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Objective: This article presents shear wave generation by remotely stimulating aluminum patches through a transient magnetic field, and its preliminary application in the cross-correlation approach based ultrasound elastography. Methods: A transient magnetic field is employed to remotely vibrate the patch actuators through the Lorentz force. The origin, and the characteristics of the Lorentz force are confirmed using an interferometric laser probe. The shear wave displacement fields generated in the soft medium are studied through the ultrafast ultrasound imaging. The potential of the shear wave fields generated through the patch actuators for the cross-correlation approach based elastography is confirmed through experiments on an agar phantom sample. Results: Under a transient magnetic field of changing rate of 10.44 kT/s, the patch actuator generates a shear wave source of amplitude of 100 $\mu$ m in a polyvinyl alcohol (PVA) phantom sample. The shear wave fields created by experiments agree qualitatively well with those by theory. From the shear wave velocity map computed from 100 frames of shear wave fields, the boundaries of cylindrical regions of different stiffness can be clearly recognized, which are completely concealed in the ultrasound image. Conclusion: Shear wave fields in the level of 100 $\mu$ m can be remotely generated in soft medium through stimulating aluminum patches with a transient magnetic field, and qualitative shear wave velocity maps can be reconstructed from the shear wave fields generated. Significance: The proposed method allows potential application of the cross-correlation approach based elastography in intravascular-based or catheter-based cardiology.

This work focuses on the evaluation of a type of piezoelectric lithotripter with similar dimensions of a commercial lithotripter and composed of either 3 or 4 large lens focused piezoelectric transducers set either in a confocal coplanar C-shape or a confocal spherical shape. Each transducer is made with a 92 mm diameter 220 kHz flat piezoelectric ceramic disc and a 3D printed acoustic lens. Both confocal setups pressure field were measured with a fiber optic hydrophone, and in vitro fragmentations of 13 mm diameter and 14 mm length cylindrical model stones were done in a 2 mm mesh basket. The acoustic characterization of the three transducers confocal setup revealed a disc shaped focal volume, with a 2.2 mm width on one axis and a 9.6 mm width on the other, and a peak positive pressure of 40.9 MPa and a peak negative pressure of −16.9 MPa, while the focus of the four transducers confocal setup was similar to a traditional narrow focus high pressure lithotripter with a focus width of 2.1 mm, and a peak positive pressure of 71.9 MPa and peak negative pressure of −24.3 MPa. Both confocal setups showed in vitro fragmentation efficiency close to a commercial electroconductive lithotripter.

Usually, piezoelectric lithotripters consist of a high quantity of small flat piezoelectric discs tied to a spherical structure, where the focus is the geometric center of the sphere. The small diameter of the ceramics compared to the distance to the focus of the lithotripter means that only a fraction of the surface pressure will arrive to the focus, and also results in a very small focal diameter. This work focus on the evaluation of a new type of piezoelectric lithotripter with similar dimensions of a commercial lithotripter and composed of either 3 or 4 large lens focused piezoelectric transducers with focal pressure up to 25 MPa each, set either in a confocal C-shape or confocal ring-shape. Each transducer is made with a 92 mm diameter flat piezoelectric ceramic disc of 220, 300, or 400 kHz thickness frequency and the acoustic lens shape was calculated using finite element optimization in order to maximize its focusing capability. Comparison of artificial stone comminution efficiency depending on the frequency, pressure, and the setup of the piezoelectric transducers were made and compared to commercially available lithotripters. [Work supported by an industrial grant from EDAP-TMS.]Usually, piezoelectric lithotripters consist of a high quantity of small flat piezoelectric discs tied to a spherical structure, where the focus is the geometric center of the sphere. The small diameter of the ceramics compared to the distance to the focus of the lithotripter means that only a fraction of the surface pressure will arrive to the focus, and also results in a very small focal diameter. This work focus on the evaluation of a new type of piezoelectric lithotripter with similar dimensions of a commercial lithotripter and composed of either 3 or 4 large lens focused piezoelectric transducers with focal pressure up to 25 MPa each, set either in a confocal C-shape or confocal ring-shape. Each transducer is made with a 92 mm diameter flat piezoelectric ceramic disc of 220, 300, or 400 kHz thickness frequency and the acoustic lens shape was calculated using finite element optimization in order to maximize its focusing capability. Comparison of artificial stone comminution efficiency depending on the...

The objective of this project was to integrate a LEFUS-system to a patch-clamp platform for exploration of LEFUS-modulated and/or -stimulated electrophysiological responses from individual cultured neurons. Mouse primary neurons and human neural progenitor cells were cultured and plated onto 35-mm diameter Petri dishes. A whole-cell patch-clamp setup in current-clamp mode was used to record electrophysiological activity generated by the neurons. The LEFUS system consisted of a 2.2-MHz planar transducer (diameter: 10-mm), administering 0.5–10 ms pulses at pressures of 6–50 kPa. Neuromodulation studies consisted in measuring changes in the activation threshold to electrical stimulation (current density required to trigger an action potential: AP) in LEFUS-treated neurons. Neurostimulation experiments consisted in measuring electrophysiological responses to LEFUS exposures in the form of triggered APs or electrical discharges from the patched neuron. Neuromodulation results showed that the activation threshold required for triggering APs could be either elevated or lowered by approximately 25% following LEFUS treatment. In neurostimulation experiments, LEFUS pressures of 25 kPa and pulse durations of 10 ms were sufficient for either disturbing the membrane potential of the cell and, occasionally, depolarizing the neuron by approximately 70 mV. [This project was supported by the French National Research Agency (ANR-16-TERC-0017), LabEx DevWeCan, and Focused Ultrasound Foundation (Centers of Excellence).]

