脑胶质瘤T_1WI DCE-PWI与病理分级及VEGF表达的相关性研究
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摘要
目的:探讨磁共振T_1WI DCE-PWI技术在预测脑胶质瘤术前病理分级方面的诊断价值及与血管内皮生长因子表达的相关性。
方法:对22例脑胶质瘤患者,2例正常人进行研究。胶质瘤患者年龄13-74岁,平均30.0岁,其中男14例,女8例。按2000年WHO标准对胶质瘤进行病理分级,其中工级3例,Ⅱ级7例,Ⅲ级7例,Ⅳ级5例,幕下1例,幕上21例。先行常规MR检查,再行DCE-PWI扫描,最后行常规增强扫描。DCE-PWI使用标准头部线圈,Turbo-FLASH序列采集图像(TR/TE 199/1.05ms;TI 100ms;层厚6mm;层距1.2mm;翻转角20~0;矩阵128×96；视野260×210)。选取病灶最大层面为中间层面,时间分辨率为4秒,共扫描90个时相,成像时间为360秒。对比剂为钆喷替酸葡甲胺(Gd-DTPA)注射液,剂量为0.4ml/kg,由高压注射泵经肘前静脉注药,速率为4 ml/s。注药时机选择为扫描过程中第6个时相,对比剂团注结束后再注入同等容积生理盐水冲洗导管。采用Tofts-kermode两腔室模型分析数据,用NORDICIC软件对原始灌注成像数据进行后处理,构建K~(trans)、K_(ep)、Ve值的参数图,参照T1增强图像,将感兴趣区设置在肿瘤K~(trans)值最大的部位,计算出三者的平均值。患者均在检查后2周内手术,术后获取肿瘤标本使用二步法行VEGF免疫组化检查。一例高级别胶质瘤标本行电镜检查。
结果:脑胶质瘤各渗透参数结果示正常脑组织K~(trans)值低于胶质瘤患者,大约为Ⅰ级胶质瘤的1/10。Ⅲ-Ⅳ胶质瘤的K~(trans),K_(ep)及V_e值明显高于Ⅰ-Ⅱ级,高级别胶质瘤K~(trans)及K_(ep)值较低级别胶质瘤增加约4倍。K~(trans)在Ⅱ与Ⅲ间有差异,在级别Ⅰ与Ⅱ,Ⅲ与Ⅳ间无差异。K~(trans),Kep及Ve与肿瘤级别相关性采用spearman秩相关分析,K~(trans)值的相关系数r=0.770(p<0.001)最大,表明K~(trans)值与肿瘤级别存在正相关,且关系最密切。区别低级别和高级别肿瘤的K~(trans)的最佳临界点(阈值)=0.85,特异度=0.90,灵敏度=0.92。VEGF表达与K~(trans)值spearman秩相关分析,r=0.551(p=0.008)。VEGF免疫组化示Ⅰ,Ⅱ级以阴性表达为主,Ⅲ级阳性表达率为85.72%,Ⅳ级阳性表达率为100%。经秩和检验,χ~2值为12.647,经spearman秩相关分析,r=0.706(p<0.001)。电镜示高级别胶质瘤内皮细胞间隙增宽,基底膜有断裂。
结论:T_1WI DCE-PWI是一种无创的定量分析脑胶质瘤微血管渗透情况的良好方法,特别是渗透参数K~(trans)值与胶质瘤的病理分级密切相关,可定量评价脑胶质瘤微血管的生成情况,为胶质瘤的恶性程度分级提供新的参考指标,鉴别高、低级别胶质瘤的阂值为0.85(特异度=0.90,灵敏度=0.92)。K~(trans)值与VEGF表达存在正相关性。
Purpose To investigate the diagnostic value of magnetic resonance T1-weighted DCE-PWI in predicting the pathological grade of glioma in the preoperative setting, and its relationship with tumor grade and vascular endothelial growth factor expression.
Method 22 patients with glioma and 2 normal persons were investigated. Patients were aged 13-74 years, average 30.0 years, 14 cases were male and 8 were females. According to WHO criteria in 2000 for postoperative pathological classification of gliomas, three cases were of gradeⅠ, 7 cases gradeⅡ, 7 cases gradeⅢ, 5 cases gradeⅣ. One of the lesions was infratentorial while the others were supratentorial. Conventional MR examination was first carried out in all patients, followed by DCE-PWI scan, and then routine enhancement scan. DCE-PWI scanning was done using a standard head coil with Turbo-FLASH sequence with the following parameters: TR / TE 199/1.05ms; TI 100ms; slice thickness 6mm; slice distance 1.2mm; flip angle 20~0; matrix 128×96; FOV 260×210. The intermediate level was selected as the largest level of glioma, and the time resolution was 4 seconds, a total of 90 time phases were scanned with an imaging time of 360 seconds. Gd-DTPA was injected from an antecubital vein with a dose of 0.4 ml/kg, using a high-pressure injection pump, at a rate of 4 ml/s. Contrast was injected during the sixth phase followed by administration of the same volume of normal saline to flush the catheter. Data was analyzed using Tofts and Kermode two-compartment pharmacokinetic model and the NORDICIC software to build K~(trans)、K_(ep) and V_e maps. Then, with T1 enhanced images as reference, the areas of greatest value of K~(trans) in the tumor were chosen as regions of interest to calculate the average of the three parameters. Patients were operated within two weeks of the exam. VEGF immunohistochemical analysis was carried out after obtaining tumor samples using two-step method. One case of high-grade glioma was examined under electron microscope.
