Experimental Study On Quantitative Assessment Of Microscopic Infiltrating Area And Simple Edema Area Of VX2 Malignant Bone Tumor In Rabbits By IVIM-DWI And DCE-MRI

Objective:The quantitative parameters of intravoxel incoherent motion diffusion weighted imaging（IVIM-DWI）and dynamic contrast-enhanced magnetic resonance imaging（DCE-MRI）were analyzed and compared with pathology,to investigate the value of quantitative parameters of DCE-MRI and IVIM-DWI in differentiating microscopic infiltration area and simple edema area in the transitional zone of VX2malignant bone tumors in rabbits.Methods:The right tibial metaphysis of New Zealand white rabbits was selected to establish a rabbit VX2 malignant bone tumor model.Twenty-six model rabbits with microscopic infiltrating area and simple edema area were included in the study.All of the26 cases underwent routine MRI,IVIM-DWI and DCE-MRI examinations after 2 weeks of feeding,and the right leg was retained for gross specimens and pathological sections（HE staining）.Observing the marginal area of the tumor in the medullary cavity of the pathological section,using pathology as the gold standard and imaging images,point-to-point comparison was carried out to determine the microscopic invasion area and simple edema area in the tumor transition area on IVIM-DW images and DCE-MR images,respectively in each of the selected region of interest area（ROI）,using MR Body to process IVIM-DW images,Syngo via workstations to process DCE-MR image,get the value of True Diffusion（D）,Perfusion-related pseudodiffusion（D*）and perfusion fraction（f）,the value of Volume transfer constant(K^trans),Reflux constant(K_ep),Extra-vascular extra-cellular volume fraction（V_e）in micro infiltration area and simple edema area value.The data consistent with normal distribution is represented by（?）±s,and the data non-normal distribution is represented by the median（upper and lower quartiles）,using independent sample t-test or Mann-Whitney U test to compare various parameter values in whether there is statistical difference between different areas.Logistic regression analysis was used to evaluate the value of IVIM-DWI combined with DCE-MRI in distinguishing the microscopic invasion area from the simple edema area of malignant bone tumor.Receiver Operating Characteristic Curve（ROC Curve）was drawn for each parameter to distinguish different regions.According to the Area Under Curve（AUC）,the diagnostic efficiency,optimal parameters and threshold values of different parameters to distinguish different regions of tumor boundary were calculated.Spearman correlation analysis was used to analyze the correlation between the perfusion parameters D*and f values of IVIM-DWI and the perfusion indexes K^trans,K_epand V_eof DCE-MRI.SPSS24.0 software was used for statistical processing.Results（1）Preparation of model rabbits,imaging examination and preparation of pathological sectionsA total of 56 model rabbits were prepared,and 37 of them survived and successfully completed DCE-MRI,IVIM-DWI examination and pathological sections（HE staining）.The pathological sections were observed,among which 11 cases showed no microscopic infiltrating area at the tumor edge,while 26 cases showed microscopic infiltrating area and simple edema area.Therefore,26 cases of malignant bone tumor model rabbits were included in the experimental study.（2）Statistical results of IVIM parameters in microscopic infiltrating area and simple edema areaThe D value of the tumor microinvasion area and the simple edema area were（0.901±0.195）×10^-3mm²/s,（1.180±0.271）×10^-3mm²/s,and the value of f were13.355±5.311 and 9.674±4.914,respectively.The difference between the value of D and f in the two areas was statistically significant（t=-4.245,P=0.000;t=2.594,P=0.012）.D*values were（1.070±0.377）and（1.109±0.557）×10^-3mm²/s,respectively.The difference of D*values in the two regions was not statistically significant（t=-0.301,P=0.765）.D,D*,f corresponding quantitative parameters area under curve（AUC）were 0.822,0.500,0.740,true diffusion coefficient D has the highest diagnostic efficiency,and the value of D is0.988×10^-3mm²/s,which is the threshold for distinguishing the microscopic infiltrating area from the simple edema area in the transitional area of malignant bone tumor.The sensitivity and specificity were 84.62%and 76.92%,respectively.（3）Statistical results of DCE-MRI parameters in microscopic infiltrating area and simple edema areaThe values of K^transin the tumor microinvasion area and the simple edema area were0.340（0.272,0.388）,0.212（0.165,0.285）min^-1,K_epvalues were（0.642±0.192）,（0.491±0.186）min^-1,and V_evalues were 0.532（0.478,0.589）,0.392（0.338,0.637）min^-1,respectively.The values of K^trans,K_epand V_ein the microinvasion area and the simple edema area were higher than those in the simple edema area.The differences of K^transand K_epvalues in the two regions were statistically significant（Z=-4.320,P=0.000;t=2.890,P=0.006）,and there was no statistically significant difference in V_evalue between the two regions（Z=-1.483,P=0.138）.The area under the curve（AUC）of the quantitative parameters K^trans,K_epand V_ewere 0.849,0.739 and 0.620,respectively.K^transhad the highest diagnostic efficiency.The K^transvalue of 0.297min^-1was the threshold value for distinguishing the microscopic invasion area from the simple edema area in the transitional region of malignant bone tumor,and the sensitivity and specificity were92.31%and 65.38%,respectively.（4）IVIM-DWI combined with DCE-MRI was used to distinguish the microscopic infiltrating area of malignant bone tumor from the simple edema areaCombined IVIM-DWI and DCE-MRI parameters were analyzed,and the results showed that the combined diagnostic efficiency was improved,and the AUC of K^trans+D and K^trans+f reached 0.865 and 0.856.（5）Correlation between DCE-MRI and IVIM-DWI perfusion parametersThere was a moderate positive correlation between the perfusion parameters K^transof DCE-MRI and f of IVIM-DWI（r=0.409,P=0.003）,but there was no significant correlation between other parameters.Conclusion:The value of D of IVIM-DWI quantitative parameters had the highest diagnostic efficiency for distinguishing the microscopic infiltrating area of rabbit VX2malignant bone tumor from the pure edema area,while the value of K^transof DCE-MRI quantitative parameters had the highest diagnostic efficiency.Compared with the value of K^transof DCE-MRI,the quantitative parameter K^transof DCE-MRI has a higher diagnostic efficiency in distinguishing the microscopic infiltrating area from the pure edema area,and the combined application of the two parameters(K^trans+D and K^trans+f)can improve the diagnostic efficiency.Perfusion parameters K^transof DCE-MRI and f of IVIM-DWI were positively correlated to a moderate degree.