Assessment of pathophysiology of stroke by positron emission tomography


In stroke patients, multitracer positron emission tomography (PET) permits the assessment of acute changes in regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen consumption (rCMRO2) and glucose metabolism (rCMRgl), which are the initial steps in the complex molecular and biochemical process leading to ischaemic cell damage. While early infarcts exhibit low flow and oxygen consumption, increased oxygen extraction fraction (OEF) due to preserved metabolism at reduced flow suggests viability of tissue. However, most initially “viable” tissue will be metabolically deranged and will become necrotic in the further course; only in a few instances do these tissue compartments recover to normal function. Increased glucose uptake at reduced oxygen supply induces non-oxidative glycolysis with noxious lactacidosis, whereas hyperperfusion beyond the metabolic demand is of controversial effect. In subacute or chronic states after ischaemia reduced flow can be compensated by increased blood volume; when perfusional reserve is exhausted, oxygen extraction increases. Such findings may guide therapeutic decisions and predict the severity of permanent deficits. Functional deactivation of tissue remote from the lesion is found regularly as a sign of damaged connecting pathways. Flow and metabolic studies during the performance of specific tasks help to detect alternative functional loops and may yield prognostic information. Repeat studies in the course of stroke are employed for the evaluation of therapeutic strategies targeted to improve reperfusion or to effect metabolic or biochemical alterations. In the future PET may gain additional clinical importance when patients are selected for elective treatment according to the prevailing pathophysiological pattern.

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  1. 1.

    Heiss W-D. Experimental evidence for ischemic thresholds and functional recovery. Stroke 1992;23:1668–1672.

    Google Scholar 

  2. 2.

    Benveniste H. The excitotoxin hypothesis in relation to cerebral ischemia. Cerebrovasc Brain Metab Rev 1991;3:213–245.

    Google Scholar 

  3. 3.

    Choi DW. Methods for antagonizing glutamate neurotoxicity. Cerebrovasc Brain Metab Rev 1990;2:105–147.

    Google Scholar 

  4. 4.

    Ginsberg MD. Local metabolic responses to cerebral ischemia. Cerebrovasc Brain Metab Rev 1990;2:58–93.

    Google Scholar 

  5. 5.

    Siesjö BK, Katsura K, Pahlmark K, Smith ML. The multiple causes of ischemic brain damage: a speculative synthesis. In: Krieglstein J, Oberpichler-Schwenk H, eds. Pharmacology of cerebral ischemia 1992. Stuttgart: Wissenschaftliche Verlagsgesellschaft; 1992:511–525.

    Google Scholar 

  6. 6.

    Baron JC, Rougemont D, Bousser MG, Lebrun-Grandié P, Iba-Zizen MT, Chiras J. Local CBF, oxygen extraction fraction (OEF), and CMRO2: prognostic value in recent supratentorial infarction in humans. J Cereb Blood Flow Metab 1983;3 Suppl 1:S1-S2.

    Google Scholar 

  7. 7.

    Powers WJ, Grubb RL Jr, Darriet D, Raichle ME. Cerebral blood flow and cerebral metabolic rate of oxygen requirements for cerebral function and viability in humans. J Cereb Blood Flow Metab 1985;5:600–608.

    Google Scholar 

  8. 8.

    Baron JC. Ischemic stroke studied by 150-labeled compounds: misery perfusion and luxury perfusion. In: Heiss W-D, Pawlik G, Herholz K, Wienhard K, eds. Clinical efficacy of positron emission tomography. Dordrecht: Martinus Nijhoff; 1987:15–23.

    Google Scholar 

  9. 9.

    Powers WJ, Grubb RL Jr, Raichle ME. Physiological responses to focal cerebral ischemia in humans. Ann Neurol 1984;16:546–552.

    Google Scholar 

  10. 10.

    Baron JC, Bousser MG, Comar D, Soussaline F, Castaigne P. Noninvasive tomographic study of cerebral blood flow and oxygen metabolism in vivo: potentials, limitations and clinical applications in cerebral ischemic disorders. Eur Neurol 1981;20:273–284.

    Google Scholar 

  11. 11.

    Kuhl DE, Phelps ME, Kowell AP, Metter EJ, Selin C, Winter J. Effects of stroke on local cerebral metabolism and perfusion: mapping by emission computed tomography of 18FDG and 13NH3. Ann Neurol 1980;8:47–60.

