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International audience; This study presents the rst observation of elastic shear waves generated in soft solids using a dynamic electromagnetic eld. The rst and second experiments of this 5 study showed that Lorentz force can induce a displacement in a soft phantom and that this displacement was detectable by an ultrasound scanner using speckle-tracking algorithms. For a 100 mT magnetic eld and a 10 ms, 100 mA peak-to-peak electrical burst, the displacement reached a magnitude of 1 m. In the third experiment, we showed that Lorentz force can induce shear waves in a phantom. A physical model 10 using electromagnetic and elasticity equations was proposed. Computer simulations were in good agreement with experimental results. The shear waves induced by Lorentz force were used in the last experiment to estimate the elasticity of a swine liver sample.

Communication with and transmission of energy to remote devices, such as deeply-implanted physiological recorders, using ultrasound presents several technical problems. In particular, device detection and piezoelectric sensor targeting remains difficult. Both tasks require differentiating the device from the surrounding fully passive tissues. Like radiofrequency identification devices, ultrasonic transponders have the capacity to rapidly change the impedance of their piezoelectric elements, which modulates their backscattering coefficient and allows the device to "flash" periodically at a very low energy cost, and, in particular situations, to communicate with an external device. A method for localizing the device by interpreting this flashing as movement is presented here. An ultrasound Doppler scan sequence is implemented using a programmable scanner, and radio-frequency data are collected and processed. The data are then analyzed for different excitation lengths and flashing frequencies to determine the optimum detection parameters. Measurements show that 1) detection can be achieved and is maximal when the excitation length reaches that of the Doppler processing window, and 2) when the flashing frequency is in a specific range. A study of the incidence angle also showed that 3) the sensor of the device can be detected over a given angular window. The conclusion is that by using ultrasound color Doppler sequences, impedance-switching piezoelectric devices can be detected under the conditions provided in the present study, and can be distinguished from fully passive structures.

International audience; A Lorentz-force hydrophone consists of a thin wire placed inside a magnetic field. When under the influence of an ultrasound pulse, the wire vibrates and an electrical signal is induced by the Lorentz force that is proportional to the pulse amplitude. In this study a compact prototype of such a hydrophone is introduced and characterized, and the hydrodynamic model previously developed is refined. It is shown that the wire tension has a negligible effect on the measurement of pressure. The frequency response of the hydrophone reaches 1 MHz for wires with a diameter ranging between 70 and 400 \micro m. The hydrophone exhibits a directional response such that the signal amplitude differs by less than 3dB as the angle of the incident ultrasound pulse varies from -20 degrees and +20 degrees. The linearity of the measured signal is confirmed across the 50 kPa to 10 MPa pressure range, and an excellent resistance to cavitation is observed. This hydrophone is of interest for high pressure ultrasound measurements including High Intensity Focused Ultrasound (HIFU) and ultrasonic measurements in difficult environments.

—Biliary cancer is very difficult to treat, mainly because of the advanced stage at which such tumours are detected and the low efficacy of systemic therapeutic modalities like radiotherapy. Palliative measures designed to clear the duct (either by means of surgery or an endoscopic procedure) are presently performed. A relatively noninvasive alternative could be developed to fill this gap in the therapeutic arsenal. To this end, we have designed an interstitial ultrasound (US) applicator suitable for use with a digestive endoscope. This applicator is based on a water-cooled plane transducer that operates at 10 MHz. Although, because the target zone is cylindrical in shape, it might have seemed more logical to use a cylindrical transducer. Nevertheless, a plane transducer was chosen because the pressure field from this kind of emitter decreases less quickly, which means faster and deeper heating. However, to generate coagulation necrosis all around the duct, the applicator has to be rotated around its axis; this is achieved by means of a flexible metallic shaft (2 m in length and 3.8 mm in diameter) that joins the device’s active head (which contains the transducer) to the casing with all the connectors. A holder is fixed at the endoscope channel inlet; it controls the rotation of the applicator. Trials were conducted on pigs. The duodenoscope was introduced via the oesophagus down through the duodenum as far as the hepatopancreatic ampulla. Using a guide wire, the applicator was navigated into the duct via the endoscope instrument channel. Well defined, reproducible volumes of coagulation necrosis with a diameter of 20 mm were generated in the biliary tissue and the liver. These promising results indicate that this kind of endoscopic US delivery system may represent an effective tool for the treatment of biliary tumours in humans. An Independent Ethics Committee recently approved preliminary clinical trials of this applicator.

Extracorporeal HIFU techniques still cannot be used to treat tumours of the digestive tract, therefore an interstitial applicator has been developed to fill this gap. The object of the study was to validate the use of a plane ultrasonic transducer in an interstitial applicator to obtain large sector based or cylindrical coagulation necrosis. Two very different shot sequences were performed in vitro and in vivo and compared with numerical calculations. Each sequence consisted of 20 shots. After each shot the applicator was rotated through an angle of 18 degrees. Each shot in sequence 1 lasted 20 s, with a 2-min interval between shots which can be considered as independent. The second sequence involved coupling the shots so that each benefits from the heat deposited by the preceding ones. The first shot lasted 20 s to establish the lesion, then the duration of the subsequent 19 shots was 10 s to take into account the temperature rise due to preceding shots. In both cases, it was shown that cylindrical necrosis resulted in vivo and in vitro: 20 mm diameter and 8mm in height. The dimensions and the shapes of the necrosed volumes agreed with numerical predictions: the necrosed area induced by sequence 1 had a serrated border, whereas that of the second sequence was much more uniform. It was also shown that, for the two sequences, less than 20 s were necessary to coagulate the tissues in each direction. The results with sequence 2 showed that coupling the shots could be used to reduce treatment time without modifying the necrosed volume.

