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

Abstract

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.

Magnetic resonance imaging and spectroscopy for monitoring liver steatosis

“…Quantitation of steatosis using 1 H MRS or MRI was closely correlated with histological assessment in patients with chronic liver disease of varying etiology and severity, and serial examinations showed a reduction in hepatic fat content with weight loss. This is consistent with previous studies reporting a correlation between MRS and histomorphometric data (9,10,24).…”

“…Results of MRS have shown to correlate closely with biochemical and histological assessments of liver triglyceride content (9,10), and to demonstrate a decrease in liver fat content following rosiglitazone therapy (11) or weight reduction (12,13). Other imaging modalities, such as ultrasonography and computed to-mography (CT), provide limited quantitative assessment (14,15).…”

Non-invasive assessment of lower extremity muscle composition after incomplete spinal cord injury

“…IMCL (85 ms) and EMCL (75 ms) T 2 relaxation times measured in this study match lipid T 2 relaxation values reported in the literature. 14 In concurrence with other studies, the overall lipid, IMCL and EMCL content in our study were expressed as a ratio using the spectral water peak as an internal reference. 6 …”

Age Dependency of Myocardial Triglyceride Content: A 3T High-Field 1H-MR Spectroscopy Study

“…In consequence, a total of four 1 H-MR spectra (two with and two without water suppression) were collected for each observation, utilizing the proton signal from water in cardiac tissue as an internal reference for chemical shift offset and fat concentration ( • " Fig. 2a) [3, 13,14].…”