A Comparative Study Of DCE-MRI And Pathology For Evaluation Of Early Periosteal Anomaly After Radiotherapy On Rabbit VX2 Bone Tumor Model

Objective:By analyzing the parameters of Dynamic contrast-enhanced MRI（DCE-MRI）and comparing it with pathology,the differences of parameters among the tumor invasion area,transitional area and thickened and oedematous area of early periosteal reaction after radiotherapy for VX2 malignant bone tumors in rabbits were studied,and the application value of DCE-MRI in the evaluation of early periosteum changes after radiotherapy for malignant bone tumors were discussed.Methods:30 rabbit VX2 malignant bone tumor models were established and randomly divided into experimental group and control group with 15 rabbits after two weeks.The experimental group received local radiotherapy（10Gy/1 time）and DCE-MRI scan was performed 1 day before radiotherapy and 3 days after radiotherapy,respectively.The DCE-MRI scan of control group was performed at the same time with the experimental group without any treatment.The gross specimen of the right tibia was collected after the end of the second MRI scan for HE staining and immunohistochemical staining.Observe the abnormal areas of periosteum in gross specimens and HE stained specimens and the abnormal areas of periosteum can be divided into tumor invasion area,transitional area and thickened and oedematous area,which can be matched with MRI images.Choose ROI in each region,and the parameters of ROI were generated through the hemodynamic two-compartment model for quantitative analysis.The parameters of DCE-MRI include K^trans,Kep,Ve and i AUC.Independent-samples T test and one-way analysis of variance were used to compare the differences of parameters among different areas of periosteal anomaly in the early stage after radiotherapy,and the receiver operating curve was drawn.The accuracy of DCE-MRI parameters in differentiating different areas of periosteum abnormalities was calculated according to the area under the curve（AUC）,and the correlation between the changes of parameters and MVD count and the expression of VEGF was discussed.Results:1.MVD count and VEGF expression in the periosteum tumor infiltrating area,transitional area after radiotherapy in the experimental group and control group:MVD count in the periosteum tumor infiltrating area and transitional area after radiotherapy in the experimental group was 22.89±2.05 and 15.72±1.81,respectively,while MVD count in the control group was 34.88±4.19 and 25.71±2.86,respectively,the differences between the two groups were statistically significant（P<0.05）.After radiotherapy of experimental group,the expression of VEGF in the tumor invasion area and transitional area was4.25±0.54 and 3.26±0.40,respectively,while that in the control group was 6.23±0.79 and4.53±0.42,respectively,with statistical significance between the two groups（P<0.05）.2.Comparison of DCE-MRI parameters between the experimental group and the control group in different regions with abnormal periosteum before and after treatment:After radiotherapy,the K^trans value of the periosteum tumor infiltrating area in the experimental group was lower than before,and the difference was statistically significant（P<0.05）.The values of K^trans and i AUC in the transitional zone was decreased after radiotherapy,and the differences were statistically significant（P<0.05）.There were no significant differences in K^trans,Kep,Ve and i AUC in the thickened and oedematous area before and after radiotherapy（P>0.05）.The values of K^trans,Kep and i AUC in the infiltrating area and transitional area in the control group were all increased at the same period after radiotherapy,with statistical significance（P<0.05）.There were no significant differences in K^trans,Kep,Ve and i AUC in the thickened and oedematous area before and after radiotherapy（P>0.05）.After radiotherapy,there were statistically significant differences in the values of K^trans,Kep and i AUC in the infiltrating area and transitional area between the experimental group and the control group within the same period（P<0.05）.3.Comparison of diagnostic efficacy of DCE-MRI parameters in different regions of periosteum between the experimental group and the control group after radiotherapy:Compared with the control group,the diagnostic efficiency of K^trans was the highest,with a threshold of 0.398,a sensitivity of 86.70%and a specificity of 73.70%.In the comparison of indicators of periosteum tumor transition zone in the experimental group after radiotherapy and the control group at the same period,K^trans value had the highest diagnostic efficiency with a threshold of 0.214,a sensitivity of 80.00%and a specificity of86.30%.4.Comparison of DCE-MRI parameters between the experimental group and the control group in different abnormal areas of periosteum:there were statistically significant differences in K^trans,Kep,Ve and i AUC values between the three groups before and after radiotherapy in the periosteum tumor invasion area,transitional area and periosteum thickened and oedematous area in the experimental group（P<0.05）.There were statistically significant differences in K^trans,Kep,Ve and i AUC values between the three groups before and after radiotherapy in the same period of the control group（P<0.05）.5.After radiotherapy,DCE-MRI parameters in the experimental group and control group were correlated with MVD count and VEGF expression:MVD count in the tumor infiltrating area of periosteum in the experimental group was positively correlated with K^trans and Kep values（r=0.959,P<0.05;r=0.713,P<0.05）;The expression level of VEGF was positively correlated with K^trans and Kep values（r=0.846,P<0.05;r=0.611,P<0.05）.In the experimental group,the MVD count in the periosteum tumor transitional zone after radiotherapy was positively correlated with K^trans and Kep values（r=0897,P<0.05;r=0.703,P<0.05）;The expression level of VEGF was positively correlated with K^trans and Kep values（r=0.818,P<0.05;r=0.564,P<0.05）.In the control group,there was a positive correlation between the MVD count and the K^trans and Kep values（r=0.895,P<0.05;r=0.893,P<0.05）;The expression level of VEGF was positively correlated with K^trans and Kep values（r=0.870,P<0.05;r=0.872,P<0.05）.In the control group,the MVD count in the periosteum tumor transitional zone was positively correlated with K^trans and Kep values（r=0.650,P<0.05;r=0.542,P<0.05）;The expression level of VEGF was positively correlated with K^trans and Kep values（r=0.843,P<0.05;r=0.780,P<0.05）.Conclusion:The quantitative parameters of DCE-MRI,Ktrans value and Kep value,were positively correlated with MVD count and VEGF expression in VX2 malignant bone tumors,which could distinguish the different area of periosteum of malignant bone tumors and reflect the change of tumor microvessel density and tumor growth status under the periosteum,so as to quantitatively evaluate the early periosteum changes after radiotherapy for malignant bone tumors.