This study examined the feasibility of high-intensity focused ultrasound (HIFU) for glaucoma treatment with conformal coagulation of the ciliary bodies (CB). A miniaturized high frequency (21 MHz) device was developed, based on the geometry of the eye and adapted to the anatomy of the rabbit eyeball. Six line-focus lesions were distributed along a circle and produced by six cylindrical transducers. To be conformal, the numerical model predicted an intensity of 6.9 W/cm2, with exposure duration of 3 s ON (powered per sector). In vivo experiments were conducted on two rabbits. A significant intraocular pressure reduction was noted (–45% and –31%). Histology demonstrated conformal and homogeneous coagulation of the CB without side effects. (E-mail: thomas.charrel@inserm.fr )

Image-guided thermal ablation offers minimally invasive options for treating hepatocellular carcinoma and colorectal metastases in liver. Here, the feasibility and the potential benefit of active temperature control for MR-guided percutaneous ultrasound ablation was investigated in pig liver. An MR-compatible interstitial ultrasound applicator (flat transducer), a positioning system with rotation-translation guiding frame, and an orbital ring holder were developed. Step-by-step rotated elementary lesions were produced, each being formed by directive heating of a flame-shaped volume of tissue. In vivo feasibility of automatic temperature control was investigated on two pigs. Proton Resonance Frequency Shift (PRFS)-based MR thermometry was performed on a 1.5-T clinical scanner, using SENSE acceleration and respiratory gating. MR follow-up of animals and macroscopic analysis were performed at 3 and, respectively, 4 days postprocedure. No sonication-related radiofrequency artifacts were detected on MR images. The temperature controller converged to the target elevation within +/-2 degrees C unless the requested power level exceeded the authorized limit. Large variability of the controller's applied powers from one sonication to another was found both ex vivo and in vivo, indicating highly anisotropic acoustic coupling and/or tissue response to identical beam pattern along different radial directions. The automatic control of the temperature enabled reproducible shape of lesions (15 +/- 2 mm radial depth).

Unresectable liver tumors are often treated with interstitial probes that modify tissue temperature, and efficacious treatment relies on image guidance for tissue targeting and assessment. Here, we report the in vivo evaluation of an interstitial applicator with a mechanically oscillating five-element dual-mode transducer. After thoroughly characterizing the transducer, tissue response to high-intensity ultrasound was numerically calculated to select parameters for experimentation in vivo. Using perfused porcine liver, B-mode sector images were formed before and after a 120-s therapy period, and M-mode imaging monitored the therapy axis during therapy. The time-averaged transducer surface intensity was 21 or 27 W/cm (2). Electroacoustic conversion efficiency was maximally 72 +/- 3% and impulse response length was 295 +/- 1.0 ns at -6 dB. The depth of thermal damage measured by gross histology ranged from 10 to 25 mm for 13 insertion sites. For six sites, M-mode data exhibited a reduction in gray-scale intensity that was interpreted as the temporal variation of coagulation necrosis. Contrast ratio analysis indicated that the gray-scale intensity dropped by 7.8 +/- 3.3 dB, and estimated the final lesion depth to an accuracy of 2.3 +/- 2.4 mm. This paper verified that the applicator could induce coagulation necrosis in perfused liver and demonstrated the feasibility of real-time monitoring.

The standard methods for recanalyzing thrombosed vessels are vascular stenting or administration of thrombolytic drugs. However, these methods suffer from uncertain success rate and side-effects. Therefore, minimally-invasive ultrasound methods have been investigated. In this article, we propose to use shockwaves after pre-exposure to fibrinolytic agent for disrupting thrombus. Shockwaves were delivered by an extracorporeal piezocomposite generator (120 mm in diameter, focused at 97 mm, pulse length = 1.4 micros). In vitro blood clots, made from human blood, were placed at the focal point of the generator. The clots were exposed to shockwaves either with or without prior immersion in a solution of streptokinase. The percentage of lysed clot was determined by weighing the clot before and after treatment. The proportion of lysed clot increased with the pressure at the focus and with the number of shocks. A mean clot reduction of 91% was obtained for 42 MPa in 4-min treatment duration only, without using streptokinase. For a treatment of 2 min at 29 MPa, the clot reduction increased significantly (p0.01) from 47% without streptokinase to 82% when streptokinase was used prior to shockwaves. These results also showed no significant damage to streptokinase due to exposure to shockwaves. This study suggests that extracorporeal shockwaves combined with streptokinase is a promising pharmaco-mechanical method for treating occlusive thrombus, and should be confirmed by in vivo trials. Additional studies must also be conducted with other fibrinolytic agents, whose abilities to penetrate clots are different.

High intensity ultrasounds are routinely used for thermal ablation of some cancers. However, for treating hepatic tumours with physical agents, RF applicators and cryoprobes are still preferred. The goal of the present study was to demonstrate the feasibility of using interstitial ultrasound probes in liver following two approaches: percutaneous and intra-tissular or endo vascular. In vivo trials on a porcine model demonstrated the minimally invasive nature of both procedures. Homogeneous and reproducible thermal lesions, up to 20 mm deep, were obtained. The work on these two original approaches deserves to be completed with more extended prospective studies. The association with an imaging method will have to be studied before proceeding to clinical trials.

International audience; In some patients at risk of disease recurrence of renal cancers, maximum conservation of the kidney is possible through partial nephrectomy. However, bloodless surgery is difficult to achieve. The article describes an ultrasonic clamp, which optimises energy deposition and monitors lesion development with an echo-based technique. Using this novel apparatus, coagulation necroses have been obtained in vitro on substantial thicknesses (23 to 38 mm) over exposure durations ranging from 10 s to 130 s, and with acoustic intensities of less than 15 W/cm(2) per transducer. When used for coagulation purposes, two transducers situated on opposite arms of the clamp are driven, while for monitoring, only one is used. Lesions are monitored in real time by analysing the echo signal returned by the opposite arm of the clamp. The presence of a lesion is evaluated on the basis of energy changes and echo phase as a function of time. Both kidneys of two pigs (30 to 36 mm thick) were treated in vivo with the clamp, and the partial nephrectomies performed proved to be bloodless.

