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Liposome encapsulation of drugs is an interesting approach in cancer therapy to specifically release the encapsulated drug at the desired treatment site. In addition to thermo-, pH-, light-, enzyme- or redox-responsive liposomes, which have had promising results in (pre-) clinical studies, ultrasound-triggered sonosensitive liposomes represent an exciting alternative to locally trigger the release from these cargos. Localized drug release requires precise tumor visualization to produce a targeted and ultrasound stimulus. We used ultrasound molecular imaging (USMI) with BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasound contrast agent, to guide ultrasound-triggered release of sonosensitive liposomes encapsulating doxorubicin (L-DXR) in an orthotopic prostatic rodent tumor model. Forty-eight hours after L-DXR injection, local release of doxorubicin was triggered with a confocal ultrasound device with two focused transducers, 1.1-MHz center frequency, and peak positive and negative pressures of 20.5 and 13 MPa at focus. Tumor size decreased by 20% in 2 wk with L-DXR alone (n = 9) and by 70% after treatment with L-DXR and confocal ultrasound (n = 7) (p0.01). The effect of doxorubicin on perfusion/vascularity and VEGFR2 expression was evaluated by USMI and immunohistochemistry of CD31 and VEGFR2 and did not reveal differences in perfusion or VEGFR2 expression in the absence or after the triggered release of liposomes. USMI can provide precise guidance for ultrasound-triggered release of liposomal doxorubicin mediated by a confocal ultrasound device; moreover, the combination of B-mode imaging and USMI can help to follow the response of the tumor to the therapy.

Chemotherapeutic agents such as doxorubicin induce cell cytotoxicity through induction of DNA double-strand breaks. Recent studies have reported the occurrence of DNA double-strand breaks in different cell lines exposed to cavitational ultrasound. As ultrasound stable cavitation can potentiate the therapeutic effects of cytotoxic drugs, we hypothesized that combined treatment with unseeded stable cavitation and doxorubicin would lead to increased DNA damage and would reduce cell viability and proliferation in vitro. In this study, we describe how we determined, using 4T1 murine mammary carcinoma as a model cell line, that unseeded stable cavitation combined with doxorubicin leads to additive DNA double-strand break induction. Combined treatment with doxorubicin and unseeded stable cavitation significantly reduced cell viability and proliferation at 72 h. A mechanistic study of the potential mechanisms of action of the combined treatment identified the presence of cavitation necessary to increase early DNA double-strand break induction, likely mediated by a bystander effect with release of extracellular calcium.

Exposure to ultrasound combined with intravenous injection of microbubbles is a technique that can be used to temporarily disrupt the blood-brain barrier. Transcranial monitoring of cavitation can be done with one or more passive cavitation detectors (PCDs). However, the positioning of the PCDs relative to the cavitation site and the attenuation of these signals by the skull are two sources of error in the quantification of cavitation activity. The aim of this study was to evaluate in vitro the amplitude variation of cavitation signals that can be expected for an excised porcine skull model. The variation caused by the relative positioning of the PCD with respect to the cavitation site was quantified. A position-based correction of the signal amplitude was evaluated. Pig skull samples were used to assess variation in signal amplitude caused by bone. The overall coefficient of variation of the signals owing to these measurement biases was estimated at 30.8%.

This work describes the use of therapeutic ultrasound as a treatment of cardiovascular disease including recent, state of the art approaches. Therapeutic ultrasound researchers have made recent advances in the highly dynamic and changing world of interventional cardiology where they are confronted with several challenges, such as of the complexity of ultrasound propagation in the highly heterogeneous environment of the thorax or the complexity of the heart (in term of motion and physiology). It is believed that with these recent innovations, therapeutic ultrasound for cardiac applications will soon have a place in the toolkit of cardiologists.

Electrical impedance of a medium helps to predict the behavior of electrical currents in a medium. Electrical impedance refers indeed to the “difficulty”, for an electrical current, to spread through the medium. While the first impedance measurements were focused on cardiovascular parameters, techniques are now being applied to the whole body, as electrical impedance present important variations through the human body and could then offer a new source of contrast. Combining electrical current, magnetic fields, and acoustics in various ways have led to interesting techniques to image this parameter: Electrical Impedance Tomography, Magnetic Resonance Electrical Impedance Tomography, Acousto-Electric Imaging, Lorentz Force Electrical Impedance Tomography and Magneto-Acoustic Tomography. These techniques are detailed in this review.

