脑星形细胞瘤MRI表现与血管内皮生长因子表达的关系

目的:探讨脑星形细胞瘤血管内皮生长因子的表达与MRI表现的关系.材料和方法:收集手术病理证实的脑星形细胞瘤42例,分析其M RI表现.采用免疫组织化学技术染色VEGF,并分析其表达程度与M RI表现的关系.结果:星形细胞瘤的VEGF表达与其病理分级、患者复发密切相关.星形细胞瘤MRI信号的不均匀性、边界清楚与否、瘤周水肿范围、占位效应及增强程度与VEGF表达明显相关,但星形细胞瘤的大小、部位与VEGF表达无明显相关性.结论:星形细胞瘤的MRI征象能反映星形细胞瘤的VEGF表达.术前分析星形细胞瘤的MRI征象与VEGF表达的关系,能更好地指导临床治疗方案的选择和评估患者的预后.     

星形细胞瘤动态增强MRI与VEGF表达的相关性研究

目的探讨星形细胞瘤动态增强MRI与血管内皮生长因子(VEGF)表达的相关性. 资料与方法对33例星形细胞瘤术前采用TurboFLASH序列进行动态增强扫描,通过对时间-信号强度曲线分析,获得对比剂首过期曲线的最大斜率(SSmax)和Tm1两参数.术后取病检分别进行VEGF和微血管密度(MVD)免疫组织化学染色,计算每一标本的VEGF表达程度及MVD.将VEGF表达与SSmax、Tm1分别进行相关分析. 结果 VEGF不同表达程度的星形细胞瘤之间的SSmax或Tm1差异有统计学意义(P＜0.05).星形细胞瘤的SSmax与VEGF表达程度成正相关,rs值为0.68;Tm1与VEGF表达程度成负相关,rs值为-0.697,P值均＜0.001.VEGF表达程度与MVD存在相关性. 结论星形细胞瘤的VEGF表达程度与SSmax、Tm1之间存在显著性的相关,其病理生理学基础是VEGF促进星形细胞瘤血管生成.对星形细胞瘤动态增强MRI曲线分析有助于预测星形细胞瘤的VEGF表达.     

星形细胞瘤MRI瘤周水肿与肿瘤血管形成的相关性研究

目的：探讨星形细胞瘤瘤周水肿与肿瘤血管生成及病理分级的相关性，资料与方法：对68例MRI术前诊断及手术病理证实的幕上星形细胞瘤石蜡标本进行免疫组化染色，测定微血管密度（MVD），并测量MR图像上肿瘤大小和瘤周水肿范围。结果：MR图像中，星形细胞瘤大小与MVD无相关性（P＞0．05），瘤周水肿与病理分级，MVD明显相关，随着病理级别的增加和MVD值的增高，瘤周水肿范围增大（P＜0．01），结论：星形细胞瘤瘤周水肿与血管生成，病理分级密切相关，MRI图像显示的瘤周水肿范围可作为预测星形细胞瘤恶性程度和预后的重要征象。     

星形细胞瘤MR灌注成像的有关病理学基础

目的 探讨MR灌注成像在星形细胞瘤术前病理分级中的应用价值,并与血管内皮生长因子(VEGF)表达 对照,评估VEGF表达与脑血容量的相关性。资料与方法 28例星形细胞瘤患者术前行MR常规及MR灌注扫 描,术后经病理组织学检查,并采用免疫组织化学染色,观察VEGF表达情况。原始灌注图像数据经工作站软件处 理,获得MR灌注曲线及彩色图谱,测量肿瘤实质部分及瘤周水肿区最大相对脑血容量(rCBV)并将所测数值进行 统计学分析。免疫组织化学染色计算每一标本的VEGF表达程度,将VEGF表达程度与rCBV进行相关分析。结 果 在MR灌注曲线及彩色图谱中,高分级星形细胞瘤实质部分及瘤周水肿区最大灌注处表现为高灌注,低分级星 形细胞瘤表现为等或低灌注为主。低分级星形细胞瘤实质部分及瘤周水肿区最大rCBV值为1．88±0．84,1．03± 0．40。高分级星形细胞瘤实质部分及瘤周水肿区最大rCBV值为3．07±1．23,1．61±0．70;两组间肿瘤实质部分及瘤 周水肿区最大rCBV值差异均有统计学意义(P<0．01,P<0．05)。VEGF不同表达程度的rCBV差异有统计学意义 (P<0．01),VEGF表达程度与rCBV成正相关,r8值为0．817,P<0．001。 结论 星形细胞瘤MR灌注成像与病理 分级和VEGF有良好相关性,结合常规MR,可显著提高星形细胞瘤术前病理分级的准确性,具有重要临床价值。     