    Google Scholar 

  12. 12.

    Hakim AM, Evans AC, Berger L, et al. The effect of nimodipine on the evolution of human cerebral infarction studied by PET. J Cereb Blood Flow Metab 1989;9:523–534.

    Google Scholar 

  13. 13.

    Wise RJS, Bernardi S, Frackowiak RSJ, Legg NJ, Jones T. Serial observations on the pathophysiology of acute stroke. Brain 1983;106:197–222.

    Google Scholar 

  14. 14.

    Wise RJS, Rhodes CG, Gibbs JM, Hatazawa J, Palmer T, Frackowiak RSJ, Jones T. Disturbance of oxidative metabolism of glucose in recent human cerebral infarcts. Ann Neurol 1983;14:627–637.

    Google Scholar 

  15. 15.

    Berkelbach van der Sprenkel JWB, Luyten PR, Vanrijen PC, Tulleken CAF, Den Hollander JA. Cerebral lactate detected by regional proton magnetic-resonance spectroscopy in a patient with cerebral infarction. Stroke 1988;19:1556.

    Google Scholar 

  16. 16.

    Bruhn H, Frahm J, Gyngell ML, Merboldt KD, Hanicke W, Sauter R. Cerebral metabolism in man after acute stroke —new observations using localized proton NMR spectroscopy. Magn Reson Med 1989;9:126–131.

    Google Scholar 

  17. 17.

    Heiss W-D, Huber M, Fink G, Herholz K, Pietrzyk U, Wagner R, Wienhard K. Progressive derangement of periinfarct viable tissue in ischemic stroke. J Cereb Blood Flow Metab 1992;12:193–203.

    Google Scholar 

  18. 18.

    Baron JC, Frackowiak RSJ, Herholz K, Jones T, Lammertsma AA, Mazoyer B, Wienhard K. Use of PET methods for measurement of cerebral energy metabolism and hemodynamics in cerebrovascular disease. J Cereb Blood Flow Metab 1989;9:723–742.

    Google Scholar 

  19. 19.

    Pietrzyk U, Herholz K, Heiss W-D. Three-dimensional alignment of functional and morphological tomograms. J Comput Assist Tomogr 1990;14:51–59.

    Google Scholar 

  20. 20.

    Lassen NA. The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain. Lancet 1966;II:1113–1115.

    Google Scholar 

  21. 21.

    Ackerman RH, Correia JA, Alpert NM, Haley EC Jr, Buxton RB, Elmaleh DR, Taveras JM. PET studies of stroke. In: Reivich M, Alavi A, eds. Positron Emission tomography. New York: Liss;1985:249–262.

    Google Scholar 

  22. 22.

    Herholz K, Heiss W-D. Use of PET to evaluate acute stroke and other cerebrovascular disorders. In: Diksic M, Reba RC, eds. Radiopharmaceuticals and brain pathology studied with PET and SPECT Boca Raton: CRC Press; 1991:217–239.

    Google Scholar 

  23. 23.

    Fink GR, Herholz K, Pietrzyk U, Huber M, Heiss W-D. Periinfarct perfusion in human ischemia: its relation to tissue metabolism, morphology, and clinical outcome. J Stroke Cerebrovasc Dis 1993;3:123–131.

    Google Scholar 

  24. 24.

    Marchal G, Serrati C, Rioux P, et al. PET imaging of cerebral perfusion and oxygen consumption in acute ischaemic stroke: relation to outcome. Lancet 1993;341:925–927.

    Google Scholar 

  25. 25.

    Hakim AM, Hogan MJ. In vivo binding of nimodipine in the brain. The effect of focal cerebral ischemia. J Cereb Blood Flow Metab 1991;11:762–770.

    Google Scholar 

  26. 26.

    Shimada N, Graf R, Rosner G, Heiss W-D. Ischemia-induced accumulation of extracellular amino acids in cerebral cortex, white matter, and cerebrospinal fluid. J Neurochem 1993;60:66–71.

    Google Scholar 

  27. 27.

    Welsh FA, Moyer DJ, Harris VA. Regional expression of heat shock protein-70 mRNA and c-fos mRNA following focal ischemia in rat brain. J Cereb Blood Flow Metab 1992;12:204–212.

    Google Scholar 

  28. 28.

    Baron JC, Bousser MG, Comar D, Castaigne P. “Crossed cerebellar diaschisis” in human supratentorial brain infarction. Trans Am Neurol Assoc 1980;105:459–461.

