theoretically. Overpressure significantly reduced calculated (100–2 s) and measured (55–0.5 s) bubble lifetimes. At 1.5 bar static pressure, a dense bubble cluster was measured with clinically high PRF (2–3 Hz) and a sparse cluster with clinically low PRF (0.5–1 Hz), indicating bubble lifetimes of 0.5–1 s, consistent with calculations. In contrast to cavitation in water, high-speed photography showed that overpressure did not suppress cavitation of bubbles stabilized on a cracked surface. These results suggest that a judicious use of overpressure and PRF in lithotripsy could reduce cavitation damage of tissue while maintaining cavitation comminution of stones.

Kidney damage and renal functional changes are minimized by waveform control that suppresses cavitation in shock wave lithotripsy

Evan, A.P., L.R. Willis, J.A. McAteer, M.R. Bailey, B.A. Connors, Y. Shao, J.E. Lingeman, J.C. Williams Jr., N.S. Fineberg, and L.A. Crum, "Kidney damage and renal functional changes are minimized by waveform control that suppresses cavitation in shock wave lithotripsy," J. Urol., 168(4 Pt. 1), 1556-1562, 2002.

1 Oct 2002

Role of cavitation in stone fragmentation by shock wave lithotripsy

McAteer, J.A., J.C. Williams, Jr., A.P. Evan, R.O. Cleveland, M.R. Bailey, and L.A. Crum, "Role of cavitation in stone fragmentation by shock wave lithotripsy," J. Acoust. Soc. Am., 112, 2316, 2002.

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1 Oct 2002

Several strategies were used to assess the importance of cavitation in the breakage of stones by an electrohydraulic lithotripter in vitro. (1) Stones exposed to SWs at atmospheric pressure broke readily. However, stones treated at high overpressure (OP~125%u2009atm) sufficient to eliminate cavitation did not break into fragments even with twice the number of SWs. Stones at OP did, however, develop transverse fractures typical of spall. This suggests that cavitation contributes to stone fragmentation, but is clearly not the only mechanism involved in stone breakage. (2) Cylindrical model stones positioned vertically in the acoustic field of a research%u2010EHL showed proximal erosion and spall. However, placement of a mylar disk against the flat leading face of the stone eliminated cavitation%u2010erosion, and spall did not occur. This suggests that cavitation may contribute to stone fracture by spall. (3) Time reversal of the lithotripter wave form using a pressure release reflector (Prel) also prevented stone fragmentation. With the Prel insert the tensile phase of the SW preceding the compressive wave bubble growth is interrupted by P and, thus, cavitation is suppressed. Together, these results suggest that cavitation plays an important role in the breakage of stones by lithotripter shock waves.

Ultrasound detection and computer segmentation of high intensity focused ultrasound (HIFU) lesions

Owen, N.R., M.R. Bailey, Y. Kim, and L.A. Crum, "Ultrasound detection and computer segmentation of high intensity focused ultrasound (HIFU) lesions," J. Acoust. Soc. Am., 112, 2369, 2002.

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1 Oct 2002

High intensity focused ultrasound (HIFU) can necrose tumors or cauterize tissue bleeds at intensities on the order of 1000 w/cm2. A synchronized HIFU and B-mode ultrasound system reveals a hyperechoic region at the treatment site, which grows with treatment duration and intensity. Our goal was to segment the hyperechoic region representing the lesion via image analysis and measure the ratio of its major and minor axes. Our algorithm uses the RF data as input, processes it, and outputs a binary image that represents the lesions cross-sectional profile. With depth settings from the clinical ultrasound imager, it is possible to calculate lesion dimensions from the binary image. The algorithm was tested with lesions made in a transparent polyacrylamide tissue phantom that became opaque in response to focal heating during HIFU exposure. Lesion size was recorded simultaneously with ultrasound and a CCD camera, and both measurements agreed well. Additionally, computer segmentation agreed well with segmentation by HIFU users blinded to the experimental conditions. The average difference of the determined ratio was 13% for lesions less than 0.5 cm in length. Thus, it is possible to localize precisely the treated tissue region.

In vitro sonoluminescence and sonochemistry studies with an electrohydraulic shock wave lithotripter

Matula, T.J., P.R. Hilmo, M.R. Bailey, and L.A. Crum, "In vitro sonoluminescence and sonochemistry studies with an electrohydraulic shock wave lithotripter," Ultrasound Med. Biol., 28, 1199-1207, 2002.

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1 Sep 2002

Sonoluminescence and sonochemistry from a cavitation field generated by an electrohydraulic shock-wave lithotripter were investigated as functions of spark discharge voltage (13 to 21 kV) and pulse-repetition frequency (PRF) (0.5 to 2.0 Hz). Sonochemical activity, measured with an iodide dosimeter, increased with both voltage and PRF. Sonoluminescence was measured in an acoustically matched light-tight box. The envelope of the light intensity was measured in a temporally gated region extending from the initial arrival of the shock wave (resulting in bubble compression) to the final inertial collapse of the bubble cloud, which follows hundreds of micros after passage of the shock wave. The initial compression resulted in greater sonoluminescence emissions, suggesting that the initial bubble compression due to the leading positive pressure spike from the lithotripter generated higher temperatures than the inertial collapse of the bubble. These unexpected results are consistent with some recent calculations in which the vapor pressure of the liquid limits compressional heating.

Cavitation control by dual frequency high intensity focused ultrasound

Bailey, M.R., D.J. Halaas, R. Martin, A.A. Chulichkov, and V.A. Khokhlova, "Cavitation control by dual frequency high intensity focused ultrasound," Proceedings, 16th International Symposium on Nonlinear Acoustics, Moscow, Russia, 19-23 August, 127 (2002).

