The Ischemic Penumbra: Overview, Definition, and Criteria

The Ischemic Penumbra

Volumn , Issue , 2007, Pages 7-20

  Donnan, Geoffrey A ^a   Baron, Jean Claude ^b   Davis, Stephen M ^c   Sharp, Frank R ^d  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c ROYAL MELBOURNE HOSPITAL   (Australia)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 34648861297     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.3109/9781420047356-6     Document Type: Chapter

References (88)

1. Albers GW, Caplan LR, Easton JD, et al. Transient ischemic attack-proposal for a new definition. N Engl J Med 2002; 347:1713-1716.
2. Symon L, Pasztor E, Branston NM. The distribution and density of reduced cerebral blood flow following acute middle cerebral artery occlusion: An experimental study by the technique of hydrogen clearance in baboons. Stroke 1974; 5:355-364.
3. Branston NM, Symon L, Crockard HA, Pasztor E. Relationship between the cortical evoked potential and local cortical blood flow following acute middle cerebral artery occlusion in the baboon. Exp Neurol 1974; 45:195-208.
4. Branston NM, Symon L. Proceedings: Depression of the cortical evoked potential with reduction of local blood flow in baboons. J Physiol 1974; 241:98P-99P.
5. Astrup J, Symon L, Branton N, Lassen N. Thresholds of cerebral ischemia. In: Schmiedek P, ed. Microsurgery for Stroke. Berlin: Springer, 1976:16-21.
6. Branston NM, Strong AJ, Symon L. Extracellular potassium activity, evoked potential and tissue blood flow. Relationships during progressive ischaemia in baboon cerebral cortex. J Neurol Sci 1977; 32:305-321.
7. Astrup J, Symon L, Branston NM, Lassen NA. Cortical evoked potential and extracellular k+ and h+ at critical levels of brain ischemia. Stroke 1977; 8:51-57.
8. Astrup J, Siesjo BK, Symon L. Thresholds in cerebral ischemia-the ischemic penumbra. Stroke 1981; 12:723-725.
9. The Concise Oxford Dictionary (p 1012). Oxford University Press, 1995.
10. Boysen G, Engell HC, Henriksen H. The effect of induced hypertension on internal carotid artery pressure and regional cerebral blood flow during temporary carotid clamping for endarterectomy. Neurology 1972; 22:1133-1144.
11. Sharbrough FW, Messick JM Jr, Sundt TM Jr. Correlation of continuous electroencephalograms with cerebral blood flow measurements during carotid endarterectomy. Stroke 1973; 4:674-683.
12. Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 1969; 164:719-721.
13. Simon RP, Swan JH, Griffiths T, Meldrum BS. Blockade of N-methyl-d-aspartate receptors may protect against ischemic damage in the brain. Science 1984; 226:850-852.
14. Jones TH, Morawetz RB, Crowell RM, et al. Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 1981; 54:773-782.
15. Garcia JH, Mitchem HL, Briggs L, et al. Transient focal ischemia in subhuman primates. Neuronal injury as a function of local cerebral blood flow. J Neuropathol Exp Neurol 1983; 42:44-60.
16. Olsen TS, Larsen B, Herning M, Skriver EB, Lassen NA. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke. Stroke 1983; 14:332-341.
17. Baron JC, Bousser M-G, Comar D, Kellershon C. Human hemispheric infarction studied by positron emission tomography and the 15O inhalation technique. In: Caillé JM, Salamon G, eds. Computerized Tomography. Berlin: Springer-Verlag, 1980:231-237.
18. 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. A case study with 15O Positron Emission Tomography. Stroke 1981; 12:454-459.
19. 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.
20. Lenzi GL, Frackowiak RS, Jones T. Cerebral oxygen metabolism and blood flow in human cerebral ischemic infarction. J Cereb Blood Flow Metab 1982; 2:321-335.
21. Wise RJ, Bernardi S, Frackowiak RS, Legg NJ, Jones T. Serial observations on the pathophysiology of acute stroke. The transition from ischaemia to infarction as reflected in regional oxygen extraction. Brain 1983; 106(Pt 1):197-222.
22. 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.
23. Hakim AM, Pokrupa RP, Villanueva J, et al. The effect of spontaneous reperfusion on metabolic function in early human cerebral infarcts. Ann Neurol 1987; 21:279-289.
