首页> 外文期刊>IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control >Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging: In Vitro and In Vivo Evaluation
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Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging: In Vitro and In Vivo Evaluation

机译:微泡成分和高频对比增强超声成像的制备:体外和体内评估。

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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 resulted in UCAs with smaller microbubbles (number weighted mean diameter ~1 μm ) than sonication (number weighted mean diameter ~2 μm ). 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.
机译:尽管高频超声成像在各种应用中引起了人们的注意,但几乎没有任何专用于此类频率(> 15 MHz)的超声造影剂(UCA)可用于造影增强超声(CEUS)成像。此外,用于高频CEUS(hfCEUS)的有限的商用UCA的组成在很大程度上是未知的,而壳的性能已被证明是其性能的重要因素。我们研究的目的是为hfCEUS内部生产UCA。通过超声或机械搅拌制备了十二种不同的UCA制剂A-L。气芯由C4F10组成,主要包衣脂质为1,2-二硬脂酰基-sn-甘油-3-磷酸胆碱(DSPC; AF配方)或1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱(DPPC; GL)公式)。机械搅拌导致UCA具有比超声处理(数量加权平均直径〜2μm)更小的微气泡(数量加权平均直径〜1μm)。具有相似的尺寸分布但主要脂质成分不同的UCA配方表明,使用Vevo2100高频临床前扫描仪(FUJIFILM VisualSonics,Inc.),基于DPPC的UCA配方在hfCEUS的体外基频和亚谐波频率下均具有更高的非线性响应。另外,通过机械搅拌制成的UCA制剂F(基于DSPC)和L(基于DPPC)在体外的性能与市售的Target-Ready MicroMarker(FUJIFILM VisualSonics,Inc.)类似。在猪中,UCA制剂F在体内的表现也与Target-Ready MicroMarker相似,肾脏内的平均对比强度相似(n = 7),但是制剂L没有。这可能是由于制剂L在体内的较低稳定性。我们的研究表明,通过机械搅拌产生的基于DSPC的微气泡会产生具有高非线性响应的小微气泡,适用于hfCEUS成像。

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