Gas-bubble enhanced heating in rabbit thigh in vivo

In this study, we propose a focused ultrasound surgery protocol that induces and then uses gas bubbles at the focus to enhance the ultrasound absorption and ultimately create larger lesions in vivo. MRI and ultrasound visualization and monitoring methods for this heating method are also investigated. Larger lesions created with a carefully monitored single ultrasound exposure could greatly improve the speed of tumor coagulation with focused ultrasound. All experiments were performed under MRI (clinical, 1.5T) guidance with one of two eight-sector spherically curved piezoelectric transducers (1.1 and 1.7 MHz). An ultrasound detector ring was fixed with the therapy transducer to monitor gas bubble activity during treatment. FUS exposures were delivered to the thighs of seven New Zealand white rabbits. The experimental, gas bubble-enhanced heating exposures consisted of a high amplitude 300 acoustic watt, half second pulse followed by a 7 W, 14 W, or 21 W continuous wave exposure for 19.5 seconds. The respective control sonications were 20-second exposures of 14 W, 21 W, and 28 W. During the exposures, MR thermometry was obtained, and MR T2-enhanced imaging was used to evaluate the resulting lesions. Specific metrics were used to evaluate the differences between the gas-bubble enhanced exposures and their respective control sonications: temperatures with respect to time and space, lesion size and shape, and their agreement with thermal dose predictions. The bubble-enhanced exposures showed a faster temperature rise and higher overall temperatures than the sonications without bubble formation. The MRI derived spatial temperature and thermal dose maps closely correlated with the resulting lesion as examined by T2-wieghted imaging. The lesions created with the gas-bubble enhanced heating exposures were 3 times larger by volume, were consistently more spherical in shape, and closer to the transducer than the control exposures. The study demonstrates that gas bubbles can reliably be used to create significantly larger lesions in vivo.