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Liver hemorrhage, the major cause of death in hepatic trauma, is notoriously difficult to control. We report on the use of high-intensity focused ultrasound (HIFU) to arrest the bleeding from incisions made in rabbit livers. A HIFU transducer, with a spherically curved aperture of 6.34 cm2 area, a focal length of 4 cm and a frequency of 3.3 MHz was used. In approximately 94% of the incisions, the hemorrhage was reduced to a slow oozing of blood in less than 2 min. The maximum temperature of liver tissue around the incision area, during HIFU application, was measured to be 86°C. The mechanism of hemostasis, confirmed by histological examination, appears to be coagulative necrosis of a volume of liver tissue around the incision. We believe that acoustic hemostasis, with the unique characteristic of “volume cauterization”, offers a novel method for the management of liver hemorrhage and, thus, has major clinical implications.

Accurate monitoring of high intensity focused ultrasound (HIFU) therapy is critical for widespread clinical use. Pulse-echo diagnostic ultrasound (DU) is known to exhibit temperature sensitivity through relative changes in time-of-flight between two sets of radio frequency (RF) backscatter measurements, one acquired before and one after therapy. These relative displacements, combined with knowledge of the exposure protocol, material properties, heat transfer, and measurement noise statistics, provide a natural framework for estimating the administered heating, and thereby therapy. The proposed method, termed displacement analysis, identifies the relative displacements using linearly independent displacement patterns, or modes, each induced by a particular time-varying heating applied during the exposure interval. These heating modes are themselves linearly independent. This relationship implies that a linear combination of displacement modes aligning the DU measurements is the response to an identical linear combination of heating modes, providing the heating estimate. Furthermore, the accuracy of coefficient estimates in this approximation is determined a priori, characterizing heating, thermal dose, and temperature estimates for any given protocol. Predicted performance is validated using simulations and experiments in alginate gel phantoms. Evidence for a spatially distributed interaction between temperature and time-of-flight changes is presented.

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

Previously, noninvasive methods of estimating local tissue thermal and acoustic properties using backscattered ultrasound have been proposed in the literature. In this article, a noninvasive method of estimating local thermal diffusivity in situ during focused ultrasound heating using beamformed acoustic backscatter data and applying novel signal processing techniques is developed. A high intensity focused ultrasound (HIFU) transducer operating at subablative intensities is employed to create a brief local temperature rise of no more than 10 degrees C. Beamformed radio-frequency (RF) data are collected during heating and cooling using a clinical ultrasound scanner. Measurements of the time-varying "acoustic strain", that is, spatiotemporal variations in the RF echo shifts induced by the temperature related sound speed changes, are related to a solution of the heat transfer equation to estimate the thermal diffusivity in the heated zone. Numerical simulations and experiments performed in vitro in tissue mimicking phantoms and excised turkey breast muscle tissue demonstrate agreement between the ultrasound derived thermal diffusivity estimates and independent estimates made by a traditional hot-wire technique. The new noninvasive ultrasonic method has potential applications in thermal therapy planning and monitoring, physiological monitoring and as a means of noninvasive tissue characterization.

Coded excitation (CE) imaging enables large time-bandwidth waveform transmissions, which are often pulse-compressed by matched filtering (MF). Much research investigates schemes for reducing MF sidelobes to decrease clutter with distributed targets. The goal of this presentation is to harmonize CE transmission with the image quality of Synthetic Transmit Aperture (STA) imaging at high frame rates. We propose a two-step process that estimates medium impulse responses (IR), then retrospectively images using the IR set. In this way, the probing code sequence is used optimally yet is decoupled from the imaging step, circumventing the sidelobe problem. The method first estimates transmit-receive (TR) pair IR of the acoustic medium, using random codes transmitted simultaneously across channels and acquisition intervals. Linear model theory solves for unbiased estimates of the IR set. In the second step, retrospective STA imaging excites the estimated IR set, using it as a simulation of the medium. Retrospective transmit signals and apodizing can differ at each pixel. We show the resulting beamformed pixels are unbiased estimates of STA pixels, and that time diversity in codes improves estimation error over static codes. To address tissue motion, the model is extended to polynomial and Fourier basis. We also demonstrate retrospective transmission of a transducer-compensated pulse in the imaging step, bypassing the limited precision of tri-state transmitter hardware.

This project implements previously developed techniques for guiding and monitoring thermal HIFU therapy using imaging arrays with a spherically shaped therapeutic array for dual-mode operation. Three-dimensional motion tracking, thermal strain measurement, and radiation force rebound measurement within the HIFU steering volume are performed using only the therapy array. The techniques have typically been studied for conventional ultrasound imaging using linear, curvilinear, or phased arrays which are usually placed coaxially in the center of the HIFU array. While the dual-mode approach does not provide the image quality and wide field of view of an imaging array, the perfect co-registration of the therapy array, and its 3D view of the region of interest present a valuable opportunity for ultrasound-guided focused ultrasound (USgFUS) therapy systems. A family of Sonic Concepts broadband spherically-focused HIFU array transducers, driven with the Verasonics HIFU-configured ultrasound system, is used to assess real-time performance of the dual-mode approach, in simulation and experiment. Simulations using the Verasonics acquisition software with a set of point scatterers produce the RF backscatter data used by the monitoring algorithms. The particles are displaced in time using motions that mimic the true or apparent displacements of tissue-like media either in translation, heated by a HIFU focus, or deformed by a radiation force beam. Preliminary experiments using a 128-element HIFU array and a scattering hydrogel phantom indicate that the simulations are effective for studying a range of tradeoffs in transducer design and therapy monitoring approaches.

