Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada M4N 3M5.
Ultrasound Med Biol. 2013 Mar;39(3):475-89. doi: 10.1016/j.ultrasmedbio.2012.10.004. Epub 2013 Jan 11.
Because many tumors possess blood vessels permeable to particles with diameters of 200 nm, it is possible that submicron perfluorocarbon droplets could constitute a novel extravascular ultrasound contrast agent capable of selectively enhancing tumors. Under exposure to bursts of ultrasound of sufficient rarefactional pressure, droplets can undergo vaporization to form echogenic microbubbles. In this study, phase-change thresholds of 220-nm-diameter droplets composed of perfluoropentane were studied in polyacrylamide gel phantoms maintained at temperatures of 21-37°C, exposed to high-pressure bursts of ultrasound with frequencies ranging from 5-15 MHz and durations of 1 μs to 1 ms. The thresholds were found to depend inversely and significantly (p < 0.001) on ultrasound frequency, pulse duration, and droplet temperature, ranging from 9.4 ± 0.8 MPa at 29°C for a 1-μs burst at 5 MHz to 3.2 ± 0.5 MPa at 37°C for a 1-ms burst at 15 MHz. The diameters of microbubbles formed from droplets decreased significantly as phantom stiffness increased (p < 0.0001), and were independent of pulse duration, although substantially more droplets were converted to microbubbles for 1-ms pulse durations compared with briefer exposures. In vivo experiments in a mouse tumor model demonstrated that intravenously injected droplets can be converted into highly echogenic microbubbles 1 h after administration.
由于许多肿瘤都具有对直径为 200nm 的粒子具有通透性的血管，因此亚微米级的全氟碳液滴有可能成为一种新型的血管外超声对比剂，能够选择性地增强肿瘤。在足够稀疏压力的超声脉冲的作用下，液滴可以蒸发形成声致微泡。在这项研究中，在温度为 21-37°C 的聚丙烯酰胺凝胶模型中研究了由全氟戊烷组成的 220nm 直径液滴的相变阈值，这些液滴暴露于频率范围为 5-15MHz、持续时间为 1μs-1ms 的高压超声脉冲中。发现这些阈值与超声频率、脉冲持续时间和液滴温度呈显著的反比关系（p<0.001），范围从 29°C 时 1μs 脉冲、5MHz 时的 9.4±0.8MPa 到 37°C 时 1ms 脉冲、15MHz 时的 3.2±0.5MPa。从液滴形成的微泡直径随着模型刚性的增加而显著减小（p<0.0001），并且与脉冲持续时间无关，尽管与较短的暴露时间相比，1ms 脉冲持续时间下转化为微泡的液滴数量要多得多。在小鼠肿瘤模型的体内实验中，静脉注射的液滴在给药后 1 小时可转化为高回声的微泡。
