Measurement of intracellular triglyceride stores by H-1 spectroscopy: validation in vivo

We validate the use of H-1 magnetic resonance spectroscopy (MRS) to quantit atively differentiate between adipocyte and intracellular triglyceride (TG) stores by monitoring the TG methylene proton signals at 1.6 and 1.4 ppm, r espectively. In two animal models of intracellular TG accumulation, intrahe patic and intramyocellular TG accumulation was confirmed histologically. Co nsistent 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 wa s unchanged. In response to induced fat accumulation, the TG concentration in liver derived from H-1 MRS increased from 0 to 44.9 +/- 13.2 mu mol/g, a nd this was matched by increases measured biochemically(2.1 +/- 1.1 to 46.1 +/- 10.9 mu mol/g). Supportive evidence that the methylene signal at 1.6 p pm in muscle is derived from investing interfascial adipose tissue was the finding that, in four subjects with generalized lipodystrophy, a disease ch aracterized by absence of interfacial fat, no signal was detected at 1.6 pp m; however, a strong signal was seen at 1.4 ppm. An identical methylene che mical shift at 1.4 ppm was obtained in human subjects with fatty liver wher e the fat is located exclusively within hepatocytes. In experimental animal s, there was a close correlation between hepatic TG content measured in viv o by H-1 MRS and chemically by liver biopsy [R = 0.934; P < .0001; slope 0. 98, confidence interval(CI) 0.70-1.17; gamma-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 s ubjects and 7.9% in obese subjects and of extramyocellular (adipocyte) fat was 22.6 and 52.5%, respectively. This study demonstrates for the first tim e that noninvasive in vivo H-1 MRS measurement of intracellular TG, includi ng that within myocytes, is feasible at 1.5-T field strengths and is compar able in accuracy to biochemical measurement. In addition, in mixed tissue s uch as muscle, the method is clearly advantageous in differentiating betwee n TG from contaminating adipose tissue compared with intramyocellular lipid s.