Passive mapping of cavitation activity for monitoring of drug delivery.

Abstract

Acoustic cavitation has been recently shown to have tremendous potential as a mechanism for releasing and enabling improved uptake and biodistribution of therapeutic agents for the pharmacological treatment of cancer, cardiovascular, and neurodengenerative diseases. Passive cavitation mapping makes it possible to localize, characterize, and quantify cavitation activity by detecting the acoustic emissions produced by cavitating bubbles on an array of receivers, which are then back-propagated to form a cavitation-selective image with high spatio-temporal accuracy. In the present study, a 64-element diagnostic linear array was used to construct passive cavitation maps during pulsed HIFU exposure of a narrow channel transporting fluorescent dextran nanoparticles through a biocompatible porous hydrogel in the presence or absence of ultrasound contrast agents. Spectral analysis of the resulting acoustic emissions confirmed that different cavitation regimes were successfully instigated over the HIFU parameter range that was investigated. Superposition of cavitation selective images over the treatment course was used to construct maps of cavitation activity and dose as a function of location for treatment assessment and was found to correlate well with dextran extravasation. It is concluded that passive mapping of cavitation activity shows great promise for assessment and real-time monitoring of cavitation based drug delivery.