脑星形细胞瘤血管内皮生长因子表达与CT表现的相关性研究

目的 探讨脑星形细胞瘤血管内皮生长因子（VEGF）的表达与CT征象间的关系。材料与方法 搜集经手术病理证实的脑星形细胞瘤82例,分析其CT表现。采用免疫组化技术对肿瘤细胞内的VEGF染色,并分析其表达程度与CT表现的关系。结果 星形细胞瘤的VEGF表达的程度与其病理分级、病变复发密切相关。星形细胞瘤CT密度的不均匀性、瘤周水肿范围、占位效应的程度、增强程度与VEGF表达程度明显相关,但星形细胞瘤的大小、部位与VEGF表达无明显相关性。结论 星形细胞瘤的CT征象能反映星形细胞瘤的VEGF表达程度。术前分析星形细胞瘤的CT征象与VEGF表达的关系,能更好地指导临床治疗方案的选择和评估患者的预后。     

脑星形细胞瘤MRI表现与GFAP表达的关系

目的 :探讨星形细胞瘤MRI表现与GFAP表达的关系。方法 :收集手术病理证实的脑星形细胞瘤 4 1例 ,分析其MRI表现。采用免疫组化方法标记肿瘤GFAP。对照GFAP表达程度与MRI表现的关系。结果 :星形细胞瘤GFAP表达强弱与病理级别相关 ,星形细胞瘤信号均匀性、边界清楚与否、瘤周水肿程度及增强程度与GFAP表达之间有统计学差异 ,但肿瘤部位及大小与GFAP表达没有相关性。结论 :星形细胞瘤MRI表现 ,特别是脑水肿、增强程度等征象 ,在一定程度上可以反映GFAP表达强弱。     

脑星形细胞瘤血管内皮生长因子基因蛋白表达及临床意义

 目的检测脑星形细胞瘤组织中血管内皮生长因子(VEGF)基因蛋白表达,分析其表达变化与不同病理类型肿瘤的相关性.方法选用54例Ⅰ～Ⅳ级星形细胞瘤手术后存档蜡块标本为实验标本;应用流式细胞术(FCM)分别定量检测不同病理类型星形细胞瘤组织中VEGF基因蛋白表达量.结果VEGF蛋白在星形细胞瘤中的表达量(FI值)增加,并随肿瘤恶性度的升高而增加.VEGF蛋白表达量与病理组织学分级有明显相关性(P＜0.01).Ⅰ～Ⅳ级星形细胞瘤VEGF蛋白表达阳性率分别为23.1%、46.2%、100%和100%.结论VEGF基因蛋白在星形细胞瘤中的表达量显著增加,并随肿瘤恶性度的升高而增加,说明VEGF过度表达在星形细胞瘤形成和由低恶性度向高恶性度演化过程中起重要作用.     

星形胶质细胞瘤微血管成分改变与瘤周水肿MRI相关因素分析

目的探讨星形胶质细胞瘤血管成分中血管内皮生长因子(VEGF)及其受体mRNA表达改变与瘤周水肿MRI的关系及肿瘤增殖能力对血管成分的影响,并探讨两者之间的关系.材料和方法采用半定量逆转录-聚合酶链反应(RT-PCR)方法,对49例脑胶质瘤手术切除标本以及12例脑外伤内减压术中得到的正常脑组织检测了VEGF、mRNA表达水平.另外,用免疫组化SP法对胶质瘤及正常脑组织的微血管密度(WVD)并与星形胶质细胞瘤MRI、病理学资料进行分析.结果胶质瘤组织中的VEGF、mRNA表达水平明显增高,达65.3%,随着病理分级的提高其表达水平有升高趋势,HUVEC及3株胶质瘤细胞表达水平亦较高,而正常脑组织表达水平及表达率较低.胶质瘤中的微血管密度(MVD)与胶质瘤级别之间有等级相关性,VEGF、mRNA的表达同MVD呈正相关.同样,采用MRI评分方法,随着病理级别增加,MRI分值亦随之增加(P＜0.01～0.001).增强形态(CE-HET)、瘤周水肿、增强程度(CE-D)已被证明与病理级别良、恶性程度密切相关.经多元线性偏回归分析p＜0.001.结论VEGF的高表达同MVD对胶质瘤的恶性生物学行为的评估有重要意义,星形胶质细胞瘤的微血管成分改变对MRI增强程度、瘤周水肿、信号不均匀、增强形态有明显影响,血管丰富、病理级别高的肿瘤易伴瘤周水肿,而MRI强化明显,表明肿瘤增殖能力,血管生成明显.     

