Imaging Non-alcoholic Fatty Liver Disease Model Using H-1 and F-19 MRI

Abstract

Purpose: We explore the use of intravenously delivered perfluorocarbon (PFC) nanoemulsion and ¹⁹F MRI for detecting inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD). Correlative studies of ¹H-based liver proton density fat fraction (PDFF) and T₁ measurements and histology are also evaluated.

Procedures: C57BL/6 mice were fed standard or high-fat diet (HFD) for 6 weeks to induce NAFLD. ¹H MRI measurements of PDFF and T₁ relaxation time were performed at baseline to assess NAFLD onset prior to administration of a PFC nanoemulsion to enable ¹⁹F MRI of liver PFC uptake. ¹H and ¹⁹F MRI biomarkers were acquired at 2, 21, and 42 days post-PFC to assess changes. Histopathology of liver tissue was performed at experimental endpoint.

Results: Significant increases in liver volume, PDFF, and total PFC uptake were noted in HFD mice compared to Std diet mice. Liver fluorine density and T₁ relaxation time were significantly reduced in HFD mice.

Conclusions: We demonstrated longitudinal quantification of multiple MRI biomarkers of disease in NAFLD mice. The changes in liver PFC uptake in HFD mice were compared with healthy mice that suggests that ¹⁹F MRI may be a viable biomarker of liver pathology.

Keywords: Fatty liver disease; Fluorine-19; In vivo; Inflammation; MRI; Macrophage; NAFLD; NASH; Nanoemulsion; Perfluorocarbon; Steatohepatitis; Steatosis.