Inhibition of glioma growth by microbubble activation in a subcutaneous model using low duty cycle ultrasound without significant heating.
Inhibition of glioma growth by microbubble activation in a subcutaneous model using low duty cycle ultrasound without significant heating.
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DOI：
10.3171/2010.11.jns101201
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发表时间：
2011-06
影响因子：
4.1
通讯作者：
Price RJ
中科院分区：
文献类型：
--
作者：
Burke CW;Klibanov AL;Sheehan JP;Price RJ
在这项研究中，作者试图确定脉冲低占空比超声破坏微泡（MB）是否可用于通过非热微血管消融减少脑肿瘤灌注和生长。使用皮下接种C6神经胶质瘤细胞的C57 BLJ 6/Rag-1小鼠的研究得到了机构动物护理和使用委员会的批准。静脉注射微泡，每5秒对肿瘤施加1 MHz超声，占空比变化，持续60分钟。在治疗期间，量化肿瘤加热。治疗后，测量肿瘤生长、血流动力学、坏死和凋亡。治疗后肿瘤血流量立即显著减少，治疗后流量范围为治疗前流量的36%（0.00002占空比）至4%（0.01占空比）。治疗后7天，所有治疗组的肿瘤坏死和凋亡均显著增加，而与未治疗的肿瘤相比，超声占空比为0.005和0.01的治疗分别抑制了63%和75%的肿瘤生长。虽然观察到肿瘤内温度的适度占空比依赖性增加，但不太可能发生热组织消融。在皮下C6神经胶质瘤模型中，用低占空比1 MHz超声破坏MB可用于显著抑制生长，而不会显著加热肿瘤组织。这些结果可能对经颅高强度聚焦超声治疗不适合热消融的脑肿瘤的发展有影响。
In this study, the authors sought determine whether microbubble (MB) destruction with pulsed low duty cycle ultrasound can be used to reduce brain tumor perfusion and growth through nonthermal microvascular ablation. Studies using C57BLJ6/Rag-1 mice inoculated subcutaneously with C6 glioma cells were approved by the institutional animal care and use committee. Microbubbles were injected intravenously, and 1 MHz ultrasound was applied with varying duty cycles to the tumor every 5 seconds for 60 minutes. During treatment, tumor heating was quantified. Following treatment, tumor growth, hemodynamics, necrosis, and apoptosis were measured. Tumor blood flow was significantly reduced immediately after treatment, with posttreatment flow ranging from 36% (0.00002 duty cycle) to 4% (0.01 duty cycle) of pretreatment flow. Seven days after treatment, tumor necrosis and apoptosis were significantly increased in all treatment groups, while treatment with ultrasound duty cycles of 0.005 and 0.01 inhibited tumor growth by 63% and 75%, respectively, compared with untreated tumors. While a modest duty cycle–dependent increase in intratumor temperature was observed, it is unlikely that thermal tissue ablation occurred. In a subcutaneous C6 glioma model, MB destruction with low–duty cycle 1-MHz ultrasound can be used to markedly inhibit growth, without substantial tumor tissue heating. These results may have a bearing on the development of transcranial high-intensity focused ultrasound treatments for brain tumors that are not amenable to thermal ablation.