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Stroke: imaging and differential diagnosis

  • J. C. Baron
Conference paper

Summary

Structural and vascular imaging helps to differentiate haemorrhagic from acute ischemic stroke (AIS) and rule out non-stroke causes, as well as identify specific subtypes of stroke such as carotid dissection and venous thrombosis. However, it is negative in most AIS patients within 3–6hrs of onset and thus does not allow efficient patient classification for management purposes. Physiologic neuroimaging with PET, SPECT and combined diffusion- and perfusion-weighted MR gives access to tissue perfusion and cell function/homeostasis. It has near 100% sensitivity in AIS, even in small cortical or brainstem strokes. In middle-cerebral artery (MCA) stroke, physiologic imaging also allows pathophysiological differentiation into four tissue subtypes: i) already irreversibly damaged (“core”); ii) severely hypoperfused (“penumbra”), which represents the main target for therapy; iii) mildly hypoperfused (“oligaemia”), not at risk of infarction unless secondary complications arise; and iv) reperfused/hyperperfused. PET studies have evidenced the penumbra in man, shown its largely cortical topography, documented its anticipated impact on both acute-stage neurological deficit and recovery therefrom, and shown its persistence up to 16hrs after stroke onset in some patients. However, some patients acutely exhibit extensive irreversible damage, which places them at considerable risk of malignant MCA infarction, and others early spontaneous reperfusion, which is almost invariably associated with rapid and complete recovery. Thrombolytics and/or neuroprotective agents would therefore be expected to benefit, and hence should ideally be reserved to, only those patients in whom a substantial penumbra is documented by physiologic neuroimaging, even perhaps beyond the 3 to 6hrs rule. In addition, excluding from thrombolytic therapy those patients with substantial necrotic core should avoid many instances of symptomatic haemorrhagic transformations. Finally, patients with extensive core might benefit from early decompressive surgery, and those with early extensive reperfusion from anti-inflammatory agents. Overall, therefore, the pathophysiologic heterogeneity underlying AIS may account for both the complications from thrombolysis and the limited success of clinical trials of neuroprotective agents, despite apparent benefit in the laboratory. Pathophysiological diagnosis as afforded by neuroimaging should now be incorporated in the design of clinical trials as well as in the routine management of stroke.

Keywords

Apparent Diffusion Coefficient Acute Stroke Acute Ischemic Stroke Cerebral Blood Volume Mean Transit Time 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ackerman RH, Correia JA, Alpert NM, Baron JC, Gouliamos A, Grotta JC, Brownell GL, Taveras JM (1981) Positron imaging in ischemic stroke disease using compounds labeled with oxygen-15. Arch Neurol 38: 537–543PubMedCrossRefGoogle Scholar
  2. Ahmed N, Nasman P, Wahlgren NG (2000) Effects of intravenous nimodipine on blood pressure and outcome after stroke. Stroke 31:1250–1255PubMedCrossRefGoogle Scholar
  3. Albers GW (1999) Expanding the window for thrombolytic therapy in acute stroke. The potential role of acute MRI for patient selection. Stroke 30: 2230–2237PubMedCrossRefGoogle Scholar
