Toward dynamic isotopomer analysis in the rat brain in vivo: automatic quantitation of 13C NMR spectra using LCModel.
The LCModel method was adapted to analyze localized in vivo (13)C NMR spectra obtained from the rat brain in vivo at 9.4 T. Prior knowledge of chemical-shifts, J-coupling constants and J-evolution was included in the analysis. Up to 50 different isotopomer signals corresponding to 10 metabolites were quantified simultaneously in 400 microl volumes in the rat brain in vivo during infusion of [1,6-(13)C(2)]glucose. The analysis remained accurate even at low signal-to-noise ratio of the order of 3:1. The relative distribution of isotopomers in glutamate, glutamine and aspartate determined in vivo in 22 min was in excellent agreement with that measured in brain extracts. Quantitation of time series of (13)C spectra yielded time courses of total (13)C label incorporation into up to 16 carbon positions, as well as time courses of individual isotopomer signals, with a temporal resolution as low as 5 min (dynamic isotopomer analysis). The possibility of measuring in vivo a wealth of information that was hitherto accessible only in extracts is likely to expand the scope of metabolic studies in the intact brain.
Henry
Pierre-Gilles
PG
Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota Medical School, 2021 6th Street SE, Minneapolis, MN 55455, USA. henry@cmrr.umn.edu
Oz
Gülin
G
Provencher
Stephen
S
Gruetter
Rolf
R
D000465:Algorithms; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes / Q000493:pharmacokinetics*; D046508:Culture Techniques; D005240:Feasibility Studies; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008657:Metabolic Clearance Rate; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013194:Staining and Labeling / Q000379:methods; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002247:Carbon Isotopes; D018377:Neurotransmitter Agents; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D005947:Glucose