Tandem Pulse Sequence: Immediate Appearance of Hypoechoic Liquefaction Region and Increased Lesion Size after Boiling Histotripsy

Boiling histotripsy (BH) is a high-intensity focused ultrasound (HIFU) method to disintegrate various soft tissues through cavitation effects in extensive ex vivo and in vivo studies. While the liquefied tissue appears as hypoechoic in sonography, serving as a dependable and sensitive measure of treatment outcome, the BH-induced bubbles and their nuclei in the focal region typically require several minutes to completely dissolve, transiting from hyperechoic to hypoechoic. For clinical assessment, a quicker bubble dissolution is highly desirable. To address this, a novel tandem pulse sequence, high-power short BH pulse sequences being succeeded by low-power long ultrasound pulses, has been proposed to expedite bubble collapse for an immediate hypoechoic display in sonography. Its performance was assessed through red blood cell (RBC) phantom and ex vivo tissue experiments. However, to maintain the same output energy, the number of bursts delivered was adjusted correspondingly. In RBC phantom experiments, the traditional BH sequences resulted in a hypoechoic pattern in sonography after 4.63±1.26 minutes, with cross-section liquefied areas measuring 2.36±0.88 mm2(n=9). The new sequences achieved the hypoechoic appearance immediately after BH treatment (0 minutes, p<0.05) and with a liquefied area of 18.43±5.15 mm2 (p<0.05). The enhanced bubble collapse was captured using highspeed photography, corroborating our hypothesis. Ex vivo bovine liver experiments showed similar results, with hypoechoic appearance of >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, n=5). Altogether, our findings suggest that the judicious modulation of cavitation activities can not only expedite the immediate hypoechoic appearance in sonography but also increase the size of the BHinduced disintegration.