Application of IVIM-DWI in Detecting the Tumor Vasculogenic Mimicry Under Antiangiogenesis Combined With Oxaliplatin Treatment
Application of IVIM-DWI in Detecting the Tumor Vasculogenic Mimicry Under Antiangiogenesis Combined With Oxaliplatin Treatment
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DOI：
10.3389/fonc.2020.01376
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发表时间：
2020-08-18
影响因子：
4.7
通讯作者：
Xie, Chuanmiao
中科院分区：
文献类型：
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作者：
Liang, Jianye;Li, Zhipeng;Xie, Chuanmiao
目的：本研究旨在使用体素内非相干运动弥散加权成像（IVIM-DWI）检测抗血管治疗期间血管正常化的时间窗。同时评价肿瘤的侵袭性和血管生成拟态，并采用IVIM-DWI对血管生成抑制剂联合常规化疗的疗效进行综合评价。材料与方法：将HCT 116细胞接种于BALB/C裸鼠右侧皮下，建立结肠癌移植瘤模型。将32只荷瘤小鼠随机分为4组，分别腹腔注射生理盐水（A组或对照组）、贝伐珠单抗（B组）、奥沙利铂单药治疗（C组）和奥沙利铂联合贝伐珠单抗（D组）。在治疗后第0、3、6、9、12和15天进行IVIM-DWI。另取51只荷瘤小鼠进行病理学检查。采用α-平滑肌肌动蛋白（SMA）和CD31双染、过碘酸-希夫（PAS）和CD31双染、苏木精-伊红（HE）、Ki-67和E-cadherin染色。观察肿瘤生长情况及各项指标的动态变化。结果：D组肿瘤体积最小，抑瘤率最高。抗血管生成治疗后，微血管密度显著降低，但伴随着血管生成拟态增加。奥沙利铂治疗逆转了这一趋势。贝伐单抗治疗后3-12 d，血管成熟指数与D * 和f-值呈相似趋势，从0~9 d缓慢上升，然后短暂下降，D-值与血管生成拟态和Ki-67显著相关，而D * 和f-值与微血管密度和上皮-间质转化指标E-cadherin呈正相关。结论：奥沙利铂对血管生成拟态有抑制作用。IVIM-DWI可检测到贝伐单抗通过短暂时间内血管正常化增强肿瘤化疗效果，D * 和f值可预测肿瘤侵袭性，而D上级可反映抗肿瘤治疗过程中血管生成拟态和Ki-67表达。
Objectives:This study aimed to detect the time window of vascular normalization during anti-vascular treatment using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). Simultaneously, we evaluated the tumor invasiveness and vasculogenic mimicry and performed synthetic assessment of treatment efficacy of angiogenesis inhibitor combined with conventional chemotherapy using IVIM-DWI. Materials and Methods:HCT116 cells were subcutaneously administered into the right flank of BALB/C nude mice to build a colon cancer xenograft model. Thirty-two tumor-bearing mice were randomly divided into four groups and intraperitoneally administered with normal saline (Group A or control group), bevacizumab (Group B), oxaliplatin monotherapy (Group C), and oxaliplatin combined with bevacizumab (Group D). The IVIM-DWI was performed on days 0, 3, 6, 9, 12, and 15 after the treatments. Another 51 tumor-bearing mice were included in the pathological examinations. alpha-Smooth muscle actin (SMA) and CD31 double-staining, periodic acid-Schiff (PAS) and CD31 double-staining, hematoxylin and eosin (HE), Ki-67, and E-cadherin staining were performed. The tumor growth and dynamic change of each parameter were noted. Results:The mice in Group D manifested the smallest tumor volume and highest tumor inhibition rate. Microvessel density was significantly decreased but accompanied by increased vasculogenic mimicry after antiangiogenic treatment. The trend was reversed by oxaliplatin treatment. Treated with bevacizumab, the vessel maturity index shared a similar trend withD*andf-values during days 3-12, which slowly increased from days 0 to 9 and then decreased briefly.D-value significantly correlated with vasculogenic mimicry and Ki-67, whileD*andf-values showed positive correlations with microvessel density and E-cadherin, an indicator of epithelial-mesenchymal transition. Conclusion:Oxaliplatin performed an inhibited effect on vasculogenic mimicry. Bevacizumab can enhance the tumor chemotherapy through vascular normalization within a transient time period, which can be detected by IVIM-DWI.D*andf-values are able to predict the tumor invasiveness whileDis superior in reflecting vasculogenic mimicry and Ki-67 expression during antitumor treatment.