IEEE Trans Ultrason Ferroelectr Freq Control. 2017 Mar;64(3):555-567. doi: 10.1109/TUFFC.2016.2640342. Epub 2016 Dec 15.
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 CF 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 resulted in UCAs with smaller microbubbles (number weighted mean diameter ~1 [Formula: see text]) than sonication (number weighted mean diameter ~2 [Formula: see text]). UCA formulations with similar size distributions but different main lipid components showed that the DPPC-based UCA formulations had higher nonlinear responses at both the fundamental and subharmonic frequencies in vitro for hfCEUS using the Vevo2100 high-frequency preclinical scanner (FUJIFILM VisualSonics, Inc.). In addition, UCA formulations F (DSPC-based) and L (DPPC-based) that were made by mechanical agitation performed similar in vitro to the commercially available Target-Ready MicroMarker (FUJIFILM VisualSonics, Inc.). UCA formulation F also performed similar to Target-Ready MicroMarker in vivo in pigs with similar mean contrast intensity within the kidney ( n = 7 ), but formulation L did not. This is likely due to the lower stability of formulation L in vivo. Our study shows that DSPC-based microbubbles produced by mechanical agitation resulted in small microbubbles with high nonlinear responses suitable for hfCEUS imaging.
虽然高频超声成像在各种应用中受到关注，但几乎没有专门用于高频（>15MHz）的超声对比剂（UCAs）可用于对比增强超声（CEUS）成像。此外，用于高频 CEUS（hfCEUS）的有限商业上可用的 UCAs 的组成在很大程度上是未知的，而壳特性已被证明是其性能的一个重要因素。我们的研究旨在内部生产用于 hfCEUS 的 UCAs。通过超声或机械搅拌制备了 12 种不同的 UCAs 制剂 A-L。气体核由 CF 组成，主要涂层脂质为 1,2-二硬脂酰-sn-甘油-3-磷酸胆碱（DSPC；A-F 制剂）或 1,2-二月桂酰基-sn-甘油-3-磷酸胆碱（DPPC；G-L 制剂）。机械搅拌产生的微泡比超声（数均粒径约 2μm）小（数均粒径~1μm）。具有相似粒径分布但不同主要脂质成分的 UCAs 制剂表明，基于 DPPC 的 UCAs 制剂在使用 Vevo2100 高频临床前扫描仪（FUJIFILM VisualSonics，Inc.）进行 hfCEUS 时，在基频和次谐波频率下具有更高的非线性响应。此外，通过机械搅拌制备的 UCAs 制剂 F（基于 DSPC）和 L（基于 DPPC）在体外与市售的 Target-Ready MicroMarker（FUJIFILM VisualSonics，Inc.）性能相似。UCAs 制剂 F 也在体内与 Target-Ready MicroMarker 在猪体内表现相似，在肾脏内具有相似的平均对比强度（n=7），但制剂 L 则没有。这可能是由于制剂 L 在体内的稳定性较低。我们的研究表明，通过机械搅拌产生的基于 DSPC 的微泡产生了适合 hfCEUS 成像的小而具有高非线性响应的微泡。
