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In Vivo 13C Magnetic Resonance Spectroscopy and Metabolic Modeling: Methodology

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Neural Metabolism In Vivo

Abstract

In vivo 13C NMR spectroscopy combined with infusion of 13C-enriched substrates allows non-invasive investigation of brain metabolism in animals and humans. Time courses of 13C label incorporation from the infused substrate(s) into brain metabolites can be analyzed with metabolic models to quantify metabolic rates through specific metabolic pathways such as the neuronal and glial TCA cycles, pyruvate carboxylase, or the glutamate-glutamine cycle. In this chapter, we review the methodology for successful in vivo 13C MRS measurements and metabolic modeling studies. The various aspects of this methodology are described with a focus on challenges specific to in vivo measurements in the brain. References in this review are current as of March 2008.

Authors are listed in alphabetical order except for the first author.

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Notes

  1. 1.

    Unless otherwise stated, thete terms ‘13C MRS’ and ‘13C MR spectra’ in this chapter refer to both direct 13C detection (at 13C frequency) and indirect 1H[13C] detection (at 1H frequency).

  2. 2.

    In principle, the presence of the 13C isotope can alter the rate at which the labeled substrate is metabolized (isotopic effect). In 13C MRS studies, however, it is generally assumed that isotopic effects are negligible, because the presence of 13C atoms does not significantly modify the molecular weight of the substrate.

References

  • Adriany G, Gruetter R (1997) A half-volume coil for efficient proton decoupling in humans at 4 Tesla. J Magn Reson 125:178–184

    Article  PubMed  CAS  Google Scholar 

  • Alger JR, Sillerud LO, Behar KL, Gillies RJ, Shulman RG, Gordon RE, Shae D, Hanley PE (1981) In vivo carbon-13 nuclear magnetic resonance studies of mammals. Science 214:660–662

    Article  PubMed  CAS  Google Scholar 

  • Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M, Golman K (2003) Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR. Proc Natl Acad Sci USA 100:10158–10163

    Article  PubMed  CAS  Google Scholar 

  • Bachelard H (1998) Landmarks in the application of 13C-magnetic resonance spectroscopy to studies of neuronal/glial relationships. Dev Neurosci 20:277–288

    Article  PubMed  CAS  Google Scholar 

  • Badar-Goffer RS, Bachelard HS, Morris PG (1990) Cerebral metabolism of acetate and glucose studied by 13C-n.m.r. spectroscopy. A technique for investigating metabolic compartmentation in the brain. Biochem J 266:133–139

    PubMed  CAS  Google Scholar 

  • Bax A (1983) A simple method for the calibration of the decoupler radiofrequency field strength. J Magn Reson 52:76–80

    CAS  Google Scholar 

  • Beckmann N, Turkalj I, Seelig J, Keller U (1991) 13C NMR for the assessment of human brain glucose metabolism in vivo. Biochemistry 30:6362–6366

    Article  PubMed  CAS  Google Scholar 

  • Behar KL, Petroff OAC, Prichard JW, Alger JR, Shulman RG (1986) Detection of metabolites in rabbit brain by 13C NMR spectroscopy following administration of [1-13C]Glucose. Magn Reson Med 3:911–920

    Article  PubMed  CAS  Google Scholar 

  • Bhattacharya P, Chekmenev EY, Perman WH, Harris KC, Lin AP, Norton VA, Tan CT, Ross BD, Weitekamp DP (2007) Towards hyperpolarized (13)C-succinate imaging of brain cancer. J Magn Reson 186:150–155

    Article  PubMed  CAS  Google Scholar 

  • Bluml S, Moreno-Torres A, Ross BD (2001a) [1-13C]glucose MRS in chronic hepatic encephalopathy in man. Magn Reson Med 45:981–993

    Article  PubMed  CAS  Google Scholar 

  • Bluml S, Moreno A, Hwang JH, Ross BD (2001b) 1-(13)C glucose magnetic resonance spectroscopy of pediatric and adult brain disorders. NMR Biomed 14:19–32

    Article  PubMed  CAS  Google Scholar 

  • Bluml S, Moreno-Torres A, Shic F, Nguy CH, Ross BD (2002) Tricarboxylic acid cycle of glia in the in vivo human brain. NMR Biomed 15:1–5