Result The results showed that the permeability parameter K~(trans) values of normal brain tissue was lower than glioma patients, about one tenth that of gradeⅠgliomas. K~(trans), K_(ep) and V_e of gradeⅢ-Ⅳgliomas were significantly higher than those of gradeⅠ-Ⅱ. K~(trans) and Kep of high-grade gliomas were increased four times more than in low-grade ones. K~(trans) values were different between gradesⅡandⅢ, but there was no difference between gradesⅠandⅡ, and between gradesⅢandⅣ. Correlation of K~(trans), K_(ep) and Ve with tumor grade was analyzed using spearman rank correlation. Correlation coefficient of K~(trans) was greater (r=0.770, p<0.001) showing K~(trans) values was positively correlated with tumor grade with a close relationship. In differentiating between low-grade and high-grade tumors the most appropriate K~(trans) critical point ( threshold value) was 0.85 with specificity = 0.90 and sensitivity = 0.92. Using spearman rank correlation analysis of VEGF expression and K~(trans) values, r = 0.551 (p = 0.008). Immunohistochemical analysis showed that VEGF expression in gradesⅠandⅡwere mainly negative, in gradeⅢthere was a positive rate of 85.72%, in gradeⅣpositive rate was 100%. Rank sum test gaveχ~2 of 12.647 (p = 0.005). With spearman rank correlation analysis, r = 0.706 (p <0.001). Electronmicroscopy showed that in high grade glioma there was an increase in theextracellular space of endothelial cells, with a disrupted basementmembrane.
Conclusion T_1WI DCE-PWI is a good non-invasive quantitativemethod of analysis of microvascular permeability of glioma, especially the permeability parameter K~(trans) value being closely related to the pathological grade of glioma. It can be used for the quantitative evaluation of microangiogenesis in glioma and provide a new reference for the degree of glioma malignancy. The threshold value for the differentiation between high- and low-grade glioma was 0.85 (specificity = 0.90, sensitivity = 0.92). There was a positive correlation between VEGF expression and K~(trans) value.
方法:对22例脑胶质瘤患者,2例正常人进行研究。胶质瘤患者年龄13-74岁,平均30.0岁,其中男14例,女8例。按2000年WHO标准对胶质瘤进行病理分级,其中工级3例,Ⅱ级7例,Ⅲ级7例,Ⅳ级5例,幕下1例,幕上21例。先行常规MR检查,再行DCE-PWI扫描,最后行常规增强扫描。DCE-PWI使用标准头部线圈,Turbo-FLASH序列采集图像(TR/TE 199/1.05ms;TI 100ms;层厚6mm;层距1.2mm;翻转角20~0;矩阵128×96；视野260×210)。选取病灶最大层面为中间层面,时间分辨率为4秒,共扫描90个时相,成像时间为360秒。对比剂为钆喷替酸葡甲胺(Gd-DTPA)注射液,剂量为0.4ml/kg,由高压注射泵经肘前静脉注药,速率为4 ml/s。注药时机选择为扫描过程中第6个时相,对比剂团注结束后再注入同等容积生理盐水冲洗导管。采用Tofts-kermode两腔室模型分析数据,用NORDICIC软件对原始灌注成像数据进行后处理,构建K~(trans)、K_(ep)、Ve值的参数图,参照T1增强图像,将感兴趣区设置在肿瘤K~(trans)值最大的部位,计算出三者的平均值。患者均在检查后2周内手术,术后获取肿瘤标本使用二步法行VEGF免疫组化检查。一例高级别胶质瘤标本行电镜检查。
结果:脑胶质瘤各渗透参数结果示正常脑组织K~(trans)值低于胶质瘤患者,大约为Ⅰ级胶质瘤的1/10。Ⅲ-Ⅳ胶质瘤的K~(trans),K_(ep)及V_e值明显高于Ⅰ-Ⅱ级,高级别胶质瘤K~(trans)及K_(ep)值较低级别胶质瘤增加约4倍。K~(trans)在Ⅱ与Ⅲ间有差异,在级别Ⅰ与Ⅱ,Ⅲ与Ⅳ间无差异。K~(trans),Kep及Ve与肿瘤级别相关性采用spearman秩相关分析,K~(trans)值的相关系数r=0.770(p<0.001)最大,表明K~(trans)值与肿瘤级别存在正相关,且关系最密切。区别低级别和高级别肿瘤的K~(trans)的最佳临界点(阈值)=0.85,特异度=0.90,灵敏度=0.92。VEGF表达与K~(trans)值spearman秩相关分析,r=0.551(p=0.008)。VEGF免疫组化示Ⅰ,Ⅱ级以阴性表达为主,Ⅲ级阳性表达率为85.72%,Ⅳ级阳性表达率为100%。经秩和检验,χ~2值为12.647,经spearman秩相关分析,r=0.706(p<0.001)。电镜示高级别胶质瘤内皮细胞间隙增宽,基底膜有断裂。
结论:T_1WI DCE-PWI是一种无创的定量分析脑胶质瘤微血管渗透情况的良好方法,特别是渗透参数K~(trans)值与胶质瘤的病理分级密切相关,可定量评价脑胶质瘤微血管的生成情况,为胶质瘤的恶性程度分级提供新的参考指标,鉴别高、低级别胶质瘤的阂值为0.85(特异度=0.90,灵敏度=0.92)。K~(trans)值与VEGF表达存在正相关性。
Purpose To investigate the diagnostic value of magnetic resonance T1-weighted DCE-PWI in predicting the pathological grade of glioma in the preoperative setting, and its relationship with tumor grade and vascular endothelial growth factor expression.
