Skeletal muscle lipid quantification in lean and diabetic subjects using in vivo proton MR spectroscopy

Abstract

Purpose: To quantify and compare the intramyocellular (IMCL), extramyocellular (EMCL) lipids and total fat fraction in human vastus lateralis muscle between lean and type 2 diabetic (T2DM) subjects using long echo time (TE) STEAM proton MR spectroscopy ( 1 H-MRS).Methods: 1 H-MRS using single voxel (15 × 15 × 15 mm 3 ) stimulated acquisition mode (STEAM) was performed in right vastus lateralis m. on 10 lean controls (age: 28.3 ± 3.94 yo, BMI: 24.25 ± 3.20 kg/m 2 ) and 7 type 2 diabetic (age: 54.28 ± 6.42 yo, BMI: 31.34 ± 3.13 kg/m 2 ) subjects with Siemens 3T MRI and a four-channel flex coil. Unsuppressed water spectra (NSA = 16) with TR/TE = 3000/30 ms, TM = 10 ms BW = 2000 Hz, and water-suppressed spectra (NSA = 128) with TR/TE = 3000/270 ms, TM = 10 ms, fixed water suppression BW = 50 Hz were acquired. Spectral intensity ratios of IMCL-CH2, EMCL-CH2 and total lipid (IMCL + EMCL) with unsuppressed water signal (W) were converted into absolute concentrations expressed in mmol/kg. Fat fraction (100 × F/(W+F)) was also calculated, where F includes the signal intensities of IMCL and EMCL methylene (CH2)n, peaks only.Results: Comparison of IMCL (controls: 11.70 ± 6.7, T2DM: 21.74 ± 10.2, p < 0.01), EMCL (controls: 22.89 ± 18.42, T2DM: 77.21 ± 33.4, p < 0.001) and total lipid (64.35 mmol/kg less in controls, p < 0.001) showed statistical significance using two-tailed student's t-test. Mean fat fraction (%) exhibited considerable inter-individual variability for controls (3.14 ± 2.09; range: 1.34 -7.04) and T2DM (9.34 ± 2.88; range: 4.15 -13.67) and deemed significant (p < 0.05).Conclusion: Single voxel STEAM 1 H-MRS at long TE provides a robust non-invasive method for characterizing lipids within localized muscle regions, with well-resolved IMCL/EMCL peak separation. Regional lipid estimate and fat fraction in vastus lateralis muscle is significantly different in T2DM compared to normal lean controls. -------------------------------------------------------------------Impact: Single-voxel proton MR spectroscopy ( 1 H-MRS) with STEAM at long echo time (TE = 270ms) provides a robust non -invasive method for characterizing muscle lipids in vivo. This method offers rapid and convenient acquisition of high -resolution spectra with improved baseline and better lipid peak separation in skeletal muscle and allows for fat quantification with superior sensitivity and dynamic range over other MR imaging methods. This study quantified IMCL, EMCL and fat fraction using 1 H-MRS from vastus lateralis m., predominantly utilized in ex vivo physiological studies for histochemical evaluation of muscle lipid metabolism in diabetes and obesity. The method described can be combined with biochemical assays to provide insights on excess skeletal muscle fat interference with insulin signaling in obese and diabetic states in longitudinal clinical research studies . Cite this article as: Valaparla SK, Boone GRE, Ripley EM, Giuseppe D, Duong TQ, Abdul-Ghani M, Clarke GD. Skeletal muscle lipid quantification in lean and diabetic subjects...

Serum Levels of Myonectin Are Lower in Adults with Metabolic Syndrome and Are Negatively Correlated with Android Fat Mass

“…In the case of ELISA, the proportion of subjects with and without MS was maintained constant in each kit to avoid inter-assay variations that could affect the results. Regarding 1 H-MRS analyses, we further performed some quality controls by showing that subjects with MS had higher intramuscular lipid concentrations than younger subjects without risk factors ( Supplementary Material Figure S1 ), similar to what has been previously reported in the literature [ 12 , 40 ], demonstrating the feasibility of the technique to identify subjects with different amounts of intramuscular lipids. Not all participants had intramuscular lipid measurements; however, the sample of subjects evaluated with intramuscular lipids by 1 H-MRS remains higher than previous studies with this technique [ 12 , 40 , 41 ].…”