  4. Astrup J, Siesjo BK, Symon L (1981) Thresholds in cerebral ischemia: the ischemic penumbra. Stroke 12: 723–725PubMedCrossRefGoogle Scholar
  5. Baird AE, Warach S (1998) Magnetic resonance imaging in acute stroke. J Cereb Blood Flow Metabol 18: 583–609Google Scholar
  6. Baird AE, Donnan GA, Austin MC, MacKay WJ (1995) Early reperfusion in the “spectacular shrinking deficit” demonstrated by single-photon emission computed tomography. Neurology 45: 1335–1339PubMedCrossRefGoogle Scholar
  7. Baird AE, Benfield A, Schlaug G, Siewert B, Lövblad KO, Edelman RR, Warach S (1997) Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging. Ann Neurol 41: 581–589PubMedCrossRefGoogle Scholar
  8. Baird AE, Lövblad KO, Dashe JF, Connor A, Burzynski C, Schlaug G, Straroselskaya, Edelman R, Warach S (2000) Clinical correlations of diffusion and perfusion lesion volumes in acute ischemic stroke. Cerebrovasc Dis 10: 441–448PubMedCrossRefGoogle Scholar
  9. Barber PA, Davis SM, Darby DG, Desmond PM, Gerraty RP, Yang Q, Donnan GA, Tress BM (1999) Absent middle cerebral artery flow predicts the presence and evolution of the ischemic penumbra. Neurology 52: 1125–1132PubMedCrossRefGoogle Scholar
  10. Baron JC (1999) Mapping the ischaemic penumbra with PET: implications for acute stroke treatment. Cerebrovasc Dis 9:193–201PubMedCrossRefGoogle Scholar
  11. Baron JC (2001) Mapping the ischaemic penumbra with PET: a new approach. Brain 124: 2–4PubMedCrossRefGoogle Scholar
  12. Baron JC, Marchal G (2000) Functional imaging in vascular disorders. In: Mazziotta et al (eds) Brain mapping: the disorders. Academic Press, San Diego, pp 299–316CrossRefGoogle Scholar
  13. Baron JC, Bousser MG, Comar D, et al (1981) Non invasive tomographic study of cerebral blood flow and oxygen metabolism in vivo: potentials, limitations and clinical applications in cerebral ischemic disorders. Eur Neurol 20: 273–284PubMedCrossRefGoogle Scholar
  14. Baron JC, Bousser MG, Rey A, et al (1981) Reversal of focal “misery-perfusion syndrome” by extra-intracranial arterial bypass in hemodynamic cerebral ischemia: a case study with 1 50 positron tomography. Stroke 12: 454–459PubMedCrossRefGoogle Scholar
  15. Baron JC, Frackowiak RSJ, Herholz K, et al (1989) Use of positron emission tomography in the investigation of cerebral hemodynamics and energy metabolism in cerebrovascular disease. J Cereb Blood Flow Metab 9: 723–742PubMedCrossRefGoogle Scholar
  16. Baron JC, von Kummer R, Del Zoppo, GJ (1995) Treatment of acute ischemic stroke: challenging the concept of a rigid and universal time window. Stroke 26: 2219–2221PubMedCrossRefGoogle Scholar
  17. Beaulieu C, et al (1999) Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: evolution of lesion volume and correlation with clinical outcome. Ann Neurol 46: 568–578PubMedCrossRefGoogle Scholar
  18. Berrouschot J, Barthel H, von Kummer R, et al (1998) 99m technetium-ethyl-cysteinatedimer single-photon emission CT can predict fatal ischemic brain edema. Stroke 12:2556–2562CrossRefGoogle Scholar
  19. Berrouschot J, Barthel H, Hesse S, et al (1998) Differentiation between transient ischemic attack and ischemic stroke within the first six hours after onset of symtoms by using 99mTc-ECD-SPECT. J Cereb Blood Flow Metab 18: 921–929PubMedCrossRefGoogle Scholar
