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

The standard methods for recanalyzing thrombosed vessels are vascular stenting or administration of thrombolytic drugs. However, these methods suffer from uncertain success rate and side-effects. Therefore, minimally-invasive ultrasound methods have been investigated. In this article, we propose to use shockwaves after pre-exposure to fibrinolytic agent for disrupting thrombus. Shockwaves were delivered by an extracorporeal piezocomposite generator (120 mm in diameter, focused at 97 mm, pulse length = 1.4 micros). In vitro blood clots, made from human blood, were placed at the focal point of the generator. The clots were exposed to shockwaves either with or without prior immersion in a solution of streptokinase. The percentage of lysed clot was determined by weighing the clot before and after treatment. The proportion of lysed clot increased with the pressure at the focus and with the number of shocks. A mean clot reduction of 91% was obtained for 42 MPa in 4-min treatment duration only, without using streptokinase. For a treatment of 2 min at 29 MPa, the clot reduction increased significantly (p < 0.01) from 47% without streptokinase to 82% when streptokinase was used prior to shockwaves. These results also showed no significant damage to streptokinase due to exposure to shockwaves. This study suggests that extracorporeal shockwaves combined with streptokinase is a promising pharmaco-mechanical method for treating occlusive thrombus, and should be confirmed by in vivo trials. Additional studies must also be conducted with other fibrinolytic agents, whose abilities to penetrate clots are different.

In vitro sonodynamic cytotoxicity in regulated cavitation conditions.

Sonodynamic toxicity has always been linked to the cavitation phenomenon. In this work, sonodynamic effect with Photofrin was evaluated with a new ultrasound device: a regulated cavitation generator. In this way, acoustic intensity was substituted with cavitation level as ultrasound parameter. Photofrin potentiated significantly the cavitation cytotoxicity even for low setpoints where no inertial cavitation appeared. Therefore sonodynamic mechanism was principally mechanical, facilitated by the Photofrin insertion in cellular cytoplasmic membranes. This assertion was also supported by the fact that sonodynamic cytotoxicity was independent from the Photofrin presence or absence in the extracellular medium. Reproducible sonodynamic efficiency was perfectly obtained with this new regulated cavitation generator.

Feasibility of using ultrasound contrast agents to increase the size of thermal lesions induced by non-focused transducers: in vitro demonstration in tissue mimicking phantom.

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.

Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results.

BACKGROUND: 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 can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap. METHODS: Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single 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 operating at a frequency of 12 MHz. The mechanical 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. RESULTS: Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases. CONCLUSION: This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.

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

PURPOSE: Delivering a drug close to the targeted cells improves its benefit versus risk ratio. A possible method for local drug delivery is to encapsulate the drug into solid microscopic carriers and to release it by ultrasound. The objective of this work was to use shock waves for delivering a molecule loaded in polymeric microcapsules. MATERIAL AND METHODS: Ethyl benzoate (EBZ) was encapsulated in spherical gelatin shells by complex coacervation. A piezocomposite shock wave generator (120 mm in diameter, focused at 97 mm, pulse length 1.4 micros) was used for sonicating the capsules and delivering the molecule. Shock parameters (acoustic pressure, number of shocks and shock repetition frequency) were varied in order to measure their influence on EBZ release. A cavitation-inhibitor liquid (Ablasonic) was then used to evaluate the role of cavitation in the capsule disruption. RESULTS: The measurements showed that the mean quantity of released EBZ was proportional to the acoustic pressure of the shock wave (r2 > 0.99), and increased with the number of applied shocks. Up to 88% of encapsulated EBZ could be released within 4 min only (240 shocks, 1 Hz). However, the quantity of released EBZ dropped at high shock rates (above 2Hz). Ultrasound imaging sequences showed that cavitation clouds might form, at high shock rates, along the acoustic axis making the exposure inefficient. Measurements done in Ablasonic showed that cavitation plays a major role in microcapsules disruption. CONCLUSIONS: In this study, we designed polymeric capsules that can be disrupted by shock waves. This type of microcapsule is theoretically a suitable vehicle for carrying hydrophobic drugs. Following these positive results, encapsulation of drugs is considered for further medical applications.

