Publications by authors named "Wayne Kreider"

38 Publications

Design and Characterization of an Ultrasound Transducer for Combined Histotripsy-Thrombolytic Therapy.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 17;PP. Epub 2021 Sep 17.

Chronic thrombi of the deep veins of the leg are resistant to dissolution or removal by current interventions and can act as thrombogenic sources. Histotripsy, a focused ultrasound therapy, uses the mechanical activity of bubble clouds to liquefy target tissues. In vitro experiments have shown that histotripsy enhances thrombolytic agent recombinant tissue plasminogen activator in a highly retracted clot model resistant to lytic therapy alone. Although these results are promising, further refinement of the acoustic source is necessary for in vivo studies and clinical translation. The source parameters for use in vivo were defined, and a transducer was fabricated for transcutaneous exposure of porcine and human iliofemoral deep venous thrombosis (DVT) as the target. Based on the design criteria, a 1.5-MHz elliptical source with 6-cm focal length and a focal gain of 60 was selected. The source was characterized by fiber-optic hydrophone and holography. High speed photography showed that the cavitation cloud could be confined to dimensions smaller than the specified vessel lumen. The source was also demonstrated in vitro to create confined lesions within clots. The results support that this design offers an appropriate clinical prototype for combined histotripsy-thrombolytic therapy.
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http://dx.doi.org/10.1109/TUFFC.2021.3113635DOI Listing
September 2021

Factors Affecting Tissue Cavitation during Burst Wave Lithotripsy.

Ultrasound Med Biol 2021 08 31;47(8):2286-2295. Epub 2021 May 31.

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA.

Burst wave lithotripsy (BWL) is a technology under clinical investigation for non-invasive fragmentation of urinary stones. Under certain ranges of ultrasound exposure parameters, this technology can cause cavitation in tissue leading to renal injury. This study sought to measure the focal pressure amplitude needed to cause cavitation in vivo and determine its consistency in native tissue, in an implanted stone model and under different exposure parameters. The kidneys of eight pigs were exposed to transcutaneous BWL ultrasound pulses. In each kidney, two locations were targeted: the renal sinus and the kidney parenchyma. Each was exposed for 5 min at a set pressure level and parameters, and cavitation was detected using an active cavitation imaging method based on power Doppler ultrasound. The threshold was determined by incrementing the pressure amplitude up or down after each 5-min interval until cavitation occurred/subsided. The pressure thresholds were remeasured postsurgery, targeting an implanted stone or collecting space (in sham). The presence of a stone or sham surgery did not significantly impact the threshold for tissue cavitation. Targeting parenchyma instead of kidney collecting space and lowering the ultrasound pulse repetition frequency both resulted in an increased pressure threshold for cavitation.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259501PMC
August 2021

"HIFU Beam:" A Simulator for Predicting Axially Symmetric Nonlinear Acoustic Fields Generated by Focused Transducers in a Layered Medium.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 27;68(9):2837-2852. Epub 2021 Aug 27.

"HIFU beam" is a freely available software tool that comprises a MATLAB toolbox combined with a user-friendly interface and binary executable compiled from FORTRAN source code (HIFU beam. (2021). Available: http://limu.msu.ru/node/3555?language=en). It is designed for simulating high-intensity focused ultrasound (HIFU) fields generated by single-element transducers and annular arrays with propagation in flat-layered media that mimic biological tissues. Numerical models incorporated in the simulator include evolution-type equations, either the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation or one-way Westervelt equation, for radially symmetric ultrasound beams in homogeneous and layered media with thermoviscous or power-law acoustic absorption. The software uses shock-capturing methods that allow for simulating strongly nonlinear acoustic fields with high-amplitude shocks. In this article, a general description of the software is given along with three representative simulation cases of ultrasound transducers and focusing conditions typical for therapeutic applications. The examples illustrate major nonlinear wave effects in HIFU fields including shock formation. Two examples simulate propagation in water, involving a single-element source (1-MHz frequency, 100-mm diameter, 90-mm radius of curvature) and a 16-element annular array (3-MHz frequency, 48-mm diameter, and 35-mm radius of curvature). The third example mimics the scenario of a HIFU treatment in a "water-muscle-kidney" layered medium using a source typical for abdominal HIFU applications (1.2-MHz frequency, 120-mm diameter, and radius of curvature). Linear, quasi-linear, and shock-wave exposure protocols are considered. It is intended that "HIFU beam" can be useful in teaching nonlinear acoustics; designing and characterizing high-power transducers; and developing exposure protocols for a wide range of therapeutic applications such as shock-based HIFU, boiling histotripsy, drug delivery, immunotherapy, and others.
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http://dx.doi.org/10.1109/TUFFC.2021.3074611DOI Listing
September 2021

Inertial Cavitation Behaviors Induced by Nonlinear Focused Ultrasound Pulses.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 27;68(9):2884-2895. Epub 2021 Aug 27.

