Evaluation Of Early Changes Of Rabbit VX2 Malignant Bone Tumor After Radiotherapy By MR-DKI:An Experimental Study

Objective:To compare the correlation between the quantitative parameters of diffusion kurtosis imaging（DKI）and the expression of tumor cell density（TCD）and apoptosis index（AI）before and after radiotherapy for rabbit VX2 malignant bone tumors,and to explore the application value of DKI in monitoring the curative effect of early radiotherapy for malignant bone tumors.Methods:The post-radiotherapy response was evaluated in a rabbit VX2 bone tumor model（n=35）using magnetic resonance imaging（MRI）,diffusion weighted imaging（DWI）,DKI,and comparison with histopathologic examinations.Rabbit bone tumor models were randomly divided into three groups:pre-treatment,post-treatment,and untreated control groups.MR scans were performed on day 1 and day 3 after 2 weeks of tumor implantation in the treatment group and the control group.The post-treatment group received a single dose of 10 Gy radiotherapy,and rabbits were evaluated by longitudinal MR scan after three days.Subjects were divided into good response and poor response groups according to the treatment response.Quantitative analysis of images by dispersion model,apparent diffusion coefficient（ADC）and DKI parameters（mean diffusion coefficient[MD]and mean kurtosis[MK]）were recorded.Hematoxylin-eosin（HE）staining and TUNEL immunohistochemical examination were performed.The independent samples t-test was used to compare the differences between the ADC and DKI parameters,TCD,and cellular apoptosis in the tumors in each group.Pearson’s correlation coefficient was used to analyze the correlations between pathological indices and the corresponding ADC and DKI parameters.The diagnostic efficacy of MR parameters in good response group and adverse reaction group was evaluated by receiver operating characteristic curve（ROC）.Results:（1）Comparison of quantitative parameters of DKI in solid area of tumor between pre-and post-treatment group and control group.The values of ADC and MD in solid area of tumor after treatment were higher than those before treatment,and the difference was statistically significant（p<0.05）.There was significant difference in MD value between good reaction group and adverse reaction group（p<0.05）,but there was no significant difference in ADC value between the two groups（p>0.05）.The value of MK in the good response group was significantly lower than that before treatment（p<0.05）,but there was no significant difference between the good reaction group and the adverse reaction group（p>0.05）.In the control group,the values of ADC,MD and MK in the solid area of tumor were not significantly different from those before treatment（p>0.05）.（2）Comparison of histopathological parameters of DKI in solid area of tumor between pre-treatment,post-treatment and control group.The density of tumor cells in the solid area of the tumor after treatment was lower than that before treatment,and the number of apoptotic cells was higher than that before treatment（p<0.05）.There was significant difference between the good reaction group and the adverse reaction group（p<0.05）.There was no significant difference in tumor cell density and apoptosis index in the control group compared with those before treatment（p>0.05）.（3）Correlation between pathological indexes and quantitative parameters of ADC and DKI.MD and ADC were negatively correlated with TCD（r=-0.771 and r=-0.760,p<0.001,respectively）and positively correlated with apoptosis(（r=0.625,p<0.001 and r=0.543,p=0.001）.MK was not significantly correlated with cell density and apoptosis.（4）Analysis of diagnostic efficiency of MR quantitative parameters.The AUC values of ADC,MD and MK between the two groups after treatment were 0.813（95%CI:0.521-0.965）,0.917（95%CI:0.646-0.997）and 0.708（95%CI:0.413-0.913）,respectively.ROC suggested that the optimal threshold of MD was 0.91×10^-3mm²/s,with a sensitivity of 75%and specificity of 100%.Conclusion:The MD value of DKI parameter has a significant negative correlation with TCD count and AI expression of VX2 malignant bone tumor,which can reflect the changes of rabbit VX2 malignant bone tumor after radiotherapy to some extent,suggesting that MD value is the best potential biomarker for alternative imaging.