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Le generateur electrohydraulique utilise en lithotritie est constitue d'un bol ellipsoidal rempli d'eau au foyer duquel sont disposees deux electrodes reliees a un condensateur par l'intermediaire d'un interrupteur. A la fermeture, un arc s'etablit, liberant une energie suffisante pour creer une onde de choc. L'etablissement du regime d'arc est un phenomene peu reproductible induisant des variations importantes de la valeur de la pression generee. Nous montrons que l'utilisation d'un liquide fortement conducteur a la place de l'eau permet de reduire l'ecart type sur les valeurs de pression mesurees de 30 a 2 %. La mesure des parametres electriques suggere que la decharge du condensateur ne se fait plus par l'intermediaire d'un arc mais par l'intermediaire de la resistance formee par le liquide situe entre les electrodes dont la valeur est proche de la resistance critique.

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

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.

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...

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.

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.

Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that high intensity ultrasound (HIU) can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of this cancer, we designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap. Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Elementary lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm2 for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe. The rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to in vivo studies on pig esophagi. In this study, four patients with esophageal tumors included in a pilot study have been treated using this ultrasound applicator. The treatment of esophageal tumors is done under fluoroscopic guidance and ultrasound imaging. Tumor response was observed in all cases. This clinical work demonstrated the efficacy of interstitial high intensity ultrasound therapy for local tumor destruction in the esophagus

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.

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

In an electrohydraulic generator, two underwater metal electrodes are connected in series with a high voltage capacitor. When the circuit is switched on a plasma occurs reaching temperatures of thousands of degrees Celsius resulting in a compressive pressure pulse. Plasma formation is ;I particularly non-reproducible phenomenon inducing large variations in pressure pulse values. We show that the use of conducting liquid, instead of water, reduces the standard deviation of pressure measurements at the second focus after focalisation from 30 LTO to 3 9% and that the mean level of pressure is increased by 50 9%. Electrical measurements suggest that the plasma is no longer present and that the capacitor is discharged through the resistance given by the conductive liquid between the two electrodes.

In this paper we reported an evaluation of the efficacy of a new technique called Tumor Ablation with Focused Ultrasound (TAFU) in the treatment of Dunning tumors. TAFU was administered with a prototype whose active element was a 10 cm diameter 1 MHz transducer focused at 10 cm. Dunning tumor were transplanted subcutaneously into a series of Fisher Copenhagen rats which were divided into experimental groups : one for untreated controls and other groups which received TAW with different ultrasonic doses. Tumor volume in all treated animals was significantly smaller than in controls, indicating that TAFU significantly reduces tumor size when compared with controls rats with Dunning tumors. In some cases, it was shown that tumor growth was suppressed when special experimental conditions were applied.

The cavitation noise is a suitable and accurate indicator of the cavitation activity induced in a liquid. Frohly (2000) proposed a quantitative indicator of the transient cavitation calculated as a cavitation spectrum integration in a logarithmic scale and called CNP cavitation noise power indicator. This work studied the relation between a new indicator CMS based on CNP and the exposed-cell mortality in the following conditions. The cell suspension to be insonified (prostatic cells AT2 at 2.5 10/sup 6/ cells/mL) is placed in a medium sample tray (12 wells/tray, 2 mL/well, well diameter: 20 mm). This tray is submerged at mid-depth in degassed water and positioned 5 mm above the face of a flat ultrasonic transducer (diameter 22 mm, frequency: 445.5 kHz; intensity: 0.08-1.09 W/cm/sup 2/, exposure time: 30 sec-4 min). This technical configuration was admitted to be conducive to standing-wave generation through reflection at the air/medium interface in the well thus enhancing the cavitation phenomenon. Laterally to the transducer, a homemade hydrophone (PVDF film of 10 min diameter molded in araldite AY103) was oriented to receive the acoustical signal from the bubbles. From this spectral signal (0.1 to 7.1 MHz bandwidth) recorded every 3 sec on a computer during the exposure condition, CNP was calculated. Its mean value was compared to the cell mortality measured just after ultrasound exposure with a flow cytometer (FACScan) by counting 10000 events. This was accomplished by adding 7AAD solution (Via-Probe kit). Ten exposure conditions were chosen. Two of them corresponded to the experimental limits: no effects on cells (i.e. 0.08 W/cm/sup 2/; 4 min) - complete destruction of cells (i.e. 1.09 W/cm/sup 2/; 30 sec). 3 to 8 measures were realized for each exposure condition. The mortality due to cavitation effect varied from 0.1% to 85.5% and was compared to CMS mean given in relative value (from 3.8% to 97.5%). A simply linear relation between these parameters was given by a correlation coefficient of r/sup 2/=0.81. This correlation coefficient came better when exposed times were considered (for 1 min r/sup 2/=0.82 and for 2 min r/sup 2/=0.95). These results show that CNP is a good indicator of the effect induced by the cavitation phenomenon in cell culture medium in vitro.

