实时灰阶超声造影评价肝癌动物模型抗血管生成治疗的研究  

Assessment of antiangiogenic therapy in a nude murine hepatocellular carcinoma model with real-time gray-scale contrast-enhanced ultrasonography

作　　者：范培丽[1] 丁红[1] 朱小东[2] 林希元[1] 张巨波[2] 王文平[1] 孙惠川[2] 

机构地区：[1]复旦大学附属中山医院超声诊断科,上海200032 [2]复旦大学附属中山医院肝癌研究所,上海200032

出　　处：《中华超声影像学杂志》2009年第8期708-712,共5页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金（30872409）

摘　　要：目的应用实时灰阶超声造影评估肝癌动物模型抗血管生成治疗时肿瘤内微血管血流灌注变化，探讨超声造影定量分析的应用价值。方法建立30只皮下肝癌裸鼠异种移植瘤模型，15只裸鼠作为治疗组，使用血管内皮生长因子受体抑制剂（Pazopanib）灌胃治疗，15只设为对照组。分别在治疗前3d、治疗后7d、14d和21d对肿瘤进行体积测量和超声造影检查。脱机采用超声定量分析软件获得肿瘤的时间强度曲线和定量参数，并与病理坏死指数进行相关性分析。结果治疗21d后，治疗组相对肿瘤增殖率为41％。治疗组肿瘤强度增量（ISI）、曲线下面积（AUC）和血流量系数（BF）明显低于对照组，另外峰值减半斜率（a2）和曲线上升斜率（a3）明显大于对照组（P〈0．05）。定量参数与肿瘤体积增长率正相关（P〈0．05）。a3和ISI与坏死指数负相关（r=-0．54，P=0．008；r=-0．46，P=0．027）。结论实时灰阶超声造影能反映肿瘤内血流灌注变化，有助于监测肿瘤抗血管生成治疗的血管反应。Objective To assess intratumoral microvascular perfusion changes by real-time gray-scale contrast-enhanced ultrasonography（CEUS） in a nude murine hepatocellular carcinoma model treated with angiogenesis inhibitor,and to investigate the applicative value of quantitative analysis of CEUS. Methods Human hepatocellular carcinoma xenograft model was established in thirty nude mice subcutaneously. Fifteen nude mice were treated with an inhibitor of vascular endothelial growth factor receptors （pazopanib） by oral administration and fifteen nude mice were set as control. Volume measurement and CEUS were performed 3 days before treatment,7 days, 14 days and 21 days after treatment, respectively. Regions of interest within tumors were analyzed off-line to perform time-intensity curves and determine CEUS parameters. The relation between CEUS parameters and necrosis index of pathology were investigated. Results The relative tumor proliferation rate in the treatment group was 41% on 21 days after treatment. Increased signal intensity （ISI） ,area under the curve （AUC） and blood flow coefficient （BF） were lower in the treatment tumors than those in the control tumors,in addition slope of decrease to half of peak （a2） and slope of rise time （a3） was higher （ P 〈0.05）. CEUS parameters correlated with the volume growth rate in treatment tumors,respectively （ P 〈0.05）. A3 and ISI were negative correlated with necrosis index （ r = -0.54, P =0.008; r = -0.46, P = 0.027）. Conclusions Real-time gray-scale CEUS reflects changes of microvaseular perfusion in tumors objectively, which is potential in monitoring tumor vascular response to antiangiogenie therapy.

关 键 词：超声检查 微气泡 肝肿瘤 实验性 新生血管性 病理性 

分 类 号：R686[医药卫生—骨科学]