Resume L’application d’ultrasons a des liposomes sonosensibles charges de chimiotherapie offre de nouvelles perspectives dans le traitement du cancer. Dans ce travail, des essais in vitro ont permis de definir un indice de cavitation pour permettre le suivi des traitements. Cet indice permet egalement d’evaluer la sonosensibilite de liposomes prototypes. Des experimentations ont ete conduites chez des rats porteurs de tumeurs sous-cutanees. Le temps de 48 heures apres injection a ete choisi pour l’application des ultrasons. Concernant le traitement, les liposomes ralentissent significativement la dynamique tumorale. Les ultrasons combines aux liposomes semblent contribuer au ralentissement du developpement de la tumeur. Cependant, la grande efficacite des liposomes seuls et la possible faible interaction avec les ultrasons ne permettent pas de garantir que l’effet des ultrasons est significatif.

Background: Many digestive tract tumors spread inside the lumen and are not amenable to curative surgical treatment. An intraluminal method of tumor destruction would be useful for palliative or even curative purposes. High-intensity ultrasound (US) is suitable for such purposes. Our objective was to perform experiments with animal models that would lead to development of a high-intensity US probe for intraductal tumor destruction suitable for insertion through a large-channel endoscope. Methods: The active part of the high-intensity US applicator consisted of a water-cooled piezoceramic plane transducer (3 × 10 mm) operating at 5 MHz for deep or 10 MHz for shallow tissue penetration. A cylinder of tissue was destroyed by means of rotating the transducer on its axis through a flexible shaft. Experiments were conducted in vitro on livers of butchered pigs (10 lesions), in vivo on exteriorized pig livers (15 lesions), and on metastatic Dunning tumors (AT 2 subline) implanted subcutaneously in 28 rats (treated n=16, controls n=12). Results: In experiments on pig livers, high-intensity US induced highly reproducible cylinders of coagulation necrosis (diameter 20 ± 1 mm, height 8 ± 1 mm) with sharply demarcated and serrated boundaries. The exposure duration to achieve such lesions was 5 minutes. Regions of coagulation necrosis obtained in vivo were similar in size and shape. All 12 control rats died or were killed because of diffuse cancer by day 15 after implantation; 64% of the treated rats were tumor free 30 days after treatment, and 36% had local recurrences. Conclusion: This high-intensity US probe induces highly reproducible cylinders of coagulation necrosis and is effective against tumors in animals.

Although interstitial techniques are invasive, they are still the first-line therapeutic modalities for certain types of tumour. They are mainly relevant to tumours that are either inoperable or located so deep that access is complicated. Of the various types of radiation that can be delivered by the interstitial route, ultrasound is the most suitable for deep heating. The study compares the efficacy of two types of applicator with respect to their ability to induce cylindrical zones of coagulation necrosis. The transducer of the first applicator is tubular, whereas the second is plane and can rotate around its axis. Both have an external diameter of 4 mm, are fitted with surface cooling systems and operate at 10.7 MHz and 14 W.cm-2. Comparison involves mathematical modelling of ablated tissue in the targeted area by resolving the bioheat transfer equation (BHTE) using an algorithm based on finite differences. The BHTE gives a temperature value from which the thermal dose can be determined. It is shown that tissue ablation by tubular transducers is slow, and, in consequence, perfusion disturbs the heating pattern: in vivo, irradiation with a tubular transducer lasting 1081 s would be required to ablate a tissue mass with a radius of 8 mm. The corresponding period using a rotating plane transducer with 20 firing angles is only 618 s. The mean exposure time of each shot lasts 31 +/- 7 s. Therefore perfusion would have much less impact in the case of therapy administered using a plane transducer than that using a tubular one.

The extracorporeal high-intensity focused ultrasound (HIFU) techniques are not still transposable for tumors of the digestive tract because of their locations. This study was designed to evaluate the feasibility of interstitial applicators (3.8 mm O.D.) to comply with this therapeutic lack and to demonstrate the possibility of producing coagulation necrosis by a specially designed probe and with a short exposure time (20 s). The active surface of the applicators consists of plane water-cooled PZT transducers working at 10 or 5 MHz. They were evaluated in terms of acoustic power emitted as a function of the frequency, and applied electrical input (electroacoustic efficiency of 75% at their working frequency) and in vitro and in vivo pig liver tissue destruction. The in vitro and in vivo necroses depth from the applicator surface ranged from 8 to 20 mm. This showed the advantage of a nondivergent source: the pressure decay is only due to the tissue absorption in the Fresnel zone. The lesions dimensions are slightly dependent on perfusion: 8 ± 2 mm deep in vitro for a 10.7-MHz transducer working at 14 W/cm 2 against 10 mm in vivo . Operating at 5 MHz makes it possible to increase the therapeutic heating depth. For example, at a similar close-to-transducer temperature, the 5-MHz applicator induced, at a depth of 10 mm, a temperature elevation of 27°C against 15°C for that working at 10 MHz.

