Magnetic resonance T1ρ relaxation in patients with liver fibrosis: a systematic review and meta-analysis

Mechanisms of hepatic fibrosis.

ObjectivesTo determine the potential of intravoxel incoherent motion (IVIM) MR imaging for staging of hepatic fibrosis (HF).MethodsWe searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D). The effect estimate was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI), using the fixed-effects model.ResultsOverall, we included six papers (406 patients) in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83–4.09, P = 0.006; WMD 13.10, 95% CI 9.53–16.67, P < 0.001; WMD 14.34, 95% CI 10.26–18.42, P < 0.001, respectively). Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06–3.18, P = 0.027; WMD 5.63, 95% CI 2.74–8.52, P < 0.001; WMD 3.30, 95% CI 2.10–4.50, P < 0.001, respectively). However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01─0.11, P = 0.105; WMD 0.04, 95% CI -0.01─0.10, P = 0.230; WMD 0.02, 95% CI -0.02─0.06, P = 0.378, respectively).ConclusionsIVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF.

Normal and fibrotic liver parenchyma respond differently to irreversible electroporation ablation

Liver cirrhosis is often associated with elevated levels of prolactin (PRL). This is commonly attributed to impaired hepatic metabolism of estrogens. However, there is evidence suggesting that PRL may be an important factor in hepatic tissue regeneration. To investigate the role of PRL in the pathogenesis of liver cirrhosis, we used RT-PCR and immunhistochemical staining to analyze changes in the expression and the histological distribution of the prolactin receptor (PRLR) in normal, fibrotic and cirrhotic hepatic tissue. Liver tissue was obtained from 29 surgically explanted human livers. The histological examination demonstrated normal liver tissue (n=9) as well as different grades of fibrosis (n=10) and cirrhosis (n=10). In liver cirrhosis and fibrosis, PRLR-mRNA was expressed at a higher level compared to normal liver specimens. Immunohistochemical staining of normal liver tissue demonstrated homogeneous distribution of the PRLR in the hepatocytes and in the epithelial cells of the bile ducts. This pattern of distribution was lost in fibrosis, where an accumulation of the PRLR was observed in the damaged hepatocytes. As no PRL-mRNA was detectable in normal, fibrotic or cirrhotic tissue, PRL does not act through autocrine or paracrine mechanisms. These data confirm previous results, which we obtained using an animal model for experimental liver cirrhosis in rats suggesting a metabolic function of PRL in normal liver and a regenerative function in fibrotic and cirrhotic liver. In conclusion, PRL might be involved in the pathogenesis of liver cirrhosis.

miR-185 Inhibits Fibrogenic Activation of Hepatic Stellate Cells and Prevents Liver Fibrosis.

Diagnostic potential of T1ρ and T2 relaxations in assessing the severity of liver fibrosis and necro-inflammation

Cell cycle-related protein expression in regenerating fibrotic and cirrhotic rat liver following partial hepapectomy

Mast cells in the liver.

Translating an Understanding of the Pathogenesis of Hepatic Fibrosis to Novel Therapies

Failure of Fibrotic Liver Regeneration in Mice Is Linked to a Severe Fibrogenic Response Driven by Hepatic Progenitor Cell Activation

