Robot-assisted ultrasound navigation platform for 3D HIFU treatment planning: Initial evaluation for conformal interstitial ablation.

Interstitial Ultrasound-guided High Intensity Focused Ultrasound (USgHIFU) therapy has the potential to deliver ablative treatments which conform to the target tumor. In this study, a robot-assisted US-navigation platform has been developed for 3D US guidance and planning of conformal HIFU ablations. The platform was used to evaluate a conformal therapeutic strategy associated with an interstitial dual-mode USgHIFU catheter prototype (64 elements linear-array, measured central frequency f = 6.5 MHz), developed for the treatment of HepatoCellular Carcinoma (HCC). The platform included a 3D navigation environment communicating in real-time with an open research dual-mode US scanner/HIFU generator and a robotic arm, on which the USgHIFU catheter was mounted. 3D US-navigation was evaluated in vitro for guiding and planning conformal HIFU ablations using a tumor-mimic model in porcine liver. Tumor-mimic volumes were then used as targets for evaluating conformal HIFU treatment planning in simulation. Height tumor-mimics (ovoid- or disc-shaped, sizes: 3-29 cm3) were created and visualized in liver using interstitial 2D US imaging. Robot-assisted spatial manipulation of these images and real-time 3D navigation allowed reconstructions of 3D B-mode US images for accurate tumor-mimic volume estimation (relative error: 4 ± 5%). Sectorial and full-revolution HIFU scanning (angular sectors: 88-360°) could both result in conformal ablations of the tumor volumes, as soon as their radii remained ≤ 24 mm. The presented US navigation-guided HIFU procedure demonstrated advantages for developing conformal interstitial therapies in standard operative rooms. Moreover, the modularity of the developed platform makes it potentially useful for developing other HIFU approaches.

High-intensity focused ultrasound applied to the placenta using a toroidal transducer: a preliminary ex-vivo study.

OBJECTIVE: To demonstrate in an ex-vivo model the feasibility of applying high-intensity focused ultrasound (HIFU) using a toroidal transducer for the creation of placental lesions. METHODS: In this study we used a toroidal transducer, composed of 32 ring-shaped emitters with an ultrasound probe at the center, operating at a frequency of 2.5 MHz. We examined 45 human placentae, following either normal vaginal delivery or medical termination of pregnancy between 17 and 40 gestational weeks. First, the attenuation coefficients of 12 human placentae were measured and integrated into a numerical model for simulating HIFU lesions. Then, using acoustic parameters from this preliminary study, we performed ex-vivo experiments with 33 human placentae, each overlain with an animal abdominal wall to simulate the maternal wall. We created single HIFU lesions in 25 of these placentae, and a series of six juxtaposed lesions in eight, studying these both sonographically and macroscopically. RESULTS: Human placental attenuation coefficients of the 12 human placentae ranged from 0.072 to 0.098 Np/cm/MHz, according to gestational age. The 25 single HIFU lesions created had an average diameter of 7.1 ± 3.2 mm and an average depth of 8.2 ± 3.1 mm. The average diameter of the eight series of six juxtaposed HIFU lesions was 23.0 ± 5.0 mm and the average depth was 11.0 ± 4.7 mm. The average thickness of the abdominal walls was 10.5 ± 1.8 mm. No lesions or damage were observed in intervening tissues. CONCLUSION: This study demonstrates, using an ex-vivo model, the feasibility, reproducibility, harmlessness and effectiveness of HIFU applied to the human placenta.

Imaging of shear waves induced by Lorentz force in soft tissues.

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

Salvage high-intensity focused ultrasound ablation for prostate cancer local recurrence after external-beam radiation therapy: prognostic value of prostate MRI.

