Multi-echo Dixon And HISTO Quantitative Techniques At MR To Assess A Rabbit Model Of NAFLD With Fibrosis

Objective: A rabbit model of NAFLD with varying degrees of fibrosis was established to investigate whether the presence of liver fibrosis has an impact on the relevance and diagnostic efficacy of MR multi-echo Dixon and HISTO sequences for quantifying hepatic steatosis.Methods:1.SubjectsTwenty-six New Zealand rabbits were randomly divided into the high-fat group(n=21)and the control group(n=5).MR multi-echo Dixon and HISTO sequences were performed at 3 to 22 weeks to measure lipid density fat fraction.HE staining,Masson staining and Prussian blue staining were applied to observe liver fatty liver grading,fibrosis grading and iron deposition distribution.Liver fat content was obtained by acid hydrolysis.2.Statistical analysisComparisons between the two groups were made using the independent samples T-test.Pearson or Spearman correlation analysis was used to calculate the correlation between each index and the pathological and biochemical findings,and the correlation coefficients were compared using the r to z Fisher transformation and assessed using the Z-test.The diagnostic performance and threshold of ME Dixon-PDFF and HISTO-PDFF in identifying moderate or severe steatosis versus mild or no steatosis was evaluated by depicting ROC curves,and the area under the ROC curve was compared using the Z-test.Results:1.Four rabbits died in the high-fat group,the remaining 17 were eventually moulded successfully and all five rabbits in the normal group survived.2.There was a high positive correlation between ME Dixon-PDFF and HISTO-PDFF values measured by MRI in all experimental rabbits(n=22)(r=0.949,P=0.000)and the difference between the two serial measurements was not statistically significant(P=0.539).3.ME Dixon-PDFF and HISTO-PDFF were all positively correlated with LFC in the high-fat group(r=0.682 and 0.495,P < 0.05).The rabbits in the high-fat group were grouped according to fibrosis classification.With no or early fibrosis stage(F0,F1),ME Dixon-PDFF and HISTO-PDFF were both highly positively correlated with LFC(r=0.951 and 0.941,P < 0.05).In both progressive and advanced liver fibrosis stages(F2-F4),ME Dixon-PDFF and HISTO-PDFF did not correlate with LFC(P > 0.05).4.The area under the curve for the ME Dixon-PDFF to distinguish moderate or severe steatosis from mild or no steatosis was 0.981,with a threshold of 6.12%;the area under the curve for the HISTO-PDFF to distinguish moderate or severe steatosis from mild or no steatosis was 0.976,with a threshold of 2.98%.The diagnostic efficacy of ME Dixon-PDFF and HISTO-PDFF was not significantly altered after exclusion of rabbits with progressive and advanced stages of liver fibrosis(F2-F4).Conclusion:1.The high-fat and high-cholesterol diet induced non-alcoholic fatty liver model with fibrosis in rabbits is feasible and simple.2.Quantification of liver fat using PDFF of MRI is feasible,but the presence of fibrosis reduces ME Dixon-PDFF and HISTO-PDFF correlation with liver tissue biopsy.3.In the presence of concomitant fibrosis,the multi-echo Dixon technique must be more accurate than the HISTO technique for quantifying liver fat.