Hawighorst H, Knapstein P G, Knopp M V, Weikel W, Brix G, Zuna I, Schönberg S O, Essig M, Vaupel P, van Kaick G
Department of Radiological Diagnostics, German Cancer Research Center, Heidelburg, Germany.
Cancer Res. 1998 Aug 15;58(16):3598-602.
Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as for therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this study to: (a) examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis [microvessel density (MVD) and vascular endothelial growth factor (VEGF)]; and (b) determine the ultimate value of a histomorphological and a dynamic MRI approach by the correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) and standard parameters [the maximum signal intensity increase over baseline (SI-I) and the steepest signal intensity-upslope per second (SI-U/s)] were calculated from a contrast-enhanced dynamic MRI series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD and VEGF) were compared to MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found between MVD and A (P < 0.01) and SI-I (P < 0.05). No significant relationships were observed between VEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based on k21 and SI-U/s showed that tumors with high k21 and SI-U/s values had a significantly (P < 0.05 and 0.001, respectively) worse disease outcome than did tumors with low k21 and SI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD and VEGF) had any significant power to predict patient survival. It is concluded that in patients with uterine cervical cancer: (a) the pathophysiological basis for differences in dynamic MRI is MVD but not VEGF expression; (b) a functional, dynamic MRI approach (both standard and pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than are the current histomorphological-based markers of tumor angiogenesis; and (c) compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assess MVD or patient survival.
基于钆的造影剂在磁共振成像（MRI）中的动态研究越来越多地用于肿瘤特征描述以及治疗反应监测。由于关于病理生理特性的详细知识（而这些特性又导致了对比增强的差异）仍相当不确定，本研究的目的是：（a）研究动态MRI中时间 - 强度曲线的标准分析和药代动力学分析与肿瘤血管生成的组织形态学标志物[微血管密度（MVD）和血管内皮生长因子（VEGF）]之间的关联；（b）通过将这些数据与子宫颈原发性癌患者的疾病转归相关联，确定组织形态学和动态MRI方法的最终价值。从37例经活检证实为原发性宫颈癌的患者的对比增强动态MRI系列中计算药代动力学参数（幅度，A；交换速率常数，k21）和标准参数[相对于基线的最大信号强度增加（SI-I）和每秒最陡的信号强度上升斜率（SI-U/s）]。在手术全层标本上，将肿瘤血管生成的组织形态学标志物（MVD和VEGF）与MRI衍生参数进行比较。对于MRI和组织形态学数据，计算Kaplan-Meier生存曲线并使用对数秩统计进行比较。发现MVD与A（P < 0.01）和SI-I（P < 0.05）之间存在显著关联。未观察到VEGF表达与所有动态MRI参数之间存在显著关系。基于k21和SI-U/s的Kaplan-Meier曲线表明，k21和SI-U/s值高的肿瘤的疾病转归明显（分别为P < 0.05和0.001）比k21和SI-U/s值低的肿瘤更差。用于评估肿瘤血管生成的组织形态学金标准标志物（MVD和VEGF）均没有预测患者生存的显著能力。得出的结论是，对于子宫颈癌患者：（a）动态MRI差异的病理生理基础是MVD而非VEGF表达；（b）就患者生存而言，功能性动态MRI方法（标准分析和药代动力学分析）可能比当前基于组织形态学的肿瘤血管生成标志物更适合评估血管生成活性；（c）与标准分析相比，时间 - 强度曲线的简单药代动力学分析在评估MVD或患者生存方面并不优越。