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

Backscattered radio frequency (RF) data collected in a series of in vitro experiments, in which HIFU lesions were created in bovine liver tissue, were analyzed using two signal processing approaches to visualize temporal evolution of lesion formation. Change in round-trip travel time provides information related to temperature change during and after therapy. Changes in the RF spectrum related to changes in scattering properties of the heated region were observed before visible changes appeared on B-mode images. Effect of increased attenuation in the necrosed tissue region was also observed. Results demonstrate potential for these two techniques in image-guided HIFU therapy.

This paper describes a series of high intensity focused ultrasound (HIFU) phased array transducers with a single Archimedean spiral close packed element arrangement on a spherical surface extending from the central axis outward. Simulation and measurement reveal using the spiral element arrangement on a spherical bowl reduces grating side lobes while maximizing power density at the focus.

Objective. To develop a noninvasive method for treatment of uterine fibroid tumors using high-intensity focused ultrasound. Optimal high-intensity focused ultrasound treatment would be dependent on quantitative information about ultrasonic tissue characteristics. Methods. Ultrasonic attenuation and the sound speed of fresh human fibroid tumors and myometrium were measured as a function of frequency (1-3 MHz) by using a pulse transmission technique before and after in vitro high-intensity focused ultrasound treatment (3.5 MHz at an intensity of 2000 W/cm 2 ) Results. The ranges of the attenuation coefficients, before and after high-intensity focused ultrasound treatment, were 0.9 to 2.2 and 1.8 to 3.9 dB/cm 2 , respectively, for fibroid tumors and 0.5 to 1.6 and 1.7 to 3.3 dB/cm 2 , respectively, for myometrium. Although the sound speed appeared to be independent of frequency (1611 to 1616 m/s at 1 to 3 MHz) in both types of tissues, a slight increase of approximately 4 to 14 m/s was observed after high-intensity focused ultrasound treatment. Conclusions. The results of this study represent our first reported values of the attenuation coefficient and sound speed in fibroid tumors and myometrium before and after high-intensity focused ultrasound treatment.

Improved high-intensity focused ultrasound (HIFU) surgical applicators are required for use in a surgical environment. We report on the performance and characteristics of a new solid-cone HIFU applicator. Previous HIFU devices used a water-filled stand-off to couple the ultrasonic energy from the transducer to the treatment area. The new applicator uses a spherically-focused element and a solid aluminum cone to guide and couple the ultrasound to the tissue. Compared with the water-filled applicators, this new applicator is simpler to set up and manipulate, cannot leak, prevents the possibility of cavitation within the coupling device, and is much easier to sterilize and maintain during surgery. The design minimizes losses caused by shear wave conversion found in tapered solid acoustic velocity transformers operated at high frequencies. Computer simulations predicted good transfer of longitudinal waves. Impedance measurements, beam plots, Schlieren images, and force balance measurements verified strong focusing and suitable transfer of acoustic energy into water. At the focus, the -3 dB beam dimensions are 1.2 mm (axial)/spl times/0.3 mm (transverse). Radiation force balance measurements indicate a power transfer efficiency of 40%. In vitro and in vivo tissue experiments confirmed the applicator's ability to produce hemostasis.

High-intensity focused ultrasound (HIFU) has been shown to control bleeding from liver incisions, and blood vessel punctures and incisions. The objective of the current study was to investigate the capability of HIFU to stop bleeding from splenic injuries in a pig model.Surgical incisions, 25 to 50 mm in length and 2 to 8 mm in depth, were made in the spleens of five anesthetized pigs. HIFU with a frequency of 5 MHz was applied within 5 seconds of making the incision. A total of 39 incisions and HIFU treatments were performed.Bleeding from all incisions was stopped completely after HIFU treatment. The average times to control and completely arrest the hemorrhage were 28 and 55 seconds, respectively. The mechanisms of hemostasis appeared to be thermally induced coagulation necrosis of splenic tissue and occlusion of blood vessels by a mechanically induced homogenized splenic tissue.HIFU may provide a useful method of hemostasis for actively bleeding spleen. Because of its ability to induce hemostasis at adjustable depth, HIFU may prove to be a useful cauterization method both in the operating room and for patients who are managed nonoperatively.

Using human whole blood samples with and without contrast agent (CA), we evaluated the effect of exposures to focused, continuous wave (CW) 1.1-MHz ultrasound for durations of 10 ms to 1 s at spatial average intensities of 560 to 2360 W/cm2. Cavitation was monitored with a passive cavitation detector and hemolysis was determined with spectroscopy. In whole blood alone, no significant cavitation, heating or hemolysis was detected at any exposure condition. Conversely, cavitation and hemolysis, but not heating, were detected in whole blood with CA. A CA concentration as low as 0.28 microL CA per mL whole blood at an intensity of 2360 W/cm2 for 1 s resulted in measurable cavitation and a 6-fold increase in hemolysis compared to shams. Cavitation and hemolysis increased proportional to the concentration of CA and duration of exposure. In samples containing 4.2 microL CA per mL whole blood exposed for 1 s, a threshold was seen at 1750 W/cm2 where cavitation and hemolysis increased 10-fold compared to exposures at lower intensities. HIFU exposure of whole blood containing CA leads to significant hemolysis in vitro and may lead to clinically significant hemolysis in vivo.

