13C NMR for the assessment of human brain glucose metabolism in vivo.

Proton-decoupled 13C NMR spectra of the human head were obtained during hyperglycemic glucose clamping using intravenous infusions of [1-13C]glucose in normal volunteers. In addition to 13C signals of mobile lipids, a variety of new metabolite resonances could be resolved for the first time in the human brain. At an enrichment level of 20% [1-13C]glucose, the signals of alpha- and beta-glucose at 92.7 and 96.6 ppm, respectively, could be detected in the human brain after only an infusion period of 15 min. The spatial localization of the different regions of interest was confirmed by 13C NMR spectroscopic imaging with a time resolution of 9 min. Increasing the enrichment level to 99% [1-13C]glucose not only improved the time resolution but allowed the detection of metabolic breakdown products of [1-13C]glucose. The time course of 13C label incorporation into the C2, C3, and C4 resonances of glutamate/glutamine and into lactate could be recorded in the human brain. These results suggest the possibility of obtaining time-resolved, spatially selective, and chemically specific information on the human body.

[1]  S. Cerdán,et al.  NMR studies of metabolism. , 1990, Annual review of biophysics and biophysical chemistry.

[2]  R. Shulman,et al.  Natural-abundance 13C NMR study of glycogen repletion in human liver and muscle. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J. Brainard,et al.  Use of multiple 13C-labeling strategies and 13C NMR to detect low levels of exogenous metabolites in the presence of large endogenous pools: measurement of glucose turnover in a human subject. , 1989, Analytical biochemistry.

[4]  N. Beckmann,et al.  13C spectroscopic imaging. A simple approach to in vivo 13C investigations , 1989, Magnetic resonance in medicine.

[5]  R. Shulman,et al.  Detection of metabolites in rabbit brain by 13C NMR spectroscopy following administration of [1‐13C]glucose , 1986, Magnetic resonance in medicine.

[6]  A. Heerschap,et al.  Broadband proton decoupled natural abundance 13C NMR spectroscopy of humans at 1.5 T , 1989, NMR in biomedicine.

[7]  S K Hilal,et al.  Field inhomogeneity correction and data processing for spectroscopic imaging , 1985, Magnetic resonance in medicine.

[8]  R. Shulman,et al.  Detection of human muscle glycogen by natural abundance 13C NMR. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[9]  R. DeFronzo,et al.  The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization , 1981, Diabetes.

[10]  J. Seelig,et al.  Analysis of glycogen storage disease by in vivo 13C NMR comparison of normal volunteers with a patient , 1990, Magnetic resonance in medicine.

[11]  H. Mandel,et al.  Determination of fructose metabolic pathways in normal and fructose-intolerant children: a 13C NMR study using [U-13C]fructose. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. London 13C labeling in studies of metabolic regulation , 1988 .

[13]  M. Bárány,et al.  Natural‐abundance 13C NMR of brain , 1985, Magnetic resonance in medicine.

[14]  C Verdonk,et al.  Insulin increases the maximum velocity for glucose uptake without altering the Michaelis constant in man. Evidence that insulin increases glucose uptake merely by providing additional transport sites. , 1982, The Journal of clinical investigation.

[15]  S. Korman,et al.  Estimation of glucose carbon recycling in children with glycogen storage disease: A 13C NMR study using [U-13C]glucose. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Uğurbil,et al.  NMR chemical shift imaging in three dimensions. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Ray Freeman,et al.  Broadband Decoupling in High-Resolution Nuclear Magnetic Resonance Spectroscopy , 1984 .

[18]  R G Shulman,et al.  Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. , 1990, The New England journal of medicine.