INVESTIGATING THE ACCUMULATION OF SUBMICRON PHASE-CHANGE DROPLETS IN TUMORS

INVESTIGATING THE ACCUMULATION OF SUBMICRON PHASE-CHANGE DROPLETS IN TUMORS
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研究肿瘤中亚微米相变液滴的积累

DOI:
10.1016/j.ultrasmedbio.2020.06.021
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发表时间:
2020-10-01
影响因子:
2.9
通讯作者:
Burns, Peter N.
Burns, Peter N.
中科院分区:
医学3区
文献类型:
--
作者:
Helfield, Brandon L.;Yoo, Kimoon;Burns, Peter N.

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亚微米相变微滴是一类新兴的超声造影剂。与微泡相比,其相对较小的尺寸和增加的稳定性提供了通过增强的渗透性和保留效应在实体瘤中被动外渗和积聚的可能性。在暴露于足够强大的超声下,这些液滴可以转化为原位气体微泡,从而用作血管外特异性造影剂。然而,检测外渗液滴的体内成像方法尚未建立。在这里,我们开发了一种在诊断安全范围内的超声成像脉冲序列,以选择性地检测肿瘤中的液滴外渗。给荷瘤小鼠注射亚微米全氟丁烷液滴,并用我们的成像-汽化-成像序列进行询问。通过使用脉冲减法,相对于肿瘤内总信号的中值液滴外渗信号估计为E-肿瘤= 37 +/-5%,而肾脏E-肾脏= -2 +/-8%(p < 0.001)。这项工作有助于促进挥发性相移液滴作为下一代超声成像和治疗剂。(C)2020年世界医学和生物学超声联合会。All rights reserved.
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-tumor = 37 +/- 5% compared with the kidney E-kidney = -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. (C) 2020 World Federation for Ultrasound in Medicine & Biology. All rights reserved.