  20. Calamante F, et al (1999) Measuring cerebral blood flow using magnetic resonance imaging techniques. J Cereb Blood Flow Metab 19: 701–735PubMedCrossRefGoogle Scholar
  21. Firlik AD, Rubin G, Yonas H, Wechsler LR (1998a) Relation between cerebral blood flow and neurologic deficit resolution in acute ischemic stroke. Neurology 51:177–182PubMedCrossRefGoogle Scholar
  22. Firlik AD, Yonas H, Kaufmann AM, Wechsler LR, Jungreis CA, Fukui MB, Williams RL (1998b) Relationship between cerebral blood flow and the development of swelling and life-threatening herniation in acute ischemic stroke. J Neurosurg 89: 243–249PubMedCrossRefGoogle Scholar
  23. Fisher M, Albers GW (1999) Application of diffusion-perfusion MRI in acute ischemic stroke. Neurology 52: 1750–1756PubMedCrossRefGoogle Scholar
  24. Furlan M, Marchal G, Viader F, et al (1996) Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra. Ann Neurol 40: 216–226PubMedCrossRefGoogle Scholar
  25. Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F (1999) Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. JAMA 282:2003–2011PubMedCrossRefGoogle Scholar
  26. Gillard JH, Barker PB, Van Zijl PC, Bryan RN, Oppenheimer SM (1996) Proton MR spectroscopy in acute middle cerebral artery stroke. Am J Neuroradiol 17: 873–886PubMedGoogle Scholar
  27. Ginsberg MD, Bogousslavsky J (eds) (1998) Cerebrovascular diseases. Blackwell Science, New York, 2067 ppGoogle Scholar
  28. Giubilei F, Lenzi GL, Di Piero V, et al (1990) Predictive value of brain perfusion singlephoton emission computed tomography in acute ischemic stroke. Stroke 21: 895–900PubMedCrossRefGoogle Scholar
  29. Grandin, Duprez TP, Smith AM, Mataigne F, Peeters A, Oppenheim C, Cosnard G (2001) Usefulness of magnetic resonance-derived quantitative measurements of cerebral blood flow and volume in prediction of infarct growth in hyperacute stroke. Stroke 32: 1147–1153PubMedCrossRefGoogle Scholar
  30. Heiss WD, Huber M, Fink GR, Herholz K, Pietryk U, Wagner R, Wienhard K (1992) Progressive derangement of periinfarct viable tissue in ischemic stroke. J Cereb Blood Flow Metab 12: 193–203PubMedCrossRefGoogle Scholar
  31. Heiss WD, Graf R, Lottgen J, Ohta K, Fujita T, Wagner R, Grond M, Wienhard K (1997) Repeat positron emission tomographic studies in transient middle cerebral artery occlusion in cats: residual perfusion and efficacy of postischemic reperfusion. J Cereb Blood Flow Metab 17: 388–400PubMedCrossRefGoogle Scholar
  32. Heiss WD, Grond M, Thiel A, Von Stockhausen HM, Rudolf J, Ghaemi M, Lottgen J, Stenzel C, Pawlik G (1998a) Tissue at risk of infarction rescued by early reperfusion: a positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke. J Cereb Blood Flow Metab 18: 1298–1307PubMedCrossRefGoogle Scholar
  33. Heiss WD, Grond M, Thiel A, Ghaemi M, Sobesky J, Rudolf J, Bauer B, Wienhard K (1998b) Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke. Stroke 29: 454–461PubMedCrossRefGoogle Scholar
  34. Heiss W-D, Thiel A, Grond M, et al (1999) Which targets are relevant for therapy of acute ischemic stroke? Stroke 30: 1486–1489PubMedCrossRefGoogle Scholar
  35. Heiss WD, Kracht L, Grond M, Rudolf J, Bauer B, Wienhard K, et al (2000) Early 11Cflumazenil/ H20 positron emission tomography predicts irreversible ischemic cortical damage in stroke patients receiving acute thrombolytic therapy. Stroke 31: 366–369PubMedCrossRefGoogle Scholar
