Validation of ¹³c nmr measurement of human skeletal muscle glycogen by direct biochemical assay of needle biopsy samples

Abstract

Recent developments in I3C nuclear magnetic resonance ( NMR) spectroscopy have permitted noninvasive assessment of glycogen concentration in human skeletal muscle. Before these indirect measurements could be accepted as accurate, it was essential that validation should be carried out by comparing the widely used method of muscle biopsy and direct biochemical assay for glycogen concentration with measurement by NMR. Eight normal subjects underwent six NMR scans of gastrocnemius and three biopsies of the same muscle on the same day. The overall mean for muscle glycogen concentration was 87.4 mM by NMR and 88.3 m M by biopsy. There was a close correlation between the pairs of observations on each subject (R = 0.95; P < 0.0001 ). The mean coefficient of variation for NMR measurement was 4.3 f 2.1% and that for biopsy was 9.3 +-5.9%. The performance of the muscle biopsies was accompanied by a small but significant rise in plasma-free fatty acids (529 f 157 to 667 f 250; P < 0.01 ), epinephrine ( 17 2 6 to 25 t 8 pg/ml; P < 0.02), and norepinephrine (318 2 119 to 400 f 140 pg/ml; P < 0.02) but no change in plasma glucose, plasma insulin, nor muscle glycogen concentration assessed by NMR. The study demonstrates that in vivo I3C NMR measurement of human muscle glycogen can be regarded as accurate, and the technique is associated with a higher precision than biopsy with direct biochemical assessment. o

Metabolic and hormonal response to intermittent high-intensity and continuous moderate intensity exercise in individuals with type 1 diabetes: a randomised crossover study

“…MRS Glycogen content in quadriceps muscle and liver was assessed using natural abundance 13 C MRS [25,26]. Measurements were performed on a 3 Tesla MR system (Trio, Siemens, Erlangen, Germany) before and after exercise.…”

Steady‐State Cerebral Glucose Concentrations and Transport in the Human Brain

“…Quantification of '3C signals was performed using the external reference method as used in previous '3C MRS studies of the human head (Gruetter et a!., 1992a(Gruetter et a!., ,b, 1994b and verified by comparison with chemical extraction (Gruetter et al, 1991(Gruetter et al, , 1994aTaylor et al, 1992). In brief, the effect of variable coil loading on sensitivity was assessed by measuring the fully relaxed signal of the formic acid sphere.…”

“…Pulse widths and power for the PRECISELY sequence were set according to the position relative to the coil based on previous calibrations. During acquisition (171 ms) WALTZ-16 decoupling was applied, which resulted in a 5.6% duty cycle (TR = 3 s) and an average power of <3 W, which is well within Food and Drug Administration guidelines for specific absorption rates.Quantification of '3C signals was performed using the external reference method as used in previous '3C MRS studies of the human head (Gruetter et a!., 1992a(Gruetter et a!., ,b, 1994b and verified by comparison with chemical extraction (Gruetter et al, 1991(Gruetter et al, , 1994aTaylor et al, 1992). In brief, the effect of variable coil loading on sensitivity was assessed by measuring the fully relaxed signal of the formic acid sphere.…”

MRI detection of glycogen in vivo by using chemical exchange saturation transfer imaging (glycoCEST)

“…Because there are numerous practical disadvantages to measuring glycogen by tissue biopsy in humans, there has been widespread interest in detection of glycogen in vivo by 13 C magnetic resonance (MR) spectroscopy (MRS) in multiple organs, including the heart (2), liver (3), skeletal muscle (4), and brain (5). Although glycogen is a large molecule, 13 C NMR allows accurate measurements of glycogen content in liver (6) and in skeletal muscle (7), presumably because internal motions remain sufficiently unrestricted in vivo (8). Detection of glycogen using 1 H NMR also has been demonstrated (9)(10)(11).…”