    Google Scholar 

  29. 29.

    Pawlik G, Herholz K, Beil C, Wagner R, Wienhard K, Heiss W-D. Remote effects of focal lesions on cerebral blood flow and metabolism. In: Heiss W-D, ed. Functional mapping of the brain in vascular disorders. Berlin Heidelberg New York: Springer;1985:59–84.

    Google Scholar 

  30. 30.

    Mies G, Auer LM, Ebhardt G, Traupe H, Heiss W-D. Flow and neuronal density in tissue surrounding chronic infarction. Stroke 1983;14:22–27.

    Google Scholar 

  31. 31.

    Feeney DM, Baron JC. Diaschisis. Stroke 1986;17:817–830

    Google Scholar 

  32. 32.

    Metter EJ, Mazziotta JC, Itabashi HH, Mankovich NJ, Phelps ME, Kuhl DE. Comparison of glucose metabolism, x-ray CT, and post-mortem data in a patient with multiple cerebral infarcts. Neurology 1985;35:1695–1701.

    Google Scholar 

  33. 33.

    Kushner M, Alavi A, Reivich M, Dann R, Burke A, Robinson G. Contralateral cerebellar hypometabolism following cerebral insult: a positron emission tomographic study. Ann Neurol 1984;15:425–434.

    Google Scholar 

  34. 34.

    Martin WRW Raichle ME. Cerebellar blood flow and metabolism in cerebral hemisphere infarction. Ann Neurol 1983;14:168–176.

    Google Scholar 

  35. 35.

    Baron JC, D'Antona R, Pantano P, Serdaru M, Samson Y Bousser MG. Effects of thalamic stroke on energy metabolism of the cerebral cortex. A positron tomography study in man. Brain 1986;109:1243–1259.

    Google Scholar 

  36. 36.

    Szelies B, Herholz K, Pawlik G, Karbe H, Hebold I, Heiss WD. Widespread functional effects of discrete thalamic infarction. Arch Neurol 1991;48:178–182.

    Google Scholar 

  37. 37.

    Kushner M, Reivich M, Fieschi C, Silver F, Chawluk J, Rosen M, Greenberg J, Burke A, Alavi A. Metabolic and clinical correlates of acute ischemic infarction. Neurology 1987;37:1103–1110.

    Google Scholar 

  38. 38.

    Metter EJ, Kempler D, Jackson C, Hanson WR, Mazziotta JC, Phelps ME. Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia. Arch Neurol 1989;46:27–34.

    Google Scholar 

  39. 39.

    Karbe H, Herholz K, Szelies B, Pawlik G, Wienhard K, Heiss W-D. Regional metabolic correlates of Token test results in cortical and subcortical left hemispheric infarction. Neurology 1989;39:1083–1088.

    Google Scholar 

  40. 40.

    Metter EJ, Riege WH, Hanson WR, Jackson CA, Kempler D, van Lancker D. Subcortical structures in aphasia. An analysis based on (F-18) fluorodeoxyglucose, positron emission tomography, and computed tomography. Arch Neurol 1988;45:1229–1234.

    Google Scholar 

  41. 41.

    von Monakow C. Die Lokalisation im Großhirn and der Abbau der Funktion durch kortikale Herde. Wiesbaden: Bergmann, 1914.

    Google Scholar 

  42. 42.

    Reivich M. Crossed cerebellar diaschisis. Am J Neuroradiology 1992;13:62–64.

    Google Scholar 

  43. 43.

    Fisher CM. Ataxic hemiparesis: a pathologic study. Arch Neurol 1978;35:126–138.

    Google Scholar 

  44. 44.

    Gibbs JM, Wise RJS, Leenders KL, Jones T. Evaluation of cerebral perfusion reserve in patients with carotid-artery occlusion. Lancet 1984;1:310–314.

    Google Scholar 

  45. 45.

    Powers WJ, Press GW Grubb RL Jr, Gado M, Raichle ME. The effect of hemodynamically significant carotid artery disease on the hemodynamic status of the cerebral circulation. Ann Intern Med 1987;106:27–35.

    Google Scholar 

  46. 46.

    Itoh M, Hatazawa J, Pozzilli C, et al. Hemodynamics and oxygen metabolism in patients after reversible ischemic attack or minor ischemic stroke assessed with positron emission tomography. Neuroradiology 1987;29:416–421.