The use of Doppler ultrasound was investigated to determine if it would aid in guiding the application of high-intensity focused ultrasound (HIFU) to stop bleeding from punctured vessels. Major vessels (abdominal aorta, illiac, carotid, common femoral and superficial femoral arteries and the jugular vein) were surgically exposed, punctured and treated in anesthetized pigs. Treatment was applied when the Doppler sounds indicated the focus coincided with the bleeding site. In 89 treatment trials, the average time to achieve major hemostasis (a point where bleeding was reduced to a level of only oozing) was 8 s, and for complete hemostasis was 13 s. These times were significantly shorter than those of an identical former study in which only visual guidance was used. In that study, the average times for major and complete hemostasis were 40 and 62 s, respectively. The advantage of Doppler guidance in applying HIFU in treating bleeding vessels was demonstrated.

Conventional hardware for arbitrary waveform formation uses Digital-to-Analog Converters (DAC) and linear amplifiers. Proposed here are methods for encoding a tri-state pulser to approximate arbitrary waveforms. Algorithms are evaluated by simulation and experiment using the Verasonics, Inc. Vantage research ultrasound system, which transmits with 4 ns edge resolution. Two problems were considered: 1) matching the waveform produced by an ideal DAC given a particular transducer, and 2) compensating for the impulse response of a given transducer to reproduce a signal. The problems require the transducer impulse response in one-way and two-way propagation geometries, estimated here in water using a hydrophone and the ATL L7-4 transducer. Within measured nonlinear propagation effects, error in these four scenarios for an LFM waveform was consistent with simulated performance. In another test, a Gaussian pulse is encoded for transducer compensation, and compared to equivalent-bandwidth monopulse excitation in planewave imaging on a phantom. Here, a pin-trailing pedestal artifact is reduced by 3 dB over a span equal to the peak resolution (FWHM).

A twinkling artifact (TA) associated with urinary calculi has been described as rapidly changing colors on Doppler ultrasound. The purpose of this study was to investigate the mechanism of the TA. Doppler processing was performed on raw per channel radio-frequency data collected when imaging human kidney stones in degassed water. Suppression of twinkling by an ensemble of computer generated replicas of a single received signal demonstrated that the TA arises from variability among the acoustic signals and not from electronic signal processing. This variability was found to be random in nature, and its suppression by elevated static pressure, and its return when the pressure was released, suggests that the presence of surface bubbles on the stone is the mechanism of the TA. Submicron size bubbles are often trapped in crevices on solid objects, but the presence of these bubbles in vivo is unexpected. To further check this mechanism under conditions identical to in vivo, stone-producing porcine kidneys were harvested en bloc with a ligated ureter and then placed into a pressure chamber and imaged at elevated atmospheric pressure. The result was similar to in vitro. Work supported by NIH DK43881, DK092197, RFBR 11-02-01189, 12-02-00114, and NSBRI through NASA NCC 9-58.

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

Vector velocity blood flow imaging gives speed and direction of blood flow at each pixel. An imaging algorithm proposed earlier [2] requires multiple angles of planewave (PW) transmissions to construct a robustly invertible model for vector velocity estimates. Here we demonstrate a vector velocity estimation approach that requires only a single planewave transmission angle. The proposed algorithm uses PW transmission and reconstruction to generate a blood motion image sequence in the B-mode flow (B-Flow) modality, at frame rates in the Doppler PRF regime. Pixel ensembles in the image sequence at point p = [x, z] and pulse t are comprised of IQ magnitude values, computed from the IQ data at each pixel p after wall filtering the ensemble. The sequence of values thus captures motion at a framerate equal to the PRF, revealing fine-scale flow dynamics as a moving texture in the blood reflectivity. Using the chain rule, spatial and temporal derivatives resulting from the space-time gradient of the image sequence couple to the texture flow velocity vector field [vx(x, z, t), vz(x, z, t)] at each pixel p and PRI t. The resulting Gauss-Markov models are solved by least squares to give the vector velocity estimates, which are formulated in the model to be constant over the estimation window. We also evaluate variants that include in the observation, lag-product samples (autocorrelation summands) at non-zero lags, as well as instantaneous Doppler-derived axial velocity estimates. Compared to the multi-angle planewave algorithm presented in [2], this approach allows for a longer time interval for wall filtering, as the frame is not partitioned into separate segments for different planewave angles. This permits wall filters with steeper transition bands, and allows flexibility in balancing framerate and sensitivity, suggesting application to vector flow imaging of deep tissue where efficiently achieving planewave angle diversity at the target becomes difficult. Using a Philips L7-4 transducer and a Verasonics (TM) acquisition system, we evaluate single-angle PWT vector velocity imaging on a Doppler string phantom, and demonstrate it successfully on a carotid artery.

A new method for computing wave scattering from rough surfaces, called the operator expansion (OE) method, has been proposed by D. M. Milder [J. Acoust. Soc. Am. 89(2), 529–541 (1991)]. In this paper, the OE method is examined in its application to acoustic scattering from one‐dimensional randomly rough surfaces with Gaussian and Pierson–Moskowitz roughness spectra satisfying the pressure release (Dirichlet) boundary condition. The operator expansion solution, which is expressed in a systematic series, is found to converge rapidly and monotonically for moderately rough surfaces, that is, for surfaces whose slope‐height roughness parameter khs, given by the product of acoustic wave number k, rms surface height h, and rms surface slope s, is less than about 0.25. Through comparison with a numerically exact integral equation solution, the OE method is found to be accurate over a wide range of incident and scattering angles. The method is currently used in a Monte Carlo computation of the scattering cross sec...

