DCE-MRI定量参数与脑胶质瘤Ki-67标记指数的相关性分析
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摘要
目的:探讨磁共振动态对比增强扫描(DCE-MRI)定量参数预测脑胶质瘤细胞增殖的价值。方法:回顾性分析经病理证实的40例脑胶质瘤患者的病例资料,其中WHOⅡ～Ⅳ级胶质分别为18、7和15例。所有肿瘤术后均行Ki-67指数免疫组化检测,所有患者在术前行常规平扫及DCE-MRI扫描,经后处理软件分析获得肿瘤的DCE-MRI定量参数值,包括容积转运常数(K_(trans))、血管外细胞外容积分数(V_e)、速率常数(K_(ep))和血浆容积分数(V_p)共四项渗透相关参数,及脑血流量(CBF)和脑血容量(CBV)两项灌注参数,计算相对脑血流量(rCBF)和相对脑血容量(rCBV)。采用两独立样本t检验比较各参数在高级别和低级别胶质瘤之间的差异,并对各参数与Ki-67指数进行Spearman相关性分析。结果:高级别胶质瘤组的各项DCE-MRI参数值及Ki-67指数均高于低级别胶质瘤组,差异在两组间有统计学意义(P<0.05);K_(trans)、V_e、rCBV和rCBF值与Ki-67指数呈正相关(r=0.742、0.636、0.642、0.633,P<0.001),K_(ep)值与Ki-67指数亦呈正相关(r=0.490,P=0.002),V_p值与Ki-67指数间无显著相关性(r=0.238,P=0.145)。结论:DCE-MRI定量参数均可评估胶质瘤的病理分级,其中K_(trans)、V_e、K_(ep)、rCBV和rCBF值与Ki-67指数呈正相关,可作为术前评估胶质瘤细胞增殖程度的指标。
Objective:The purpose of this study was to explore the value of quantitative parameters of dynamic contrast-enhanced MRI for tumor cell proliferation in glioma.Methods:The medical data of 40 patients with glioma(18 with WHO-Ⅱ grade,7 with WHO-Ⅲ grade and 15 with WHO-Ⅳgrade)and the Ki-67 labeling index obtained by immunohistochemical detection in post-operative pathology were retrospectively analyzed.All patients were scanned at a 3.0 T MRI system using T1 WI,T2 WI,T2-FLAIR and dynamic contrast enhanced(DCE)sequence.DCE-MRI parameters,including volume transfer constant(K_(trans)),fractional volume of the extravascular to extracellular space(V_e),fractional volume of the intravascular compartment(V_p),the rate constant(K_(ep)),cerebral blood flow(CBF)and cerebral blood volume(CBV),were measured and analyzed in different grades.Relative CBV(rCBV)and CBF(rCBF)were calculated based on normalized mirror regions.T-test of two independent samples was used to analyze the statistical difference of each parameter mentioned above between different grades.The correlation of DCE-MRI quantitative parameters with Ki-67 labeling index(LI)were analyzed using the Spearman correlation test.Results:All quantitative parameters from DCE-MRI and Ki-67 LI were statistically different between the high-grade group and low-grade group(P<0.05).The K_(trans),V_e,rCBV and rCBF values associated with Ki-67 LI(r=0.742,0.636,0.642 and 0.633,P<0.001).The K_(ep)value was also associated with Ki-67 LI(r=0.490,P=0.002).The V_p value was not associated with Ki-67 LI(r=0.238,P=0.145).Conclusion:All the quantitative parameters from DCE-MRI are useful to differentiate low-grade from high-grade gliomas.The K_(trans),V_e,K_(ep),rCBV and rCBF values significantly correlated with Ki-67 LI respectively,thus can be used as non-invasive indexes for prediction of cell proliferation in glioma before surgery.