23 Aug 2002

Nonlinear regimes of lesion formation by HIFU in tissue-mimicking phantom

Khokhlova, V.A., P.J. Kaczkowski, B.W. Cunitz, M.R. Bailey, and L.A. Crum, "Nonlinear regimes of lesion formation by HIFU in tissue-mimicking phantom," Proceedings, 16th International Symposium on Nonlinear Acoustics, Moscow, Russia, 19-23 August, 129 (2002).

23 Aug 2002

Effect of ultrasound waveform on cavitation bubble dynamics

Chulichkov, A.A., V.A. Khokhlova, and M.R. Bailey, "Effect of ultrasound waveform on cavitation bubble dynamics," Proceedings, 11th Session of the Russian Acoustical Society, Moscow, Russia, 19-23 November, 49-52 (2001).

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19 Nov 2001

It is known that oscillations of single spherically symmetric bubble exposed to the ultrasound may have violent collapses. The impact of ultrasound on bubble dynamics strongly depends on the relation between the ultrasound frequency and the resonance frequency of the bubble, which depends on the bubble radius and on the diffusion of gas through the wall of the bubble. If high intensity ultrasound is applied, the effect of acoustic nonlinearity on ultrasound propagation results in generation of harmonics of the fundamental frequency and corresponding broadening of the wave spectrum. The bubbles with resonant frequencies close to the fundamental one of the wave, and to frequencies of multiple harmonics, can be therefore effectively excited. Another important effect on cavitation is gas diffusion — the quantity of gas diffused to and from the bubble during one cycle are not equal to each other. It results in the growth of bubble and decrease of its resonant frequency. The idea of the work is to study the effect of various acoustic waveforms on the dynamics of bubbles with different radii. The Gilmore–Akulichev equation is used as a mathematical model of cavitation. The solutions of the equation are obtained numerically using the fifth order Runge–Kutta method. The dynamic of bubbles exposed to harmonic ultrasound wave, periodic sawtooth waves, and frequency modulated waves are considered.

An optimal protocol for shock wave delivery by the dual-pulse lithotripter

Sokolov, D.L., M.R. Bailey, and L.A. Crum, "An optimal protocol for shock wave delivery by the dual-pulse lithotripter," J. Acoust. Soc. Am., 110, 2614, doi:10.1121/1.1394221, 2001.

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1 Nov 2001

Dual pulses, generated by opposing, confocal, and simultaneously triggered electrohydraulic shock wave sources, can be used to localize and intensify cavitation for application to lithotripsy. It has been reported that the dual-pulse lithotripter (DPL) may be a safer and more effective lithotripter [Sokolov et al., J. Acoust. Soc. Am. 100 (2001)]. Fragmentation of cement stones and hemolysis in dilute suspensions of human red blood cells were assessed at several positions along the focal axis of the DPL. Pulse repetition frequency was varied from 0.5 to 2 Hz and charging voltage was varied from 12 to 20 kV. At 1 Hz and 15 kV, the number of stone fragments > 1.5 mm, at the focus, remained the same while hemolysis, 2 cm away, decreased by one-half, when compared to the conventional lithotripter at the same PRF and a higher voltage of 18 kV. By varying PRF and voltage, an optimal in vitro protocol for shock wave delivery that maximizes stone fragmentation at the focus and minimizes hemolysis away from the focus might be determined. Results support the hypothesis that cavitation plays a more significant role than shock waves in both stone fragmentation and cell damage in the dual-pulse lithotripter.

Bubbles and acoustic image-guided high intensity focused ultrasound

Bailey, M.R., S. Vaezy, J.C. Yuen, A. Anand, N.A. Miller, P.J. Kaczkowski, and L.A. Crum, "Bubbles and acoustic image-guided high intensity focused ultrasound," J. Acoust. Soc. Am., 110, 2643, 2001.

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1 Nov 2001

Clinical diagnostic ultrasound (US) can be used to target and to monitor in real-time high-intensity focused ultrasound (HIFU) therapy. In our system, the HIFU transducer (3.5 MHz, 35 mm aperture, 55 mm radius of curvature) and US scan head (several were tested, center frequencies 3–8 MHz) are fixed with the HIFU focus in the imaging plane. HIFU and US are either synchronized real time to relegate interference to the image fringe or HIFU and US are interlaced for nearly real-time imaging. HIFU produces a localized hyperechoic region visible on B-mode US. Coagulatively necrosed lesions produced have similar size, shape, and location to measurements made from the corresponding US images. Thresholds are also comparable. However, in vivo, if HIFU is turned off as soon as hyperecho appears, no lesion is seen (the tissue was fixed within four hours of treatment). Thus, a short HIFU burst can be used to target treatment. Bubbles appear to be largely but perhaps not entirely responsible for the increase in echogenicity. Times for dissipation of the hyperecho and dissolution of a bubble as a function of hydrostatic pressure compare well. Significant overpressure (50 bar) can suppress hyperecho produced by HIFU.

Modeling and direct visualization of temperature rise induced by high-intensity ultrasound in tissue

Khokhlova, V.A., N. Miller, R. Ollos, R. Martin, M. Bailey, Y. Mohammadian, and M. Naghavi, "Modeling and direct visualization of temperature rise induced by high-intensity ultrasound in tissue," J. Acoust. Soc. Am., 110, 2613, doi:10.1121/1.1369097, 2001.