神经胶质瘤相对性脑血流容积与血管内皮生长因子蛋白表达及微血管密度的相关性研究

目的　探讨胶质瘤相对性脑血流容积 (rCBV)与血管内皮生长因子 (VEGF)蛋白表达及肿瘤微血管密度 (MVD)间的相关性。方法　对 4 6例术前疑为幕上胶质瘤的患者行MR检查 ,术后经病理组织学证实 ,并采用免疫组织化学染色 ,观察VEGF蛋白表达情况及定量研究肿瘤MVD ,探讨rCBV与VEGF表达及MVD间的相关性。MR扫描顺序为常规MR平扫、灌注成像 (PWI)及常规MR增强扫描。PWI序列为单次激发梯度回波 平面回波 准T2 加权成像 (GRE EPI T 2 WI) ,原始灌注图像数据 ,经工作站软件计算出脑血流容积 (CBV)图 ,在CBV图上获取胶质瘤最大rCBV值。按VEGF表达阳性与阴性分为两组 ,即VEGF阳性组与VEGF阴性组 ,做统计学分析 (Mann WhitneyU检验 ) ,观察两组间最大rCBV值是否有统计学差异。采用非参数相关性分析法 (Spearman检验 )观察胶质瘤最大rCBV值与MVD间的关系。结果　 4 6例中 ,星形细胞瘤 12例 ,少枝胶质瘤 3例 ,混合性胶质瘤 1例 ,间变性星形细胞瘤 14例 ,多形性胶质母细胞瘤 16例。其中VEGF表达阴性 14例 ,VEGF表达阳性 32例。VEGF阴性组胶质瘤最大rCBV值为 0 33～ 6 6 3,中位数为 3 0 8;VEGF阳性组胶质瘤最大rCBV值为 1 0 3～ 10 6 8,中位数为 5 95。统计学分析表明 ,两组间rCBV值差异有非常显著意义 (Mann Whitney     

脑星形细胞瘤的MRI征象与MMP-9表达相关性的研究

目的 探讨星形细胞瘤MRI征象与基质金属蛋白酶-9（matrix metalloproteinase,MMP-9）表达的相关性。资料与方法 采用免疫组织化学（S-P）法,用抗MMP-9抗体对40例星形细胞瘤组织标本进行标记分析,并测定MRI图像上肿瘤信号的均匀度、水肿程度及强化程度。结果 星形细胞瘤MRI征象与MMP-9的表达明显相关（P〈0．01）,而且随着肿瘤恶性程度的增加,MMP-9的表达也增高（P〈0．01）。结论 星形细胞瘤的MRI征象与MMP-9的表达密切相关。可以间接地反映星形细胞瘤的某些分子生物学特性。     

大鼠C6脑胶质瘤生长的MRI评价及与其病理组织学的关系

目的:探讨大鼠C6脑胶质瘤MR I所测参数与其组织病理学的相关性。材料和方法:运用立体定向方法建立大鼠C6胶质瘤模型,并于C6细胞植入后1、2、3周行MR I平扫及增强扫描,同期取脑行病理组织学检查,对MR I所测肿瘤体积、肿瘤增强程度和EI与MVD和VEGF表达进行相关分析。结果:大鼠C6脑胶质瘤MR影像表现与文献报道相似,新生肿瘤血管和VEGF表达主要位于肿瘤周边;随着C6细胞植入时间的延长,肿瘤体积、EI、MVD逐渐增大,其差别具有统计学意义;VEGF表达与MVD呈正相关,二者分别与肿瘤体积、肿瘤增强程度、EI之间呈正相关。结论:MR I能够反映大鼠C6脑胶质瘤的动态生长特征,与VEGF表达和MVD的动态变化密切相关。     