    Article  PubMed  CAS  Google Scholar 

  • Boumezbeur F, Besret L, Valette J, Vaufrey F, Henry PG, Slavov V, Giacomini E, Hantraye P, Bloch G, Lebon V (2004) NMR measurement of brain oxidative metabolism in monkeys using 13C-labeled glucose without a 13C radiofrequency channel. Magn Reson Med 52:33–40

    Article  PubMed  CAS  Google Scholar 

  • Boumezbeur F, Besret L, Valette J, Gregoire MC, Delzescaux T, Maroy R, Vaufrey F, Gervais P, Hantraye P, Bloch G, Lebon V (2005) Glycolysis versus TCA cycle in the primate brain as measured by combining (18)F-FDG PET and (13)C-NMR. J Cereb Blood Flow Metab 25:1418–1423

    Google Scholar 

  • Cerdan S, Kunnecke B, Seelig J (1990) Cerebral metabolism of [1,2-13C2]acetate as detected by in vivo and in vitro 13C NMR. J Biol Chem 265:12916–12926

    PubMed  CAS  Google Scholar 

  • Chance MC, Seeholzer SH, Kobayashi K, Williamson JR (1983) Mathematical analysis of isotope labeling in the citric acid cycle with applications to 13C NMR studies in perfused rat hearts. J Biol Chem 258:13785–13794

    PubMed  CAS  Google Scholar 

  • Chassain C, Bielicki G, Donnat JP, Renou JP, Eschalier A, Durif F (2005) Cerebral glutamate metabolism in Parkinson’s disease: an in vivo dynamic (13)C NMS study in the rat. Exp Neurol 191:276–284

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Adriany G, Zhu X-H, Gruetter R, Ugurbil K (1998) Detecting natural abundance carbon signal of NAA metabolite within 12-cm3 localized volume of human brain 1H-{13C} NMR spectroscopy. Magn Reson Med 40:180–184

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Zhu XH, Gruetter R, Seaquist ER, Adriany G, Ugurbil K (2001) Study of tricarboxylic acid cycle flux changes in human visual cortex during hemifield visual stimulation using 1H-{13C} MRS and fMRI. Magn Reson Med 45:349–355

    Article  PubMed  CAS  Google Scholar 

  • Chhina N, Kuestermann E, Halliday J, Simpson LJ, Macdonald IA, Bachelard HS, Morris PG (2001) Measurement of human tricarboxylic acid cycle rates during visual activation by (13)C magnetic resonance spectroscopy. J Neurosci Res 66:737–746

    Article  PubMed  CAS  Google Scholar 

  • Choi IY, Gruetter R (2004) Dynamic or inert metabolism? Turnover of N-acetyl aspartate and glutathione from D-[1-13C]glucose in the rat brain in vivo. J Neurochem 91:778–787

    Article  PubMed  CAS  Google Scholar 

  • Choi IY, Tkac I, Ugurbil K, Gruetter R (1999) Noninvasive measurements of [1-13C]glycogen concentrations and metabolism in rat brain in vivo. J Neurochem 73:1300–1308

    Article  PubMed  CAS  Google Scholar 

  • Choi IY, Tkac I, Gruetter R (2000) Single-shot, three-dimensional “non-echo” localization method for in vivo NMR spectroscopy. Magn Reson Med 44:387–394

    Article  PubMed  CAS  Google Scholar 

  • Collins CM, Liu W, Wang J, Gruetter R, Vaughan JT, Ugurbil K, Smith MB (2004) Temperature and SAR calculations for a human head within volume and surface coils at 64 and 300 MHz. J Magn Reson Imaging 19:650–656

    Article  PubMed  Google Scholar 

  • de Graaf RA (2005) Theoretical and experimental evaluation of broadband decoupling techniques for in vivo nuclear magnetic resonance spectroscopy. Magn Reson Med 53:1297–1306

    Article  PubMed  CAS  Google Scholar 

  • de Graaf RA, Brown PB, Mason GF, Rothman DL, Behar KL (2003a) Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H- [13C]-NMR spectroscopy. Magn Reson Med 49:37–46

    Article  PubMed  CAS  Google Scholar 

  • de Graaf RA, Mason GF, Patel AB, Behar KL, Rothman DL (2003b) In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism. NMR Biomed 16:339–357

