Skip to main content
SpringerLink
Log in

Advanced In Vivo Heteronuclear MRS Approaches for Studying Brain Bioenergetics Driven by Mitochondria

  • Protocol
Dynamic Brain Imaging

Part of the book series: METHODS IN MOLECULAR BIOLOGY™ ((MIMB,volume 489))

Abstract

The greatest merit of in vivo magnetic resonance spectroscopy (MRS) methodology used in biomedical research is its ability for noninvasively measuring a variety of metabolites inside a living organ. It, therefore, provides an invaluable tool for determining metabolites, chemical reaction rates and bioenergetics, as well as their dynamic changes in the human and animal. The capability of in vivo MRS is further enhanced at higher magnetic fields because of significant gain in detection sensitivity and improvement in the spectral resolution. Recent progress of in vivo MRS technology has further demonstrated its great potential in many biomedical research areas, particularly in brain research. Here, we provide a review of new developments for in vivo heteronuclear 31P and 17O MRS approaches and their applications in determining the cerebral metabolic rates of oxygen and ATP inside the mitochondria, in both animal and human brains.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Boyer PD. What makes ATP synthase spin? Nature 1999;402(6759):247, 249.

    CAS  PubMed  Google Scholar 

  2. Stock D, Leslie AG, Walker JE. Molecular architecture of the rotary motor in ATP synthase. Science 1999;286(5445):1700–1705.

    CAS  PubMed  Google Scholar 

  3. Siesjo BK. Brain energy metabolism. New York: Wiley; 1978. p 101–110.

    Google Scholar 

  4. Raichle ME. Circulatory and metabolic correlates of brain function in normal humans. In: Mountcastle VB, Plum F, Geiger SR, editors. Handbook of Physiology-The Nervous System. Bethesda: American Physiological Society; 1987. p 643–674.

    Google Scholar 

  5. Clarke DD, Sokoloff L. Circulation and energy metabolism of the brain. In: Siegel GJ, al. e, editors. Basic Neruochemistry: Molecular, Cellular and Medical Aspects. Philadephia: Lippincott-Raven Publishers; 1999. p 633–669.

    Google Scholar 

  6. Shulman RG, Rothman DL, Behar KL, Hyder F. Energetic basis of brain activity: Implications for neuroimaging. Trends Neurosci 2004;27(8):489–495.

    CAS  PubMed  Google Scholar 

  7. Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL, Shulman RG. Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J Cereb Blood Flow Metab 2006;26(7):865–877.

    CAS  PubMed  Google Scholar 

  8. Raichle ME, Mintun MA. Brain work and brain imaging. Annu Rev Neurosci 2006;29:449–476.

    CAS  PubMed  Google Scholar 

  9. Hevner RF, Wong-Riley MT. Regulation of cytochrome oxidase protein levels by functional activity in the macaque monkey visual system. J Neurosci 1990;10(4):1331–1340.

    CAS  PubMed  Google Scholar 

  10. Hevner RF, Duff RS, Wong-Riley MT. Coordination of ATP production and consumption in brain: Parallel regulation of cytochrome oxidase and Na+, K+-ATPase. Neurosci Lett 1992;138(1): 188–192.

    CAS  PubMed  Google Scholar 

  11. Rolfe DF, Brown GC. Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 1997;77(3):731–758.

    CAS  PubMed  Google Scholar 

  12. Attwell D, Laughlin SB. An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 2001;21(10):1133–1145.

    CAS  PubMed  Google Scholar 

  13. Shulman RG, Rothman DL, Hyder F. Stimulated changes in localized cerebral energy consumption under anesthesia. Proc Natl Acad Sci USA 1999;96(6): 3245–3250.

    CAS  PubMed  Google Scholar 

  14. Magistretti PJ, Pellerin L, Rothman DL, Shulman RG. Energy on demand. Science 1999;283(5401):496–497.

    CAS  PubMed  Google Scholar 

  15. Wallimann T, Hemmer W. Creatine kinase in non-muscle tissues and cells. Mol Cell Biochem 1994;133–134:193–220.

    Google Scholar 

  16. Saks VA, Ventura-Clapier R, Aliev MK. Metabolic control and metabolic capacity: Two aspects of creatine kinase functioning in the cells. Biochim Biophys Acta 1996;1274(3):81–88.

    PubMed  Google Scholar 

  17. Kemp GJ. Non-invasive methods for studying brain energy metabolism: what they show and what it means. Dev Neurosci 2000;22(5–6):418–428.

    CAS  PubMed  Google Scholar 

  18. Shulman RG, Brown TR, Ugurbil K, Ogawa S, Cohen SM, den Hollander JA. Cellular applications of 31P and 13C nuclear magnetic resonance. Science 1979;205(4402):160–166.

    CAS  PubMed  Google Scholar 

  19. Ackerman JJH, Grove TH, Wong GG, Gadian DG, Radda GK. Mapping of metabolites in whole animals by 31P NMR using surface coils. Nature 1980;283:167–170.

    CAS  PubMed  Google Scholar 

  20. Lei H, Ugurbil K, Chen W. Measurement of unidirectional Pi to ATP flux in human visual cortex at 7 Tesla using in vivo 31P magnetic resonance spectroscopy. Proc Natl Acad Sci U S A 2003;100:14409–14414.

