In vitro assessment of the relationship between medium stiffness and bubble activity for histotripsy-induced liquefaction

Abstract

Histotripsy is a focused ultrasound therapy that ablates tissue via the mechanical activity of bubble clouds. While effective for healthy tissues, histotripsy-induced bubble expansion will be mitigated in stiff chronic pathologies. In this study, the bubble cloud activity necessary for liquefaction of agarose phantoms with elastic moduli ranging from 12.3 ± 3.67 to 142 ± 44.9 kPa was investigated. Bubble clouds were initiated with 1-MHz pulses of 5-μs duration and peak negative pressures of 12 to 24 MPa. Bubble cloud emissions were mapped via passive cavitation imaging, and correlated with liquefaction using receiver operating characteristic analysis. The maximum power of emissions, and azimuthal location of the maximum power, were recorded for each experimental condition. For phantoms with elastic moduli between 12.3 and 85.8 kPa, no change was indicated in the bubble activity necessary for liquefaction. A larger acoustic power was associated with liquefaction of phantoms with elastic moduli of 142 kPa compared to 22.1 kPa. For a given peak negative pressure of the histotripsy pulse, no change in the peak power or azimuthal location of peak emissions was observed. These results indicate that a fixed bubble activity dose predicts histotripsy liquefaction over a wide range of medium stiffness.