Simultaneous optical and acoustical observations of contrast agents

The increasing interest in the use of encapsulated microbubbles for ultrasound contrast agents and drug delivery mechanisms requires an understanding of the insonified microbubble on a microscopic scale. With the use of a video microscopy system coupled to either a microscopic ultrasound flow phantom or a chamber for insonifying stationary bubbles, we show that ultrasound has significant effects on encapsulated microbubbles. A train of ultrasound pulses can alter the structure of an albumin-shelled bubble or instigate various mechanisms of bubble destruction. Ultrasonic transmission also produces a primary radiation force which can displace contrast agents with each acoustic pulse, and we demonstrate this in-vivo as well as in-vitro. Secondary radiation force is shown to cause changes in effective scatterer size, echo characteristics, and persistence.