Evaluation of the Feasibility, Safety, and Accuracy of an Intraoperative High-intensity Focused Ultrasound Device for Treating Liver Metastases

This medical device, which uses focused ultrasound, can provide a new therapeutic option for patients with unresectable liver metastases. The main advantage of this technique is that it can achieve fast, safe, wide tolerated large liver ablations with a puncture and the available ultrasound imaging guidance. Demonstrating the preparation of the HIFU device will be Marie Jo, a specialized nurse from the operating room.

After disinfecting the incision site use a monopolar knife to perform a laparotomy on the anesthetized patient. And use scissors to free the liver from its peritoneal and vascular attachments. To prepare the device cover the sterilized HIFU probe with a dedicated sterile envelope containing a sterile ultrasound coupling liquid.

Place a protective 20 by 20 centimeter abdominal gauze sponge with X-ray detectable threads under the targeted area to inhibit any ultrasound propagation and unintended HIFU damage to adjacent organs. Bring the HIFU probe in contact with the liver surface. Move the HIFU probe across the surface of the liver until the position of the expected HIFU ablation as represented by the white cone superimposed on the sonogram is at the right location.

Take care with the placement of the expected HIFU ablation since the temperature rise will be the same in normal tissues and internal tissues and will increase above 80 degrees Celsius leading to immediate cell death in both tissues. To activate the HIFU exposure activate each emitter with the same phase for 40 seconds. As the ultrasound resection images are not synchronized with the HIFU exposures the interferences are visible in the sonogram during ablation.

Boiling is observed in liver tissues treated during HIFU single exposures with a cloud of abolition typical appearing for about one minute at the location of the lesion. The single lesion will appear on the sonogram as a hyperechoic zone at its center and a hypoechoic zone at its boundaries. Next reset the liver by using a kelly clamp to crush the liver parenchyma.

And use scissors to extract the marked tissue. Then close the incision according to standard protocols. Use a surgical marker to indicate the position of the acoustic axis of the HIFU probe at the surface of the liver and use the integrated ultrasound imaging probe to measure the dimensions of the HIFU ablations along two orthogonal planes after each HIFU exposure.

After the surgery use a scalpel to separate the HIFU ablations and areas of colorectal liver metastases. Excising the ablations along the exposure axis. Then obtain images of the ablations for macroscopic and histological analysis.

In a phase one trial a total of 12 HIFU ablations were successfully created in the six phase one patients. Deep HIFU lesions were placed at a mean depth of approximately 10 millimeters and up to 20 millimeters. As required by the study design three more patients were included and all six additional HIFU lesions were correctly created at a fixed distance from all six metallic markers.

Here examples of two metastases imaged using the ultrasound imaging probe integrated with the HIFU device and the same two metastases after resection are shown. The HIFU focal region was superimposed on the sonogram and displayed in the user interface, making it possible to precisely identify the location of the metastases. The delimitation between the treated and untreated liver is very sharp with an about 200 micrometer halo of congestive tissues around all of the HIFU ablations.

This new HIFU device safely achieves large volume of liver ablations in 40 seconds with a one two millimeter precision that can be easily identified in ultrasonic imaging and by measurable traces. These initial clinical results justified the next steps in clinical development in which we will attempt HIFU ablation on small metastases less than 30 millimeters in diameter with safety margin of five millimeters in healthy perilesional liver. If the ability to target liver metastases is confirmed during phase 2B the next step would be to design a multi-center group of patients treated with curative intent using this new HIFU an device.