This work presents experimental responses of single ultrasound contrast agents to short, large amplitude pulses, characterized using double passive cavitation detection. In this technique, two matched, focused receive transducers were aligned orthogonally to capture the acoustic response of a microbubble from within the overlapping confocal region. The microbubbles were categorized according to a classification scheme based on the presence or absence of postexcitation signals, which are secondary broadband spikes following the principle oscillatory response of the ultrasound contrast agent and are indicative of the transient collapse of the microbubble. Experiments were conducted varying insonifying frequencies (0.9, 2.8, 4.6, and 7.1 MHz) and peak rarefactional pressures (200 kPa to 6.2 MPa) for two types of contrast agents (Definity and Optison). Results were fit using logistic regression analysis to define pressure thresholds where at least 5% and 50% of the microbubble populations collapsed for each frequency. These thresholds were found to occur at lower pressures for Definity than for Optison over the range of frequencies studied; additionally, the thresholds occurred at lower pressures with lower frequencies for both microbubble types in most cases, though this trend did not follow a mechanical index scaling.

Passive cavitation detection was used to improve the experimental characterization of single ultrasound contrast agent microbubble responses to short, large amplitude pulses. Two situations were examined: isolated microbubbles in an unconstrained environment, and isolated microbubbles flowing through a tube. The microbubbles were categorized according to a classification scheme based on the presence or absence of postexcitation signals, which are secondary broadband spikes that may follow the principle oscillation of the ultrasound contrast agent in response to an insonifying pulse. Experiments were conducted for different frequencies, peak rarefactional pressures, flow rates, and types of microbubble. Postexcitation activity was found to increase as frequency decreased, acoustic pressure increased, and flow rate increased. Additionally, lipidshelled microbubbles were found to exhibit greater postexcitation at lower acoustic pressure thresholds than albumin-shelled microbubbles.

Double passive cavitation detection involves the confocal alignment of one transmit and two passive receive transducers. Highly dilute mixtures of ultrasound contrast agents (UCAs), including Definity, Optison, and non-commercial microbubbles, were prepared such that on average only a single UCA was present at the confocal region. A 3-cycle incident pulse repeating at 10 Hz was varied in frequency from 0.9 to 7.1 MHz and in peak rarefactional pressure (PRP) from 200 kPa to 6 MPa. The acquired signals were classified according to the presence or absence of a postexcitation signal (PES), a quantifiable aspect of the acquired temporal signal which is hypothesized to occur due to the rupture of the UCA shell and therefore indicate the collapse of the microbubble. The resulting percentages of UCAs with PES were fitted with modified logistic regression curves to determine percentage collapse thresholds. The percentage of signals exhibiting PES was found to increase as frequency decreased or as PRP increased while holding other acoustic parameters constant, in agreement with alternative methods of measuring collapse. Definity was found to have a lower threshold of collapse than Optison, while the thresholds of the non-commercial UCAs depended on their physical properties. (Work supported by NIH Grant No. R37EB002641.)