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1 Nov 2001

High-intensity focused ultrasound (HIFU) creates localized heating deep in tissues which can be used to necrose tumors or cauterize vessels. Imaging of the temperature field in tissue is important for guiding HIFU treatment. Temperature rise in excised and degassed bovine liver exposed to high-intensity focused ultrasound was visualized experimentally and simulated numerically. An infrared camera, which records surface temperature only, was used to measure spatial temperature distribution. Two blocks of tissue were stacked, and their interface was placed along the axis of the ultrasound beam. A single element concave transducer (2 MHz, 35-mm aperture, 51-mm radius of curvature) was used. After exposure to ultrasound, the upper piece was immediately removed, and the temperature on the axial plane was infrared imaged. The absorption coefficient of liver was measured and then used for numerical simulations. The theoretical model employs a KZK-type equation for the acoustic pressure field combined with a bioheat equation. It is shown that experiment and theory agree well on the location, shape, and dimensions of the heated region. The dependence of absorption coefficient in liver on exposure to ultrasound, to air, and to degassing process was studied.

Ultrasound-guided localized detection of cavitation during lithotripsy in pig kidney in vivo

Sapozhnikov, O.A., M.R. Bailey, L.A. Crum, et al., "Ultrasound-guided localized detection of cavitation during lithotripsy in pig kidney in vivo," Ultrason. Symp. Proc., 2, 1347-1350, 2001.

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7 Oct 2001

It is supposed that inertial cavitation plays a significant role in tissue damage during extracorporeal shock wave lithotripsy (ESWL). In this work we attempted to detect cavitation in tissue. In vivo experiments with pigs were conducted in a Dornier HM3 electrohydraulic lithotripter. Kidney alignment was made using fluoroscopy and B-mode ultrasound. Cavitation was detected by a dual passive cavitation detection (DPCD) system consisting of two confocal spherical bowl PZT transducers (1.15 MHz, focal length 10 cm, radius 10 cm). An ultrasound scanhead was placed between the transducers, an hyperechoic spots in the image indicated pockets of bubbles during ESWL. A coincidence-detection algorithm and the confocal transducers made it possible to localize cavitation to within a 4 mm diameter region. The signals from both the collecting system and kidney tissue were recorded. The targeting of the DPCD focus was confirmed by using the DPCD transducers as high intensity focused ultrasound (HIFU) sources at HIFU durations below the lesion formation threshold. In this HIFU regime, a bright spot appears in the B-mode image indicating the position of the DPCD focus. In this way we could confirm that refraction and scattering in tissue did not cause a misalignment. The tissue region interrogated was also marked with a lesion produced by HIFU. Clear cavitation signals were detected from the collecting system and from pools of blood that formed near the kidney capsule and weak signals were recorded from tissue during the ESWL treatment.

Localized cavitation detection in lithotripsy in vivo

Bailey, M.R., L.A. Crum, N. Miller, L.N. Couret, O.A. Sapozhnikov, Y.A. Pishchalnikov, J.A. McAteer, B. Connors, and A.P. Evan, "Localized cavitation detection in lithotripsy in vivo," Proceedings, Seventeenth International Congress on Acoustics, Rome Italy, 2-7 September (ICA, Rome, 2001).

2 Sep 2001

Use of a dual-pulse lithotripter to generate a localized and intensified cavitation field

Sokolov, D.L., M.R. Bailey, and L.A. Crum, "Use of a dual-pulse lithotripter to generate a localized and intensified cavitation field," J. Acoust. Soc. Am., 110, 1685-1695, 2001.

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1 Sep 2001

Localizing cavitation to the kidney stone in extracorporeal shock wave lithotripsy may be desirable since cavitation appears to play a major role in both stone comminution and renal tissue damage. A method has been developed to localize and intensify cavitation damage in vitro. Cavitation fields in water were filmed with a high-speed digital video camera. In a conventional lithotripter (CL), the shock wave produced by a single source creates a 2x10 cm cylindrical cloud of bubbles in water. Bubbles in the CL field collapse simultaneously along the focal axis to produce a nearly uniform 1-mm x 8-cm line of pits in 25-µm-thick aluminum foil. Our dual-pulse lithotripter (DPL) uses two shock wave sources, facing each other, confocal, and triggered simultaneously to create a 4x5 cm cylindrical cloud of bubbles that collapse over a range of times and strengths such that the greatest pit damage on foils is contained within a few square millimeters of the focus. The time for bubbles to grow and collapse was measured with a focused hydrophone and compared with calculations based on the Gilmore equation. Pressure doubling due to synchronous arrival of the two pulses at the focus created increased bubble growth and increased foil pit depth. Asynchronous timing between the two pulses elsewhere in the DPL field resulted in disruption of radial dynamics and negligible pitting to foils. Translation of bubbles was also investigated, both numerically and experimentally. While net translation was calculated to be <0.3 mm in all cases, the rapid acceleration of bubbles in a small region may contribute to their premature destruction in that region. Overall, radial dynamics were found to be largely responsible for the observed pattern of cavitation in the dual-pulse lithotripsy field.

Effect of ultrasound waveform on dynamics of cavitating bubbles with different radii

Chulichkov, A.A., V.A. Khokhlova, and M.R. Bailey, "Effect of ultrasound waveform on dynamics of cavitating bubbles with different radii," Progress in Nonlinear Science, Nizhny Novgorod, Russia, 2-6 July, 126 (Institute of Physics, Nizhny Novgorod, Russia, 2001).

2 Jul 2001

Overpressure and the role of bubbles in focused ultrasound lesion shape

Bailey, M.R., L.N. Couret, O.A. Sapozhnikov, V.A. Khokhlova, G. ter Haar, S. Vaezy, X. Shi, R. Martin, and L.A. Crum, "Overpressure and the role of bubbles in focused ultrasound lesion shape," Proceedings, First International Workshop on the Application of High Intensity Focused Ultrasound (HIFU) in Medicine, 10-12 May, Chongqing, China, edited by G. R. ter Haar and F. Wu, 22 (2001).