BackgroundLiver fibrosis is a public health problem worldwide. There is a need of noninvasive imaging based methods for better diagnosis of this disease. In the current study, we aim to evaluate the potential of T1ρ MRI technique in detecting and characterizing different grades of liver fibrosis in vivo in humans.MethodsHealthy subjects and patients with liver fibrosis were prospectively recruited for T1ρ MRI of liver on a 1.5 T MR scanner. Single slice T1ρ weighted images were acquired at different spin lock duration (0, 10, 20 and 30 ms) with spin lock amplitude of 500 Hz in a single breath-hold. Additionally, liver’s T1ρ images were acquired from five healthy subjects on the same day (n = 2) and different day (n = 2) sessions for test–retest study. Liver biopsy samples from patients were obtained and used to calculate the METAVIR score to define the stage of fibrosis and inflammation grade. T1ρ maps were generated followed by computation of mean and standard deviation (SD) values. Coefficient of variation (COV) of T1ρ values between two MRI scans was computed to determine reproducibility in liver. T test was used to compare T1ρ values between healthy and fibrotic liver. Pearson correlation was performed between stages of liver fibrosis and T1ρ values.ResultsThe mean (SD) T1ρ value among subject with healthy liver was 51.04 (3.06) ms. The COV of T1ρ values between two repetitions in the same day session was 0.83 ± 0.8 % and in different day session was 5.4 ± 2.7 %. T1ρ values in fibrotic liver were significantly higher compared to those of healthy liver (p < 0.05). A statically significant correlation between stages of fibrosis and T1ρ values was observed (r = 0.99, p < 0.05). Inflammation score for one patient was 2 and for remaining patients it was 1.ConclusionsProposed T1ρ pulse sequence design and protocol enabled acquisition of a single slice T1ρ weighted images in a single breath-hold and hence mitigated breathing motion related artifacts. Preliminary results have shown the sensitivity of T1ρ values to changes induced by liver fibrosis, and may potentially be used as a clinical biomarker to delineate the stages of liver fibrosis. Further, studies on a large number of subjects are required to validate the observations of the current study. Nevertheless, T1ρ imaging can be easily setup on a clinical scanner to monitor the progression of liver fibrosis and to the evaluate efficacy of anti-fibrotic drugs.

Combined Statistical and Multiscale View on Ultrasonic Liver Images for Characterization

Hepatic stellate cells and intralobular innervation in human liver cirrhosis

Objective To investigate the value of susceptibility weighted imaging (SWI) with T1ρ imaging in staging of hepatic fibrosis(HF) in rabbits. Methods Eighty selected white rabbits from New Zealand were randomly divided into the HF group (n=60) and the control group (n=20). Rabbits in the HF group were injected subcutaneously with 50% CCl4 oil solution to establish HF model,and the normal control rabbits were injected with saline solution subcutaneously.The HF group(n=15) and control group(n=5) were randomly selected at the 4th, 5th, 6th and 10th week after injection, to undergo liver MR scan. The liver signal intensity (SI liver), the muscle signal intensity (SI muscle),liver-to-muscle SI ratios (SIR) and liver T1ρ values were measured. Scheuer was adopted to stage the rabbits in HF.One-way analysis of variance was used to compare the differences between SIR and T1ρ values in different stages of HF pathological. Spearman correlation was used to analyze the correlation between SIR and T1ρ values in the different stage of HF pathological.The ROC were used to compare the efficacy between SIR and T1ρ values in the diagnosis of HF pathological stage. Results Among the final qualified 68 rabbits in the study, 17 in F0 phase, 11 in F1 phase, 16 in F2 phase, 11 in F3 phase, and 13 in F4 phase. The SIR were (0.977±0.013), (0.960±0.015), (0.802±0.026), (0.786±0.022), (0.541±0.116); T1ρ values were (22.301±1.849), (24.034±0.867), (25.374±1.309),(25.364±1.945),(30.948±2.925) ms.There were statistically significant in SIR between F0 and F2,F0 and F3,F0 and F4,F1 and F2,F1 and F3,F1 and F4,F2 and F4,F3 and F4 (P 0.966) ,and the AUC of the SIR was greater than T1ρ values in the other groups. Conclusion SWI and T1ρ values can provide an important objective basis in staging of HF. Both of them have great clinical application prospects but SIR diagnostic efficiency is slightly better than that of T1ρ values. Key words: Magnetic resonance imaging; Hepatic fibrosis; Magnetic susceptibility weighted imaging; T1ρrelaxation

Location, location, location: Cell-level mechanics in liver fibrosis.