Study Objective Demonstrate the feasibility of Trans Rectal High intensity focused ultrasound (HIFU) treatment in patients presenting rectosigmoid endometriosis Design Phase I, non-controlled, prospective monocentric clinical study Setting Patients filled questionnaires on gynecologic and intestinal symptoms, and on quality of life (MOS-SF36 score, EHP-5) before and at one, three and six months after treatment. Patients or Participants patients older than 25 years, who presented a symptomatic single rectosigmoid location and after failure of hormonal therapy. All lesions were assessed using transvaginal sonography and MRI. Interventions Trans Rectal HIFU treatment Using the FocalOne Probe. Measurements and Main Results Twenty-three patients were included between September 2015 and October 2018. All the lesions were visualized. Twenty lesions were treated (“feasibility rate”: 87.0%): thirteen entirely and seven partially. The mean duration of the procedure was 55.6 minutes. We observed a significant improvement in visual analogic scales at six month for dysmenorrhea (-3.6, p=0.004), dyspareunia (-2.4, p=0.006), diarrhea (-3.0, p=0.006), constipation (-3, p=0.002), dyschezia (-3.2, p=0.003), false urges to defecate (-3.3, p=0.007), posterior pelvic pain (-3.8, p=0.002), and asthenia (-4.3, p=0.002).There was also a significant improvement of the MOS-SF36 with an increase of both Physical Composite Score (+9.3%, p=0.002) and Mental Composite Score (+10.9%, p=0.017) at six months. No major complications occurred during and after the procedure. Conclusion HIFU therapy for rectosigmoid location is feasible. It could be an interesting minimally invasive alternative to surgery for the treatment of rectosigmoid endometriosis. A prospective multicentric study is presently performed in France to confirm these preliminary results.

Objectifs Evaluer les resultats preliminaires du traitement par HIFU de sauvetage chez les patients presentant une recidive locale d’un cancer de prostate (CaP) dans la loge de prostatectomie apres chirurgie puis radiotherapie adjuvante ou de rattrapage. Methodes De juillet 2009 a novembre 2018, tous les patients traites par HIFU pour une recidive locale apres chirurgie puis radiotherapie adjuvante/rattrapage ont ete evalues, etude retrospective monocentrique. La recidive locale etait confirmee par Pet-TDM a la choline, IRM et biopsies transrectales. La survie sans echec (SSE) etait definie comme l’absence de CaP dans la loge de prostatectomie et/ou de metastases et/ou d’introduction de traitement systemique ; la survie sans progression (SSP) comme l’absence de metastases et/ou d’introduction de traitement systemique ; la survie sans recidive biochimique (SSRB) comme l’absence de deux augmentations du PSA ≥ 0,2 ng/mL au-dessus du nadir post-HIFU. Les complications et la continence etaient evaluees. Resultats Vingt-deux patients ont ete inclus avec un suivi moyen de 3,83 ans. Les caracteristiques de la population lors de la prostatectomie radicale, lors de la radiotherapie et lors de l’HIFU sont presentes dans le Tableau 1 . A 3 ans, la SSE etait de 49,7 %, la SSP de 60,4 % ( Fig. 1 ) et la SSRB de 35,3 %. Vingt patients (90,9 %) avaient une decroissance du PSA et 11 patients (50 %) avaient un nadir de PSA ≤ 0,2 ng/mL. La SSE et la SSP etaient significativement ameliorees chez les patients avec un nadir de PSA ≤ 0,2 par rapport a ceux avec un nadir > 0,2 ng/mL (p = 0,037, p = 0,003, respectivement). Les complications grade IIIb sont survenues chez 6 patients (27,3 %) ; la survenue d’une incontinence grade II/III etait significativement differente selon la localisation de la recidive (peri-anastomotique : 36,4 %, retrovesicale : 0 %, p = 0,027) ( Tableau 2 ). Conclusion L’HIFU de sauvetage chez les patients presentant une recidive locale dans la loge de prostatectomie apres chirurgie puis radiotherapie adjuvante ou de rattrapage prolonge l’histoire naturelle du CaP, retarde la survenue de metastases, l’introduction de traitement systemique et pourrait meme guerir certains patients aux depens d’une morbidite acceptable. La localisation de la recidive par rapport au sphincter influence la continence.

Catheter ablation for the treatment of arrhythmia is associated with significant complications and often-repeated procedures. Consequently, a less invasive and more efficient technique is required. Because high-intensity focused ultrasound (HIFU) enables the generation of precise thermal ablations in deep-seated tissues without harming the tissues in the propagation path, it has the potential to be used as a new ablation technique. A system capable of delivering HIFU into the heart by a transesophageal route using ultrasound (US) imaging guidance was developed and tested in vivo in six male pigs. HIFU exposures were performed on atria and ventricles. At the time of autopsy, visual inspection identified thermal lesions in the targeted areas in three of the animals. These lesions were confirmed by histologic analysis (mean size: 5.5 mm(2) × 11 mm(2)). No esophageal thermal injury was observed. One animal presented with bradycardia due to an atrio-ventricular block, which provides real-time confirmation of an interaction between HIFU and the electrical circuits of the heart. Thus, US-guided HIFU has the potential to minimally invasively create myocardial lesions without an intra-cardiac device.

