Quantitative Assessment Of Peritumoral Microscopic Changes In Rabbit VX2 Liver Tumors And Prediction Of Tumor Growth Rate Based On T1 And T2 Mapping

【Background】During the progression of liver tumors,pathological changes have occurred in the peri-tumor region,but the peri-tumor changes cannot be observed visually using conventional MRI.Through changes in tissue relaxation time,T1 mapping and T2 mapping can provide insight into structural changes that cannot be observed by conventional MRI.【Objective】The purpose of this study was to evaluate the diagnostic efficacy of T1 mapping and T2mapping for peritumoral microscopic changes in a rabbit VX2 liver tumor model and to investigate the predictive value of changes in peritumoral T1 and T2 values for tumor progression.【Materials and Methods】Twenty-three normal New Zealand White rabbits were the subject of this study.Seventeen white rabbits were randomly selected as the experimental group after VX2 tumor implantation in the left liver lobe,and six white rabbits were sham-operated as the sham-operated group.The MRI scans were performed at different time points（14,21,28,and 35 days）after tumor implantation in the experimental group of white rabbits（N=17）.The same MRI scans were performed on day 14 after tumor implantation in the sham-operated group of white rabbits（N=6）.Two white rabbits in the experimental group were randomly selected for euthanasia and pathologic examination（HE stain and Masson’s stain）after each scan.All white rabbits in the sham-operated group were euthanized at the end of the first scan and pathologically examined（HE stain and Masson’s stain）.All MRI data measurements were performed independently by2 radiologists with more than 5 years of professional experience.The 3 mm and 3 mm-6 mm annular regions around the tumor were defined as ROI2 and ROI3,respectively,and the distribution of TI and T2 values in these region were defined as T1_ROI2,T1_ROI3,T2_ROI2,and T2_ROI3.The tumor growth rate（TGR）was expressed as the proportional change in the area of the largest dimension of the tumor from one week to the next.The data measured by 2radiologists were tested for consistency using Kendall’s W-coefficient.An independent samples t-test was performed to analyze the differences in T1_ROI2,T1_ROI3,T2_ROI2,and T2_ROI3 for all time points in the sham-operated group and in the experimental group.One-way ANOVA was used to analyze the variance of T1_ROI2,T1_ROI3,T2_ROI2 and T2_ROI3 at each time point of the experimental group.The diagnostic efficacy of T1_ROI2,T1_ROI3,T2_ROI2,and T2_ROI3 for positive peri-tumor changes was verified using the area under the curve（AUC）of the subject’s working characteristic.Pearson correlation analysis and multiple linear regression analysis were performed for T1ROI2,T1ROI3,T2ROI2,T2ROI3,and TGR.【Results】T1 and T2 values of peritumoral tissues in experimental group gradually increased with time,and fibrosis and edema appearing in peritumoral area in experimental group also increased with time.The liver tissue in the sham-operated group showed no significant abnormal changes on magnetic resonance imaging,and the histopathological findings of the liver in the sham-operated group showed no significant injurious changes or tumor cells.There was high agreement between the data measured by the two radiologists（Kendall’s coefficient of 0.988,P<0.05）.Independent samples t-test showed significant differences in T1_ROI2（P<0.05）,T1_ROI3（P<0.05）,T2_ROI2（P<0.05）and T2_ROI3（P<0.05）between the experimental and sham-operated groups.There were significant differences in T1_ROI2,T1_ROI3,T2_ROI2 and T2_ROI3 at each time point in the experimental group（P<0.05）.The AUC values of T1_ROI2,T1_ROI3,T2_ROI2 and T2_ROI3were 0.986（95%CI:0.9579 to 1.000,P<0.05）、0.969（95%CI:0.9240 to 1.000,P<0.05）、0.932（95%CI:0.8596 to 1.000,P<0.05）及0.748（95%CI:0.5281 to 0.9685,P<0.05）,respectively.GTR was positively correlated with T1_ROI2（r=0.535,P<0.05）,T1_ROI3（r=0.704,P<0.05）,T2_ROI2（r=0.481,P<0.05）,and T2_ROI3（r=0.430,P<0.05）.The results of multiple linear regression analysis showed significant linear correlations between TGR and T1_ROI2（P=0.014）,T1_ROI3（P=0.003）,and T2_ROI3（P=0.035）.There was no significant linear correlation between TGR and T2_ROI2（P=0.608）.【Conclusion】1.T1 mapping and T2 mapping can provide quantitative assessment of peritumoral microscopic differences in rabbit VX2 liver tumors.2.T1 mapping and T2 mapping can be used to predict the growth rate of the tumor to a certain extent.