Harmonic motion imaging for focused ultrasound (HMIFU): a fully integrated technique for sonication and monitoring of thermal ablation in tissues

Abstract

FUS (focused ultrasound), or HIFU (high-intensity-focused ultrasound) therapy, a minimally or non-invasive procedure that uses ultrasound to generate thermal necrosis, has been proven successful in several clinical applications. This paper discusses a method for monitoring thermal treatment at different sonication durations (10 s, 20 s and 30 s) using the amplitude-modulated (AM) harmonic motion imaging for focused ultrasound (HMIFU) technique in bovine liver samples in vitro. The feasibility of HMI for characterizing mechanical tissue properties has previously been demonstrated. Here, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) transducer, was used. The therapy transducer was driven by a low-frequency AM continuous signal at 25 Hz, producing a stable harmonic radiation force oscillating at the modulation frequency. A pulser/receiver was used to drive the pulse-echo transducer at a pulse repetition frequency (PRF) of 5.4 kHz. Radio-frequency (RF) signals were acquired using a standard pulse-echo technique. The temperature near the ablation region was simultaneously monitored. Both RF signals and temperature measurements were obtained before, during and after sonication. The resulting axial tissue displacement was estimated using one-dimensional cross correlation. When temperature at the focal zone was above 48 °C during heating, the coagulation necrosis occurred and tissue damage was irreversible. The HMI displacement profiles in relation to the temperature and sonication durations were analyzed. At the beginning of heating, the temperature at the focus increased sharply, while the tissue stiffness decreased resulting in higher HMI displacements. This was confirmed by an increase of 0.8 µm °C−1(r = 0.93, p < .005). After sustained heating, the tissue became irreversibly stiffer, followed by an associated decrease in the HMI displacement (−0.79 µm °C−1, r = −0.92, p < 0.001). Repeated experiments showed a reproducible pattern of the HMI displacement changes with a temperature at a slope equal to 0.8 ± 0.11 and − 0.79 ± 0.14 µm °C−1, prior to and after lesion formation in seven bovine liver samples, respectively. This technique was thus capable of following the protein-denatured lesion formation based on the variation of the HMI displacements. This method could, therefore, be applied for real-time monitoring of temperature-related stiffness changes of tissues during FUS, HIFU or other thermal therapies.