Performance evaluation of an automatic controlled sonoporation therapy device

Sonoporation is the transient unspecific permeability of the cell membrane by ultrasound, which is increased by the presence of microbubbles. Therapy success strongly depends on the parameters of the acoustic excitation. High sound pressures cause high numbers of dead cells, whereas low pressures result in low sonoporation rates. However, tissue attenuation and constructive wave interference at reflecting interfaces inhibit reliable prediction of pressure at the therapy site. Consequently, we developed a sonoporation device allowing automatic control of the pressure at the therapy site by acoustic observation of microbubble destruction and tissue attenuation estimation. The sonoporation device consists of a custom designed 1 MHz therapy transducer with a central opening for an imaging array of a programmable medical ultrasound machine. The imaging array allows image guided positioning of the therapy focus before and during therapy and the monitoring of MB behavior. The resulting tissue transfer function is estimated by an algorithm combining microbubble destruction detection and attenuation estimation to control the pressure at the therapy site. For performance evaluation, a flow phantom with a flow of SonoVue microbubble solution in a tissue mimicking phantom with varying attenuation was used. An evaluation control sequence with a PI controller revealed an improved RMSE of 5.5% compared to 7.7% without the regulation to a set point of 700 kPa. This study shows the feasibility of the presented sonoporation device to control therapy pressure by microbubble destruction detection and attenuation estimation.