Inertial cavitation induced by pulsed high-intensity focused ultrasound (pHIFU) has previously been shown to successfully permeabilize tumor tissue and enhance chemotherapeutic drug uptake. In addition to HIFU frequency, peak rarefactional pressure ( p ), and pulse duration, the threshold for cavitation-induced bioeffects has recently been correlated with asymmetric distortion caused by nonlinear propagation, diffraction and formation of shocks in the focal waveform, and therefore with the transducer F -number. To connect previously observed bioeffects with bubble dynamics and their attendant physical mechanisms, the dependence of inertial cavitation behavior on shock formation was investigated in transparent agarose gel phantoms using high-speed photography and passive cavitation detection (PCD). Agarose phantoms with concentrations ranging from 1.5% to 5% were exposed to 1-ms pulses using three transducers of the same aperture but different focal distances ( F -numbers of 0.77, 1.02, and 1.52). Pulses had central frequencies of 1, 1.5, or 1.9 MHz and a range of p at the focus varying within 1-18 MPa. Three distinct categories of bubble behavior were observed as the acoustic power increased: stationary near-spherical oscillation of individual bubbles, proliferation of multiple bubbles along the pHIFU beam axis, and fanned-out proliferation toward the transducer. Proliferating bubbles were only observed under strongly nonlinear or shock-forming conditions regardless of frequency, and only where the bubbles reached a certain threshold size range. In stiffer gels with higher agarose concentrations, the same pattern of cavitation behavior was observed, but the dimensions of proliferating clouds were smaller. These observations suggest mechanisms that may be involved in bubble proliferation: enhanced growth of bubbles under shock-forming conditions, subsequent shock scattering from the gel-bubble interface, causing an increase in the repetitive tension created by the acoustic wave, and the appearance of a new growing bubble in the proximal direction. Different behaviors corresponded to specific spectral characteristics in the PCD signals: broadband noise in all cases, narrow peaks of backscattered harmonics in the case of stationary bubbles, and broadened, shifted harmonic peaks in the case of proliferating bubbles. The shift in harmonic peaks can be interpreted as a Doppler shift from targets moving at speeds of up to 2 m/s, which correspond to the observed bubble proliferation speeds.
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http://dx.doi.org/10.1109/TUFFC.2021.3073347DOI Listing
September 2021

Holographic extraction of plane waves from an ultrasound beam for acoustic characterization of an absorbing layer of finite dimensions.

J Acoust Soc Am 2021 Jan;149(1):386

Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia.

For the acoustic characterization of materials, a method is proposed for interpreting experiments with finite-sized transducers and test samples in terms of the idealized situation in which plane waves are transmitted through an infinite plane-parallel layer. The method uses acoustic holography, which experimentally provides complete knowledge of the wave field by recording pressure waveforms at points on a surface intersected by the acoustic beam. The measured hologram makes it possible to calculate the angular spectrum of the beam to decompose the field into a superposition of plane waves propagating in different directions. Because these waves cancel one another outside the beam, the idealized geometry of an infinite layer can be represented by a sample of finite size if its lateral dimensions exceed the width of the acoustic beam. The proposed method relies on holograms that represent the acoustic beam with and without the test sample in the transmission path. The method is described theoretically, and its capabilities are demonstrated experimentally for silicone rubber samples by measuring their frequency-dependent phase velocities and absorption coefficients in the megahertz frequency range.
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http://dx.doi.org/10.1121/10.0003212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816771PMC
January 2021

Bilayer aberration-inducing gel phantom for high intensity focused ultrasound applications.

J Acoust Soc Am 2020 12;148(6):3569

Department of Acoustics, Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia.

Aberrations induced by soft tissue inhomogeneities often complicate high-intensity focused ultrasound (HIFU) therapies. In this work, a bilayer phantom made from polyvinyl alcohol hydrogel and ballistic gel was built to mimic alternating layers of water-based and lipid tissues characteristic of an abdominal body wall and to reproducibly distort HIFU fields. The density, sound speed, and attenuation coefficient of each material were measured using a homogeneous gel layer. A surface with random topographical features was designed as an interface between gel layers using a 2D Fourier spectrum approach and replicating different spatial scales of tissue inhomogeneities. Distortion of the field of a 256-element 1.5 MHz HIFU array by the phantom was characterized through hydrophone measurements for linear and nonlinear beam focusing and compared to the corresponding distortion induced by an ex vivo porcine body wall of the same thickness. Both spatial shift and widening of the focal lobe were observed, as well as dramatic reduction in focal pressures caused by aberrations. The results suggest that the phantom produced levels of aberration that are similar to a real body wall and can serve as a research tool for studying HIFU effects as well as for developing algorithms for aberration correction.
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http://dx.doi.org/10.1121/10.0002877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097711PMC
December 2020

A Prototype Therapy System for Boiling Histotripsy in Abdominal Targets Based on a 256-Element Spiral Array.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 May 26;68(5):1496-1510. Epub 2021 Apr 26.

Boiling histotripsy (BH) uses millisecond-long ultrasound (US) pulses with high-amplitude shocks to mechanically fractionate tissue with potential for real-time lesion monitoring by US imaging. For BH treatments of abdominal organs, a high-power multielement phased array system capable of electronic focus steering and aberration correction for body wall inhomogeneities is needed. In this work, a preclinical BH system was built comprising a custom 256-element 1.5-MHz phased array (Imasonic, Besançon, France) with a central opening for mounting an imaging probe. The array was electronically matched to a Verasonics research US system with a 1.2-kW external power source. Driving electronics and software of the system were modified to provide a pulse average acoustic power of 2.2 kW sustained for 10 ms with a 1-2-Hz repetition rate for delivering BH exposures. System performance was characterized by hydrophone measurements in water combined with nonlinear wave simulations based on the Westervelt equation. Fully developed shocks of 100-MPa amplitude are formed at the focus at 275-W acoustic power. Electronic steering capabilities of the array were evaluated for shock-producing conditions to determine power compensation strategies that equalize BH exposures at multiple focal locations across the planned treatment volume. The system was used to produce continuous volumetric BH lesions in ex vivo bovine liver with 1-mm focus spacing, 10-ms pulselength, five pulses/focus, and 1% duty cycle.
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http://dx.doi.org/10.1109/TUFFC.2020.3036580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191454PMC
May 2021

Pilot in vivo studies on transcutaneous boiling histotripsy in porcine liver and kidney.