AIM: To assess the prognostic value of magnetic resonance imaging (MRI) before salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after external-beam radiotherapy (EBRT). MATERIALS AND METHODS: Forty-six patients who underwent prostate MRI before salvage HIFU for locally recurrent prostate cancer after EBRT were retrospectively studied. HIFU failure was defined as a prostate-specific antigen (PSA) value >nadir + 2 ng/ml (Phoenix criteria) or positive follow-up biopsy or initiation of any other salvage therapy. The following prognostic parameters were assessed: neoadjuvant hormone therapy, clinical stage and Gleason score of recurrence, PSA level and velocity at HIFU treatment, and six MRI-derived parameters (prostate volume, tumour volume, extracapsular extension, seminal vesicle invasion, tumour extension into the apex or anterior to the urethra). RESULTS: Two factors were significant independent predictors of salvage HIFU failure: the PSA level at HIFU treatment (p < 0.012; risk ratio: 1.15, 95% CI: 1.03-1.29) and the tumour extension anterior to the urethra, as assessed by MRI (p = 0.046, risk ratio: 2.51, 95% CI: 1.02-6.16). CONCLUSION: The location of cancer recurrence anterior to the urethra on MRI is an independent significant predictor of salvage HIFU failure for locally recurrent prostate cancer after EBRT. Therefore, MRI may be useful for patient selection before post-EBRT salvage HIFU ablation.

Visualisation of liver tumours using hand-held real-time strain imaging: results of animal experiments.

OBJECTIVE: Surgical resection is the only curative option for colorectal hepatic metastases. Intra-operative localisation of these metastases during hepatic resection is performed by intra-operative B-mode imaging and palpation. Because liver metastases are stiffer than normal tissues, elastography may be a useful complement to B-mode imaging. This paper reports quantitative measures of the image quality attained during intra-operative real-time elastographic visualisation of liver metastasis. METHODS: VX2 tumours were implanted in the liver of eight rabbits and were scanned in vivo. Measurements of the tumour dimensions obtained via elastography were compared with those obtained using B-mode imaging and with gross pathology. RESULTS: Measurements of tumour diameters were similar when obtained by intra-operative elastography and pathological measurement methods (mean difference±standard deviation, 0.1±0.9 mm). The contrast between tumours and normal tissues was significantly higher (p<0.05) in elastograms (26±10 dB contrast) than in sonograms (1±1 dB contrast). Sensitivity and specificity for detecting tumours using intra-operative elastography were 100% and 88%, respectively, and positive and negative predictive values were 89% and 100%, respectively. In two cases elastograms were able to detect a tumour that was ambiguous in B-mode images. CONCLUSION: Combined hand-held B-mode/strain imaging may provide additional information that is relevant for detection of liver metastases that may be missed by standard B-mode imaging alone, such as small and/or isoechoic tumours.

Assisted hepatic resection using a toroidal HIFU device: an in vivo comparative study in pig.

PURPOSE: Bleeding is the main cause of postoperative complications during hepatic surgery. Blood loss and transfusions increase tumor recurrence in liver metastases from colorectal cancer. A high intensity focused ultrasound (HIFU) device with an integrated ultrasound imaging probe was developed for the treatment of colorectal liver metastasis. METHODS: The HIFU toroidal-shaped transducer contains 256 elements (working frequency: 3 MHz) and can create a single conical lesion of 7 cm3 in 40 s. Then, the volume of treatment can be significantly increased by juxtaposing single lesions. Presented here is the use of this device in an animal model as a complementary tool to improve surgical resection in the liver. Before transecting the liver, a wall of coagulative necrosis was performed using this device in order to minimize blood loss and dissection time during hepatectomy. Resection assisted by HIFU was compared to classical dissections with clamping [intermittent Pringle maneuver (IPM) group] and without clamping (control group). For each technique, 14 partial liver resections were performed in seven pigs. Blood loss per dissection surface area and resection time were the main outcome parameters. RESULTS: Conserving liver blood inflow during hepatic resection assisted by HIFU did not increase total blood loss (7.4 +/- 3.3 ml cm(-2)) compared to hepatic resection performed during IPM and controlled blood inflow (11.2 +/- 2.2 ml cm(-2)). Lower blood loss was measured on average when using HIFU, even though difference with clamping (IPM) was not statistically significant (p = 0.09). Resection assisted by HIFU reduced blood loss by 50% compared to control group (14.0 +/- 3.4 ml cm(-2), p = 0.03). The duration of transection when using HIFU (13 +/- 3 min) was significantly lower compared to clamping (23 +/- 4 min, p < 0.01) and control (18 +/- 3 min, p = 0.02). Precoagulation also resulted in sealing blood vessels with a diameter of less than 5 mm, and therefore the number of clips needed in the HIFU group was significantly lower (0.8 +/- 0.2 cm(-2)) when compared to clamping (1.6 +/- 0.2 cm(-2), p < 0.01) and control (1.8 +/- 0.4 cm(-2), p < 0.01). CONCLUSIONS: This method holds promise for future clinical applications in resection of liver metastases.