    Article  PubMed  CAS  Google Scholar 

  • de Graaf RA, Mason GF, Patel AB, Rothman DL, Behar KL (2004) Regional glucose metabolism and glutamatergic neurotransmission in rat brain in vivo. Proc Natl Acad Sci USA 101: 12700–12705

    Article  PubMed  Google Scholar 

  • de Graaf RA, Patel AB, Rothman DL, Behar KL (2006) Acute regulation of steady-state GABA levels following GABA-transaminase inhibition in rat cerebral cortex. Neurochem Int 48:508–514

    Article  PubMed  CAS  Google Scholar 

  • Deelchand DK, Ugurbil K, Henry PG (2006) Investigating brain metabolism at high fields using localized 13C NMR spectroscopy without 1H decoupling. Magn Reson Med 55:279–286

    Article  PubMed  CAS  Google Scholar 

  • Deelchand DK, Nelson C, Shestov AA, Ugurbil K, Henry P-G (2008a) Simultaneous measurement of neuronal and glial metabolism in rat brain in vivo using co-infusion of [1,6-13C2]glucose and [1,2-13C2]acetate. In: Proceedings of the 16th ISMRM, Toronto, ON, Canada

    Google Scholar 

  • Deelchand DK, Iltis I, Marjanska M, Nelson C, Ugurbil K, Henry P-G (2008b) Localized detection of hyperpolarized [1-13C]pyruvate and its metabolic products in rat brain. In: Proceedings of the 16th ISMRM, Toronto, ON, Canada

    Google Scholar 

  • Ebert D, Haller RG, Walton ME (2003) Energy contribution of octanoate to intact rat brain metabolism measured by 13C nuclear magnetic resonance spectroscopy. J Neurosci 23:5928–5935

    PubMed  CAS  Google Scholar 

  • Fitzpatrick SM, Hetherington HP, Behar KL, Shulman RG (1990) The flux from glucose to glutamate in the rat brain in vivo as determined by 1H-observed, 13C-edited NMR spectroscopy. J Cereb Blood Flow Metab 10:170–179

    Article  PubMed  CAS  Google Scholar 

  • Golman K, Petersson JS (2006) Metabolic imaging and other applications of hyperpolarized 13C. Acad Radiol 13:932–942

    Article  PubMed  Google Scholar 

  • Golman K, in’t Zand R, Thaning M (2006) Real-time metabolic imaging. Proc Natl Acad Sci USA 103:11270–11275

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez SV, Nguyen NH, Rise F, Hassel B (2005) Brain metabolism of exogenous pyruvate. J Neurochem 95:284–293

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R (2002) In vivo 13C NMR studies of compartmentalized cerebral carbohydrate metabolism. Neurochem Int 41:143–154

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R (2003) Glycogen: the forgotten cerebral energy store. J Neurosci Res 74:179–183

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R, Boesch C (1992) Fast, noniterative shimming of spatially localized signals. In vivo analysis of the magnetic field along axes. J Magn Reson 96:323

    CAS  Google Scholar 

  • Gruetter R, Tkac I (2000) Field mapping without reference scan using asymmetric echo-planar techniques. Magn Reson Med 43:319–323

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R, Rothman DL, Novotny EJ, Shulman RG (1992) Localized 13C NMR spectroscopy of myo-inositol in the human brain in vivo. Magn Reson Med 25:204–210

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R, Novotny EJ, Boulware SD, Mason GF, Rothman DL, Shulman GI, Prichard JW, Shulman RG (1994) Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose. J Neurochem 63:1377–1385

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R, Adriany G, Merkle H, Andersen PM (1996) Broadband decoupled, 1H-localized 13C MRS of the human brain at 4 Tesla. Magn Reson Med 36:659–664

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R, Seaquist ER, Kim S, Ugurbil K (1998) Localized in vivo 13C-NMR of glutamate metabolism in the human brain: initial results at 4 Tesla. Dev Neurosci 20:380–388

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R, Seaquist ER, Ugurbil K (2001) A mathematical model of compartmentalized neurotransmitter metabolism in the human brain. Am J Physiol 281:E100–E112

    CAS  Google Scholar 

  • Gruetter R, Adriany G, Choi I-Y, Henry P-G, Lei H-X, Oz G (2003) Localized in vivo 13C NMR spectroscopy of the brain. NMR Biomed 16:313–338

    Article  PubMed  CAS  Google Scholar 

  • Hassel B, Brathe A (2000) Cerebral metabolism of lactate in vivo: evidence for neuronal pyruvate carboxylation. J Cereb Blood Flow Metab 20:327–336

