David Melodelima

THERMAL ABLATION BY HIGH-INTENSITY-FOCUSED ULTRASOUND USING A TOROID TRANSDUCER INCREASES THE COAGULATED VOLUME. RESULTS OF ANIMAL EXPERIMENTS

Surgical resection is the only treatment of colorectal liver metastases that can ensure long-term survival and cure in some patients. However, only 20% of patients are suitable for surgery. As a result, many nonresectional modalities of treatment have been assessed to provide an alternative to liver resection. Several limitations have been observed when using these techniques and available evidence is limited. Here, we report that a new design of high intensity focused ultrasound transducer can significantly enlarge the coagulated volume over short periods of time and that treatment in the liver can be guided in real-time using an integrated ultrasound imaging probe. Our long-term objective is to develop a device that can be used during surgery for eventual clinical use in conjunction with resection. Eight ultrasound emitters, divided into 256 elements, were created by sectioning a single toroid piezocomposite transducer. The focal zone was conical in shape and located 70 mm from the transducer; enabling the treatment of deep-seated tumors. A single thermal lesion was created when the eight emitters performed alternative and consecutive 5-s ultrasound exposures. This article presents in vivo evidence that the coagulated volume obtained from a 40 s total exposure in the liver was 7.0 +/- 2.5 cm(3) (minimum 1.5 - maximum 20.0 cm(3)) with an average diameter of 17.5 +/- 3.8 mm (minimum 10.0 - maximum 29.0 mm). All lesions were visible with high contrast on sonograms. The correlation between the diameter of lesions observed on sonograms and during gross examination was 92%. This method also allowed the user to easily enlarge the coagulated volume by juxtaposing single lesions. This approach may have a role in treating unresectable colorectal liver metastases and may also be used in conjunction with resection to extend its limits.

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°C for respiratory gating and ± 3.1°C for cardiac gating. Gd‐enhanced T1‐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. Magn Reson Med, 2005.

Interstitial devices for minimally invasive thermal ablation by high-intensity ultrasound.

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

Ultrasound surgery with a toric transducer allows the treatment of large volumes over short periods of time

Thermal ablation by physical agents is widely used in clinical settings, but it generally results in a small coagulated volume. Here, we report that a technologically advanced high intensity focused ultrasound transducer can significantly enlarge the coagulated volume over short periods of time. Eight ultrasound emitters were created by sectioning a single toric piezocomposite transducer. A single thermal lesion is created when the eight emitters perform alternative and consecutive 5s ultrasound exposures. This paper presents in vivo evidence that the coagulated volume obtained from a 40s total exposure in the liver was 8.6±4.8cm3.

Thermal ablation produced using a surgical toroidal high-intensity focused ultrasound device is independent from hepatic inflow occlusion

In the liver, the efficacy of radiofrequency or high-intensity focused ultrasound (HIFU) ablation is impaired by blood perfusion. This can be overcome by hepatic inflow occlusion. Here we report the in vivo evaluation of ablations performed in the liver using a surgical toroidal HIFU device used during an open procedure with and without hepatic inflow occlusion. The HIFU device was composed of 256 toroidal-shaped emitters working at 3 MHz and an integrated ultrasound imaging probe working at 7.5 MHz. Using an intermittent Pringle maneuver (IPM), thermal ablations were created in three pigs with hepatic inflow occlusion (IPM group) and in three pigs with normal perfusion (NoIPM group). The ablations were studied on sonograms, macroscopically and microscopically 14 days after the treatment. In the NoIPM group, the average coagulated volume obtained after a 40 s exposure was 7.4 +/- 3.8 cm(3) (2.2-16.6). In the IPM group, the average ablated volume was 6.3 +/- 2.9 cm(3) (2.6-12.1). There was no significant difference between the two groups in terms of ablated volume (p = 0.25), diameter (p = 0.37) or depth (p = 0.61). Therefore, a toroidal-shaped HIFU device allows treatment in the liver that can be considered as independent from hepatic inflow occlusion.

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.

