Enhancing boiling histotripsy efficacy with a tandem pulse sequence: Immediate hypoechoic Sonograhy and expanded lesion size

Boiling histotripsy (BH) has proven effective in noninvasively disintegrating various soft tissues through cavitation effects. Although liquefied tissue appears as hypoechoic in sonography, the transition of BH-induced bubbles from hyperechoic to hypoechoic in the focal region typically requires several minutes. To facilitate rapid clinical assessment, a tandem pulse sequence of high-power BH pulses (with an acoustic power of 1484 W, a pulse duration of 10 ms, and a pulse repetition frequency of 1 Hz) followed by low-power long ultrasound pulses (with an acoustic power of 240 W, a pulse duration of 100 ms, and a pulse repetition frequency of 1 Hz) was introduced to expedite bubble clearance, resulting in an immediate hypoechoic presentation in sonography. This method was evaluated through high-speed photography, red blood cell (RBC) phantom, and ex vivo tissue experiments. High-speed photography experiments captured the enhanced bubble clearance induced by the low-power long pulses, validating our hypothesis. In RBC phantom experiments, conventional BH sequences yielded hypoechic patterns after 4.39 ± 0.84 min, whereas the tandem pulse sequences achieved hypoechic appearance instantaneously post-treatment (p < 0.05). Moreover, the tandem pulse sequences increased the erosion area in the RBC layer by 7.8 folds, from 2.36 ± 0.88 mm² to 18.43 ± 5.15 mm² (p < 0.05), at the equivalent energy output. Ex vivo bovine liver experiments mirrored these findings, with hypoechoic appearance at > 10 min vs. 0 min (p < 0.05) and liquefied areas of 33.78 ± 3.28 mm² vs. 66.52 ± 11.24 mm² (p < 0.05), respectively. In summary, our results suggest that the strategic modulation of cavitation activities not only accelerates the immediate hypoechoic appearance in sonography but also enlarges the area of BH-induced disintegration. The tandem pulse sequence strategy presents a promising avenue for enhancing the efficacy and efficiency of BH treatment in clinical applications.