Dual-mode ultrasound transducer for image-guided interstitial thermal therapy.

Deep-seated tumors can be treated by minimally invasive interstitial ultrasound thermal therapy. A miniature transducer emitting high-intensity acoustic waves is placed in contact with the targeted area to induce local thermal necrosis. Accurate positioning of the probe and treatment monitoring must be achieved for the technique to be effective. A piezocomposite technology was used for obtaining both high-quality imaging and effective treatment with the same transducer. Prototypes were designed and built to be compatible with an endoscopic approach for treating cholangiocarcinomas in the biliary ducts. The transducer had dimensions of 2.5 x 7.5 mm(2), it was cylindrically focused at 10 mm and it was operated at a center frequency of 11 MHz. Transducer efficiency was measured at 71%, and the impulse response corresponded to an axial resolution of 0.2 mm. In-vitro tests were conducted on samples of pig liver in which lesions up to 10 mm in depth were induced. B-mode images were obtained by mechanically rotating the transducer. Treatments were monitored in three ways: (i) classical M-mode images, (ii) images of local deformation of ultrasound lines during heating and (iii) comparison of the displacements induced in the tissue by radiation force, before and after treatments. The successful use of piezocomposite materials to manufacture dual-mode transducers opens new perspectives for interstitial ultrasound thermal therapy.

Developing an interstitial ultrasound applicator for thermal ablation in liver: results of animal experiments.

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.

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

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

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

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

Intraluminal high intensity ultrasound treatment in the esophagus under fast MR temperature mapping: in vivo studies.

New curative and palliative treatments are needed to respond to the poor prognosis of esophageal cancer. The purpose of this study was to determine whether magnetic resonance imaging (MRI) and MR thermometry can be used to monitor the thermal ablation induced by an intraluminal high-intensity ultrasound applicator positioned in the esophagus. Experiments were performed in vivo in 2 pig esophagi (25 thermal lesions per pig). Respiratory gated or cardiac gated MR thermometry was performed with segmented echo-planar imaging gradient echo sequences. All MR acquisitions were performed without susceptibility artifacts or radiofrequency interference with the ultrasound device. The experimental procedure proposed for accurate measurement of temperature in the esophagus was found to achieve an SD of +/- 1.5 degrees C for respiratory gating and +/- 3.1 degrees C for cardiac gating. Gd-enhanced T(1)-weighted images were used to depict coagulation necrosis. Autopsy was performed immediately after the treatment. Ultrasound effects were inspected visually, and the dimensions of the lesions in the liver neighboring the esophagus were compared with those determined on the MRI images. The visually assessed thermal lesions showed good correlation with the MRI data (10% mean volume difference). The feasibility of esophageal thermal ablation using intraluminal high-intensity ultrasound and of on-line MR temperature monitoring was demonstrated.

Monitoring the formation of thermal lesions with heat-induced echo-strain imaging: a feasibility study.

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.

[Haemostatic efficacy of a high intensity focused ultrasound applicator in lower pole partial nephrectomy in the pig]. / Efficacité hémostatique d'un applicateur a ultrasons collimatés de haute intensité dans la néphrectomie partielle sous hilaire chez le porc.

OBJECTIVE: To evaluate the haemostatic property of a high intensity focused ultrasound (HIFU) applicator in lower pole partial nephrectomy in a porcine model. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

New clinical concepts in lithotripsy demand smaller shock heads. Reducing the size of piezoelectric shock heads requires increasing the surface pressure of each transducer so that the total pressure at the focus remains the same. A new method allowing generation of large surface pressures is described. The hypothesis is that piezoelectric plots in piezo-composite material are more fragile in extension than in compression. For this reason, actuators are mechanically prestressed between two flasks. This method cannot be used for transducers working at high frequencies, such as 0.5 MHz. So we tried to electrically prestrain compressively the piezoelectric material by applying a high-electrical field in the opposite direction of polarization. Three protocols were tested and compared to classically driven transducers. In the first protocol, prestrain is permanently applied, in the second protocol prestrain is applied for 100 micros before the compressive impulse, and in the third protocol prestrain is applied for 100 micros and followed by a bipolar field that allows the material to be repoled between two successive pulses. With the two first protocols, rapid depoling and repoling in the opposite direction was noticed. Only with the last protocol was it possible to increase the maximum surface pressure. This increase was approximately the same whether the material was hard or soft. Using this protocol, aging tests were conducted on three samples of each kind of material, and a pressure of 4 MPa was obtained over 10(6) shocks. This value seems to be enough to develop a piezoelectric shock-wave generator with a diameter of approximately 20 cm instead of the 45-cm commercially available.