    CAS  PubMed  Google Scholar 

  21. Gadian DG, Williams SR, Bates TE, Kauppinen RA. NMR spectroscopy: current status and future possibilities. Acta Neurochir Suppl (Wien) 1993;57:1–8.

    CAS  Google Scholar 

  22. Weiner MW. NMR spectroscopy for clinical medicine. Animal models and clinical examples. Ann N Y Acad Sci 1987;508:287–299.

    CAS  Google Scholar 

  23. Hossmann KA. Studies of experimental cerebral ischemia with NMR spectroscopy. Arzneimittelforschung 1991;41(3A):292–298.

    CAS  PubMed  Google Scholar 

  24. Lei H, Zhu XH, Zhang XL, Ugurbil K, Chen W. In vivo 31P magnetic resonance spectroscopy of human brain at 7 T: An initial experience. Magn Reson Med 2003;49:199–205.

    CAS  PubMed  Google Scholar 

  25. Petroff OA, Prichard JW, Behar KL, Alger JR, den Hollander JA, Shulman RG. Cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy. Neurology 1985;35(6):781–788.

    CAS  PubMed  Google Scholar 

  26. Burt CT, Ribolow HJ. A hypothesis: Noncyclic phosphodiesters may play a role in membrane control. Biochem Med 1984;31(1):21–30.

    CAS  PubMed  Google Scholar 

  27. Burt CT, Ribolow H. Glycerol phosphorylcholine (GPC) and serine ethanolamine phosphodiester (SEP): Evolutionary mirrored metabolites and their potential metabolic roles. Comp Biochem Physiol Biochem Mol Biol 1994;108(1):11–20.

    CAS  PubMed  Google Scholar 

  28. Ross BM, Moszczynska A, Blusztajn JK, Sherwin A, Lozano A, Kish SJ. Phospholipid biosynthetic enzymes in human brain. Lipids 1997;32(4):351–358.

    CAS  PubMed  Google Scholar 

  29. Podo F. Tumour phospholipid metabolism. NMR Biomed 1999;12(7):413–439.

    CAS  PubMed  Google Scholar 

  30. Young RS, Chen B, Petroff OA, Gore JC, Cowan BE, Novotny EJ, Jr., Wong M, Zuckerman K. The effect of diazepam on neonatal seizure: In vivo 31P and 1H NMR study. Pediatr Res 1989;25(1):27–31.

    CAS  PubMed  Google Scholar 

  31. Welch KM, Levine SR, Martin G, Ordidge R, Vande Linde AM, Helpern JA. Magnetic resonance spectroscopy in cerebral ischemia. Neurol Clin 1992;10(1):1–29.

    CAS  PubMed  Google Scholar 

  32. Duncan JS. Imaging and epilepsy. Brain 1997;120(Pt 2):339–377.

    PubMed  Google Scholar 

  33. Hetherington HP, Pan JW, Spencer DD. 1H and 31P spectroscopy and bioenergetics in the lateralization of seizures in temporal lobe epilepsy. J Magn Reson Imaging 2002;16(4):477–483.

    PubMed  Google Scholar 

  34. Brown GG, Levine SR, Gorell JM, Pettegrew JW, Gdowski JW, Bueri JA, Helpern JA, Welch KM. In vivo 31P NMR profiles of Alzheimer’s disease and multiple subcortical infarct dementia. Neurology 1989;39(11):1423–1427.

    CAS  PubMed  Google Scholar 

  35. Pettegrew JW, Klunk WE, Panchalingam K, McClure RJ, Stanley JA. Magnetic resonance spectroscopic changes in Alzheimer’s disease. Ann N Y Acad Sci 1997;826:282–306.

    CAS  PubMed  Google Scholar 

  36. Riehemann S, Volz HP, Smesny S, Hubner G, Wenda B, Rossger G, Sauer H. Phosphorus 31 magnetic resonance spectroscopy in schizophrenia research. Pathophysiology of cerebral metabolism of high-energy phosphate and membrane phospholipids. Nervenarzt 2000;71(5):354–363.

    CAS  PubMed  Google Scholar 

  37. Jensen JE, Al-Semaan YM, Williamson PC, Neufeld RW, Menon RS, Schaeffer B, Densmore M, Drost DJ. Region-specific changes in phospholipid metabolism in chronic, medicated schizophrenia: 31P-MRS study at 4.0 Tesla. Br J Psychiatry 2002;180:39–44.

    PubMed  Google Scholar 

  38. Ramadan NM, Halvorson H, Vande-Linde A, Levine SR, Helpern JA, Welch KM. Low brain magnesium in migraine. Headache 1989;29(9):590–593.

    CAS  PubMed  Google Scholar 

  39. Altura BM, Altura BT. Role of magnesium and calcium in alcohol-induced hypertension and strokes as probed by in vivo television microscopy, digital image microscopy, optical spectroscopy, 31P-NMR, spectroscopy and a unique magnesium ion-selective electrode. Alcohol Clin Exp Res 1994;18(5):1057–1068.

    CAS  PubMed  Google Scholar 

  40. Nioka S, Zaman A, Yoshioka H, Masumura M, Miyake H, Lockard S, Chance B. 31P magnetic resonance spectroscopy study of cerebral metabolism in developing dog brain and its relationship to neuronal function. Dev Neurosci 1991;13(2):61–68.

