The impact of vaporized nanoemulsions on ultrasound-mediated ablation.
The impact of vaporized nanoemulsions on ultrasound-mediated ablation.
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DOI：
10.1186/2050-5736-1-2
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Porter TM
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文献类型：
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作者：
Zhang P;Kopechek JA;Porter TM
使用高强度聚焦超声（HIFU）消融实体瘤的临床可行性受到所需的高声压和长治疗时间的限制。超声处理过程中微泡的存在可以增加声能的吸收并加速加热。然而，在肿瘤组织内形成微泡仍然是一个挑战。已经开发了相移纳米乳液（PSNE）作为在肿瘤内产生微泡的手段。PSNE是亚微米级、脂质涂层和液态全氟化碳液滴的乳液，可以使用短（<1 ms）、高振幅（>5 MPa）的声脉冲将其蒸发成微泡。在本研究中，在体外研究了汽化相移纳米乳剂对HIFU介导的热损伤形成所需的时间和声功率的影响。使用超声处理和挤出的组合，生产具有窄的尺寸分布和低于200 nm的平均直径的含有十二碳戊烷的PSNE。将PSNE分散在含白蛋白的聚丙烯酰胺凝胶模型中进行实验测试。白蛋白在高于58°C的温度下变性并变得不透明，使得能够目视检测由变性白蛋白形成的病变。使用30个周期、3.2 MHz、声功率为6.4 W（自由场强度为4，586 W/cm 2）的脉冲，从单元件聚焦高功率换能器中蒸发PSNE。汽化脉冲后立即发出15 s连续波、3.2 MHz信号，以诱导超声介导的加热。使用相同的程序进行对照实验，而不使用汽化脉冲。通过在超声处理期间获取视频帧并对图像进行后处理以进行分析来检测损伤形成。惯性空化（IC）的宽带排放被动检测与聚焦，2 MHz的换能器。使用针形热电偶获得温度测量值。通过PSNE汽化在HIFU焦点处形成的气泡增强了HIFU介导的加热。在HIFU暴露过程中检测到的宽带发射与测量的加速加热时间相吻合，这表明IC在气泡增强加热中发挥了重要作用。在存在气泡的情况下，形成9 mm 3病变所需的声功率降低了72%，白蛋白变性开始所需的暴露时间显著减少（4 s），前提是聚丙烯酰胺凝胶中的PSNE体积分数至少为0.008%。通过将PSNE蒸发成气泡，在凝胶体模中形成损伤所需的时间或声功率显著减少。这些结果表明，PSNE可以提高HIFU介导的实体瘤热消融的效率;因此，需要进一步研究以确定气泡增强HIFU是否可能成为癌症治疗的可行选择。
The clinical feasibility of using high-intensity focused ultrasound (HIFU) for ablation of solid tumors is limited by the high acoustic pressures and long treatment times required. The presence of microbubbles during sonication can increase the absorption of acoustic energy and accelerate heating. However, formation of microbubbles within the tumor tissue remains a challenge. Phase-shift nanoemulsions (PSNE) have been developed as a means for producing microbubbles within tumors. PSNE are emulsions of submicron-sized, lipid-coated, and liquid perfluorocarbon droplets that can be vaporized into microbubbles using short (<1 ms), high-amplitude (>5 MPa) acoustic pulses. In this study, the impact of vaporized phase-shift nanoemulsions on the time and acoustic power required for HIFU-mediated thermal lesion formation was investigated in vitro. PSNE containing dodecafluoropentane were produced with narrow size distributions and mean diameters below 200 nm using a combination of sonication and extrusion. PSNE was dispersed in albumin-containing polyacrylamide gel phantoms for experimental tests. Albumin denatures and becomes opaque at temperatures above 58°C, enabling visual detection of lesions formed from denatured albumin. PSNE were vaporized using a 30-cycle, 3.2-MHz, at an acoustic power of 6.4 W (free-field intensity of 4,586 W/cm2) pulse from a single-element, focused high-power transducer. The vaporization pulse was immediately followed by a 15-s continuous wave, 3.2-MHz signal to induce ultrasound-mediated heating. Control experiments were conducted using an identical procedure without the vaporization pulse. Lesion formation was detected by acquiring video frames during sonication and post-processing the images for analysis. Broadband emissions from inertial cavitation (IC) were passively detected with a focused, 2-MHz transducer. Temperature measurements were acquired using a needle thermocouple. Bubbles formed at the HIFU focus via PSNE vaporization enhanced HIFU-mediated heating. Broadband emissions detected during HIFU exposure coincided in time with measured accelerated heating, which suggested that IC played an important role in bubble-enhanced heating. In the presence of bubbles, the acoustic power required for the formation of a 9-mm3 lesion was reduced by 72% and the exposure time required for the onset of albumin denaturation was significantly reduced (by 4 s), provided that the PSNE volume fraction in the polyacrylamide gel was at least 0.008%. The time or acoustic power required for lesion formation in gel phantoms was dramatically reduced by vaporizing PSNE into bubbles. These results suggest that PSNE may improve the efficiency of HIFU-mediated thermal ablation of solid tumors; thus, further investigation is warranted to determine whether bubble-enhanced HIFU may potentially become a viable option for cancer therapy.