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 endovascular 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 protocols with higher peak rarefactional acoustic pressures, inertial and stable cavitation doses also increased. A complex 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 distribution of cavitation activity. CONCLUSION: Our cavitation dose metric based on energy density enabled the impact of different acoustic parameters on cavitation activity to be measured. Depending on the type of cavitation to be promoted or suppressed, particular pulsing schemes could be employed in future studies, for example, to correlate cavitation dose with sonothrombolytic efficacy.

2D and 3D real-time passive cavitation imaging of pulsed cavitation ultrasound therapy in moving tissues.

Pulsed cavitation ultrasound therapy (PCUT) is an effective non-invasive therapeutic approach in various medical indications that relies on the mechanical effects generated by cavitation bubbles. Even though limited by the poor contrast, conventional ultrasound B-Mode imaging has been widely used for the guidance and monitoring of the therapeutic procedure, allowing the visualization of the cavitation bubble cloud. However, the visualization of the bubble cloud is often limited in deep organs such as the liver and the heart and remains moreover completely subjective for the operator. Our goal is to develop a new imaging mode to better identify the cavitation cloud. Active and passive cavitation imaging methods have been developed but none of them has been able to locate the cavitation bubble created by PCUT in real-time and in moving organs. In this paper we propose a passive ultrasound imaging approach combined with a spatiotemporal singular value decomposition filter to detect and map the bubble cloud with high sensitivity and high contrast. In moving applications at a maximal motion speed of 10 mm s-1, the contrast-to-noise ratio for passive cavitation imaging is up to 10 times higher than for active cavitation imaging, with a temporal resolution of about 100 ms. The mapping of the bubble cloud can be overlaid in real-time to the conventional B-Mode, which permits to locate the cavitation phenomena in relation to the anatomic image. Finally, we extend the technique to volumetric imaging and show its feasibility on moving phantoms.