Effect of elastic modulus and fiber spacing on boiling histotripsy bubble dynamics in collagenous tissues

Collagenous tissues, such as tendon, are resistant to fractionation by boiling histotripsy (BH), possibly from their high elasticity and close fiber spacing. To account for parallel collagen fibers, a numerical bubble model was adapted from blood vessel applications (Hay, 2012) to predict bubble expansion/collapse during BH exposure and compared to experimental results. Ex vivo cervine Achilles tendons (n = 12) were harvested, and assigned to tendinopathic (soaked in 1% w/v collagenase for 7 days) or healthy (soaked in PBS for 7 days) groups. Tendons were exposed to either load-to-failure mechanical testing or 1.5-MHz BH (p + = 127 MPa/p− = 35 MPa; 10-ms pulses at 1-Hz). During BH, bubble activity was monitored using passive cavitation imaging (Philips/ATL L7-4; Vantage® ultrasound system). Model inputs were determined from load-to-failure tests and fiber spacings from microscopy of fibrin gels. Results showed tendinopathic tendons had significantly higher cavitation amplitudes than healthy tendons (0.22±0.04 and 0.08±0.03 V2, respectively; p = 0.009). Additionally, the numerical model indicated that an order-of-magnitude reduction in elastic modulus increased bubble expansion by only 0.1%. However, an order-of-magnitude increase in fiber spacing resulted in a 57% increase in bubble expansion. These results suggest that fiber spacing may influence BH bubble dynamics more than elastic modulus. [Work supported by NIHR01EB032860.]