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arXiv 2103.15895physics.med-ph
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用于超声造影成像的全氟己烷纳米液滴的重复声蒸发

Repeated Acoustic Vaporization of Perfluorohexane Nanodroplets for Contrast-Enhanced Ultrasound Imaging

Austin Van Namen, Sidhartha Jandhyala, Tomas Jordan, Geoffrey Luke

摘要:

过热的全氟化碳纳米液滴是新兴的超声成像造影剂,具有生物相容性成分、独特的相变动力学和治疗负载能力。在暴露于足够高强度的声能脉冲时,纳米液滴全氟化碳核经历液体到气体的相变,并变成回声微泡,提供超声造影。可控的激活导致高对比度图像,而纳米液滴的小尺寸促进更长的循环时间和更好的体内稳定性。然而,一个缺点是纳米液滴只能蒸发一次,限制了它们的多功能性。最近,我们和其他人通过使用全氟己烷核心来解决这个问题,全氟己烷的沸点高于体温。因此,在蒸发之后,微泡再冷凝回到其稳定的纳米液滴形式。以前的工作与全氟己烷纳米液滴依赖于光学激活通过脉冲激光吸收的封装染料。这种策略限制了该方法的成像深度和时间分辨率。在这项研究中,我们克服了这些限制,证明声学液滴汽化与1.1兆赫高强度聚焦超声。聚焦超声的短持续时间、高振幅脉冲提供足够强的峰值负压以启动汽化。当使用具有高频换能器的定制成像序列时,可以在聚丙烯酰胺组织模拟体模中可视化全氟己烷纳米滴的重复声激活。我们证明了数百个汽化事件的检测,从个别nanodrops的激活阈值远低于组织空化限制。总的来说,这种方法有可能在临床相关深度产生可靠的对比增强超声成像。

英文摘要:

Superheated perfluorocarbon nanodroplets are emerging ultrasound imaging contrast agents boasting biocompatible components, unique phase-change dynamics, and therapeutic loading capabilities. Upon exposure to a sufficiently high intensity pulse of acoustic energy, the nanodroplet perfluorocarbon core undergoes a liquid-to-gas phase change and becomes an echogenic microbubble, providing ultrasound contrast. The controllable activation leads to high-contrast images, while the small size of the nanodroplets promotes longer circulation times and better in-vivo stability. One drawback, however, is that the nanodroplets can only be vaporized a single time, limiting their versatility. Recently, we and others have address this issue by using a perfluorohexane core, which has a boiling point above body temperature. Thus after vaporization, the microbubbles recondense back into their stable nanodroplets form. Previous work with perfluorohexane nanodroplets relied on optical activation via pulse laser absorption of an encapsulated dye. This strategy limits the imaging depth and temporal resolution of the method. In this study we overcome these limitations by demonstrating acoustic droplet vaporization with 1.1-MHz high intensity focused ultrasound. A short-duration, high-amplitude pulse of focused ultrasound provides a sufficiently strong peak negative pressure to initiate vaporization. When using a custom imaging sequence with a high-frequency transducer, the repeated acoustic activation of perfluorohexane nanodroplets can be visualized in polyacrylamide tissue-mimicking phantoms. We demonstrate detection of hundreds of vaporization events from individual nanodroplets with activation thresholds well below the tissue cavitation limit. Overall, this approach has the potential to result in reliable contrast-enhanced ultrasound imaging at clinically relevant depths.

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