Doppler-based assessment of boiling histotripsy-induced volumetric tissue liquefaction in vivo

Boiling histotripsy (BH) is a promising method for mechanical tissue fractionation and liquefaction, utilizing millisecond-long high-intensity focused ultrasound (HIFU) pulses with shock fronts. Recent study has reported that cavitation bubbles induced during the BH pulse can move within the liquefied treated volume for a few milliseconds to seconds after each BH pulse ends. These bubble motions can be observed by ultrasound Doppler measurements, with maximum Doppler velocity showing significant potential as a metric to determine the treatment completion, as previously demonstrated in ex vivo setting. Here, this velocity metric was tested based on the results of in vivo pig experiments, along with tissue liquefaction levels evaluated from histology. A 256-element 1.5 MHz spiral HIFU array with a center opening for the imaging probe installation was used for BH pulse control. A sequence of 10 ms BH pulses with a 1 Hz pulse repetition frequency (PRF) was delivered to the predesigned two-dimensional target grid to generate large liquefied volumes. A small aperture (around 2 cm) imaging probe was mounted at the center opening of HIFU transducer and used for planewave Doppler and B-mode imaging. To increase the maximum measurable Doppler velocity, a high PRF regime was applied instead of the conventional pulse-echo regime. The results showed that the maximum velocity increased over the treatment from 40 to 100 cm/s as the tissue progressively changed from intact to completely liquefied. The distribution of elevational averaged maximum velocity along the lateral target volumes aligned well with the lesion shown in the corresponding histological image and statistically significantly correlated with the liquefaction grade. A maximum velocity above 84 cm/s ensured the complete liquefaction level, reinforcing its potential as a metric to determine successful treatment.