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.

Background and objective Differentiating an epicardial from an endocardial ventricular tachycardia (VT) can be really challenging despite the latest technologies available. We intended to develop a new tool method based on electromechanical wave imaging (EWI) to improve arrhythmogenic substrate activation analysis. Methods Experiments were conducted on a left ventricle of a swine isolated working heart model. Our protocol aimed to demonstrate that, thanks to ultrasounds, a different pattern of mechanical activation could be obtained whether the ventricle was in sinus rhythm, paced from the epicardium or from the endocardium. Results EWI electrocardiogram-gated systematically differentiated with success endocardial from epicardial foci. When in paced ventricle, the origin of the wave front was focal and coming from the endocardium or the epicardium. In sinus rhythm, wave front was global and activating from the entire endocardium towards the epicardium at a speed of 1.47 ± 0.42 ms−1. Wave front speed through the thickness of the ventricle was similar when the endocardium was paced (1.42 ± 0.38 ms−1) and much slower when the epicardium was paced (0.59 ± 0.19 ms−1). Conclusion EWI activation mapping can locate ventricular activation inside the left ventricular wall thickness and calculate the propagation of the wave front through the muscle. In the future, this technology might help to differentiate endocardial from epicardial VT during complex ablation procedures.

Atrial fibrillation is the most frequent cardiac arrhythmia. Recently, an ultrasound-guided transesophageal high-intensity focused ultrasound (HIFU) device has been designed to perform minimally invasive pulmonary vein isolation. It was made with a 3 MHz 8-ring HIFU transducer including in its center a 5 MHz 64-element imaging transducer. The HIFU transducer could focus the ultrasound beam over a broad range of depths from 17 to 55 mm to perform lesions in various locations, while preserving intervening tissues. Those characteristics having been demonstrated in vitro, the aim of this study was to perform deep cardiac lesions in pig model under ultrasound guidance. A first ex vivo/in situ experiment gave promising results. Indeed, wide linear lesions were obtained in depth at desired locations. In vivo investigations are ongoing to confirm those preliminary results.

Dioeleoylphosphatidylethanolamine (DOPE)-based liposomes were recently reported as a new class of liposomes for ultrasound (US)-mediated drug delivery. The liposomes showed both high stability and in vitro US-mediated drug release (sonosensitivity). In the current study, in vivo proof-of-principle of US triggered release in tumoured mice was demonstrated using optical imaging. Confocal non-thermal US was used to deliver cavitation to tumours in a well-controlled manner. To detect in vivo release, the near infrared fluorochrome Al (III) Phthalocyanine Chloride Tetrasulphonic acid (AlPcS₄) was encapsulated into both DOPE-based liposomes and control liposomes based on hydrogenated soy phosphatidylcholine (HSPC). Encapsulation causes concentration dependent quenching of fluorescence that is recovered upon AlPcS₄ release from the liposomes. Exposure of tumours to US resulted in a significant increase in fluorescence in mice administered with DOPE-based liposomes, but no change in the mice treated with HSPC-based liposomes. Thus, DOPE-based liposomes showed superior sonosensitivity compared to HSPC-based liposomes in vivo.

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 )

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.

Objectives To evaluate the long-term hemostatic efficacy of a new high-intensity collimated ultrasonic (HICU) applicator for open subhilar partial nephrectomy (PN) in the porcine model. Methods An applicator was designed with a planar 3.78-MHz HICU transducer and a reflector to optimize the delivery of acoustic energy to coagulate renal tissue. Six female pigs underwent right PN, followed at day 7 by left PN. The 6 pigs were killed on day 14. The treatment consisted of delivering HICU to a lower pole subhilar location, under a vascular clamp, then releasing the clamp, and cutting the kidney lower pole. The immediate and delayed hemostatic efficacy, treatment parameters, blood loss, complications, and renal function were evaluated at each surgical event and at necropsy. Results Perfect hemostasis was achieved with all 12 kidneys, with a mean treatment time of 7.2 minutes (range 5 to 9.2). The mean proportion of resected parenchyma was 21% (range 14% to 32%). No renal function impairment and no major complications were recorded. At necropsy, no secondary hematoma was observed, and three urinomas (25%) were found. Conclusions Our HICU applicator has shown promising results during PN in the pig model with no other method of hemostasis. More studies are needed to refine our probe for laparoscopic surgery, improve its ergonomics, and extend our experiments to human laparoscopic nephron-sparing surgery.