Method 22 patients with glioma and 2 normal persons were investigated. Patients were aged 13-74 years, average 30.0 years, 14 cases were male and 8 were females. According to WHO criteria in 2000 for postoperative pathological classification of gliomas, three cases were of gradeⅠ, 7 cases gradeⅡ, 7 cases gradeⅢ, 5 cases gradeⅣ. One of the lesions was infratentorial while the others were supratentorial. Conventional MR examination was first carried out in all patients, followed by DCE-PWI scan, and then routine enhancement scan. DCE-PWI scanning was done using a standard head coil with Turbo-FLASH sequence with the following parameters: TR / TE 199/1.05ms; TI 100ms; slice thickness 6mm; slice distance 1.2mm; flip angle 20~0; matrix 128×96; FOV 260×210. The intermediate level was selected as the largest level of glioma, and the time resolution was 4 seconds, a total of 90 time phases were scanned with an imaging time of 360 seconds. Gd-DTPA was injected from an antecubital vein with a dose of 0.4 ml/kg, using a high-pressure injection pump, at a rate of 4 ml/s. Contrast was injected during the sixth phase followed by administration of the same volume of normal saline to flush the catheter. Data was analyzed using Tofts and Kermode two-compartment pharmacokinetic model and the NORDICIC software to build K~(trans)、K_(ep) and V_e maps. Then, with T1 enhanced images as reference, the areas of greatest value of K~(trans) in the tumor were chosen as regions of interest to calculate the average of the three parameters. Patients were operated within two weeks of the exam. VEGF immunohistochemical analysis was carried out after obtaining tumor samples using two-step method. One case of high-grade glioma was examined under electron microscope.
Result The results showed that the permeability parameter K~(trans) values of normal brain tissue was lower than glioma patients, about one tenth that of gradeⅠgliomas. K~(trans), K_(ep) and V_e of gradeⅢ-Ⅳgliomas were significantly higher than those of gradeⅠ-Ⅱ. K~(trans) and Kep of high-grade gliomas were increased four times more than in low-grade ones. K~(trans) values were different between gradesⅡandⅢ, but there was no difference between gradesⅠandⅡ, and between gradesⅢandⅣ. Correlation of K~(trans), K_(ep) and Ve with tumor grade was analyzed using spearman rank correlation. Correlation coefficient of K~(trans) was greater (r=0.770, p<0.001) showing K~(trans) values was positively correlated with tumor grade with a close relationship. In differentiating between low-grade and high-grade tumors the most appropriate K~(trans) critical point ( threshold value) was 0.85 with specificity = 0.90 and sensitivity = 0.92. Using spearman rank correlation analysis of VEGF expression and K~(trans) values, r = 0.551 (p = 0.008). Immunohistochemical analysis showed that VEGF expression in gradesⅠandⅡwere mainly negative, in gradeⅢthere was a positive rate of 85.72%, in gradeⅣpositive rate was 100%. Rank sum test gaveχ~2 of 12.647 (p = 0.005). With spearman rank correlation analysis, r = 0.706 (p <0.001). Electronmicroscopy showed that in high grade glioma there was an increase in theextracellular space of endothelial cells, with a disrupted basementmembrane.
Conclusion T_1WI DCE-PWI is a good non-invasive quantitativemethod of analysis of microvascular permeability of glioma, especially the permeability parameter K~(trans) value being closely related to the pathological grade of glioma. It can be used for the quantitative evaluation of microangiogenesis in glioma and provide a new reference for the degree of glioma malignancy. The threshold value for the differentiation between high- and low-grade glioma was 0.85 (specificity = 0.90, sensitivity = 0.92). There was a positive correlation between VEGF expression and K~(trans) value.
引文
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