    CAS  PubMed  Google Scholar 

  41. Nioka S, Smith DS, Mayevsky A, Dobson GP, Veech RL, Subramanian H, Chance B. Age dependence of steady state mitochondrial oxidative metabolism in the in vivo hypoxic dog brain. Neurol Res 1991;13(1):25–32.

    CAS  PubMed  Google Scholar 

  42. Chance B, Leigh JS, Jr., Nioka S, Sinwell T, Younkin D, Smith DS. An approach to the problem of metabolic heterogeneity in brain: Ischemia and reflow after ischemia. Ann N Y Acad Sci 1987;508:309–320.

    CAS  PubMed  Google Scholar 

  43. Frosen S, Hoffman RA. Study of moderately rapid chemical exchange by means of nuclear magnetic double resonance. J Chem Phys 1963;39:2892–2901.

    Google Scholar 

  44. Alger JR, Shulman RG. NMR Studies of enzymatic rates in vitro and in vivo by magnetization transfer. Quart Rev Biophys 1984;17:83–124.

    CAS  Google Scholar 

  45. Ugurbil K. Magnetization transfer measurements of individual rate constants in the presence of multiple reactions. J Magn Reson 1985;64:207–219.

    CAS  Google Scholar 

  46. Ugurbil K. Magnetization transfer measurements of creatine kinase and ATPase rates in intact hearts. Circulation 1985;72(Supp. IV):IV94- IV96.

    Google Scholar 

  47. Degani H, Laughlin M, Campbell S, Shulman RG. Kinetics of creatine kinase in heart: a 31P NMR saturation- and inversion-transfer study. Biochemistry 1985;24(20): 5510–5516.

    CAS  PubMed  Google Scholar 

  48. Bottomley PA, Ouwerkerk R, Lee RF, Weiss RG. Four-angle saturation transfer (FAST) method for measuring creatine kinase reaction rates in vivo. Magn Reson Med 2002;47(5):850–863.

    CAS  PubMed  Google Scholar 

  49. Shoubridge EA, Briggs RW, Radda GK. 31P NMR saturation transfer measurements of the steady state rates of creatine kinase and ATP synthetase in the rat brain. FEBS Lett 1982;140(2):289–292.

    CAS  PubMed  Google Scholar 

  50. Du F, Zhu XH, Qiao H, Zhang X, Chen W. Efficient in vivo 31P magnetization transfer approach for noninvasively determining multiple kinetic parameters and metabolic fluxes of ATP metabolism in the human brain. Magn Reson Med 2006;57(1):103–114.

    Google Scholar 

  51. Mateescu GD, Yvars GM, Dular T. Water, Ions and O-17 Magnetic Resonance Imaging. In: Lauger P, Packer L, Vasilescu V, editors. Water and Ions in Biological Systems. Basel-Boston-Berlin: Birkhauser Verlag; 1988. p 239–250.

    Google Scholar 

  52. Pekar J, Ligeti L, Ruttner Z, Lyon RC, Sinnwell TM, van Gelderen P, Fiat D, Moonen CT, McLaughlin AC. In vivo measurement of cerebral oxygen consumption and blood flow using 17O magnetic resonance imaging. Magn Reson Med 1991;21(2):313–319.

    CAS  PubMed  Google Scholar 

  53. Fiat D, Ligeti L, Lyon RC, Ruttner Z, Pekar J, Moonen CT, McLaughlin AC. In vivo 17O NMR study of rat brain during 17O2 inhalation. Magn Reson Med 1992;24(2):370–374.

    CAS  PubMed  Google Scholar 

  54. Zhu XH, Zhang Y, Tian RX, Lei H, Zhang N, Zhang X, Merkle H, Ugurbil K, Chen W. Development of 17O NMR approach for fast imaging of cerebral metabolic rate of oxygen in rat brain at high field. Proc Natl Acad Sci U S A 2002;99(20):13194–13199.

    CAS  PubMed  Google Scholar 

  55. Zhu XH, Zhang N, Zhang Y, Zhang X, Ugurbil K, Chen W. In vivo 17O NMR approaches for brain study at high field. NMR Biomed 2005;18(2):83–103.

    CAS  PubMed  Google Scholar 

  56. Ernst RR, Bodenhausen G, Wokaun A. Principles of Nuclear Magnetic Resonance in One and Two Dimensions. New York: Oxford University Press; 1991.

    Google Scholar 

  57. Hoult DI, Richards RE. The signal-to-noise ratio of nuclear magnetic resonance experiment. J Magn Reson 1976;24:71–85.

    Google Scholar 

  58. Wen H, Chesnick AS, Balaban RS. The design and test of a new volume coil for high field imaging. Magn Reson Med 1994;32:492–498.

    CAS  PubMed  Google Scholar 

  59. Wang Z, Wang DJ, Noyszewski EA, Bogdan AR, Haselgrove JC, Reddy R, Zimmerman RA, Leigh JS. Sensitivity of in vivo MRS of the N-δ proton in proximal histidine of deoxymyoglobin. Magn Reson Med 1992;27(2):362–367.

    CAS  PubMed  Google Scholar 

  60. Qiao H, Zhang X, Zhu XH, Du F, Chen W. In vivo 31P MRS of human brain at high/ultrahigh fields: A quantitative comparison of NMR detection sensitivity and spectral resolution between 4 T and 7 T. Magn Reson Imaging 2006;24(10):1281–1286.