[Outcomes of HIFU for localised prostate cancer using the Ablatherm Integrate Imaging® device]. / Traitement du cancer localisé de la prostate avec l'appareil Ablatherm Imagerie Intégrée® : résultats carcinologiques et fonctionnels.

OBJECTIVES: To report the functional and oncological outcomes of HIFU for prostate cancer using the Ablatherm Integrate Imaging(®) device. METHODS: Between January 2005 and June 2009, all patients treated with HIFU as a primary care option for localized prostate cancer and fulfilling the French Urological Association (AFU) guideline were included in this study. Validated questionnaires were used to assess continence, potencies and quality of life. RESULTS: A total of 297 patients met the inclusion criteria: 149 were low risk and 148 were intermediate risk according to d'Amico's risk group. The median prostate specific antigen (PSA) nadir was 0.12ng/ml with 65% of patients reaching a nadir less than 0.3 ng/ml. Systematic control biopsies were performed on 175 patients with 89% of negative biopsies. The disease free survival rate at 40 months was 79% for low risk group and 62% for intermediate risk group. The pre and post-HIFU treatment International Prostate Symptoms Score (IPSS) score and quality of life questionnaire were not statistically different. In the opposite, the pre and post-HIFU erection function and continence status were significantly different. CONCLUSION: Local control and Biochemical Free Survival Rate achieved with HIFU were similar to those expected with conformal external radiation beam therapy. Among the functional outcomes, potency was the most impacted by the treatment.

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.

In vivo preclinical evaluation of the accuracy of toroidal-shaped HIFU treatments using a tumor-mimic model.

The pig is an ideal animal model for preclinical evaluation of HIFU treatments, especially in the liver. However, there is no liver tumor model available for pigs. In this work, we propose to study an in vivo tumor-mimic model as a tool for evaluating if a sonographycally guided HIFU treatment, delivered by a toroidal-shaped device dedicated for the treatment of liver metastases, is correctly located in the liver. One centimeter tumor-mimics were created in liver tissues. These tumor-mimics were detectable on ultrasound imaging and on gross pathology. Two studies were carried out. First, an in vivo study of tolerance at mid-term (30 days, 10 pigs) revealed that tumor-mimics are suitable for studying HIFU treatments at a preclinical stage, since local and biological tolerances were excellent. The dimensions of the tumor-mimics were reproducible (diameter at day 0: 9.7 +/- 2.0 mm) and were the same as a function of time (p = 0.64). A second in vivo study was carried out in ten pigs. Tumor mimics were used as targets in liver tissues in order to determine if the HIFU treatment is correctly located in the liver. A procedure of extensive HIFU ablation using multiple HIFU lesions juxtaposed manually was then tested on eight tumor-mimics. In 88% of the cases (seven out of eight), tumor-mimics were treated with negative margins (>or=1 mm) in all directions. On average, negative margins measured 10.0 +/- 6.7 mm. These tumor-mimics constitute an excellent reference for studying in vivo the accuracy of HIFU therapy in the liver.

Dual-mode transducers for ultrasound imaging and thermal therapy.

