Shear Wave Generation by Remotely Stimulating Aluminum Patches With a Transient Magnetic Field and Its Preliminary Application in Elastography.

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  µm 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  µm 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.

Automatic temperature control for MR-guided interstitial ultrasound ablation in liver using a percutaneous applicator: ex vivo and in vivo initial studies.

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).

Confocal lens focused piezoelectric lithotripter.

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.

Percutaneous sonographically guided interstitial US ablation: experimentation in an in vivo pig liver model.

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.

Delivery by shock waves of active principle embedded in gelatin-based capsules.

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 micros) 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) 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 (r2 > 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 2Hz). 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 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.

High intensity ultrasound clamp for bloodless partial nephrectomy: In vitro and in vivo experiments.

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.

Numerical field intensity factor calculations for 1-3 piezocomposite structures.

The 1-3 piezocomposite transducers used in specific medical applications--as lithotripsy--must be excited by intense electrical impulses. By inference, the composite material is subjected to high-stress levels. To explain possible failure, a numerical tool for analyzing singular two- and three-dimensional stress fields in piezocomposite structures is proposed. Following a finite-element iterative method, singularity parameters values and intensity factors for the mechanical stresses and the electrical field are computed in several bimaterial configurations. The finite-element analysis uses commercial software.

Ultrasound cylindrical phased array for transoesophageal thermal therapy: initial studies.

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.

Generation of higher pressure pulses at the surface of piezo-composite materials using electrical pre-strain.

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 micros before the compressive impulse, and in the third protocol prestrain is applied for 100 micros 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 10(6) 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.

Numerical simulation of the electro-acoustical response of a transducer excited by a time-varying electrical circuit.

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.

Damping, amplitude, aging tests of stacked transducers for shock wave generation.

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.

Comparison of two methods of treatment for intraluminal thermal ablation using an ultrasound cylindrical phased array.

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 degrees 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/cm(2), respectively. In the first case, the depth was up to 17 mm compared to 6 mm in the second case.

Contribution of inertial cavitation in the enhancement of in vitro transscleral drug delivery.

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.

Heart ablation using a planar rectangular high intensity ultrasound transducer and MRI guidance.

The aim of this study was to evaluate a flat rectangular (3×10mm(2)) MRI compatible transducer operating at 5MHz. The main task was to explore the feasibility of creating deep lesions in heart at a depth of at least 15mm. 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 an excised lamb heart. In this study, we were able to create lesions of 15mm deep with acoustic power of 6W for an exposure of approximately 1min. The contrast to noise ratio (CNR) between lesion and heart tissue was evaluated using fast spin echo (FSE). The CNR value was approximately 22 using T1W FSE. Maximum CNR was achieved with repetition time (TR) between 300 and 800ms. Using T2W FSE, the corresponding CNR was approximately 13 for the 14 in vivo experiments. The average lesion depth was 11.93mm with a standard deviation of 0.62mm. In vivo irradiation conditions were 6W for 60s. The size of the lesion in the other two dimensions was close to 3×10mm(2) (size of the transducer element).

Development of a miniaturized HIFU device for glaucoma treatment with conformal coagulation of the ciliary bodies.

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/cm(2), 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.

In vivo evaluation of a mechanically oscillating dual-mode applicator for ultrasound imaging and thermal ablation.

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.

Blood clot disruption in vitro using shockwaves delivered by an extracorporeal generator after pre-exposure to lytic agent.

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 (p < 0.01) 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.