Numerical Investigations of Cavitation-Induced Tissue Damage

Abstract

Cavitation occurs when a sufficient pressure rarefaction causes explosive growth of material defects or nuclei into larger cavities (bubbles) which can damage their surroundings. Specifically, high stresses, strains and strain rates are induced locally during bubble growth and are further concentrated during bubble collapse. Although cavitation in water has received significant attention, cavitation dynamics in tissue remain poorly understood. Cavitation-induced tissue damage can occur in high strain rate injuries and can be controlled for therapeutic purposes in focused ultrasound procedures. An improved understanding of cavitation damage mechanisms could inform the development of new damage metrics for injury diagnostics and focused ultrasound treatment planning. However, experimental studies of cavitation in tissue face limitations in spatial and temporal resolution. Numerical bubble dynamics models offer insight into highly localized and transient cavitation damage mechanisms but have historically neglected non--Newtonian effects such as viscoelasticity that are essential to understanding the physics of cavitation in tissue.

This work investigates cavitation-induced tissue damage using numerical simulations of bubble dynamics validated with experimental data obtained by collaborating research groups. We first introduce a single--bubble model for cavitation in water exposed to a time-varying tensile pressure waveform with an amplitude equal to the experimental threshold for acoustic cavitation. Simulation results are then validated using experimental measurements of bubble radius as a function of time for bubbles generated at threshold. A method is presented that combines single-bubble experimental data and simulations to infer the distribution of nuclei sizes at the acoustic cavitation threshold in water. The size distribution obtained is lognormal with a mean nucleus radius of 2.88 nm. This approach is subsequently extended to validate a bubble dynamics model for viscoelastic media using experiments performed in agarose gel. We obtain distributions for agarose properties including pore size, shear modulus, and viscosity using experiments performed at various gel concentrations. The general applicability of these results to high strain rate material characterization is addressed.

The validated model is used to investigate tissue damage in focused ultrasound procedures by quantifying stress, strain, and strain rate fields developed around an ultrasound--nucleated cavitation bubble. A dimensionless parameter combining tissue and waveform characteristics is derived that dictates the dominant damage mechanism (strain vs. strain rate) as a function of distance from the bubble nucleus. These results motivate the proposal of a strain--based damage metric which can explain experimental observations of tissue--selective ablation in intrinsic threshold histotripsy treatments. The metric predicts single--bubble damage zones with radii of $30$ to $500$ microns determined by tissue mechanical properties and histotripsy sonication parameters. Simulation results are consistent with observed histology of histotripsy-treated ex vivo tissue samples. The implications of these results for selective focused ultrasound ablation of solid tumors are discussed.