Medical imaging is a vital component of high intensity focused ultrasound (HIFU) therapy, which is gaining clinical acceptance for tissue ablation and cancer therapy. Imaging is necessary to plan and guide the application of therapeutic ultrasound, and to monitor the effects it induces in tissue. Because they can transmit high intensity continuous wave ultrasound for treatment and pulsed ultrasound for imaging, dual-mode transducers aim to improve the guidance and monitoring stages. Their primary advantage is implicit registration between the imaging and treatment axes, and so they can help ensure before treatment that the therapeutic beam is correctly aligned with the planned treatment volume. During treatment, imaging signals can be processed in real-time to assess acoustic properties of the tissue that are related to thermal ablation. Piezocomposite materials are favorable for dual-mode transducers because of their improved bandwidth, which in turn improves imaging performance while maintaining high efficiency for treatment. Here we present our experiences with three dual-mode transducers for interstitial applications. The first was an 11-MHz monoelement designed for use in the bile duct. It had a 25x7.5 mm(2) aperture that was cylindrically focused to 10mm. The applicator motion was step-wise rotational for imaging and therapy over a 360 degrees, or smaller, sector. The second transducer had 5-elements, each measuring 3.0x3.8 mm(2) for a total aperture of 3.0x20 mm(2). It operated at 5.6 MHz, was cylindrically focused to 14 mm, and was integrated with a servo-controlled oscillating probe designed for sector imaging and directive therapy in the liver. The last transducer was a 5-MHz, 64-element linear array designed for beam-formed imaging and therapy. The aperture was 3.0x18 mm(2) with a pitch of 0.280 mm. Characterization results included conversion efficiencies above 50%, pulse-echo bandwidths above 50%, surface intensities up to 30 W/cm(2), and axial imaging resolutions to 0.2 mm. The second transducer was evaluated in vivo using porcine liver, where coagulation necrosis was induced up to a depth of 20 mm in 120 s. B-mode and M-mode images displayed a hypoechoic region that agreed well with lesion depth observed by gross histology. These feasibility studies demonstrate that the dual-mode transducers had imaging performance that was sufficient to aid the guidance and monitoring of treatment, and could sustain high intensities to induce coagulation necrosis in vivo.

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.

[MR detection of local prostate cancer recurrence after transrectal high-intensity focused US treatment: preliminary results]. / Détection par IRM des récidives locales du cancer de prostate après traitement par ultrasons focalisés de haute intensité (HIFU) transrectaux: étude préliminaire.

PURPOSE: To assess T2W and dynamic: contrast-enhanced (DCE) MR imaging in the detection of local tumor recurrence after transrectal high-intensity focused US (HIFU) treatment. MATERIALS AND METHODS: Fifteen patients treated by HIFU for prostate cancer were referred for MR due to biological evidence of tumor recurrence. Axial, sagittal and coronal T2W images and DCE images (12 3-mm thick axial images, temporal resolution: 15 seconds) were obtained first. Transrectal biopsies were then obtained under US guidance. MR findings were compared to biopsy results for 10 prostate sectors. RESULTS: Biopsies demonstrated tumor recurrence in 13/15 patients (23/108 sectors). On T2W images, the treated prostate tissue was diffusely hypointense which interfered with interpretation. Three patients (5 sectors) had suspicious areas of T2W signal abnormality and 15 patients (29 sectors) had suspicious areas on DCE scans. An analysis per sector for T2W and DCE imaging showed sensitivity, specificity, positive predictive and negative predictive values respectively of 0.13, 0.98, 0.6 and 0.81 and 0.70, 0.85, 0.55 and 0.91. DCE MR was strongly predictive of positive biopsy results (Odds ratio: 12.8 (95% confidence interval: 4.4-37.3)) whereas T2W imaging was not (Odds ratio: 4.0 (95% confidence interval: 0.5-30)). CONCLUSION: MR, especially DCE MR, is promising for the detection and localization of local prostate cancer recurrence after transrectal HIFU treatment.

[Locally recurrent prostatic adenocarcinoma after exclusive radiotherapy: results of high intensity focused ultrasound]. / Adénocarcinome prostatique en récidive locale après radiothérapie exclusive: résultats du traitement par ultrasons focalisés.