肝细胞癌CT强化类型与病理、MVD、VEGF的相关性研究

目的 探讨肝细胞癌(HCC)CT动态增强表现的强化类型与瘤内MVD及VEGF表达之间的关系.方法 运用免疫组化SP法,检测45例经手术切除并病理证实的肝细胞癌瘤内MVD及VEGF的表达,所有病例术前均行CT平扫及增强扫描.结果 (1)病理分级、MVD及VEGF间的关系:Ⅰ、Ⅱ、Ⅲ级和Ⅳ级的MVD分别为22.9±12.6、36.7±16.2、51.1±17.3和67.8±21.4,VEGF阳性表达率分别为28.6%(2/7)、53.3%(8/15)、90.9%(10/11)和100.0%(12/12),Ⅰ级与Ⅲ/Ⅳ级和Ⅱ级与Ⅳ级之间的MVD、VEGF阳性表达率差异显著(P＜0.05),Ⅰ级与Ⅱ级、Ⅱ级与Ⅲ级和Ⅲ级与Ⅳ级之间的MVD,VEGF阳性表达率无显著性差异(P＞0.05).(2)动脉供血型、双重供血型及少血供型肝细胞癌的MVD分别为70.6±22.9、65.7±21.6和25.1±13.5,VEGF阳性表达率分别为85.1%(23/27)、63.6%(7/11)和28.6%(2/7).动脉供血型和双重供血型、双重供血型和少供血型之间VEGF阳性表达率差异均无显著性(P＞0.05),动脉供血型或动脉供血型和双重供血型合并组与少供血型之间VEGF阳性表达率差异有显著性(P＜0.05);动脉供血型和双重供血型的肝细胞癌,其MVD计数均高于少血供型,组间有显著性差异(P＜0.01),动脉供血型与双重供血型MVD计数无显著性差异(P＞0.1).结论 MVD及VEGF表达可在一定程度上反映HCC的分化程度及血供分型.     

非小细胞肺癌MR动态增强表现与肿瘤血管生成的相关性

目的　探讨非小细胞肺癌 (NSCLC)的微血管密度 (MVD)及其血管内皮生长因子 (VEGF)与MR动态增强指标间的关系。资料与方法　以 3 3例经手术证实为NSCLC的病例作为研究对象 ,分析肿块的最大强化斜率 (Smax)和峰值到达时间 (TTP)。组织切片经CD3 4和VEGF免疫组织化学染色 ,分析MVD和VEGF表达的阳性率。将Smax和TTP分别与肿瘤的病理类型以及免疫组织化学结果 (MVD、VEGF)进行各自的比较。结果　 ( 1 )肺癌的Smax与MVD和VEGF之间呈显著正相关 (r分别为 0 .6 1 5 ,0 .72 3 ,P <0 .0 0 1 ) ;( 2 )TTP与MVD和VEGF之间呈显著的负相关(r分别为 - 0 .4 78和 - 0 .5 3 8,P <0 .0 1和 0 .0 0 1 )。结论　MR动态增强指标Smax和TTP能够反映NSCLC的MVD和VEGF表达的高低 ,从而推测其血管生成状况。     

Correlative study of angiogenesis and dynamic contrast-enhanced magnetic resonance imaging features of hepatocellular carcinoma