    CAS  PubMed  Google Scholar 

  61. Boska MD, Hubesch B, Meyerhoff DJ, Twieg DB, Karczmar GS, Matson GB, Weiner MW. Comparison of 31P MRS and 1H MRI at 1.5 and 2.0 T. Magn Reson Med 1990;13(2):228–238.

    CAS  PubMed  Google Scholar 

  62. Hardy CJ, Bottomley PA, Roemer PB, Redington RW. Rapid 31P spectroscopy on a 4-T whole-body system. Magn Reson Med 1988;8(1):104–109.

    CAS  PubMed  Google Scholar 

  63. Hetherington HP, Spencer DD, Vaughan JT, Pan JW. Quantitative 31P spectroscopic imaging of human brain at 4 Tesla: assessment of gray and white matter differences of phosphocreatine and ATP. Magn Reson Med 2001;45:46–52.

    CAS  PubMed  Google Scholar 

  64. Evelhoch JL, Ewy CS, Siegfried BA, Ackerman JJ, Rice DW, Briggs RW. 31P spin-lattice relaxation times and resonance linewidths of rat tissue in vivo: Dependence upon the static magnetic field strength. Magn Reson Med 1985;2(4):410–417.

    CAS  PubMed  Google Scholar 

  65. Mathur-De Vre R, Maerschalk C, Delporte C. Spin-lattice relaxation times and nuclear Overhauser enhancement effect for 31P metabolites in model solutions at two frequencies: Implications for in vivo spectroscopy. Magn Reson Imaging 1990; 8(6):691–698.

    CAS  PubMed  Google Scholar 

  66. Abragam A. The Principles of Nuclear Magnetism. Mott NF, Bullard EC, Wilkinson DH, editors. London: Oxford University Press; 1961.

    Google Scholar 

  67. Zhu XH, Merkle H, Kwag JH, Ugurbil K, Chen W. 17O relaxation time and NMR sensitivity of cerebral water and their field dependence. Magn Reson Med 2001;45(4):543–549.

    CAS  PubMed  Google Scholar 

  68. Thelwall PE, Blackband SJ, Chen W. Field dependence of 17O T1, T2 and SNR - in vitro and in vivo studies at 4.7, 11 and 17.6 Tesla. In: Proc Intl Soc Mag Reson Med (ISMRM) 2003; Toronto. p 504.

    Google Scholar 

  69. Mateescu GD, Yvars G, Pazara DI, Alldridge NA, LaManna JC, Lust DW, Mattingly M, Kuhn W. 17O-1H magnetic resonance imaging in plants, animals, and materials. In: Baillie TA, Jones JR, editors. Synthesis and Application of Isotopically Labeled Compounds. Amsterdam: Elsevier; 1989. p 499–508.

    Google Scholar 

  70. Hopkins AL, Barr RG. Oxygen-17 compounds as potential NMR T2 contrast agents: Enrichment effects of H2 17O on protein solutions and living tissues. Magn Reson Med 1987;4(4):399–403.

    CAS  PubMed  Google Scholar 

  71. Kwong KK, Hopkins AL, Belliveau JW, Chesler DA, Porkka LM, McKinstry RC, Finelli DA, Hunter GJ, Moore JB, Barr RG, Rosen BR. Proton NMR imaging of cerebral blood flow using H2 17O. Magn Reson Med 1991;22(1):154–158.

    CAS  PubMed  Google Scholar 

  72. Arai T, Nakao S, Mori K, Ishimori K, Morishima I, Miyazawa T, Fritz-Zieroth B. Cerebral oxygen utilization analyzed by the use of oxygen-17 and its nuclear magnetic resonance. Biochem Biophys Res Commun 1990;169(1):153–158.

    CAS  PubMed  Google Scholar 

  73. Pekar J, Sinnwell T, Ligeti L, Chesnick AS, Frank JA, McLaughlin AC. Simultaneous measurement of cerebral oxygen consumption and blood flow using 17O and 19F magnetic resonance imaging. J Cereb Blood Flow Metab 1995;15(2):312–320.

    CAS  PubMed  Google Scholar 

  74. Ronen I, Navon G. A new method for proton detection of H2 17O with potential applications for functional MRI. Magn Reson Med 1994;32(6):789–793.

    CAS  PubMed  Google Scholar 

  75. Ronen I, Merkle H, Ugurbil K, Navon G. Imaging of H2 17O distribution in the brain of a live rat by using proton-detected 17O MRI. Proc Natl Acad Sci U S A 1998;95(22):12934–12939.

    CAS  PubMed  Google Scholar 

  76. Reddy R, Stolpen AH, Leigh JS. Detection of 17O by proton T1 rho dispersion imaging. J Magn Reson B 1995;108(3):276–279.

    CAS  PubMed  Google Scholar 

  77. Chen W, Zhu XH, Ugurbil K. Imaging cerebral metabolic rate of oxygen consumption (CMRO2) using 17O NMR approach at ultra-high field. In: Shulman RG, Rothman DL, editors. Brain Energetics and Neuronal Activity. New York: John Wiley & Sons Ltd; 2004. p 125–146.

    Google Scholar 

  78. Arai T, Mori K, Nakao S, Watanabe K, Kito K, Aoki M, Mori H, Morikawa S, Inubushi T. In vivo oxygen-17 nuclear magnetic resonance for the estimation of cerebral blood flow and oxygen consumption. Biochem Biophys Res Commun 1991;179(2):954–961.

