High-intensity focused ultrasound ablation enhancement in vivo via phase-shift nanodroplets compared to microbubbles.
High-intensity focused ultrasound ablation enhancement in vivo via phase-shift nanodroplets compared to microbubbles.
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DOI：
10.1186/s40349-015-0029-4
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Dayton PA
中科院分区：
文献类型：
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作者：
Moyer LC;Timbie KF;Sheeran PS;Price RJ;Miller GW;Dayton PA
在高强度聚焦超声（HIFU）外科手术过程中，需要快速消融病理组织，同时最小化对健康组织的损伤。目前的技术受到相对较长的手术时间和健康组织的脱靶加热风险的限制。一种可能的解决方案是使用微泡，其可以提高HIFU手术期间热能递送的效率。然而，微泡也受到诸如低空间选择性和短体内循环时间的限制。在这项研究中，使用双全氟化碳纳米液滴，可以增强热消融，但保留高空间选择性和循环半衰期，在体内进行了评估，并与传统的微泡剂在大鼠肝脏的HIFU消融。高强度聚焦超声（1.1 MHz，4.1 MPa，15-s连续波）应用于大鼠肝脏在体内，并通过磁共振测温法监测加热过程中超声处理。分析温度测量数据，以量化靶点和预焦点处的温升和消融面积，在静脉注射纳米液滴或微泡剂后5、15或95分钟应用HIFU。还进行了假对照实验（未注射试剂）。在所有三个时间点，纳米液滴显著增强了对目标的热传递，实现了比无试剂对照超声处理高130%的温度和大30倍的消融面积。纳米液滴没有显著增强偏离目标的表面加热。微泡也导致显著更大的热传递，但加热集中在动物的近端表面，导致皮肤灼伤。此外，与对照情况相比，微泡导致对期望目标的热传递更低，95分钟时间点的显著例外。结果表明，这里研究的纳米液滴配方可以大大增加在声焦点处的热传递，同时避免焦前加热。相比之下，微泡导致更大的预焦加热和更少的加热在目标。此外，纳米液滴足够稳定以在注射后至少1.5小时内增强体内HIFU消融。如本文所述的双全氟化碳纳米液滴制剂的使用可以显著减少HIFU手术时间而不增加皮肤烧伤的风险。
During high-intensity focused ultrasound (HIFU) surgical procedures, there is a need to rapidly ablate pathological tissue while minimizing damage to healthy tissue. Current techniques are limited by relatively long procedure times and risks of off-target heating of healthy tissue. One possible solution is the use of microbubbles, which can improve the efficiency of thermal energy delivery during HIFU procedures. However, microbubbles also suffer from limitations such as low spatial selectivity and short circulation time in vivo. In this study, the use of a dual-perfluorocarbon nanodroplet that can enhance thermal ablation, yet retains high spatial selectivity and circulation half-life, was evaluated in vivo and compared to traditional microbubble agents during HIFU ablations of rat liver. High-intensity focused ultrasound (1.1 MHz, 4.1 MPa, 15-s continuous wave) was applied to rat liver in vivo, and heating was monitored during sonication by magnetic resonance thermometry. Thermometry data were analyzed to quantify temperature rise and ablated area, both at the target and prefocally, for HIFU applied 5, 15, or 95 min after intravenous injection of either nanodroplet or microbubble agents. Sham control experiments (no injected agents) were also performed. At all three time points, nanodroplets significantly enhanced thermal delivery to the target, achieving temperatures 130 % higher and ablated areas 30 times larger than no-agent control sonications. Nanodroplets did not significantly enhance off-target surface heating. Microbubbles also resulted in significantly greater thermal delivery, but heating was concentrated at the proximal surface of the animal, causing skin burns. Furthermore, microbubbles resulted in lower thermal delivery to the desired target than even the control case, with the notable exception of the 95-min time point. Results indicate that the nanodroplet formulation studied here can substantially increase thermal delivery at the acoustic focus while avoiding prefocal heating. In contrast, microbubbles resulted in greater prefocal heating and less heating at the target. Furthermore, nanodroplets are sufficiently stable to enhance HIFU ablation in vivo for at least 1.5 h after injection. The use of a dual-perfluorocarbon nanodroplet formulation as described herein could substantially reduce HIFU procedure times without increasing the risk of skin burns.