The acoustic nonlinear parameter, B∕A, is an important piece of data whenever high intensity pressure fields are under consideration. In this work, an alternative method is proposed to measure this parameter. First, the method involves measuring the sound velocity and nonlinear waveform distortion of a finite amplitude plane wave propagating through a medium, Butanediol, whose density and attenuation law have been preliminarily determined. Measurements were performed in the nearfield of a piston where plane wave propagation regime exists. Impulse response of the hydrophone was determined and pressure waveforms were obtained by a convolution process. Then, the method involves modeling, in time domain and under experimental conditions, the theoretical nonlinear waveform distortion and fitting it to the experimental results by adjusting the B∕A parameter. Comparative measurements were performed using the technique of parametric interaction. The respective results for the two methods (B∕A=11.0±10% and 10.9±5%...

New clinical concepts in lithotripsy demand smaller shock heads. Reducing the size of piezoelectric shock heads requires increasing the surface pressure of each transducer so that the total pressure at the focus remains the same. A new method allowing generation of large surface pressures is described. The hypothesis is that piezoelectric plots in piezo-composite material are more fragile in extension than in compression. For this reason, actuators are mechanically prestressed between two flasks. This method cannot be used for transducers working at high frequencies, such as 0.5 MHz. So we tried to electrically prestrain compressively the piezoelectric material by applying a high-electrical field in the opposite direction of polarization. Three protocols were tested and compared to classically driven transducers. In the first protocol, prestrain is permanently applied, in the second protocol prestrain is applied for 100 /spl mu/s before the compressive impulse, and in the third protocol prestrain is applied for 100 /spl mu/s and followed by a bipolar field that allows the material to be repoled between two successive pulses. With the two first protocols, rapid depoling and repoling in the opposite direction was noticed. Only with the last protocol was it possible to increase the maximum surface pressure. This increase was approximately the same whether the material was hard or soft. Using this protocol, aging tests were conducted on three samples of each kind of material, and a pressure of 4 MPa was obtained over 10e shocks. This value seems to be enough to develop a piezoelectric shock-wave generator with a diameter of approximately 20 cm instead of the 45-cm commercially available.

Intraluminal (within the alimentary tract) thermal surgery has been shown to be a useful therapeutic option when extracorporeal focused ultrasound applicators cannot be used since their beam may not reach the target site. If plane transducers are used for the treatment of alimentary tract tumours, the applicator must be rotated in order to generate a cylindrical volume of necrosis. However, rotating these applicators and controlling their shooting direction presents technical difficulties. If tubular transducers are used it is difficult to treat arbitrary angles with a large therapeutic length. To solve these difficulties, the feasibility of an ultrasound phased array applicator has been evaluated using a cylindrical prototype (outer diameter 10.6 mm), which is composed of 16 elementary transducers working at 4.55 MHz and arranged on a quarter of the cylinder. Using this applicator it is possible to generate plane or cylindrical waves. Plane waves were generated by exciting eight successive elements of the array with appropriate delay times. The exposure direction was changed by exciting a different set of eight elements. In this way, the ultrasound beam was electronically rotated through the tissues. Cylindrical waves were generated by exciting several transducers without delay times. Imaging was provided using a miniature echographic probe. Ex vivo experiments were carried out in pig liver to compare two approaches of treatment. The first consisted of generating successive plane waves separated from each other by a 6° angle. The second one consisted of exciting all the 16 elements without delay times. In the two cases, the lesions were well-defined and occupied a quarter of cylinder. In both sets of experiments, the sonication time and the intensity were 20 s and 17 W/cm2, respectively. In the first case, the depth was up to 17 mm compared to 6 mm in the second case.

New clinical concepts in lithotripsy demand small shock heads. Reducing the size of piezoelectric shock heads will be possible only if the pressure generated at the surface of each transducer can be increased so that the total pressure at the focus remains the same. To solve this problem, different solutions were proposed. For example, it has been demonstrated that piezocomposite material, as opposed to piezoceramic material, allows the generation of a higher surface pressure before breaking, mainly because radial modes are dramatically reduced. In addition, in a previous paper, we showed the feasibility of generating high-pressure pulse waves without increasing the transducer voltage by using sandwiched transducers, which are a stack of two or more transducers. Some discrepancies appeared, however, between the pressure measured at the surface of the front transducer and the arithmetic sum of the pressures generated by each transducer constituting the stack. In fact, development of such stacked transducers capable of generating surface pressures in the range of 2 to 5 MPa is very complex, which may explain why no aging tests have been reported in the literature thus far. In the first part of this paper, we theoretically determine the importance of the electroacoustical coupling between the two transducers on the generated surface pressure. We show that pressure losses due to these electroacoustical couplings are less than 5%. Experimental measurements done on a stacked transducer assembled and tightened in a castor oil-filled tank are in excellent accordance with the theoretical measurements. Using this assembly technique, it was possible to obtain, on average, out of four elements, a pressure of 7.5 MPa for the duration of 4 million shocks, which would allow the treatment of approximately 1000 patients.

The aim of this study is to demonstrate the feasibility of a new spherically curved 1.5-D phased array for the treatment of localized prostatic cancer. The device is designed to conform to the Ablatherm(R) machine (EDAP-Technomed. France), a commercially available machine in which high intensity focused ultrasound (HIFU) treatment for prostate cancer is administered transrectally. It uses high intensity electronically focused ultrasound to steer a beam along two axes, allowing enough depth to be reached to treat large prostates and eliminating two degrees of mechanical movement. Through computer simulation, it was determined that a curved 1.5-D configuration offered the optimal design. Two configurations were then proposed, and their ability to steer a beam within a target volume centered on the geometric focus of the transducer was simulated. An eight-element prototype was constructed to test the piezo-composite material and its electro-acoustical efficiency. Then, an array was constructed, and a multichannel amplifier and control system were added, to permit remote operation. Acoustical and electrical measurements were made to verify performance. Finally, the 1.5-D array was tested in vitro on samples of pig liver to confirm the ability to induce lesions.