Several physical methods can be used to coagulate the ciliary body and decrease intra-ocular pressure in patients with glaucoma. The study described here investigated the short- and long-term effects of high-intensity focused ultrasound (HIFU) cyclocoagulation on the aqueous humor production structures and outflow pathways. Thirty-four rabbit eyes were sonicated with a ring-shaped probe containing six miniaturized HIFU transducers. Light, scanning electron and transmission electron microscopy and corrosion casts were performed. In the affected regions, the epithelium of the ciliary processes was degenerated or necrotic and sloughed off. Examinations performed several months afterward revealed involution of the ciliary processes. Vascular corrosion cast revealed focal interruption of the ciliary body microvasculature. In most animals, a sustained fluid space was seen between the sclera, the ciliary body and the choroid, likely indicating an increase in the aqueous outflow by the uveoscleral pathway. These results suggest that HIFU cyclocoagulation has a dual effect on aqueous humor dynamics.

International audience; This article describes a method called Lorentz Force Electrical Impedance Tomography. The electrical conductivity of biological tissues can be measured through their sonication in a magnetic field: the vibration of the tissues inside the field induces an electrical current by Lorentz force. This current, detected by electrodes placed around the sample, is proportional to the ultrasonic pressure, to the strength of the magnetic field and to the electrical conductivity gradient along the acoustic axis. By focusing at different places inside the sample, a map of the electrical conductivity gradient can be established. In this study experiments were conducted on a gelatin phantom and on a beef sample, successively placed in a 300 mT magnetic field and sonicated with an ultrasonic transducer focused at 21 cm emitting 500 kHz bursts. Although all interfaces are not visible, in this exploratory study a good correlation is observed between the electrical conductivity image and the ultrasonic image. This method offers an alternative to detecting pathologies invisible to standard ultrasonography.

Long-lasting lifting is a key factor during endoscopic submucosal dissection (ESD) and can be obtained by water-jet injection of saline solution or by injection of viscous macromolecular solutions. Combination of the jet injection and the macromolecular viscous solutions has never been used yet. We assessed the ability of a new water-jet system to inject viscous solutions in direct viewing and in retroflexion. We compared jet injection of saline solution and hyaluronate 0.5 % to perform ESD on ex vivo pig stomachs in order to evaluate the benefits of macromolecular solutions when injected by a jet-injector system. This is a prospective comparative study in pig stomachs. Using the jet injector, four viscous solutions were tested: hydroxyethyl starch, glycerol mix, hyaluronate sodic (0.5 %), and poloxamer mix. Ten ESDs larger than 25 mm (five in direct viewing and five in retroflexion) and one larger than 10 cm were performed with each solution. ESD with hyaluronate jet injection was then compared with ESD with saline jet injection by performing 50 ESDs in each group. A single, minimally-experienced operator conducted all the procedures. All 145 resections were complete, including all marking points with two perforations. Eleven jet ESDs per solution were conducted without any injection issue. In the second part of the study, when compared with saline, significant benefit of hyaluronate was observed on dissection speed (0.80 vs. 1.08 cm2/min, p

One of the main challenge in shear wave elastography is the shear wave source. Most of nowadays techniques are using external vibrator or acoustic radiation force. Otherwise, by applying an electrical current in a conductor submitted to a magnetic field, a displacement is induced by Lorentz force. This displacement is propagating as a combination of compressional and shear waves. In this study, we observed for the first time shear waves induced by Lorentz force in a tissue-mimicking phantom. In our experiment, a 10 ms long, 80 V peak-to-peak electrical signal was applied with two electrodes in a gelatin phantom placed in a 300 mT magnetic field. The phantom has an electrical conductivity of 1 S/m, close to the human soft tissue conductivity. An ultrasonic probe was acquiring an image in ultrafast mode at 1000 frames per second with a Verasonics ultrasound scanner. Displacements in the phantom were measured with a speckle-tracking technique based on correlations between each image. Results showed that a displacement of a few micrometers is induced by Lorentz force which results in a shear wave propagation at a speed of 1.4 ± 0.1 m/s. These results could lead to a shear wave elastography technique based on the combination of electrical current and magnetic field.

The blood-brain barrier (BBB) is a major impediment to the intracerebral diffusion of drugs used in the treatment of gliomas. Previous studies have demonstrated that pulsed focused ultrasound (US) in conjunction with a microbubble contrast agent can be used to open the BBB. To apply the US-induced opening of the BBB in clinical practice, the authors designed an innovative unfocused US device that can be implanted in the skull and used to transiently and repeatedly open the BBB during a standard chemotherapy protocol. The goal of this preliminary work was to study the opening of the BBB induced by the authors' small unfocused US transducer and to evaluate the effects of the sonications on brain parenchyma.Craniectomy was performed in 16 healthy New Zealand White rabbits; epidural application of a single-element planar ultrasonic transducer operating at 1 MHz was then used with a pulse-repetition frequency of 1 Hz, pulse lengths of 10-35 msec, in situ acoustic pressure levels of 0.3-0.8 MPa, and sonication for 60-120 seconds. SonoVue was intravenously injected during the US applications, and opening of the BBB was determined by detecting extravasation of Evans blue dye (EBD) in brain tissues, quantitative measurement of EBD with UV-visible spectrophotometry, and contrast enhancement after Gd injection in 4.7-T MRI. A histological study was performed to determine adverse effects.An opening of the BBB was observed over a large extent of the US beam in the brain corresponding to in situ pressures of greater than 0.2 MPa. The BBB opening observed was highly significant for both EBD (p0.01) and MRI Gd enhancement (p0.0001). The BBB opening was associated with minor adverse effects that included perivascular red blood cell extravasations that were less than 150 μm in size and not visible on MR images. Moderate edema was visible on FLAIR sequences and limited to the extent of the sonication field.The results demonstrate that the BBB can be opened in large areas of the brain in rabbits with low-power, pulsed, and unfocused US with limited damage to healthy tissue.

