Experimental observations of the growth and collapse of acoustically and laser-nucleated single bubbles in water and agarose gels of varying stiffness are presented. The maximum radii of generated bubbles decreased as the stiffness of the media increased for both nucleation modalities, but the maximum radii of laser-nucleated bubbles decreased more rapidly than acoustically nucleated bubbles as the gel stiffness increased. For water and low stiffness gels, the collapse times were well predicted by a Rayleigh cavity, but bubbles collapsed faster than predicted in the higher stiffness gels. The growth and collapse phases occurred symmetrically (in time) about the maximum radius in water but not in gels, where the duration of the growth phase decreased more than the collapse phase as gel stiffness increased. Numerical simulations of the bubble dynamics in viscoelastic media showed varying degrees of success in accurately predicting the observations.

Histotripsy is an ultrasound ablation method that depends on the initiation of a dense cavitation bubble cloud to fractionate soft tissue. Previous work has demonstrated that a cavitation cloud can be formed by a single acoustic pulse with one high amplitude negative cycle, when the negative pressure amplitude exceeds a threshold intrinsic to the medium. The intrinsic thresholds in soft tissues and tissue phantoms that are water-based are similar to the intrinsic threshold of water over an experimentally verified frequency range of 0.3–3 MHz. Previous work studying the histotripsy intrinsic threshold has been limited to experiments performed at room temperature (~ 20°C). In this study, we investigate the effects of temperature on the histotripsy intrinsic threshold in water, which is essential to accurately predict the intrinsic thresholds expected over the full range of in vivo therapeutic temperatures. Based on previous work studying the histotripsy intrinsic threshold and classical nucleation theory, we hypothesize that the intrinsic threshold will decrease with increasing temperature. To test this hypothesis, the intrinsic threshold in water was investigated both experimentally and theoretically. The probability of generating cavitation bubbles was measured by applying a single pulse with one high amplitude negative cycle at 1 MHz to distilled, degassed water at temperatures ranging from 10°C–90°C. Cavitation was detected and characterized by passive cavitation detection and high-speed photography, from which the probability of cavitation was measured vs. pressure amplitude. The results indicate that the intrinsic threshold (the negative pressure at which the cavitation probability = 0.5) significantly decreases with increasing temperature, showing a nearly linear decreasing trend from 29.8±0.4 MPa at 10°C to 14.9±1.4 MPa at 90°C. Overall, the results of this study support our hypothesis that the intrinsic threshold is highly dependent upon the temperature of the medium, which may allow for better predictions of cavitation generation at body temperature in vivo and at the elevated temperatures commonly seen in high intensity focused ultrasound (HIFU) regimes.

A variety of approaches have been used to model the dynamics of a single, isolated bubble nucleated by a microsecond length high–amplitude ultrasound pulse (e.g. a histotripsy pulse). Until recently, the lack of single–bubble experimental radius vs. time data for bubble dynamics under a well–characterized driving pressure has limited model validation efforts. This study uses radius vs. time measurements of single, spherical histotripsy–nucleated bubbles in water to quantitatively compare and validate a variety of bubble dynamics modeling approaches, including compressible and incompressible models as well as different thermal models. A strategy for inferring an analytic representation of histotripsy waveforms directly from experimental radius vs. time and cavitation threshold data is presented. We compare distributions of a calculated validation metric obtained for each model applied to 88 experimental data sets. There is minimal distinction (<1%) among the modeling approaches for compressibility and thermal effects considered in this study. These results suggest that our proposed strategy to infer the waveform, combined with simple models minimizing parametric uncertainty and computational resource demands accurately represent single–bubble dynamics in histotripsy, including at and near the maximum bubble radius. Remaining sources of parametric and model–based uncertainty are discussed.

Characterization of soft materials is challenging due to their high compliance and the strain-rate dependence of their mechanical properties. The inertial microcavitation-based high strain-rate rheometry (IMR) method [Estrada et al.,...