    CAS  PubMed  Google Scholar 

  79. Fiat D, Kang S. Determination of the rate of cerebral oxygen consumption and regional cerebral blood flow by non-invasive 17O in vivo NMR spectroscopy and magnetic resonance imaging: Part 1. Theory and data analysis methods. Neurol Res 1992;14(4):303–311.

    CAS  Google Scholar 

  80. Fiat D, Dolinsek J, Hankiewicz J, Dujovny M, Ausman J. Determination of regional cerebral oxygen consumption in the human: 17O natural abundance cerebral magnetic resonance imaging and spectroscopy in a whole body system. Neurol Res 1993;15(4):237–248.

    CAS  PubMed  Google Scholar 

  81. Fiat D, Kang S. Determination of the rate of cerebral oxygen consumption and regional cerebral blood flow by non-invasive 17O in vivo NMR spectroscopy and magnetic resonance imaging. Part 2. Determination of CMRO2 for the rat by 17O NMR, and CMRO2, rCBF and the partition coefficient for the cat by 17O MRI. Neurol Res 1993; 15(1):7–22.

    CAS  PubMed  Google Scholar 

  82. Mateescu GD. Functional oxygen-17 magnetic resonance imaging and localized spectroscopy. Adv Exp Med Biol 2003;510:213–218.

    CAS  PubMed  Google Scholar 

  83. Stolpen AH, Reddy R, Leigh JS. 17O-decoupled proton MR spectroscopy and imaging in a tissue model. J Magn Reson 1997;125(1):1–7.

    CAS  PubMed  Google Scholar 

  84. Reddy R, Stolpen AH, Charagundla SR, Insko EK, Leigh JS. 17O-decoupled 1H detection using a double-tuned coil. Magn Reson Imaging 1996;14(9):1073–1078.

    CAS  PubMed  Google Scholar 

  85. de Crespigny AJ, D’Arceuil HE, Engelhorn T, Moseley ME. MRI of focal cerebral ischemia using 17O-labeled water. Magn Reson Med 2000;43(6):876–883.

    PubMed  Google Scholar 

  86. Zhu XH, Zhang Y, Zhang N, Ugurbil K, Chen W. Noninvasive and three-dimensional imaging of CMRO2 in rats at 9.4 T: Reproducibility test and normothermia/hypothermia comparison study. J Cereb Blood Flow Metab 2007;27(6):1225–1234.

    PubMed  Google Scholar 

  87. Zhang N, Zhu XH, Lei H, Ugurbil K, Chen W. Simplified methods for calculating cerebral metabolic rate of oxygen based on 17O magnetic resonance spectroscopic imaging measurement during a short 17O2 inhalation. J Cereb Blood Flow Metab 2004;24(8):840–848.

    CAS  PubMed  Google Scholar 

  88. Ter-Pogossian MM, Eichling JO, Davis DO, Welch MJ. The measure in vivo of regional cerebral oxygen utilization by means of oxyhemoglobin labeled with radioactive oxygen-15. J Clin Invest 1970;49:381–391.

    CAS  PubMed  Google Scholar 

  89. Lenzi GL, Jones T, Frackowiak RS. Positron emission tomography: state of the art in neurology. Prog Nucl Med 1981;7:118–137.

    CAS  PubMed  Google Scholar 

  90. Mintun MA, Raichle ME, Martin WR, Herscovitch P. Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. J Nucl Med 1984;25(2): 177–187.

    CAS  PubMed  Google Scholar 

  91. Fox PT, Raichle ME, Mintun MA, Dence C. Nonoxidative glucose consumption during focal physiologic neural activity. Science 1988;241:462–464.

    CAS  PubMed  Google Scholar 

  92. Kety SS, Schmidt CF. The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations. Am J Physiol 1945;143:53–66.

    CAS  Google Scholar 

  93. Kety SS, Schmidt CF. Nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure and normal values. J Clin Invest 1948;27:476–483.

    Google Scholar 

  94. Kety SS, Schmidt CF. Effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 1948;27:484–492.

    CAS  Google Scholar 

  95. Herscovitch A, Raichle ME. What is the correct value for the brain-blood partition coefficient for water? J Cereb Blood Flow Metab 1985;5:65–69.

    CAS  PubMed  Google Scholar 

  96. Herscovitch P, Raichle ME, Kilbourn MR, Welch MJ. Positron emission tomographic measurement of cerebral blood flow and permeability-surface area product of water using [15O]water and [11C]butanol. J Cereb Blood Flow Metab 1987;7(5):527–542.

    CAS  PubMed  Google Scholar 

  97. Zhang X, Zhu XH, Tian R, Zhang Y, Merkle H, Chen W. Measurement of arterial input function of 17O water tracer in rat carotid artery by using a region-defined (REDE) implanted vascular RF coil. Magma 2003;16(2):77–85.

    PubMed  Google Scholar 

  98. Nakao Y, Itoh Y, Kuang TY, Cook M, Jehle J, Sokoloff L. Effects of anesthesia on functional activation of cerebral blood flow and metabolism. Proc Natl Acad Sci U S A 2001;98(13):7593–7598.