Minimally invasive techniques using miniaturised ultrasound applicators have been developed for surgical and medical applications. However, the volume of treatment remains limited. Therefore, we propose to combine cavitation with a thermal effect to enhance the treatment depth. This study was conducted in vivo on pig liver, 51 exposures were performed on the surface of the liver, with a miniaturised applicator using a plane transducer (3/spl times/10 mm/sup 2/) operating at 4.75 MHz. This study aimed to compare two methods of treatment. The first one produced the thermal effect exclusively. The second method used cavitation in addition to the thermal effect. Cavitation bubbles were initiated along the beam axis by a 60 W/cm/sup 2/ pulse (0.5 s) followed by a continuous exposure, which generated the thermal effect. The method using cavitation produced the deepest lesions. At an intensity of 30 W/cm/sup 2/ applied for 30 s, the lesions induced with cavitation bubbles were 1.7 times deeper than those produced without cavitation bubbles. Histological analysis shows that they correspond to coagulation necroses. Thus, these results show that the initiation of cavitation bubbles prior to the exposure increases the therapeutic depth significantly. Consequently, this method might open the way to the treatment of large diameter tumours.

The goal of this study was to evaluate the hemostatic ability of a new interstitial applicator composed of a planar ultrasonic transducer with a reflector, during partial nephrectomy in a porcine model. The new applicator was designed to make effective use of all the acoustic energy to coagulate the renal tissue . Placement of the reflector opposite the transducer allows use of all the acoustic energy for coagulation. Despite the low transmission frequency, it is possible to work at a relatively weak intensity, with the aid of the reflector. As a result, intense cooling of the transducer is no longer needed. The transducer functions at a frequency of 3.78 MHz. A movable brass plate was mounted to the applicator, parallel to the transducer, to reflect energy that was not absorbed during ultrasound wave transmission. Additionally, the plate served to immobilize the kidney during the treatment. Our methodology was to expose the kidneys of 9 pigs through abdominal laparotomy. An initial series of experiments on 5 pigs allowed exposure conditions to be selected. Thermocouples were implanted in the kidneys after exposure at 15, 20, and 25 mm from the renal capsule surface. The remaining 4 pigs underwent ultrasound treatment with the applicator before a bilateral lower pole partial nephrectomy. The treatment consisted of juxtaposing elementary lesions (made at an intensity of 26 W/cm2 for 50 seconds) circumferentially in a subhilar location. The hemostatic efficacy was evaluated just after the shots and during the 30 minutes that followed the sectioning of the kidney’s lower pole. In the event of persistent bleeding, an it was possible form an elementary lesion opposite the insufficiently treated zone. For an exposure duration of 50 seconds at 26 W/cm2, the lesions obtained covered the total thickness of the kidney, which varied between 22 and 36 mm. The temperatures observed within the treated tissues were 62°, 59°, and 58°C at 15, 20 and 25 mm respectively from the kidney surface. The system with the reflector allowed uniform temperatures to be obtained through the complete thickness of the kidney. By applying between 6 and 9 elementary lesions, all partial nephrectomies were performed without hemorrhagic problems, except for one partial nephrectomy (1 of 8 kidneys; 12.5%) for which a central artery could not be controlled. In conclusion, our ultrasound applicator is an excellent hemostatic tool allowing effective coagulation of a highly vascularized organ such as the kidney. The experiment will be repeated for a longitudinal study in order to better verify the persistence of hemostasis. The possibility of adapting this applicator ergonomically as well as the possibility to utilize it for laparoscopy is presently under investigation.