Sci Rep 2019 12 27;9(1):20176. Epub 2019 Dec 27.

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, WA, USA.

Boiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. BH treatments with real-time ultrasound (US) guidance allowed by BH-generated bubbles were previously demonstrated ex vivo and in vivo in exposed porcine liver and small animals. Here, the feasibility of US-guided transabdominal and partially transcostal BH ablation of kidney and liver in an acute in vivo swine model was evaluated for 6 animals. BH parameters were: 1.5 MHz frequency, 5-30 pulses of 1-10 ms duration per focus, 1% duty cycle, peak acoustic powers 0.9-3.8 kW, sonication foci spaced 1-1.5 mm apart in a rectangular grid with 5-15 mm linear dimensions. In kidneys, well-demarcated volumetric BH lesions were generated without respiratory gating and renal medulla and collecting system were more resistant to BH than cortex. The treatment was accelerated 10-fold by using shorter BH pulses of larger peak power without affecting the quality of tissue fractionation. In liver, respiratory motion and aberrations from subcutaneous fat affected the treatment but increasing the peak power provided successful lesion generation. These data indicate BH is a promising technology for transabdominal and transcostal mechanical ablation of tumors in kidney and liver.
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http://dx.doi.org/10.1038/s41598-019-56658-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934604PMC
December 2019

Evaluation of Renal Stone Comminution and Injury by Burst Wave Lithotripsy in a Pig Model.

J Endourol 2019 10 27;33(10):787-792. Epub 2019 May 27.

Department of Urology, University of Washington School of Medicine, Seattle, Washington.

Burst wave lithotripsy is an experimental technology to noninvasively fragment kidney stones with focused bursts of ultrasound (US). This study evaluated the safety and effectiveness of specific lithotripsy parameters in a porcine model of nephrolithiasis. A 6- to 7-mm human kidney stone was surgically implanted in each kidney of three pigs. A burst wave lithotripsy US transducer with an inline US imager was coupled to the flank and the lithotripter focus was aligned with the stone. Each stone was exposed to burst wave lithotripsy at 6.5 to 7 MPa focal pressure for 30 minutes under real-time image guidance. After treatment, the kidneys were removed for gross, histologic, and MRI assessment. Stone fragments were retrieved from the kidney to determine the mass comminuted to pieces <2 mm. On average, 87% of the stone mass was reduced to fragments <2 mm. In three of five treatments, stones were completely comminuted to <2-mm fragments. In two of five treatments, stones were partially disintegrated, but larger fragments remained. One stone was not treated because no suitable acoustic window was identified. No injury was detected through gross, histologic, or MRI examination in the parenchymal tissue, although petechial damage and surface erosion were identified on the urothelium of the collecting system limited to the area around the stone. Burst wave lithotripsy can consistently produce stone fragments small enough to spontaneously pass by transcutaneous administration of US pulses. The data suggest that such exposures produce minimal injury to the kidney and urinary tract.
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http://dx.doi.org/10.1089/end.2018.0886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798804PMC
October 2019

The Impact of Dust and Confinement on Fragmentation of Kidney Stones by Shockwave Lithotripsy in Tissue Phantoms.

J Endourol 2019 05 1;33(5):400-406. Epub 2019 Feb 1.

2 Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington.

The goal was to test whether stone composition and kidney phantom configuration affected comminution in extracorporeal shockwave lithotripsy (SWL) laboratory tests. Confinement may enhance the accumulation of dust and associated cavitation bubbles in the fluid surrounding the stone. It is known that high shockwave delivery rates in SWL are less effective because bubbles generated by one shockwave do not have sufficient time to dissolve, thereby shielding the next shockwave. Experiments were conducted with a lithotripter coupled to a water bath. The rate of comminution was measured by weighing fragments over 2 mm at 5-minute time points. First, plaster and crystal stones were broken in four phantoms: a nylon wire mesh, an open polyvinyl chloride (PVC) cup, a closed PVC cup, and an anatomical kidney model-the phantoms have decreasing fluid volumes around the stone. Second, the fluid volume in the kidney model was flushed with water at different rates (0, 7, and 86 mL/min) to remove dust. The efficiency of breakage of stones decreases for the dust emitting plaster stones (percentage of breakage in 5 minutes decreased from 92% ± 2% [ = 3] in wire mesh to 19% ± 3% [ = 3] in model calix) with increasing confinement, but not for the calcite crystal stones that produced little dust (percentage of breakage changed from 87% ± 3% [ = 3] in wire mesh to 81% ± 3% [ = 3] in kidney model). Flushing the kidney phantom at the fastest rate improved comminution of smaller plaster stones by 27%. Phantoms restricting dispersion of dust were found to affect stone breakage in SWL and experiments should replicate kidney environments. The dust around the stone and potential cavitation may shield the stone from shockwaves and reduce efficacy of SWL. Understanding of stone composition and degree of hydronephrosis could be used to adapt patient-specific protocols.
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http://dx.doi.org/10.1089/end.2018.0516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533787PMC
May 2019

Energy shielding by cavitation bubble clouds in burst wave lithotripsy.

J Acoust Soc Am 2018 11;144(5):2952

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 Northeast 40th Street, Seattle, Washington 98105, USA.

