Department of Biomedical Engineering, University of North Carolina at Chapel Hill, 109 Mason Farm Road, 304 Taylor Hall, CB 7575, Chapel Hill, North Carolina 27599, USA.
J Acoust Soc Am. 2013 Aug;134(2):1473-82. doi: 10.1121/1.4812866.
Ultrasound contrast agents are known to enhance high intensity focused ultrasound (HIFU) ablation, but these perfluorocarbon microbubbles are limited to the vasculature, have a short half-life in vivo, and may result in unintended heating away from the target site. Herein, a nano-sized (100-300 nm), dual perfluorocarbon (decafluorobutane/dodecafluoropentane) droplet that is stable, is sufficiently small to extravasate, and is convertible to micron-sized bubbles upon acoustic activation was investigated. Microbubbles and nanodroplets were incorporated into tissue-mimicking acrylamide-albumin phantoms. Microbubbles or nanodroplets at 0.1 × 10(6) per cm(3) resulted in mean lesion volumes of 80.4 ± 33.1 mm(3) and 52.8 ± 14.2 mm(3) (mean ± s.e.), respectively, after 20 s of continuous 1 MHz HIFU at a peak negative pressure of 4 MPa, compared to a lesion volume of 1.0 ± 0.8 mm(3) in agent-free control phantoms. Magnetic resonance thermometry mapping during HIFU confirmed undesired surface heating in phantoms containing microbubbles, whereas heating occurred at the acoustic focus of phantoms containing the nanodroplets. Maximal change in temperature at the target site was enhanced by 16.9% and 37.0% by microbubbles and nanodroplets, respectively. This perfluorocarbon nanodroplet has the potential to reduce the time to ablate tumors by one-third during focused ultrasound surgery while also safely enhancing thermal deposition at the target site.
超声造影剂已被证实可增强高强度聚焦超声（HIFU）消融效果，但这些全氟碳微泡仅限于血管，在体内半衰期短，并且可能导致目标部位以外的意外加热。在此，研究了一种纳米级（100-300nm）、双全氟碳（十氟丁烷/十二氟戊烷）液滴，它具有稳定性、足够小的尺寸以便逸出血管，并且在声激活后可转化为微米级的气泡。微泡和纳米液滴被纳入组织模拟丙烯酰胺-白蛋白水凝胶体模中。当以 0.1×10(6)个/cm(3)的浓度存在微泡或纳米液滴时，在持续 20s、频率为 1MHz、峰值负压为 4MPa 的 HIFU 后，与无造影剂水凝胶体模中 1.0±0.8mm(3)的损伤体积相比，分别得到 80.4±33.1mm(3)和 52.8±14.2mm(3)的平均损伤体积。在含有微泡的水凝胶体模中进行 HIFU 时的磁共振测温图证实了非目标表面的过热，而在含有纳米液滴的水凝胶体模中，过热发生在声聚焦处。与微泡相比，纳米液滴使靶区的最大温度变化提高了 16.9%，与无造影剂水凝胶体模相比提高了 37.0%。这种全氟碳纳米液滴有可能将聚焦超声手术中消融肿瘤的时间缩短三分之一，同时安全地增强目标部位的热沉积。