High intensity ultrasound has shown considerable ability to produce precise and deep thermal coagulation necrosis. Focused, cylindrical, spherical or plane transducers have been used to induce high temperature elevation in tissues, in order to coagulate proteins and kill cells. Magnetic Resonance Imaging (MRI) has been used, with focused transducers and cylindrical interstitial applicators, to monitor temperature distribution and provide temperature feedback control during heating procedures. The active part of intraluminal applicators is positioned very close to the target region. It is therefore essential to provide accurate monitoring of heat deposition in the tissue layer near the transducer, in order to control the extension of coagulation necrosis. The purpose of this study was to develop a 10‐mm diameter intraluminal ultrasound applicator, designed to treat oesophageal cancers and compatible with “real‐time” MR temperature mapping. The ultrasound applicator was tested in vivo under real time, PRF b...

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

A harmonic acoustic wave, fed back by a reflecting target, modifies the electric impedance of the emitter. This effect is studied using a tightly focused beam and various flat targets with known reflection coefficients, which are placed at pressure maxima or minima of the standing wave in the focal zone. It is possible to establish relationships that allow one to determine, for flat targets with unknown acoustic properties, the acoustic impedance and reflection coefficient of the target as well as the acoustic pressure present at the target, only from measurements of the absorbed power and the emitter voltage.

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

It is now accepted that High Intensity Focused Ultrasound (HIFU) lesion formation is the result of a complex process that involves interaction between acoustical thermal effects and cavitation phenomena of micro-bubbles within biological tissue. In the present study, a sound propagation model that takes into account the cumulative effects of nonlinearity, diffraction and absorption in the presence of cavitation bubbles is analytically established. The model is based on a modified expression of the parabolic KZK equation where bubble dynamics is included. Then, this modified expression and the volume version of the Rayleigh-Plesset equation am written in the special case of quasi-linear wave motions. Finally, the equation system is solved by representing the source emanating from the focused transducer as a superposition of Gaussian beams. In this context, results are presented for the pressure field generated by the fundamental and second harmonics when the source is an axisymmetric transducer and the biological tissue is separated from the transducer by water. Good agreement is found between the pressure field calculations and measurements obtained with a needle hydrophone for the case of a water-only volume and a 3.0 MHz: transducer focused at 40 mm.

New curative and palliative treatments must be proposed in order to respond to the bad long-term prognosis of esophageal cancers. It has been demonstrated that High Intensity Ultrasound (HIU) can induce rapid, complete and well-defined coagulation necrosis. For the treatment of this cancer, we designed an applicator that uses an intraductal approach. The active part is an air-backed plane transducer. It has an external water-cooling system and operates at 10 MHz. Ex vivo experiments conducted on pig liver demonstrated the ability of this applicator to generate, by rotating the transducer, circular or sector-based coagulation necroses at predetermined depths up to 13 mm with an excellent angular precision. The treatment of sector-based esophageal tumour may be critical where both malignant and healthy tissues are covered by the ultrasound beam. Thus, in vivo trials were conducted on five healthy pig esophaguses in order to determine the maximal thermal dose that will not induce a perforation of the esophagus or surrounding tissues. From the results of previous studies, this dose is high enough in order to treat pathological tissues. These promising results indicate that this ultrasound system represents a safe and effective tool for the clinical treatment of esophageal tumours.