Combined laboratory experiment and numerical simulation are conducted on bubble clouds nucleated on the surface of a model kidney stone to quantify the energy shielding of the stone caused by cavitation during burst wave lithotripsy (BWL). In the experiment, the bubble clouds are visualized and bubble-scattered acoustics are measured. In the simulation, a compressible, multi-component flow solver is used to capture complex interactions among cavitation bubbles, the stone, and the burst wave. Quantitative agreement is confirmed between results of the experiment and the simulation. In the simulation, a significant shielding of incident wave energy by the bubble clouds is quantified. The magnitude of shielding can reach up to 90% of the energy of the incoming burst wave that otherwise would be transmitted into the stone, suggesting a potential loss of efficacy of stone comminution. There is a strong correlation between the magnitude of the energy shielding and the amplitude of the bubble-scattered acoustics, independent of the initial size and the void fraction of the bubble cloud within a range addressed in the simulation. This correlation could provide for real-time monitoring of cavitation activity in BWL.
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http://dx.doi.org/10.1121/1.5079641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258362PMC
November 2018

Mechanical decellularization of tissue volumes using boiling histotripsy.

Phys Med Biol 2018 Dec 4;63(23):235023. Epub 2018 Dec 4.

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, WA, United States of America.

High intensity focused ultrasound (HIFU) is rapidly advancing as an alternative therapy for non-invasively treating specific cancers and other pathological tissues through thermal ablation. A new type of HIFU therapy-boiling histotripsy (BH)-aims at mechanical fractionation of into subcellular fragments, with a range of accompanying thermal effects that can be tuned from none to substantial depending on the requirements of the application. The degree of mechanical tissue damage induced by BH has been shown to depend on the tissue type, with collagenous structures being most resistant, and cellular structures being most sensitive. This has been reported for single BH lesions, but has not been replicated in large volumes. Such tissue selectivity effect has potential uses involving tissue decellularization for biofabrication technologies as well as mechanical ablation by BH while sparing critical structures. The goal of this study was to investigate tissue decellularization effect in larger, clinically relevant liquefied volumes of tissue, and to evaluate the accumulated thermal effect in the volumetric lesions under different exposure parameters. All BH exposures were performed with a 256-element 1.2 MHz array of a magnetic resonance imaging-guided HIFU (MR-HIFU) clinical system (Sonalleve V1, Profound Medical Inc, Mississauga, Canada). The volumetric BH lesions were produced in degassed ex vivo bovine liver using 1-10 ms long pulses with in situ shock amplitudes of 75-100 MPa at the focus and pulse repetition frequencies (PRFs) of 1-10 Hz covering a range of effects from pure mechanical homogenization to thermal ablation. Multimodal analysis of the lesions was then performed, including microstructure (histological), ultrastructure (electron microscopy), and molecular (biochemistry) methods. Results show a range of tissue effects in terms of the degree of tissue selectivity and the amount of heat generated in large BH lesions, thereby demonstrating potential for treatments tailored to different clinical applications.
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http://dx.doi.org/10.1088/1361-6560/aaef16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527100PMC
December 2018

Dependence of inertial cavitation induced by high intensity focused ultrasound on transducer -number and nonlinear waveform distortion.

J Acoust Soc Am 2018 09;144(3):1160

Department of Acoustics, Faculty of Physics, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119991, Russia.

Pulsed high intensity focused ultrasound was shown to enhance chemotherapeutic drug uptake in tumor tissue through inertial cavitation, which is commonly assumed to require peak rarefactional pressures to exceed a certain threshold. However, recent studies have indicated that inertial cavitation activity also correlates with the presence of shocks at the focus. The shock front amplitude and corresponding peak negative pressure ( ) in the focal waveform are primarily determined by the transducer -number: less focused transducers produce shocks at lower . Here, the dependence of inertial cavitation activity on the transducer -number was investigated in agarose gel by monitoring broadband noise emissions with a coaxial passive cavitation detector (PCD) during pulsed exposures (pulse duration 1 ms, pulse repetition frequency 1 Hz) with varying within 1-15 MPa. Three 1.5 MHz transducers with the same aperture, but different focal distances (-numbers 0.77, 1.02, 1.52) were used. PCD signals were processed to extract cavitation probability, persistence, and mean noise level. At the same , all metrics indicated enhanced cavitation activity at higher -numbers; specifically, cavitation probability reached 100% when shocks formed at the focus. These results provide further evidence supporting the excitation of inertial cavitation at reduced by waveforms with nonlinear distortion and shocks.
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http://dx.doi.org/10.1121/1.5052260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125138PMC
September 2018

Modeling and numerical simulation of the bubble cloud dynamics in an ultrasound field for burst wave lithotripsy.

Proc Meet Acoust 2018 Nov 26;35(1). Epub 2018 Dec 26.

University of Washington, Seattle, WA.

Modeling and numerical simulation of bubble clouds induced by intense ultrasound waves are conducted to quantify the effect of cloud cavitation on burst wave lithotripsy, a proposed non-invasive alternative to shock wave lithotripsy that uses pulses of ultrasound with an amplitude of O(1) MPa and a frequency of O(100) kHz. A unidirectional acoustic source model and an Eulerian-Lagrangian method are developed for simulation of ultrasound generation from a multi-element array transducer and cavitation bubbles, respectively. Parametric simulations of the spherical bubble cloud dynamics reveal a new scaling parameter that dictates both the structure of the bubble cloud and the amplitude of the far-field, bubble-scattered acoustics. The simulation further shows that a thin layer of bubble clouds nucleated near a kidney stone model can shield up to 90% of the incoming wave energy, indicating a potential loss of efficacy during the treatment due to cavitation. Strong correlations are identified between the far-field, bubble-scattered acoustics and the magnitude of the shielding, which could be used for ultrasound monitoring of cavitation during treatments. The simulations are validated by companion experiments in vitro.
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http://dx.doi.org/10.1121/2.0000946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328995PMC
November 2018

Field Characterization and Compensation of Vibrational Nonuniformity for a 256-Element Focused Ultrasound Phased Array.

