Comparative Characterization of Nonlinear Ultrasound Fields Generated by Sonalleve V1 and V2 MR-HIFU Systems.

A Sonalleve magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) clinical system (Profound Medical, Mississauga, ON, Canada) has been shown to generate nonlinear ultrasound fields with shocks up to 100 MPa at the focus as required for HIFU applications such as boiling histotripsy of hepatic and renal tumors. The Sonalleve system has two versions V1 and V2 of the therapeutic array, with differences in focusing angle, focus depth, arrangement of elements, and the size of a central opening that is twice larger in the V2 system compared to the V1. The goal of this study was to compare the performance of the V1 and V2 transducers for generating high-amplitude shock-wave fields and to reveal the impact of different array geometries on shock amplitudes at the focus. Nonlinear modeling of the field in water using boundary conditions reconstructed from holography measurements shows that at the same power output, the V2 array generates 10-15-MPa lower shock amplitudes at the focus. Consequently, substantially higher power levels are required for the V2 system to reach the same shock-wave exposure conditions in histotripsy-type treatments. Although this difference is mainly caused by the smaller focusing angle of the V2 array, the larger central opening of the V2 array has a nontrivial impact. By excluding coherently interacting weakly focused waves coming from the central part of the source, the presence of the central opening results in a somewhat higher effective focusing angle and thus higher shock amplitudes at the focus. Axisymmetric equivalent source models were constructed for both arrays, and the importance of including the central opening was demonstrated. These models can be used in the "HIFU beam" software for simulating nonlinear fields of the Sonalleve V1 and V2 systems in water and flat-layered biological tissues.

Functional and Morphological Changes Associated with Burst Wave Lithotripsy-Treated Pig Kidneys.

Purpose: Burst wave lithotripsy (BWL) is a new technique for comminution of urinary stones. This technology is noninvasive, has a low positive pressure magnitude, and is thought to produce minor amounts of renal injury. However, little is known about the functional changes related to BWL treatment. In this study, we sought to determine if clinical BWL exposure produces a functional or morphological change in the kidney. Materials and Methods: Twelve female pigs were prepared for renal clearance assessment and served as either sham time controls (6) or were treated with BWL (6). In the treated group, 1 kidney in each pig was exposed to 18,000 pulses at 10 pulses/s with 20 cycles/pulse. Pressure levels related to each pulse were 12 and -7 MPa. Inulin (glomerular filtration rate, GFR) and para-aminohippuric acid (effective renal plasma flow, eRPF) clearance was measured before and 1 hour after treatment. Lesion size analysis was performed to assess the volume of hemorrhagic tissue injury created by each treatment (% FRV). Results: No visible gross hematuria was observed in any of the collected urine samples of the treated kidneys. BWL exposure also did not lead to a change in GFR or eRPF after treatment, nor did it cause a measurable amount of hemorrhage in the tissue. Conclusion: Using the clinical treatment parameters employed in this study, BWL did not cause an acute change in renal function or a hemorrhagic lesion.

Development of Tough Hydrogel Phantoms to Mimic Fibrous Tissue for Focused Ultrasound Therapies.

Tissue-mimicking gels provide a cost-effective medium to optimize histotripsy treatment parameters with immediate feedback. Agarose and polyacrylamide gels are often used to evaluate treatment outcomes as they mimic the acoustic properties and stiffness of a variety of soft tissues, but they do not exhibit high toughness, a characteristic of fibrous connective tissue. To mimic pathologic fibrous tissue found in benign prostate hyperplasia (BPH) and other diseases that are potentially treatable with histotripsy, an optically transparent hydrogel with high toughness was developed that is a hybrid of polyacrylamide and alginate. The stiffness was established using shear wave elastography (SWE) and indentometry techniques and was found to be representative of human BPH ex vivo prostate tissue. Different phantom compositions and excised ex vivo BPH tissue samples were treated with a 700-kHz histotripsy transducer at different pulse repetition frequencies. Post-treatment, the hybrid gels and the tissue samples exhibited differential reduction in stiffness as measured by SWE. On B-mode ultrasound, partially treated areas were present as hyperechoic zones and fully liquified areas as hypoechoic zones. Phase contrast microscopy of the gel samples revealed liquefaction in regions consistent with the target lesion dimensions and correlated to findings identified in tissue samples via histology. The dose required to achieve liquefaction in the hybrid gel was similar to what has been observed in ex vivo tissue and greater than that of agarose of comparable or higher Young's modulus by a factor >10. These results indicate that the developed hydrogels closely mimic elasticities found in BPH prostate ex vivo tissue and have a similar response to histotripsy treatment, thus making them a useful cost-effective alternative for developing and evaluating different treatment protocols.

