Simultaneous trapping and imaging of microbubbles at clinically relevant flow rates

Mechanisms for non-invasive target drug delivery using microbubbles and ultrasound have attracted growing interest. Microbubbles can be loaded with a therapeutic payload and tracked via ultrasound imaging to selectively release their payload at ultrasound-targeted locations. In this study, an ultrasonic trapping method is proposed for simultaneously imaging and controlling the location of microbubbles in flow by using acoustic radiation force. Targeted drug delivery methods are expected to benefit from the use of the ultrasonic trap, since trapping will increase the MB concentration at a desired location in human body. The ultrasonic trap was generated by using an ultrasound research system UARP II and a linear array transducer. The trap was designed asymmetrically to produces a weaker radiation force at the inlet of the trap to further facilitate microbubble entrance. A pulse sequence was generated that can switch between a long duration trapping waveform and short duration imaging waveform. High frame rate plane wave imaging was chosen for monitoring trapped microbubbles at 1 kHz. The working principle of the ultrasonic trap was explained and demonstrated in an ultrasound phantom by injecting SonoVue microbubbles flowing at 80 mL/min flow rate in a 3.5 mm diameter vessel.