Quantifying the Effect of Acoustic Parameters on Temporal and Spatial Cavitation Activity: Gauging Cavitation Dose

Objective: Cavitation-enhanced delivery of therapeutic agents is under development for the treatment of cancer and neurodegenerative and cardiovascular diseases, including sonothrombolysis for deep vein thrombosis. The objective of this study was to quantify the spatial and temporal distribution of cavitation activity nucleated by Definity infused through the EKOS catheter over a range of acoustic parameters controlled by the EKOS endovas-cular system. Methods: Three insonation protocols were compared in an in vitro phantom mimicking venous flow to measure the effect of peak rarefactional pressure, pulse duration and pulse repetition frequency on cavitation activity energy, location and duration. Inertial and stable cavitation activity was quantified using passive cavitation imaging, and a metric of cavitation dose based on energy density was defined. Results: For all three insonation protocols, cavitation was sustained for the entire 30 min Definity infusion. The evolution of cavitation energy during each pulse duration was similar for all three protocols. For insonation proto-cols with higher peak rarefactional acoustic pressures, inertial and stable cavitation doses also increased. A com-plex relationship between the temporal behavior of cavitation energy within each pulse and the pulse repetition frequency affected the cavitation dose for the three insonation protocols. The relative predominance of stable or inertial cavitation dose varied according to insonation schemes. Passive cavitation images revealed the spatial dis-tribution of cavitation activity. Conclusion: Our cavitation dose metric based on energy density enabled the impact of different acoustic parame-ters on cavitation activity to be measured. Depending on the type of cavitation to be promoted or suppressed, par-ticular pulsing schemes could be employed in future studies, for example, to correlate cavitation dose with sonothrombolytic efficacy.

Automated summary

The objective of this study was to quantify the spatial and temporal distribution of cavitation activity induced by Definity infused through the EKOS catheter. Different acoustic parameters were found to have a significant impact on the energy, location, and duration of cavitation activity. A cavitation dose metric based on energy density was used to measure the influence of different acoustic parameters on cavitation activity.