The Study Of Contrast-enhanced Ultrasound To Nude Mice Gallbladder Carcinoma Transplant Tumor Blood Perfusion And Correlation With Angiogenesis

Objective:Analysis the nude mice gallbladder carcinoma transplant tumor perfusion characteristics and Contrast-enhanced ultrasound(CEUS) quantitative parameters with the correlation of tumor angiogenesis. To investigate the value of CEUS technology in the evaluation of malignant tumor blood perfusion and tumor angiogenesis.Methods:Use the tumor tissue mass and cell suspension subcutaneous planting method to establish nude mice gallbladder carcinoma transplant tumor model. After the success of the modeling 21 ~ 24 days to accept CEUS inspection, Injection SonoVue through the tail vein,Application of low mechanical index real-time ultrasound imaging technology and TIC-analysis software analysis tumor contrast-enhanced ultrasound blood perfusion characteristics and control with pathological. By immunohistochemical techniques detection the expression level MVD, VEGF and PCNA of tumor, and making the correlative analysis with CEUS quantitative parameters.Results:10 models were successful established, and sum to 20 masses. There are 16 tumors contrast-enhanced ultrasound was successful.(1)Nude mice gallbladder carcinoma subcutaneous transplant tumor CEUS performed the rapid circular enhancement in early phase of enhancement. The tumors were divided into the uniform enhancement group and the the circular enhancement group according to whether the tumor center enhance or not in the peak.5 of them performed uniform enhancement, and 11 of them performed the circular enhancement, in which we could see the non-enhanced area in the central parts of the tumor. After the peak, the tumor in the uniform enhancement group cleared gradually performed low enhancement, while in thecircular enhancement group, the edge parts of the tumor cleared gradually performed low enhancement, the central parts of the tumor still no enhanced.(2)The group of the uniform enhancement showed that the tumor was whole pale white, texture was tough, and there were no necrosis areas. HE staining showed that the tumor cells are uniformly distributed, no obvious necrosis areas. The group of the circular enhancement showed that the central parts of the tumor were pale yellow chyliform putrescence, the edge parts of the tumor were pale, texture was tough. HE staining showed that the cell structure disappeared in the necrosis areas, the nuclear fragmented, these ingredients and disintegration of the interstitial fused into a piece of fuzzy granular,amorphous red dye substance.(3)There was positive correlation between MVD and peak intensity(PI)(r=0.64,P=0.008), but MVD showed no correlation with other CEUS quantitative parameters. The expression of VEGF were not correlated with TIC parameters(all P>0.05). There was positive correlation between PCNA and peak intensity(PI)(r=0.51, P=0.042), but PCNA showed no correlation with other CEUS quantitative parameters. MVD had positive correlation with expression of VEGF(r=0.68, P=0.004), MVD had positive correlation with expression of PCNA(r=0.65, P=0.006), VEGF had positive correlation with expression of PCNA(r=0.61, P=0.012).Conclusion:(1)Nude mice gallbladder carcinoma transplant tumor enhancement characteristics were consistent with pathology, CEUS can reflects nude mice gallbladder carcinoma transplant tumor blood perfusion characteristics and distribution.(2)The peak intensity(PI) of CEUS quantitative parameters have positive correlation with MVD, PCNA in nude mice gallbladder carcinoma transplant tumor, it can indirectly reflect the MVD, PCNA and may be helpful to evaluate tumor angiogenesis and cell proliferation state.(3)The relationships between MVD and PCNA and between MVD and VEGF and between VEGF and PCNA are all of positive linear correlation. It indicate there is the relationship of reciprocal promotion between tumor angiogenesis and cell proliferation,which is good for tumor growth.