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.

This work examines the use of lanthanide-based contrast agents and magnetic resonance imaging in monitoring liposomal behavior in vivo. Dysprosium (Dy) and gadolinium (Gd) chelates, Dy-diethylenetriaminepentaacetic acid bismethylamide (Dy-DTPA-BMA) and Gd-DTPA-BMA, were encapsulated in pegylated distearoylphosphatidylethanolamine-based (saturated) liposomes, and then intravenously injected into Copenhagen rats with subcutaneous Dunning AT2 xenografts. Liposome-encapsulated Dy chelate shortens transverse relaxation times (T(2) and T(2)*) of tissue; thus, liposomal accumulation in the tumor can be monitored by observing the decrease in T(2)* relaxation time over time. The tumor was treated at the time of maximum liposomal accumulation (48 h) with confocal, cavitating high-intensity focused ultrasound to induce liposomal payload release. Using liposome-encapsulated Gd chelate at high enough concentrations and saturated liposomal phospholipids induces an exchange-limited longitudinal (T(1)) relaxation when the liposomes are intact; when the liposomes are released, exchange limitation is relieved, thus allowing in vivo observation of payload release as a decrease in tumor T(1).

International audience; The velocity and pressure of an ultrasonic wave can be measured by an electromagnetic hydrophone made of a thin wire and a magnet. The ultrasonic wave vibrates the wire inside a magnetic field, inducing an electrical current. Previous articles reported poor spatial resolution of comparable hydrophones along the axis of the wire. In this study, submillimetric spatial resolution has been achieved by using a tomographic method. Moreover, a physical model is presented for obtaining absolute measurements. A pressure differential of 8% has been found between piezoelectric and electromagnetic hydrophone measurements. These characteristics show this technique as an alternative to standard hydrophones.

Therapeutic ultrasound, although less well known than ultrasound for diagnostic imaging, has become a topic of growing interest in ophthalmology. High intensity focused ultrasound (HIFU) for the treatment of glaucoma and ultrasonic drug delivery are the two main areas of research and potential clinical applications. For the treatment of glaucoma, the specific advantage of HIFU, particularly when compared to the laser, is that the energy can be focused through optically opaque media, especially through the sclera which is a strongly light-scattering medium. HIFU is therefore a possible method for partial coagulation of the ciliary body (an anatomical structure responsible for the production of the liquid filling the eye) and, hence, reducing intraocular pressure and the risk of glaucoma. Ocular drug bioavailability also remains a challenge, being limited by multiple barriers to drug entry and lacrimal drainage, and making it difficult to achieve a sufficient drug concentration for numerous diseases of the front and back of the eye. As the front wall of the eye (cornea and anterior sclera) is a pathway for topically applied drugs, locally applied ultrasound has been proposed as a way of enhancing the delivery and activity of drugs and genes. Despite the fact that experimental studies seem to confirm the potential benefit of ultrasound ocular drug delivery, there is still a lack of clinical evidence. The aim of this contribution is to provide an update on recent advances in the field of therapeutic ultrasound in ophthalmology.

International audience; Non-linear Ultrasound imaging has been used extensively for enhancing the visualization of the accumulation of micro-bubble contrast agents. The goal of this study is to apply this approach to adipose tissue, a tissue type with a high non-linear coefficient, in order to enhance the visibility of visceral adipose tissue depots using ultrasound. The technique used in this study was pulse subtraction. This technique, implemented on an Ultrasonix RP 500 scanner with a 5 MHz centre frequency probe, is based on taking a single pulse Bb-mode image, then constructing a virtual image for a two pulse b-mode image, then subtracting this virtual image from an actual two-pulse b-mode image. The imaging parameters were first optimized using both oil-based, and aqueous gel phantoms. The parameters were tested ex vivo using a section of pork belly, then the protocol was used in vivo to image the retroperitoneal fat depot on a healthy wistar rat. The ratio of cancellation for each pixel was then calculated and mapped. It was found that tissues with higher non-linear coefficients had a lower cancellation ratio.

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.

The goal of this study is to optimize the transfer of acoustic energy deep in the body. In order to find suitable acoustic paths for the energy transfer to be efficient, we propose a model of ultrasound propagation that takes into account a realistic geometry of the tissue layers inside the human body. The data from the Visible Human Project is used to identify the tissues between the transducer array and the target point located on the epicard of the heart. The model is validated by comparison with measurements of the pressure field radiated by a focused 64-element array in water. Then, model results are presented in a realistic configuration, choosing a suitable input acoustic power so that adverse bio-effects are minimized. The model predicts the amount of acoustic energy that can be obtained at the target point, and is therefore useful to select the best acoustic path among several possibilities.

Interstitial ultrasound applicators can be a minimally invasive alternative for treating targets that are unresectable or are inaccessible by extracorporeal methods. Dual-mode transducers for ultrasound imaging and therapy were developed to address the constraints of a miniaturized applicator and real-time treatment monitoring. We propose an original treatment strategy that combines ultrasound imaging and therapy using a dual-mode transducer rotating at 8 revolutions per second. Real-time B-mode imaging was interrupted to emit high-intensity ultrasound over a selected therapy aperture. A full 360 degrees image was taken every 8th rotation to image the therapy aperture. Numerical simulations were performed to study the effect of rotation on tissue heating, and to study the effect of the treatment sequence on transducer temperature. With the time-averaged transducer surface intensity held at 12 W/cm(2) to maintain transducer temperature below 66 degrees C, higher field intensities and deeper lesions were produced by narrower therapy apertures. A prototype system was built and tested using in vitro samples of porcine liver. Lesions up to 8 mm were produced using a time-averaged transducer surface intensity of 12 W/cm(2) applied for a period of 240 s over a therapy aperture of 40 degrees. Apparent strain imaging of the therapy aperture improved the contrast between treated and spared tissues, which could not be differentiated on B-mode images. With appropriate limits on the transducer output, real-time imaging and deep thermal ablation are feasible and sustainable using a rotating dual-mode transducer.