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

The properties of nonlinear acoustic wave propagation are known to be able to improve the resolution of ultrasound imaging, and could be used to dynamically estimate the physical properties of tissue. However, transducers capable of launching a wave that becomes nonlinear through propagation do not typically have the necessary bandwidth to detect the higher harmonics. Here we present the design and characterization of a novel multilayer transducer for high intensity transmit and broadband receive. The transmit layer was made from a narrow‐band, high‐power piezoceramic (PZT), with nominal frequency of 2.0 MHz, that was diced into an array of 32 elements. Each element was 0.300 mm wide and 6.3 mm in elevation, and with a pitch of 0.400 mm the overall aperture width was 12.7 mm. A quarter‐wave matching layer was attached to the PZT substrate to improve transmit efficiency and bandwidth. The overlaid receive layer was made from polyvinylidene fluoride (PVDF) that had gold metalization on one side. A custom two‐sided flex circuit routed electrical connections to the PZT elements and patterned the PVDF elements; the PZT and PVDF elements had identical apertures. A low viscosity and electrically nonconductive epoxy was used for all adhesion layers. Characterization of electrical parameters and acoustic output were performed per standard methods, where transmit and receive events were driven by a software‐controlled ultrasound engine. Echo data, collected from ex vivo tissue and digitized at 45 MS/s, exhibited frequency content up to the 4th harmonic of the 2 MHz transmit frequency.

The success of surgical management of lower pole stones is principally dependent on stone fragmentation and residual stone clearance. Choice of surgical method depends on stone size, yet all methods are subjected to post-surgical complications resulting from residual stone fragments. Here we present a novel method and device to reposition kidney stones using ultrasound radiation force delivered by focused ultrasound and guided by ultrasound imaging. The device couples a commercial imaging array with a focused annular array transducer. Feasibility of repositioning stones was investigated by implanting artificial and human stones into a kidney-mimicking phantom that simulated a lower pole and collecting system. During experiment, stones were located by ultrasound imaging and repositioned by delivering short bursts of focused ultrasound. Stone motion was concurrently monitored by fluoroscopy, ultrasound imaging, and video photography, from which displacement and velocity were estimated. Stones were seen to move immediately after delivering focused ultrasound and successfully repositioned from the lower pole to the collecting system. Estimated velocities were on the order of 1 cm/s. This in vitro study demonstrates a promising modality to facilitate spontaneous clearance of kidney stones and increased clearance of residual stone fragments after surgical management.

A partial nephrectomy, a surgery that preserves renal function, is desired for patients with small renal tumors. The system described in this paper applies high-intensity therapeutic ultrasound to obtain coagulation necroses of the renal blood vessels and hence protect the incised kidney from bleeding. The paper provides a brief description of the design and construction of the transducers, as well as presents the results of the acoustic characterization, dosimetry studies in tissue mimicking phantoms and dosimetry studies in ex vivo tissue. With optimum acoustic parameters, approximately 95% ablation was achieved during an in vivo perfused kidney study and the bleeding rate was decreased by 93%. The result suggests that the system can be used to control rapid bleeding; however, to achieve complete hemostasis consistently, more studies need to be conducted.

For high-intensity focused ultrasound (HIFU) to be widely applicable in the clinic, robust methods of treatment planning, guidance and delivery need to be developed. These technologies would greatly benefit if patient specific tissue parameters could be provided as inputs so that the treatment planning and monitoring schemes are customized and tailored on a case by case basis. A noninvasive method of estimating the local in situ acoustic heating rate using the heat transfer equation (HTE) and applying novel signal processing techniques is presented in this article. The heating rate is obtained by experimentally measuring the time required to raise the temperature of the therapeutic focus from a baseline temperature to boiling (here assumed to be 100 degrees C for aqueous media) and then solving the heat transfer equation iteratively to find the heating rate that results in the onset of boiling. The onset of boiling is noninvasively detected by measuring the time instant of onset of acoustic emissions in the audible frequency range due to violent collapse of bubbles. In vitro experiments performed in a tissue mimicking alginate phantom and excised turkey breast muscle tissue demonstrate that the noninvasive estimates of heating rate are in good agreement with those obtained independently using established methods. The results show potential for the applicability of these techniques in therapy planning and monitoring for therapeutic dose optimization using real-time acoustic feedback.

Nonlinear mechanisms of lesion formation by high intensity focused ultrasound (HIFU) were investigated experimentally and numerically in a transparent polyacrylamide gel phantom. Numerical predictions were made with a finite‐amplitude acoustic propagation model. A 2‐MHz transducer of 42‐mm diameter and 44.5‐mm radius of curvature was operated above the cavitation threshold of the gel phantom at various peak acoustic powers and duty cycles. Acoustic waveforms were recorded in the gel by a fiber optic hydrophone. Bubble activity was detected actively by B‐mode diagnostic imaging, passively by a remote focused hydrophone, and optically by CCD and high‐speed cameras. Elevated static pressure was applied to suppress bubble activity and increase the boiling temperature, thus isolating the pure effect of acoustic nonlinearity. In overpressure experiment performed at 32 W acoustic power, both cavitation and nonlinear ultrasound propagation accelerated lesion inception and growth, but acoustic nonlinearity, which led to shock formation, played the dominant role. Rapid localized heating, particularly by increased absorption in the shocked wave, led to boiling and then to proximal growth and migration of the lesion even at low overpressure. At 90W acoustic power, boiling was observed and predicted in less than 50 ms.