10 May 2001

Use of overpressure to assess the role of bubbles in focused ultrasound lesion shape in vitro

Bailey, M.R., L.N. Couret, O.A. Sapozhnikov, V.A. Khokhlova, G. ter Haar, S. Vaezy, X. Shi, R. Martin, and L.A. Crum, "Use of overpressure to assess the role of bubbles in focused ultrasound lesion shape in vitro," Ultrasound Med. Biol., 27, 695-708, 2001.

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1 May 2001

Overpressure–elevated hydrostatic pressure–was used to assess the role of gas or vapor bubbles in distorting the shape and position of a high-intensity focused ultrasound (HIFU) lesion in tissue. The shift from a cigar-shaped lesion to a tadpole-shaped lesion can mean that the wrong area is treated. Overpressure minimizes bubbles and bubble activity by dissolving gas bubbles, restricting bubble oscillation and raising the boiling temperature. Therefore, comparison with and without overpressure is a tool to assess the role of bubbles. Dissolution rates, bubble dynamics and boiling temperatures were determined as functions of pressure. Experiments were made first in a low-overpressure chamber (0.7 MPa maximum) that permitted imaging by B-mode ultrasound (US). Pieces of excised beef liver (8 cm thick) were treated in the chamber with 3.5 MHz for 1 to 7 s (50% duty cycle). In situ intensities (ISP) were 600 to 3000 W/cm2. B-mode US imaging detected a hyperechoic region at the HIFU treatment site. The dissipation of this hyperechoic region following HIFU cessation corresponded well with calculated bubble dissolution rates; thus, suggesting that bubbles were present. Lesion shape was then tested in a high-pressure chamber. Intensities were 1300 and 1750 W/cm2 ( ± 20%) at 1 MHz for 30 s. Hydrostatic pressures were 0.1 or 5.6 MPa. At 1300 W/cm2, lesions were cigar-shaped, and no difference was observed between lesions formed with or without overpressure. At 1750 W/cm2, lesions formed with no overpressure were tadpole-shaped, but lesions formed with high overpressure (5.6 MPa) remained cigar-shaped. Data support the hypothesis that bubbles contribute to the lesion distortion.

Real-time visualization of high-intensity focused ultrasound treatment using ultrasound imaging

Vaezy, S., X. Shi, R.W. Martin, E. Chi, P.I. Nelson, M.R. Bailey, and L.A. Crum, "Real-time visualization of high-intensity focused ultrasound treatment using ultrasound imaging," Ultrasound Med. Biol., 27, 33-43, 2001.

1 Jan 2001

Effect of dual-reflector lithotripter on stone fragmentation and cell damage

Sokolov, D.L., M.R. Bailey, and L.A. Crum, "Effect of dual-reflector lithotripter on stone fragmentation and cell damage," J. Acoust. Soc. Am., 108, 2518, 2000.

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1 Nov 2000

An electrohydraulic lithotripter uses an ellipsoidal reflector to focus shock waves on to a kidney stone. The shock wave generates a cylindrical cavitation field, ~1-cm wide x 10-cm long, that has been implicated in both stone fragmentation and damage to healthy tissue during lithotripsy treatment. A dual-reflector lithotripter, consisting of two identical spark-gap lithotripters facing each other and firing simultaneously, creates a more localized cavitation field, ~3 cm wide x 5 cm long (Sokolov, Berlin 1999). Such a field may increase the rate of stone fragmentation while mitigating damage to surrounding tissue. Breakage of model stones at the focus and hemolysis of red blood cells 3 cm from the focus were assessed for both conventional lithotripsy (CL) and dual-reflector lithotripsy (DRL). To equalize total energy input, the number of shots was halved from CL to DRL. Stones subjected to DRL were broken into several major fragments while stones subjected to CL remained intact except for some dust. Human blood was diluted to 3% hematocrit in degassed PBS and placed in acoustically transparent sample tubes. There was no statistical difference in percent hemolysis between CL (5.12±1.01%) and DRL (5.39±0.57%).

Real-time observation of inception and growth of HIFU-induced tissue lesions

Lafon, C., M.R. Bailey, L.N. Couret, P.J. Kaczkowski, A.A. Brayman, L.A. Crum, and O.A. Sapozhnikov, "Real-time observation of inception and growth of HIFU-induced tissue lesions," J. Acoust. Soc. Am., 108, 2546, 2000.

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1 Nov 2000

To study the biological effects of high-intensity focused ultrasound (HIFU), experiments are usually performed on isolated or perfused tissues. Indeed, the complex phenomena occurring in tissue during HIFU-induced coagulation necrosis is difficult to mimic with synthetic phantoms. A good phantom should first match the acoustical and thermal properties of tissues. Furthermore, heating above a thermal threshold should induce a permanent, localized and observable change corresponding to protein denaturing in tissue. Lastly, the choice of a transparent material makes possible real-time examination of the development of coagulation necroses. We have used bovine eye lenses in this aim. The density, sound speed, attenuation, and thermal threshold for irreversible damage to the bovine lens were measured and found to be similar to those for liver or muscle, common tissues for HIFU experiments, although acoustic attenuation is slightly higher in the lens. Transparency of the lens allowed us to observe HIFU-induced lesion evolution in real time. The shape and size of the lesions obtained in the lens agreed well with results obtained in liver. In conclusion, the transparent bovine eye lens is a useful model for visualization of thermal lesions.

Design and characterization of a research electrohydraulic lithotripter patterned after the Dornier HM3

Cleveland, R.O., M.R. Bailey, N. Fineberg, B. Hartenbaum, M. Lokhandwalla, J.A. McAteer, and B. Sturtevant, "Design and characterization of a research electrohydraulic lithotripter patterned after the Dornier HM3," Rev. Sci. Instrum., 71, 2514-2525, 2000.

