超声造影评价抗血管生成治疗小鼠肝癌的实验研究

目的 探讨超声造影在评价抗肿瘤血管生成治疗中的作用.方法 小鼠H22肝癌皮下接种次日起随机分为2组:治疗组给予沙利度胺(200 mg/kg)灌胃,对照组给予0.5%羧甲基纤维素钠灌胃,连续7 d,末次给药次日行超声造影检查,测量两组肿瘤最大横切面的面积和无强化区面积,计算无强化区面积比例.病理切片测量两组肿瘤最大横切面积及坏死面积并计算坏死面积比例.结果 超声造影及病理切片测量肿瘤的最大横切面积在两组之间差异无统计学意义(P>0.05).超声造影测量的肿瘤无强化区面积及其比例和病理切片上测量的肿瘤坏死面积及其比例在治疗组均明显大于对照组(均P<0.005).超声造影测量的肿瘤最大横切面积、无强化区面积及其比例分别与病理切片测量的肿瘤最大横切面积、坏死面积及其比例具有很好的相关性(r>0.8,P<0.001).结论 超声造影可以在肿瘤体积发生改变前检测出抗血管生成治疗引起的肿瘤内坏死和血流灌注的变化.

Assessment of antiangiogenic therapeutics effect in a mouse hepatoma model using contrast-enhanced gray-scale ultrasound

Objective To evaluate antiangiogenic therapeutics effect with contrast-enhanced gray-scale ultrasound.Methods Kun-min mouse with subcutaneously implanted H22 mice hepatoma were treated with thalidomide or placebo by oral gavage over 7 days, starting at clay 2 post-implantation.Contrast-enhanced gray-scale ultrasound was performed on day 8.The tumor maximum cross-sectional area and non-enhanced area in ultrasound imaging were measured on the ultrasound machine.The percent of non-enhanced area from contrast-enhanced gray-scale ultrasound was calculated.Immediately after imaging, minces were euthanized and tumor tissue removed for fixation in a 10% formalin solution.The section equivalent to ultrasound imaging plane was stained with Hematoxylin and Eosin(HE) to allow for assessment of maximum cross-section area and necrotic area.The percent of necrotic area from HE stained section was calculated.Results The difference of maximum cross-sectional area measured in ultrasound and pathology slice was not significant between control and treated tumors (P >0.05).Ultrasound measurement of the tumor non-enhanced area and the percent of non-enhanced area were significantly larger in treated tumors than in control tumors (P <0.001).The necrotic area and the percent of necrotic area measured from HE stained section were also significantly larger in treated tumors than in control tumors (P < 0.001).The maximum cross-sectional area determined by the two methods was well corrected (r = 0.815, P < 0.001).There was good correlation between the non-enhanced area in contrast-enhanced gray-scale ultrasound and the necrotic area in pathology slides (r = 0.909, P <0.001).The percent of non - enhanced area calculated from ultrasound highly correlated with necrotic area estimated by pathology slides (r = 0.910, P <0.001).Conclusions Contrast-enhanced gray-scale ultrasound can detect the intratumoral necrosis and changes of tumor perfusion caused by antiangiogenic treatment before apparent change in tumor volume.