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

Transcutaneous surgical procedures performed with a high intensity focused ultrasound (HIFU) therapy system can be monitored in real-time with an ultrasound imaging system if the HIFU is gated appropriately. Without synchronization, gated or continuous HIFU saturates the imaging system and interference occludes the image. If a gating signal is synchronized with the imaging cycle from any commercial imager, the location of any interference can be controlled and the HIFU treatment region can he visualized in real-time. Synchronization typically requires that an imaging system be customized for HIFU therapy, which is expensive and time consuming. We have developed a low-cost prototype system that synchronizes a HIFU therapy system with an arbitrary unmodified imaging system by using the HIFU transducer as a focused receiver that can detect scattered acoustic signals transmitted by the imaging probe. The receive signal is processed into a trigger that is used to control the gating and phasing of the HIFU relative to the imaging cycle. The technique is tested using a B-mode imager to monitor the formation of a lesion in a transparent tissue phantom; exposure time is 60 seconds with 40 W (time-averaged) electrical power delivered to the transducer. Performance is evaluated by recording the position of interference on the B-mode images and by comparing the B-mode images with CCD images that provide an optical view of lesion formation.

An optically transparent phantom was developed for use in high-intensity focused ultrasound (US), or HIFU, dosimetry studies. The phantom is composed of polyacrylamide hydrogel, embedded with bovine serum albumin (BSA) that becomes optically opaque when denatured. Acoustic and optical properties of the phantom were characterized as a function of BSA concentration and temperature. The speed of sound (1544 m/s) and acoustic impedance (1.6 MRayls) were similar to the values in soft tissue. The attenuation coefficient was approximately 8 times lower than that of soft tissues (0.02 Np/cm/MHz for 9% BSA). The nonlinear (B/A) coefficient was similar to the value in water. HIFU lesions were readily seen during formation in the phantom. In US B-mode images, the HIFU lesions were observed as hyperechoic regions only if the cavitation activity was present. The phantom can be used for fast characterization and calibration of US-image guided HIFU devices before animal or clinical studies.

The use of moving high‐intensity focused ultrasound (HIFU) treatment protocols is of interest in achieving efficient formation of large‐volume thermal lesions in tissue. Judicious protocol design is critical in order to avoid collateral damage to healthy tissues outside the treatment zone. A KZK‐BHTE model, extended to simulate multiple, moving scans in tissue, is used to investigate protocol design considerations. Prediction and experimental observations are presented which 1) validate the model, 2) illustrate how to assess the effects of acoustic nonlinearity, and 3) demonstrate how to assess and control collateral damage such as prefocal lesion formation and lesion formation resulting from thermal conduction without direct HIFU exposure. Experimental data consist of linear and circular scan protocols delivered over a range of exposure regimes in ex vivo bovine liver.

This report summarizes research efforts conducted under the ONR grant entitled An Acoustic Hemostasis Device for Acute Arterial Bleeding, " Lawrence Crum, Principal Investigator. The revised scope of effort concentrated on four tasks: Bleeding Detection, Therapy Delivery, Systems Design and Development, and Animal Testing of Systems. The revised performance period was 19 February 2002 - 31 December 2003.

A hydrogel acoustic coupling medium was investigated as a practical alternative to water for clinical applications of focused ultrasound (US) therapy. Material characterization and functional testing of polyacrylamide gel couplers were performed. Acoustic, bulk and thermal properties were measured. Conical couplers were designed and fabricated to fit a 3.5-MHz, spherically concave transducer for functional tests, including Schlieren imaging, power efficiency measurements and in vivo hemostasis experiments. Polyacrylamide was shown to have favorable acoustic properties that varied linearly with acrylamide concentration from 10% to 20% weight in volume. Attenuation coefficient, sound speed and impedance ranged from 0.08 to 0.14 dB/cm at 1 MHz, 1546 to 1595 m/s and 1.58 to 1.68 Mrayl, respectively. An intraoperative in vivo hemostasis experiment in a sheep model demonstrated that the gel-coupled transducer was capable of inducing hemostasis in actively bleeding splenic and hepatic incisions. The results of this study show that polyacrylamide may be a promising coupling material for focused US therapy.

Recent interest in using High Intensity Focused Ultrasound (HIFU) for surgical applications such as hemostasis and tissue necrosis has stimulated the development of image-guided systems for non-invasive HIFU therapy. Seeking an all-ultrasound therapeutic modality, we have developed a clinical HIFU system comprising an integrated applicator that permits precisely registered HIFU therapy delivery and high quality ultrasound imaging using two separate arrays, a multi-channel signal generator and RF amplifier system, and a software program that provides the clinician with a graphical overlay of the ultrasound image and therapeutic protocol controls. Electronic phasing of a 32 element 2 MHz HIFU annular array allows adjusting the focus within the range of about 4 to 12 cm from the face. A central opening in the HIFU transducer permits mounting a commercial medical imaging scanhead (ATL P7-4) that is held in place within a special housing. This mechanical fixture ensures precise coaxial registration between the HIFU transducer and the image plane of the imaging probe. Recent enhancements include development of an acoustic lens using numerical simulations for use with a 5-element array. Our image-guided therapy system is very flexible and enables exploration of a variety of new HIFU therapy delivery and monitoring approaches in the search for safe, effective, and efficient treatment protocols.

