The Experimental Study Of Multi-parametic Functional MRI For Assessing Liver Fibrosis

Part Ⅰ Intravoxel Incoherent Motion DWI for Assessing Liver Fibrosis:the Pilot Study of Optimal Selection of b ValuesPurpose To investigate the optimal selection of bvalue in IVIM-DWI for assessing the rat model of liver fibrosis.Materialsand Methods Liver fibrosis in rats was induced by intraperitoneal injection of 1ml/kg 50% CCl4 twice a week for 14 weeks.Control rats were injected with saline.IVIM-DWIwas performed for all rats,the images were processed by Fire Voxel software.Fitting DT,DP and f using three b value schemes(Scheme A : 0,10,20,40,80,200,400,800 s/mm28 b values;Scheme B : 0,10,20,80,200,800s/mm26 b values;Scheme C : 0,10,80,800 s/mm24 b values),according to the IVIM-DWI biexponential model.Liver fibrosis was graded using the Metavir score system: no fibrosis(F0),mild fibrosis(F1-F2)and advanced fibrosis(F3-F4).The three groups of DT,DP and f were compared by one way ANOVA test,and ROC analysis and Z test was used to compare the predicting performance of DT,DP and f for staging hepatic fibrosis.Results Sixty-one rats were included: no fibrosis(n=11),mild fibrosis(n=25)and advanced fibrosis(n=25).All the 61 rats were examined IVIM-DWI successfully.There were significant differences in the DT1,f1 and DT2 of the Scheme A and Scheme B between the three group rats(P < 0.05).ROC analysis and Z test results showed that DT1 was better than f1 and DT2 for predicting F0,and DT1 was better than DT2 for predicting F3-F4.Conclusion Scheme A is the best program in the b value schemes,because of the good results of the IVIM-DWI parameter fitting.Scheme B can reduce 1/3scan time,and IVIM-DWI fitting parameter DT had prediction value for liver fibrosis stage,so Scheme B had the potential valueof clinical application.Application of bvalues of less than the scheme B can not suitable for the implementation of IVIM-DWI biexponential fitting.Part Ⅱ Value of IVIM-DWI Histogram Analysis in the In Vivo Evaluation of Liver Fibrosis in a Rat ModelPurpose To investigate the in vivo noninvasive assessment value of quantitative parameters and their derived histogram parameters of the biexponential IVIM-DWI model on liver fibrosis in a rat model.Materialsand Methods Liver fibrosis in rats was induced by intraperitoneal injection of 1ml/kg 50% CCl4 twice a week for 14 weeks.Control rats were injected with saline.8b values(0,10,20,40,80,200,400,800 s/mm2)IVIM-DWIwas performed for all rats,the images were processed by Fire Voxel software.Fitting DT,DP,f and ADC using the IVIM-DWI biexponential and monoexponential model,and using SPSS 19.0 to calculate the histogram parameters,including skewness,kurtosis and the 25,50,75 percentile.After MRI examination,the rats were sacrificed to obtain liver specimens,HE,Masson staining and CD31,VEGF and HIF-1α immunofluorescence staining were performed.Liver fibrosis was graded using the Metavir score system: no fibrosis(F0),mild fibrosis(F1-F2)and advanced fibrosis(F3-F4).The three groups of DT,DP and f and their histogram parameters were compared by one way ANOVA,Spearman test was used to analyze correlation between DT,DP and f and their histogram parameters and liver fibrosis stage and immunofluorescent biomarkers,and ROC analysis and Z test was used to compare the predicting performance of DT,DP and f and their histogram parameters for staging hepatic fibrosis.Results Sixty-one rats were included: no fibrosis(n=11),mild fibrosis(n=25)and advanced fibrosis(n=25).All the 61 rats were examined IVIM-DWI successfully.DT and its 25,50,75 Percentiles,f and its 25,50 Percentiles were decreased with the progression of hepatic fibrosis,and there was a difference between the three groups(P <0.05).There was a high-to-moderate degree of negative correlation between DT histogram parameters and liver fibrosis stage and immunofluorescent biomarkers,and there was most closely correlation between the DT and hepatic fibrosis stage(r=-0.891),CD31(r=-0.777),between DT75 and VEGF(r=-0.630),and between Ktrans and HIF1α(r=-0.665).The results of ROC analysis and Z test showed that the prediction performancs of DT,DT50 and DT75 on F0 was better than that of f25,and the prediction performancs of DT on F3-F4 was better than that of f.Conclusion Water molecular diffusion and blood perfusion leads to apparent diffusion changes during the progression of liver fibrosis,DT and f has potential value in clinical application in early diagnosis and monitoring liver fibrosis,and DT is better than f.Histogram analysis method can provide more meaningful noninvasive quantitative parameters,percentiles of DT and f may be reflect the heterogeneity of liver fibrosis.Part Ⅲ Correlation Between Diffusion Kurtosis Imaging Quantitative Parameters and Liver Fibrosis Staging in a Rat ModelPurpose To investigate the non-Gaussian diffusion characteristics of hepatic fibrosis and the value of hepatic fibrosis staging in a rat model by DKI model.Materialsand Methods Liver fibrosis in rats was induced by intraperitoneal injection of 1ml/kg 50% CCl4 twice a week