Acta Neurochirurgica

, 151:51 | Cite as

A combined microdialysis and FDG-PET study of glucose metabolism in head injury

  • Peter J. Hutchinson
  • Mark T. O’Connell
  • Alex Seal
  • Jurgens Nortje
  • Ivan Timofeev
  • Pippa G. Al-Rawi
  • Jonathan P. Coles
  • Timothy D. Fryer
  • David K. Menon
  • John D. Pickard
  • Keri L. H. Carpenter
Clinical Article



Microdialysis continuously monitors the chemistry of a small focal volume of the cerebral extracellular space. Positron emission tomography (PET) establishes metabolism of the whole brain but only for the scan’s duration. This study’s objective was to apply these techniques together, in patients with traumatic brain injury, to assess the relationship between microdialysis (extracellular glucose, lactate, pyruvate, and the lactate/pyruvate (L/P) ratio as a marker of anaerobic metabolism) and PET parameters of glucose metabolism using the glucose analogue [18F]-fluorodeoxyglucose (FDG). In particular, we aimed to determine the fate of glucose in terms of differential metabolism to pyruvate and lactate.

Materials and methods

Microdialysis catheters (CMA70 or CMA71) were inserted into the cerebral cortex of 17 patients with major head injury. Microdialysis was performed during FDG-PET scans with regions of interest for PET analysis defined by the location of the gold-tipped microdialysis catheter. Microdialysate analysis was performed on a CMA600 analyser.


There was significant linear relationship between the PET-derived parameter of glucose metabolism (regional cerebral metabolic rate of glucose; CMRglc) and levels of lactate (r = 0.778, p < 0.0001) and pyruvate (r = 0.799, p < 0.0001), but not with the L/P ratio.


The results suggest that in this population of patients, glucose was metabolised to both lactate and pyruvate, but was not associated with an increase in the L/P ratio. This suggests an increase in glucose metabolism to both lactate and pyruvate, as opposed to a shift towards anaerobic metabolism.


Microdialysis Positron emission tomography Cerebral metabolism Glucose Glycolysis Traumatic brain injury 


