Investigation of the mechanism of ARFI-based Color Doppler feedback of histotripsy tissue fractionation

Histotripsy controls cavitating bubble clouds to fractionate tissue using high pressure ultrasound pulses. Over the histotripsy treatment, the tissue is increasingly fractionated and eventually liquefied. This process can be monitored in real time using color Doppler synchronized with histotripsy pulses, but the mechanism is not fully understood. We hypothesize that there are two motion phases after each histotripsy pulse: 1) chaotic motion due to cavitation followed by 2) coherent motion induced by acoustic radiation force impulse (ARFI) from the histotripsy pulse. By delaying the Doppler acquisition after the chaotic motion phase, color Doppler can be used to detect the ARFI-induced motion in the treatment tissue, providing real-time feedback for histotripsy tissue fractionation. The residual nuclei from cavitation can persist after the collapse to provide strong acoustic scatterers for Doppler. An agarose tissue phantom was treated with 2-cycle pulses at > 30 MPa using a 500 kHz phased array transducer. Ultrasound acquisitions and high-speed optical images were acquired for 19 ms after every 10th therapy pulse to estimate the motion of the residual cavitation nuclei (the only scatterers in the phantom). PIV and Doppler results showed a brief period of chaotic motion (0.5-2.0 ms depending on the fractionation level) followed by coherent motion first moving away from the transducer (3-6 ms) and then rebounding back (up to 19 ms). Over the course of the treatment in both phantom and ex vivo porcine liver, the duration of the push and rebound increased with increasing number of therapy pulses, and eventually peaked. Using an appropriate delay between the Doppler and the histotripsy pulse to monitor the ARFI motion, the Doppler velocity increased with the number of therapy pulses and peaked, likely when the tissue was liquefied. The results support our hypothesis that appropriately timed color Doppler can measure the coherent ARFI-induced motion in the tissue treated with histotripsy without cavitation inference, providing real-time therapy feedback.