Histotripsy of healthy and tendinopathic ex vivo bovine tendons

Abstract

Histotripsy has successfully fractionated most soft tissues; however, highly collagenous tissues like tendon have been resistant to histotripsy fractionation. Previously, we showed that some histotripsy parameters could create mild mechanical microdamage in healthy ex vivo rat tendons. Our objective here is to evaluate whether complete histotripsy fractionation is possible in tendons. Eight bovine tendons were injected with collagenase to induce tendinopathy; an additional four tendons were unaltered. Tendons were exposed to single- or dual-frequency histotripsy at 1.07-, 1.5-, and/or 3.68-MHz with 10-ms pulses delivered at 1 Hz for 60 s. Treatments were monitored with passive cavitation detection (PCD) and samples were evaluated for damage. Results show that exposure of tendinopathic tendons to 1.5- and 3.68-MHz dual-frequency histotripsy produces a distinct, fractionated hole; 1.5- and 3.68-MHz single-frequency histotripsy produces partial fractionation without a distinct hole. No fractionation was observed in healthy tendons, or in tendinopathic tendons exposed to 1.07 MHz single- or dual-frequency histotripsy. Histologically, all tendons showed evidence of thermal necrosis independent of whether a hole was observed. PCD showsincreases in amplitude and sustainment of cavitation in exposures that successfully fractionated tendon. These results suggest histotripsy fractionation is possible in tendinopathic tendons. [Work supported by NIH R21EB027886 and R01EB032860.]