IEEE Trans Ultrason Ferroelectr Freq Control 2018 09 27;65(9):1618-1630. Epub 2018 Jun 27.

Multielement focused ultrasound phased arrays have been used in therapeutic applications to treat large tissue volumes by electronic steering of the focus, to target multiple simultaneous foci, and to correct aberration caused by inhomogeneous tissue pathways. There is an increasing interest in using arrays to generate more complex beam shapes and corresponding acoustic radiation force patterns for manipulation of particles such as kidney stones. Toward this end, experimental and computational tools are needed to enable accurate delivery of desired transducer vibrations and corresponding ultrasound fields. The purpose of this paper was to characterize the vibrations of a 256-element array at 1.5 MHz, implement strategies to compensate for variability, and test the ability to generate specified vortex beams that are relevant to particle manipulation. The characterization of the array output was performed in water using both element-by-element measurements at the focus of the array and holography measurements for which all the elements were excited simultaneously. Both methods were used to quantify each element's output so that the power of each element could be equalized. Vortex beams generated using both compensation strategies were measured and compared to the Rayleigh integral simulations of fields generated by an idealized array based on the manufacturer's specifications. Although both approaches improved beam axisymmetry, compensation based on holography measurements had half the error relative to the simulation results in comparison to the element-by-element method.
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http://dx.doi.org/10.1109/TUFFC.2018.2851188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344030PMC
September 2018

The role of trapped bubbles in kidney stone detection with the color Doppler ultrasound twinkling artifact.

Phys Med Biol 2018 01 9;63(2):025011. Epub 2018 Jan 9.

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40th St., Seattle, WA 98105, United States of America. Department of Mechanical Engineering, University of Washington, Stevens Way, Box 352600, Seattle, WA 98195, United States of America. Current address: Graduate Program in Acoustics, The Pennsylvania State University, 201E Applied Science Building, University Park, PA 16802, United States of America. Author to whom any correspondence should be addressed.

The color Doppler ultrasound twinkling artifact, which highlights kidney stones with rapidly changing color, has the potential to improve stone detection; however, its inconsistent appearance has limited its clinical utility. Recently, it was proposed stable crevice bubbles on the kidney stone surface cause twinkling; however, the hypothesis is not fully accepted because the bubbles have not been directly observed. In this paper, the micron or submicron-sized bubbles predicted by the crevice bubble hypothesis are enlarged in kidney stones of five primary compositions by exposure to acoustic rarefaction pulses or hypobaric static pressures in order to simultaneously capture their appearance by high-speed photography and ultrasound imaging. On filming stones that twinkle, consecutive rarefaction pulses from a lithotripter caused some bubbles to reproducibly grow from specific locations on the stone surface, suggesting the presence of pre-existing crevice bubbles. Hyperbaric and hypobaric static pressures were found to modify the twinkling artifact; however, the simple expectation that hyperbaric exposures reduce and hypobaric pressures increase twinkling by shrinking and enlarging bubbles, respectively, largely held for rough-surfaced stones but was inadequate for smoother stones. Twinkling was found to increase or decrease in response to elevated static pressure on smooth stones, perhaps because of the compression of internal voids. These results support the crevice bubble hypothesis of twinkling and suggest the kidney stone crevices that give rise to the twinkling phenomenon may be internal as well as external.
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http://dx.doi.org/10.1088/1361-6560/aa9a2fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791757PMC
January 2018

A Prototype Therapy System for Transcutaneous Application of Boiling Histotripsy.

IEEE Trans Ultrason Ferroelectr Freq Control 2017 10 14;64(10):1542-1557. Epub 2017 Aug 14.

Boiling histotripsy (BH) is a method of focused ultrasound surgery that noninvasively applies millisecond-length pulses with high-amplitude shock fronts to generate liquefied lesions in tissue. Such a technique requires unique outputs compared to a focused ultrasound thermal therapy apparatus, particularly to achieve high in situ pressure levels through intervening tissue. This paper describes the design and characterization of a system capable of producing the necessary pressure to transcutaneously administer BH therapy through clinically relevant overlying tissue paths using pulses with duration up to 10 ms. A high-voltage electronic pulser was constructed to drive a 1-MHz focused ultrasound transducer to produce shock waves with amplitude capable of generating boiling within the pulse duration in tissue. The system output was characterized by numerical modeling with the 3-D Westervelt equation using boundary conditions established by acoustic holography measurements of the source field. Such simulations were found to be in agreement with directly measured focal waveforms. An existing derating method for nonlinear therapeutic fields was used to estimate in situ pressure levels at different tissue depths. The system was tested in ex vivo bovine liver samples to create BH lesions at depths up to 7 cm. Lesions were also created through excised porcine body wall (skin, adipose, and muscle) with 3-5 cm thickness. These results indicate that the system is capable of producing the necessary output for transcutaneous ablation with BH.
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http://dx.doi.org/10.1109/TUFFC.2017.2739649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871228PMC
October 2017

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

Ultrasound Med Biol 2017 10 22;43(10):2318-2328. Epub 2017 Jul 22.

Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Aerospace Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Therapeutic ultrasound can drive bubble activity that damages soft tissues. To study the potential mechanisms of such injury, transparent agar tissue-mimicking phantoms were subjected to multiple pressure wave bursts of the kind being considered specifically for burst wave lithotripsy. A high-speed camera recorded bubble activity during each pulse. Various agar concentrations were used to alter the phantom's mechanical properties, especially its stiffness, which was varied by a factor of 3.5. However, the maximum observed bubble radius was insensitive to stiffness. During 1000 wave bursts of a candidate burst wave lithotripsy treatment, bubbles appeared continuously in a region that expanded slowly, primarily toward the transducer. Denser bubble clouds are formed at higher pulse repetition frequency. The specific observations are used to inform the incorporation of damage mechanisms into cavitation models for soft materials.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2017.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562535PMC
October 2017

Dependence of Boiling Histotripsy Treatment Efficiency on HIFU Frequency and Focal Pressure Levels.

