Cationized ferritin as a magnetic resonance imaging probe to detect microstructural changes in a rat model of non‐alcoholic steatohepatitis

Abstract

The goal of this work was to detect disease-related microstructural changes to the liver using magnetic resonance imaging. Chronic liver disease can cause microstructural changes in the liver that reduce plasma access to the perisinusoidal space--the site of exchange between the blood plasma and the hepatic parenchyma. The reduced plasma access to the perisinusoidal space inhibits hepatic function and contributes to the ∼30,000 chronic liver disease-related deaths per year. The extracellular matrix-specific cationized ferritin magnetic resonance imaging probe was injected intravenously into healthy rats and a rat model of the chronic liver disease non-alcoholic steatohepatitis. Rats were subsequently imaged with T2*-weighted magnetic resonance imaging. This work demonstrates that the binding of cationized ferritin to the perisinusoidal extracellular matrix is reduced by 55% in a rat model of non-alcoholic steatohepatitis compared to healthy controls. This reduced binding is detectable in vivo with magnetic resonance imaging. Immunofluorescence and electron microscopy indicated that the reduced binding is due to inhibited macromolecular access to the perisinusoidal space caused by non-alcoholic steatohepatitis-related microstructural changes. The reduced accumulation of intravenously injected cationized ferritin may report on changes in macromolecular access to the liver parenchyma in chronic liver disease.