Optical and acoustical observations of the effects of ultrasound on contrast agents

Optimal use of encapsulated microbubbles for ultrasound contrast agents and drug delivery requires an understanding of the complex set of phenomena th at affect the contrast agent echo and persistence. With the use of a video microscopy system coupled to either an ultrasound flow phantom or a chamber for insonifying stationary bubbles, we show that ultrasound has significan t effects on encapsulated microbubbles. In vitro studies show that a train of ultrasound pulses can alter the structure of an albumin-shelled bubble, initiate various mechanisms of bubble destruction or produce aggregation th at changes the echo spectrum. In this analysis, changes observed optically are compared with those observed acoustically for both albumin and lipid-sh elled agents. We show that, when insonified with a narrowband pulse at an a coustic pressure of several hundred kPa, a phospholipid-shelled bubble can undergo net radius fluctuations of at least 15%; and an albumin-shelled bub ble initially demonstrates constrained expansion and contraction. If the al bumin shell contains air, the shell may not initially experience surface te nsion; therefore, the echo changes more significantly with repeated pulsing ;. A set of observations of contrast agent destruction is presented, which inc ludes the slow diffusion of gas through the shell and formation of a shell defect followed by rapid diffusion of gas into the surrounding liquid. Thes e observations demonstrate that the low-solubility gas used in these agents can persist for several hundred milliseconds in solution. With the transmission of a high-pulse repetition rate and a low pressure, t he echoes fi om contrast agents can be affected by secondary radiation forc e. Secondary radiation force is an attractive farce for these experimental conditions, creating aggregates with distinct echo characteristics and exte nded persistence. The scattered echo from an aggregate is several times str onger and more narrowband than echoes from individual bubbles.