The ability to accurately track and monitor the progress of lesion formation during HIFU (High Intensity Focused Ultrasound) therapy is important for the success of HIFU-based treatment protocols. To aid in the development of algorithms for accurately targeting and monitoring formation of HIFU induced lesions, we have developed a software system to perform RF data acquisition during HIFU therapy using a commercially available clinical ultrasound scanner (ATL HDI 1000, Philips Medical Systems, Bothell, WA). The HDI 1000 scanner functions on a software dominant architecture, permitting straightforward external control of its operation and relatively easy access to quadrature demodulated RF data. A PC running a custom developed program sends control signals to the HIFU module via GPIB and to the HDI 1000 via Telnet, alternately interleaving HIFU exposures and RF frame acquisitions. The system was tested during experiments in which HIFU lesions were created in excised animal tissue. No crosstalk between the HIFU beam and the ultrasound imager was detected, thus demonstrating synchronization. Newly developed acquisition modes allow greater user control in setting the image geometry and scanline density, and enables high frame rate acquisition. This system facilitates rapid development of signal-processing based HIFU therapy monitoring algorithms and their implementation in image-guided thermal therapy systems. In addition, the HDI 1000 system can be easily customized for use with other emerging imaging modalities that require access to the RF data such as elastographic methods and new Doppler-based imaging and tissue characterization techniques.

Several mechanisms are postulated to be responsible for acoustically-induced hemostasis. Both mechanical and thermal aspects of ultrasound energy are thought to play a role. Thermal effects may be important when tissue shrinkage is necessary to close a bleeding site. A moderate temperature rise may also accelerate clotting when hypothermia and coagulopathy is present. Tissue welding via collagen restructuring may be promoted via a thermal effect. The mechanical effects of streaming and radiation pressure may assist in stopping the flow of blood out of a wound and, if directed properly, may cause insertion of blood vessel wall material into a breached region to plug the hole, and aid the natural clotting mechanism. Streaming may provide shearing forces on platelets, facilitating their activation for subsequent aggregation and adhesion to the vessel wall. Cavitation may produce tissue disruption that exposes collagen and tissue factors to platelets thus assisting in triggering clotting. These mechanisms are discussed, and supportive evidence given.

We have examined the operator expansion (OE) method in computing scattering over a wide range of scattering regimes, for l-D Dirichlet surfaces with Gaussian spectra, and with Pierson-Moskowitz spectra (used to model the ocean surface). We give a brief review of a derivation of the standard OE solution, and show how the short series are obtained. Numerical examples are presented illustrating the rapid convergence and wide accuracy of the various forms of the OE solution in several scattering regimes. Our results indicate that the short series provide efficient and accurate alternatives to the standard solution, a finding which is of significant practical value in treating scattering from 2-D surfaces. In general, our results for scattering from l-D surfaces suggest that the OE is a very attractive method for computing scattering from a wide range of realistic 2-D rough surfaces with a Dirichlet boundary condition. We also present the alternative forms of the OE solution and give one example for scattering from surfaces with a Gaussian spectrum. >

While many tissue-mimicking phantoms have been developed for ultrasound imaging applications, none is suitable for exploration of the high temperature and pressure regimes involved in High Intensity Focused Ultrasound (HIFU). HIFU dosimetry studies are usually performed on biological tissues, but this approach has two drawbacks: 1) tissues are opaque and development of coagulative lesions cannot be visually observed in real-time, and 2) the natural heterogeneous structure of tissue may complicate direct comparison with numerical models. To address these issues, a new optically transparent tissue phantom was developed. It is a polyacrylamide hydrogel with a thermally sensitive indicator protein (Bovine Serum Albumin, 3 - 9%) that becomes optically diffusive when denatured. We describe various measurements undertaken to characterize this material and to demonstrate how well it matches tissue in terms of bulk acoustic and thermal properties. In summary, this new phantom material simulates many of the lesion-forming characteristics of soft tissue under HIFU exposures.

The relative performance of two different ultrasonic units commonly used clinically for post removal was evaluated using tips designed specifically for post vibration. Twenty-four extracted maxillary and mandibular cuspids with crowns removed at the labial cementoenamel junction were treated endodontically. Post spaces were made 10 mm into the roots before cementing a 16 mm #5 (0.050-inch) Para-Post with zinc phosphate cement. The teeth were divided into three similar groups of eight. Post retention was assessed in group 1. Ultrasonic vibration was applied to groups 2 and 3 until post removal. The average force required to dislodge the posts from the teeth in group 1 (control group, no ultrasound) was 40.5 kg (SD = 12.3 kg). The average time for post removal in group 2 (Spartan) was 4:52 min (SD = 2:26). The average time for post removal in group 3 (Enac) was 1:31 min (SD = 0:34). The difference between groups 2 and 3 was statistically significant (p < 0.005). Use of ultrasonic tips designed for post vibration and maximization of audible sound level during ultrasonic treatment of posts seem to play an important role in the effectiveness and efficiency of post removal. The results obtained indicate that both the Enac ultrasonic unit with the ST-09 vibration tip and the Spartan ultrasonic unit with the Analytic VT-S tip were effective. Nevertheless, the Enac ultrasonic unit with the ST-09 vibration tip was clearly more efficient under these study conditions, resulting in typical post removal times of

