Real-time imaging-guided microbubble mediated high intensity focused ultrasound heating in an ex-vivo machine-perfused pig liver

Abstract

High intensity focused ultrasound (HIFU) is used clinically for the ablation of prostate and liver tumors. More recently, HIFU has been used in the brain for locally controlled thermal treatment of nonessential tremors. However, the thermal lesion location is restricted to a small area in the tissue due to geometric and boundary limitations (avoiding skin and bone burns). Bubble-enhanced heating (BEH) allows for the use of lower power and can generate spatially controlled thermal lesions in regions not currently accessible with conventional HIFU. We have studied BEH in vitro and in a machine perfused pig liver (MPL). The MPL presents a versatile platform for perfusion and BEH studies because it is clinically relevant and allows for delivery of microbubbles under ultrasound imaging. We first applied conventional HIFU and BEH in vitro, in an enclosure with acoustic windows contaiing glycerin and microbubbles while monitoring the temperature with a fine wire thermocouple. A focused 1 MHz transducer and various clinically approved microbubbles were used. Then we applied BEH on the MPL by introducing microbubbles under image guidance. With this initial study, we have observed that BEH has resulted in 5-10x energy reduction for the formation of a reference lesion in vitro, and 3-6x in the MPL.