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).

The purpose of this study was to define and validate an inertial cavitation dose (CD) based on the detection of broadband noise, designed to monitor ultrasound-mediated drug release from liposomes. The validation consists of using the terephthalate dosimeter to quantify by fluorescence measurements the extent of hydroxyl radical ( OH) production during inertial cavitation. Sonication of samples was performed using tone bursts (pulse repetition frequency (PRF): 10 Hz −1 kHz, duty cycle (dc): 5–25%, Isppa: 4100–12,200 W/cm 2 ) generated by a 1 MHz focused transducer. Three sets of ultrasound parameters with different PRF and dc were selected to be more precisely compared. Results demonstrated an excellent correlation between OH radical production and CD for each set of parameters, but significant differences in hydroxyl radical levels were observed among the sets of parameters. The results were compared with other studies, and the same tendency of variation with pulse duration was demonstrated. Results also showed that the CD was not distorted by peak intensity variations and was a much more reliable indicator than sonication time. Consequently, one validated parameter was selected to monitor drug release from two liposome formulations, and compare their ultrasound sensitivity.

Medical imaging is a vital component of high intensity focused ultrasound (HIFU) therapy, which is gaining clinical acceptance for tissue ablation and cancer therapy. Imaging is necessary to plan and guide the application of therapeutic ultrasound, and to monitor the effects it induces in tissue. Because they can transmit high intensity continuous wave ultrasound for treatment and pulsed ultrasound for imaging, dual-mode transducers aim to improve the guidance and monitoring stages. Their primary advantage is implicit registration between the imaging and treatment axes, and so they can help ensure before treatment that the therapeutic beam is correctly aligned with the planned treatment volume. During treatment, imaging signals can be processed in real-time to assess acoustic properties of the tissue that are related to thermal ablation. Piezocomposite materials are favorable for dual-mode transducers because of their improved bandwidth, which in turn improves imaging performance while maintaining high efficiency for treatment. Here we present our experiences with three dual-mode transducers for interstitial applications. The first was an 11-MHz monoelement designed for use in the bile duct. It had a 25 × 7.5 mm 2 aperture that was cylindrically focused to 10 mm. The applicator motion was step-wise rotational for imaging and therapy over a 360°, or smaller, sector. The second transducer had 5-elements, each measuring 3.0 × 3.8 mm 2 for a total aperture of 3.0 × 20 mm 2 . It operated at 5.6 MHz, was cylindrically focused to 14 mm, and was integrated with a servo-controlled oscillating probe designed for sector imaging and directive therapy in the liver. The last transducer was a 5-MHz, 64-element linear array designed for beam-formed imaging and therapy. The aperture was 3.0 × 18 mm 2 with a pitch of 0.280 mm. Characterization results included conversion efficiencies above 50%, pulse-echo bandwidths above 50%, surface intensities up to 30 W / cm 2 , and axial imaging resolutions to 0.2 mm. The second transducer was evaluated in vivo using porcine liver, where coagulation necrosis was induced up to a depth of 20 mm in 120 s. B-mode and M-mode images displayed a hypoechoic region that agreed well with lesion depth observed by gross histology. These feasibility studies demonstrate that the dual-mode transducers had imaging performance that was sufficient to aid the guidance and monitoring of treatment, and could sustain high intensities to induce coagulation necrosis in vivo.

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.

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.

article; High-intensity contact ultrasound (HICU) under MRI guidance may provide minimally invasive treatment of endocavitary digestive tumors in the esophagus, colon or rectum. In this study, a miniature receive-only coil was integrated into an endoscopic ultrasound applicator to offer high-resolution MRI guidance of thermotherapy. A cylindrical plastic support with an incorporated single element flat transducer (9.45 MHz, water cooling tip) was made and equipped with a rectangular RF loop coil surrounding the active element. The integrated coil provided significantly higher sensitivity than a four-element extracorporeal phased array coil, and the standard deviation of the MR thermometry (SDT) improved up to a factor of 7 at 10 mm depth in tissue. High-resolution morphological images (T1w-TFE and IR-T1w-TSE with a voxel size of 0.25 x 0.25 x 3 mm3) and accurate thermometry data (the PRFS method with a voxel size of 0.5 x 0.5 x 5 mm3, 2.2 s/image, 0.3 degree C voxel-wise SDT) were acquired in an ex vivo esophagus sample, on a clinical 1.5T scanner. The endoscopic device was actively operated under automatic temperature control, demonstrating a high level of accuracy (1.7% standard deviation, 1.1% error of mean value), which indicates that this technology may be suitable for HICU therapy of endoluminal cancer

International audience; This letter describes a temperature-varying attenuation approach for preoperative planning of high intensity ultrasound interstitial targeted therapy. Such approach is mainly aimed at the treatment of primary liver cancer for which a precise lesion control must be achieved. It is shown through simulation that the shape and size of the resulting necrotic volume is significantly different from the one obtained when this tissue property is considered constant in time.