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1 Jun 2000

An electrohydraulic lithotripter has been designed that mimics the behavior of the Dornier HM3 extracorporeal shock wave lithotripter. The key mechanical and electrical properties of a clinical HM3 were measured and a design implemented to replicate these parameters. Three research lithotripters have been constructed on this design and are being used in a multi-institutional, multidisciplinary research program to determine the physical mechanisms of stone fragmentation and tissue damage in shock wave lithotripsy. The acoustic fields of the three research lithotripters and of two clinical Dornier HM3 lithotripters were measured with a PVDF membrane hydrophone. The peak positive pressure, peak negative pressure, pulse duration, and shock rise time of the focal waveforms were compared. Peak positive pressures varied from 25 MPa at a voltage setting of 12 kV to 40 MPa at 24 kV. The magnitude of the peak negative pressure varied from -7 to -12 MPa over the same voltage range. The spatial variations of the peak positive pressure and peak negative pressure were also compared. The focal region, as defined by the full width half maximum of the peak positive pressure, was 60 mm long in the axial direction and 10 mm wide in the lateral direction. The performance of the research lithotripters was found to be consistent at clinical firing rates (up to 3 Hz). The results indicated that pressure fields in the research lithotripters are equivalent to those generated by a clinical HM3 lithotripter.

Bubble translation due to radiation force in SWL

Sokolov, D.L., M.R. Bailey, L.A. Crum, and O.A Sapozhnikov, "Bubble translation due to radiation force in SWL," J. Acoust. Soc. Am., 107, 2838, 2000.

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1 May 2000

The clustering of cavitation bubbles may lead to enhanced stone comminution and influence the extent of tissue damage during shock wave lithotripsy (SWL) treatment. Recent research has focused on changing the SWL pulse, or timing between pulses, to intensify or mitigate collapse or localize these clusters. Such research has targeted radial, not translational motion. We investigate whether bubble translation due to radiation force is sufficiently large to influence cluster formation. The translational dynamics of a single spherical bubble were modeled according to the formulation proposed by Watanabe and Kukita [Phys. Fluids 5(11) (1993)]. After radius-time data were obtained using the Gilmore equation, translational motion was calculated by numerical integration of the Watanabe equation. Calculations were performed for a range of bubble sizes (R0=2–20 μm) and pressure rise times (10-9 – 10-7 s). The results show that, during bubble growth and collapse induced by a single pulse or two pulses with microsecond delays, bubble translations are ~0.1 mm. Although bubble translation from a single pulse may not have a noticeable effect on bubble distribution, the effect may be cumulative for the +1000 shots fired during clinical SWL treatment.

Simultaneous detection of acoustic and light emissions from cavitation bubbles in shock wave lithotripsy

Matula, T.J., M.R. Bailey, P.R. Hilmo, D.L. Sokolov, and L.A. Crum, "Simultaneous detection of acoustic and light emissions from cavitation bubbles in shock wave lithotripsy," J. Acoust. Soc. Am., 107, 2838, doi:10.1121/1.429165, 2000.

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1 May 2000

A typical pulse in electrohydraulic shock wave lithotripsy (SWL) consists of an intense positive pressure pulse, followed by a longer negative-pressure tail. Computer models of the bubble dynamics associated with such a pulse suggest that the positive pressure pulse compresses the bubble (R{0}=3–10 μm) to a submicron size. The negative-pressure tail then causes the bubble to undergo a dramatic expansion, followed by an inertially dominated (presumably spherical) collapse hundreds of microseconds later. Acoustic and light emissions are generated at both collapses. We have examined the simultaneous acoustic and optical emission from a cavitation field generated by SWL in order to determine whether the sonoluminescence is principally due to the initial compression of the bubble, or the final inertial collapse. Using two confocal 1-MHz, piezoceramic hydrophones and a PMT mounted on a light-tight water-filled container, we have observed acoustic and light emission corresponding to both the compression and inertial collapse of the bubble field. Our initial results suggest that the light emission occurs most frequently during the initial bubble compression. These results may have implications for understanding the sphericity of the bubble dynamics produced in SWL.

SWL stone fragmentation in vitro is improved by slowing SW delivery rate

Lifshitz, D.A., J.C. Williams Jr., A.P. Evan, D.L. Rietjens, J.A. McAteer, M.R. Bailey, L.A. Crum, and O.A. Sapozhnikov, "SWL stone fragmentation in vitro is improved by slowing SW delivery rate," J. Acoust. Soc. Am., 107, 2838, doi:10.1121/1.429162, 2000.

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1 May 2000

Fast shock wave (SW) rates in lithotripsy (SWL) generate enhanced cavitation that could promote stone fragmentation. We tested the idea that SWL at the high end of clinical SW rate (2 Hz) acts to improve stone comminution. Model stones (Ultracal-30 cement) were exposed to SWs (20 kV, 400 SWs) at 0.2, 0.5, 1, and 2 Hz in a research electrohydraulic lithotripter. Fragmentation was assessed by measuring number, size, and projected surface area of the fragments. Stones treated at 0.2 Hz exhibited significantly greater fragmentation (p<0.01) than stones at 1 or 2 Hz, while fragmentation between 0.2 and 0.5 Hz was similar. Mean ± SEM for fragment area increase was 370±53% at 0.2 Hz (n=10 stones), 280±34 at 0.5 Hz (8), 130±31 at 1 Hz (5), and 101±16 at 2 Hz (20). This pronounced enhancement of fragmentation at very slow SW rate was unexpected. High-speed camera images of cavitation at solid objects show an increased bubble cloud at faster SW rates. The bubble cloud may interfere with transmission of acoustic energy to the stone surface. These in vitro data suggest the possibility that patient treatment at fast SW delivery rates may decrease the efficiency of stone comminution.

