Acoustic sizing of an ultrasound contrast agent

Because the properties of ultrasound contrast agent populations after administration to patients are largely unknown, methods able to study them noninvasively are required. In this study, we acoustically performed a size distribution measurement of the ultrasound contrast agent Definity(®). Single lipid-shelled microbubbles were insonified at 25 MHz, which is considerably higher than their resonance frequency, so that their acoustic responses depended on their geometrical cross sections only. We calculated the size of each microbubble from their measured backscattered pressures. The acoustic size measurements were compared with optical reference size measurements to test their accuracy. Our acoustic sizing method was applied to 88 individual Definity(®) bubbles to derive a size distribution of this agent. The size distribution obtained acoustically showed a mean diameter (2.5 μm) and a standard deviation (0.9 μm) in agreement within 8% with the optical reference measurement. At 25 MHz, this method can be applied to bubble sizes larger than 1.2 μm in diameter. It was observed that similar sized bubbles can give different responses (up to a factor 1.5), probably because of shell differences. These limitations should be taken into account when implementing the method in vivo. This acoustic sizing method has potential for estimating the size distribution of an ultrasound contrast agent noninvasively.