动态对比增强MRI评价大鼠C6胶质瘤肿瘤边缘新生血管的实验研究

Tumor-associated Neovascularization in C6 Glioma Tumor Margin Measured with Dynamic Contrast-enhanced MRI

目的研究大鼠C6胶质瘤肿瘤边缘区肿瘤新生血管的方式,探讨动态对比增强MRI(DCE-MRI)评价胶质瘤肿瘤新生血管的可能性。材料与方法清洁级SD大鼠24只,建立C6胶质瘤原位移植模型,移植后4 d、8 d、12 d、16 d、20 d、24 d行常规及DCE-MRI扫描。取大鼠脑组织行病理和免疫组化检查,观察肿瘤边缘区肿瘤细胞及肿瘤新生血管。结果距肿瘤组织边缘(257.658±53.663)μm范围内观察到血管共生现象,各观察点血管共生指数差异有统计学意义(P<0.01)。增殖细胞核抗原、基质金属蛋白酶-2染色示共生血管周围肿瘤细胞为强阳性。α-平滑肌肌动蛋白、细胞黏合素C染色于移植第16天发现共生血管的退化及转化现象。DCE-MRI示移植第12天、第16天肿瘤边缘区转运常数(Ktrans)、反流速率常数(Kep)明显高于另外4个观察时间点(P<0.05),且与血管共生指数呈负相关(r=-0.9243、-0.8347,P<0.05),血浆容积分数差异无统计学意义(P>0.05)。结论 C6胶质瘤在肿瘤边缘区肿瘤新生血管类型为血管共生;DCE-MRI定量参数Ktrans、Kep与血管共生指数有较好的相关性,有望成为有效检测胶质瘤新生血管的影像学标志物。

PurposeTo investigate the formation of neovascularization using dynamic contrast-enhanced MRI （DCE-MRI） in C6 glioma margin in rats, and to explore its utility.Materials and MethodsC6 glioma model was created in 24 SD rats. Routine and DCE-MRI was performed 4 days, 8 days, 12 days, 16 days, 20 days and 24 days after transplantation. Pathology and immunohistochemistry exams were also obtained to evaluate marginal tumor cells and neovascularization.ResultsNeovascularization was observed in C6 glioma margin within （257.658±53.663）μm range. Vessel co-option index difference was statistically significant （P〈0.01）. Tumor cells surrounding the co-opted vessels were strongly positive on proliferating cell nuclear antigen and matrix metallopeptidase 2 staining. Vessel co-option regression and transformation were observed on day 16 on Tenascin-C andα smooth muscle actin staining. For DCE-MRI analysis, Ktrans and Kep were higher on day 12 and 16 （P〈0.05）. There was significant negative correlation between co-option index and Ktrans （r=-0.9243 and-0.8347,P〈0.05）. Vp showed no statistically significant difference at all time points （P〉0.05）.Conclusion The neovascularization in tumor margin demonstrates vessel co-option. DCE-MRI parameters Ktrans and Kep are negatively correlated with co-option index, indicating that Ktrans and Kep could be a well-defined imaging-based biomarker for glioma neovascularization.