An Experimental Study Of Contrast-enhanced Ultrasound In Quantitative Evaluation Of Chemotherapy Efficacy In Transplanted Tumors Of Laryngopharyngeal Squamous Cell Carcinoma

Objective:To investigate the feasibility of quantitative parameters of time-intensity curve of contrast-enhanced ultrasound in evaluating the efficacy of cisplatin chemotherapy and tumor angiogenesis in laryngeal squamous cell carcinoma graft model of nude mice.Method:The transplanted tumor model of human laryngopharyngeal squamous cell carcinoma in nude mice of FaDu was established and randomly divided into normal saline control group,low-dose cisplatin chemotherapy group(3mg·kg^-1·d^-1),medium-dose cisplatin chemotherapy group(4mg·kg^-1·d^-1),and high-dose cisplatin chemotherapy group(5mg·kg^-1·d^-1)with 8 mice in each group.When the tumor block volume of the transplanted tumor reached 100mm³,CEUS examination was performed to determine the size of the transplanted tumor in each group.Dynamic imaging was analyzed by the built-in analysis software of the machine,time-intensity curve was drawn,and quantitative parameters were obtained:peak intensity（PI）,area under curve（AUC）,time to peak（TTP）and arrival time（AT）.One week after administration,CEUS examination was performed again,tumor size and CEUS quantitative parameters were recorded,tumor volume differences of transplanted tumors were compared among the groups,tumor inhibition rate was calculated,and quantitative parameters differences of CEUS among the groups were analyzed and compared.The nude mice were sacrificed after CEUS,and the tumors were stripped for pathological observation.Immunohistochemical method was used to detect tumor microvascular density,and the correlation between CEUS quantitative parameters and immunohistochemical MVD,immunohistochemical MVD and tumor graft volume,and immunohistochemical MVD and tumor graft volume was analyzed.Results:1.The tumor volume of transplanted nude mice after chemotherapy was significantly different between the normal saline control group and the cisplatin high-medium low-dose chemotherapy group（P<0.05）,and the tumor inhibitory rate increased with the increase of the dose given to each group.2.Quantitative parameters of contrast-enhanced ultrasound（PI,AUC and TTP）were significantly different between normal saline control group and cisplatin chemotherapy group（P<0.05）,while AT was not significantly different among all groups（P>0.05）.3.Pearson correlation analysis showed that quantitative parameters PI and AUC were positively correlated with pathological MVD（r=0.708,r=0.866,both P<0.05）.There was a positive correlation between tumor volume and MVD（r=0.752,P<0.05）.The quantitative parameters of contrast-enhanced ultrasound PI and AUC were positively correlated with the tumor volume of transplanted tumor（r=0.0.730,r=0.866,P<0.05）.Conclusions:1.Cisplatin chemotherapy can inhibit the growth of human laryngopharyngeal squamous cell carcinoma transplanted in nude mice of FaDu.2.CEUS quantitative parameters PI,AUC and TTP showed significant differences between the control group and the cisplatin chemotherapy group,suggesting that they could be used as reliable indicators for CEUS to quantitatively evaluate the efficacy of cisplatin chemotherapy in xenograft models of laryngopharyngeal squamous cell carcinoma in nude mice,indicating that CEUS quantifying blood perfusion of laryngopharyngeal squamous cell carcinoma has certain value for evaluating the efficacy of cisplatin chemotherapy and angiogenesis.3.The quantitative parameters PI and AUC of CEUS in nude mice transplanted tumors are positively correlated with MVD,which can indirectly reflect the microvascular density of transplanted tumors,which is conducive to the evaluation of tumor angiogenesis and provides important information for clinical research on the angiogenesis and tumor growth of laryngopharyngeal squamous cell carcinoma.