Ultrasound Med Biol 2017 09 20;43(9):1975-1985. Epub 2017 Jun 20.

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, WA, USA; Faculty of Physics, M.V. Lomonosov Moscow State University, Moscow, Russia.

Boiling histotripsy (BH) is a high-intensity focused ultrasound (HIFU)-based method of mechanical tissue fractionation that utilizes millisecond-long bursts of HIFU shock waves to cause boiling at the focus in milliseconds. The subsequent interaction of the incoming shocks with the vapor bubble mechanically lyses surrounding tissue and cells. The acoustic parameter space for BH has been investigated previously and an inverse dependence between the HIFU frequency and the dimensions of a BH lesion has been observed. The primary goal of the present study was to investigate in more detail the ablation rate and reliability of BH in the frequency range relevant to treatment of deep abdominal tissue targets (1-2 MHz). The second goal was to investigate the effect of focal peak pressure levels and shock amplitude on BH lesion formation, given a constant duty factor, a constant ratio of the pulse duration to the time to reach boiling and a constant number of BH pulses. A custom-built 12-element sector array HIFU transducer with F-number = 1.05 was used in all experiments. BH pulses at 5 different frequencies (1, 1.2, 1.5, 1.7 and 1.9 MHz) were delivered to optically transparent polyacrylamide gel phantoms and ex vivo bovine liver and myocardium tissue to observe cavitation and boiling bubble activity with high-speed photography and B-mode ultrasound imaging, correspondingly. In gel phantoms, a cavitation bubble cloud was shown to form prefocally and to shield the focus in all exposures at 1 and 1.2 MHz and in the highest amplitude exposures at 1.5-1.7 MHz; shielding was not observed at 1.9 MHz. In ex vivo tissue, this shielding effect was observed in 25% of exposures when peak negative in situ pressure exceeded 10.2 MPa at 1 MHz and 14.5 MPa at 1.5 MHz. When shielding occurred, the exposures resulted in mild tissue disruption in the prefocal region, but not liquefaction. The dimensions of liquefied lesions followed the inverse proportionality trend with frequency; consequently, the frequency range of 1.2-1.5 MHz appeared to be preferable for BH exposures in terms of the compromise between the ablation rate and reliability. The lesion size was independent of the duration of the BH pulses (or the total "HIFU on" time), provided that the number of pulses was constant and boiling was induced within each pulse. Thus, the use of shorter (1 ms vs. 10 ms), higher amplitude BH pulses allowed up to 10-fold reduction in treatment time for a given duty factor.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2017.04.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547902PMC
September 2017

Detection and Evaluation of Renal Injury in Burst Wave Lithotripsy Using Ultrasound and Magnetic Resonance Imaging.

J Endourol 2017 08 16;31(8):786-792. Epub 2017 Jun 16.

2 Department of Urology, University of Washington School of Medicine , Seattle, Washington.

Purpose: Burst wave lithotripsy (BWL) is a transcutaneous technique with potential to safely and effectively fragment renal stones. Preclinical investigations of BWL require the assessment of potential renal injury. This study evaluates the capabilities of real-time ultrasound and MRI to detect and evaluate BWL injury that was induced in porcine kidneys.

Materials And Methods: Ten kidneys from five female farm pigs were treated with either a 170 or 335 kHz BWL transducer using variable treatment parameters and monitored in real-time with ultrasound. Eight kidneys were perfusion fixed and scanned with a 3-Tesla MRI scanner (T1-weighted, T2-weighted, and susceptibility-weighted imaging), followed by processing via an established histomorphometric technique for injury quantification. In addition, two kidneys were separately evaluated for histologic characterization of injury quality.

Results: Observed B-mode hyperechoes on ultrasound consistent with cavitation predicted the presence of BWL-induced renal injury with a sensitivity and specificity of 100% in comparison to the histomorphometric technique. Similarly, MRI detected renal injury with a sensitivity of 90% and specificity of 100% and was able to identify the scale of lesion volumes. The injuries purposefully generated with BWL were histologically similar to those formed by shock wave lithotripsy.

Conclusions: BWL-induced renal injury can be detected with a high degree of sensitivity and specificity by real-time ultrasound and post-treatment ex vivo MRI. No injury occurred in this study without cavitation detected on ultrasound. Such capabilities for injury detection and lesion volume quantification on MRI can be used for preclinical testing of BWL.
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http://dx.doi.org/10.1089/end.2017.0202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567874PMC
August 2017

Shock formation and nonlinear saturation effects in the ultrasound field of a diagnostic curvilinear probe.

J Acoust Soc Am 2017 04;141(4):2327

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40th Street, Seattle, Washington 98105, USA.

Newer imaging and therapeutic ultrasound technologies may benefit from in situ pressure levels higher than conventional diagnostic ultrasound. One example is the recently developed use of ultrasonic radiation force to move kidney stones and residual fragments out of the urinary collecting system. A commercial diagnostic 2.3 MHz C5-2 array probe has been used to deliver the acoustic pushing pulses. The probe is a curvilinear array comprising 128 elements equally spaced along a convex cylindrical surface. The effectiveness of the treatment can be increased by using higher transducer output to provide a stronger pushing force; however nonlinear acoustic saturation can be a limiting factor. In this work nonlinear propagation effects were analyzed for the C5-2 transducer using a combined measurement and modeling approach. Simulations were based on the three-dimensional Westervelt equation with the boundary condition set to match low power measurements of the acoustic pressure field. Nonlinear focal waveforms simulated for different numbers of operating elements of the array at several output power levels were compared to fiber-optic hydrophone measurements and were found to be in good agreement. It was shown that saturation effects do limit the acoustic pressure in the focal region of a diagnostic imaging probe.
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http://dx.doi.org/10.1121/1.4979261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910004PMC
April 2017

Design of HIFU Transducers for Generating Specified Nonlinear Ultrasound Fields.

