Repeated Acoustic Vaporization of Perfluorohexane Nanodroplets for Contrast-Enhanced Ultrasound Imaging.
Repeated Acoustic Vaporization of Perfluorohexane Nanodroplets for Contrast-Enhanced Ultrasound Imaging.
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DOI：
10.1109/tuffc.2021.3093828
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发表时间：
2021-12
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影响因子：
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通讯作者：
Luke GP
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文献类型：
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作者：
Namen AV;Jandhyala S;Jordan T;Luke GP
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。当暴露于足够高强度的声能脉冲时，纳米液滴的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沸点高于体温的全氟己烷核心来解决这个问题。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。开发了定制成像序列，以实现HIFU换能器和线性阵列成像换能器的同步。我们展示了聚丙烯酰胺组织模拟体模中全氟己烷纳米液滴的重复声激活的可视化。我们进一步证明了从单个纳米液滴中检测到数百个汽化事件，其激活阈值远低于组织空化极限。总的来说，这种方法有可能在临床相关深度产生可靠和可重复的对比增强超声成像。
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’s 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 addressed 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 nanodroplet form. Previous work with perfluorohexane nanodroplets relied on optical activation via pulsed 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. A custom imaging sequence was developed to enable the synchronization of a HIFU transducer and a linear array imaging transducer. We show visualization of repeated acoustic activation of perfluorohexane nanodroplets in polyacrylamide tissue-mimicking phantoms. We further 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 and repeatable contrast-enhanced ultrasound imaging at clinically relevant depths.