Existing methods for the modeling of piezoelectric transducer response are generally frequency domain-based. The major disadvantage of this type of model is that they cannot take into account the electrical elements present in the emitting or receiving circuit whose values vary with respect to time. The need for a method that accounts for time-varying elements arises, for example, when the circuit comprises active electrical elements, such as diodes, or when the transducer is excited by capacitive discharge via a switch. Indeed, in this last example, it is known that the output impedance of the generator depends on the state of the switch: if it is off, its value is high; if it is on, its value is low. A time domain-based method is presented to compute the electro-acoustical response of a piezoelectric transducer and its electrical circuit, taking into account the presence of time-varying elements. An application to a current example makes it possible to show the influence of these elements on waveforms and the capacity of our model to account for them.

Recently, the instruments commonly used in urology have been organized in modules which are designed specially for use with a multi-purpose “urology table”. In order to fit into this design, the size of piezoelectric lithotripters will have to be reduced. With this goal in mind, experiments have been performed to identify a piezoelectric material which can generate the greatest possible number of high pressure shots. The experimental protocol was designed to classify various materials on the basis of their capacity to fulfill these functions. Two different classes of material were investigated, namely piezoceramics (P1-60, P7-62, P1-88, P1-91, P1-94, Quartz & Silice, France) and piezocomposites (IMA021, IMA022, IMA023, Imasonic, France). Analysis of the behavior of these different types of material showed that the composites were more suitable for the application concerned; in particular, two of these materials (IMA022 and IMA023) gave surface pressures of over 4.5 MPa whereas the highest pressure obtained with a piezoceramic material was only 2.5 MPa. Pressure measurements made close to the surface of transducers showed that radial waves were generated in the ceramic transducers which could account for why they tend to break sooner than composite ones.

In ocular drug delivery, the sclera is a promising pathway for administering drugs to both the anterior and posterior segments of the eye. Due to the low permeability of the sclera, however, efficient drug delivery is challenging. In this study, pulsed ultrasound (US) was investigated as a potential method for enhancing drug delivery to the eye through the sclera. The permeability of rabbit scleral tissue to a model drug compound, sodium fluorescein, was measured after US-irradiation at 1.1 MHz using time-averaged acoustic powers of 0.5–5.4 W (6.8–12.8 MPa peak negative pressure), with a fixed duty cycle of 2.5% for two different pulse repetition frequencies of 100 and 1000 Hz. Acoustic cavitation activity was measured during exposures using a passive cavitation detector and was used to quantify the level of bubble activity. A correlation between the amount of cavitation activity and the enhancement of scleral permeability was demonstrated with a significant enhancement in permeability of US exposed samples compared to controls. Transmission electron microscopy showed no evidence of significant alteration in viability of tissue exposed to US exposures. A pulsed US protocol designed to maximum cavitation activity may therefore be a viable method for enhancing drug delivery to the eye.

During a few past years a series of shock-wave generators for lithotripsy and/or tissue destruction studies have been developed in our laboratory. Based on the experiences in shock wave measurements and the drawbacks in existing hydrophones, we have developed a very low-cost, wideband, reproducible shock-wave hydrophone. The key element of this device is the rapidly mounting, disposable PVDF membrane. This is a commercially available PVDF shock gauge which is poled by a patented cyclic poling technique. To obtain the widest possible bandwidth, we have adopted a special coplanar membrane design. The PVDF film is sandwiched between the surfaces of a P.V.C. and a metallic plate of brass which the latter is in contact with the surrounding medium. On the other hand, the active lead is isolated from medium and it is in contact with an isolating liquid (degassed petroleum) held in a cylindrical chamber over the membrane. By the incorporation of this design, the hydrophone can be used for shock wave measurements even in conductive media like different physiological liquids, with a negligible change of sensitivity.

Shock-wave generators are now currently used for the treatment of renal stones. In all these generators the focal zone is determined by their geometrical parameters. We propose, for the first time, a piezocomposite shock-wave generator with electronic focusing. The system is composed of a two-dimensional array and its electronic hardware. The array is composed of 121 independent piezocomposite transducers arranged in a spherical shell 20 cm in diameter and focused at 190 mm. The electronic hardware includes 121 x 6 kV-impulse generators. The interdelay of each channel can be adjusted between 10 ns to 100 microseconds by steps of 10 ns. The results show: the use of composite material is possible for the generation of high amplitude pressure waves; the pressure-voltage relationship is linear up to a pressure of about 28 x 10(5) Pa at the transducer front face; the material can be used for a long period of time; i.e., after one million shocks, no decrease in sensitivity, no alteration in its electrical behaviour and no time wave form distortion were observed. Electronic focusing is efficient in an ellipsoidal region of about 4 cm in diameter and 6 cm in length. The pressure in the focal zone is about 600 x 10(5) Pa.

The aim of this study was to evaluate the performance of a flat rectangular (3×10 mm2) MRI compatible transducer operating at 5 MHz in creating deep lesions in heart at a depth of at least 15 mm. The size of thermal necrosis in heart tissue was estimated as a function of power and time using a simulation model. The system was then tested in freshly excised heart of pig and lamb. In this study we were able to create lesions 15 mm deep with an acoustic power of 6W for an exposure of approximately one minute. The contrast to noise ratio (CNR) between lesion and heart tissue was evaluated using Fast Spin Echo (FSE). With T1W FSE the CNR value was approximately 22. Maximum CNR was achieved with repetition times (TR) between 300 and 800 ms. With T2W FSE the corresponding CNR was approximately 13. The transducer was tested in rabbits in vivo and despite the motion of the heart; it was possible to create thermal lesions. © 2011 American Institute of Physics.

Image-guided thermal ablation offers minimally invasive options for treating hepatocellular carcinoma and colorectal metastases in liver. Here, the feasibility and the potential benefit of active temperature control for MR-guided percutaneous ultrasound ablation was investigated in pig liver. An MR-compatible interstitial ultrasound applicator (flat transducer), a positioning system with rotation-translation guiding frame, and an orbital ring holder were developed. Step-by-step rotated elementary lesions were produced, each being formed by directive heating of a flame-shaped volume of tissue. In vivo feasibility of automatic temperature control was investigated on two pigs. Proton Resonance Frequency Shift (PRFS)-based MR thermometry was performed on a 1.5-T clinical scanner, using SENSE acceleration and respiratory gating. MR follow-up of animals and macroscopic analysis were performed at 3 and, respectively, 4 days postprocedure. No sonication-related radiofrequency artifacts were detected on MR images. The temperature controller converged to the target elevation within +/-2 degrees C unless the requested power level exceeded the authorized limit. Large variability of the controller's applied powers from one sonication to another was found both ex vivo and in vivo, indicating highly anisotropic acoustic coupling and/or tissue response to identical beam pattern along different radial directions. The automatic control of the temperature enabled reproducible shape of lesions (15 +/- 2 mm radial depth).