Stable cavitation is produced on the surface of a special target, i.e., an abrasive foil with a grain size of about 15 microm, insonified by a 473 kHz focused beam. Cavitation bubbles are first created by a pressure of about 2 MPa. Progressive reduction of the pressure to about 100 kPa leads to a state of stable cavitation characterized by strong stable emission of the half-order subharmonic. This state can be maintained for five hours if the defining parameters (position and pressure) are optimized and constant to within a few percent. There is strong evidence for the presence of "latent" cavitation bubbles, which can persist for a few minutes without being excited.

The frequent late diagnosis and the poor efficiency of systemic therapy such as radiotherapy generate huge difficulties in the treatment of ducts cancers. Palliative techniques of bilary debulking, either surgical or by endoscopic route, are actually performed. A light invasive local treatment would allow to fill up this therapeutic gap. Thus, the authors developed an ultrasound applicator for interstitial thermal therapy compatible with classical techniques of digestive endoscopy. The applicator is fitted with a water-cooled plane transducer, operating at 10 MHz, to produce rapid and deep coagulation necroses in a perfused environment. The rotation of the applicator around its axis is necessary to necrose the tissues surrounding the bilary lumen. A flexible metallic shaft (2 m long and 3.8 mm outer diameter), joining the active head with the transducer to the connecting end, enables the remote rotational motion control from the outside of the endoscope. In vivo experiments were conducted on pigs. An abdominal laparotomy was carried out to perform surgically the sphincterotomy of the bilary ducts. Then, the duodenoscope was slid, through the oesophagus, into the duodenum in front of the opened ampulla of Vater. A guide wire was positioned to drive the applicator through the endoscope operating channel into the bilary ducts. Sharp and repetitive coagulation necroses, 8-10 mm in depth, were generated both in the bilary ducts and the liver. These results demonstrated encouraging possibilities for the bilary ducts cancers treatment thanks to the authors' applicator.

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

A special ultrasonic transducer is described for the mean frequency estimation in local attenuation measurement. Unlike the classical focusing transducer, this probe has a diffraction pattern that is frequency independent within its main lobe, so that the mean frequency of the signal received by any scatterer does not depend on its location in the ultrasonic field. A-lines have been computed for different simulated media, both with this probe and with a classical focusing monotransducer. The results of the mean frequency processing exhibit some improvements, especially when small volumes are considered and when inhomogeneities are introduced inside the medium. >

The authors propose a novel method for bubble sizing, based on the double frequency technique, in which f/sub i/ (the imaging frequency) is pulsed at a frequency f/sub r/. The received signal from a range cell at a given depth is processed in the same way as in a conventional pulsed Doppler velocimeter. In most cases the pump frequency f/sub p/ is greater than f/sub r/, and the demodulated signal is undersampled. If f/sub p/ is different from nf/sub r/, it is shown by min mod f/sub p/+or-nf/sub r/ mod that the longitudinal resolution and the lateral resolution are the same as in conventional Doppler flowmeters (less than 1 mm), and that the measurement of the bubble size is not affected by the pulsed field. >

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

The potentialities of HIFU for selective non-invasive tissue destruction have demonstrated experimentally and clinically for extracorporeal or transrectal applications. We have now developed small HIFU transducers for endoscopic purposes. Two probes were built and tested with in vivo tissues. The transducers were piezocomposite spherical strips with a working frequency of 3.0 MHz. Targeting was achieved with a ultrasound linear array (5 MHz). Thirty New Zealand hybrid rabbits were used for therapeutic parameter determination. The beam was directed transcutaneously to the liver at depths of 22 mm from the abdominal wall. The endoscopic feasibility was assessed by using rabbits bearing a percutaneous gastrostomy and targeting volumes of liver through the gastric wall. Autopsies were performed 7 hours after treatment. For transabdominal application, a 3.15 cm/sup 3/ mean volume of coagulation necrosis were reproducibly obtained in the liver at the desired site with a reference ultrasound power of 10 W (Focal Power without absorption) and a timespan of 12 s. For transgastric application, the mean volume was 5.5 cm/sup 3/ with 7.5 W and 5 s, respectively. No gastric wall burns were observed with the treatment parameters defined. HIFU can be applied successfully with small transducers readily adaptable to the tip of an endoscope, thus opening a new perspective for endotherapy.

