Neurocritical Care

, 9:319

Early Derangements in Oxygen and Glucose Metabolism Following Head Injury: The Ischemic Penumbra and Pathophysiological Heterogeneity

  • M. Giulia Abate
  • Monica Trivedi
  • Tim D. Fryer
  • Piotr Smielewski
  • Doris A. Chatfield
  • Guy B. Williams
  • Franklin Aigbirhio
  • T. Adrian Carpenter
  • John D. Pickard
  • David K. Menon
  • Jonathan P. Coles
Original Article

Abstract

Introduction

Conclusive evidence of cerebral ischemia following head injury has been elusive. We aimed to use 15O and 18Fluorodeoxyglucose positron emission tomography (PET) to investigate pathophysiological derangements following head injury.

Results

Eight patients underwent PET within 24 h of injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), oxygen extraction fraction (OEF), and cerebral glucose metabolism (CMRglc). Physiological regions of interest (ROI) were generated for each subject using a range of OEF values from very low (<10), low (10–30), normal range (30–50), high (50–70), and critically high (≥70%). We applied these ROIs to each subject to generate data that would examine the balance between blood flow and metabolism across the injured brain independent of structural injury.

Discussion

Compared to the normal range, brain regions with higher OEF demonstrate a progressive CBF reduction (P < 0.01), CMRO2 increase (P < 0.05), and no change in CMRglc, while regions with lower OEF are associated with reductions in CBF, CMRO2, and CMRglc (P < 0.01). Although all subjects demonstrate a decrease in CBF with increases in OEF > 70%, CMRO2 and CMRglc were generally unchanged. One subject demonstrated a reduction in CBF and small fall in CMRO2 within the high OEF region (>70%), combined with a progressive increase in CMRglc.

Conclusions

The low CBF and maintained CMRO2 in the high OEF ROIs is consistent with classical cerebral ischemia and the presence of an ‘ischemic penumbra’ following early head injury, while the metabolic heterogeneity that we observed suggests significant pathophysiological complexity. Other mechanisms of energy failure are clearly important and further study is required to delineate the processes involved.

Keywords

Head injury Oxygen metabolism Glucose metabolism Ischemia Positron emission tomography Traumatic penumbra 