Interstitial probes have been shown as effective devices to deliver high-intensity ultrasound therapy. Here, cylindrically-focused dual-mode transducers with either one or 5-elements were characterized, and a monoelement probe was evaluated in vitro. In therapy mode, the transducers were maximally efficient (or =70%) at 5.6 MHz with surface intensities up to 20 W/cm(2). In imaging mode, fractional bandwidths were 46% and 50+/-4% (ave+/-std) for the monoelement and 5-element transducers respectively. Axial and lateral resolutions were 0.5 mm and 1.0 mm, respectively, for both transducers as measured with a point scatterer in the focal plane. After characterization, the oscillating probe was used to image and apply therapy to porcine liver. B-mode images over a 140 degrees sector were formed before and after therapy, which was applied for 90 s at each of 5 angles separated by 20 degrees (e.g. -40 degrees , -20 degrees, 0 degrees, 20 degrees, 40 degrees) to form a composite lesion. Transducer surface intensity was 18 W/cm(2). Therapy was interrupted at 125 ms intervals to collect pulse/echo data along the therapy axes. Data were displayed in real-time as an M-mode image to monitor therapy. B-mode images adequately represented the liver tissue. M-mode image data agreed well with the formation of lesions in the liver.

International audience; Purpose: Delivering a drug close to the targeted cells improves its benefit versus risk ratio. A possible method for local drug delivery is to encapsulate the drug into solid microscopic carriers and to release it by ultrasound. The objective of this work was to use shock waves for delivering a molecule loaded in polymeric microcapsules. Material and methods: Ethyl benzoate (EBZ) was encapsulated in spherical gelatin shells by complex coacervation. A piezocomposite shock wave generator (120 mm in diameter, focused at 97 mm, pulse length 1.4 ls) was used for sonicating the capsules and delivering the molecule. Shock parameters (acoustic pressure, number of shocks and shock repetition frequency) were varied in order to measure their influence on EBZ release. A cavitation-inhibitor liquid (Ablasonic Ò) was then used to evaluate the role of cavitation in the capsule disruption. Results: The measurements showed that the mean quantity of released EBZ was proportional to the acoustic pressure of the shock wave (r 2 > 0.99), and increased with the number of applied shocks. Up to 88% of encapsulated EBZ could be released within 4 min only (240 shocks, 1 Hz). However, the quantity of released EBZ dropped at high shock rates (above 2 Hz). Ultrasound imaging sequences showed that cavitation clouds might form, at high shock rates, along the acoustic axis making the exposure inefficient. Measurements done in Ablasonic Ò showed that cavitation plays a major role in microcapsules disruption. Conclusions: In this study, we designed polymeric capsules that can be disrupted by shock waves. This type of microcapsule is theoretically a suitable vehicle for carrying hydrophobic drugs. Following these positive results, encapsulation of drugs is considered for further medical applications.

Acoustic cavitation generates very large localized pressures and temperatures, and thus provides a mechanism whereby physical and biological effects are produced in a high-intensity acoustic field. In this work, we studied the influence of the temporal form of a pressure pulse waveform on the destructive effects of transient cavitation. Two different shock pressure-time waveforms with nearly the same acoustic energy content were used. The first pressure waveform starts with a tensile wave followed by a compressive one, and the second pressure waveform starts with a compressive wave followed by a tensile one. These two pressure waveforms are called direct and inverse-mode pulses respectively. Based on the measurements presented in this work, we can state that, between the two types of shock pressure pulses studied, the direct-mode pulse amplifies systematically tile cavitation effect. This conclusion was achieved from a series of several quantitative and qualitative experiments: cavitation bubble collapse time, disintegration efficacy of plaster balls (a kidney stone-mimicking material), macroscopic study of lesions in agar gel and in vitro isolated rabbit liver tissue destruction. Considering these results and those obtained by other research groups, we can express that the temporal form of a shock pressure pulse has a major role on the cavitation effects.

Purpose To test the feasibility and efficacy of a percutaneous sonographically guided high-intensity interstitial ultrasound (US) ablation applicator to create "macrolesions" of confluent coagulation in an in vivo pig liver model. Materials and Methods Eight pigs and an interstitial US ablation applicator were used for this study. Elementary lesions and macrolesions created by the confluence of several elementary lesions were successively analyzed. The first phase of the study was performed by varying the acoustic intensity (AI) to create elementary lesions. The second phase of the study aimed at creating macrolesions in three target zones previously defined in the liver. Mean (± SD) maximum and minimum diameters of the macrolesions were calculated. Results The elementary lesions created with AIs of 30, 40, and 55 W/cm 2 measured 14.9 mm ± 3, 19.8 mm ± 5, and 13.2 mm ± 3, respectively. The AI retained for the second experimental phase was 40 W/cm 2 . Because of the flamelike aspect of the elementary lesions, the macrolesion appeared as a cylinder with crenelated contours. On macroscopic examination, mean maximum diameters of the macrolesions were 28.7 mm ± 3, 34.1 mm ± 2, and 27.8 mm ± 5 and mean minimum diameters of the macrolesions were 14 mm ± 3, 18.7 mm ± 2, and 14 mm ± 3 for the three target zones, respectively. A single major complication, puncture of the gallbladder, occurred in one animal. Conclusions A percutaneous sonographically guided interstitial ablation applicator is able to create macrolesions of coagulation in pig liver.

