A tri-phasic relationship between T2 relaxation time and magnetic resonance imaging (MRI)-derived apparent diffusion coefficient (ADC)

Early detection and grading of liver inflammation are important for the management of nonalcoholic fatty liver disease (NAFLD) patients. There is still lack of a noninvasive way for the inflammation characterization in NAFLD.

Water Specific MRI T1 Mapping for Evaluating Liver Inflammation Activity Grades in Rats With Methionine‐Choline‐Deficient Diet‐Induced Nonalcoholic Fatty Liver Disease

http://www.cell.com/article/S240584402203002X/pdf

Effects of chronic caffeine intake and withdrawal on neural activity assessed via resting-state functional magnetic resonance imaging in mice

Liver fibrosis represents one of the greatest challenges in medicine. The fact that it develops with the progression of numerous diseases with high prevalence (NAFLD, viral hepatitis, etc.) makes liver fibrosis an even greater global health problem. Accordingly, it has received much attention from numerous researchers who have developed various in vitro and in vivo models to better understand the mechanisms underlying fibrosis development. All these efforts led to the discovery of numerous agents with antifibrotic properties, with hepatic stellate cells and the extracellular matrix at the center of these pharmacotherapeutic strategies. This review focuses on the current data on numerous in vivo and in vitro models of liver fibrosis and on various pharmacotherapeutic targets in the treatment of liver fibrosis.

https://www.mdpi.com/1467-3045/45/5/270/pdf?version=1683800166

Preclinical Models and Promising Pharmacotherapeutic Strategies in Liver Fibrosis: An Update

Abstract Partial bile duct ligation (pBDL) is considered a well-tolerated cholestatic model. Magnetic resonance imaging (MRI) is one of the most widely used tools in noninvasive imaging. However, no systematic studies have reported the possible effects of repeated MRI assessments in the pBDL model. Sixty BALB/C mice were investigated. MRI images of each mouse were recorded once every 2 weeks for 6 weeks after pBDL or sham surgery. The reproducibility of the pBDL model and the reliability of MRI were examined by behavioral, physiological, biochemical, and pathological parameters. The mice showed no alterations on behavioral and physiological tests ( P &gt; 0.05) at 2, 4, and 6 weeks after pBDL. Repeated general anesthesia did not result in any impairment after pBDL ( P &gt; 0.05). The behavioral and biochemical parameters were not affected by repeated MRIs or repeated contrast-enhanced MRIs ( P &gt; 0.05). Pathological staining showed the homogeneous formation of collagenous fiber in the pBDL mice and did not indicate any influence of repeated contrast-enhanced MRI on the number of inflammatory cells or fibrotic formation ( P &gt; 0.05). Thus, pBDL is a reproducible model with many advantages for animal welfare and scientific research. Additionally, MRI, as a safe tool for longitudinal evaluation and is well tolerated in mice with cholestasis. 

/pdf/impact-of-partial-bile-duct-ligation-with-or-without-3gpzyc0e.pdf

Impact of partial bile duct ligation with or without repeated magnetic resonance imaging examinations in mice

BACKGROUND Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL Established PBDL models. POPULATION Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE 1 TECHNICAL EFFICACY: Stage 2.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmri.27925

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging.

Background In experimental animal models, implantation location might influence the heterogeneity and overall development of the tumor, leading to an interpretation bias. Purpose To investigate the effects of implantation location in experimental tumor model using magnetic resonance imaging (MRI) and pathological findings. Study type Prospective. Subjects Forty-five breast cancer-bearing mice underwent orthotopic (N = 15) and heterotopic (intrahepatic [N = 15] and subcutaneous [N = 15]) implantation. Field strength/sequence Sequences including: T1-weighted turbo spin echo sequence, T2-weighted blade sequence, diffusion-weighted imaging, pre- and post-contrast T1 mapping, multi-echo T2 mapping at 3.0 T. Assessment MRI was performed at 7, 14, and 21 days after implantation. Native T1, post-contrast T1, T2, and apparent diffusion coefficient (ADC) of tumors, the tumor volume and necrosis volume within tumor were obtained. Lymphocyte cells from HE day 14: 459.00 ± 26.11 vs. 436.83 ± 26.01 vs. 377.00 ± 27.83; day 21: 463.50 ± 23.49 vs. 458.00 ± 34.28 vs. 375.00 ± 30.55) were significantly different between three groups. Necrosis volumes of subcutaneous and intrahepatic tumors were significantly lower than those of orthotopic tumors. The CD31-positive rate in the intrahepatic implantation was significantly higher than in orthotopic and subcutaneous groups. Necrosis volume (r = -0.71), ADC (r = -0.85), and post-contrast T1 (r = -0.75) were strongly correlated with vascular invasion index. Data conclusion Orthotopic and heterotopic tumors have their unique growth kinetics, necrosis volume, and vascular invasion. Non-invasive MR quantitative parameters, including ADC and post-contrast T1, may reflect vascular invasion in mice. Level of evidence 1 TECHNICAL EFFICACY: Stage 3.

Orthotopic Versus Allotopic Implantation: Comparison of Radiological and Pathological Characteristics.

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Papers

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging.

Orthotopic Versus Allotopic Implantation: Comparison of Radiological and Pathological Characteristics.