OBJECTIVES: To determine the efficacy and adverse effects of high intensity focused ultrasound (HIFU) for the treatment of local recurrence of prostate cancer after exclusive external beam radiotherapy. MATERIAL AND METHODS: Seventy-two patients with histologically and biologically documented local recurrence after radiotherapy were treated by HIFU. The mean age was 68.27+/-5.93 years, and mean PSA was 6.64+/-7.26ng/ml. Thirty patients were treated according to standard parameters and 42 according to specific parameters. ASTRO 2005 criteria, specific for salvage therapy (Phoenix consensus), were used to define recurrence. Progression-free survival was calculated by the Kaplan-Meier method. RESULTS: Mean follow-up was 39+/-28 months. The negative biopsy rate was 80% and the median nadir PSA was 0.10ng/ml. Specific survival was 94% at three years and 90% at five years, and progression-free survival was 50% at three years and 44% at five years. The urinary incontinence rate was 44% (grade 1 : 12%, grade 2/3 : 32%) and the urethral stricture or bladder neck stenosis rate was 30%. The use of specific parameters reduced the incidence of severe incontinence (19% versus 50, P=0.005) and stenosis (24% versus 40). CONCLUSIONS: Treatment with HIFU achieved a five-year progression-free survival of 44%, but patients must be clearly informed about the high rate of adverse effects.

Morphological analysis of the interstitial ultrasonic ablation in porcine liver in vivo.

BACKGROUND: The shape of the induced thermal ablation area is as important as its dimension. The aim of this study was to analyze the size reproducibility and the aspect of the interstitial ultrasonic ablation obtained by a planar transducer in porcine liver in vivo. METHODS: Five pigs were used. Two complete ultrasonic lesions were made in each animal under pedicle clamping. All the lesions underwent MR examination on day 7 and then a histological analysis. RESULTS: The tested probe has the advantage of providing a step-by-step and highly directional treatment in the target zone. The ultrasonic lesions presented as well-defined and homogenous areas of tissue coagulation. The lesion volumes ranged from 8.1 to 92.3 cm3 with an averaged lesion length of 56 mm at gross examination. Three-dimensional reconstruction of the lesions from the MR images showed cylindrical and conical shapes. Large intrahepatic vessels distorted the lesion shape, and the vicinity of the application to the liver surface increased significantly the volume of the ultrasonic necrosis. Histological examination showed complete necrosis in the area of damage. CONCLUSION: The ultrasonic ablation has a regular shape, always with sharply defined borders. However, it showed some variability in the size of the induced lesions.

New integrated imaging high intensity focused ultrasound probe for transrectal prostate cancer treatment.

The present study proposes a new integrated imaging (II) high-intensity focused ultrasound (HIFU) probe intended as an improvement to the Ablatherm prostate cancer treatment. Because of a perforation in the center of the II probe, the expected lesion differs from the one obtained for the original Ablatherm probe. In this paper, the new geometry and the strategy followed to establish the treatment parameters are presented. The original probe has a 40-mm focal length, a 50-mm aperture and is truncated at 31 mm. The II probe has a 45-mm focal length, a 61-mm aperture, a central perforation of 25 mm and is truncated at 31 mm. Both probes operate at 3 MHz. A mathematical model for lesion prediction was used for setting the treatment parameters for the II probe. These parameters should ensure equivalence between the lesions obtained with the original and II probes. Simulation-obtained parameters were validated by in-vitro and in-vivo (on liver of 70 New Zealand rabbits) experiments. The new II probe was used clinically to treat 30 patients. The mean age was 70.9 +/- 5.3 years (SD), the mean prostate volume 26.9 +/- 7.7 mL and the mean serum prostate specific antigen (PSA) concentration before treatment was 9.2 +/- 5.5 ng/mL. Simulations showed that for the II probe acoustical power and duration when the transducer is inactive should be reduced of 14% and 1s. In-vitro and in-vivo experiments confirmed the equivalence between the lesions obtained with the two probes. The lesion volume obtained under in-vitro conditions (for a traversed tissue depth of 16 mm to the focus) was 5 +/- 0.4 cm(3) and 5.1 +/- 0.5 cm(3) for the original and II probes, respectively. Under in-vivo conditions, the lesion volume (for a traversed tissue depth of 18 mm) was 5.3 +/- 1.1 cm(3) and 5.1 +/- 1.1 cm(3) for the original and II probes, respectively. During the clinical trial, a correction of + 1s in the exposure time was required to recreate the same degree of efficacy observed with the original probe (p = 0.97): 66.7 % of negative biopsies and 75% of patients with PSA at 3 mo < or =1 ng/mL. The morbidity observed was minimal and identical to that observed with the original probe.