Improving Burst Wave Lithotripsy Effectiveness for Small Stones and Fragments by Increasing Frequency: Theoretical Modeling and Ex Vivo Study.

Introduction and Objective: In clinical trial NCT03873259, a 2.6-mm lower pole stone was treated transcutaneously and ex vivo with 390-kHz burst wave lithotripsy (BWL) for 40 minutes and failed to break. The stone was subsequently fragmented with 650-kHz BWL after a 4-minute exposure. This study investigated how to fragment small stones and why varying the BWL frequency may more effectively fragment stones to dust. Methods: A linear elastic theoretical model was used to calculate the stress created inside stones from shock wave lithotripsy (SWL) and different BWL frequencies mimicking the stone's size, shape, lamellar structure, and composition. To test model predictions about the impact of BWL frequency, matched pairs of stones (1-5 mm) were treated at (1) 390 kHz, (2) 830 kHz, and (3) 390 kHz followed by 830 kHz. The mass of fragments >1 and 2 mm was measured over 10 minutes of exposure. Results: The linear elastic model predicts that the maximum principal stress inside a stone increases to more than 5.5 times the pressure applied by the ultrasound wave as frequency is increased, regardless of the composition tested. The threshold frequency for stress amplification is proportionate to the wave speed divided by the stone diameter. Thus, smaller stones may be likely to fragment at a higher frequency, but not at a lower frequency below a limit. Unlike with SWL, this amplification in BWL occurs consistently with spherical and irregularly shaped stones. In water tank experiments, stones smaller than the threshold size broke fastest at high frequency (p = 0.0003), whereas larger stones broke equally well to submillimeter dust at high, low, or mixed frequencies. Conclusions: For small stones and fragments, increasing frequency of BWL may produce amplified stress in the stone causing the stone to break. Using the strategies outlined here, stones of all sizes may be turned to dust efficiently with BWL.

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

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-vein thrombosis (DVT) as the target. Based on the design criteria, a 1.5-MHz elliptical source with a 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.

Factors Affecting Tissue Cavitation during Burst Wave Lithotripsy.

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.

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

"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.

Inertial Cavitation Behaviors Induced by Nonlinear Focused Ultrasound Pulses.

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.

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

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.

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

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.

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

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.

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

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.

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

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

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

Objective: 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. Materials and Methods: 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. Results: The efficiency of breakage of stones decreases for the dust emitting plaster stones (percentage of breakage in 5 minutes decreased from 92% ± 2% [n = 3] in wire mesh to 19% ± 3% [n = 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% [n = 3] in wire mesh to 81% ± 3% [n = 3] in kidney model). Flushing the kidney phantom at the fastest rate improved comminution of smaller plaster stones by 27%. Conclusions: Phantoms restricting dispersion of dust were found to affect stone breakage in SWL and in vitro 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.

Energy shielding by cavitation bubble clouds in burst wave lithotripsy.

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.

Mechanical decellularization of tissue volumes using boiling histotripsy.

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.

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

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 (p -) in the focal waveform are primarily determined by the transducer F-number: less focused transducers produce shocks at lower p -. Here, the dependence of inertial cavitation activity on the transducer F-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 p- varying within 1-15 MPa. Three 1.5 MHz transducers with the same aperture, but different focal distances (F-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 p -, all metrics indicated enhanced cavitation activity at higher F-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 p - by waveforms with nonlinear distortion and shocks.

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

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.

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

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.

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

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.