It is known that the magnitude of the flow component transverse to the sound beam from a transducer can be estimated from the spectral bandwidth. It is shown here that the direction as well as the magnitude of the velocity component in the plane normal to the beam axis can be estimated from the Doppler spectrum, provided that the transducer lacks an axis of circular symmetry along the beam direction. >

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

A novel hydrophone with nonmetallic electrodes is proposed. The polyvinylidene fluoride (PVDF) film hydrophone is polarized over a small area at its center. The electrical charges on this sensitive area are then driven electrically to the external leads through an electrolyte. With a thin 9-mm PVDF foil and an unmetallized sensitive area of 1 mm, the resulting hydrophone has a sensitivity of 12 mV/MPa over a bandwidth of about 20 MHz. More than 10/sup 5/ focused shock pulses of 30 MPa have been measured without any significant decrease in hydrophone sensitivity. >

Thresholds are reported for the production of in vivo focal ultrasonic tissue ablation, in rat kidneys, for single-shot irradiation at 1 MHz and 2.25 MHz with time durations ranging from 10 ms to 1 s. Several investigators have studied ultrasonic dosages for tissue damage, whereas here thresholds are given to produce total tissue ablation. It is shown that with short bursts, at the thresholds for tissue ablation, lesions as well as cavities surrounded by a small ring of coagulating necrosis which always appears at the focus of the sound wave are produced. However, when the intensity is increased, the lesions are more diffuse and do not necessarily appear at the focus, but at random positions. Sometimes for the highest intensities no lesion is present, suggesting that cavities form in the coupling medium. >

In an electrohydraulic generator, two underwater metal electrodes are connected in series with a capacitor charged to a high voltage. When the circuit is switched on, a plasma occurs reaching temperatures of thousands of degrees Celsius and resulting in a compressive pressure pulse. The formation of the plasma is a particular nonreproducible phenomenon inducing great variations in the pressure pulse values. Measurements obtained by triangulation show that the origin of the plasma changes and that the center of the spherical divergent shock wave can be located largely outside the interelectrode gap when tap water is used. However, the center of the shock wave is always located at the same place when electrolyte is used. The plasma duration was also photographed to better study the nonreproducibility of the shock-wave amplitudes. >

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

The present report compares acoustical fields radiated in water from two focused transducers of the same geometrical parameters (aperture diameter 100 mm, focal length 100 mm, resonance frequency 1 MHz), but made of different materials (PZT piezoceramic and piezocomposite). Both continuous wave and pulsed regimes of transducer excitation were used. A discrepancy between the O'Neil theory (1949) and experiment was noticed, which was essential in the case of the PZT radiator and of little importance for the piezocomposite source. It is shown that this disagreement is accounted for by Lamb waves propagating in the piezoceramic transducer material. O'Neil theory is not applicable to describe the pressure field, as long as the effect of Lamb waves is not taken into account for PZT transducers. On the contrary, O'Neil theory is able to describe approximately the pressure field of highly focused piezocomposite transducers.