Miniature flat ultrasound transducers have shown to be effective for a large variety of thermal therapies, but the associated superficial heating implicates developing original strategies in order to extend therapeutic depth. The goal of the present paper is to use ultrasound contrast agents (UCA) to increase remote attenuation and heating. Theoretical simulations demonstrated that increasing attenuation from 0.27 to 0.8 Np/cm at 10 MHz beyond a distance of 18 mm from the transducer should result in longer thermal damages due to protein coagulation in a tissue mimicking phantom. Contrast agents (BR14, Bracco, Plan-les-Ouates, Switzerland) were embedded in thermo-sensitive gel and attenuations ranging from 0.27 to 1.33 Np/cm were measured at 10 MHz for concentrations of BR14 between 0 and 4.8%. Thermal damages were then induced in several gels, which had different layering configurations. Thermal damages, 12.8mm in length, were obtained in homogeneous gels. When mixing contrast agents at a concentration of 3.2% beyond a first 18 mm-thick layer of homogeneous gel, the thermal damages reached 21.5mm in length. This work demonstrated that contrast agents can be used for increasing attenuation remotely and extending therapeutic depth induced by a non-focused transducer. Additional work must be done in vivo in order to verify the remote-only distribution of bubbles and associated increase in attenuation.

article; International audience; High intensity ultrasound was demonstrated to provide an effective and minimally invasive therapeutic tool for in situ ablation of localized cancers. MRI guidance of the treatment allows excellent volume targeting, together with accurate on line measurement of the actual temperature in tissues. Spatial and temporal automatic feedback control of the procedure can guarantee effectiveness and safety against tissue and individual biovariability of physical parameters. This paper provides a general overview of authors' experience on the active control of the therapy with MR-compatible applicators of extracorporeal and endocavitary high intensity ultrasound.

This paper begins with an overview and a description of the interactions between ultrasound and biological tissues encountered during treatment protocols. In a second part of this seminar, two clinical applications of therapeutic ultrasound will be described in details: -Kidney stone destruction by ultrasound (lithotripsy) and High Intensity Focused Ultrasound for treating prostate cancer (HIFU).

Although it is possible to both measure temperature and monitor the damage caused by HIFU treatment sessions with magnetic resonance imaging, a number of studies have been carried out proposing an ultrasound solution. Conventional B-mode ultrasound seems to be valid, but cannot be applied to all organs, and the hyperechogenic areas often observed during HIFU treatments do not necessarily and exactly correspond to the thermal damage. The aim of this paper is to summarize recent work in this field. The various techniques have been divided into three main groups, characterizing the lesions by measuring the acoustic properties, mechanical properties or vascularization.

Deep‐seated tumours can be treated by high intensity interstitial ultrasound using a miniature transducer brought in contact with the target. A dual mode transducer was designed for performing simultaneous imaging. Two therapeutic strategies are envisaged in this study. First, the transducer can be rotated step‐by‐step and therapy interrupted periodically for acquiring echo lines. In a second approach, fast rotation of the transducer allows 2D‐imaging and therapy is applied transiently over a small angular sector. Simultaneous imaging and therapy were performed in vitro with the designed transducer (2.5×7.5mm2, cylindrically focused at 10mm, 11MHz) following these two approaches. Up to 10mm deep lesions were obtained with the immobile transducer emitting an intensity of 17W/cm2 for 120s. M‐mode images were constructed on‐line during treatment. For the second strategy, the transducer rotated at a 7 rotations per second pace. Each turn, imaging was interrupted for ≈0.02s in order to perform therapy at insta...

Effective treatment of malignant tumours demands well controlled energy deposition in the region of interest. Generally, two major steps must be fulfilled: pre‐operative optimal planning of the thermal dosimetry and per‐operative active control of the delivered thermal dose. The first issue is addressed here in the particular case of the ultrasound therapy for endocavitary tumours (oesophagus, colon or rectum) with phased array cylindrical contact applicators. Computation is divided into two main parts: 1. definition of the heating sequence parameters (the total sonication time, the number of independent beams, the orientation and the applied time for every beam), and 2. calculation of the corresponding thermal dose. One slice orthogonal to the symmetry axis of the High Intensity Contact Ultrasound (HICU) device is considered. User defined tumoral geometry is divided into a regular polar grid (5.625 degrees step). The different duration applied for interleaved fast switched beams corresponding to selected...

10 pages; Interstitial ultrasound applicators have been proposed for treating deep-seated tumours that cannot be reached with extra-corporeal high-intensity focused ultrasound. In addition, interstitial ultrasound offers several advantages compared with conventional ablation technology (radiofrequency, microwaves, cryotherapy) in terms of penetration, speed of coagulation, ability to direct and control the thermal lesion and compatibility with image monitoring. The ultrasound source is brought as close as possible to the target in order to minimize the effects of attenuation and phase aberration along the ultrasound pathway. The present paper is a review of the interstitial applicators that were described during the last decade in the literature. It is presented in three sections. The technical aspects common to all applicators are first described. For example, most-described applicators are sideview applicators whose active element is water-cooled and operates at rather high frequency (above 3 MHz) in order to promote heating. Then the different potential techniques for monitoring treatment administered by the interstitial route are presented and illustrated through a review of image-guided interstitial thermal ablation. Three major techniques of imaging are used for guiding interstitial treatment: MRI, ultrasound and fluoroscopy. The third section goes in to further detail on diverse described medical applications.