Utility of a Tumor-Mimic Model for the Evaluation of the Accuracy of HIFU Treatments. Results of In Vitro Experiments in the Liver

Presented in this article is a tumor-mimic model that allows the evaluation, before clinical trials, of the targeting accuracy of a high intensity focused ultrasound (HIFU) device for the treatment of the liver. The tumor-mimic models are made by injecting a warm solution that polymerizes in hepatic tissue and forms a 1 cm discrete lesion that is detectable by ultrasound imaging and gross pathology. First, the acoustical characteristics of the tumor-mimics model were measured in order to determine if this model could be used as a target for the evaluation of the accuracy of HIFU treatments without modifying HIFU lesions in terms of size, shape and homogeneity. On average (n = 10), the attenuation was 0.39 +/- 0.05 dB.cm(-1) at 1 MHz, the ultrasound propagation velocity was 1523 +/- 1 m.s(-1) and the acoustic impedance was 1.84 +/- 0.00 MRayls. Next, the tumor-mimic models were used in vitro in order to verify, at a preclinical stage, that lesions created by HIFU devices guided by ultrasound imaging are properly positioned in tissues. The HIFU device used in this study is a 256-element phased-array toroid transducer working at a frequency of 3 MHz with an integrated ultrasound imaging probe working at a frequency of 7.5 MHz. An initial series of in vitro experiments has shown that there is no significant difference in the dimensions of the HIFU lesions created in the liver with or without tumor-mimic models (p = 0.3049 and p = 0.8796 for the diameter and depth, respectively). A second in vitro study showed that HIFU treatments performed on five tumor-mimics with safety margins of at least 1 mm were properly positioned. The margins obtained were on average 9.3 +/- 2.7 mm (min. 3.0 - max. 20.0 mm). This article presents in vitro evidence that these tumor-mimics are identifiable by ultrasound imaging, they do not modify the geometry of HIFU lesions and, thus, they constitute a viable model of tumor-mimics indicated for HIFU therapy.

Intra-operative ultrasound hand-held strain imaging for the visualization of ablations produced in the liver with a toroidal HIFU transducer: first in vivo results

The use of hand-held ultrasound strain imaging for the intra-operative real-time visualization of HIFU (high-intensity focused ultrasound) ablations produced in the liver by a toroidal transducer was investigated. A linear 12 MHz ultrasound imaging probe was used to obtain radiofrequency signals. Using a fast cross-correlation algorithm, strain images were calculated and displayed at 60 frames s(-1), allowing the use of hand-held strain imaging intra-operatively. Fourteen HIFU lesions were produced in four pigs. Intra-operative strain imaging of HIFU ablations in the liver was feasible owing to the high frame rate. The correlation between dimensions measured on gross pathology and dimensions measured on B-mode images and on strain images were R = 0.72 and R = 0.94 respectively. The contrast between ablated and non-ablated tissue was significantly higher (p < 0.05) in the strain images (22 dB) than in the B-mode images (9 dB). Strain images allowed equivalent or improved definition of ablated regions when compared with B-mode images. Real-time intra-operative hand-held strain imaging seems to be a promising complement to conventional B-mode imaging for the guidance of HIFU ablations produced in the liver during an open procedure. These results support that hand-held strain imaging outperforms conventional B-mode ultrasound and could potentially be used for the assessment of thermal therapies.

Cancer treatment by ultrasound: Increasing the depth of necrosis

Tissue coagulation by high-intensity ultrasound is a well-established method of cancer treatment. It suffers, however, from insufficient depth of action in the case of deep-seated tumors where endoscopic or interstitial applicators are used. It is demonstrated here that this depth can be increased by temporarily creating cavitation bubbles in such a way that ultrasound attenuation becomes stronger in the zone where tissue heating is insufficient. In vitro experiments in liver tissue confirm that bubbles are indeed located in this zone and that the effective depth of coagulation necrosis is doubled.

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

BackgroundEsophageal 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.MethodsThermal 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.ResultsHere 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.ConclusionThis clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.