Assessing histotripsy-induced tissue damage by monitoring the evolution of cavitation lifespans

Exposure to cavitation during histotripsy incrementally mechanically fractionatates targeted tissues and, given sufficient exposure, ultimately reduces them to liquefied acellular homogenates. Fractionation by histotripsy alters the material properties of the targeted tissues, which correspondingly results in changes in the dynamics of generated bubbles. This can be detected acoustically by monitoring the shockwaves emitted during cavitation nucleation and collapse to assess the cavitation lifespan. By developing appropriate models of how damage generation during histotripsy corresponds to tissue property changes, measurements of the cavitation lifespan can be used to track and evaluate induced tissue damage. Previous studies have shown that the cavitation lifespan increases as tissues are increasingly exposed to cavitation before eventually plateauing once the tissue has been completely liquefied. While this has enabled reliable detection of treatment completion, effective models linking the observed evolution of cavitation lifespan to changes in the material properties/tissue damage have not been established. Here, we describe a simplified viscoelastic model of tissue whose elasticity and viscosity change in proportion to the cumulative areal exposure of tissues to cavitation. This model accurately captures a range of behaviors in the cavitation lifespan observed experimentally, including the non-linear ramp up of the lifespan at low exposures, and non-asymptotic/monotonic behaviors of the lifespan at higher exposures.