Dose-dependent effects of ultrasound therapy on hepatocellular carcinoma.
Dose-dependent effects of ultrasound therapy on hepatocellular carcinoma.
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DOI：
10.1109/ius46767.2020.9251660
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Sehgal CM
中科院分区：
文献类型：
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作者：
Sultan LR;D'Souza JC;Karmacharya MB;Hunt SJ;Brice AK;Gade T;Wood AK;Sehgal CM
非侵入性缺血性癌症治疗需要减少血流量，而药物输送和放射治疗需要增加肿瘤灌注以获得更好的反应。在本研究中，我们探讨了不同剂量的抗血管超声治疗（AVUS）对肝细胞癌（HCC）肿瘤血流的影响。采用二乙基亚硝胺（DEN）灌胃12周诱导22只Wistar大鼠肝细胞癌。大鼠分别接受低剂量和高剂量的AVUS治疗。低剂量组超声1瓦/cm2，持续1分钟，注射微泡0.2 mL静脉注射；高剂量组超声2瓦/cm2，持续2分钟，注射微泡0.7 mL静脉注射。假手术组不做任何治疗。超声造影检测AVUS前后肿瘤灌注情况。定量灌注测量：取各AVUS剂量的灌注指数（PI）和峰值增强（PE）。高剂量AVUS后，PE和PI分别平均下降58.1±4.9%和49.1±6.5%。相反，低剂量AVUS后，PE和PI分别比基线平均增加47.8±4.5%和20.3±2.4%。高剂量AVUS治疗可减少肿瘤灌注，这一效果可用于无创缺血性治疗。相反，低剂量治疗增加了肿瘤灌注，这可能改善药物传递或放射治疗。这些相反的治疗效果可以支持AVUS通过调节肿瘤血流在癌症治疗中的多种作用。
Non-invasive ischemic cancer therapy requires reduced blood flow whereas drug delivery and radiation therapy require increased tumor perfusion for a better response. In this study we investigate the hypothesis that different dose models of antivascular ultrasound therapy (AVUS) can have opposite effects on hepatocellular carcinoma (HCC) tumor blood flow. HCC was induced in 22 Wistar rats by ingestion of diethylnitrosamine (DEN) for 12 weeks. Rats received AVUS treatment at low and high doses. Low dose group received 1 watt/cm2 ultrasound for 1 min with 0.2 mL microbubbles injected IV. High dose group received 2 watts/cm2 for 2 min with 0.7 mL microbubbles IV. A sham group did not receive any treatment. Tumor perfusion was measured before and after AVUS with contrast-enhanced ultrasound. Quantitative perfusion measures: perfusion index (PI) and peak enhancement (PE) were obtained from each AVUS dose. After high-dose AVUS, PE and PI decreased by an average of 58.1 ± 4.9% and 49.1 ± 6.5 % respectively. Conversely, following low dose AVUS, PE and PI increased from baseline by an average of 47.8 ± 4.5% % and 20.3 ± 2.4 %, respectively. The high-dose AVUS therapy decreased tumoral perfusion, an effect that could be used for noninvasive ischemic therapy. Conversely, low-dose therapy increased tumor perfusion, which may improve drug delivery or radiation therapy. These opposite therapy effects can support multiple roles for AVUS in cancer therapy by tunable modulation of blood flow in tumors.