There is growing evidence that acoustic cavitation plays an important role in stone fragmentation during extracorporeal shock wave lithotripsy (ESL) treatment. In addition, side effects of the treatment, such as the hemorrhage and destruction of the tissue in the vicinity of the stone are also ascribed to cavitation phenomenon. Since cavitation is associated with the maximum negative pressure in the shock pulse, it would thus appear that possibility of controlling this pressure would be desirable in ESL applications. This paper describes a novel technique developed to control the ratio of compressional peak (P+) to rarefactional peak pressure (P-) of the shock wave for use in lithotripsy treatment. The procedure is based on the finite amplitude wave generation by focused piezoelectric transducers and subsequent interaction of the shocked waves in the common focal region. The highly asymmetrical shock wave is produced in the focal region by providing an appropriate time delay to each of the high voltage electrical excitation signals which drive the transducers. The degree of relative reduction of negative halfcycles and the corresponding positive halfcycles amplification increases with the number of the acoustic sources used. The practical implementation of the shock wave generator was obtained by using 5 cm diameter, focused 1 MHz transmitter, and additional transducers of identical construction having frequencies corresponding to the harmonics and subharmonics of the 1 MHz frequency. The importance of the results for the future development of lithotripters, and stone treatment efficiency is pointed out.

New clinical concepts in lithotripsy demand small shock heads. Reducing the size of piezoelectric shock heads will only be possible if the pressure generated at the surface of each transducer can be increased so that, the total pressure at the focus remains very high. So, we propose a new method allowing the generation of large surface pressures. It is well known that the piezoelectric rods in piezocomposite material are more fragile in the extension mode than in the compression mode. For this reason, actuators are mechanically pre-stressed between two flasks. This method cannot be used for transducers working at high frequencies, about 0.5 MHz. For this reason, we proposed to electrically pre-strain the piezoelectric material by applying high electric field in the opposite direction of the polarisation. In a first mode we proposed to pre-strain in continuous mode the transducer. Unfortunately we noticed a rapid de-poling and re-poling in the inverse direction. In a second mode to reduce depolarisation, this field was applied only during a short time just before the generation of the pulse which generate the compressive wave and in a third mode, the transducer was re-poled between two successive electrical pulses. Using this last method, it was possible to increase the maximum pressure at the surface of a 20 mm diameter plane piston to 20% and reach 4 MPa. According to this idea a very compact shock wave generator was designed. The generator made of a 1-3 piezocomposite material has a diameter of 120 mm and focused at 120 mm. The maximum pressure and the width of the compressive wave at the focus were, respectively, 60 MPa and 1.5 micros. The focal zone measured at -3 dB is an ellipsoid 6 mm high in the propagating axis and 3 mm width in the perpendicular direction. The efficacy of this generator was measured as the number of shocks necessary to totally disintegrate plaster balls 15 mm in diameter mimicking the kidney stones. At full power the number of shocks was only 150 which is rather the same number as the one obtained using electrohydraulic machine generally considered as the gold standard. This results show that piezoelectric material may be advantageously used for the manufacturing of shock wave generators.

New clinical concepts in therapy demand small shock heads. Reducing the size of piezoelectric shock heads will only be possible if the pressure generated at the surface of the shell can be increased so that, the total pressure at the focus remains very high. We propose to electrically pre-stress the piezoelectric material by applying a high electric field in the opposite direction of the polarization. To avoid depolarization, this field has to be applied only during a short time just before the emitting pulse which generates the compressive wave. Using this method, it was possible to reach, on a plane piston 20 mm diameter, a 5 MPa pressure value. According to this idea a very compact shock wave generator was designed. The generator made of a 1-3 piezo composite material has a diameter of 120 mm and a focal length of 120 mm too. The maximum pressure and the width of the compressive wave at the focus were respectively 60 MPa and 1.5 /spl mu/s. The focal zone measured at - 3dB is an ellipsoid 6 mm high in the propagating axis and 3 mm width in the perpendicular direction. The efficacy of this generator was measured as the number of shocks necessary to totally disintegrate plaster balls 15 mm in diameter mimicking the kidney stones. At full power the number of shocks was only 150 which is rather the same number as the one obtained using electrohydraulic machine generally considered as the gold standard. This results show that piezoelectric material may be advantageously used for the manufacturing of shock wave generators.

High Intensity Focused Ultrasound (HIFU) has been used successfully to treat localized prostate cancer. The systems currently used involve fixed-focus therapeutic probes. This study describes a new probe able to electronically focus the ultrasound beam in the prostate's sagittal plane. Its form is that of a section of a spherical shell containing 126 elements, all with the same area and arranged in a 1.5D configuration. Initially, simulations of the acoustic beam were undertaken to determine the ideal configuration of the array for dynamic focusing in a sagittal plane of 2/spl times/2 cm/sup 2/ in area centered on the geometric focus of the shell. An array containing 210 elements (with an inter-element spacing of 0.97 mm) was then built using a piezocomposite material. The section consists of a central, 11 mm-wide strip with 4 lateral strips of 5.5 mm, each containing 42 elements. To limit the number of electrically independent elements to 126 in total, the lateral strip elements are connected in pairs symmetrically with respect to the central strip. The array elements are arranged on a piezocomposite spherical shell of the same dimensions and properties as those of previously used probes. Power is supplied to the transducer elements from a 126-channel amplifier (2 W per channel). Simulation results and acoustic measurements show that this 126-element 1.5D array can be electronically adjusted to steer the focal point around the predefined 2/spl times/2-cm/sup 2/ area. The electroacoustic efficiency of this 126-element array is 40.44%, i.e. relatively low for this kind of material (which usually yields between 70 and 80% with single-element probes).

