Superheated perfluorocarbon nanodroplets are emerging ultrasound imaging contrast agents that boast 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 (HIFU). 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 a visualization of repeated acoustic activation of perfluorohexane nanodroplets in polyacrylamide tissue-mimicking phantoms. We further demonstrate the 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.

中文翻译：

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全氟己烷纳米液滴的重复声学汽化用于对比增强超声成像。

过热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心经历液-气相变，并变成回声微泡，提供超声对比度。可控的激活可产生高对比度图像，而小尺寸的纳米液滴可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解决了这个问题。因此，蒸发后，微泡重新凝结成稳定的纳米液滴形式。以前对全氟己烷纳米液滴的研究依赖于通过脉冲激光吸收封装染料的光学激活。这种策略限制了该方法的成像深度和时间分辨率。在本研究中，我们通过使用 1.1 MHz 高强度聚焦超声 (HIFU) 演示声学液滴汽化来克服这些限制。持续时间短、高振幅的聚焦超声波脉冲提供足够强的峰值负压来启动汽化。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重复声激活的可视化。我们进一步证明了对单个纳米液滴的数百个汽化事件的检测，其激活阈值远低于组织空化极限。总体而言，这种方法有可能在临床相关深度产生可靠且可重复的对比增强超声成像。