In vitro evaluation of an oscillating dual-mode ultrasound probe for sector imaging and directive therapy.

Interstitial probes have been shown as effective devices to deliver high-intensity ultrasound therapy. Here, cylindrically-focused dual-mode transducers with either one or 5-elements were characterized, and a monoelement probe was evaluated in vitro. In therapy mode, the transducers were maximally efficient (> or =70%) at 5.6 MHz with surface intensities up to 20 W/cm(2). In imaging mode, fractional bandwidths were 46% and 50+/-4% (ave+/-std) for the monoelement and 5-element transducers respectively. Axial and lateral resolutions were 0.5 mm and 1.0 mm, respectively, for both transducers as measured with a point scatterer in the focal plane. After characterization, the oscillating probe was used to image and apply therapy to porcine liver. B-mode images over a 140 degrees sector were formed before and after therapy, which was applied for 90 s at each of 5 angles separated by 20 degrees (e.g. -40 degrees , -20 degrees, 0 degrees, 20 degrees, 40 degrees) to form a composite lesion. Transducer surface intensity was 18 W/cm(2). Therapy was interrupted at 125 ms intervals to collect pulse/echo data along the therapy axes. Data were displayed in real-time as an M-mode image to monitor therapy. B-mode images adequately represented the liver tissue. M-mode image data agreed well with the formation of lesions in the liver.

Influence of the docetaxel administration period (neoadjuvant or concomitant) in relation to HIFU treatment on the growth of Dunning tumors: results of a preliminary study.

The objective of this study was to evaluate mechanisms of the synergy between high intensity-focused ultrasound (HIFU) and docetaxel and to determine the best sequence of chemotherapy administration in relation to HIFU treatment for obtaining optimum control of tumoral growth. A total of 15 days after s.c. implantation of the tumor, 52 Copenhagen rats studied were randomized in 4 groups of 13: controls, docetaxel alone (group 1), HIFU and docetaxel concomitant (group 2) and HIFU and docetaxel administered 24 h before treatment (group 3). The number of HIFU shots was calculated in order to cover 75% of the tumor volume. The effects of docetaxel, HIFU and their interaction on tumor volumes were analyzed using a linear regression. The distributions of the tumor volumes were significantly greater in the control group than in the group 1 (P=0.002) and than in both groups 2 and 3 (P < 0.0001 and P = 0.0001). These volumes were also significantly greater in group 1 than in both groups 2 and 3 and there was no difference between the groups 2 and 3. The tumor doubling times were 7.8 days for the group 1, 43.8 days for the group 2, 16.1 days for the group 3 and 5.9 days for the controls. The mechanism of the synergy between HIFU and docetaxel on the growth of Dunning tumors is apparently multifaceted. The results are encouraging because in the two groups of rats treated with the combination of HIFU and docetaxel, the percentage of complete remission was approximately 30%.

[A tumour-mimic pig liver model for guiding focused ultrasound thermal ablation]. / Modèle de pseudotumeur pour guider l'ablation thermique par ultrasons focalisés: étude sur le porc.

There is no established liver tumour model in pigs to study the efficacy of ablative treatment options available for the treatment of liver tumours by physical agents. A tumour-mimic model visible with high contrast on sonograms and on gross pathology has been studied at mid-term on 20 pigs. The aim was to determine if these tumour-mimics are well tolerated and can be used to validate the use of thermal therapies at a preclinical stage. The dimensions of the tumour-mimics measured on sonograms were reproducible (diameter: 9.6 +/- 1.9 mm) and correlated with those performed in gross pathology (R(2)=0.73). The accuracy of focused ultrasound thermal therapy can be evaluated preclinically using these tumour-mimics.