24. Heiss WD, Huber M, Fink GR, et al. Progressive derangement of periinfarct viable tissue in ischemic stroke. J Cereb Blood Flow Metab 1992; 12:193-203.
25. Ackerman R, Lev M, Mackay B, et al. PET studies in acute stroke: Findings and relevance to therapy. J Cereb Blood Flow Metab 1989; 9:S359.
26. Baron JC, Rougemont D, Bousser M, Lebrun-Grandie P, Iba-Zizen M, Chiras J. The characteristics of the misery-perfusion syndrome in the cute phase of cerebral infarction. In: Lassen N, Symon L, Baron J, eds. Penombre et Ischemie Cerebrale. Paris: Libbey, 1986:25-30.
27. Moseley ME, Kucharczyk J, Mintorovitch J, et al. Diffusion-weighted MR imaging of acute stroke:correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats. AJNR Am J Neuroradiol 1990; 11(13):423-429.
28. Warach S, Gaa J, Siewert B, Wielopolski P, Edelman R. Acute human stroke studied by whole brain echo planar diffusion-weighted magnetic resonance imaging. Ann Neurol 1995; 37:231-241.
29. 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.
30. Marchal G, Rioux P, Serrati C, et al. Value of acute-stage positron emission tomography in predicting neurological outcome after ischemic stroke: Further assessment. Stroke 1995; 26:524-525.
31. Marchal G, Furlan M, Beaudouin V, et al. Early spontaneous hyperperfusion after stroke. A marker of favourable tissue outcome? Brain 1996; 119(Pt 2):409-419.
32. Marchal G, Furlan M, Beaudouin V, et al. Early spontaneous hyperperfusion after stroke: A marker of favourable tissue outcome? Brain 1996; 119:409-419.
33. Furlan M, Marchal G, Viader F, Derlon JM, Baron JC. Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra. Ann Neurol 1996; 40:216-226.
34. Baron JC, von Kummer R, del Zoppo GJ. Treatment of acute ischemic stroke. Challenging the concept of a rigid and universal time window. Stroke 1995; 26:2219-2221.
35. Heiss WD, Kracht LW, Thiel A, Grond M, Pawlik G. Penumbral probability thresholds of cortical flumazenil binding and blood flow predicting tissue outcome in patients with cerebral ischaemia. Brain 2001; 124:20-29.
36. Heiss WD, Graf R, Fujita T, et al. Early detection of irreversibly damaged ischemic tissue by flumazenil positron emission tomography in cats. Stroke 1997; 28:2045-2051; discussion 2051-2042.
37. Sette G, Baron JC, Young AR, et al. In vivo mapping of brain benzodiazepine receptor changes by positron emission tomography after focal ischemia in the anesthetized baboon. Stroke 1993; 24:2046-2057; discussion 2057-2048.
38. Lassen NA, Vorstrup S. Ischemic penumbra results in incomplete infarction: Is the sleeping beauty dead? [letter]. Stroke 1984; 15:755-758.
39. Lassen N, Olsen T, Hojgaard K, Skriver E. Incomplete infarction: a CT-negative irreversible ischaemic brain lesion. J Cereb Blood Flow Metab 1983; 3:602-603.
40. Baron JC. Mapping the ischaemic penumbra with PET: a new approach. Brain 2001; 124:2-4.
41. Markus R, Donnan GA, Kazui S, et al. Statistical parametric mapping of hypoxic tissue identified by 18F-fluoromisonidazole and positron emission tomography following acute ischemic stroke. Neuroimage 2002; 16:425-433.
42. Markus R, Reutens DC, Kazui S, et al. Topography and temporal evolution of hypoxic viable tissue identified by 18F-fluoromisonidazole positron emission tomography in humans after ischemic stroke. Stroke 2003; 34:2646-2652.
43. Markus R, Reutens DC, Kazui S, et al. Hypoxic tissue in ischaemic stroke: Persistence and clinical consequences of spontaneous survival. Brain 2004; 127:1427-1436.
44. Markus R, Donnan G, Kazui S, Read S, Reutens D. Penumbral topography in human stroke:Methodology and validation of the ‘penumbragram’. Neuroimage 2004; 21:1252-1259.
45. Donnan GA, Davis SM. Neuroimaging, the ischaemic penumbra, and selection of patients for acute stroke therapy. Lancet Neurol 2002; 1:417-425.
46. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 1999; 22:391-397.
47. Sharp FR, Lu A, Tang Y, Millhorn DE. Multiple molecular penumbras after focal cerebral ischemia. J Cereb Blood Flow Metab 2000; 20:1011-1032.
48. Wintermark M, Reichhart M, Cuisenaire O, et al. Comparison of admission perfusion computed tomography and qualitative diffusion-and perfusion-weighted magnetic resonance imaging in acute stroke patients. Stroke 2002; 33:2025-2031.
49. Wintermark M, Reichhart M, Thiran JP, et al. Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients. Ann Neurol 2002; 51:417-432.
50. van Zijl PC, Eleff SM, Ulatowski JA, et al. Quantitative assessment of blood flow, blood volume and blood oxygenation effects in functional magnetic resonance imaging. Nat Med 1998; 4:159-167.
51. Edelman RR, Siewert B, Darby DG, et al. Qualitative mapping of cerebral blood flow and functional localization with echo-planar mr imaging and signal targeting with alternating radio frequency. Radiology 1994; 192:513-520.
52. Williams DS, Detre JA, Leigh JS, Koretsky AP. Magnetic resonance imaging of perfusion using spin inversion of arterial water. Proc Natl Acad Sci U.S.A. 1992; 89:212-216.
53. Heiss WD, Graf R. The ischemic penumbra. Curr Opin Neurol 1994; 7:11-19.
54. Kinouchi H, Sharp FR, Koistinaho J, Hicks K, Kamii H, Chan PH. Induction of heat shock hsp70 mrna and hsp70 kda protein in neurons in the ‘penumbra’ following focal cerebral ischemia in the rat. Brain Res 1993; 619:334-338.
55. Hossmann KA. Viability thresholds and the penumbra of focal ischemia. Ann Neurol 1994; 36:557-565.
56. Hakim AM. The cerebral ischemic penumbra. Can J Neurol Sci 1987; 14:557-559.
57. Baron JC. Mapping the ischaemic penumbra with PET: Implications for acute stroke treatment. Cerebrovasc Dis 1999; 9:193-201.
58. Donnan G, Davis S. Errata -“definition of ischaemic penumbra” panel missing from original publication (lancet neurology 1:417-425, 2002.). Lancet Neurol 2003; 2:594.
59. Lythgoe MF, Williams SR, Busza AL, et al. The relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow and hypoxia in an animal stroke model. Magn Reson Med 1999; 41:706-714.
60. Lythgoe MF, Williams SR, Wiebe LI, McEwan AJ, Gordon I. Autoradiographic imaging of cerebral ischaemia using a combination of blood flow and hypoxic markers in an animal model. Eur J Nucl Med 1997; 24:16-20.
61. Saita K, Chen M, Spratt NJ, et al. Imaging the ischemic penumbra with 18f-fluoromisonidazole in a rat model of ischemic stroke. Stroke 2004; 35:975-980.
62. Hata R, Maeda K, Hermann D, Mies G, Hossmann KA. Evolution of brain infarction after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab 2000; 20:937-946.
63. Hata R, Maeda K, Hermann D, Mies G, Hossmann KA. Dynamics of regional brain metabolism and gene expression after middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 2000; 20:306-315.
64. Lammertsma A, Hoffman J, Frackowiak R, Huang S, Weinberg I, Phelps M. A new dynamic technique to measure regional cerebral blood flow. J Cereb Blood Flow Metab 1987; 7:S577.
65. Dey HM, Seibyl JP, Stubbs JB, et al. Human biodistribution and dosimetry of the spect benzodiazepine receptor radioligand iodine-123-iomazenil. J Nucl Med 1994; 35:399-404.
66. Donnan G, Wright P, Markus R, Phan TG, Reutens D. The ischaemic penumbra: The evolution of a concept. In: Davis S, Fisher M, Warach S, eds. Magnetic resonance imaging in stroke. Cambridge:Cambridge University Press, 2003:191-206.
67. Ho PW, Reutens DC, Phan TG, et al. Is white matter involved in patients entered into typical trials of neuroprotection? Stroke 2005; 36(12):2742-2744.