  36. Heiss WD, Kracht LW, Thiel A, Grond M, Pawlik G (2001) Penumbral probability thresholds of cortical flumazenil binding and blood flow predicting tissue outcome in patients with cerebral ischaemia. Brain 124: 20–29PubMedCrossRefGoogle Scholar
  37. Heiss W-D, Forsting M, Diener H-C (2001) Imaging in cerebrovascular diseases. Curr Opin Neurol 14: 67–75PubMedCrossRefGoogle Scholar
  38. Jones TH, Morawetz RE, Crowell RM, et al (1981) Thresholds of focal cerebral ischaemia in awake monkeys. J Neurosurg 54: 773–782PubMedCrossRefGoogle Scholar
  39. Kamada K, Saguer M, Moller M, Wicklow K, Katenhauser M, Kober H, Vieth J (1997) Functional and metabolic analysis of cerebral ischemia using magnetoencephalography and proton magnetic resonance spectroscopy. Ann Neurol 42: 554–563PubMedCrossRefGoogle Scholar
  40. Kidwell C, Saver J, Mattiello J, et al (2000) Thrombolytic reversal of acute human cerebral ischaemic injury shown by diffussion/perfusion magnetic resonance imaging. Ann Neurol 47: 462–469PubMedCrossRefGoogle Scholar
  41. Lassen NA (1966) The luxury perfusion syndrome and its possible relation to acute metabolic acidosis localised within the brain. Lancet 11: 1113–1115CrossRefGoogle Scholar
  42. Mahagne MH, Darcourt J, Migneco O, Fournier JP, Ducoeur S, Thiercelin D, Bertrand F, Bussiere F, Chatel M, Baron JC (2000) Early 99mTc-ECD brain SPECT in the acute phase of stroke: a strong predictor of neurological recovery. Cerebrovasc Dis 10: 364–373PubMedCrossRefGoogle Scholar
  43. Marchal G, Serrati C, Rioux P, et al (1993) PET imaging of cerebral perfusion and oxygen consumption in acute ischaemic stroke: relation to outcome. Lancet 341: 925–927PubMedCrossRefGoogle Scholar
  44. Marchal G, Rioux P, Serrati C, et al (1995) Value of acute-stage PET in predicting neurological outcome after ischemic stroke: further assessment. Stroke 26: 524–525PubMedGoogle Scholar
  45. Marchal G, Beaudouin V, Rioux P, et al (1996) Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke: a correlative PET-CT study with voxel-based data analysis. Stroke 27: 599–606PubMedCrossRefGoogle Scholar
  46. Marchal G, Furlan M, Beaudouin V, et al (1996) Early spontaneous hyperperfusion after stroke: a marker of favorable tissue outcome? Brain 119: 409–419PubMedCrossRefGoogle Scholar
  47. Marchal G, Benali K, Iglesias S, et al (1999a) Voxel-based mapping of irreversible tissue damage by PET in the acute stage of ischemic stroke. Brain 123: 2387–2400CrossRefGoogle Scholar
  48. Marchal G, Young AR, Baron JC (1999b) Early post-ischaemic hyperperfusion: pathophysiological insights from positron emission tomography. J Cereb Blood Flow Metab 19: 467–482PubMedCrossRefGoogle Scholar
  49. Marchal G, Bouvard G, Iglesias S, Sebastien B, Benali K, Defer G, Viader F, Baron JC (2000) Predictive value of 99mTc-HMPAO for neurological outcome/recovery in the acute stage of stroke. Cerebrovasc Dis 10: 8–17PubMedCrossRefGoogle Scholar
  50. Minematsu K, et al (1992) Reversible focal ischemic injury demonstrated by diffusionweighted magnetic resonance imaging in rats. Stroke 23:1304–1310PubMedCrossRefGoogle Scholar
  51. Nakano S, Iseda T, Ikeda T, Yoneyama T, Wakisaka S (2000) Thresholds of ischemia salvageable with intravenous tissue plasminogen activator therapy: evaluation with cerebral blood flow single-photon emission computed tomographic measurements. Neurosurgery 47: 68–73PubMedGoogle Scholar
