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.

Active MR-temperature feedback control of dynamic interstitial ultrasound therapy in brain: in vivo experiments and modeling in native and coagulated tissues.

PURPOSE: The recent clinical emergence of minimally invasive image-guided therapy has demonstrated promise in the management of brain metastasis, although control over the spatial pattern of heating currently remains limited. Based on experience in other organs, the delivery of high-intensity contact ultrasound energy from minimally invasive applicators can enable accurate spatial control of energy deposition, large treatment volumes, and high treatment rate. In this acute study, the feasibility of active MR-Temperature feedback control of dynamic ultrasound heat deposition for interstitial thermal ablation in brain was evaluatedin vivo. METHODS: A four-element linear ultrasound transducer (f=8.2 MHz) originally developed for transurethral ultrasound therapy was used in a porcine model for generating thermal ablations in brain interstitially. First, the feasibility of treating and retreating preciselyin vivo brain tissues using stationary (non-rotating device) ultrasound exposures was studied in two pigs. Experimental results were compared to numerical simulations for maximum surface acoustic intensities ranging from 5 to 20 W cm(-2). Second, active MRT feedback-controlled ultrasound treatments were performed in three pigs with a rotating device to coagulate target volumes of various shapes. The acoustic power and rotation rate of the device were adjusted in real-time based on MR-thermometry feedback control to optimize heat deposition at the target boundary. Modeling of in vivo treatments were performed and compared to observed experimental results. RESULTS: Overall, the time-space evolution of the temperature profiles observedin vivo could be well estimated from numerical simulations for both stationary and dynamic interstitial ultrasound exposures. Dynamic exposures performed under closed-loop temperature control enabled accurate elevation of the brain tissues within the targeted region above the 55 °C threshold necessary for the creation of irreversible thermal damage. Treatment volumes ranging from 1 to 9 cm3 were completed within 8±3 min with a radial targeting error<2 mm on average (treatment rate: 0.7±0.5 cm3/min). Tissue changes were visible on T1-weighted contrast-enhanced (T1w-CE) images immediately after treatment. These changes were also evident on T2-weighted (T2w) images acquired 2 h after the 1st treatment and correlated well with the MR-thermometry measurements. CONCLUSIONS: These results support the feasibility of active MRT feedback control of dynamic interstitial ultrasound therapy ofin vivo brain tissues and confirm the feasibility of using simulations to predict spatial heating patterns in the brain.

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.

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.

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.

A tumor-mimic model for evaluating the accuracy of HIFU preclinical studies: an in vivo study.

To date, the efficacy of ablative technologies such as HIFU for the treatment of liver tumors in humans has been studied in animal models without tumors or in small animals like rats and rabbits with established tumors. Because of the small size of these animals, the lesion produced by HIFU devices has to be small. Thus, the local and systemic effects of the treatment as encountered in humans cannot be studied. The purpose of this study was to use an in vivo tumor-mimic model to evaluate the accuracy of HIFU ablation in the liver in preclinical studies. Tumor mimics were created in in vivo porcine livers by injecting a 1-cc warm mixture of agarose, cellulose, glycerol and methylene blue, which formed 1-cm hyperechoic discrete lesions on sonograms. Three studies were carried out: (i) in vitro experiments were conducted to study the acoustical proprieties of the tumor mimics; (ii) in vivo experiments were conducted in 10 pigs to evaluate the tolerance of the tumor mimics when injected in the liver; (iii) ultrasound-guided HIFU ablation was performed in 10 pigs to demonstrate that it is possible to treat a predetermined zone accurately. It was shown that the acoustical properties of tumor mimics are visible in sonograms and do not modify the shape and dimensions of HIFU lesions. The local and biological tolerance of tumor mimics was excellent. In addition, it was demonstrated that the average difference between the predetermined location of the HIFU ablation and the actual coagulated area was 32%. Therefore, this tumor mimic can be used to teach HIFU ablation before starting clinical studies, especially if the ultrasound device is to be used manually, as the one presented in this study was.