超声造影时间信号强度曲线对人肺腺癌裸鼠异位移植瘤微血管生成特点的定量研究

Quantitative Study on Angiogenesis Features of Human Lung Adenocarcinoma Xenografted into Nude Mouse Model Using Time-intensity Curve Parameters with Contrast Enhanced Ultrasonography

通过超声造影时间信号曲线获得人肺腺癌异位移植瘤血流灌注参数,进一步探究肿瘤不同生长时间微血管生成特点。本文选取21只裸鼠,建立人肺腺癌异位移植瘤模型,于7d、14d及28d进行超声造影(CEUS),获得肿瘤血流灌注图像及时间信号参数,包括上升时间(RT)、峰值强度(PI)和曲线下面积(AUC)。CD34免疫组化染色获得肿瘤微血管密度(MVD)。实验结果显示,7d、14d及28d的PI与AUC逐渐降低(P<0.05)。RT随着肿瘤生长时间延长逐渐增高(P<0.05)。在有坏死的肿瘤中,非坏死区域的PI、AUC比坏死区域大(P<0.05)。CD34染色发现坏死肿瘤的MVD较无坏死肿瘤低[(7.50±3.44)条vs.(12.44±5.74)条,P=0.034]。MVD与PI呈正相关(r=0.668,P=0.008)。本文研究结果表明,超声造影对人肺腺癌异位移植瘤血流灌注研究具有一定价值。时间信号曲线的PI、AUC及RT可以反映肿瘤的微血管生成情况。

This research is to explore the perfusion time-intensity curve parameters of a lung adenocarcinoma xenograft into nude mouse model with contrast enhanced ultrasonography（CEUS）;and to investigate the angiogenesis features of tumor at different growth time.Twenty one lung adenocarcinoma xenografted nude mice were divided into three groups and inculcated with human lung adenocarcinoa.Time window for examining CEUS were respectively in7-day,14-day and 28-day.The perfusion parameters including rise time（RT）,peak intensity（PI）,area under the curve（AUC）of lung tumor were obtained on CEUS images by using off-line software Q lab.Immunohistochemically staining for CD34 was used to observe the microvessel density（MVD）.The 7-day group had the highest AUC and PI;AUC and PI of 14-day and 28-day group decreased gradually（P〈0.05）.RT was increased as tumor growth.In tumor with necrosis,AUC and PI of non-necrosis part were also larger than necrosis part（P〈0.05）.Immunohistochemically staining for CD34 of all tumors reflected that the density of microvessels in necrosis tumor was significantly higher than those without necrosis（7.50±3.44 vs.12.44±5.74,P=0.034）.Pearson correlation indicated that PI was positively related with MVD（r=0.668,P=0.008）.Lung adenocarcinoma perfusion characteristic can be accessed from time-intensity curve parameters by using noninvasively and non-radiative contrast enhanced ultrasonography.Time-intensity curve parameters including AUC,PI and RT may reflect tumor angiogenesis.