Robust adaption algorithm for effective and safe sonoporation therapy

Abstract

Sonoporation is the transient permeability of cell membranes caused by ultrasound. Large scale oscillation of nearby microbubbles (MB) is considered to be the primary effect in sonoporation whereas inertial cavitation is associated with increased cell damage. MB behavior and therefore therapy success strongly depend on acoustic excitation parameters. We introduce a robust method to identify an adequate working point for effective sonoporation therapy despite un-known tissue attenuation. The presented algorithm identifies the inertial cavitation threshold of a MB cloud by correlating double pulse echoes. Its performance is demonstrated in simulations of the dynamic behavior of SonoVue MBs in a sound field and verified by measurements in a setup with acoustical and optical observation of the MBs. Sonoporation therapy of monolayers of SW480 cells in this setup reveals that the pressure amplitude just below inertial cavitation generates the highest sonoporation rate. This algorithm is further implemented on an image guided small animal sonoporation therapy system and a phantom with varying attenuation (0.1-4 dB. The inertial cavitation threshold is correctly identified with an RMSE of 0.14 dB). The proposed method allows safe, effective and reproducible MB therapy in in vitro and in vivo applications without time consuming calibration or reference measurements. © 2012, by Walter de Gruyter Berlin Boston. All rights reserved.