  1. 1.
    Archer DP, Elphinstone MG, Pappius HM (1990) The effect of pentobarbital and isoflurane on glucose metabolism in thermally injured rat brain. J Cereb Blood Flow Metab 10:624–630PubMedGoogle Scholar
  2. 2.
    Bartnik BL, Sutton RL, Fukushima M, Harris NG, Hovda DA, Lee SM (2005) Upregulation of pentose phosphate pathway and preservation of tricarboxylic acid cycle flux after experimental brain injury. J Neurotrauma 22:1052–1065PubMedCrossRefGoogle Scholar
  3. 3.
    Bartnik BL, Hovda DA, Lee PW (2007a) Glucose metabolism after traumatic brain injury: estimation of pyruvate carboxylase and pyruvate dehydrogenase flux by mass isotopomer analysis. J Neurotrauma 24:181–194PubMedCrossRefGoogle Scholar
  4. 4.
    Bartnik BL, Lee SM, Hovda DA, Sutton RL (2007b) The fate of glucose during the period of decreased metabolism after fluid percussion injury: a 13C NMR study. J Neurotrauma 24:1079–1092PubMedCrossRefGoogle Scholar
  5. 5.
    Bellander BM Cantais E, Enblad P, Hutchinson P, Nordstrom CH, Robertson C, Sahuquillo J, Smith M, Stocchetti N, Ungerstedt U, Unterberg A, Olsen NV (2004) Consensus meeting on microdialysis in neurointensive care. Intensive Care Med 30:2166–2169CrossRefGoogle Scholar
  6. 6.
    Bergsneider M, Hovda DA, Shalmon E, Kelly DF, Vespa PM, Martin NA, Phelps ME, McArthur DL, Caron MJ, Kraus JF, Becker DP (1997) Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg 86:241–251PubMedGoogle Scholar
  7. 7.
    Bullock R, Zauner A, Woodward JJ, Myseros J, Choi SC, Ward JD, Marmarou A, Young HF (1998) Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg 89:507–518PubMedCrossRefGoogle Scholar
  8. 8.
    Coles JP, Fryer TD, Smielewski P, Chatfield DA, Steiner LA, Johnston AJ, Downey SP, Williams GB, Aigbirhio F, Hutchinson PJ, Rice K, Carpenter TA, Clark JC, Pickard JD, Menon DK (2004) Incidence and mechanisms of cerebral ischemia in early clinical head injury. J Cereb Blood Flow Metab 24:202–211PubMedCrossRefGoogle Scholar
  9. 9.
    Dohmen C, Kumura E, Rosner G, Heiss WD, Graf R (2005) Extracellular correlates of glutamate toxicity in short-term cerebral ischemia and reperfusion: a direct in vivo comparison between white and gray matter. Brain Res 1037:43–51PubMedCrossRefGoogle Scholar
  10. 10.
    Dusick JR, Glenn TC, Lee WN, Vespa PM, Kelly DF, Lee SM, Hovda DA, Martin NA (2007) Increased pentose phosphate pathway flux after clinical traumatic brain injury: a [1,2-13C2]glucose labeling study in humans. J Cereb Blood Flow Metab 27:1593–1602PubMedCrossRefGoogle Scholar
  11. 11.
    Editorial (1992) Microdialysis. Lancet 339:1326–1327CrossRefGoogle Scholar
  12. 12.
    Enblad P, Valtysson J, Andersson J, Lilja A, Valind S, Antoni G, Langstrom B, Hillered L, Persson L (1996) Simultaneous intracerebral microdialysis and positron emission tomography in the detection of ischemia in patients with subarachnoid hemorrhage. J Cereb Blood Flow Metab 16:637–644PubMedCrossRefGoogle Scholar
  13. 13.
    Engström M, Polito A, Reinstrup P, Romner B, Ryding E, Ungerstedt U, Nordström CH (2005) Intracerebral microdialysis in severe brain trauma: the importance of catheter location. J Neurosurg 102:460–469PubMedGoogle Scholar
  14. 14.
    Feng D, Ho D, Chen K, Wu L-C, Wang J-K, Liu R-S, Yeh S-H (1995) An evaluation of the algorithms for determining local cerebral metabolic rates of glucose using positron emission tomography dynamic data. IEEE Trans Med Imag 14:697–710CrossRefGoogle Scholar
  15. 15.
    Hattori N, Huang SC, Wu HM, Yeh E, Glenn TC, Vespa PM, McArthur D, Phelps ME, Hovda DA, Bergsneider M (2003) Correlation of regional metabolic rates of glucose with Glasgow Coma Scale after traumatic brain injury. J Nucl Med 44:1709–1716PubMedGoogle Scholar
  16. 16.
    Hillered L, Vespa PM, Hovda DA (2005) Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis. J Neurotrauma 22:3–41PubMedCrossRefGoogle Scholar
  17. 17.
    Hillered L, Persson L, Nilsson P, Ronne-Engstrom E, Enblad P (2006) Continuous monitoring of cerebral metabolism in traumatic brain injury: a focus on cerebral microdialysis. Curr Opin Crit Care 12:112–118PubMedCrossRefGoogle Scholar
  18. 18.
    Hlatky R, Valadka AB, Goodman JC, Contant CF, Robertson CS (2004) Patterns of energy substrates during ischemia measured in the brain by microdialysis. J Neurotrauma 21:894–906PubMedCrossRefGoogle Scholar
  19. 19.
    Huang SC, Phelps ME, Hoffman EJ, Sideris K, Selin CJ, Kuhl DE (1980) Noninvasive determination of local cerebral metabolic rate of glucose in man. Am J Physiol 238:E69–E82PubMedGoogle Scholar
  20. 20.
    Hutchinson PJ, Hutchinson DB, Barr RH, Burgess F, Kirkpatrick PJ, Pickard JD (2000) A new cranial access device for cerebral monitoring. Br J Neurosurg 14:46–48PubMedCrossRefGoogle Scholar
  21. 21.
    Hutchinson PJ, Gupta AK, Fryer TF, Al-Rawi PG, Chatfield DA, Coles JP, O’Connell MT, Kett-White R, Minhas PS, Aigbirhio FI, Clark JC, Kirkpatrick PJ, Menon DK, Pickard JD (2002) Correlation between cerebral blood flow, substrate delivery, and metabolism in head injury: a combined microdialysis and triple oxygen positron emission tomography study. J Cereb Blood Flow Metab 22:735–745PubMedCrossRefGoogle Scholar
  22. 22.