Objective:The purpose of this study was to explore the value of quantitative parameters of dynamic contrast-enhanced MRI for tumor cell proliferation in glioma.Methods:The medical data of 40 patients with glioma(18 with WHO-Ⅱ grade,7 with WHO-Ⅲ grade and 15 with WHO-Ⅳgrade)and the Ki-67 labeling index obtained by immunohistochemical detection in post-operative pathology were retrospectively analyzed.All patients were scanned at a 3.0 T MRI system using T1 WI,T2 WI,T2-FLAIR and dynamic contrast enhanced(DCE)sequence.DCE-MRI parameters,including volume transfer constant(K_(trans)),fractional volume of the extravascular to extracellular space(V_e),fractional volume of the intravascular compartment(V_p),the rate constant(K_(ep)),cerebral blood flow(CBF)and cerebral blood volume(CBV),were measured and analyzed in different grades.Relative CBV(rCBV)and CBF(rCBF)were calculated based on normalized mirror regions.T-test of two independent samples was used to analyze the statistical difference of each parameter mentioned above between different grades.The correlation of DCE-MRI quantitative parameters with Ki-67 labeling index(LI)were analyzed using the Spearman correlation test.Results:All quantitative parameters from DCE-MRI and Ki-67 LI were statistically different between the high-grade group and low-grade group(P<0.05).The K_(trans),V_e,rCBV and rCBF values associated with Ki-67 LI(r=0.742,0.636,0.642 and 0.633,P<0.001).The K_(ep)value was also associated with Ki-67 LI(r=0.490,P=0.002).The V_p value was not associated with Ki-67 LI(r=0.238,P=0.145).Conclusion:All the quantitative parameters from DCE-MRI are useful to differentiate low-grade from high-grade gliomas.The K_(trans),V_e,K_(ep),rCBV and rCBF values significantly correlated with Ki-67 LI respectively,thus can be used as non-invasive indexes for prediction of cell proliferation in glioma before surgery.
引文
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[12]Seow P,Wong JHD,Ahmad-Annuar A,et al.Quantitative magnetic resonance imaging and radiogenomic biomarkers for glioma characterisation:a systematic review[J/OL].Br J Radiol,2018,91(1092):20170930.DOI:10.1259/bjr.20170930.
[13]Chen WJ,He DS,Tang RX,et al.Ki-67is a valuable prognostic factor in gliomas:evidence from a systematic review and meta-analysis[J].Asian Pac J Cancer Prev,2015,16(2):411-420.
[14]李欣蓓,宋玉坤,朱筱磊,等.氨基质子转移MRI对脑胶质瘤分级及预测肿瘤细胞增殖的诊断价值[J].放射学实践,2017,32(4):355-359.
[15]Nielsen LAG,Bangso JA,Lindahl KH,et al.Evaluation of the proliferation marker Ki-67in gliomas:Interobserver variability and digital quantification[J].Diagn Pathol,2018,13(1):38-46.
[16]Manasa LP,Uppin MS,Sundaram C.Correlation of p53and Ki-67expression with grade and subtype of ependymoma[J].Indian J Pathol Microbiol,2012,55(3):308-313.
[17]Cai J,Zhang C,Zhang W,et al.ATRX,IDH1-R132Hand Ki-67immunohistochemistry as a classification scheme for astrocytic tumors[J].Oncoscience,2016,3(7-8):258-265.
[18]胡铁民,褚会松,田甜,等.ADAM17、EGFR和Ki-67在脑胶质瘤中的表达及临床预后评估[J].中国地方病防治杂志,2017,32(6):619-621.
[19]Gupta A,Young RJ,Shah AD,et al.Pretreatment dynamic susceptibility contrast MRI perfusion in glioblastoma:prediction of EGFR gene amplification[J].Clin Neuroradiol,2015,25(2):143-150.
[20]Chaloob MK,Ali HH,Qasim BJ,et al.Immunohistochemical expression of Ki-67,PCNA and CD34in astrocytomas:a clinicopathological study[J].Oman Med J,2012,27(5):368-374.
[21]吴静,汪文胜,李松涛,等.3D-ASL参数对胶质瘤术前分级的价值及与Ki-67、MVD表达间关系的对照研究[J].实用放射学杂志,2018,34(5):654-657.
[22]董飞,张佩佩,蒋飚,等.动态对比增强MRI容积转移常数定量评估胶质瘤Ki-67标记指数的价值[J].中华放射学杂志,2017,51(8):568-571.
[2]杨孝燕,王春红,胡昌辰,等.胶质瘤相关分子标记物的研究进展[J].中国药物与临床,2018,18(3):396-400.