Sonoporation using low-frequency high-pressure ultrasound (US) is a non-viral approach for in vitro and in vivo gene delivery. We developed a new sonoporation device designed for spatial and temporal control of ultrasound cavitation. This device was evaluated for the in vitro transfection efficiency of a plasmid coding for Green Fluorescent Protein (peGFP- C1) in adherent and non-adherent cell lines. The frequency spectrum of the signal receive by a hydrophone is used to compute a cavitation index (CI) representative of the inertial cavitation activity. The influence of the CI on transfection efficiency, as well as reproducibility were determined. A real-time feedback loop control on CI was integrated in the process to regulate the cavitation level during sonoporation. In both adherent and non-adherent cell lines, the sonoporation device produced a highly efficient transfection of peGFP-C1 (40-80%), as determined by flow cytometry analysis of GFP expression, along with a low rate of mortality assessed by propidium iodide staining. Moreover, the sonoporation of non-adherent cell lines Jurkat and K562 was found to be equivalent to nucleofection in terms of efficiency and toxicity while these two cell lines were resistant to transfection with lipofection.

Propagation through heterogeneous tissues may hamper the ability to correctly focus ultrasound, especially when targeting a tumor for drug delivery applications. To solve this issue, we propose to use ultrasound molecular imaging (USMI) for treatment planning of drug delivery triggered by focused ultrasound. In a model of orthotopic rat prostate tumor having heterogeneous B-mode appearance, we show that tumor extend can be precisely delineated with USMI targeting VEGFR-2 receptors. High intensity ultrasound bursts (Peak negative pressure −15 MPa) are then delivered within this delineated 3D volume to trigger the release of liposomal-encapsulated chemotherapy, by local initiation of inertial cavitation. Real time imaging show that cavitation is indeed restricted to the targeted area. In the animal group receiving both chemotherapy and cavitational ultrasound, a potentiation of the therapeutic effect of the drug is clearly observed. This study demonstrates experimentally that USMI is an effective imaging method to characterize heterogeneous tissues and to guide therapeutic ultrasound.

International audience; BACKGROUND: In this project, an interstitial ultrasound applicator was developed for the treatment of primary and secondary cancers of the liver. Experiments on animals were used to check the destructive capabilities of this probe within the hepatic parenchyma of the pig in vivo, with a study of the physical parameters of the ultrasound treatment. In parallel, the possibility of visualizing the lesions induced by means of ultrasound imaging was also studied. MATERIALS AND METHODS: Thirteen pigs were used in this project, which had received the prior approval of the ethics committee of Lyon Veterinary School. Ultrasound lesions were performed by varying the physical parameters of the treatment (acoustic intensity and shot time) with the aim of obtaining larger and larger areas of destruction. An operative device was developed to ensure precision in treatments. Two types of lesions were performed: elementary lesions corresponding to single shots at 40 degrees to 50 degrees rotation intervals, and cylindrical lesions obtained by a continuous rotary deployment of the probe. The effect of hepatic pedicle clamping on the size of ultrasound lesions was studied. The aspect and dimension of the lesions were analyzed by means of operative ultrasound imaging and macroscopic examination. Histological analysis showed the impact of the treatment on the hepatic parenchyma. RESULTS: This work made it possible to study the elementary ultrasound lesions produced by our probe. Seventy elementary ultrasound lesions were analyzed. Treatments could be performed on all pigs without any difficulty. There were no operative incidents. The ultrasound-induced elementary lesions showed complete necrosis, with lesion length of up to 37 mm obtained without resort to pedicle clamping; this must be considered as a radius of the final lesion obtained over a complete rotary deployment (360 degrees ), then a diameter of 7 cm of thermal ablation can theoretically be obtained. The effect of pedicle clamping was studied and showed improvement of the lesion length. Results of continuous rotary deployment of the probe were encouraging. Operative ultrasound imaging proved to be a simple tool for directing and positioning the applicator in the target zone on the one hand and which, on the other hand, enabled accurate, real-time visualization of the ultrasound lesions. On histological analysis, the ultrasound-induced necrosis was complete and well defined. CONCLUSION: This work shows that it is feasible to treat cancers of the liver using interstitial ultrasound probe. Thermal damage obtained on the hepatic parenchyma of pigs in vivo is complete and can be monitored using simple diagnostic ultrasound. The ultrasound parameters can be adapted to obtain destruction of variable size.

Background and Objectives Cryosurgical ablation (CSA) allows the focal destruction of unresectable liver metastases after previous liver resection. The abdominal approach may be difficult for recurrent colorectal cancer metastases located in the upper part of the remaining liver, close to the inferior vena cava (IVC), the hepatic veins, and the diaphragm. A transpleurodiaphragmatic access was assessed for safety and efficacy. Methods Between September 1999 and July 2004, 13 patients with recurrent unresectable colorectal liver metastases underwent transpleurodiaphragmatic CSA via limited right thoracotomy. Seventeen lesions were treated; median diameter was 31 mm (range 13–40 mm). One to three cryoprobes were used, depending on the size and location of metastases. Results There was no operative death; three patients developed minor complications (23%). Median hospital stay was 10 days (8–14 days). After a median follow-up of 26 months (range 8–69 months), 9 patients were alive, and 5 were disease-free. Six patients had liver recurrences outside the cryolesion. Median disease free survival was 12 months with 60% 3-year survival after CSA and 58% 5-year survival after first liver surgery. Conclusions Transpleurodiaphragmatic CSA is safe and effective in selected patients with unresectable recurrent liver metastases from colorectal cancer. J. Surg. Oncol. 2006;93: 268–272. © 2006 Wiley-Liss, Inc.