We attempt to optimise the electrical excitation of a piezoelectric transducer in order to generate high power unipolar pressure pulses. In this method the electrical excitation voltage is a ramp with a duration equal to the time of flight T of ultrasonic waves through the transducer thickness. Moreover, the backing material and the transducer have equal acoustical impedances. In this case the resulting pressure waveform is a strictly positive pulse with a duration of 2/spl times/T. The choice of piezocomposite materials agrees well with the condition on the backing impedance. Indeed, the low acoustical impedance of such materials easily permits one to build appropriate backing materials. Low voltage (32 V) and high voltage trials (3.8 kV) were successively conducted using different transducers. In both cases a 1-3 piezocomposite material was used for the building of the transducers, which consisted of plates with a diameter of 20 mm. This material had an acoustical impedance of 9.7 MRayl. The transducer used in low voltage essays was 1.7 mm-thick, while a 2.4 mm-thick transducer was used for high voltage trials. A material with a 9 MRayl impedance backed both transducers. In both trials pressure waveforms were close to the predicted shape. During high voltage essays a 3 MPa pressure pulse was obtained. A simple inversion of the excitation voltage leads to the generation of strictly negative pressure pulses.

This work was undertaken to investigate the feasibility of constructing a cylindrical phased array composed of 64 elements spread around the periphery (OD 10.6 mm) for transoesophageal ultrasound thermotherapy. The underlying operating principle of this applicator is to rotate a plane ultrasound beam electronically. For this purpose, eight adjacent transducers were successively excited with appropriate delay times so as to generate a plane wave. The exposure direction was changed by exciting a different set of eight elements. For these feasibility studies, we used a cylindrical prototype (OD 10.6 mm) composed of 16 elementary transducers distributed over a quarter of the cylinder, all operating at 4.55 MHz. The active part was mechanically reinforced by a rigid damper structure behind the transducers. It was shown that an ultrasound field similar to that emitted by a plane transducer could be generated. Ex vivo experiments on pig's liver demonstrated that the ultrasound beam could be accurately rotated to generate sector-based lesions to a suitable depth (up to 19 mm). Throughout these experiments, exposures lasting 20 s were delivered at an acoustic intensity of 17 W cm(-2). By varying the power from exposure to exposure, the depth of the lesion at different angles could be controlled.

Electrohydraulic, electromagnetic and piezoelectric shock wave generators used in the treatment of renal calculi and gallstones have their focal zone determined by their geometrical parameters. A piezoelectric shock wave generator with electronic focalization is proposed. The system is composed of a bidimensional array of 25 piezoelectric independent transducers arranged in a spherical shell 10 cm in diameter. The electronic circuitry of the system includes 25 pulsers. The interdelay of each channel can be adjusted between 10 ns and 100 mu s by steps of 10 ns. The pressure at the surface of the shell was 22*10/sup 5/ Pa. The focal point can be electronically moved in an ellipsoidal zone 3 cm in diameter and 4 cm long. These values are large enough to follow the displacement of the renal calculus during respiration. >

In this work, the authors intend to study the influence of the temporal form of a pressure pulse waveform on the destructive effects of transient cavitation. Two different shock pressure-time waveforms with nearly the same acoustic energy content were used. The first pressure waveform starts with a tensile wave followed by a compressive one, and the second pressure waveform starts with a compressive wave followed by a tensile one. Based on the measurements presented in this work, the authors can state that the first time-waveform amplifies systematically the cavitation effect. This conclusion was achieved from 3 different experiments, i.e. cavitation bubble collapse time, disintegration efficacy of plaster balls (a kidney stone-mimicking material), and macroscopic study of lesions in Agar-Agar gel.

New clinical concepts in lithotripsy demand small shock heads. Reducing the size of piezoelectric shock heads will only be possible if the pressure generated at the surface of each transducer can be increased so that, the total pressure at the focus remains very high. So, we propose a new method allowing the generation of large surface pressures. It is well known that the piezoelectric plots in piezo composite material are more fragile in the extension mode than in the compression mode. For this reason, actuators are mechanically pre-stressed between two flasks. This method can not be used for transducers working at high frequencies, about 0.5 MHz. For this reason, we proposed to electrically pre-stress the piezoelectric material by applying high electric field in the opposite direction of the polarization. In a first mode we proposed to pre-stress in continuous mode the transducer. Unfortunately we noticed a rapid de-poling and re-poling in the inverse direction. In a second mode to reduce depolarization, this field was applied only during a short time just before the generation of the pulse which generate the compressive wave and in a third mode, the transducer was re-poled between two successive electrical pulses.

A model to predict the size and shape of high intensity focused ultrasound (HIFU)-induced lesions was recently published. This model adapts the classical "bioheat transfer equation" (BHTE) to account for the presence of oscillating microbubbles that naturally form in the tissue during HIFU. Preliminary simulation results have already helped us to better understand how an increase in acoustic power significantly shifts the lesion toward the transducer and may create skin lesions. These simulations are in good agreement with observed clinical results and it can be expected that this approach can be used to improve firing sessions. In the present work, simulations were performed to predict the size, shape and position of lesion induced by an annular array specially designed for transrectal prostate cancer therapy; in-vitro experiments were carried out to test the model. Good agreement was found between the values predicted by the model and the in-vitro results. Then, a target volume was defined and several trials were made to optimize firing parameters (power, shot duration, waiting time between shots, frequency and dynamic focus) to achieve the desired lesion. In a laparotomy procedure, a series of 29 HIFU lesions were induced in 9 pig livers in-vivo. Seven days after treatment, at animal sacrifice, all the experimental lesions were in good agreement with the simulations. The results show that it is possible to predict the shape and the position of HIFU-induced lesions with this model and that it can be used to reduce the number of in-vivo experiments necessary. We believe this model will be useful in setting clinical parameters not only for prostate cancer therapy but also for other HIFU applications.

New clinical concepts in lithotripsy demand small shock heads. Reducing the size of piezoelectric shock heads will only be possible if the pressure generated at the surface of each transducer can be increased so that the total pressure at the focus remains very high. We propose for the first time to increase the pressure without increasing the transducer voltage by using sandwiched transducers, which are a combination of several stacked transducers. When excited at appropriate time intervals, the pressure waves generated by each one reinforce when they reach the load. This new technique has been successfully tested. A pressure of 2.5 MPa was generated with two stacked, 5 mm-thick 1-3 piezocomposite transducers operating at an excitation voltage of 8 kV. No transducer damage was detected after 10(6) shocks, which corresponds approximately to the treatment of 500 patients.