Accurate differentiation between stagnant blood and soft tissue or clotted and unclotted blood has potential value in managing trauma patients with internal hemorrhage. Determination by regular ultrasound (US) imaging is sometimes difficult because the sonographic appearance of blood, clots and soft tissue may be similar. A hematoma model was developed to investigate the use of acoustic streaming for hematoma diagnosis in an in vivo environment. The results showed that a derated spatial peak temporal average (SPTA) intensity of 30 W/cm(2) was needed to generate color-Doppler-detectable streaming in stirred blood. The streaming velocity increased in proportion to the derated intensity. Streaming was also detected in stagnant blood, but at higher intensities. In clots, streaming was not detected even at high intensities. The streaming detection may be a valuable tool for improving the distinction between liquid blood and clots or soft tissue in hematoma diagnosis.

▪ Abstract The potential role of therapeutic ultrasound in medicine is promising. Currently, medical devices are being developed that utilize high-intensity focused ultrasound as a noninvasive method to treat tumors and to stop bleeding (hemostasis). The primary advantage of ultrasound that lends the technique so readily to use in noninvasive therapy is its ability to penetrate deep into the body and deliver to a specific site thermal or mechanical energy with submillimeter accuracy. Realizing the full potential of acoustic therapy, however, requires precise targeting and monitoring. Fortunately, several imaging modalities can be utilized for this purpose, thus leading to the concept of image-guided acoustic therapy. This article presents a review of high-intensity focused ultrasound therapy, including its mechanisms of action, the imaging modalities used for guidance and monitoring, some current applications, and the requirements and technology associated with this exciting and promising field.

Objective: High-intensity focused ultrasound (HIFU) has been shown to be effective in controlling hemorrhage from punctures in blood vessels. The objective of the current study was to investigate the capability of HIFU to stop bleeding after a more severe type of vascular injury, namely longitudinal incisions of arteries and veins. Methods: The superficial femoral arteries, common femoral arteries, carotid arteries, and jugular veins of four anesthetized pigs were exposed surgically. A longitudinal incision, 2 to 8 mm in length, was produced in the vessel. HIFU treatment was applied within 5 seconds of the onset of the bleeding. The HIFU probe consisted of a high-power, 3.5-MHz, piezoelectric transducer with an ellipsoidal focal spot that was 1 mm in cross section and 9 mm in axial dimension. The entire incision area was scanned with the HIFU beam at a rate of 15 to 25 times/second and a linear displacement of 5 to 10 mm. A total of 76 incisions and HIFU treatments were performed. Results: Control of bleeding (major hemosatsis) was achieved in all 76 treatments, with complete hemostasis achieved in 69 treatments (91%). The average treatment times of major and complete hemostasis were 17 and 25 seconds, respectively. After the treatment, 74% of the vessels in which complete hemostasis was achieved were patent with distal blood flow and 26% were occluded. The HIFU-treated vessels showed a consistent coagulation of the adventitia surrounding the vessels, with a remarkably localized injury to the vessel wall. Extensive fibrin deposition at the treatment site was observed. Conclusion: HIFU may provide a useful method of achieving hemostasis for arteries and veins in a variety of clinical applications. (J Vasc Surg 1999;29:533-42.)

The hemorrhagic complications of vascular injury can be significant. We report on the use of high-intensity focused ultrasound (HIFU) to stop the hemorrhage of punctured blood vessels in pigs. Two HIFU transducers with frequencies of 3.5 and 2.0 MHz, each equipped with a water-filled conical housing, were used. Major blood vessels (femoral artery and vein, axillary artery, carotid artery and jugular vein), 2-10 mm in diameter, of anesthetized pigs were exposed surgically and punctured with 14- and 18-gauge needles to produce moderate to profuse bleeding. Complete hemostasis was achieved in less than 3 min of HIFU treatment in most blood vessels, and all vessels were patent after the treatment. Both HIFU frequencies were effective in producing hemostasis. Gross examination of the HIFU-treated vessels showed a consistent hardening of the soft tissue surrounding the blood vessels, providing a seal for the puncture hole. Microscopic examination of the vessels showed a remarkably localized HIFU treatment, resulting in coagulation of the adventitia, and an extensive fibrin network around the vessels and in the puncture hole. The vessel walls exhibited focal swelling, without evidence of irreversible injury. HIFU may provide a useful method for achieving hemostasis of punctured and traumatized blood vessels in a variety of clinical settings.

Therapeutic ultrasound has an increasing number of applications in urology, including shockwave lithotripsy, stone propulsion, tissue ablation, and hemostasis. However, the threshold of renal injury using ultrasound is unknown. The goal of this study was to determine kidney injury thresholds for a range of intensities between diagnostic and ablative therapeutic ultrasound. A 2 MHz annular array generating spatial peak pulse average intensities (ISPPA) up to 30,000 W/cm2 in water was placed on the surface of in vivo porcine kidneys and focused on the adjacent parenchyma. Treatments consisted of pulses of 100 μs duration triggered every 3 ms for 10 min at various intensities. The perfusion-fixed tissue was scored by three blinded independent experts. Above a threshold of 20,000 W/cm2, the majority of injury observed included emulsification, necrosis, and hemorrhage. Below this threshold, almost all injury presented as focal cell and tubular swelling and/or degeneration. These findings provide evidence for a wide range of potentially therapeutic ultrasound intensities that has a low probability of causing injury. While this study did not examine all combinations of treatment parameters of therapeutic ultrasound, tissue injury appears dose-dependent. [Work supported by NIH DK43881, DK092197, and NSBRI through NASA NCC 9-58.]