To evaluate the haemostatic property of a high intensity focused ultrasound (HIFU) applicator in lower pole partial nephrectomy in a porcine model.An applicator with a flat HIFU transducer operating at a frequency of 3.78 MHz was designed. Nine female pigs weighing between 35 and 39 kg were used. The kidneys of 5 pigs were used to characterize basic lesions, study haemostatic efficacy and measure the temperature rise in treated tissues. The following 4 pigs were treated by HIFU prior to bilateral lower pole partial nephrectomy. Treatment consisted of circumferential juxtaposition of basic lesions in the lower pole with vascular clamping. Haemostatic efficacy was evaluated immediately and 30 minutes after lower pole resection.A 50-second ultrasound pulse with an intensity of 26 W/cm2 induced a full thickness lesion of the kidney, between 22 and 36 mm. Lesions were reproducible. The temperature rise observed in treated tissues was 62 +/- 12, 59 +/- 9 and 58 +/- 11 degrees C at distances of 15, 20 and 25 mm from the transducer, respectively. All lower pole partial nephrectomies were exsanguinated, except for one case (12.5%), in which a central renal artery was not controlled.Our HIFU applicator is an excellent haemostatic tool ensuring effective coagulation of the renal parenchyma, allowing dry lower pole partial nephrectomy. Improvement of the ergonomics of this applicator and adaptation to laparoscopy are currently under investigation.

Techniques using intracavitary or interstitial applicators have been proposed because extracorporeal HIFU techniques are not always suitable for deep‐seated tumors. Bones or gaseous pockets may indeed be located in the intervening tissue. The objective is to bring the ultrasound source as close as possible to the target through natural routes in order to minimize the effects of attenuation and phase aberration along the ultrasound pathway. Under these circumstances, it becomes possible to use higher frequency, thus increasing the ultrasonic absorption coefficient and resulting in more efficient heating of the treatment region. In contrast to extra‐corporeal applicators, the design of interstitial probes imposes additional constraints relative to size and ergonomy. The goal of this paper is to present the range of miniature interstitial applicators we developed at INSERM for various applications. The sources are rotating plane water‐cooled transducers that operate at a frequency between 3 and 10 MHz depending on the desired therapeutic depth. The choice of a plane transducer rather than divergent sources permits to extend the therapeutic depth and to enhance the angular selectivity of the treatment Rotating single element flat transducer can also be replaced by cylindrical arrays for rotating electronically a reconstructed plane wave. When extended zone of coagulation are required, original therapeutic modalities combining cavitation and thermal effects are used. These methods consist in favoring in depth heating by increasing the acoustic attenuation away from the transducer with the presence of bubbles. When associated to modern imaging modalities, these minimally invasive therapeutic devices offer very promising options for cancer treatment. For examples, two versions of an image‐guided esophageal applicator are designed: one uses a retractable ultrasound mini probe for the positioning of the applicator, while the other is MRI compatible and offers on line monitoring of temperature. Beyond these engineering considerations, our clinical experience demonstrates that following interstitial routes for applying HIFU is an interesting therapeutic option when targeted sites cannot be reached from outside the patient.

High intensity focused ultrasound has been shown to be very effective for thermally ablating localised tumours through extracorporeal or endocavitary routes. More recently, miniature interstitial ultrasound probes have been investigated for the treatment of deep-seated tumours. All treatments must be performed under imaging guidance in order to bring the probe focus precisely on the targeted site and to monitor the treatment on-line. Imaging objectives and constraints may vary depending on the targeted organs, access routes, and treatment process. MRI provides high contrast images and is presently recognized as the gold standard for thermal mapping. MRI compatible high intensity ultrasound transducers have been designed for this purpose. Conventional B mode imaging is efficient at visualising scattering gas bodies. Many other ultrasound techniques have been tested and are likely to be further developed in order to make use of the large potential of ultrasound for targeting and monitoring the treatments. More recently it has been shown that dual mode transducers can be used for both imaging and therapeutic objectives. This again opens new possibilities for extracorporeal, endo-cavitary and interstitial applications. In all the cases, the therapeutic transducer has to be designed with the chosen imaging modality in mind

It has been shown that a very deep and selective interstitial thermal therapy can be performed using a rotating flat miniature ultrasound transducer. This heating modality would be significantly improved by implementing imaging and monitoring. The space limitations in interstitial applications require combining imaging and therapy on the same transducer. In conventional endoscopic ultrasound imaging, a miniprobe can be positioned inside the lumen of an organ and fast rotation of a single element transducer enables real time peripheral imaging of the lumen. Based on this idea, we proposed an original therapeutic strategy. Imaging can be interrupted for a short period of time corresponding to an angle Deltaalpha in order to apply high intensity ultrasound for thermal ablation. First, theoretical simulations were conducted. A 1D thermal model of the transducer demonstrated that this operating mode is not critical for the transducer. Simulations using the BioHeat Transfer Equation showed that Deltaalpha=pi/4 induced efficient therapy. An applicator was built in order to test this treatment strategy. The active element consisted in a 2.5 times 7.5 mm2 dual mode single element transducer operating at a frequency of 11 MHz. The applicator was driven in rotation at 7-turns per second pace. Experiments were performed in vitro on porcine liver. Ultrasound images were reconstructed and the size of the -6 dB point spread function at focal distance was 0.55 mm times 0.25 mm. The electronics for performing the therapeutic strategy considered above was set up. Up to 8 millimeters-deep thermal lesions were obtained with Deltaalpha=pi/4 and peak intensity of 110 W/cm 2. This work demonstrated that thermal lesions can be performed with a fast-rotating dual mode transducer. This approach enabled real-time image-guided therapy

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.