Optimizing Sensitivity of Ultrasound Contrast-Enhanced Super-Resolution Imaging by Tailoring Size Distribution of Microbubble Contrast Agent

Ultrasound contrast-enhanced super-resolution imaging has recently attracted attention because of its extraordinary ability to image vascular features much smaller than the ultrasound diffraction limit. This method requires sensitive detection of separable microbubble events despite a noisy tissue background to indicate the microvasculature, and any approach that could improve the sensitivity of the ultrasound system to individual microbubbles would be highly beneficial. In this study, we evaluated the effect of varying microbubble size on super-resolution imaging sensitivity. Microbubble preparations were size sorted into different mean diameters and then were imaged at equal concentrations. Commercially manufactured Definity and Optison were also imaged for comparison. Both in vitro experiments in phantom vessels and in vivo experiments imaging rat tumors revealed that the sensitivity of contrast-enhanced super-resolution imaging can be improved by using microbubbles with a larger diameter.