    Article  PubMed  CAS  Google Scholar 

  • Henry P-G, Roussel R, Vaufrey F, Dautry C, Bloch G (2000) Semiselective POCE NMR spectroscopy. Magn Reson Med 44:395–400

    Article  PubMed  CAS  Google Scholar 

  • Henry PG, Lebon V, Vaufrey F, Brouillet E, Hantraye P, Bloch G (2002) Decreased TCA cycle rate in the rat brain after acute 3-NP treatment measured by in vivo 1H-[13C] NMR spectroscopy. J Neurochem 82:857–866

    Article  PubMed  CAS  Google Scholar 

  • Henry P-G, Tkac I, Gruetter R (2003a) 1H-localized broadband 13C NMR spectroscopy of the rat brain in vivo at 9.4 Tesla. Magn Reson Med 50:684–692

    Article  PubMed  CAS  Google Scholar 

  • Henry P-G, Oz G, Provencher S, Gruetter R (2003b) Toward dynamic isotopomer analysis in the rat brain in vivo: automatic quantitation of 13C NMR spectra using LCModel. NMR Biomed 16:400–412

    Article  PubMed  CAS  Google Scholar 

  • Henry P, Crawford S, Oz G, Ugurbil K, Gruetter R (2003c) Glucose and glial-neuronal metabolism in α-chloralose anesthetized rats measured by in vivo 13C NMR spectroscopy. In: Proceedings of the International Society for Magnetic Resonance in Medicine, Toronto, p 1967

    Google Scholar 

  • Henry P-G, Oz G, Seaquist ER, Ugurbil K, Gruetter R (2006a) Localized 13C NMR measurement of NAA and GSH turnover in the human brain over multiple days. In: 14th ISMRM, Seattle, WA, p 402

    Google Scholar 

  • Henry PG, Marjanska M, Walls JD, Valette J, Gruetter R, Ugurbil K (2006b) Proton-observed carbon-edited NMR spectroscopy in strongly coupled second-order spin systems. Magn Reson Med 55:250–257

    Article  PubMed  CAS  Google Scholar 

  • Henry PG, Adriany G, Deelchand D, Gruetter R, Marjanska M, Oz G, Seaquist ER, Shestov A, Ugurbil K (2006c) In vivo 13C NMR spectroscopy and metabolic modeling in the brain: a practical perspective. Magn Reson Imaging 24:527–539

    Article  PubMed  CAS  Google Scholar 

  • Henry P-G, Criego AB, Kumar A, Seaquist ER (2008) Brain oxidative glucose metabolism in patients with Type 1 diabetes and hypoglycemia unawareness: an in vivo 13C MRS study. In: American Diabetes Association’s 68th Scientific Sessions, San Francisco, CA, pp 19-OR

    Google Scholar 

  • Hyder F, Chase JR, Behar KL, Mason GF, Siddeef M, Rothman DL, Shulman RG (1996) Increased tricarboxylic acid cycle flux in the rat brain during forepaw stimulation detected with 1H [13C] NMR. Proc Natl Acad Sci USA 93:7612–7617

    Article  PubMed  CAS  Google Scholar 

  • Hyder F, Rothman DL, Mason GF, Rangarajan A, Behar KL, Shulman RG (1997) Oxidative glucose metabolism in rat brain during single forepaw stimulation: A spatially localized 1H[13C] nuclear magnetic resonance study. J Cereb Blood Flow Metab 17:1040–1047

    Article  PubMed  CAS  Google Scholar 

  • Hyder F, Renken R, Rothman DL (1999) In vivo carbon-edited detection with proton echo-planar spectroscopic imaging (ICED PEPSI): [3,4-13CH2]glutamate/glutamine tomography in rat brain. Magn Reson Med 42:997–1003

    Article  PubMed  CAS  Google Scholar 

  • Iltis I, Deelchand DK, Marjanska M, Nelson C, Ugurbil K, Henry P-G (2008) First studies with hyperpolarized [2-13C]pyruvate in the rat brain. In: Proceedings of the 16th ISMRM, Toronto, ON, Canada

