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Changes of native T1, T1ρ, and T2 values during liver fibrosis in rats at 11.7T MRI
Yimei Lu1, Qianfeng Wang2, and Dengbin Wang1
1Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, shanghai, China, 2Fudan University, Institute of Science and Technology for Brain-Inspired Intelligence, shanghai, China

Synopsis

The relaxation times (including T1, T2, and T1ρ) are tissue-specific parameters , and depend on the physical, chemical and biological characteristics of the tissue. In liver fibrosis, the deposition of macromolecules (such as collagen fibers, proteoglycans, etc.) in the extracellular matrix may affect the movement of free protons, resulting in tissue relaxation times change. Many studies have shown that native T1 and T2 values are related to the degree of liver fibrosis. We investigate the influence of different pathological changes on T1 mapping, T1ρ, and T2 mapping in two vivo animal models of liver fibrosis, with a focus on liver fibrosis.

Purpose

Purpose: To investigate the influence of different pathological changes on T1 mapping, T1ρ, and T2 mapping in two vivo animal models of liver fibrosis, with a focus on liver fibrosis, and further to explore the accuracy of the quantitative parameters for staging liver fibrosis at 11.7T magnetic resonance imaging (MRI).

Methods

Methods: Using the intraclass correlation coefficient (ICC) to explore the repeatability of the quantitative parameters in 8 rats. Two animal models, the bile duct ligation (BDL) and carbon tetrachloride (CCl4), induced different degrees of liver fibrosis in 120 rats. The fibrosis stages, inflammatory activity grades, steatosis content, iron deposition, and cytokeratin 19 (CK19) expression were semi-quantified by using histology stain. To test differences in quantitative parameters and tissue analyses among groups by using one-way ANOVA. To explore independent influencing factors of quantitative parameters by using multiple regression analysis. The interaction between the two animal models on each quantitative parameter was tested by factorial design ANOVA. The ability of each quantitative parameters to stage liver fibrosis was quantified by using receiver operating characteristic (ROC) curve analysis.

Results

Results: Native T1, T2, and T1ρ values shared similar and excellent repeatability (ICC:0.86-0.92). The most sensitive and accurate method for staging liver fibrosis was native T1 mapping in both animal models, followed by T1ρ. We observed strong and moderate positive correlations between liver fibrosis stages and native T1 value (rho = 0.732 for the BDL model, and rho = 0.797 for the CCl4 model) as well as T1ρ value (rho = 0.676 for the BDL model, and rho = 0.611 for the CCl4 model). In addition, the area under the receiver operating curve (AUC) of native T1 value for distinguishing early (≤ F2) from late ( ≥ F3) fibrosis was higher than T1ρ value in the CCl4 model (AUC: 0.93 vs. 0.73, P < .05). T2 mapping showed a model-dependent pattern, revealing good performance in the BDL model but poor performance in the CCl4 model.

Conclusion

Conclusion: Native T1 mapping and T1ρ may be more valuable tools for noninvasively evaluating liver fibrosis than T2mapping. Compared with T1ρ, native T1 mapping may provide better accuracy for diagnosing early fibrosis.

Keywords

Keywords: Liver fibrosis · Magnetic resonance imaging · Native T1 mapping · T1ρ · T2 mapping

Acknowledgements

We thank Dr. XiaoyingWang, Department of Pathology (Xinhua Hospital), for the pathological analysis of liver specimens. We are also grateful to Xi Zhang, Ph.D. (ClinicalResearch Unite, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China), for her statistical support of this study.

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Figures

Fig 1. Images show liver specimens characterization of changes in fibrosis (Metavir stages F0-F4) in BDL and CCl4 model. Representative images of H&E-stained (top row) and Sirius red-stained (bottom row) liver tissue from each experimental group. H&E, hematoxylin and eosin, 200×original magnification; Sirius red stain, 200×original magnification. CCl4, carbon tetrachloride; BDL, bile duct ligation

Fig 2. Images show liver specimens characterization of changes in cytokeratin in BDL and CCl4 model of liver fibrosis. (a) Representative liver specimens (Metavir stages F0-F4) immunostained for cytokeratin 19 (CK19) in BDL and CCl4 model (400×original magnification). (b) CK19 positive area quantified using ImageJ by analyzing tissue sections stained with immunohistochemistry. (c) Scatterplots show correlations between T1, T2, T1ρ values and CK19 positive areas for the BDL and CCl4 model of rats. CCl4, carbon tetrachloride; BDL, bile duct ligation

Fig 3. Images show MRI measurements in vivo for BDL and CCl4 model of liver fibrosis. Representative axial images of (a) native T1 maps, (b) T1 ρ maps and (c) T2 maps for each group (Metavir stages F0-F4). The images (d-f) show the corresponding data for all rats in BDL and CCl4 model. One-way ANOVA followed by Scheffe post hoc test was performed. *P < 0.05, **P < 0.01, ***P < 0.001.

Fig 4. Graphs show receiver operating characteristic curves of native (a-c) T1, (d-f) T1ρ and (g-i) T2 values for diagnosing (a, d, g) significant fibrosis, (b, e, h) advanced fibrosis, and (c, f, i) cirrhosis. The pairwise comparison of independent ROC curves is used to compare the BDL model with the CCl4 model. P values are given for each comparison.

Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)
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