The twinkling artifact can highlight kidney stones during ultrasound color Doppler imaging with high sensitivity for stone detection. The mechanism of the twinkling artifact is still under debate. It was reported previously that twinkling appeared distal to the echogenic reflection from the stone surface in cases with no signal saturation. [Lu etal., JASA 129(4), p. 2376]. In this report, the effect of specular reflections on twinkling was investigated. Human kidney stones (5-9 mm in length) were embedded in a polyacrylamide gel phantom. Radio-frequency (RF) data were recorded from pulse-echo ensembles using a software-programmable ultrasound system. The variability within the beamformed Doppler ensemble, which is responsible for twinkling, was traced back to the unbeamformed RF channel data to identify whether variability arose disproportionately on channels receiving the specular reflection. The results showed that the specular reflection did not saturate individual channels and that the variability was observed on most channels with similar magnitude, which indicates that the appearance of twinkling does not rely on the specular reflection from the stone surface. Instead in the beamformer, the varying signals have the appearance of arising from a point source within the stone. [Work supported by NIH DK43881, DK086371, DK092197, and NSBRI through NASA NCC 9-58.]

Phase propagation using the Rytov method has recently been proposed as a means for modeling the time‐of‐flight changes induced by thermal therapy [Speyer et al., J. Acoust. Am. 127]. These results are extended to measurements from a linear array, under which the general problem of imaging material changes is cast. The linear array offers several design components, which can be exploited for therapy monitoring, including the apodization and probing frequency. Phase propagation models are shown to be consistent with many aspects of conventional modeling, linearizing material changes around the same operating points as have been proposed by other researchers, and providing time‐of‐flight changes linearly related to the temperature distribution under these conditions. Beyond expanding on model properties, experimental evidence is presented, which indicates that phase propagation modeling is significantly more consistent with backscattered ultrasound data than conventional ray approaches. [Work supported by NI...

Noninvasive ablative high intensity focused ultrasound (HIFU) therapy must be guided with precision, and monitored in real‐time. Magnetic resonance imaging (MRI) can provide both high resolution tissue‐specific images and temperature maps, but even the most recently developed MRI methods cannot do so in less than a few seconds. Ultrasonic imaging techniques using a sequence of rf frames to measure heating‐induced apparent strain have been developed to produce heating maps, but the approach is challenging due to lack of sensitivity and substantial variability in tissue properties. To improve estimates of temperature rise, constraints based on heat diffusion modeling are imposed, thus minimizing the effects of noise and nonmonotonicity of the speed of sound with respect to temperature throughout the therapeutic range. Furthermore, noninvasive protocols for measuring relevant HIFU field and tissue properties in the region of interest enable patient‐calibrated mapping of temperature rise during HIFU, at ultra...

The Verasonics ultrasound system is a highly programmable data acquisition and processing platform designed to facilitate development of new medical ultrasound imaging methods. In contrast to conventional commercial ultrasound systems, individual element digitized rf data are available to the developer. All beamforming and postprocessing are done in software, and both the hardwaredata acquisition sequence and the host computer processing flow are programmable by the user using a MATLABinterface. Because the system is designed to be highly flexible, it can also be useful as a practical tool in teaching acoustic wave physics, transducer and array design, and data processing concepts, using benchtop scale homemade acoustic and elastic media, including flow models. For script evaluation and testing, the Verasonics system includes a hardware simulator that uses a simple point scatterer numerical model to compute rf backscatter data. rf data can also be recorded during a hardware acquisition, and then reprocessed using different user‐developed algorithms for comparative study. Because the system is easy to learn, many fundamental concepts can be explored in a laboratory setting, using scattering media or custom transducers fabricated as part of the student experimental plan. The system enables sophisticated hands‐on experience with acoustics beyond the numerical world.

Shock‐wave heating and millisecond boiling in high intensity focused ultrasound fields have been shown to result in mechanical emulsification of ex‐vivo tissue. In this work, the same in situ exposures were applied in vivo in pig liver and in mice bearing 5–7 mm subcutaneous tumors (B16 melanoma) on the hind limb. Lesions were produced using a 2‐MHz annular array in the case of pig liver (shock amplitudes up to 98 MPa) and a 3.4‐MHz single‐element transducer in the case of mouse tumors (shock amplitude of 67 MPa). The parameters of the pulsing protocol (1–500 ms pulse durations and 0.01–0.1 duty factor) were varied depending on the extent of desired thermal effect. All exposures were monitored using B‐mode ultrasound. Mechanical and thermal tissue damage in the lesions was evaluated histologically using H&E and NADH‐diphorase staining. The size and shape of emulsified lesions obtained in‐vivo agreed well with those obtained in ex‐vivo tissue samples using the same exposure parameters. The lesions were successfully produced both in bulk liver tissue at depths of 1–2 cm and in superficial tumors at depths less than 1 mm without damaging the skin. [Work supported by NIH (DK070618, EB007643, and DK007742) and NSBRI through NASA NCC 9‐58.]