    Google Scholar 

  • Inubushi T, Morikawa S, Kito K, Arai T (1993) 1H-detected in vivo 13C NMR spectroscopy and imaging at 2 T magnetic field: efficient monitoring of 13C-labeled metabolites in the rat brain derived from 1-13C glucose. Biochem Biophys Res Commun 191:866–872

    Article  PubMed  CAS  Google Scholar 

  • Jeffrey FM, Reshetov A, Storey CJ, Carvalho RA, Sherry AD, Malloy CR (1999) Use of a single (13)C NMR resonance of glutamate for measuring oxygen consumption in tissue. Am J Physiol 277:E1111–1121

    PubMed  CAS  Google Scholar 

  • Klomp DW, Renema WK, van der Graaf M, de Galan BE, Kentgens AP, Heerschap A (2006) Sensitivity-enhanced 13C MR spectroscopy of the human brain at 3 Tesla. Magn Reson Med 55:271–278

    Article  PubMed  CAS  Google Scholar 

  • Klomp DW, Kentgens AP, Heerschap A (2008) Polarization transfer for sensitivity-enhanced MRS using a single radio frequency transmit channel. NMR Biomed 21(5):444–452

    Article  CAS  Google Scholar 

  • Lebon V, Petersen KF, Cline GW, Shen J, Mason GF, Dufour S, Behar KL, Shulman GI, Rothman DL (2002) Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci 22:1523–1531

    PubMed  CAS  Google Scholar 

  • Lewandowski ED, Yu X, LaNoue KF, White LT, Doumen C, O’Donnell JM (1997) Altered metabolite exchange between subcellular compartments in intact postischemic rabbit hearts. Circ Res 81:165–175

    PubMed  CAS  Google Scholar 

  • Li S, Chen Z, Zhang Y, Lizak M, Bacher J, Innis RB, Shen J (2005) In vivo single-shot, proton-localized 13C MRS of rhesus monkey brain. NMR Biomed 18:560–569

    Article  PubMed  CAS  Google Scholar 

  • Lin AP, Shic F, Enriquez C, Ross BD (2003) Reduced glutamate neurotransmission in patients with Alzheimer’s disease – an in vivo (13)C magnetic resonance spectroscopy study. MAGMA 16:29–42

    Article  PubMed  CAS  Google Scholar 

  • Marjanska M, Henry P-G, Gruetter R, Garwood M, Ugurbil K (2004) A new method for proton detected carbon edited spectroscopy using LASER. In: Proceedings of the 12th ISMRM, Kyoto, Japan, p 679

    Google Scholar 

  • Mason GF, Rothman DL (2004) Basic principles of metabolic modeling of NMR (13)C isotopic turnover to determine rates of brain metabolism in vivo. Metab Eng 6:75–84

    Article  PubMed  CAS  Google Scholar 

  • Mason GF, Behar KL, Rothman DL, Shulman RG (1992a) NMR determination of intracerebral glucose concentration and transport kinetics in rat brain. J Cereb Blood Flow Metab 12:448–455

    Article  PubMed  CAS  Google Scholar 

  • Mason GF, Rothman DL, Behar KL, Shulman RG (1992b) NMR determination of the TCA cycle rate and α-ketoglutarate/glutamate exchange rate in rat brain. J Cereb Blood Flow Metab 12:434–447

    Article  PubMed  CAS  Google Scholar 

  • Mason GF, Gruetter R, Rothman DL, Behar KL, Shulman RG, Novotny EJ (1995) Simultaneous determination of the rates of the TCA cycle, glucose utilization, α-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. J Cereb Blood Flow Metab 15:12–25

    Article  PubMed  CAS  Google Scholar 

  • Mason GF, Pan JW, Chu W-J, Newcomer BR, Zhang Y, Orr R, Hetherington HP (1999) Measurement of the tricarboxylic acid cycle rate in human grey and white matter in vivo by 1H-[13C] magnetic resonance spectroscopy at 4.1 T. J. Cereb. Blood Flow Metab 19: 1179–1188

    Article  CAS  Google Scholar 

  • Mason GF, Falk Petersen K, de Graaf RA, Kanamatsu T, Otsuki T, Rothman DL (2003) A comparison of (13)C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-(13)C]glucose. Brain Res Protocols 10:181–190

    Article  CAS  Google Scholar 

  • Mason GF, Petersen KF, Lebon V, Rothman DL, Shulman GI (2006) Increased brain monocarboxylic acid transport and utilization in type 1 diabetes. Diabetes 55:929–934