for 14 weeks.Control rats were injected with saline.6b values(0,50,500,1000,1500,2000 s/mm2)DKI was performed for all rats,the images were processed by Fire Voxel software,fitting MK,MD and ADC using the DKI and monoexponential model,and using SPSS 19.0 to calculate the histogram parameters,including skewness,kurtosis and the 25,50,75 percentile.After MRI examination,the rats were sacrificed to obtain liver specimens,HE and Masson fiber staining were performed.Liver fibrosis was graded using the Metavir score system: no fibrosis(F0),mild fibrosis(F1-F2)and advanced fibrosis(F3-F4).The three groups of MK,MD and ADC and their histogram parameters were compared by one way ANOVA,Spearman test was used to analyze correlation between MK,MD and ADC and their histogram parameters and liver fibrosis stage,and ROC analysis and Z test was used to compare the predicting performance of MK,MD and ADC and their histogram parameters for staging hepatic fibrosis.Results Sixty-one rats were included: no fibrosis(n=11),mild fibrosis(n=25)and advanced fibrosis(n=25).All the 61 rats were examined DKI successfully.The difference of MK,MD and ADC and their 25,50,75 percentiles between the three groups was statistically significant(P < 0.01),MD,ADC values decreased with the progression of fibrosis,and MK increased with the progression of fibrosis.There was a moderate positive correlation between MK histogram parameters and liver fibrosis stage,and the relationship between MK75 and liver fibrosis stage(r=0.780)was the most closely related.The results of ROC analysis showed that MK was better than ADC in the prediction of F3-F4.Conclusion DKI provides a noninvasive quantitative evaluation method for liver fibrosis induced by CCl4 in rats,MK reflect the degree deviates from the ideal Gaussian diffusion behavior in the progression of liver fibrosis,which contribute to the assessment of the staging of liver fibrosis.Histogram analysis method provides more valuable noninvasive quantitative parameters,MK and its derived histogram parameters can reflect the liver fibrosis heterogeneity.Part Ⅳ Experimental Study of Perfusion Parameters of DCE-MRI for Assessing the Angiogenesis of Hepatic FibrosisPurpose To investigate the utility of the quantitative perfusion parameters and their derived histogram parameters using dynamic contrast-enhanced MRI(DCE-MRI)for staging liver fibrosis induced by carbontetrachloride(CCl4)in rats and assessing its angiogenesis in fibrogenesis.Materialsand Methods Liver fibrosis in rats was induced by intraperitoneal injection of 1ml/kg 50% CCl4 twice a week for 14 weeks.Control rats were injected with saline.T1 MAP and DCE-MRI was performed for all rats successfully,using e-THRIVE sequence with 75 phases,and the time resolution was 5S,the images were processed by Omni-Kinetics 2.0 software.Ktrans,Kep,Ve and i AUC of the liver parenchyma were measured,and using SPSS 19.0 to calculate the histogram parameters of Ktrans and i AUC,including skewness,kurtosis and the 25,50,75 percentile.After MRI examination,the rats were sacrificed to obtain liver specimens,HE,Masson staining and CD31,VEGF and HIF-1αimmunofluorescence staining were performed.Liver fibrosis was graded using the Metavir score system: no fibrosis(F0),mild fibrosis(F1-F2)and advanced fibrosis(F3-F4).The three groups of DCE-MRI quantitative and semi-quantitative perfusion parameters were compared by one way ANOVA,Spearman test was used to analyze correlation between perfusion parameters and liver fibrosis stage and immunofluorescent biomarkers,and the ROC analysis was used to compare the predicting performance of Ktrans and i AUC for staging hepatic fibrosis.Results Sixty-one rats were included: no fibrosis(n=11),mild fibrosis(n=25)and advanced fibrosis(n=25).Ktrans,i AUC and its 25,50,75 Percentiles were decreased with the progression of hepatic fibrosis,and there was a significant difference between the three groups(P < 0.01).There was a high-to-moderate degree of negative correlation between Ktrans histogram parameters and liver fibrosis stage and immunofluorescent biomarkers,and there was most closely correlation between the median of Ktrans and hepatic fibrosis stage(r=-0.90),CD31(r=-0.82)and VEGF(r=-0.64),and between Ktrans and HIF1α(r=-0.58).The results of ROC analysis showed that the performancs of Ktrans and i AUC were almost equivalent to the prediction of F0,and the prediction performancs of Ktrans on F3-F4 was better than that of i AUC.Conclusion DCE-MRI provides a noninvasive and quantitative evaluation method for rat model of hepatic fibrosis,Ktrans was better than i AUC for the detection and staging of rat liver fibrosis induced by CCl4.DCE-MRI quantitative perfusion parameter Ktrans was correlated with the stage and angiogenesis of hepatic fibrosis,which reflected the changes of the permeability of the hepatic sinusoid during the course of the sinusoidal capillarization.The histogram analysis of DCE-MRI quantitative parameters had added value to the hepatic fibrosis assessment,percentiles of Ktrans may be reflect the heterogeneity of liver fibrosis.