Monitoring Fractionation in Elastic Tissues Using High Frame-Rate Doppler Ultrasound

Objective: Passive cavitation imaging (PCI) and bubble-induced color Doppler (BCD) have been used successfully to monitor liquefaction of soft tissues during histotripsy. However, it is unclear whether PCI and BCD can be similarly used in highly elastic tissues, which fractionate rather than liquefy. Our objective was to compare PCI with BCD for monitoring histotripsy fractionation of elastic tissues and tissue-mimicking phantoms. Methods: Telocollagen and elastic resin phantoms (n = 3 each) were fabricated for BCD validation; an additional 5 telocollagen gels were fabricated for direct comparison to ex vivo bovine superficial digital flexor tendons soaked in phosphate-buffered saline (healthy) or collagenase (tendinopathic; 3 each) for 1 week. All samples were treated with 1.5 MHz focused ultrasound (FUS) using 10 ms pulses repeated at 1 Hz (p₊ = 127 MPa, p_- = 35 MPa) and treatment progression was monitored with PCI or BCD using a Verasonics Vantage-128 ultrasound system and an ATL L7-4 transducer. Results: At 6.7 ms post-FUS pulse, BCD better correlated with liquefaction in telocollagen samples than PCI (r = 0.75 ± 0.22 and r = -0.40 ± 0.48, respectively). In tendon, histotripsy produced grossly observable fractionation in 4/12 phosphate-buffered saline- and 10/12 collagenase-soaked treatment locations. Monitoring with BCD indicated that fractionation produced higher regression coefficient magnitudes in BCD (|r| = 0.63 ± 0.19) than PCI (|r| = 0.26 ± 0.21); however, regression directions in BCD were inconsistent. Conclusion: Regression trends associated with Doppler metrics suggest the potential for BCD or perhaps a combination of PCI and BCD for monitoring FUS-induced fractionation in highly elastic tissues.