A dual passive cavitation detector for localized detection of lithotripsy-induced cavitation in vitro

Cleveland, R.O., O.A., Sapozhnikov, J.C. Bailey, and L.A. Crum, "A dual passive cavitation detector for localized detection of lithotripsy-induced cavitation in vitro," J. Acoust. Soc. Am., 107, 1745-1758, 2000.

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1 Mar 2000

A passive cavitation detector (PCD) identifies cavitation events by sensing acoustic emissions generated by the collapse of bubbles. In this work, a dual passive cavitation detector (dual PCD), consisting of a pair of orthogonal confocal receivers, is described for use in shock wave lithotripsy. Cavitation events are detected by both receivers and can be localized to within 5 mm by the nature of the small intersecting volume of the focal areas of the two receivers in association with a coincidence detection algorithm. A calibration technique, based on the impulse response of the transducer, was employed to estimate radiated pressures at collapse near the bubble. Results are presented for the in vitro cavitation fields of both a clinical and a research electrohydraulic lithotripter. The measured lifetime of the primary growth-and-collapse of the cavitation bubbles increased from 180 to 420 μs as the power setting was increased from 12 to 24 kV. The measured lifetime compared well with calculations based on the Gilmore–Akulichev formulation for bubble dynamics. The radiated acoustic pressure 10 mm from the collapsing cavitation bubble was measured to vary from 4 to 16 MPa with increasing power setting; although the trends agreed with calculations, the predicted values were four times larger than measured values. The axial length of the cavitation field correlated well with the 6-dB region of the acoustic field. However, the width of the cavitation field (10 mm) was significantly narrower than the acoustic field (25 mm) as bubbles appeared to be drawn to the acoustic axis during the collapse. The dual PCD also detected signals from "rebounds," secondary and tertiary growth-and-collapse cycles. The measured rebound time did not agree with calculations from the single-bubble model. The rebounds could be fitted to a Rayleigh collapse model by considering the entire bubble cloud as an effective single bubble. The results from the dual PCD agreed well with images from high-speed photography. The results indicate that single-bubble theory is sufficient to model lithotripsy cavitation dynamics up to time of the main collapse, but that upon collapse bubble cloud dynamics becomes important.

Edge wave on axis behind an aperture or disk having a ragged edge

Menounou, P., M.R. Bailey, and D.T. Blackstock, "Edge wave on axis behind an aperture or disk having a ragged edge," J. Acoust. Soc. Am. 107, 103-111, 2000.

1 Jan 2000

Inventions

Methods to Determine Optimal Ultrasound Pulse Parameters to Fragment Urinary Calculi Using Acoustic Feedback

Record of Invention Number: 47078

Adam Maxwell, Mike Bailey, Bryan Cunitz, Oleg Sapozhnikov

Disclosure

6 Oct 2014

Ultrasound Image Feedback for Lithotripsy

Record of Invention Number: 47077

Adam Maxwell, Mike Bailey, Bryan Cunitz, Wayne Kreider, Oleg Sapozhnikov

Disclosure

6 Oct 2014

Applications of Ultrasonic Propulsion

Record of Invention Number: 47073

Mike Bailey, Bryan Cunitz, Barbrina Dunmire

Disclosure

3 Oct 2014

More Inventions

Assortment of Push Profiles for Pushing a Variety of Kidney Stones

Record of Invention Number: 47072

Mike Bailey, Bryan Cunitz, Barbrina Dunmire, Oleg Sapozhnikov

Disclosure

3 Oct 2014

Single Element Broadly Focused Ultrasonic Propulsion Device

Record of Invention Number: 47074

Mike Bailey, Bryan Cunitz, Barbrina Dunmire

Disclosure

3 Oct 2014

Ultrasound to rotate an obstructing kidney stone

Record of Invention Number: 47066

Mike Bailey, Bryan Cunitz, Barbrina Dunmire

Disclosure

29 Sep 2014

Ultrasound Technique for Trapping and Displacing Solid Objects Using a Vortex Acoustic Beam Created by a Multi-element Sector Array Transducer

Record of Invention Number: 47037

Mike Bailey, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov

Disclosure

18 Aug 2014

Ultrasound to Detach Kidney Stones from Plaque or Tissue

Record of Invention Number: 46981

Mike Bailey

Disclosure

13 Jun 2014

Derating Method for Therapeutic Applications of High Intensity Focused Ultrasound

Patent Number: 8,668,658

Vera Khokhlova, Olga Bessonova, Michael Canney, Mike Bailey, Oleg Sapozhnikov, Larry Crum

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Patent

11 Mar 2014

Methods of derating a nonlinear ultrasound field and associated systems are disclosed herein. A method of derating a nonlinear ultrasound field in accordance with an embodiment of the present technology can include, for example, calibrating an ultrasound source to a first source voltage (Vw) and generating a nonlinear acoustic wave from the ultrasound source into water. The method can further include measuring a focal waveform of the nonlinear acoustic wave and determining a second source voltage (Vt) of the ultrasound source that generates the same focal waveform in tissue.

