Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging: In Vitro and in Vivo Evaluation

Abstract

Although high-frequency ultrasound imaging is gaining attention in various applications, hardly any ultrasound contrast agents (UCAs) dedicated to such frequencies (>15 MHz) are available for contrast-enhanced ultrasound (CEUS) imaging. Moreover, the composition of the limited commercially available UCAs for high-frequency CEUS (hfCEUS) is largely unknown, while shell properties have been shown to be an important factor for their performance. The aim of our study was to produce UCAs in-house for hfCEUS. Twelve different UCA formulations A-L were made by either sonication or mechanical agitation. The gas core consisted of C4F10 and the main coating lipid was either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC; A-F formulation) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC; G-L formulation). Mechanical agitation r