    CAS  PubMed  Google Scholar 

  99. Hyder F, Kennan RP, Kida I, Mason GF, Behar KL, Rothman D. Dependence of oxygen delivery on blood flow in rat brain: A 7 tesla nuclear magnetic resonance study. J Cereb Blood Flow Metab 2000;20(3):485–498.

    CAS  PubMed  Google Scholar 

  100. Yee SH, Lee K, Jerabek PA, Fox PT. Quantitative measurement of oxygen metabolic rate in the rat brain using microPET imaging of briefly inhaled 15O-labelled oxygen gas. Nucl Med Commun 2006;27(7): 573–581.

    CAS  PubMed  Google Scholar 

  101. Zhang NY, Zhu XH, Chen W. Evaluation of the simplified method for mapping cerebral metabolic rate of oxygen based on 17O NMR approach. In: Proc Intl Soc Mag Reson Med (ISMRM), 2006; Seattle. p 952.

    Google Scholar 

  102. Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in Mammalian central nervous system. J Cereb Blood Flow Metab 2003;23(5):513–530.

    CAS  PubMed  Google Scholar 

  103. Weiss RG, Gerstenblith G, Bottomley PA. ATP flux through creatine kinase in the normal, stressed, and failing human heart. Proc Natl Acad Sci U S A 2005;102(3):808–813.

    CAS  PubMed  Google Scholar 

  104. Balaban RS, Kantor HL, Ferretti JA. In vivo flux between phosphocreatine and adenosine triphosphate determined by two-dimensional phosphorous NMR. J Biol Chem 1983;258(21):12787–12789.

    CAS  PubMed  Google Scholar 

  105. Degani H, Alger JR, Shulman RG, Petroff OA, Prichard JW. 31P magnetization transfer studies of creatine kinase kinetics in living rabbit brain. Magn Reson Med 1987;5(1):1–12.

    CAS  PubMed  Google Scholar 

  106. Bottomley PA, Hardy CJ. Mapping creatine kinase reaction rates in human brain and heart with 4 Tesla saturation transfer 31P NMR. J Magn Reson 1992;99:443–448.

    CAS  Google Scholar 

  107. Sauter A, Rudin M. Determination of creatine kinase parameters in rat brain by NMR magnetization transfer. J Biological Chem 1993;268:13166–13171.

    CAS  Google Scholar 

  108. Chen W, Zhu X-H, Adriany G, Ugurbil K. Increase of creatine kinase activity in the visual cortex of human brain during visual stimulation: A 31P NMR magnetization transfer study. Magn Reson Med 1997;38:551–557.

    CAS  PubMed  Google Scholar 

  109. Braunova Z, Kasparova S, Mlynarik V, Mierisova S, Liptaj T, Tkac I, Gvozdjakova A. Metabolic changes in rat brain after prolonged ethanol consumption measured by 1H and 31P MRS experiments. Cell Mol Neurobiol 2000;20(6):703–715.

    CAS  PubMed  Google Scholar 

  110. Mlynarik v ZS, Brehm A, Bischof M, Roden M. An optimized protocol for measuring rate constant of creatine kinase reaction in human brain by 31P NMR saturation transfer. 13th Proc Intl Soc Mag Reson Med2005:2767.

    Google Scholar 

  111. Joubert F, Mateo P, Gillet B, Beloeil JC, Mazet JL, Hoerter JA. CK flux or direct ATP transfer: Versatility of energy transfer pathways evidenced by NMR in the perfused heart. Mol Cell Biochem 2004;256–257(1–2):43–58.

    PubMed  Google Scholar 

  112. Matthews PM, Bland JL, Gadian DG, Radda GK. A 31P-NMR saturation transfer study of the regulation of creatine kinase in the rat heart. Biochim Biophys Acta 1982;721(3):312–320.

    CAS  PubMed  Google Scholar 

  113. Mora BN, Narasimhan PT, Ross BD. 31P magnetization transfer studies in the monkey brain. Magn Reson Med 1992;26(1):100–115.

    CAS  PubMed  Google Scholar 

  114. Bittl JA, DeLayre J, Ingwall JS. Rate equation for creatine kinase predicts the in vivo reaction velocity: 31P NMR surface coil studies in brain, heart, and skeletal muscle of the living rat. Biochemistry 1987;26:6083–6090.

    CAS  PubMed  Google Scholar 

  115. Ugurbil K, Petein M, Maiden R, Michurski S, From A. Measurement of an individual rate constant in the presence of multiple exchanges: Application to myocardial creatine kinase rates. Biochemistry 1986;25: 100–108.

    CAS  PubMed  Google Scholar 

  116. Spencer RG, Balschi JA, Leigh JS, Jr., Ingwall JS. ATP synthesis and degradation rates in the perfused rat heart. 31P-nuclear magnetic resonance double saturation transfer measurements. Biophys J 1988;54(5): 921–929.

    CAS  PubMed  Google Scholar 

  117. Joubert F, Mazet JL, Mateo P, Hoerter JA. 31P NMR detection of subcellular creatine kinase fluxes in the perfused rat heart: Contractility modifies energy transfer pathways. J Biol Chem 2002;277(21):18469–18476.

    CAS  PubMed  Google Scholar 

  118. Mitsumori F, Rees D, Brindle KM, Radda GK, Campbell ID. 31P-NMR saturation transfer studies of aerobic Escherichia coli cells. Biochimica et Biophysica Acta 1988;969(2):185–193.

