Longitudinal Magnetic Resonance Imaging with ROS-Responsive Bilirubin Nanoparticles Enables Monitoring of Non-Alcoholic Steatohepatitis Progression to Cirrhosis.

Despite the vital importance of monitoring the progression of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), we currently lack an efficient imaging modality that is readily available at hospitals. In this study, we present a new magnetic resonance imaging (MRI)-based imaging modality that allows for efficient and longitudinal monitoring of NAFLD and NASH progression. Our imaging modality uses manganese ion (Mn 2+ )-chelated bilirubin nanoparticles (Mn@BRNPs) as a reactive oxygen species (ROS)-responsive MRI imaging probe. We performed longitudinal T1-weighted MR imaging of NASH model mice after injecting Mn@BRNPs intravenously. The MR signal enhancement in the liver relative to muscle gradually increased up to 8 weeks of NASH progression, but decreased significantly as NASH progressed to the cirrhosis-like stage at weeks 10 and 12. We developed a new dual input pseudo three-compartment model to provide information on NASH stage with a single MRI scan. We also demonstrated that our ROS-responsive Mn@BRNPs can be used to monitor the efficacy of potential anti-NASH drugs with conventional MRI. Our findings suggest that our ROS-responsive Mn@BRNPs have the potential to serve as an efficient MRI contrast for monitoring NASH progression and its transition to the cirrhosis-like stage. This article is protected by copyright. All rights reserved.