Dynamic Ultrasound Focusing and Centimeter-Scale Ex Vivo Tissue Ablations With a CMUT Probe Developed for Endocavitary HIFU Therapies

Thermal ablation of localized prostate tumors via endocavitary ultrasound-guided high-intensity focused ultrasound (USgHIFU) faces challenges that could be alleviated by better integration of dual modalities (imaging/therapy). Capacitive micromachined ultrasound transducers (CMUTs) may provide an alternative to existing piezoelectric technologies by exhibiting advanced integration capability through miniaturization, broad frequency bandwidth, and potential for high electroacoustic efficiency. An endocavitary dual-mode USgHIFU probe was built to investigate the potential of using CMUT technologies for transrectal prostate cancer ablative therapy. The USgHIFU probe included a planar 64-element annular high-intensity focused ultrasound (HIFU) CMUT array ( ${f} _{\text {HIFU}}$ = 3 MHz) surrounding a 256-element linear imaging CMUT array. Acoustic characterization of the HIFU array included 3-D pressure field mapping and radiation force balance measurements. Ex vivo proof-of-concept experiments consisted in generating HIFU thermal ablations with the CMUT probe on porcine liver tissues. The planar CMUT probe enabled HIFU dynamic focusing (distance range: 32–72 mm) while providing acoustic surface intensities of 1 W/cm2 that allowed producing elementary ex vivo ablations in depth of liver tissue ( ${L} \times {W}\,\,\approx \,\,10\times5$ mm). Combinations of dynamic focusing, along with probe rotation and translation produced larger thermal ablations ( ${L} \times {W}\,\,\approx \,\,20\times20$ mm) by juxtaposing multiple elementary ablations, consistent with expected results obtained through numerical modeling. The technical feasibility of using a USgHIFU probe, fully developed using CMUTs for tissue ablation purposes, was demonstrated. The HIFU-CMUT array showed tissue ablation capabilities with volumes compatible with localized cancer targeting, thus providing assets for further development of focal therapies.

I. Introduction

High-intensity focused ultrasound (HIFU) has become an attractive clinical strategy for thermal ablation of cancerous tumors in several organs [1], [2], [3], [4], [5], [6], [7]. This strategy relies on the principle of applying a focused, high-intensity ultrasound (US) wave on a target tissue over several seconds, thus increasing its local temperature to levels capable of inducing coagulation and necrosis of the tissue. This approach can be noninvasive since the focused ultrasound procedure can be designed to eliminate or minimize heat deposition and damage in intermediary tissues located in the path between the ultrasound device and the target. As such, most HIFU devices used in clinic are designed to be applied via endocavitary or extracorporeal approaches. These advantages combine to reduce the morbidity of the treatment while facilitating the recovery of patients who only endure a sedative procedure. One of the first and most widely employed clinical applications of HIFU thermal ablation therapy is for the treatment of localized prostate cancer. Indeed, tens of thousands of prostate cancer patients have been treated worldwide using a standard global treatment strategy: the ablation of the full prostate gland by HIFU, under real-time ultrasound guidance (USgHIFU) [8], [9]. For the treatment of localized cancers, however, a more desirable approach involves focal strategies capable of selectively ablating a portion of the prostate targeted on the tumors, which can provide a safe alternative to the treatment of the entire organ. Under certain conditions, more focal strategies are currently being explored such as hemiablations, which consist of treating about half of the prostate volume containing all tumors with security margins. Such strategies require locating properly all tumor sites for appropriate treatment planning. Hemiablations are thus currently performed by first acquiring MR images of the prostate prior to HIFU ablation and subsequent registration of these images with real-time ultrasound imaging guidance during treatment. As a result, accurate and precise ablation of tumor regions becomes indispensable requirements for the optimization and success of the treatment. Such requirements are highly dependent on high-resolution imaging along with spatial refinement of the treated area.