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1 Center for Diabetes Research, Departments of 2 Internal Medicine, 3 Radiology, 5 Pathology, and 6 Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75235; and 4 Department of Radiology, University of Tübingen, 72706 Tübingen, Germany
We validate the use of 1H magnetic
resonance spectroscopy (MRS) to quantitatively differentiate between
adipocyte and intracellular triglyceride (TG) stores by monitoring the
TG methylene proton signals at 1.6 and 1.4 ppm, respectively. In two
animal models of intracellular TG accumulation, intrahepatic and
intramyocellular TG accumulation was confirmed histologically.
Consistent with the histological changes, the methylene signal
intensity at 1.4 ppm increased in both liver and muscle, whereas the
signal at 1.6 ppm was unchanged. In response to induced fat
accumulation, the TG concentration in liver derived from 1H
MRS increased from 0 to 44.9 ± 13.2 µmol/g, and this was matched by
increases measured biochemically (2.1 ± 1.1 to 46.1 ± 10.9 µmol/g). Supportive evidence that the methylene signal at 1.6 ppm in
muscle is derived from investing interfascial adipose tissue was the
finding that, in four subjects with generalized lipodystrophy, a
disease characterized by absence of interfacial fat, no signal was
detected at 1.6 ppm; however, a strong signal was seen at 1.4 ppm. An
identical methylene chemical shift at 1.4 ppm was obtained in human
subjects with fatty liver where the fat is located exclusively within
hepatocytes. In experimental animals, there was a close correlation
between hepatic TG content measured in vivo by 1H MRS and
chemically by liver biopsy [R = 0.934;
P < .0001; slope 0.98, confidence interval (CI)
0.70-1.17; y-intercept 0.26, CI 
0.28 to 0.70]. When
applied to human calf muscle, the coefficient of variation of the
technique in measuring intramyocellular TG content was 11.8% in
nonobese subjects and 7.9% in obese subjects and of extramyocellular
(adipocyte) fat was 22.6 and 52.5%, respectively. This study
demonstrates for the first time that noninvasive in vivo 1H
MRS measurement of intracellular TG, including that within myocytes, is
feasible at 1.5-T field strengths and is comparable in accuracy to
biochemical measurement. In addition, in mixed tissue such as muscle,
the method is clearly advantageous in differentiating between TG from
contaminating adipose tissue compared with intramyocellular lipids.
fatty acid analysis; quantification; dog; rabbit; human; congenital generalized lipodystrophy; proton; skeletal muscle; liver
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