Real-time technique for improving molecular imaging and guiding drug delivery in large blood vessels: in vitro and ex vivo results.

Real-time technique for improving molecular imaging and guiding drug delivery in large blood vessels: in vitro and ex vivo results.
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DOI:
10.2310/7290.2011.00002
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发表时间:
2011-08
期刊:
影响因子:
2.8
通讯作者:
Hossack JA
Hossack JA
中科院分区:
医学4区
文献类型:
--
作者:
Patil AV;Rychak JJ;Klibanov AL;Hossack JA

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超声分子成像采用靶向微泡成像血管病理。这种方法也有潜力监测分子靶向微泡为基础的药物输送。我们提出了一种图像引导药物递送技术,该技术使用多个脉冲实时翻译,成像和空化微泡。这项技术既可以应用于大动脉的病理成像(大小和流量与人类相当),也可以指导血管中的局部药物输送。在生理盐水、黏性生理盐水(4cp)和牛血等多种流动介质中比较了该技术的微泡平移(或推动)效果。观察到,该方法在黏性生理盐水中的性能略好于在不同红细胞比容水平(40%,30%和10%)的牛血液中(分别提高6、4和2 dB)。通过体外和离体实验对该技术的给药效果进行了评价。高强度脉冲介导的荧光团(DiI)沉积在内皮细胞上(体外)而不引起细胞破坏。在猪颈动脉2 mm和5 mm横截面上进行的离体荧光团传递实验表明,动脉横截面的超声图像和复合荧光显微镜图像在荧光团传递的空间定位上高度对应。
Ultrasound-based molecular imaging employs targeted microbubbles to image vascular pathology. This approach also has the potential to monitor molecularly targeted microbubble-based drug-delivery. We present an image-guided drug-delivery technique that uses multiple pulses to translate, image and cavitate microbubbles in real-time. This technique can be applied to both imaging of pathology in large arteries (sizes and flow comparable to those in humans), and guiding localized drug delivery in blood vessels. The microbubble translation (or pushing) efficacy of this technique was compared in a variety of flow media: saline, viscous saline (4 cp) and bovine blood. It was observed that the performance of this approach was marginally better (by 6, 4 and 2 dB) in viscous saline than in bovine blood with varying levels of hematocrit (40%, 30% and 10%). The drug delivery efficacy of this technique was evaluated by in vitro and ex vivo experiments. High-intensity pulses mediated fluorophore (DiI) deposition on endothelial cells (in vitro) without causing cell destruction. Ex vivo fluorophore-delivery experiments conducted on swine carotids of 2 and 5 mm cross-section diameter demonstrated a high degree of correspondence in spatial localization of the fluorophore-delivery between the ultrasound and composite fluorescence-microscopy images of the arterial cross-sections.
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