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

Oesophagus cancer remains frequent with a bad prognosis despite the good short term results obtained by the association of radiochemotherapy and surgery. So, new curative and palliative treatments must be proposed. Efforts are currently undertaken to improve palliative therapy or even to achieve local tumour control by use of physical agents. It was demonstrated that High Intense Ultrasound (HIU) may induce rapid and complete coagulation necrosis with a well define geometry. Using this technique a 10 MHz transoesophageal applicator with external water cooling was developed. The active part is an air-backed plane rotating transducer to obtain sector-based or cylindrical coagulation necrosis. This applicator slides on a guide wire previously introduced in the oesophagus. The firing sequence consists to link up several shots every 10 seconds. The applicator operating at 14 W/cm/sup 2/ for 10 seconds was rotated through an angle of 18/spl deg/ after each shot. Results obtained on five healthy pig oesophagus shown that it was possible to induce homogeneous lesions without risk of perforation or lesion on surrounding tissue destruction. These promising results indicate that this ultrasound system may represent an effective tool for the treatment of oesophageal tumours in humans. An Independent Ethics Committee has recently approved an ongoing pilot clinical trial of this applicator.

Existing models for piezoelectric transducers are generally frequency domain-based. A limitation of these models is that they do not consider the fact that some components of the exciting or receiving electrical circuit can be time-dependent. This can happen when transducers are excited by capacitance discharge via a switch or when the circuit integrates active components such that diodes. In particular, in the case of capacitance discharge excitation, it is well known that the switch output impedance varies according to time. Indeed, its value is high when the switch is off and low when the switch is on. A temporal-based method is presented for the analysis of piezoelectric transducers in the thickness mode and their excitation circuit. A backing material and a matching layer are also considered. This model takes into account time-varying components by means of a step-by-step calculation process. The method has been successfully tested by comparison with measurements of transducer responses using an electrical circuit based on capacitance discharge via a transistor switch.

It is well-known that a plane sinusoidal acoustic wave propagating in nonlinear medium is transformed to a sawtooth wave with one shock per cycle. The distorted waveform may look quite different in the nearfield of intense source due to strong effect of diffraction. Two theoretical models and corresponding numerical algorithms for the description of nonlinear acoustic beams radiated from intense CW sources were previously reported. In the first model, diffraction effects are included using Rayleigh integral, nonlinearity and thermoviscous absorption are accounted for in a quasi plane approximation. The second model is based on the KZK equation, which, in contrary to the first model, accounts for diffraction in the parabolic approximation. Numerical simulations show that both models predict the possibility of development of two shocks in each wave cycle in the nearfield of a circular piston source. The motivation of this work was to experimentally verify the presence of these two shocks and their further collision. The measurements were conducted in water with a 47 mm diameter transducer working at the frequency of 1 MHz at various source pressure amplitudes up to 1 MPa. For the pressure amplitudes higher than 0.5 MPa, two shocks were observed in the waveform starting from some distances from the source. With the increase of the observation distance, the two shocks collided and formed one shock (per cycle), i.e. the waveform developed to usual sawtooth wave. The agreement between results and simulation is excellent, which is a guaranty of our two numerical models which will be used for others applications.

In the presence of a magnetic field, the propagation of ultrasound in an electrolyte produce a bulk current density due to Lorentz force. The present study describes the experimental set-up used to detect the interaction current in vitro. The used model consisted of a rectangular block of agar gel. A focused transducer produced pulses (6 /spl mu/s, 500 kHz) with a peak pressure up to 1.5 MPa. The magnetic field was applied using a purpose-build permanent magnet. The current was collected using two rectangular brass plates, parallel to the beam axis and placed on opposite sides of the gel block. The collected current was about 100 nA. The passage of the ultrasound pulse through the interfaces gel/surrounding medium produced clearly identified waveforms. The inverse filtering of the time signal enabled the 1-D reconstruction of the interfaces. The conclusion is that the interaction current is detectable and can potentially give rise to a new imaging modality.

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

Acoustic pressure alters local electrical conductivity in tissues and solutions. This work concerns the measurement of electrical conductivity in a liquid which is subjected to an acoustic pressure field created by a focused transducer. Measurements were made with four electrodes positioned in the ultrasonic focal zone, and the signal concerned is referred to as the acousto-electric interaction signal. A solution of sodium chloride in a measurement cell was subjected to ultrasound pressures of upto 1 MPa. It was shown that it is possible to quantitate the acousto-electric interaction signal once the ultrasonic vibration potential due to the Debye effect has been subtracted. The acousto-electric interaction signal was shown to be directly proportional to both the applied acoustic pressure and current. For the measurement cell used in this work, the interaction factor was found to be 5.3 microVmA(-1) MPa(-1).