We investigated the feasibility of using echo-strain images to visualize the extent of high-intensity ultrasound (US)-induced thermal lesions during their formation. Echo-strain, defined as the relative deformation of the backscattered ultrasonic signal, is due to tissue expansion and to changes in the speed of sound during heating. First, a theoretical framework was developed to predict the influence of these effects on the echo signal. Then, a simulation tool was developed to create simulated echo-strain images in thermal lesions. Finally, experimental echo-strain images were acquired in 10 porcine liver samples in vitro for various exposure durations and ultrasonic intensities (resulting in lesions that extended 3 to 8 mm deep from the surface). For this purpose, radiofrequency (RF) frames were acquired at 8 frames per s while heating. For each consecutive pair of RF frames, an echo-strain image was calculated using standard elastographic processing. The echo-strain images were cumulated and displayed. The experimental echo-strain images were compared with gross pathology. The (isoechoic) lesions were visible both in simulated and in experimental cumulated echo-strain images as apparent expansion areas (tensile echo-strain), whereas surrounding tissues exhibited apparent compression. The tensile echo-strain area underestimated the lesion in simulations, but was representative of the lesion in experiments. High correspondence was found between the lesion depth measured from experimental cumulative echo-strain images ( y ) and from gross pathology ( x ) (Pearson's correlation=0.90, linear regression y = x −0.1 mm, residual error=0 ± 0.9 mm). We hypothesized that significant tissue expansion made the thermal lesions highly visible in the experimental echo-strain images. In two cases, the ultrasonic intensity was too low to induce a lesion, and the corresponding experimental echo-strain images showed no visible lesion. We conclude that cumulative echo-strain images have the potential to monitor the formation of high-intensity US-induced thermal lesions. (E-mail: Souchon@lyon.inserm.fr)

Transurethral resection of the prostate (TURP) is the surgical method routinely used in clinics to treat benign prostate hyperplasia (BPH). The purpose of this work is to demonstrate the feasibility of a transurethral ultrasound (US) applicator based on a miniature US flat transducer to coagulate prostatic tissues. Rabbit liver was found to comply well with human prostate. A significant fall in Doppler signal amplitude immediately after treatment demonstrated the applicator's ability to achieve haemostasis. The therapeutic depth extended from 6 to 10 mm, depending on conditions of exposure, and the coagulation rate ranged between 51% and 99%. The coagulated zone pinpointed on histological examination could be easily correlated to a permanent hypoechoic zone observed on B-scans of treated zones. This observation is most likely due to temperature-related changes in the acoustic attenuation of liver and, unfortunately, may not be visible in the prostate.

Background: Local and infiltrative extension make some biliary carcinomas accessible to nonoperative intraductal destruction. This study assessed the clinical feasibility and short-term results of local tumor destruction with an intraductal high-intensity US probe during ERCP. Methods: The probe is a flexible catheter with an 8 × 2.8 mm US transducer and a lumen for a guidewire. Ten patients (6 women, 4 men; mean age 74.8 years) were treated with this device. Lesions treated included carcinoma of the papilla (3), bile duct cholangiocarcinoma (2), Bismuth grade I and II hilar cholangiocarcinomas (4), and intrahepatic cystadenocarcinoma (1). Two patients underwent US therapy before surgery. Treatment was performed during standard ERCP: the probe was inserted through the malignant stricture and US therapy was applied over 360 degrees under fluoroscopic control. Results: No serious adverse effects were observed; right upper abdominal pain developed in one patient for 12 hours. In one patient, histopathologic assessment of the resected tumor revealed extensive coagulation necrosis with inflammation up to 10 mm in depth surrounding the bile duct lumen. In the other operated patient, biopsy specimens from the treated portion of the bile duct were negative for malignancy. There was complete regression of cholangiocarcinoma of the bile duct in our patient, allowing for permanent stent removal (follow-up 30 months). A partial response was noted in 4 other patients and no response in 3 patients. Conclusions: This new method of intraductal tumor destruction by high-intensity US during ERCP is feasible and can induce objectively measurable tumor necrosis. Long-term follow-up will determine whether this method is curative in some cases and if it can reduce the need for biliary stent placement.

—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.

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.

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.

1350-4177/$ see front matter 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.ultsonch.2010.12.007 DOI of original article: 10.1016/j.ultsonch.2010.07.009 ⇑ Corresponding author at: Universite de Lyon, Lyon F-69003, France. E-mail address: lucie.somaglino@yahoo.fr (L. Somaglino). 4th paragraph (line 35 of the Section), the line ‘‘off-time duration induced a decrease of hydroxyl radical production’’ should read as follows

Objectifs pedagogiques Presentation d’experiences nouvelles avec traitement a ventre ouvert, par voie interstitielle percutanee, par voie endovasculaire. Messages a retenir Difficultes particulieres du traitement du foie par ultrasons : mobilite, cotes. Transposition chez l’homme non encore realisee. Faisabilite d’applicateurs de petite taille.