    Google Scholar 

  47. 47.

    Chollet F, DiPiero V, Wise RJS, Brooks DJ, Dolan RJ, Frackowiak RSJ. The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. Ann Neurol 1991;29:63–71.

    Google Scholar 

  48. 48.

    Weiller C, Chollet F, Friston KJ, Wise RJS, Frackowiak RSJ. Functional reorganization of the brain in recovery from striatocapsular infarction in man. Ann Neurol 1992;31:463–472.

    Google Scholar 

  49. 49.

    Heiss W-D, Kessler J, Karbe H, Fink GR, Pawlik G. Cerebral glucose metabolism as a predictor of recovery from aphasia in ischemic stroke. Arch Neurol 1993;50:958–964.

    Google Scholar 

  50. 50.

    Gibbs JM, Wise RJS, Thomas DJ, Mansfield AO, Ross Russel RW Cerebral hemodynamic changes after extracranial-intracranial bypass surgery. J Neurol Neurosurg Psychiatry 1987;50:140–150.

    CAS  PubMed  Google Scholar 

  51. 51.

    Powers WJ, Martin WRW, Herscovitch P, Raichle ME, Grubb RL Jr. Extracranial-intracranial bypass surgery: hemodynamic and metabolic effects. Neurology 1984;34:1168–1174.

    CAS  PubMed  Google Scholar 

  52. 52.

    Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 1982;239:57–69.

    Article  CAS  PubMed  Google Scholar 

  53. 53.

    Hakim AM. Hemodynamic and metabolic studies in stroke. Semin Neurol 1989;9:286–292.

    Google Scholar 

  54. 54.

    Baron JC, Bousser MG, Rey A, Guillard A, Comar D, Castaigne P. Reversal of focal “misery-perfusion syndrome” by extra-intracranial arterial bypass in hemodynamic cerebral ischemia. Stroke 1981;12:454–459.

    Google Scholar 

  55. 55.

    Yamauchi H, Fukuyama H, Fujimoto N, Nabatame H, Kimura J. Significance of low perfusion with increased oxygen extraction fraction in a case of internal carotid artery stenosis. Stroke 1992;23:431–432.

    Google Scholar 

  56. 56.

    Ogawa A, Kameyama M, Muraishi K, Yoshimoto T, Ito M, Sakurai Y. Cerebral blood flow and metabolism following superficial temporal artery to superior cerebellar artery bypass for vertebrobasilar occlusive disease. J Neurosurg 1992;76:955–960.

    Google Scholar 

  57. 57.

    Powers WJ, Grubb RL Jr, Raichle ME. Clinical results of extracranial-intracranial bypass surgery in patients with hemodynamic cerebrovascular disease. J Neurosurg 1989;70:61–67.

    Google Scholar 

  58. 58.

    EC/IC Bypass Study Group. Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. N Engl J Med 1985;313:1191–1200.

    PubMed  Google Scholar 

  59. 59.

    Gelmers HG, Gorter K, De Weerdt CJ, Wiezer HJA. A controlled trial of nimodipine in acute ischemic stroke. N Engl J Med 1988;318:203–207.

    Google Scholar 

  60. 60.

    Heiss W-D, Holthoff V, Pawlik G, Neveling M. Effect of nimodipine on regional cerebral glucose metabolism in patients with acute ischemic stroke as measured by positron emission tomography. J Cereb Blood Flow Metab 1990;10:127–132.

    Google Scholar 

  61. 61.

    The American Nimodipine Study Group. Clinical trial of nimodipine in acute ischemic stroke. Stroke 1992;23:3–8.

    Google Scholar 

  62. 62.

    Andiné P, Rudolphi KA, Fredholm BB, Hagberg H. Effect of propentofylline (HWA 285) on extracellular purines and excitatory amino acids in CAI of rat hippocampus during transient ischaemia. Br J Pharmacol 1990;100:814–818.

    Google Scholar 

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Correspondence to: W.-D. Heiss

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Heiss, WD., Herholz, K. Assessment of pathophysiology of stroke by positron emission tomography. Eur J Nucl Med 21, 455–465 (1994).

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Key words

  • Ischaemic stroke
  • Positron emission tomography
  • Cerebral blood flow
  • Cerebral oxygen consumption
  • Cerebral glucose metabolism
  • Oxygen extraction fraction