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Journal of Lipid Research, Vol. 45, 1364-1371, July 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Methods

In vivo MRS measurement of liver lipid levels in mice

J. R. Garbow^1,*,,, X. Lin^**, N. Sakata^**, Z. Chen^**, D. Koh^* and G. Schonfeld^**

^* Department of Chemistry, Washington University, St. Louis, MO 63130
Departments of Radiology, Washington University School of Medicine, St. Louis, MO 63110
^** Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110
The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110

¹ To whom correspondence should be addressed. e-mail: garbow{at}wustl.edu

A magnetic resonance spectroscopy (MRS) procedure for in vivo measurement of lipid levels in mouse liver is described and validated. The method uses respiratory-gated, localized spectroscopy to collect proton spectra from voxels within the mouse liver. Bayesian probability theory analysis of these spectra allows the relative intensities of the lipid and water resonances within the liver to be accurately measured. All spectral data were corrected for measured spin-spin relaxation. A total of 48 mice were used in this study, including wild-type mice and two different transgenic mouse strains. Different groups of these mice were fed high-fat or low-fat diets or liquid diets with and without the addition of alcohol. Proton spectra were collected at baseline and, subsequently, every 4 weeks for up to 16 weeks. Immediately after the last MRS measurement, mice were killed and their livers analyzed for triglyceride level by conventional wet-chemistry methods. The excellent correlation between in vivo MRS and ex vivo wet-chemistry determinations of liver lipids validates the MRS method.

These results clearly demonstrate that in vivo MRS will be an extremely valuable technique for longitudinal studies aimed at providing important insights into the genetic, environmental, and dietary factors affecting fat deposition and accumulation within the mouse liver.

Supplementary key words magnetic resonance spectroscopy • triglyceride • fatty liver • cirrhosis

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