PURPOSE: To explore the correlation between contrast-enhancement patterns on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and angiogenesis by analyzing microvessel density (MVD), vascular endothelial growth factor (VEGF), and P53 protein expression in hepatocellular carcinoma (HCC). MATERIAL AND METHODS: MRI was performed with a GE Signa 1.5T MR scanner using SE and FMPSPGR sequences in 30 patients (38 lesions) during the period October 1998 to March 2000. All had histopathologically proven HCC. MR images were reviewed/ analyzed retrospectively. The 30 patients were between 35 and 65 years of age (average age 58; 18 M and 12 F). SE T1WI, PDWI, and T2WI were acquired initially. The FMPSPGR sequence was acquired in the same position. The DCE-MRI was performed in the arterial, portal vein, and delay phase after a bolus injection of Gd-DTPA. The specimens were stained immunohistochemically for CD34, VEGF, and P53. MVD was highlighted by anti-CD34 antibody staining. The enhancement features of HCC lesions were studied correlatively with the tumor MVD, VEGF, and P53 expression at protein level. RESULTS: In the arterial phase, the results showed that MVD of HCC in the high-enhancement group (229.76 +/- 80.96) was higher than that in the equal-enhancement (173.09 +/- 61.38) and low-enhancement groups (153.00 +/- 108.58) (P < 0.01, respectively). VEGF expression of HCC in the high-enhancement group (68.42%) was higher than that in the equal-enhancement (36.36%) and low-enhancement groups (38.89%) (P < 0.05, respectively). In the portal vein phase, MVD of HCC in the enhancement group (259.80 +/- 93.30) was higher than that in the non-enhancement group (178.64 +/- 92.65) (P < 0.05). No significant correlation was found between VEGF expression and the enhancement feature in the portal vein phase. In the delay phase, MVD of HCC in the ring-enhancement group (269.06 +/- 57.89) was significantly higher than that in the non-ring-enhancement group (144.10 +/- 88.90) (P < 0.01). There was a significant difference in VEGF expression between the ring-enhancement group (76.47%) and the non-ring-enhancement group (42.86%) (P < 0.05). No significant correlation was detected between P53 protein expression and the enhancement feature. Relative enhancement (RE) correlated with MVD, but not with VEGF and P53 protein expression. CONCLUSION: The contrast-enhancement patterns on DCE-MRI are influenced by tumor angiogenesis, as reflected by elevated VEGF expression, and are therefore valuable indicators for accessing tumor angiogenic activity and tumor neovascularization in vivo in HCC patients.     

肝细胞癌MSCT多期增强扫描与Survivin、VEGF及MVD表达关系的研究

目的:探讨肝细胞癌(HCC)的MSCT多期增强扫描与Survivin、VEGF表达及微血管生成之间的关系。方法:对36例病理证实为HCC的患者术前行MSCT平扫及增强扫描,术后标本进行免疫组化染色测定Survivin、VEGF以及MVD表达情况,将MSCT强化特征与免疫组化结果进行分析。结果:①36例HCC组织中Survivin表达阳性率为69.4%(25/36),VEGF表达阳性率72.2%(26/36)。26例VEGF表达阳性的HCC中,20例Survivin表达阳性,Survivin表达与VEGF表达呈显著正相关。②HCC的MSCT征象中肿瘤大小及瘤体中心有无坏死与Survivin、VEGF的表达无关(P>0.05)。有静脉癌栓组的Survivin表达明显高于无癌栓组(P<0.05)。边缘不清、有静脉癌栓组的VEGF表达明显高于边缘清楚、无静脉癌栓组(P<0.05)。MVD值表达与VEGF表达相同。结论:Survivin、VEGF及MVD在HCC呈高表达且三者密切相关,HCC的MSCT表现特征在一定程度上能反映Survivin、VEGF的表达以及肿瘤微血管生成情况,可以在一定程度上从分子水平判断HCC的侵袭、转移。     

Dynamic contrast-enhanced MRI of benign prostatic hyperplasia and prostatic carcinoma: correlation with angiogenesis

AIM: To investigate the diagnostic and differential diagnostic values of dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in prostatic diseases, and to investigate the correlation between the parameters of SI-T curves and angiogenesis. MATERIALS AND METHODS: Twenty-one patients with proven prostatic carcinoma (Pca) and 29 patients with proven benign prostatic hyperplasia (BPH) were examined using DCE MRI. Diagnostic characteristics for differentiation were examined using threshold values for maximum peak time, enhancement degree, and enhancement rate. Then, the signal intensity-time curves (SI-T curves) were analysed, and the correlations between the parameters of SI-T curves and the expression levels of vascular endothelial growth factor (VEGF) and microvascular density (MVD) were investigated. All patents underwent prostatectomy. DCE MRI and histological findings were correlated. RESULTS: Pca showed stronger enhancement with an earlier peak time, higher enhancement, and enhancement rate (p<0.05). Regarding the type of SI-T curves, in the BPH group six were type A, 10 were type B, and 13 were type C, whereas in the Pca group, 14 were type A, six were type B, and only one was type C (Chi-square test, chi2=13.57, P<0.005). The VEGF and MVD expression levels of Pca were higher than those of BPH. Peak time was negatively correlated with the expression levels of VEGF and MVD, whereas the enhancement degree and enhancement rate showed positive correlations (Pearson correlation, p<0.05). CONCLUSION: Based on T2-weighted imaging, DCE MRI curves can help to differentiate benign from malignant prostate tissue. In the present study the type C curve was rarely seen with malignant disease, but these results need confirmation.     