    CAS  PubMed  Google Scholar 

  119. Campbell SL, Jones KA, Shulman RG. 31P NMR saturation-transfer measurements in Saccharomyces cerevisiae: Characterization of phosphate exchange reactions by iodoacetate and antimycin A inhibition. Biochemistry 1987;26(23):7483–7492.

    Google Scholar 

  120. Thoma WJ, Ugurbil K. Saturation-transfer studies of ATP-Pi exchange in isolated perfused rat liver. Biochimica et Biophysica Acta 1987;893(2):225–231.

    CAS  PubMed  Google Scholar 

  121. Kingsley-Hickman PB, Sako EY, Mohanakrishnan P, Robitaille PM, From AH, Foker JE, Ugurbil K. 31P NMR studies of ATP synthesis and hydrolysis kinetics in the intact myocardium. Biochemistry 1987;26(23): 7501–7510.

    CAS  PubMed  Google Scholar 

  122. Hinkle PC. P/O ratios of mitochondrial oxidative phosphorylation. Biochim Biophys Acta 2005;1706(1–2):1–11.

    CAS  PubMed  Google Scholar 

  123. Du F, Zhang Y, Friedman M, Zhu XH, Ugurbil K, Chen W. Study of correlation between brain activity and ATP metabolic rates by means of 31P magnetization transfer and electroencephalograph measurement. In: Proc Intl Soc Mag Reson Med (ISMRM), 2006; Seattle. p 2125.

    Google Scholar 

  124. Fox PT, Raichle ME. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci USA 1986; 83:1140–1144.

    CAS  PubMed  Google Scholar 

  125. Ribeiro L, Kuwabara H, Meyer E, Fujita H, Marrett S, Evans A, Gjedde A. Cerebral blood flow and metabolism during nonspecific bilateral visual stimulation in normal subjects. In: Uemura K, editor. Quantification of Brain Function in Tracer Kinetics and Image Analysis in Brain PET. New York: Elsevier Science; 1993. p 229–236.

    Google Scholar 

  126. Roland PE, Ericksson L, Stone-Elander S, Widen L. Does mental activity change the oxidative metabolism of the brain? J Neurosci 1987;7:2373–2389.

    CAS  PubMed  Google Scholar 

  127. Marrett S, Fujita H, Meyer E, Ribeiro L, Evans A, Kuwabara H, Gjedde A. Stimulus specific increase of oxidative metabolism in human visual cortex. In: Uemura K, editor. Quantification of Brain Function in Tracer Kinetics and Image Analysis in Brain PET. New York: Elsevier Science; 1993. p 217–228.

    Google Scholar 

  128. Prichard J, Rothman D, Novotny E, Petroff O, Kuwabara T, Avison M, Howseman A, Hanstock C, Shulman RG. Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation. Proc Natl Acad Sci (USA) 1992;88:5829–5831.

    Google Scholar 

  129. Shulman RG, Hyder F, Rothman DL. Cerebral energetics and the glycogen shunt: neurochemical basis of functional imaging. Proc Natl Acad Sci U S A 2001; 98(11):6417–6422.

    CAS  PubMed  Google Scholar 

  130. Vafaee MS, Meyer E, Marrett S, Paus T, Evans AC, Gjedde A. Frequency-dependent changes in cerebral metabolic rate of oxygen during activation of human visual cortex. J Cereb Blood Flow Metab 1999;19(3):272–277.

    CAS  PubMed  Google Scholar 

  131. Davis TL, Kwong KK, Weisskoff RM, Rosen BR. Calibrated functional MRI: Mapping the dynamic of oxidative metabolism. Proc Natl Acad Sci USA 1998;95:1834–1839.

    CAS  PubMed  Google Scholar 

  132. Hoge RD, Atkinson J, Gill B, Crelier GR, Marrett S, Pike GB. Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: The deoxyhemoglobin dilution model [In Process Citation]. Magn Reson Med 1999;42(5):849–863.

    CAS  PubMed  Google Scholar 

  133. Hyder F, Chase JR, Behar KL, Mason GF, Siddeek M, Rothman DL, Shulman RG. Increase tricarboxylic acid cycle flux in rat brain during forepaw stimulation detected with 1H-13C NMR. Proc Natl Acad Sci USA 1996;93:7612–7617.

    CAS  PubMed  Google Scholar 

  134. Kim SG, Rostrup E, Larsson HB, Ogawa S, Paulson OB. Determination of relative CMRO2 from CBF and BOLD changes: Significant increase of oxygen consumption rate during visual stimulation. Magn Reson Med 1999;41(6):1152–1161.

    CAS  PubMed  Google Scholar 

  135. Chen W, Zhu XH, Gruetter R, Seaquist ER, Ugurbil K. Study of oxygen utilization changes of human visual cortex during hemifield stimulation using 1H-13C MRS and fMRI. Magn Reson Med 2001;45:349–355.

    CAS  PubMed  Google Scholar 

  136. Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 2004;305(5680):99–103.

    CAS  PubMed  Google Scholar 

  137. Ogawa S, Lee T-M, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci USA 1990;87:9868–9872.

    CAS  PubMed  Google Scholar 

  138. Ogawa S, Tank DW, Menon R, Ellermann JM, Kim S-G, Merkle H, Ugurbil K. Intrinsic signal changes accompanying sensory stimulation: Functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci USA 1992; 89:5951–5955.