Ultrasound Instrumentation for Ureteroscopic and Transcutaneous Kidney Stone Removal

Record of Invention Number: 46839

Thomas Lendvay, Mike Bailey, Ryan Hsi, Brian MacConaghy, Adam Maxwell

Disclosure

4 Feb 2014

Ultrasound Based Method and Apparatus to Determine the Size of Kidney Stone Fragments Before Removal via Ureteroscopy

Patent Number: 8,607,634

Mike Bailey, Joel Teichman, Mathew Sorensen

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Patent

17 Dec 2013

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

MRI-based Methods to Target, Monitor, and Quantify Thermal and Mechanical Bioeffects in Tissue Induced by High Intensity Focused Ultrasound

Record of Invention Number: 46745

Vera Khokhlova, Mike Bailey, Tanya Khokhlova, Wayne Kreider, Donghoon Lee, Adam Maxwell, George Schade

Disclosure

26 Nov 2013

Methods to Selectively Fragment and Remove Tissue While Sparing Extracellular Matrix, Vessels and Similar Structures Using Microsecond-long High Intensity Focused Ultrasound Pulses with Shocks

Record of Invention Number: 46742

Yak-Nam Wang, Mike Bailey, Vera Khokhlova, Tanya Khokhlova, Wayne Kreider, Adam Maxwell

Disclosure

18 Nov 2013

Methods to Induce Large Volumes of Mechanically Fractionated Lesions Using Therapeutic Phased Arrays

Record of Invention Number: 46733

Vera Khokhlova, Mike Bailey, Tanya Khokhlova, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov

Disclosure

8 Nov 2013

Low-Frequency Enhancement of Boiling Histotripsy

Record of Invention Number: 46730

Vera Khokhlova, Mike Bailey, Tanya Khokhlova, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov

Disclosure

7 Nov 2013

Method to Induce Transcostal Tissue Ablation using High Intensity Focused Ultrasound with Shocks

Record of Invention Number: 46728

Vera Khokhlova, Mike Bailey, Larry Crum, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov, Leonid R. Gavrilov, Petr Yuldashev

Disclosure

6 Nov 2013

Method of Trabecular Bone Loss Mitigation Through Exposure of Adjacent Muscle to Pulsed Ultrasound of Moderate Intensity

Record of Invention Number: 46674

Mike Bailey, Tanya Khokhlova, Julianna Simon, Yak-Nam Wang

Disclosure

26 Sep 2013

Method and Apparatus to Detect the Fragmentation of Kidney Stones by Measuring Acoustic Scatter

Patent Number: 8,535,250

Niel Owen, Mike Bailey, Oleg Sapozhnikov

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Patent

17 Sep 2013

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

Improved Radio Frequency Pulse Amplifier for Driving Ultrasound Transducers

Record of Invention Number: 46507

Vera Khokhlova, Mike Bailey

Disclosure

14 May 2013

Device and Procedure for Noninvasive Removal of Ureteral Stents

Record of Invention Number: 46501

Adam Maxwell, Mike Bailey, Ryan Hsi, Hunter Wessells

Disclosure

9 May 2013

Noninvasive Fragmentation of Urinary Tract Stones with Focused Ultrasound

Record of Invention Number: 46460

Adam Maxwell, Mike Bailey, Bryan Cunitz, Ryan Hsi

Disclosure

28 Mar 2013

Method for Testing Output Force of an Ultrasonic Propulsion Device

Record of Invention Number: 46441

Bryan Cunitz, Mike Bailey, Brian MacConaghy

Disclosure

12 Mar 2013

Noninvasive Treatment of Ureteroceles with Focused Ultrasound

Record of Invention Number: 46404

Mike Bailey, Pasquale Casale, Ryan Hsi, Thomas Lendvay, Adam Maxwell

Disclosure

14 Feb 2013

Method for Noninvasive Focused Ultrasound Surgery

Record of Invention Number: 46356

Vera Khokhlova, Mike Bailey, Adam Maxwell, Oleg Sapozhnikov

Disclosure

11 Jan 2013

Method of Detecting Microbubbles in Tissue and Tissue Phantoms Using "Twinkling" Artifact of Doppler Imaging

Record of Invention Number: 46179

Oleg Sapozhnikov, Mike Bailey, Joo Ha Hwang, Tatiana Khokhlova, Vera Khokhlova

Disclosure

10 Aug 2012

Using Bubbles to Better Detect Kidney Stones

Record of Invention Number: 46062

Mike Bailey

Disclosure

30 Apr 2012

Surgical Guide for AIDS Prevention

Record of Invention Number: 46050

Brian MacConaghy, Mike Bailey

Disclosure

18 Apr 2012

Additional Details for Ultrasonic Propulsion

Record of Invention Number: 46012

Mike Bailey, Bryan Cunitz

Disclosure

21 Mar 2012

New Probe for Ultrasonic Propulsion of Kidney Stones

Record of Invention Number: 46006

Bryan Cunitz, Mike Bailey

Disclosure

20 Mar 2012

An Ultrasound Phantom for Detecting and Repositioning Kidney Stones

Record of Invention Number: 45981

Mike Bailey, Bryan Cunitz, Barbrina Dunmire

Disclosure

1 Mar 2012

Acoustic Disruption and Deactivation of Biofilms in Catheters

Record of Invention Number: 45929

Yak-Nam Wang, Mike Bailey, Francesco Curra

Disclosure

15 Jan 2012

Adipose Tissue Reduction by Boiling Histotripsy

Record of Invention Number: 45807

Vera Khokhlova, Mike Bailey, Larry Crum

Disclosure

15 Oct 2011

A New Ultrasound Imaging Regime for Improved Size Measuring of Hard Concretions Present in Soft Tissue Based on Observation of Ultrasound Shadow on a B-mode Image

Record of Invention Number: 45653

Mike Bailey, Oleg Sapozhnikov

Disclosure

8 Jun 2011

New Regime of Ultrasound Imaging of Strong Scatterers in Tissue Using Envelope-based Beamforming

Record of Invention Number: 45654

Mike Bailey, Oleg Sapozhnikov

Disclosure

8 Jun 2011

Ultrasound Technique to Separate Hard Objects from Tissue by Long Lasting Reverberation in Hard Objects

Record of Invention Number: 45655

Mike Bailey, Oleg Sapozhnikov

Disclosure

8 Jun 2011

A Method of Soft Tissue Emulsification Using a Mechanism of Ultrasonic Atomization Inside Gas or Vapor Cavities

