Accurate Measurement of Microbubble Response to Ultrasound With a Diagnostic Ultrasound Scanner

Ultrasound and microbubbles are often used to enhance drug delivery and the suggested mechanisms are extravasation and sonoporation. Drug delivery schemes with ultrasound and microbubbles at both low and high acoustic amplitudes have been suggested. A diagnostic ultrasound scanner may play a double role as both an imaging and a therapy device. It was not possible to accurately measure microbubble response with an ultrasound scanner for a large range of acoustic pressures and microbubble concentrations until now, mainly because of signal saturation issues. A method for continuously adjusting the receive gain of a scanner and limiting signal saturation was developed to accurately measure backscattered echoes from microbubbles for mechanical indexes (MIs) up to 2.1. The intensity of backscattered echoes from microbubbles increased quarticly with MI without reaching any limit. The signal intensity from microbubbles was found to be linear with concentration at both low and high MIs. However, at very high concentrations, acoustic shadowing occurs which limits the delivered acoustic pressure in deeper areas. The contrastto- tissue ratio was also measured and found to stay constant with MI. These results can be used to better guide drug delivery approaches and to also develop imaging techniques for therapy procedures.