Real-time acoustic-based feedback for histotripsy therapy

Histotripsy uses high-pressure microsecond ultrasound pulses to generate cavitation to fractionate cells in target tissues. Two acoustic-based feedback mechanisms are being investigated to monitor histotripsy therapy in real-time. First, bubble-induced color Doppler (BICD) is received by an ultrasound probe co-aligned with the histotripsy transducer to monitor the cavitation-induced motion of residual cavitation nuclei in tissue throughout treatment. Second, acoustic backscatter of the histotripsy pulse from the cavitation bubbles is received by directly probing elements of histotripsy transducer to monitor acoustic emissions from the cavitation bubbles during treatment. In these experiments, histotripsy was applied to agarose phantoms and ex vivo tissue by a 112-element, 500 kHz semi-hemispherical ultrasound array with a 15 cm focal distance. The BICD signals were collected on a Verasonics system by an L7-4 probe. The BICD and backscatter signals were compared to high-speed optical images of cavitation in phantoms and histology of tissue. A consistent trend was observed in both the BICD and backscatter waveforms throughout treatment in both tissue and agarose phantoms that correlated with high-speed imaging and histological analysis. These results suggest that BICD and acoustic backscatter can provide non-invasive, real-time, quantitative feedback of tissue treatment progression during histotripsy, thus improving treatment efficiency and accuracy.