  52. Ogasawara K, Ogawa A, Konno H, Shibanai K, Doi M, Kuroda K, Yoshimoto T (2001) Combination of early and delayed SPET imaging using technetium-99m ethyl cysteinate dimer immediately after local intra-arterial thrombolysis. Eur J Nucl Med 28: 498–505PubMedCrossRefGoogle Scholar
  53. Oppenheim C, Samson Y, Manai R, Lalam T, Vandamme X, Crozier S, Srour A, Cornu P, Dormont D, Rancurel G, Marsault C (2000) Prediction of malignant middle cerebral artery infarction by diffusion-weighted imaging. Stroke 31: 2175–2181PubMedCrossRefGoogle Scholar
  54. Oppenheim C, Grandin C, Samson Y, Smith A, Duprez T, Marsault C, Cosnard G (2001) Is there an apparent diffusion coefficient threshold in predicting tissue viability in hyperacute stroke? Stroke 32: 2486–2491PubMedCrossRefGoogle Scholar
  55. Ostergaard L, Weisskoff RM, Chesler DA, Gyldensted C, Rosen BR (1996) High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. I. Mathematical approach and statistical analysis. Magn Res Med 36: 715–725CrossRefGoogle Scholar
  56. Parsons MW, Yang Q, Barber A, Darby DG, Desmond PM, Gerraty RP, Tress BM, Davis SM (2001) Perfusion magnetic resonance imaging maps in hyperacute stroke. Relative cerebral blood flow most accurately identifies tissue destined to infarct. Stroke 32:1581–1587PubMedCrossRefGoogle Scholar
  57. Ramsay SC, Weiller C, Myers R, et al (1992) Monitoring by PET of macrophage accumulation in brain after ischaemic stroke. Lancet 239:1054–1055CrossRefGoogle Scholar
  58. Read SJ, Hirano T, Abbott DF, et al (1998) Identifying hypoxic tissue after acute ischemic stroke using PET and 18F-fluoromisonidazole. Neurology 51: 1617–1621PubMedCrossRefGoogle Scholar
  59. Read SJ, Hirano T, Abbott DF, Markus R, Sachinidis JI, Tochon-Danguy HJ, Chan JG, Egan GF, Scott AM, Bladin CF, McKay WJ, Donnan GA (2000) The fate of hypoxic tissue on 18F-fluoromisonidazole positron emission tomography after ischemic stroke. Ann Neurol 48: 228–235PubMedCrossRefGoogle Scholar
  60. Røhl L, Østergaard, Simonsen CZ, Vestergaard-Poulsen P, Andersen G, Sakoh M, Le Bihan D, Gyldensted C (2001) Viability thresholds of ischemic penumbra of hyperacute stroke defined by perfusion-weighted MRI and apparent diffusion coefficient. Stroke 32: 1140–1146PubMedCrossRefGoogle Scholar
  61. Schlaug G, et al (1997) Time course of the apparent diffusion coefficient (ADC) abnormality in human stroke. Neurology 49:113–119PubMedCrossRefGoogle Scholar
  62. Schlaug G, et al (1999) The ischemic penumbra: operationally defined by diffusion and perfusion MRI. Neurology 53: 1528–1537PubMedCrossRefGoogle Scholar
  63. Senda M, Alpert NM, Mackay BC, Buxton RB, Correia JA, Weise SB, Ackerman RH, Dorer D, Buonanno FS (1989) Evaluation of the 11CO2 positron emission tomographic method for measuring brain pH.II. Quantitative pH mapping in patients with ischemic cerebrovascular diseases. J Cereb Blood Flow Metabol 9: 859–873CrossRefGoogle Scholar
  64. Sette G, Baron JC, Young AR, et al (1993) In vivo mapping of brain benzodiazepine receptor changes by positron emission tomography after focal ischemia in the anesthetized baboon. Stroke 24: 2046–2058PubMedCrossRefGoogle Scholar
  65. Shimosegawa E, Hatazawa J, Inugami A, et al (1994) Cerebral infarction within six hours of onset: prediction of completed infarction with technetium-99m-HMPAO SPECT. J Nucl Med 35: 1097–1103PubMedGoogle Scholar