MR cerebral blood volume maps correlated with vascular endothelial growth factor expression and tumor grade in nonenhancing gliomas

BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) measurements derived from perfusion-weighted imaging (PWI) may be useful to evaluate angiogenesis and preoperatively estimate the grade of a glioma. We hypothesized that rCBV is correlated with vascular endothelial growth factor (VEGF) expression as marker of the angiogenic stimulus in presumed supratentorial low-grade gliomas (LGGs). METHODS: From February 2001 to February 2004, we examined 20 adults (16 men, four women; mean age 36 years; range, 23-60 years) with suspected (nonenhancing) supratentorial LGG on conventional MR imaging. Preoperative MR imaging used a dynamic first-pass gadolinium-enhanced, spin-echo echo-planar PWI. In heterogeneous tumors, we performed stereotactic biopsy in the high-perfusion areas before surgical resection. Semiquantitative grading of VEGF immunoreactivity was applied. RESULTS: Nine patients had diffuse astrocytomas (World Health Organization grade II), and 11 had other LGG and anaplastic gliomas. In patients with heterogeneous tumors on PWI, the high-rCBV focus had areas of oligodendroglioma or anaplastic astrocytoma on stereotactic biopsy, whereas the surgical specimens were predominantly astrocytomas. Anaplastic gliomas had high rCBV ratios and positive VEGF immunoreactivity. Diffuse astrocytomas had negative VEGF expression and mean rCBV values significantly lower than those of the other two groups. Three diffuse astrocytomas had positive VEGF immunoreactivity and high rCBV values. CONCLUSION: Our results confirmed the correlation among rCBV measurements, VEGF expression, and histopathologic grade in nonenhancing gliomas. PWI may add useful data to the preoperative assessment of nonenhancing gliomas. Its contribution in predicting tumor behavior and patient prognosis remains to be determined.     

Dynamic contrast-enhanced (DCE) derived transfer coefficient (ktrans) is a surrogate marker of matrix metalloproteinase 9 (MMP-9) expression in brain tuberculomas

PURPOSE: To correlate dynamic contrast-enhanced (DCE) MRI derived perfusion indices with immunohistochemically obtained vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in a cellular fraction of brain tuberculomas (BT). MATERIALS AND METHODS: Thirteen BT patients underwent DCE MRI. Perfusion indices (cerebral blood volume [CBV], transfer coefficient [ktrans] and leakage [ve]) maps were generated for the quantitative analysis. The CBV was corrected for the leaky blood-brain barrier (BBB). The relative CBV (rCBV), ktrans, and ve were calculated by placing 10 regions of interest (ROIs) showing the highest values in the lesion. The percentage area of VEGF and percentage area of MMP-9 and microvessel density (MVD) were quantified from 10 fields per lesion with maximal expression of the excised BT. Pearson correlation analysis between physiological indices and quantitative VEGF, MMP-9, and MVD was performed for each ROI. RESULTS: The average value of rCBV, ktrans, ve, VEGF, MMP-9, and MVD were 3.53+/-0.37, 2.04+/-0.40 min(-1), 0.71+/-0.09, 12.51+/-2.56, 18.09+/-2.06, 10.87+/-1.99, respectively. The ktrans (r=0.918, P<0.001) and ve (r=0.899, P<0.001) showed significant correlation with MMP-9, while rCBV correlated significantly with MVD (r=0.962, P<0.001) and VEGF (r=0.868, P<0.001). CONCLUSION: We conclude that the expression of MMP-9, a marker of BBB disruption and disease activity in BT correlates with DCE-derived ktrans and thus has the potential to be used as its surrogate marker.