    Article  PubMed  CAS  Google Scholar 

  • Mason GF, Petersen KF, de Graaf RA, Shulman GI, Rothman DL (2007) Measurements of the anaplerotic rate in the human cerebral cortex using 13C magnetic resonance spectroscopy and [1-13C] and [2-13C] glucose. J Neurochem 100:73–86

    Article  PubMed  CAS  Google Scholar 

  • Moreno A, Ross BD, Bluml S (2001a) Direct determination of the N-acetyl-L-aspartate synthesis rate in the human brain by (13)C MRS and [1-(13)C]glucose infusion. J Neurochem 77: 347–350

    Article  PubMed  CAS  Google Scholar 

  • Moreno A, Bluml S, Hwang JH, Ross BD (2001b) Alternative 1-(13)C glucose infusion protocols for clinical (13)C MRS examinations of the brain. Magn Reson Med 46:39–48

    Article  PubMed  CAS  Google Scholar 

  • Nabuurs CI, Klomp DW, Veltien A, Kan HE, Heerschap A (2008) Localized sensitivity enhanced in vivo (13)C MRS to detect glucose metabolism in the mouse brain. Magn Reson Med 59:626–630

    Article  PubMed  CAS  Google Scholar 

  • Öz G, Berkich DA, Henry PG, Xu Y, LaNoue K, Hutson SM, Gruetter R (2004) Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity. J Neurosci 24: 11273–11279

    Article  PubMed  CAS  Google Scholar 

  • Öz G, Henry PG, Seaquist ER, Gruetter R (2005). Noninvasive Detection of Brain Glycogen in Humans. Appl Magn Reson 29(1):159–169

    PubMed  CAS  Google Scholar 

  • Öz G, Seaquist E, Kumar A, Criego A, Benedict L, Rao J, Henry P, Van De Moortele P, Gruetter R (2007) Human brain glycogen content and metabolism: implications on its role in brain energy metabolism. Am J Physiol 292:E946–E951

    Google Scholar 

  • Pan JW, Mason GF, Vaughan JT, Chu WJ, Zhang Y, Hetherington HP (1997) 13C editing of glutamate in human brain using J-refocused coherence transfer spectroscopy at 4.1 T. Magn Reson Med 37:355–358

    Article  PubMed  CAS  Google Scholar 

  • Pan JW, Stein DT, Telang F, Lee JH, Shen J, Brown P, Cline G, Mason GF, Shulman GI, Rothman DL, Hetherington HP (2000) Spectroscopic imaging of glutamate C4 turnover in human brain. Magn Reson Med 44:673–679

    Article  PubMed  CAS  Google Scholar 

  • Pan JW, de Graaf RA, Petersen KF, Shulman GI, Hetherington HP, Rothman DL (2002) [2,4-13C2]-beta-Hydroxybutyrate metabolism in human brain. J Cereb Blood Flow Metab 22:890–898

    Article  PubMed  CAS  Google Scholar 

  • Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG, Behar KL (2005) The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Proc Natl Acad Sci USA 102:5588–5593

    Article  PubMed  CAS  Google Scholar 

  • Pfeuffer J, Tkac I, Provencher SW, Gruetter R (1999a) Toward an in vivo neurochemical profile: quantification of 18 metabolites in short-echo-time (1)H NMR spectra of the rat brain. J Magn Reson 141:104–120

    Article  PubMed  CAS  Google Scholar 

  • Pfeuffer J, Tkac I, Choi I-Y, Merkle H, Ugurbil K, Garwood M, Gruetter R (1999b) Localized in vivo 1H NMR detection of neurotransmitter labeling in rat brain during infusion of [1-13C] D-glucose. Magn Reson Med 41:1077–1083

    Article  PubMed  CAS  Google Scholar 

  • Provencher S (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679

    Article  PubMed  CAS  Google Scholar 

  • Ross BD, Higgins RJ, Boggan JE, Willis JA, Knittel B, Unger SW (1988) Carbohydrate metabolism of the rat C6 glioma. An in vivo 13C and in vitro 1H magnetic resonance spectroscopy study. NMR Biomed 1:20–26

    Article  PubMed  CAS  Google Scholar 

  • Ross B, Lin A, Harris K, Bhattacharya P, Schweinsburg B (2003) Clinical experience with 13C MRS in vivo. NMR Biomed 16:358–369

