A method for the determination of the inertial cavitation threshold of ultrasound contrast agents

Ultrasound contrast agents consist of microbubbles with diameters in the micron range. In recent developments, targeted drug delivery is effectuated using microbubbles. Microbubbles may be destroyed by inertial cavitation if the insonification amplitude is chosen high enough. The minimum threshold for inertial cavitation of a microbubble population is thus an important characteristic of an ultrasound contrast agent. This article proposes a method for the determination of ultrasound contrast agent destruction by inertial cavitation. Detection is implemented by transmission of a destruction and a probing pulse with a fixed time delay. Using an expectation maximization algorithm, modulated Gaussian pulses are fitted to the received waveform. By consideration of the time offset between each pulse, the responses to the individual pulses can be seperated and destroyed bubbles can be counted. A destruction curve for the contrast agent Definity was recorded at an insonification frequency of 2.25 MHz. At a peak negative pressure of 1.11 MPa, 18.81% of the recorded population was destroyed.