二维剪切波弹性成像定量参数评价大鼠肝转移瘤抗血管生成疗效的初步研究

Preliminary Study on Antiangiogenic Treatment Effect in Rat Liver Metastasis Using Quantitative Parameters of Two-dimensional Shear Wave Elastography

目的:探讨超声二维剪切波弹性成像(Shear wave elastography,SWE)评价大鼠肝内转移瘤抗血管生成治疗疗效的价值。方法:16只建模成功的肝内单发结肠癌转移瘤裸大鼠随机分为治疗组和对照组:治疗组分别于第0天、第4天、第7天和第11天给予雷莫芦单抗(8 mg/kg,尾静脉注射),对照组注射同等剂量的生理盐水。在第0天治疗前(Day 0)和第14天(Day 14)测量肝肿瘤的大小和计算体积。第14天行SWE检查评估肿瘤和周围肝组织的弹性,测量定量弹性参数Vs肿瘤(Vs-tumor)、Vs肝脏(Vs-liver)、E肿瘤(E-tumor)和E肝脏(E-liver),计算R-Vs(=Vs-tumor/Vs-liver)和R-E(=E-tumor/E-liver)。免疫荧光染色法检测肿瘤内基质金属蛋白酶2(Matrix metalloproteinase 2,MMP2)和转化生长因子β2(Transforming growth factor β2,TGFβ2)的表达水平。结果:治疗组和对照组肿瘤大小在第0天和第14天均无显著差异(P>0.05)。Vs-liver和E-liver在治疗组和对照组之间没有显著差异(P>0.05)。治疗组Vs-tumor和E-tumor均高于对照组,但差别无统计学意义(P>0.05);治疗组R-Vs和R-E明显高于对照组,差异有统计学意义(P<0.05)。治疗组MMP2和TGFβ2的表达水平明显高于对照组(P<0.05)。结论:SWE弹性参数有望作为抗血管生成治疗后肿瘤变硬的定量参数用于评价肿瘤抗血管生成疗效。

Objective:To study value of two-dimensional shear wave elastography(SWE)in the evaluation of antiangiogenic treatment effect of single colon cancer metastasis in liver of nude rat.Methods:Sixteen nude rats with colon cancer liver single metastasis were divided randomly into treatment group and control group.The treatment group was treated with Ramucirumab(8 mg/kg,tail vein injection)on Day 0,Day 4,Day 7 and Day 11 respectively,while the control group was injected with the same dose of saline.The tumor size and volume were measured before treatment(Day 0)and after 14 days of treatment(Day 14).On Day 14,to evaluate the stiffness of tumor and surrounding liver tissue,the liver tumor and surrounding liver tissue SWE examination were performed and the elastic parameters(including Vs-tumor,Vs-liver,E-tumor and E-liver)were measured and then the R-Vs(=Vs-tumor/Vs-liver)and R-E(=E-tumor/E-liver)were calculated respectively.Finally,expression of matrix metalloproteinase 2(MMP2)and transforming growth factor β2(TGFβ2)in tumors were detected by immunofluorescence staining.Results:There was no significant difference in the tumor size between the treatment group and the control group both on Day 0 and Day 14(P>0.05).Vs-liver and E-liver had no significant difference between the treatment group and the control group(P>0.05).Both Vs-tumor and E-tumor in treatment group were mildly higher than those in the control group,however,these differences were not statistically significant(P>0.05).In the treatment group,both R-Vs and R-E were significantly higher than those in the control group(P<0.05).The expression levels of MMP2 and TGFβ2 were significantly higher than those in control group respectively(P<0.05).Conclusion:The quantitative parameters of SWE may have the potential as an image biomarker indicating tumor stiffness for evaluating the anti-angiogenic therapy efficacy.