    Hutchinson PJ, O’Connell MT, Nortje J, Smith P, Al-Rawi PG, Gupta AK, Menon DK, Pickard JD (2005) Cerebral microdialysis methodology—evaluation of 20 kDa and 100 kDa catheters. Physiol Meas 26:423–428PubMedCrossRefGoogle Scholar
  23. 23.
    Kinahan PE, Rogers JG (1989) Analytic 3D image reconstruction using all detected events. IEEE Trans Nucl Sci 36:964–968CrossRefGoogle Scholar
  24. 24.
    Lammertsma AA, Brooks DJ, Frackowiak RS, Beaney RP, Herold S, Heather JD, Palmer AJ, Jones T (1987) Measurement of glucose utilisation with [18F]2-fluoro-2-deoxy-D-glucose: a comparison of different analytical methods. J Cereb Blood Flow Metab 7:161–172PubMedGoogle Scholar
  25. 25.
    Lee JY, Kim YH, Koh JY (2001) Protection by pyruvate against transient forebrain ischemia in rats. J Neurosci 21:RC71Google Scholar
  26. 26.
    Manning Fox JE, Meredith D, Halestrap AP (2000) Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J Physiol 529:285–293PubMedCrossRefGoogle Scholar
  27. 27.
    McKenna MC, Waagpetersen HS, Schousboe A, Sonnewald U (2006) Neuronal and astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: current evidence and pharmacological tools. Biochem Pharmacol 71:399–407PubMedCrossRefGoogle Scholar
  28. 28.
    Menon DK (1999) Cerebral protection in severe brain injury: physiological determinants of outcome and their optimisation. Br Med Bull 55:226–258PubMedCrossRefGoogle Scholar
  29. 29.
    Moncada S, Bolanos JP (2006) Nitric oxide, cell bioenergetics and neurodegeneration. J Neurochem 97:1676–1689PubMedCrossRefGoogle Scholar
  30. 30.
    Noske DP, Peerdeman SM, Comans EF, Dirven CM, Knol DL, Girbes AR, Vandertop WP (2005) Cerebral microdialysis and positron emission tomography after surgery for aneurysmal subarachnoid hemorrhage in grade I patients. Surg Neurol 64:109–115PubMedCrossRefGoogle Scholar
  31. 31.
    O’Connell MT, Seal A, Nortje J, Al-Rawi PG, Coles JP, Fryer TD, Menon DK, Pickard JD, Hutchinson PJ (2005) Glucose metabolism in traumatic brain injury: a combined microdialysis and [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) study. Acta Neurochir Suppl 95:165–168PubMedCrossRefGoogle Scholar
  32. 32.
    Patlak CS, Blasberg RG, Fenstermacher JD (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1–7PubMedGoogle Scholar
  33. 33.
    Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91:10625–10629PubMedCrossRefGoogle Scholar
  34. 34.
    Pellerin L (2003) Lactate as a pivotal element in neuron-glia metabolic co-operation. Neurochem Int 43:331–338PubMedCrossRefGoogle Scholar
  35. 35.
    Persson L, Hillered L (1992) Chemical monitoring of neurosurgical intensive care patients using intracerebral microdialysis. J Neurosurg 76:72–80PubMedGoogle Scholar
  36. 36.
    Pierre K, Pellerin L (2005) Monocarboxylate transporters in the central nervous system: distribution, regulation and function. J Neurochem 94:1–14PubMedCrossRefGoogle Scholar
  37. 37.
    Reinstrup P, Ståhl N, Mellergård P, Uski T, Ungerstedt U, Nordström CH (2000) Intracerebral microdialysis in clinical practice: baseline values for chemical markers during wakefulness, anesthesia, and neurosurgery. Neurosurgery 47:701–709PubMedCrossRefGoogle Scholar
  38. 38.
    Samuelsson C, Hillered L, Zetterling M, Enblad P, Hesselager G, Ryttlefors M, Kumlien E, Lewén A, Marklund N, Nilsson P, Salci K, Ronne-Engström E (2007) Cerebral glutamine and glutamate levels in relation to compromised energy metabolism: a microdialysis study in subarachnoid hemorrhage patients. J Cereb Blood Flow Metab 27:1309–1317PubMedCrossRefGoogle Scholar
  39. 39.
    Shulman RG, Rothman DL, Hyder F (1999) Stimulated changes in localized cerebral energy consumption under anesthesia. Proc Natl Acad Sci U S A 96:3245–3250PubMedCrossRefGoogle Scholar
  40. 40.
    Simpson IA, Carruthers A, Vannucci SJ (2007) Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab 27:1766–1791PubMedCrossRefGoogle Scholar
  41. 41.
    Spanaki MV, Siegel H, Kopylev L, Fazilat S, Dean A, Liow K, Ben-Menachem E, Gaillard WD, Theodore WH (1999) The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism. Neurology 53:1518–1522PubMedGoogle Scholar
  42. 42.
    Ungerstedt U (1991) Microdialysis-principles and applications for studies in animals and man. J Intern Med 230:365–373PubMedGoogle Scholar
  43. 43.
    Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, Glenn TC, McArthur DL, Hovda DA (2005) Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab 25:763–774PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Peter J. Hutchinson
    • 1
    • 3
  • Mark T. O’Connell
    • 1
    • 3
  • Alex Seal
    • 1
  • Jurgens Nortje
    • 2
    • 3
  • Ivan Timofeev
    • 1
  • Pippa G. Al-Rawi
    • 1
  • Jonathan P. Coles
    • 2
    • 3
  • Timothy D. Fryer
    • 3
  • David K. Menon
    • 2
    • 3
  • John D. Pickard
    • 1
    • 3
  • Keri L. H. Carpenter
    • 1
    • 3
  1. 1.Division of Neurosurgery, Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK
  2. 2.Division of Anaesthesia, Department of MedicineUniversity of CambridgeCambridgeUK
  3. 3.Wolfson Brain Imaging Centre, Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK

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