Determination of the acoustic pressure at and the reflection coefficient of a target through measurements of the absorbed power and the emitter voltage.

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.

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

Intraluminal (within the alimentary tract) thermal surgery has been shown to be a useful therapeutic option when extracorporeal focused ultrasound applicators cannot be used since their beam may not reach the target site. If plane transducers are used for the treatment of alimentary tract tumours, the applicator must be rotated in order to generate a cylindrical volume of necrosis. However, rotating these applicators and controlling their shooting direction presents technical difficulties. If tubular transducers are used it is difficult to treat arbitrary angles with a large therapeutic length. To solve these difficulties, the feasibility of an ultrasound phased array applicator has been evaluated using a cylindrical prototype (outer diameter 10.6 mm), which is composed of 16 elementary transducers working at 4.55 MHz and arranged on a quarter of the cylinder. Using this applicator it is possible to generate plane or cylindrical waves. Plane waves were generated by exciting eight successive elements of the array with appropriate delay times. The exposure direction was changed by exciting a different set of eight elements. In this way, the ultrasound beam was electronically rotated through the tissues. Cylindrical waves were generated by exciting several transducers without delay times. Imaging was provided using a miniature echographic probe. Ex vivo experiments were carried out in pig liver to compare two approaches of treatment. The first consisted of generating successive plane waves separated from each other by a 6 degrees angle. The second one consisted of exciting all the 16 elements without delay times. In the two cases, the lesions were well-defined and occupied a quarter of cylinder. In both sets of experiments, the sonication time and the intensity were 20 s and 17 W/cm(2), respectively. In the first case, the depth was up to 17 mm compared to 6 mm in the second case.

Feasibility of a transurethral ultrasound applicator for coagulation in prostate.

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.

Combination of thermal and cavitation effects to generate deep lesions with an endocavitary applicator using a plane transducer: ex vivo studies.

In the high-intensity focused ultrasound (US), or HIFU, field, it is well-known that the cavitation effect can be used to induce lesions of larger volume. The principle is based on the increase in the equivalent attenuation coefficient of the tissue in the presence of the bubbles created by cavitation. The elementary lesions produced by combination of cavitation and thermal effects, using focused transducers, were spherical and developed upstream of the focal point. This paper presents a method that combines cavitation with a thermal effect to obtain deeper lesions using a plane transducer, rather than a focused one. The cavitation effect was produced by delivering intensities of 60 W/cm2 at the face of the transducer for 0.5 s. The applicator was then rotated through 90 degrees at a constant speed of between 0.5 and 1.5 degrees /s. During this rotation, ex vivo tissues were exposed continuously to an acoustic intensity of 14 W/cm2 to combine the cavitation effect with a thermal effect. The necroses were, on average, twice as deep when the cavitation effect was used as those obtained with a thermal effect alone. Observed macroscopically, the lesions have a very well-delimited geometry. Temperature measurements made at different angles of treatment have shown that they were coagulation necroses.

Long-lasting stable cavitation.

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.

Transoesophageal ultrasound applicator for sector-based thermal ablation: first in vivo experiments.

New curative and palliative treatments must be proposed to respond to the bad long-term prognosis of oesophageal cancers. It has been demonstrated that high intensity ultrasound (US) 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 oesophageal tumours may be critical, where both malignant and healthy tissues are covered by the US beam. Thus, in vivo trials were conducted on five healthy pig oesophaguses to determine the maximal thermal dose that will not induce a perforation of the oesophagus or surrounding tissues. From the results of previous studies, this dose is high enough to treat pathological tissues. These promising results indicate that this US system represents a safe and effective tool for the clinical treatment of oesophageal tumours.

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

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