Department of Physics, Concordia University, Montreal, Canada; Department of Biology, Concordia University, Montreal, Canada.
Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada.
Ultrasound Med Biol. 2020 Oct;46(10):2861-2870. doi: 10.1016/j.ultrasmedbio.2020.06.021. Epub 2020 Jul 27.
Submicron phase-change droplets are an emerging class of ultrasound contrast agent. Compared with microbubbles, their relatively small size and increased stability offer the potential to passively extravasate and accumulate in solid tumors through the enhanced permeability and retention effect. Under exposure to sufficiently powerful ultrasound, these droplets can convert into in situ gas microbubbles and thus be used as an extravascular-specific contrast agent. However, in vivo imaging methods to detect extravasated droplets have yet to be established. Here, we develop an ultrasound imaging pulse sequence within diagnostic safety limits to selectively detect droplet extravasation in tumors. Tumor-bearing mice were injected with submicron perfluorobutane droplets and interrogated with our imaging-vaporization-imaging sequence. By use of a pulse subtraction method, median droplet extravasation signal relative to the total signal within the tumor was estimated to be E=37±5% compared with the kidney E=-2±8% (p < 0.001). This work contributes toward the advancement of volatile phase-shift droplets as a next-generation ultrasound agent for imaging and therapy.
亚微米级相变型液滴是一类新兴的超声对比剂。与微泡相比，其较小的尺寸和增加的稳定性使其有可能通过增强的通透性和保留效应被动地渗出并在实体瘤中积累。在暴露于足够强的超声下，这些液滴可以转化为原位气体微泡，从而可用作血管外特异性对比剂。然而，尚未建立用于检测渗出液滴的体内成像方法。在这里，我们在诊断安全范围内开发了一种超声成像脉冲序列，以选择性地检测肿瘤中的液滴渗出。将亚微米级全氟丁烷液滴注射到荷瘤小鼠中，并使用我们的成像-汽化-成像序列进行检测。通过使用脉冲减法方法，与肾脏 E=-2±8%（p<0.001）相比，估计相对于肿瘤内总信号，液滴渗出信号的中位数 E=37±5%。这项工作为挥发性相移液滴作为下一代超声成像和治疗剂的发展做出了贡献。