The classical "Bio Heat Transfer Equation (BHTE)" model is adapted to take into account the effects of oscillating microbubbles that occur naturally in the tissue during high-intensity focused ultrasound (HIFU) treatment. First, the Gilmore-Akulichev model is used to quantify the acoustic pressure scattered by microbubbles submitted to HIFU. Because this scattered pressure is not monochromatic, the concept of harmonic attenuation is introduced and a global attenuation coefficient is estimated for bubble-filled tissues. The first results show that this global attenuation coefficient varies significantly with respect to several parameters such as the frequency and the density of microbubbles in the medium, but also with respect to the incident acoustic pressure which thus becomes a transcendental function. Under these conditions, a layer-by-layer modeling, in the direction of propagation, is proposed to calculate the ultrasonic beam. Finally, the BHTE is solved and the HIFU-induced lesions are estimated by the calculation of the thermal dose. Using this model, it can be observed first that, when the firing power increases, the lesion develops clearly in the direction of the transducer, with a shape agreeing with in vivo experimentation. Next, it is observed that the lesion can be significantly modified in size and position, if an interface (skin or inner wall) is simulated as a zone with multiple cavitation nuclei. With a firing power increase, it is also shown how a secondary lesion can appear at the interface and how, beyond a certain threshold, this lesion develops at the main lesion expense. Finally, a better in-depth homogeneity of lesions is observed when the acoustic frequency of HIFU is increased.

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

A time-domain numerical model is presented for simulating the finite-amplitude focused acoustic pulse propagation in a dissipative and nonlinear medium with a symmetrical source geometry. In this method, the main effects responsible in finite-amplitude wave propagation, i.e., diffraction, nonlinearity, and absorption, are taken into account. These effects are treated independently using the method of fractional steps with a second-order operator-splitting algorithm. In this method, the acoustic beam propagates, plane-by-plane, from the surface of a highly focused radiator up to its focus. The results of calculations in an ideal (linear and nondissipative) medium show the validity of the model for simulating the effect of diffraction in highly focused pulse propagation. For real media, very good agreement was obtained in the shape of the theoretical and experimental pressure-time waveforms. A discrepancy in the amplitudes was observed with a maximum of around 20%, which can be explained by existing sources of error in our measurements and on the assumptions inherent in our theoretical model. The model has certain advantages over other time-domain methods previously reported in that it: (1) allows for arbitrary absorption and dispersion, and (2) makes use of full diffraction formulation. The latter point is particularly important for studying intense sources with high focusing gains.

A simple protocol to fix biological species to silica-based surfaces (silica microbeads and glass slides), using a bifunctional silane reagent (3-cyanopropyl dimethyl chlorosilane), is presented. This silane reagent was used without further derivatization. This system led to strong, but not covalent, linkage of antibodies through their glycosylated regions (OH groups) to solid supports. The use of a microsized sample revealed that the coupling process depends not only on physicochemical interactions but also on steric phenomena, and in this case, it was shown that a molecule acting as a spacer was required for more efficient cell fixation. Here, monoclonal mouse antibodies against the CD45 molecule expressed on rat lymphocytes (MAR anti CD45 Ab) were linked to lymphocytes, and as spacers, sheep anti-mouse antibodies (SAM Ab) were immobilized on silica surfaces, allowing the cells to stick to the floating hollow silica microbeads by simple incubation. Under such conditions, a single microbead can fix several cells. The potential of this hollow, low-density support is in ultrasound applications, for the destruction by cavitation phenomena of cells selectively fixed onto such a support. Such a study can serve as a basic model for various microbiosystems involving cell manipulation.