    Article  PubMed  CAS  Google Scholar 

  • Rothman DL, Behar KL, Hetherington HP, den Hollander JA, Bendall MR, Petroff OAC, Shulman RG (1985) 1H-observe/13C-decouple spectroscopic measurements of lactate and glutamate in the rat brain in vivo. Proc Natl Acad Sci USA 82:1633–1637

    Article  PubMed  CAS  Google Scholar 

  • Rothman DL, Novotny EJ, Shulman GI, Howseman AM, Petroff OAC, Mason G, Nixon T, Hanstock CC, Prichard JW, Shulman RG (1992) 1H-[13C] NMR measurements of [4-13C]glutamate turnover in human brain. Proc Natl Acad Sci USA 89:9603–9606

    Article  PubMed  CAS  Google Scholar 

  • Serres S, Bezancon E, Franconi JM, Merle M (2007) Brain pyruvate recycling and peripheral metabolism: an NMR analysis ex vivo of acetate and glucose metabolism in the rat. J Neurochem 101:1428–1440

    Article  PubMed  CAS  Google Scholar 

  • Shen J (2006) 13C magnetic resonance spectroscopy studies of alterations in glutamate neurotransmission. Biol Psychiatry 59:883–887

    Article  PubMed  CAS  Google Scholar 

  • Shen J, Petersen KF, Behar KL, Brown P, Nixon TW, Mason GF, Petroff OAC, Shulman GI, Shulman RG, Rothman DL (1999) Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proc Natl Acad Sci USA 96:8235–8240

    Article  PubMed  CAS  Google Scholar 

  • Shestov AA, Ugurbil K, Henry P-G (2007a) A new metabolic model for analysis of dynamic 13C isotopomer time courses in the brain. In: Proceedings of the 15th ISMRM, Berlin, Germany, p 196

    Google Scholar 

  • Shestov AA, Valette J, Ugurbil K, Henry PG (2007b) On the reliability of (13)C metabolic modeling with two-compartment neuronal-glial models. J Neurosci Res 15:3294–3303

    Article  CAS  Google Scholar 

  • Shestov AA, Deelchand DK, Ugurbil K, Henry P-G (2008) Improving the precision of brain 13C metabolic modeling using co-infusion of [1,2-13C2]acetate and [1,6-13C2]glucose. In: Proceedings of the 16th ISMRM, Toronto, ON, Canada

    Google Scholar 

  • Shic F, Ross B (2003) Automated data processing of [1H-decoupled] 13C MR spectra acquired from human brain in vivo. J Magn Reson 162:259–268

    Article  PubMed  CAS  Google Scholar 

  • Shulman RG, Brown TR, Ugurbil K, Ogawa S, Cohen SM, den Hollander JA (1979) Cellular applications of 31P and 13C nuclear magnetic resonance. Science 205:160–166

    Article  PubMed  CAS  Google Scholar 

  • Sibson NR, Dhankhar A, Mason GF, Behar KL, Rothman DL, Shulman RG (1997) In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proc Natl Acad Sci USA 94:2699–2704

    Article  PubMed  CAS  Google Scholar 

  • Sibson NR, Dhankhar A, Mason GF, Rothman DL, Behar KL, Shulman RG (1998) Stoichiometric coupling of brain metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci USA 95:316–321

    Article  PubMed  CAS  Google Scholar 

  • Sibson NR, Mason GF, Shen J, Cline GW, Herskovits AZ, Wall JE, Behar KL, Rothman DL, Shulman RG (2001) In vivo 13C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during [2-13C]glucose infusion. J Neurochem 76:975–989

    Article  PubMed  CAS  Google Scholar 

  • Taylor A, McLean M, Morris P, Bachelard H (1996) Approaches to studies on neuronal/glial relationships by 13C-MRS analysis. Dev Neurosci 18:434–442

    Article  PubMed  CAS  Google Scholar 

  • Terpstra M, Gruetter R, High WB, Mescher M, DelaBarre L, Merkle H, Garwood M (1998) Lactate turnover in rat glioma measured by in vivo nuclear magnetic resonance spectroscopy. Cancer Res 58:5083–5088

    PubMed  CAS  Google Scholar 

  • Tyson RL, Gallagher C, Sutherland GR (2003) 13C-Labeled substrates and the cerebral metabolic compartmentalization of acetate and lactate. Brain Res 992:43–52