[3]Kogiku M,Ohsawa I,Matsumoto K,et al.Prognosis of glioma patients by combined immunostaining for survivin,Ki-67and epidermal growth factor receptor[J].J Clin Neurosci,2008,15(11):1198-1203.
[4]Kalpathy-Cramer J,Gerstner ER,Emblem KE,et al.Advanced magnetic resonance imaging of the physical processes in human glioblastoma[J].Cancer Res,2014,74(17):4622-4637.
[5]范兵,杜华睿,王霄英,等.MRI动态增强扫描定量参数对脑胶质瘤分级诊断价值的研究[J].放射学实践,2014,29(8):893-895.
[6]Vartanian A,Singh SK,Agnihotri S,et al.GBM's multifaceted landscape:highlighting regional and microenvironmental heterogeneity[J].Neuro Oncol,2014,16(9):1167-1175.
[7]刘振清,刘鸿圣.动态对比增强MRI诊断脑胶质瘤的研究进展[J].中国医学影像技术,2016,32(10):1617-1620.
[8]李锐,刘晋红,王玉林,等.三维动脉自旋标记与磁共振动态对比增强成像参数在胶质瘤术前分级中的对照研究[J].肿瘤影像学,2016,25(3):217-222.
[9]Brendle C,Hempel JM,Schittenhelm J,et al.Glioma grading and determination of IDH mutation status and ATRX loss by DCE and ASL perfusion[J].Clin Neuroradiol,2018,28(3):421-428.
[10]Awasthi R,Rathore RK,Soni P,et al.Discriminant analysis to classify glioma grading using dynamic contrast-enhanced MRI and immunohistochemical markers[J].Neuroradiology,2012,54(3):205-213.
[11]Scholzen T,Gerdes J.The Ki-67protein:from the known and the unknown[J].J Cell Physiol,2000,182(3):311-322.
[12]Seow P,Wong JHD,Ahmad-Annuar A,et al.Quantitative magnetic resonance imaging and radiogenomic biomarkers for glioma characterisation:a systematic review[J/OL].Br J Radiol,2018,91(1092):20170930.DOI:10.1259/bjr.20170930.
[13]Chen WJ,He DS,Tang RX,et al.Ki-67is a valuable prognostic factor in gliomas:evidence from a systematic review and meta-analysis[J].Asian Pac J Cancer Prev,2015,16(2):411-420.
[14]李欣蓓,宋玉坤,朱筱磊,等.氨基质子转移MRI对脑胶质瘤分级及预测肿瘤细胞增殖的诊断价值[J].放射学实践,2017,32(4):355-359.
[15]Nielsen LAG,Bangso JA,Lindahl KH,et al.Evaluation of the proliferation marker Ki-67in gliomas:Interobserver variability and digital quantification[J].Diagn Pathol,2018,13(1):38-46.
[16]Manasa LP,Uppin MS,Sundaram C.Correlation of p53and Ki-67expression with grade and subtype of ependymoma[J].Indian J Pathol Microbiol,2012,55(3):308-313.
[17]Cai J,Zhang C,Zhang W,et al.ATRX,IDH1-R132Hand Ki-67immunohistochemistry as a classification scheme for astrocytic tumors[J].Oncoscience,2016,3(7-8):258-265.
[18]胡铁民,褚会松,田甜,等.ADAM17、EGFR和Ki-67在脑胶质瘤中的表达及临床预后评估[J].中国地方病防治杂志,2017,32(6):619-621.
[19]Gupta A,Young RJ,Shah AD,et al.Pretreatment dynamic susceptibility contrast MRI perfusion in glioblastoma:prediction of EGFR gene amplification[J].Clin Neuroradiol,2015,25(2):143-150.
[20]Chaloob MK,Ali HH,Qasim BJ,et al.Immunohistochemical expression of Ki-67,PCNA and CD34in astrocytomas:a clinicopathological study[J].Oman Med J,2012,27(5):368-374.
[21]吴静,汪文胜,李松涛,等.3D-ASL参数对胶质瘤术前分级的价值及与Ki-67、MVD表达间关系的对照研究[J].实用放射学杂志,2018,34(5):654-657.
[22]董飞,张佩佩,蒋飚,等.动态对比增强MRI容积转移常数定量评估胶质瘤Ki-67标记指数的价值[J].中华放射学杂志,2017,51(8):568-571.