IEEE Trans Ultrason Ferroelectr Freq Control. 2024 Oct;71(10):1186-1198. doi: 10.1109/TUFFC.2024.3450885. Epub 2024 Oct 10.
Phase-change nanodroplets (PCNDs) are customizable and controllable theranostic agents of particular interest in extravascular therapies such as drug delivery and histotripsy. High-bulk-boiling-point (HBP) PCNDs are preferred for their enhanced thermal stability under physiological temperature to achieve on-demand therapeutic effects on target sites-mainly in tumor tissue. However, the behavioral patterns of high-concentration, heterogeneously distributed HBP PCNDs in vivo have rarely been explored-the foci of PCND-related therapies mostly fall on the final therapeutic effect rather than the detailed behaviors of PCNDs, which may hamper the development and improvement of in vivo treatments with PCNDs. To fill the gap, we demonstrate an ultrasound-only extravascular monitoring technique to analyze the underlying behavioral patterns of intratumorally injected HBP PCNDs. In our hypothesis, recondensation and coalescence are the two predominant patterns influencing the trend of the postactivation signal of PCNDs. A "blink map" method was, thus, proposed to separate the two parts of the signal by recognizing the unique signal pattern of stochastic recondensation, and four derivative metrics were calculated for further analysis. The results revealed the postactivation patterns of PCNDs at different activation-pulse durations and activation stages throughout the activation-imaging period, and several general trends were observed and explained by existing theories, suggesting the feasibility of our extravascular monitoring technique. Overall, this work enriches the knowledge of the characteristics of HBP PCNDs as extravascular theranostic agents, and the monitoring results have the potential to provide timely feedback on PCND-related treatments underway, which may help adjust the treatment strategy and improve the therapeutic efficacy.
相变型纳米液滴（PCNDs）是一种可定制和可控的治疗剂，在血管外治疗（如药物输送和组织破碎）中特别有意义。高体积沸点（HBP）PCNDs 因其在生理温度下增强的热稳定性而受到青睐，可实现对靶位（主要是肿瘤组织）的按需治疗效果。然而，高浓度、异质分布的 HBP PCNDs 在体内的行为模式很少被探索——PCND 相关治疗的重点主要在于最终的治疗效果，而不是 PCNDs 的详细行为，这可能会阻碍 PCND 体内治疗的发展和改进。为了填补这一空白，我们展示了一种仅使用超声的血管外监测技术，以分析肿瘤内注射的 HBP PCNDs 的潜在行为模式。在我们的假设中，再冷凝和聚结是影响 PCNDs 激活后信号趋势的两种主要模式。因此，提出了一种“闪烁图”方法，通过识别随机再冷凝的独特信号模式来分离信号的两部分，并计算了四个衍生指标进行进一步分析。结果揭示了在整个激活成像期间，不同激活脉冲持续时间和激活阶段的 PCNDs 的激活后模式，观察到并通过现有理论解释了几个一般趋势，这表明我们的血管外监测技术是可行的。总的来说，这项工作丰富了 HBP PCNDs 作为血管外治疗剂的特性知识，监测结果有可能为正在进行的 PCND 相关治疗提供及时的反馈，这可能有助于调整治疗策略并提高治疗效果。
