Collagen-targeted molecular MR imaging of liver fibrosis in a mouse model

1576 Objectives Liver fibrosis is the end common pathway of chronic liver injuries. Liver biopsy, the current clinical gold standard for assessment of fibrosis, is invasive and has sampling errors, and is not optimal for screening, monitoring, or clinical decision-making. Fibrosis is characterized by excessive accumulation of extracellular matrix proteins including type I collagen. We hypothesize that a MR probe targeted to type I collagen will enable noninvasive staging of hepatic fibrosis. Methods Mice were administered carbon tetrachloride or vehicle for 6 - 18 weeks resulting in mild to severe liver fibrosis. Mice were imaged prior to and following administration of a Gd-based probe targeted to type I collagen or with non-specific Gd-DTPA. Following imaging, animals were euthanized and the livers analyzed for Gd concentration, hydroxyproline (total collagen), and stained with Sirius Red for fibrosis and scored by a board certified pathologist blinded to the study. Results MRI signal enhancement showed strong correlations with liver hydroxyproline concentration and with Ishak scoring for fibrosis. Ex vivo analysis of gadolinium showed positive linear correlations with hydroxyproline and Ishak scoring. Unenhanced MRI or Gd-DTPA enhanced MRI could not distinguish fibrotic animal from controls. Conclusions Molecular MRI with a collagen specific probe shows feasibility for non-invasive staging of liver fibrosis. Research Support Sanofi-Aventis and NCI (CA140861)