融合基因治疗大鼠C6胶质瘤的MR扩散加权成像研究

目的 观察常规MR结合扩散加权成像(DWI)在胶质瘤治疗早期疗效的作用.方法 雄性Wistar大鼠50只通过脑立体定向仪于右侧尾状核接种X6胶质瘤细胞10μl(5×105个细胞).于接种后第1周MR检查确认有肿瘤生长后再将其分为对照组和治疗组,其中治疗组大鼠采用上述接种方法于颅内相同位置注入107空斑形成单位的携带血管抑素与内皮抑素融合基因的重组单纯疱疹病毒.分别于接种后第1、2、3周行MR常规及DWI检查,并于每次检查结束后各组分别有2只(第1周)、8只(第2周)及剩余全部大鼠(第3周)安乐死后进行病理检查.对照组与治疗组间不同时间肿瘤体积、表观扩散系数(ADC)值、相同时间不同区域间ADC值的差异比较进行t检验及秩和检验.结果 共43只大鼠见肿瘤生长,成瘤率为86%.对照组与治疗组大鼠C6胶质瘤的体积在第2周时分别为90.60及91.64 mm3,2组间肿瘤体积差异无统计学意义(Z=-0.14,P＞0.05);第3周时2组大鼠肿瘤体积分别为156.64和29.64mm3,两者差异有统计学意义(Z=-3.45,P＜0.01).第2周时治疗组与对照组肿瘤中心的AI)C值分别为(1.20±0.25)×10-3、(0.99±0.08)×10-3 mm2/s,肿瘤边缘的ADC值分别为(1.00±0.25)×10=-3、(0.83±0.12)×10-3 mm2/s,治疗组不同区域的ADC值均高于对照组(t值分别为-4.11,-2.62,P值均＜0.05).第3周时治疗组与对照组肿瘤中心的ADC值分别为(0.92±0.21)×10-3、(0.99±0.09)×10-3 mm2/s,肿瘤边缘的ADC值分别为(0.8l±0.19)×10-3、(0.78±0.11)×10-3 mm2/s,不同区域2组间比较差异无统计学意义(t值分别为0.82,-0.46,P值均＞0.05).结论 DWI能有效地反映大鼠C6脑胶质瘤的组织微观情况;可以早于肿瘤体积发生变化前发现治疗对肿瘤局部细胞状态的影响,从而在肿瘤的疗效观察和预测方面将有更大的发展空间和应用价值.

Investigating effect of fusion gene therapy by MR diffusion-weighted imaging in a rat C6 glioma model

Objective To evaluate the use of diffusion-weighted imaging(DWI)for early detection of tumor response to Angiostatin-Endostatin(Statin-AE)fusion gene therapy in a rat C6 glioma model.Methods Fifty male wistar rats with C6 tumor cells implanted into the striatum were examined by a 3.0T MR scanner,then the rats beating tmors were divided into two groups,treatment group and control group.Rats in the treatment group received 107 plaque forming unit(pfu)recombinant herps simplex viral (R-HSV)mediated Statin-AE fusion gene therapy on day 7,and then the tumors were conformed on MRI.Conventional MR and DWI examination were acquired on 1,2,3 weeks after implantation with a 5-inch surface coil.Two(1 w),eight(2 w)and all the residual rats(3 w)of each group were sacrificed to perform the histopathological examination after each MBI examination.Pretreatment and post treatment tumor volulnes and apparent diffusion coefficient(ADC)values were calculated.Rank sum test and t test were employed for statistical analysis.Results On MRI,43 rats demonstrated tumors on day 7 with a successful rate of 86%,On week 2,the tumor volumes of the controh and treatment group were 90.6 and 91.64 mm3,with no significant difference(Z=-0.14,P＞0.05).On week 3,the tumor volumes of the controls and treatment group were 156.64 and 29.64 mm3,and a significant difference was observed(Z=-3.45,P＜0.01).On week 2.the ADC values of the tumor centers of the treatment group and the control group were (1.20±0.25)×10-3 and(0.99±0.08)×10-3 mm2/s,and the values of the tumor peripheral parts of the two groups were(1.00±0.25)×10-3 and(0.83±0.12)×10-3mm2/s,the ADC values of both tumor centers and peripheral parts of the treatment group were significantly higher than those of the control group (t=-0.82 and-0.46,P＜0.05).On week 3,the ADC values of the tumor centers of the treatment group and the control group were(0.92±0.21)× 10-3 and(0.99±0.09)×10-3mm2/s,and the values of the tumor peripheral parts of the two groups were(0.81±0.19)×10-3 and(0.78±0.11)×10-3 mm2/a,there were no statisfical difference between the two groups(t=0.82,and-0.46,P＜0.05).HE stained slices showed more prominent tumor interstifial edenla.swelling and death of tumor cells in the treated rats than the controls.Conclusions Combination of conventional MRI and DWI can be powerful to monitor tumor progression and therapy effecL Conventional MRI showed that the therapy slow the tumor progression in size while DWI demonstrated the tumor response even earlier than size change.DWI has potential use forthe detection of early response to antiangiogenic gene therapy.