Spleen Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a New Method for Staging Liver Fibrosis in a Piglet Model

Li Zhou,Li Li,Zhen-Feng Yang,Tian-Wu Chen,Dan Wang,Cheng-Jun Li,Xian-Yong Xie,Ting Li,Chun-Ping Li,Li-Ying Wang,Nan-Lin Zeng,Jie Li,Xiao-Ming Zhang,Bing Xu

doi:10.1371/journal.pone.0083697

Abstract

ObjectiveTo explore spleen hemodynamic alteration in liver fibrosis with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and to determine how to stage liver fibrosis with spleen DCE-MRI parameters.Materials and MethodsSixteen piglets were prospectively used to model liver fibrosis staged by liver biopsy, and underwent spleen DCE-MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease. DCE-MRI parameters including time to peak (TTP), positive enhancement integral (PEI), maximum slope of increase (MSI) and maximum slope of decrease (MSD) of spleen were measured, and statistically analyzed to stage this disease.ResultsSpearman's rank correlation tests showed that TTP tended to increase with increasing stages of liver fibrosis (r = 0.647, P<0.001), and that PEI tended to decrease from stage 0 to 4 (r = −0.709, P<0.001). MSD increased slightly from stage 0 to 2 (P>0.05), and decreased from stage 2 to 4 (P<0.05). MSI increased from stage 0 to 1, and decreased from stage 1 to 4 (all P>0.05). Mann-Whitney tests demonstrated that TTP and PEI could classify fibrosis between stage 0 and 1–4, between 0–1 and 2–4, between 0–2 and 3–4, or between 0–3 and 4 (all P<0.01). MSD could discriminate between 0–2 and 3–4 (P = 0.006), or between 0–3 and 4 (P = 0.012). MSI could not differentiate between any two stages. Receiver operating characteristic analysis illustrated that area under receiver operating characteristic curve (AUC) of TTP was larger than of PEI for classifying stage ≥1 and ≥2 (AUC = 0.851 and 0.783, respectively). PEI could best classify stage ≥3 and 4 (AUC = 0.903 and 0.96, respectively).ConclusionSpleen DCE-MRI has potential to monitor spleen hemodynamic alteration and classify liver fibrosis stages.

Highlights

Liver fibrosis, a common feature of chronic liver disease, has been demonstrated to be at high risk of progress to cirrhosis, portal hypertension, or liver failure [1]
The histological changes including pulp hyperplasia, congestion and even fibrogenesis occur in the spleen, which could alter spleen hemodynamics [4,5,6]
4 piglets had been successfully induced to liver cirrhosis, and 3 had liver fibrosis

Summary

Introduction

A common feature of chronic liver disease, has been demonstrated to be at high risk of progress to cirrhosis, portal hypertension, or liver failure [1]. Spleen is a companion solid organ associated closely with liver in the portal system, and participates actively in liver fibrosis progression because of portal hypertension [2]. The histological changes including pulp hyperplasia, congestion and even fibrogenesis occur in the spleen, which could alter spleen hemodynamics [4,5,6]. Histological evaluation is a gold standard for assessing the severity of the disease, it is limited in clinical application because of its invasive nature, high risk of intraperitoneal hemorrhage and difficult-to-sample [7]. A reproducible and reliable noninvasive method is desirable to evaluate spleen hemodynamic changes with liver fibrosis progression

Methods

Results

Conclusion