    Article  PubMed  CAS  Google Scholar 

  • Uffmann K, Gruetter R (2007) Mathematical modeling of (13)C label incorporation of the TCA cycle: the concept of composite precursor function. J Neurosci Res 85:3304–3317

    Article  PubMed  CAS  Google Scholar 

  • Ugurbil K, Brown TR, Den Hollander JA, Glynn P, Shulman RG (1978) High-resolution 13C nuclear magnetic resonance studies of glucose metabolism in Escherichia coli. Proc Natl Acad Sci USA 75:3742–3746

    Article  PubMed  CAS  Google Scholar 

  • Valette J, Shestov AA, Ugurbil K, Henry P-G (2008) 13C isotopomer metabolic modeling: automatic generation of the mathematical model. In Proceedings of the 16th ISMRM, Toronto, ON, Canada

    Google Scholar 

  • Van den Berg CJ, Krzalic L, Mela P, Waelsch H (1969) Compartmentation of glutamate metabolism in brain. Evidence for the existence of two different tricarboxylic acid cycles in brain. Biochem J 113:281–290

    PubMed  Google Scholar 

  • van den Bergh AJ, van den Boogert HJ, Heerschap A (1998) Calibration of the 1H decoupling field strength and experimental evaluation of the specific RF absorption rate in 1H-decoupled human 13C-MRS. Magn Reson Med 39:642–646

    Article  PubMed  Google Scholar 

  • van Zijl PCM, Chesnick AS, DesPres D, Moonen CTW, Ruiz-Cabello J, van Gelderen P (1993) In vivo proton spectroscopy and spectroscopic imaging of {1-13C}-glucose and its metabolic products. Magn Reson Med 30:544–551

    Article  PubMed  Google Scholar 

  • Waniewski RA, Martin DL (1998) Preferential utilization of acetate by astrocytes is attributable to transport. J Neurosci 18:5225–5233

    PubMed  CAS  Google Scholar 

  • Watanabe H, Ishihara Y, Okamoto K, Oshio K, Kanamatsu T, Tsukada Y (2000a) 3D localized 1H-13C heteronuclear single-quantum coherence correlation spectroscopy in vivo. Magn Reson Med 43:200–210

    Article  PubMed  CAS  Google Scholar 

  • Watanabe H, Umeda M, Ishihara Y, Okamoto K, Oshio K, Kanamatsu T, Tsukada Y (2000b) Human brain glucose metabolism mapping using multislice 2D 1H-13C correlation HSQC spectroscopy. Magn Reson Med 43:525–533

    Article  PubMed  CAS  Google Scholar 

  • Xu S, Shen J (2006) In vivo dynamic turnover of cerebral 13C isotopomers from [U-13C]glucose. J Magn Reson 182:221–228

    Article  PubMed  CAS  Google Scholar 

  • Yahya A, Allen PS (2005) Effect of strong homonuclear proton coupling on localized (13)C detection using PRESS. Magn Reson Med 54:1340–1350

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Shen J (2005) In vivo evidence for reduced cortical glutamate-glutamine cycling in rats treated with the antidepressant/antipanic drug phenelzine. Neuroscience 135:927–937

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Li CQ, Shen J (2005) In vivo detection of cortical GABA turnover from intravenously infused [1-13C]D-glucose. Magn Reson Med 53:1258–1267

    Article  PubMed  CAS  Google Scholar 

  • Yu X, Alpert NM, Lewandowski ED (1997) Modeling enrichment kinetics from dynamic 13C-NMR spectra: theoretical analysis and practical considerations. Am J Physiol 272:C2037–2048

    PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Dee Koski and Chris Nelson for their excellent technical support. This work was supported by NIH P41 RR008079, P30 NS057091, R01 NS038672 (P.G.H.) and the Keck Foundation. The high-resolution NMR facility at the University of Minnesota is supported with funds from the University of Minnesota Medical School, NSF (BIR-961477) and the Minnesota Medical Foundation.

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Correspondence to Pierre-Gilles Henry Ph.D. .

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Henry, PG. et al. (2012). In Vivo 13C Magnetic Resonance Spectroscopy and Metabolic Modeling: Methodology. In: Choi, IY., Gruetter, R. (eds) Neural Metabolism In Vivo. Advances in Neurobiology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1788-0_7

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