    CAS  PubMed  Google Scholar 

  139. Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE, Cohen MS, Turner R, Cheng HM, Brady TJ, Rosen BR. Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci USA 1992;89:5675–5679.

    CAS  PubMed  Google Scholar 

  140. Bandettini PA, Wong EC, Hinks RS, Tikofsky RS, Hyde JS. Time course EPI of human brain function during task activation. Magn Reson Med 1992;25:390–397.

    CAS  PubMed  Google Scholar 

  141. Frahm J, Bruhn H, Merboldt KD, Hanicke W. Dynamic MR imaging of human brain oxygenation during rest and photic stimulation. J Magn Reson Imag 1992;2(5):501–505.

    CAS  Google Scholar 

  142. Blamire AM, Ogawa S, Ugurbil K, Rothman D, McCarthy G, Ellermann JM, Hyder F, Rattner Z, Shulman RG. Dynamic mapping of the human visual cortex by high-speed magnetic resonance imaging. Proc Natl Acad Sci USA 1992;89:11069–11073.

    CAS  PubMed  Google Scholar 

  143. Barinaga M. What makes brain neurons run. Science 1997;276:196–198.

    CAS  PubMed  Google Scholar 

  144. Zhu XH, Zhang Y, Zhang NY, Zhang XL, Ugurbil K, Chen W. Direct imaging of CMRO2 in cat visual cortex at rest and visual stimulation. In: Proc Intl Soc Mag Reson Med (ISMRM), 2006; Seattle.p 457.

    Google Scholar 

  145. Lei H, Zhu XH, Li YX, Ugurbil K, Chen W. Changes of cerebral metabolism in human primary visual cortex during functional activation observed by in vivo 31P MRS at 7T. In: Proc Intl Soc Mag Reson Med (ISMRM), 2004; Kyoto, Japan. p 2361.

    Google Scholar 

  146. Maurer I, Zierz S, Moller H. Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia. Schizophr Res 2001; 48(1):125–136.

    CAS  PubMed  Google Scholar 

  147. Wong-Riley M, Antuono P, Ho KC, Egan R, Hevner R, Liebl W, Huang Z, Rachel R, Jones J. Cytochrome oxidase in Alzheimer’s disease: Biochemical, histochemical, and immunohistochemical analyses of the visual and other systems. Vision Res 1997;37(24):3593–3608.

    CAS  PubMed  Google Scholar 

  148. Maurer I, Zierz S, Moller HJ. A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol Aging 2000;21(3):455–462.

    CAS  PubMed  Google Scholar 

  149. Frackowiak RS, Herold S, Petty RK, Morgan-Hughes JA. The cerebral metabolism of glucose and oxygen measured with positron tomography in patients with mitochondrial diseases. Brain 1988;111 (Pt 5):1009–1024.

    PubMed  Google Scholar 

  150. Beal MF. Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann Neurol 1992;31(2):119–130.

    CAS  PubMed  Google Scholar 

  151. Wallace DC. Mitochondrial genetics: A paradigm for aging and degenerative diseases? Science 1992;256(5057):628–632.

    CAS  PubMed  Google Scholar 

  152. Wallace DC. Mitochondrial diseases in man and mouse. Science 1999;283(5407):1482–1488.

    CAS  PubMed  Google Scholar 

  153. Ugurbil K, Adriany G, Akgün C, Andersen P, Chen W, Garwood M, Gruetter R, Henry P-G, Marjanska M, Moeller S, Van de Moortele P-F, Prüssmann K, Tkac I, Vaughan JT, Wiesinger F, Yacoub E, Zhu X-H. High Magnetic Fields for Imaging Cerebral Morphology, Function and Biochemistry. In: Robitaille PMLaB, L.J., editor. Biological Magnetic Resonance: Ultra High Field Magnetic Resonance Imaging. Volume 26. New York: Springer; 2006. p 285–342.

    Google Scholar 

Download references

Acknowledgments

The authors would like to thank Drs. Hellmut Merkle, Run-Xia Tian, Peter Andersen, Gregor Adriany, Pete Thelwall and Mr. John Strupp for their technical assistance, support and scientific discussion. Part of the reviewed work was supported by NIH grants of NS41262, EB02632, NS39043, EB00329, P30NS057091 and P41 RR08079, the W.M. Keck Foundation and the MIND Institute.

Author information

Authors and Affiliations

  1. Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, School of Medicine, Minneapolis, MN

    Xiao-Hong Zhu, Fei Du, Nanyin Zhang, Yi Zhang, Xiaoliang Zhang, Hongyan Qiao, Kamil Ugurbil & Wei Chen

  2. State Key Laboratory of Magnetic Resonance and Molecular and Atomic Physics, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan, China

    Hao Lei

Authors
  1. Xiao-Hong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fei Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nanyin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hao Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoliang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hongyan Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kamil Ugurbil
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Yale University, New Haven, CT, USA

    Fahmeed Hyder

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Zhu, XH. et al. (2009). Advanced In Vivo Heteronuclear MRS Approaches for Studying Brain Bioenergetics Driven by Mitochondria. In: Hyder, F. (eds) Dynamic Brain Imaging. METHODS IN MOLECULAR BIOLOGY™, vol 489. Humana Press. https://doi.org/10.1007/978-1-59745-543-5_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-543-5_15

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-74-9

  • Online ISBN: 978-1-59745-543-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation