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目的采用原位移植脑胶质瘤模型,探讨MR灌注加权成像(perfusion-weighted imaging,PWI)在评估肿瘤微血管生成的应用价值。方法 15只健康清洁级SD大鼠脑原位移植C6胶质瘤细胞建立胶质瘤模型,移植后的3天、7天、10天、15天、20天和25天行常规MRI及PWI,每个时间点扫描完毕后经4%多聚甲醛左心室灌注获取脑组织标本进行相关病理分析。结果移植后10天在MR T2WI上观察到高信号肿瘤形成,肿瘤在15～20天时间段内生长迅速,4个观察点(10天、15天、20天、25天)的肿瘤体积相比差异有显著统计学意义(P<0.01)。胶质瘤生长区域在PWI上显示为高灌注,并且不同时间点间的相对脑血容量(rCBV)值差异有统计学意义(P<0.05)。血管染色显示肿瘤微血管多集中在肿瘤周边,不同瘤龄的肿瘤微血管密度(microvessel density,MVD)差异显著(P<0.01)。血管内皮生长因子(VEGF)染色阳性细胞见胞质内棕色或棕褐色颗粒,不同时间点脑组织标本的VEGF阳性细胞数比较差异有统计学意义(P<0.05)。不同检测时间点的rCBV和MVD值以及VEGF阳性细胞数之间均存在正相关。结论 rCBV值能较准确地反映肿瘤微血管的动态变化,与病理指标MVD以及VEGF之间存在较好的相关性,可以作为无创性指标术前评估胶质瘤微血管的生成情况。
Objective To evaluate the value of MR perfusion-weighted imaging (PWI) in the evaluation of tumor angiogenesis by in situ grafting of glioma model. Methods Fifty healthy SD rats were implanted with C6 glioma cells in situ to establish a glioma model. Conventional MRI and PWI were performed on days 3, 7, 10, 15, 20 and 25 after transplantation. After scanning at each time point, 4% paraformaldehyde left ventricular perfusion was used to obtain brain tissue samples for pathological analysis. Results High-signal tumor formation was observed on MR T2WI 10 days after transplantation. The tumors grew rapidly over a 15-20 day period. Tumor volumes at 4 observation sites (10 days, 15 days, 20 days, 25 days) The difference was statistically significant (P <0.01). The glioma growth area showed hyperperfusion on PWI, and the relative cerebral blood volume (rCBV) value had significant difference between different time points (P <0.05). Vascular staining showed that the tumor microvessels were mostly located in the periphery of the tumor. The difference of tumor microvessel density (MVD) between different tumor types was significant (P <0.01). Vascular endothelial growth factor (VEGF) -positive cells were observed in the cytoplasm of brown or tan particles, at different time points in the brain tissue samples of VEGF-positive cells were significantly different (P <0.05). There was a positive correlation between rCBV, MVD and VEGF positive cells at different time points. Conclusions The rCBV value can reflect the dynamic changes of tumor microvessels more accurately and has a good correlation with pathological MVD and VEGF. It can be used as a noninvasive index to evaluate the formation of glioma microvessels preoperatively.