Quantitative Body Composition Analysis in Awake Mice and Rats by Magnetic Resonance Relaxometry

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Abstract
Magnetic resonance (MR) relaxometry has recently been introduced for noninvasive body composition analysis in awake mice. The purpose of the present study was to extend the method to rats and to introduce calibration procedures that render MR relaxometry fully quantitative. Proton T(2) MR relaxometry at 4.7 Tesla was used for body composition analyses in 700 awake mice and 400 rats of different strains and conditions. Relaxograms calculated from the signal decays observed with multi-spin-echo acquisition provided well-separated contributions of tissue water and fat. Analysis of fat composition was carried out in vivo using (13)C-MR spectroscopy. Evolution of body composition in rats was assessed during drug treatment. MR relaxometry for noninvasive body composition analysis in laboratory rodents was implemented on a standard MR scanner, and a throughput of >30 animals per hour was achieved. Excellent linearity and reproducibility with coefficients of variance as low as 2.5% and 1.7% were obtained in mice and rats, respectively. The lean mass-to-water ratio (mice, 1.35 +/- 0.03; rats, 1.39 +/- 0.04) and the proton density of fat (mice, 8.1 +/- 0.2; rats, 8.9 +/- 0.2 g/mol) were determined from cross-sectional data. Fat composition analysis by (13)C-MR spectroscopy corroborated these findings and yielded information on the average acyl chain length (16.3 +/- 1.6) and contributions of saturated (27 +/- 3%), monounsaturated (22 +/- 2%), and polyunsaturated (51 +/- 3%) fatty acids. Longitudinal assessments in rats treated with sibutramine and dexfenfluramine showed dose-related changes in body composition. T(2) MR relaxometry backed by solid calibration provides a powerful means for rapid quantitative body composition analysis in awake mice and rats that is suitable for serial investigations in pharmaceutical research.