Histotripsy Bubble Dynamics in Elastic, Anisotropic Tissue-Mimicking Phantoms

Elastic, anisotropic tissue such as tendon has proven resistant to mechanical fractionation by histotripsy, a subset of focused ultrasound that uses the creation, oscillation and collapse of cavitation bubbles to fractionate tissue. Our objective was to fabricate an optically transparent hydrogel that mimics tendon for evaluation of histotripsy bubble dynamics. Ex vivo bovine deep digital flexor tendons were obtained (n = 4), and varying formulations of polyacrylamide (PA), collagen and fibrin hydrogels (n = 3 each) were fabricated. Axial sound speeds were measured at 1 MHz for calculation of anisotropy. All samples were treated with a 1.5-MHz focused ultrasound transducer with 10-ms pulses repeated at 1 Hz (p = 127 MPa, p = 35 MPa); treatments were monitored with passive cavitation imaging and high-speed photography. Dehydrated fibrin gels were found to be the most similar to tendon in cavitation emission energy (fibrin = 0.69 ± 0.24, tendon = 0.64 ± 0.19 [× 10 V]) and anisotropy (fibrin = 3.16 ± 1.12, tendon = 19.4). Bubble cloud area in dehydrated fibrin (0.79 ± 0.14 mm) was significantly smaller than most other tested hydrogels. Finally, anisotropy was found to have moderately strong linear relationships with cavitation energy and bubble cloud size (r = -0.65 and -0.80, respectively). Dehydrated fibrin shows potential as a repeatable, transparent, tissue-mimicking hydrogel for evaluation of histotripsy bubble dynamics in elastic, anisotropic tissues.