Thermal surgery has been shown to be a useful therapeutic option when external ultrasound applicators cannot be used as their beam will not reach the target site. If plane transducers are used, the ultrasound beam has to be rotated in order to generate a sufficiently large volume of necrosis. However, rotating deep-seated interstitial applicators and controlling their shooting direction presents major technical problems. The purpose of this study is to evaluate the feasibility of constructing a cylindrical array with a plane rotating beam for ablating esophageal tumors by interstitial hyperthermia. The feasibility of such an array has been initially evaluated using a plane array (which is easier to make from a technical point of view). This array was made with a new piezoelectric material because its mechanical properties make it ideal for the construction of a cylindrical array in the future. We showed that the beam of each array element is sufficiently divergent and that cross-coupling is small enough to generate a plane wave from a cylindrical array. In addition, power tests and electro-acoustic efficiency measurements demonstrated that the output was sufficient to induce tissue necrosis in the relevant conditions.

In the 80s, HIFU were successfully tested for treating refractory glaucoma (Lizzi et al.). However, more clinically feasible laser‐based approaches are now considered to be the gold standard. The new proposed ultrasonic device aims to perform a conformal, partial and fast thermal ablation of the ciliary body for reducing the production of aqueous humor and intraocular pressure (IOP). Numerical simulations and anatomical constraints were considered for designing the device. Itis made of six cylindrical transducersoperating at 21MHz for modulating and producing sharp zones of ablation. In vitro tests and animal experimentation on rabbits were performed for characterization purpose.Each transducer generated sequentially an ultrasonic beam at an acoustical power of 2W for 3s. Significant decreases of IOP were obtained in vivo and no adverse effects were evidenced on histology. The feasibility, the tolerance and the efficacy of the treatment of refractory glaucoma were assessed during a clinical pilot study on eight patients. The absence of side‐effects and the significant decrease of IOP, up 45% six months after treatment, proved the clinical relevance of this new device for treating refractory glaucoma. Glaucoma is a very frequent ophthalmologic disease. An increase of the intraocular pressure (IOP) results in mechanical damage over the retina and the optical nerve.

Many therapeutic procedures have been proposed for treating glaucoma, which remains refractory in many cases. Although HIFU treatments were successful [Lizzi et al.], laser‐based approaches proved to be more clinically feasible. The new proposed ultrasonic device aims to perform a conformal, partial, and fast thermal ablation of the ciliary bodies for reducing the production of aqueous humor and intraocular pressure (IOP). The design of the device was based on numerical simulations and consideration of anatomical constraints. The device has six cylindrical 21 MHz transducers for modulating and producing sharp zones of ablation. The applicator was characterized in vitro and tested in vivo in rabbits. Exposure conditions were set to 6 W/cm2 for 3 s applied sequentially on the transducers. A clinical pilot study was then started to assess the feasibility, the tolerance, and the efficacy of the treatment of refractory glaucoma. Results of in vivo experiments showed significant decrease of IOP and no adverse e...

In order to move the treatment area without displacing the shock wave generator, the authors propose a piezo-composite shock wave generator with electronic focusing. The array, is composed of 121 piezo-composite independent transducers arranged in a spherical shell 20 cm in diameter and focused at 190 mm. The electronic hardware includes 121t6 kV-impulse generators. The authors demonstrate experimentally that the steps of the inter-delay may be chosen up to 100 ns without a deterioration of the shock wave formation. Electronic focusing is efficient in an ellipsoidal region of about 4 cm in diameter and 6 cm in length, and the pressure at the focal point is 600t10 5 Pa. In vitro results show that it is possible to destroy plaster balls located everywhere in the focal region

Ultrasonic methods have rendered possible noninvasive quantitative blood flow measurement. In this work, a method is proposed to measure aortic blood flow in children by means of a specially designed miniaturized esophageal probe and an autonomous apparatus combining an M-mode imaging system and a pulsed Doppler. In vivo experimental results in animals are presented and demonstrate the interest of simultaneous and continuous measurement of aortic diameter and blood flow velocity giving accurate measurements. A 0.94 correlation coefficient is found when comparing blood flow in the descending aorta measured using this method and using an electromagnetic flowmeter.

Miniature dual‐mode transducers can be used for minimally invasive treatment of deep‐seated tumors. While in contact with the tissue, the transducer guides and monitors localized necrosis. Here, an oscillating 5‐element piezo‐composite transducer was characterized, and then evaluated in vitro using porcine liver. Each element was 3.0 x 3.8 mm2 with a geometric cylindrical focus of 14 mm. The transmit frequency was determined by the maximal electro‐acoustic efficiency, 65%, which was found at 5.6 MHz. The transmit‐receive impulse response was 400 ns long at ‐6 dB, and the ‐6 dB fractional bandwidth, centered at 5.6 MHz, was 30%. Axial and lateral resolution measured with a 0.1 mm diameter wire was 0.5 mm and 2.0 mm, respectively. For therapy, all elements radiated simultaneously, and for imaging, independently. Treatment was performed at increments of 20° to form a composite volume of necrosis. At each angle, ultrasound was applied for 60 s at a transducer surface intensity of 15 W/cm2. Pulse‐echo data wer...

We present a summary of Inserm's experience with high power sources, which are necessary for ultrasound thermal therapy and lithotripsy. Moreover, generating high intensity pseudo‐continuous waveforms or high pressure pulses imposes different constraints on the transducer materials, specifically heat and mechanical stress. For thermal therapy, miniature piezoceramic transducers were used for interstitial, intratumoral, and endoluminal applicators. These probes operated at surface intensities up to 50 W/cm2 and generated elementary lesions in vivo within tens of seconds. Piezocomposite transducers were developed for large‐aperture, highly‐focused beams used in extracorporeal or intraoperative treatments. Focal intensities were 1000 W/cm2 or higher and up to 256 elements were utilized. Miniaturized piezocomposite transducers are currently being developed for dual‐mode imaging and therapy. For lithotripsy, piezoelectric shock wave generators were developed as alternatives to electrohydraulic or electromagnet...