Introduction

HF( hepatic fibrosis)is the common basis of chronic liver disease[1]. Although liver biopsy is the gold standard for clinical diagnosis of HF, 25%-40% of patients will have pain, 0.3%-0.6% of patients will have bleeding, and severe cases can even lead to death[2]. (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid, Gd-EOB-DTPA) has both extracellular space and hepatocyte contrast agent characteristics [3]. Gd-EOB-DTPA T1 mapping can not only reflect the distribution of contrast agent by directly measuring the change of T1 value before and after enhancement, but also reflect the change of extracellular volume by indirectly measuring the change of extracellular volume fraction (ECV) during HF[4-5]. This study intends to explore the value of Gd-EOB-DTPA T1 mapping imaging technology quantitatively evaluate HF.

Methods

Animal model
One hundred rabbits were randomly divided into two groups: the HF group (n=80) and the control group (n=20). The HF model was established by carbon tetrachloride (CCl₄) in our experiments, whereas control rabbits received a subcutaneous injection of normal saline.
MRI experiment
MR scan using Philips Ingenia 3.0 T superconducting magnetic resonance scanner. At the 4th, 5th, 6th, and 15th weekends, 20 rabbits in the HF group and 5 rabbits in the control group were randomly selected for axial liver MRI scan: ①Axial T1WI; repetition time/echo time=400/18 ms, flip angle=90 °, layer thickness = 4 mm, layer spacing = 0.4 mm. ②Using the modified Look-Locker sequence to obtain T1 mapping images before enhancement and 10 and 20 minutes after enhancement: repetition time/echo time = 3/1 ms, flip angle = 20°, layer thickness = 4 mm, layer spacing = 0.4 mm.
Data analysis
All images are transmitted to the Philips workstation. Two doctors in the field of abdominal imaging research independently analyze MR images under the premise of double-blind. In case of differences, they will be resolved through discussion. After avoiding hepatic blood vessels, bile ducts, and liver edges on the T1_native, T1_{10 min}, and T1_{20 min} images, delineate ROIs on the left, middle, and right lobes of the liver. The area of the ROI is 15-20 mm². The average value of the obtained parameters is used as the final liver Quantitative parameter values of T1_native, T1_{10 min}, and T1_{20 min}. Finally, obtain the ECV parameter value through the formula, ECV=(1/LT1_post-1/LT1_native)/(1/AT1_post-1/AT1_native)×(1-HCT), where T1_native is the liver T1 value before enhancement, and T1_post is the post-enhancement (10, 20 min) T1 value, AT1_native is the T1 value before abdominal aorta enhancement, AT1_post is the T1 value after abdominal aorta enhancement (10, 20 min), and HCT is hematocrit.
All statistical analyses were performed in SPSS and MedCalc software. Kolmogorov-Smirnov test whether the measurement data conform to the normal distribution. Spearman correlation was used to analyze the correlation between the quantitative parameter values (T1_native, T1_{10 min}, T1_{20 min}, ECV_{10 min}, ECV_{20 min}) and HF staging. The LSD method of one-way analysis of variance was used to compare the differences in quantitative parameter values between HF stages. The ROC curve method was used to analyze the value of each quantitative parameter in the differential diagnosis of HF. P<0.05 means the difference is statistically significant.

Results

T1_{20 min} and ECV_{20 min} were significantly positively correlated with the progression of HF (r=0.818, 0.766, P＜0.001), T1_native and T1_{10 min} had a moderate positive correlation with the progression of HF (r=0.685, 0.428, P＜0.001), and ECV_{10 min} showed a weak correlation (r=0.278, P=0.01). Except for the F1 vs F2 and F3 vs F4 phases, the T1_native differences in the other HF groups were statistically significant (P<0.05). There was no significant difference in T1_{10 min} in F0 vs F2, F1 vs (F2, F3, F4), and F3 vs F4 (P>0.05). The difference in T1_{10 min} in the other groups was statistically significant (P<0.05); T1_{20 min} can effectively identify the rest of the HF groups except F0 vs F1; except for the significant difference in ECV_{10 min} in F0 vs F4 (P<0.05), there is no statistically significant difference in ECV_{10 min} in the other groups. For the ECV_{20 min} value, except for the F0 vs F1, F2 vs F3 stage ECV_{20 min} value, there was a statistical difference (P>0.05), and the ECV_{20 min} value of the other groups were statistically significant (P<0.05). T1_{20 min} differential diagnosis AUC of ≥F1, ≥F2, ≥F3, ≥F4 were 0.90, 0.93, 0.93, 0.92, respectively, which were overall higher than ECV _{20 min} (AUC=0.85, 0.89, 0.89, 0.95) and T1_native (AUC=0.98, 0.81, 0.85, 0.76), T1_{10 min} (AUC=0.80, 0.68, 0.76, 0.66) and ECV_{10 min} (AUC=0.65, 0.65, 0.66, 0.65).

Conclusion

Gd-EOB-DTPA-based enhanced T1 mapping imaging quantitative parameters and ECV values are closely related to the progress of HF, and have great diagnostic and differential diagnostic value for diagnosis and staging HF.

Acknowledgements

This work was part of Surface project of National Natural Science Foundation of China (Quantification of iron deposition in diabetic nephropathy using by MRI ).