In Vivo Lipid Profiling Using Proton Magnetic Resonance Spectroscopy in an Experimental Liver Fibrosis Model

Abstract

The aim of this study was to characterize early hepatic lipid changes in an experimental model of liver fibrosis using proton ((1)H) magnetic resonance spectroscopy (MRS) at high magnetic field in vivo. Liver fibrosis was induced in 12 Sprague-Dawley rats by twice-weekly carbon tetrachloride (CCl(4)) administration up to 4 weeks. Eight normal rats were used as controls. Single-voxel (1)H MRS experiments were performed at 7 Tesla to measure signal integrals of various lipid peaks including -CH(3), (-CH(2)-)(n), -CH(2)-C=C-CH(2)-, =C-CH(2)-C= and -CH=CH- at 0.9, 1.3, 2.0, 2.8, and 5.3 ppm, respectively, and peak from choline-containing compounds (CCC) at 3.2 ppm. Total lipid, total saturated fatty acid, total unsaturated fatty acid, total unsaturated bond, polyunsaturated bond, and CCC indices were quantified. Significant increases (P < .01) in total lipid and total saturated fatty acid indices were found in animals with CCl(4)-induced fibrosis as compared with normal animals. In addition, total unsaturated bond and polyunsaturated bond indices of animals at 4 weeks after CCl(4) insult were significantly higher than (P < .01 and P < .05, respectively) those of normal animals and animals at 2 weeks following insult; whereas there was only significant increase (P < .01) in total unsaturated fatty acid index in animals with 4-week CCl(4) insult as compared with normal animals. The hepatic lipid changes in CCl(4)-induced experimental fibrosis model were documented in vivo and longitudinally using (1)HMRSat 7 Tesla. The experimental findings suggested that total saturated fatty acid increase contributed mainly to the total lipid increase in animals with CCl(4) insult. This study also demonstrated the potential value of high field MRS to resolve lipid composition and alterations in liver fibrosis.