68. Heiss WD, Grond M, Thiel A, et al. Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke. Stroke 1998; 29:454-461.
69. JM UK-I, Trivedi RA, Graves MJ, et al. Utility of an ultrafast magnetic resonance imaging protocol in recent and semi-recent strokes. J Neurol Neurosurg Psychiatry 2005; 76:1002-1005.
70. Kidwell CS, Saver JL, Mattiello J, et al. Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging. Ann Neurol 2000; 47:462-469.
71. Kinouchi H, Sharp FR, Hill MP, Koistinaho J, Sagar SM, Chan PH. Induction of 70-KDA heat shock protein and hsp70 mrna following transient focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 1993; 13:105-115.
72. Sharp JW, Sagar SM, Hisanaga K, Jasper P, Sharp FR. The nmda receptor mediates cortical induction of fos and fos-related antigens following cortical injury. Exp Neurol 1990; 109:323-332.
73. Lassen NA, Henriksen L, Paulson O. Regional cerebral blood flow in stroke by 133xenon inhalation and emission tomography. Stroke 1981; 12:284-288.
74. Olesen J, Friberg L, Olsen TS, et al. Timing and topography of cerebral blood flow, aura, and headache during migraine attacks. Ann Neurol 1990; 28:791-798.
75. Welch KM, Windham J, Knight RA, et al. A model to predict the histopathology of human stroke using diffusion and T2-weighted magnetic resonance imaging. Stroke 1995; 26:1983-1989.
76. Knight RA, Dereski MO, Helpern JA, Ordidge RJ, Chopp M. Magnetic resonance imaging assessment of evolving focal cerebral ischemia. Comparison with histopathology in rats. Stroke 1994; 25:1252-1261; discussion 1261-1252.
77. Helpern JA, Dereski MO, Knight RA, Ordidge RJ, Chopp M, Qing ZX. Histopathological correlations of nuclear magnetic resonance imaging parameters in experimental cerebral ischemia. Magn Reson Imaging 1993; 11:241-246.
78. Dereski MO, Chopp M, Knight RA, Rodolosi LC, Garcia JH. The heterogeneous temporal evolution of focal ischemic neuronal damage in the rat. Acta Neuropathol (Berl) 1993; 85:327-333.
79. Guadagno JV, Warburton EA, Aigbirhio FI, et al. Does the acute diffusion-weighted imaging lesion represent penumbra as well as core? A combined quantitative PET/MRI voxel-based study. J Cereb Blood Flow Metab 2004; 24:1249-1254.
80. Kidwell CS, Saver JL, Starkman S, et al. Late secondary ischemic injury in patients receiving intraarterial thrombolysis. Ann Neurol 2002; 52:698-703.
81. Hoehn-Berlage M, Norris DG, Kohno K, Mies G, Leibfritz D, Hossmann KA. Evolution of regional changes in apparent diffusion coefficient during focal ischemia of rat brain: The relationship of quantitative diffusion NMR imaging to reduction in cerebral blood flow and metabolic disturbances. J Cereb Blood Flow Metab 1995; 15:1002-1011.
82. Schellinger PD, Fiebach JB, Jansen O, et al. Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia. Ann Neurol 2001; 49:460-469.
83. Rother J, Schellinger PD, Gass A, et al. Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke 6 hours. Stroke 2002; 33:2438-2445.
84. Ribo M, Molina CA, Rovira A, et al. Safety and efficacy of intravenous tissue plasminogen activator stroke treatment in the 3-to 6-hour window using multimodal transcranial doppler/MRI selection protocol. Stroke 2005; 36:602-606.
85. Baron JC, Rougemont D, Soussaline F, et al. Local interrelationships of cerebral oxygen consumption and glucose utilization in normal subjects and in ischemic stroke patients: A positron tomography study. J Cereb Blood Flow Metab 1984; 4:140-149.
86. Baird AE, Warach S. Magnetic resonance imaging of acute stroke. J Cereb Blood Flow Metab 1998; 18:583-609.
87. Read SJ, Hirano T, Abbott DF, et al. Identifying hypoxic tissue after acute ischemic stroke using PET and 18f-fluoromisonidazole. Neurology 1998; 51:1617-1621.
88. Hata R, Mies G, Wiessner C, et al. A reproducible model of middle cerebral artery occlusion in mice:Hemodynamic, biochemical, and magnetic resonance imaging. J Cereb Blood Flow Metab 1998; 18:367-375.