Ultrasonic contrast agent shell rupture detected by inertial cavitation and rebound signals.

Determining the rupture pressure threshold of ultrasound contrast agent microbubbles has significant applications for contrast imaging, development of therapeutic agents, and evaluation of potential bioeffects. Using a passive cavitation detector, this work evaluates rupture based on acoustic emissions from single, encapsulated, gas-filled microbubbles. Sinusoidal ultrasound pulses were transmitted into weak solutions of Optison at different center frequencies (0.9, 2.8, and 4.6 MHz), pulse durations (three, five, and seven cycles of the center frequencies), and peak rarefactional pressures (0.07 to 5.39 MPa). Pulse repetition frequency was 10 Hz. Signals detected with a 13-MHz, center-frequency transducer revealed postexcitation acoustic emissions (between 1 and 5 micros after excitation) with broadband spectral content. The observed acoustic emissions were consistent with the acoustic signature that would be anticipated from inertial collapse followed by "rebounds" when a microbubble ruptures and thus generates daughter/free bubbles that grow and collapse. The peak rarefactional pressure threshold for detection of these emissions increased with frequency (e.g., 0.53, 0.87, and 0.99 MPa for 0.9, 2.8, and 4.6 MHz, respectively; five-cycle pulse duration) and decreased with pulse duration. The emissions identified in this work were separated from the excitation in time and spectral content, and provide a novel determination of microbubble shell rupture

Double passive cavitation detection of Optison (TM) shell rupture

An improved understanding of ultrasound contrast agent (UCA) shell rupture is required to optimize therapeutic and diagnostic use. This experimental and theoretical study aims to explore the mechanism of UCA shell rupture by determining thresholds as a function of ultrasonic excitation parameters (driving frequency, pulse duration, and peak rarefactional pressure). The experimental setup is based on a passive cavitation detection system described in previous work. However, this system has been modified to allow simultaneous acquisition of the signals received with the 13-MHz passive receiver and the signals incident upon the lower frequency (0.9, 2.8 and 4.6 MHz) transmitting transducer functioning in the pulse-echo mode. Post-excitation signals were used to detect rupture thresholds. By allowing acquisition of the signals received by the insonifying transducer (pulse-echo during the excitation and passively at post-excitation) additional information is obtained within a frequency range and a transmission/reception configuration typical of ultrasonic diagnostic imaging. Data are analyzed to estimates the incident peak rarefactional pressure leading to 50% destruction. Comparison of experimental results with microbubble dynamics predicted using the Modified Herring equation was used to explore microbubble rupture indices based on radial expansion and peak velocity. © 2005 IEEE

Determining thresholds for contrast agent collapse

Determining the threshold of fragmentation of ultrasound contrast agents is important for both imaging and therapeutic ultrasound applications. We detected acoustic emissions from Optison™ microbubbles that were insonified by pulses of ultrasound. Our observations suggest that when the microbubbles rupture, daughter bubbles are created which subsequently grow and then collapse on a time-scale of 1-5 μs. The emission from the "rebound" collapse occurs after the end of the excitation pulse and we used the presence of this signal to determine the thresholds for the shell rupture. These shell-disruption thresholds were found to increase with frequency and decrease with pulse length. © 2004 IEEE

Clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound regression/progression studies

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality despite the widespread use of established medical therapies. This has prompted the search to identify new therapeutic approaches to achieve more effective prevention of cardiovascular events. Considerable interest has focused on the role of surrogate markers of therapeutic efficacy in the early evaluation of novel anti-atherosclerotic therapies. Monitoring changes in the extent of coronary atherosclerosis with intravascular ultrasound (IVUS) has been increasingly employed in clinical trials to assess progression and regression of atherosclerosis. This is based on the pivotal role that atherosclerotic plaque plays in the natural history of cardiovascular disease and the acceptance of validated arterial imaging approaches including coronary angiography and carotid intimal-medial thickness by regulatory authorities. The ability to generate high-resolution imaging of the entire thickness of the coronary artery wall permits evaluation of the entire burden of atherosclerotic plaque. In order to understand the differences, similarities, limitations and pitfalls of the IVUS technique among different academic core laboratories, a number of meetings of representatives from these groups were convened in 2007 and 2008. This document is result of those IVUS methodology meetings that assembled experts from core laboratories to discuss standards for image acquisition, definitions, criteria, analyses, and primary and secondary endpoints