References

  1. 1.
    Coles JP, Fryer TD, Smielewski P, et al. Incidence and mechanisms of cerebral ischemia in early clinical head injury. J Cereb Blood Flow Metab. 2004;24:202–11.PubMedCrossRefGoogle Scholar
  2. 2.
    Coles JP, Fryer TD, Smielewski P, et al. Defining ischemic burden after traumatic brain injury using 15O PET imaging of cerebral physiology. J Cereb Blood Flow Metab. 2004;24:191–201.PubMedCrossRefGoogle Scholar
  3. 3.
    Marshall LF, Marshall SB, Klauber MR, et al. A new classification of head injury based on computerized tomography. J Neurosurg. 1991;75:S14–S27.Google Scholar
  4. 4.
    Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2:81–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Jennett B, Bond M. Assessment of outcome after severe brain damage. A practical scale. Lancet. 1975;1:480–4.PubMedCrossRefGoogle Scholar
  6. 6.
    Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following head injury: effect on ischemic burden and cerebral oxidative metabolism. Crit Care Med. 2007;35:568–78.PubMedCrossRefGoogle Scholar
  7. 7.
    Kinahan PE, Rogers JG. Analytic 3D image reconstruction using all detected events. IEEE Trans Nucl Sci. 1989;36:964–8.Google Scholar
  8. 8.
    Frackowiak RS, Lenzi GL, Jones T, et al. Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values. J Comput Assist Tomogr. 1980;4:727–36.PubMedCrossRefGoogle Scholar
  9. 9.
    Lammertsma AA, Baron JC, Jones T. Correction for intravascular activity in the oxygen-15 steady-state technique is independent of the regional hematocrit. J Cereb Blood Flow Metab. 1987;7:372–4.PubMedGoogle Scholar
  10. 10.
    Herscovitch P, Raichle ME. What is the correct value for the brain-blood partition coefficient for water? J Cereb Blood Flow Metab. 1985;5:65–9.PubMedGoogle Scholar
  11. 11.
    Phelps ME, Huang SC, Hoffman EJ, et al. Validation of tomographic measurement of cerebral blood volume with C-11-labeled carboxyhemoglobin. J Nucl Med. 1979;20:328–34.PubMedGoogle Scholar
  12. 12.
    Huang SC, Phelps ME, Hoffman EJ, et al. Noninvasive determination of local cerebral metabolic rate of glucose in man. Am J Physiol. 1980;238:E69–82.PubMedGoogle Scholar
  13. 13.
    Smielewski P, Coles JP, Fryer TD, et al. Integrated image analysis solutions for pet datasets in damaged brain. J Clin Monit Comput. 2002;17:427–40.PubMedCrossRefGoogle Scholar
  14. 14.
    Miller JD. Head injury and brain ischaemia – implications for therapy. Br J Anaesth. 1985;57:120–30.PubMedCrossRefGoogle Scholar
  15. 15.
    Becker DP, Miller JD, Ward JD, et al. The outcome from severe head injury with early diagnosis and intensive management. J Neurosurg 1977;47:491–502.PubMedGoogle Scholar
  16. 16.
    Rosner MJ, Rosner SD, Johnson AH. Cerebral perfusion pressure: management protocol and clinical results. J Neurosurg. 1995;83:949–62.PubMedGoogle Scholar
  17. 17.
    Patel HC, Menon DK, Tebbs S, et al. Specialist neurocritical care and outcome from head injury. Intensive Care Med. 2002;28:547–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Yundt KD, Diringer MN. The use of hyperventilation and its impact on cerebral ischemia in the treatment of traumatic brain injury. Crit Care Clin. 1997;13:163–84.PubMedCrossRefGoogle Scholar
  19. 19.
    Coles JP, Fryer TD, Bradley PG, et al. Intersubject variability and reproducibility of (15)O PET studies. J Cereb Blood Flow Metab. 2006;26:48–57.Google Scholar
  20. 20.
    McLaughlin MR, Marion DW. Cerebral blood flow and vasoresponsivity within and around cerebral contusions. J Neurosurg. 1996;85:871–6.PubMedGoogle Scholar
  21. 21.
    Diringer MN, Yundt K, Videen TO, et al. No reduction in cerebral metabolism as a result of early moderate hyperventilation following severe traumatic brain injury. J Neurosurg. 2000;92:7–13.PubMedCrossRefGoogle Scholar
  22. 22.
    Diringer MN, Videen TO, Yundt K, et al. Regional cerebrovascular and metabolic effects of hyperventilation after severe traumatic brain injury. J Neurosurg. 2002;96:103–8.PubMedGoogle Scholar
  23. 23.
    Vespa P, Bergsneider M, Hattori N, et al. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab. 2005;25:763–74.Google Scholar
  24. 24.
    Stein SC, Graham DI, Chen XH, et al. Association between intravascular microthrombosis and cerebral ischemia in traumatic brain injury. Neurosurgery. 2004;54:687–91; discussion 691.PubMedCrossRefGoogle Scholar
  25. 25.
    Rodriguez-Baeza A, Reina-de la Torre F, Poca A, et al. Morphological features in human cortical brain microvessels after head injury: a three-dimensional and immunocytochemical study. Anat Rec A Discov Mol Cell Evol Biol. 2003;273:583–93.PubMedCrossRefGoogle Scholar
  26. 26.
    Schwarzmaier S, Kim SW, Trabold R, et al. Microcirculatory alterations following experimental TBI. J Neurotrauma. 2006;23:P4.7, p. 769.Google Scholar
  27. 27.
    Menon DK, Coles JP, Gupta AK, et al. Diffusion limited oxygen delivery following head injury. Crit Care Med. 2004;32:1384–90.PubMedCrossRefGoogle Scholar
  28. 28.
    Johnston AJ, Steiner LA, Coles JP, et al. Effect of cerebral perfusion pressure augmentation on regional oxygenation and metabolism after head injury. Crit Care Med. 2005;33:189–95; discussion 255–7.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • M. Giulia Abate
    • 1
    • 2
    • 3
  • Monica Trivedi
    • 1
    • 2
  • Tim D. Fryer
    • 2
  • Piotr Smielewski
    • 4
  • Doris A. Chatfield
    • 1
    • 2
  • Guy B. Williams
    • 2
  • Franklin Aigbirhio
    • 2
  • T. Adrian Carpenter
    • 2
  • John D. Pickard
    • 2
    • 4
  • David K. Menon
    • 1
    • 2
  • Jonathan P. Coles
    • 1
    • 2
  1. 1.The Division of Anaesthesia, Addenbrooke’s HospitalUniversity of CambridgeCambridgeUK
  2. 2.The Wolfson Brain Imaging Centre, Addenbrooke’s HospitalUniversity of CambridgeCambridgeUK
  3. 3.College of Medicine, HS GerardoThe University of Milano – BicoccaMonzaItaly
  4. 4.Department of Neurosurgery, Addenbrooke’s HospitalUniversity of CambridgeCambridgeUK

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