Jeremy Vincenot

Development of a toroidal high-intensity focused ultrasound transducer for the treatment of pancreatic tumors. In vivo study of the safety and efficacy in a porcine model

Pancreatic ductal adenocarcinoma (PDA) is the most frequent primary malignancy of the pancréas. PDA has increased in incidence during the last decade and now constitutes the fourth leading cause of cancer mortality. New focal destruction technologies such as high-intensity focused ultrasound (HIFU) may improve the prognosis of pancreatic ductal adenocarcinoma. Given the inconvenience and disadvantages of extracorporeal HIFU, we developed an intraoperative HIFU probe, initially designed for the treatment of colorectal liver metastasis, with encouraging results. The principal interest lies in the possibility of treating hepatic parenchyma in a short period. The intraoperative HIFU probe designed for the treatment of liver tumors could be used for pancreatic tumors. The aim of this preclinical study was to determine the safety and efficacy of intraoperative HIFU in vivo on pancreatic tissue in a porcine model.

Intra-operative high intensity focused ultrasound in patients with colorectal liver metastases: results of a phase I-II study in 21 patients

Managing colorectal liver metastases (CLM) is a major clinical challenge, and surgery remains the only potentially curative treatment. Five-year survival rates of up to 51% have been recently reported. However, only 10-20% of patients are eligible for surgery, which is often precluded by the number, size and/or location of metastases, or because the necessary resection will leave insufficient volume of functional liver. A toroidal transducer for HIFU ablation has been developed and tested in vivo enabling destruction of large liver volumes. Preliminary in vitro and preclinical work demonstrated the potential, feasibility and safety of such HIFU ablations. These preclinical studies are now translated into clinical practice through controlled trials, and the aim of this study was to assess the feasibility and safety of HIFU ablation in patients undergoing hepatectomy for CLM, as well to collect preliminary efficacy and accuracy data.

Two large focal zones can be created using a toroidal transducer for increasing the coagulated volume

Toroidal HIFU transducers have been shown to generate large conical ablations (7 cm3 in 40 seconds). The focal zone is composed of a first ring-shaped focal zone and an overlap of ultrasound beams behind this first focus. A HIFU device has been developed on this principle to treat liver metastases during an open procedure. Although these large lesions contribute to reduce treatment time, it is still needed to juxtapose 4 to 9 single HIFU lesions to treat liver metastasis (2 cm in diameter) with safety margins. In this work, a different toroidal geometry was used. With this transducer, the overlap area is located between the probe and the focal ring. The objective was to use this transducer with electronic focusing in order to create a spherical shape lesion with sufficient volume for the destruction of a metastasis of 2 cm in diameter without any mechanical displacement. The operating frequency of the toroidal transducer was 2.5 MHz. The radius of curvature was 70 mm with a diameter of 67 mm. The focal ring had a radius of 15 mm. The overlap zone extents between 35 to 55 mm from the emitting surface. An ultrasound-imaging probe (working at 7.5 MHz) was placed in a central circular opening of 26 mm in the HIFU transducer and was aligned with the focal plane. The transducer was divided into 32 rings of 78 mm2. Using a 32 channels amplifier with a phase resolution of 1.4 degrees, it was possible to change the diameter (0 to 15 mm) and depth (45 to 85 mm) of the focus circle to maximize dimensions of the lesion. Tests were conducted in vitro, in bovine liver samples. This toroidal geometry and the use of electronic beam steering allow the creation of roughly spherical lesions (diameter of 47 mm, depth of 35 mm). This treatment was obtained in 6 minutes and 10 seconds without any mechanical displacement of the transducer. The lesions obtained were homogeneous and no untreated area was observed. In conclusion, these results indicate that the treatment of a liver metastasis up to 2 cm in diameter is conceivable with safety margins. An in vivo validation on porcine model is under progress.

Todoidal transducer with two large focal zones for increasing the coagulated volume

Spherical transducers used for HIFU therapy produce small single lesions that are ellipsoidal in shape. These lesions must be placed side by side systematically to treat the tumor with safety margins. This can be difficult to produce in moving organs like the liver. It has been shown that a toroidal transducer makes it possible to significantly increase the focal zone. A toroidal HIFU transducer geometry generates simultaneously a first ring-shaped focal zone and an overlap of ultrasound beams beyond this first focal plane. This particular focalization allows the creation of 7 cm3 ablated volume in 40 seconds. Although these large single lesions contributes to reduce treatment time, it is still needed to juxtapose 4 to 9 single lesions to treat one liver metastases of 2 cm in diameter with safety margins. In order to improve this treatment, a new toroidal geometry of transducer was developed. The difference is that the overlap of ultrasound beams is now between the transducer and the focal ring. The objective of this work is to combine this new geometry of transducer and the use of electronic focusing in order to create without any mechanical displacement of the device a coagulated volume sufficient for the destruction of a metastasis of 2 to 3 cm in diameter. In vitro tests were conducted to validate the treatment parameters determined using a software developed in the laboratory. The diameter and the depth of the lesion obtained were 40 and 38 mm respectively. In conclusion, these results indicate that the treatment of a metastasis up to 3 cm in diameter in the liver with safety margins is conceivable using this device and no need to juxtapose single lesions.