  66. Sorensen AG, Buonanno FS, Gonzalez RG, Schwamm LH, Lev MH, Huang-Hellinger FR, Reese TG, Weisskoff RM, Davis TL, Suwanwela N, Can U, Moreira JA, Copen WA, Look RB, Finklestein SP, Rosen BR, Koroshetz WJ (1996) Hyperacute stroke: evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging. Radiology 199: 391–401PubMedGoogle Scholar
  67. Sperling B, Lassen NA (1993) Hyperfixation of HMPAO in subacute ischemic stroke leading to spuriously high estimates of cerebral blood flow by SPECT. Stroke 24:193–194PubMedCrossRefGoogle Scholar
  68. Syrota A, Samson Y, Boullais C, Wajnberg P, Loc’h C, Crouzel C, Maziere B, Soussaline F, Baron JC (1985) Tomographic mapping of brain intracellular pH and extracellular water space in stroke patients. J Cereb Blood Flow Metabol 5: 358–385CrossRefGoogle Scholar
  69. Szabo K, Kern R, Gass A, Hirsch J, Hennerici M (2001) Acute stroke patterns in patients with internal carotid artery disease. A diffusion-weighted magnetic resonance imaging study. Stroke 32:1323–1329PubMedCrossRefGoogle Scholar
  70. Thijs VN, Adami A, Neumann-Haefelin T, Moseley ME, Marks MP, Albers GW (2001) Relationship between severity of MR perfusion deficit and DWI lesion evolution. Neurology 57: 1205–1211PubMedCrossRefGoogle Scholar
  71. Touzani O, Young AR, Derlon J-M, Beaudouin V, Marchal G, Rioux P, Mezenge F, Baron JC, MacKenzie ET (1995) Sequential studies of severely hypometabolic tissue volumes after permanent middle cerebral artery occlusion. A positron emission tomographic investigation in anesthetized baboons. Stroke 26: 2112–2119PubMedCrossRefGoogle Scholar
  72. Touzani O, Young AR, Derlon JM, et al (1997) Progressive impairment of brain oxidative metabolism reversed by reperfusion following middle cerebral artery occlusion in anaesthetized baboons. Brain Res 767: 17–25PubMedCrossRefGoogle Scholar
  73. Ueda T, Hatakeyama T, Kumon Y, et al (1994) Evaluation of risk of hemorrhagic transformation in local intra-arterial thrombolysis in acute ischemic stroke by initial SPECT. Stroke 25: 298–303PubMedCrossRefGoogle Scholar
  74. Warach S, et al (1992) Fast magnetic resonance diffusion-weighted imaging of acute human stroke. Neurology 42: 1717–1723PubMedCrossRefGoogle Scholar
  75. Warach S, et al (1995) Acute human stroke studied by whole brain echo planar diffusionweighted magnetic resonance imaging. Ann Neurol 37: 231–241PubMedCrossRefGoogle Scholar
  76. Wise RJS, Bernardi S, Frackowiak RSJ, et al (1983) Serial observations on the pathophysiology of acute stroke. The transition from ischaemia to infarction as reflected in regional oxygen extraction. Brain 106: 197–222PubMedCrossRefGoogle Scholar
  77. Wu O, Koroshetz WJ, Østergaard L, Buonanno FS, Copen WA, Gonzalez G, Rordorf G, Rosen BR, Schwamm LH, Weisskoff RM, Sorensen AG ( 2001) Predicting tissue outcome in acute human cerebral ischemia using combined diffusion — and perfusion-weighted MR imaging. Stroke 32: 933–942PubMedCrossRefGoogle Scholar
  78. Young AR, Touzani O, Derlon JM, Sette G, MacKenzie ET, Baron JC (1997) Early reperfusion in the anesthetized baboon reduces brain damage following middle cerebral artery occlusion. Stroke 28: 632–638PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2002

Authors and Affiliations

  • J. C. Baron
    • 1
    • 2
  1. 1.Department of Neurology and Stroke UnitUniversity of CambridgeUK
  2. 2.Department of NeurologyAddenbrooke’s HospitalUK

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