Gd-EOB-DTPA-enhanced T1ρ Imaging Combined With Diffusion Metrics Of IVIM For Quantitative Assessment Non-alcoholic Fatty Liver Disease In Rabbits

PrefaceNon-alcoholic steatohepatitis(NASH)has potential risk of progression to cirrhosis.Early diagnosis is important for the treatment and prognosis of NAFLD.In recent years,a variety of non-invasive imaging methods have developed for assessment of hepatic fibrosis and fat content,such as transient elastography,MR spectroscopy,MR elastography,MR diffusion imaging,and T1ρ imaging etc.It has been reported that intravoxel incoherent motion(IVIM)and T1ρ imaging show some good prospects and advantages for the diagnosis of NASH.Combining with the application of GD-EOB-DTPA,it is expected to explore the mechanism of hepatocyte dysfunction due to inflammation and early fibrosis at a microscopic level.The purpose of this study was to investigate:(1)the effect of Gd-EOB-DTPA concentration on the T1ρ value and the appropriate concentration for observation of changes in T1ρ;(2)Repeatability of IVIM and Gd-EOB-DTPA enhanced T1ρ values of normal rabbits liver within a short term(one week);(3)The diagnostic performances of IVIM parameters and Gd-EOB-DTPA enhanced T1ρ to assess NASH severity,inflammation grades and early stage of fibrosis.Materials and methods:1.Effect of Gd-EOB-DTPA Concentration on T1ρ measurement0ml,0.06ml,0.12ml,0.24ml,and 0.36ml of Gd-EOB-DTPA were injected into a 50ml syringe to make a control,half to threefold dose Gd-EOB-DTPA model,and the T1ρ value and T1 signal intensity were measured.2.Feasibility and repeatability of IVIM and Gd-EOB-DTPA enhanced T1ρ mapping in normal rabbit liver imagingTen healthy New Zealand white rabbits were randomly selected for evaluating the feasibility and short-term(1 week)reproducibility of IVIM and Gd-EOB-DTPA for enhanced T1ρ mapping.Quadrant-scale method was used for subjective image quality evaluation.The inter-class correlation coefficients(ICCs)and Bland-Altman analysis were applied to evaluate the consistency and reproducibility of the IVIM and Gd-EOB-DTPA enhanced T1ρ mapping measurers.3.The evaluations of IVIM and Gd-EOB-DTPA enhanced T1ρ mapping on staging inflammation and fibrosis in NASHThis study was approved by the Ethical Committee of Medical Laboratory Animal Ethics of the Second Clinical College of Wuhan University(No.02516102B).A total of 26 male New Zealand white rabbits(6 months old,weighting 2.2-2.4 kg/body)were randomly divided into two groups:number of the control group(group A)is 6,the experimental group is 20.NASH model was established as Fu JF description,the control group was fed with standard diet,while the experimental group fed with high-fat diet(10%lard + 2%cholesterol + 88%standard feed).Duration of high fat and high cholesterol diet was 4 weeks(group B),8 weeks(group C),12 weeks(group D).Differences in T1ρ,T1ρ(HBP),ADC,f,D,and D*values among groups which divided by NAFLD scores,inflammation and fibrosis stages were compared respectively;the association of T1ρ and IVIM parameters with NAFLD scores,inflammation,and fibrosis grading was analyzed.ROC curve analysis was used to evaluate the diagnostic performance of T1ρ and IVIM parameters for NASH,inflammation grade,and hepatic fibrosis.Multiple linear regression equations were used to analyze the independent influence factors of T1ρ(HBP).Results:The T1ρ value showed an approximately linear downward trend(y=-37.1x+243.7),Gd-EOB-DTPA concentration ranged from 0.0125 mmol/l to 0.075 mmol/1,and was similar to shortened effect of T1 value on the T1WI enhancement imaging.The reduction rate of T1ρ relaxation(34.0%)on Gd-EOB-DTPA of the single-dose concentration was lower than that of T1 relaxation(61.6%).Between the initial and repeated scans,IVIM,T1ρ and T1ρ(HBP)images were all met the diagnostic requirements and these MR examinations were feasible.There was no significant difference in ICCs among IVIM,T1ρ and T1ρ(HBP)between two raters.In the IVIM parameters,the overall average ICCs between the initial and repeated scans were>0.9,and the agreement was good.However,the overall average ICCs of the ADC,D*,and f values were all<0.7 but>0.5,and the agreement was fair.The mean ICCs of both T1ρ and T1ρ(HBP)were>0.7 and the agreement was good.T1ρ(HBP)had a good consistency between the initial and repeated examinations by Bland-Altman analysis.The f value was negatively correlated with the NAS score(r=-0.530,P<0.01).The f value of the fibrosis S1-2 was significantly lower than that of the S0(P=0.0314).There was no statistical difference D,D*,ADC in NASH score,inflammation,fibrosis stage.T1ρ and T1ρ(HBP)values were positively correlated with NAS scores and inflammation grades.Fibrosis(R2=0.624,P=0.002)and inflammation(R2=0.746,P=0.002)were major independent factors of T1ρ(HBP).The AUCs for the diagnosis of NASH for T1ρ,T1ρ(HBP),ADC,D,D*,and f values were 0.849,0.949,0.728,0.596,0.522,and 0.871 respectively.The AUC of T1ρ(HBP)+f in the diagnosis of NASH,G2-3 inflammation,and F1-2 fibrosis was 0.971,0.935,and 0.903 respectively.Conclusions:1.As the concentration of Gd-EOB-DTPA increases within triple dose,the value of T1ρ decreases linearly,which is similar to the change of T1 value;the relaxation effect of T1ρ relaxation rate is lower than that of T1 relaxation.The recommended contrast agent dose for Gd-EOB-DTPA enhanced T1ρ imaging is ≥0.025 mmol/kg.2.Among the I VIM parameters,the D value is highly reproducible,and the D*and ADC values have greater variability.Both T1ρ and T1ρ(HBP)have a good repeatability.3.The f value in IVIM parameters is helpful for the detection of NASH,but D,D*,and ADC values have no significant value for NASH inflammation and S1-2 fibrosis;Tlp(HBP)has an excellent diagnostic performance for NASH score,inflammation grade and early stage of fibrosis,better than non-enhanced T1ρ;the combination of T1ρ(HBP)and f is an accurate non-invasive MR imaging biomarker for assessment of NASH.