Record of Invention Number: 45567

Mike Bailey, Vera Khokhlova, Oleg Sapozhnikov, Tatiana Khokhlova, Julianna Simon

Disclosure

28 Mar 2011

Portable Acoustic Holography System for Therapeutic Ultrasound Sources

Record of Invention Number: 45469

Mike Bailey, Peter Kaczkowski, Vera Khokhlova, Wayne Kreider, Oleg Sapozhnikov

Disclosure

21 Dec 2010

A Model of an Equivalent Focused Piston Source to Characterize Nonlinear Ultrasound Fields of 2D Therapeutic (HIFU) Arrays

Record of Invention Number: 45341

Mike Bailey, Larry Crum, Vera Khokhlova, Oleg Sapozhnikov

Disclosure

12 Aug 2010

Nonlinear MR Frequency Shifts with Temperature Changes

Record of Invention Number: 8777D

Mike Bailey, Bryan Cunitz, Donghoon Lee, Kenneth Marro

Disclosure

7 Jul 2010

A Derating Method to Determine Nonlinear Acoustic Field Parameters in Tissue for Therapeutic Applications of HIFU

Record of Invention Number: 8758D

Mike Bailey, Michael Canney, Larry Crum, Vera Khokhlova

Disclosure

9 Jun 2010

Method for Kidney Stone Detection and Targeting Using Amplitude Mode (A-mode) Ultrasound Imaging with Application to Shock Wave Lithotripsy

Record of Invention Number: 8683D

Mike Bailey, Bryan Cunitz, Neil Owen, Marla Paun, Stephen Carter

Disclosure

11 May 2010

Method of Detecting Kidney Stones Using Ultrasound

Record of Invention Number: 8633D

Mike Bailey, John Kucewicz

Disclosure

26 Mar 2010

A Test Bed to Calibrate Magnetic Resonance Thermometry

Record of Invention Number: 8532D

Mike Bailey, Bryan Cunitz, Donghoon Lee, Kenneth Marro

Disclosure

3 Dec 2009

Method and System to Synchronize Acoustic Therapy with Ultrasound Imaging

Patent Number: US 7,621,873 B2

Neil Owen, Mike Bailey, James Hossack

More Info

Patent

24 Nov 2009

Interference in ultrasound imaging when used in connection with high intensity focused ultrasound (HIFU) is avoided by employing a synchronization signal to control the HIFU signal. Unless the timing of the HIFU transducer is controlled, its output will substantially overwhelm the signal produced by the ultrasound imaging system and obscure the image it produces. The synchronization signal employed to control the HIFU transducer is obtained without requiring modification of the ultrasound imaging system. Signals corresponding to scattered ultrasound imaging waves are collected using either the HIFU transducer or a dedicated receiver. A synchronization processor manipulates the scattered ultrasound imaging signals to achieve the synchronization signal, which is then used to control the HIFU bursts so as to substantially reduce or eliminate HIFU interference in the ultrasound image. The synchronization processor can alternatively be implemented using a computing device or an application-specific circuit.

A Method of Non-invasive Mechanical Erosion of Tissue Using Shock Wave Heating and Millisecond Boiling Induced by High Intensity Focused Ultrasound

Record of Invention Number: 8493D

Mike Bailey, Michael Canney, Larry Crum, Vera Khokhlova

Disclosure

15 Oct 2009

Enhanced Signal Processing Technique for Ultrasound Thickness Measurements

Record of Invention Number: 8348D

James Hermanson, Jeramy Kimball, Mike Bailey

Disclosure

24 Apr 2009

Improved Detection of Hard Concretions Present in Soft Tissues Based on Doppler Imaging Twinkling Artifact by Means of Insonifying the Imaged Region with Additional Modulated Intense Ultrasound Beam

Record of Invention Number: 8335D

Mike Bailey, Larry Crum, Oleg Sapozhnikov

Disclosure

1 Apr 2009

Improved Detection of Hard Concretions Present in Soft Tissues Based on Ultrasound Imaging Twinkling Artifact by Means of Introducing Fluctuations in Beam Structure for Consecutive Ultrasound Pulses of Each Scan Line

Record of Invention Number: 8336D

Mike Bailey, Larry Crum, Oleg Sapozhnikov

Disclosure

1 Apr 2009

Focused Shock-Wave Devices with Direct Wave Cavitation Suppressor

Patent Number: US 7,267,654 B2

Tom Matula, Paul Hilmo, Mike Bailey

More Info

Patent

11 Sep 2007

A reflector reflects energy emitting from an energy source and focuses and directs it to a target. An aperture stop or suppressor disk is positioned between the energy source and target. The outer periphery of the aperture stop or suppressor disk is an irregular curve. This shape of the periphery prevents diffraction enhancement to the direct wave. In another embodiment, the suppressor disk is replaced by a a suppressor member that is directly mounted on a frame portion of the energy source. This energy source includes a spark-gap, or the like, and an open frame that surrounds the spark-gap or the like. This frame includes a pair of laterally spaced apart frame members on the side of the frame that faces the target. The suppressor member is connected to these frame members. It may have longitudinal grooves in its side edges into which the frame members snap-fit.

Direct Wave Cavitation Suppressor for Focused Shock-Wave Devices

Patent Number: US 7,033,328 B2

Tom Matula, Paul Hilmo, Mike Bailey

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Patent

25 Apr 2006

A reflector reflects energy emitting from an energy source and focuses and directs it to a target. An aperture stop or suppressor disk is positioned between the energy source and target. The outer periphery of the aperture stop or suppressor disk is an irregular curve. This shape of the periphery prevents diffraction enhancement to the direct wave.

Acoustics Air-Sea Interaction & Remote Sensing Center for Environmental & Information Systems Center for Industrial & Medical Ultrasound Electronic & Photonic Systems Ocean Engineering Ocean Physics Polar Science Center
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