IEEE Trans Ultrason Ferroelectr Freq Control 2017 02 20;64(2):374-390. Epub 2016 Oct 20.

Various clinical applications of high-intensity focused ultrasound have different requirements for the pressure levels and degree of nonlinear waveform distortion at the focus. The goal of this paper is to determine transducer design parameters that produce either a specified shock amplitude in the focal waveform or specified peak pressures while still maintaining quasi-linear conditions at the focus. Multiparametric nonlinear modeling based on the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation with an equivalent source boundary condition was employed. Peak pressures, shock amplitudes at the focus, and corresponding source outputs were determined for different transducer geometries and levels of nonlinear distortion. The results are presented in terms of the parameters of an equivalent single-element spherically shaped transducer. The accuracy of the method and its applicability to cases of strongly focused transducers were validated by comparing the KZK modeling data with measurements and nonlinear full diffraction simulations for a single-element source and arrays with 7 and 256 elements. The results provide look-up data for evaluating nonlinear distortions at the focus of existing therapeutic systems as well as for guiding the design of new transducers that generate specified nonlinear fields.
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http://dx.doi.org/10.1109/TUFFC.2016.2619913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300962PMC
February 2017

Cavitation-induced damage of soft materials by focused ultrasound bursts: A fracture-based bubble dynamics model.

J Acoust Soc Am 2016 08;140(2):1374

Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, 1206 West Green Street, Urbana, Illinois 61801, USA.

A generalized Rayleigh-Plesset-type bubble dynamics model with a damage mechanism is developed for cavitation and damage of soft materials by focused ultrasound bursts. This study is linked to recent experimental observations in tissue-mimicking polyacrylamide and agar gel phantoms subjected to bursts of a kind being considered specifically for lithotripsy. These show bubble activation at multiple sites during the initial pulses. More cavities appear continuously through the course of the observations, similar to what is deduced in pig kidney tissues in shock-wave lithotripsy. Two different material models are used to represent the distinct properties of the two gel materials. The polyacrylamide gel is represented with a neo-Hookean elastic model and damaged based upon a maximum-strain criterion; the agar gel is represented with a strain-hardening Fung model and damaged according to the strain-energy-based Griffith's fracture criterion. Estimates based upon independently determined elasticity and viscosity of the two gel materials suggest that bubble confinement should be sufficient to prevent damage in the gels, and presumably injury in some tissues. Damage accumulation is therefore proposed to occur via a material fatigue, which is shown to be consistent with observed delays in widespread cavitation activity.
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http://dx.doi.org/10.1121/1.4961364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848835PMC
August 2016

Experimental Study of Acoustic Radiation Force of an Ultrasound Beam on Absorbing and Scattering Objects.

AIP Conf Proc 2015 Jun;1685

Department of Acoustics, Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia; Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40th St. Seattle WA 98105.

Acoustic radiation force is a nonlinear acoustic effect caused by the transfer of wave momentum to absorbing or scattering objects. This phenomenon is exploited in modern ultrasound metrology for measurement of the acoustic power radiated by a source and is used for both therapeutic and diagnostic sources in medical applications. To calculate radiation force an acoustic hologram can be used in conjunction with analytical expressions based on the angular spectrum of the measured field. The results of an experimental investigation of radiation forces in two different cases are presented in this paper. In one case, the radiation force of an obliquely incident ultrasound beam on a large absorber (which completely absorbs the beam) is considered. The second case concerns measurement of the radiation force on a spherical target that is small compared to the beam diameter.
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http://dx.doi.org/10.1063/1.4934404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852870PMC
June 2015

Modeling and experimental analysis of acoustic cavitation bubbles for Burst Wave Lithotripsy.

J Phys Conf Ser 2015 Dec 3;656. Epub 2015 Dec 3.

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40th St, Seattle, WA 98105; Department of Urology, University of Washington School of Medicine, 1959 NE Pacific St, Seattle, WA 98195.

A combined modeling and experimental study of acoustic cavitation bubbles that are initiated by focused ultrasound waves is reported. Focused ultrasound waves of frequency 335 kHz and peak negative pressure 8 MPa are generated in a water tank by a piezoelectric transducer to initiate cavitation. The resulting pressure field is obtained by direct numerical simulation (DNS) and used to simulate single bubble oscillation. The characteristics of cavitation bubbles observed by high-speed photography qualitatively agree withs the simulation result. Finally, bubble clouds are captured using acoustic B-mode imaging that works in synchronization with high-speed photography.
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http://dx.doi.org/10.1088/1742-6596/656/1/012027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831575PMC
December 2015

An ultrasonic caliper device for measuring acoustic nonlinearity.

Phys Procedia 2016 ;87:93-98

CIMU, Applied Physics Laboratory, University of Washington, 1013 NE 40 Street, Seattle, WA 98105, USA.

