Comparison of in vitro and in vivo acoustic response of a novel 50:50 PLGA contrast agent
Comparison of in vitro and in vivo acoustic response of a novel 50:50 PLGA contrast agent
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DOI：
10.1016/j.ultras.2006.04.003
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发表时间：
2006-11-01
期刊：
影响因子：
4.2
通讯作者：
El-Sherif, Dalia
中科院分区：
文献类型：
--
作者：
Wheatley, Margaret A.;Forsberg, Flemming;El-Sherif, Dalia
本文介绍了一种直径1.2微米的新型聚乳酸-乙醇酸(50：50)(PLGA)超声造影剂的声学性能的体内外对比实验。使用脉冲-回波装置来确定体外增强。更多的体外研究进一步表征了中空微胶囊，包括衰减测量的共振频率(2.25至15 MHz)和温度效应(25摄氏度对37摄氏度)。在体内，4只兔静脉注射该药(剂量范围：0.005-0.13ml/kg)。使用音频多普勒信号的频谱功率分析离线计算体内定量的剂量反应，音频多普勒信号是从放置在手术暴露的远端主动脉周围的定制的10 MHz袖带换能器获得的。选择这个频率是因为在兔子身上遇到的非常浅的扫描深度，特别是对于直接放置在血管周围的袖带换能器，需要使用具有足够空间分辨率的高频成像设备来进行有意义的测量。为了定性评价，两只兔在造影剂(剂量：0.1ml/kg)前和造影剂后在能量多普勒模式下进行成像。据报道，在体外和体内都有显著的声学增强(高达24分贝)。此外，兔子没有表现出任何不良反应的多次注射(>；20)的药物。在体外测量的3.09至3.49 MHz之间的共振频率低于预测的类似大小的自由气泡，可能是由于胶囊壁结构的原因。在25摄氏度下，在5 MHz的辐射20分钟内，观察到最小的信号损失(类似于4分贝)，但在37摄氏度时，信号在最初的5分钟内下降到接近基线。这种温度敏感性可能是由于胶囊完整性的丧失(因此气体的损失)。潜在的原因包括水解度增加或聚合物软化，以及壳体在接近玻璃化转变温度(T-g)的温度下吸水率增加。(C)2006爱思唯尔B.V.保留所有权利。
A comparison between in vitro and in vivo experiments conducted to investigate the acoustic properties of a novel, 1.2 mu m diameter poly(lactic-co-glycolic acid) (50:50) (PLGA) ultrasound contrast agent, the development of which was described previously by us, is presented. A pulse-echo setup was used to determine enhancement in vitro. Additional in vitro studies further characterized the hollow microcapsules, including resonance frequency from attenuation measurements (from 2.25 to 15 MHz) and temperature effects (25 degrees C vs. 37 degrees C). In vivo, four rabbits received intravenous injections of the agent (dose range: 0.005-0.13 ml/kg). Quantitative in vivo dose-responses were calculated off-line using spectral power analysis of audio Doppler signals acquired from a custom-made 10 MHz cuff transducer placed around the surgically exposed distal aorta. This frequency was chosen since the very shallow scanning depths encountered in rabbits, in particular for the cuff transducer placed directly around the vessel, necessitates the use of high frequency imaging devices with sufficient spatial resolution to enable meaningful measurements. For qualitative assessments, two rabbits were imaged pre- and post-contrast administration (dose: 0.1 ml/kg) in power Doppler mode. Significant acoustic enhancements (up to 24 dB) were reported both in vitro and in vivo. Moreover, the rabbits did not show any adverse side effects from multiple injections (> 20) of the agent. Measured in vitro resonance frequency between 3.09 and 3.49 MHz was lower than predicted for a similar sized free bubble, potentially due to capsule wall structure. Minimal loss of signal (similar to 4 dB) was observed at 25 degrees C over 20 min of insonation at 5 MHz but at 37 degrees C the signal dropped close to base line within the first 5 min. This temperature sensitivity could be due to loss of capsule integrity (and hence loss of gas). Potential causes include increased hydrolysis or polymer softening and increased water uptake by the shell at temperatures closer to the glass transition temperature (T-g). (c) 2006 Elsevier B.V. All rights reserved.