In medical and industrial ultrasound, it is often necessary to measure the acoustic properties of a material. A specific medical application requires measurements of sound speed, attenuation, and nonlinearity to characterize livers being evaluated for transplantation. For this application, a transmission-mode caliper device is proposed in which both transmit and receive transducers are directly coupled to a test sample, the propagation distance is measured with an indicator gage, and receive waveforms are recorded for analysis. In this configuration, accurate measurements of nonlinearity present particular challenges: diffraction effects can be considerable while nonlinear distortions over short distances typically remain small. To enable simple estimates of the nonlinearity coefficient from a quasi-linear approximation to the lossless Burgers' equation, the calipers utilize a large transmitter and plane waves are measured at distances of 15-50 mm. Waves at 667 kHz and pressures between 0.1 and 1 MPa were generated and measured in water at different distances; the nonlinearity coefficient of water was estimated from these measurements with a variability of approximately 10%. Ongoing efforts seek to test caliper performance in other media and improve accuracy via additional transducer calibrations.
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http://dx.doi.org/10.1016/j.phpro.2016.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467533PMC
January 2016

Design of HIFU transducers to generate specific nonlinear ultrasound fields.

Phys Procedia 2016 ;87:132-138

CIMU, Applied Physics Laboratory, University of Washington, Seattle, WA.

Various clinical applications of high intensity focused ultrasound (HIFU) have different requirements on the pressure level and degree of nonlinear waveform distortion at the focus. Applications that utilize nonlinear waves with developed shocks are of growing interest, for example, for mechanical disintegration as well as for accelerated thermal ablation of tissue. In this work, an inverse problem of determining transducer parameters to enable formation of shocks with desired amplitude at the focus is solved. The solution was obtained by performing multiple direct simulations of the parabolic Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation for various parameters of the source. It is shown that results obtained within the parabolic approximation can be used to describe the focal region of single element spherical sources as well as complex transducer arrays. It is also demonstrated that the focal pressure level at which fully developed shocks are formed mainly depends on the focusing angle of the source and only slightly depends on its aperture and operating frequency. Using the simulation results, a 256-element HIFU array operating at 1.5 MHz frequency was designed for a specific application of boiling-histotripsy that relies on the presence of 90-100 MPa shocks at the focus. The size of the array elements and focusing angle of the array were chosen to satisfy technical limitations on the intensity at the array elements and desired shock amplitudes in the focal waveform. Focus steering capabilities of the array were analysed using an open-source T-Array software developed at Moscow State University.
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http://dx.doi.org/10.1016/j.phpro.2016.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451200PMC
January 2016

Acoustic holography as a metrological tool for characterizing medical ultrasound sources and fields.

J Acoust Soc Am 2015 Sep;138(3):1515-32

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 Northeast 40th Street, Seattle, Washington 98105, USA.

Acoustic holography is a powerful technique for characterizing ultrasound sources and the fields they radiate, with the ability to quantify source vibrations and reduce the number of required measurements. These capabilities are increasingly appealing for meeting measurement standards in medical ultrasound; however, associated uncertainties have not been investigated systematically. Here errors associated with holographic representations of a linear, continuous-wave ultrasound field are studied. To facilitate the analysis, error metrics are defined explicitly, and a detailed description of a holography formulation based on the Rayleigh integral is provided. Errors are evaluated both for simulations of a typical therapeutic ultrasound source and for physical experiments with three different ultrasound sources. Simulated experiments explore sampling errors introduced by the use of a finite number of measurements, geometric uncertainties in the actual positions of acquired measurements, and uncertainties in the properties of the propagation medium. Results demonstrate the theoretical feasibility of keeping errors less than about 1%. Typical errors in physical experiments were somewhat larger, on the order of a few percent; comparison with simulations provides specific guidelines for improving the experimental implementation to reduce these errors. Overall, results suggest that holography can be implemented successfully as a metrological tool with small, quantifiable errors.
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http://dx.doi.org/10.1121/1.4928396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575327PMC
September 2015

Fragmentation of urinary calculi in vitro by burst wave lithotripsy.

J Urol 2015 Jan 9;193(1):338-44. Epub 2014 Aug 9.

Department of Urology, School of Medicine, University of Washington, Seattle, Washington; Division of Urology, Department of Veteran Affairs Medical Center, Seattle, Washington.

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

Materials And Methods: Artificial and natural stones (mean ± SD size 8.2 ± 3.0 mm, range 5 to 15) were treated with ultrasound bursts using a focused transducer in a water bath. Stones were exposed to bursts with focal pressure amplitude of 6.5 MPa or less at a 200 Hz burst repetition rate until completely fragmented. Ultrasound frequencies of 170, 285 and 800 kHz were applied using 3 transducers, respectively. Time to fragmentation for each stone type was recorded and fragment size distribution was measured by sieving.

Results: Stones exposed to ultrasound bursts were fragmented at focal pressure amplitudes of 2.8 MPa or greater at 170 kHz. Fractures appeared along the stone surface, resulting in fragments that separated at the surface nearest to the transducer until the stone was disintegrated. All natural and artificial stones were fragmented at the highest focal pressure of 6.5 MPa with a mean treatment duration of 36 seconds for uric acid stones to 14.7 minutes for cystine stones. At a frequency of 170 kHz the largest artificial stone fragments were less than 4 mm. Exposure at 285 and 800 kHz produced only fragments less than 2 mm and less than 1 mm, respectively.

Conclusions: Stone comminution with burst wave lithotripsy is feasible as a potential noninvasive treatment method for nephrolithiasis. Adjusting the fundamental ultrasound frequency allows for stone fragment size to be controlled.
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http://dx.doi.org/10.1016/j.juro.2014.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384893PMC
January 2015

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

IEEE Trans Ultrason Ferroelectr Freq Control 2013 Aug;60(8):1683-98

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.
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http://dx.doi.org/10.1109/TUFFC.2013.2750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130294PMC
August 2013
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