Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-13T01:00:26.822Z Has data issue: false hasContentIssue false
  • English
  • Français

Acute Stroke Imaging Part II: The Ischemic Penumbra

Published online by Cambridge University Press:  02 December 2014

K. Butcher  and
D. Emery
K. Butcher*
Affiliation:
Division of Neurology, University of Alberta, Edmonton, Alberta, Canada
D. Emery
Affiliation:
Department of Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada
*
Division of Neurology, 2E3 WMC Health Sciences Centre, University of Alberta, 8440 112th St., Edmonton, Alberta, T6G 2B7, Canada.
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

In acute ischemic stroke, the volume of threatened but potentially salvageable tissue, i.e. the ischemic penumbra, is critical to the success of all acute therapeutic interventions, most notably thrombolysis. Despite the availability of both CT and MRI based techniques to detect and assess the penumbra, advanced imaging of this type remains under-utilized. Although the optimal selection criteria are still being refined and technical improvements are ongoing, rapid imaging of the penumbra appears to be the most promising approach to expanding the acute thrombolysis population, as well as tailoring treatment based on specific pathophysiological findings. This second article in a two-part series reviews current evidence for penumbral-based treatment selection and discusses the barriers to implementation of these advanced imaging techniques in acute stroke management protocols.

Résumé:

RÉSUMÉ:

Enphase aigue de l’accident vasculaire cerebral, le volume du tissu a risque mais potentiellement viable, c’est–a–dire la penombre ischemique, est tres important pour le succes de toute intervention therapeutique dont la thrombolyse. Malgre la disponibilite de techniques basees sur la tomodensitometrie et sur l’imagerie par resonance magnetique pour detecter et evaluer la penombre, ces types d’imageries demeurent sous–utilisees. Bien que les criteres de selection optimaux ne soient pas encore bien definis et que la technologie se perfectionne continuellement, l’approche la plus prometteuse pour augmenter la population de patients qui subissent une thrombolyse en phase aigue ainsi que pour individualiser le traitement sur la base de constatations physiopathologiques specifiques demeure l’imagerie rapide de la penombre. Ce second article de cette serie de deux articles revoit les donnees actuelles concernant le choix du traitement base sur la penombre et discute des barrieres a l’utilisation de ces techniques avancees d’imagerie dans les protocoles de prise en charge de l’accident vasculaire cerebral aigu.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 37 , Issue 1 , January 2010 , pp. 17 - 27
Copyright
Copyright © The Canadian Journal of Neurological 2010

References

1. Astrup, J, Symon, L, Branston, NM, Lassen, NA. Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke. 1977 Jan-Feb;8(1):51–7.Google Scholar
2. Symon, L, Branston, NM, Strong, AJ. The concept of thresholds of ischemia in relation to brain structure and function. J Clin Pathol. 1977;30(S11):149–54.CrossRefGoogle Scholar
3. Astrup, J, Siesjo, BK, Symon, L. Thresholds in cerebral ischemia - the ischemic penumbra. Stroke. 1981 Nov-Dec;12(6):723–5.Google Scholar
4. Marchal, G, Beaudouin, V, Rioux, P, de la Sayette, V, Le Doze, F, Viader, F, et al. Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke: a correlative PET-CT study with voxel-based data analysis. Stroke. 1996 Apr;27(4):599–606.Google Scholar
5. Marchal, G, Furlan, M, Beaudouin, V, Rioux, P, Hauttement, JL, Serrati, C, et al. Early spontaneous hyperperfusion after stroke. A marker of favourable tissue outcome? Brain. 1996 Apr;119 (Pt 2):409–19.Google Scholar
6. Heiss, WD. Ischemic penumbra: evidence from functional imaging in man. J Cereb Blood Flow Metab. 2000 Sep;20(9):1276–93.Google Scholar
7. Donnan, GA, Dewey, HM, Davis, SM. MRI and stroke: why has it taken so long? Lancet. 2007 Jan 27;369(9558):252–4.Google Scholar
8. Schellinger, PD, Fiebach, JB. Perfusion-weighted imaging/diffusion-weighted imaging mismatch on MRI can now be used to select patients for recombinant tissue plasminogen activator beyond 3 hours: pro. Stroke. 2005 May;36(5):1104–5.Google ScholarPubMed
9. Parsons, MW, Pepper, EM, Bateman, GA, Wang, Y, Levi, CR. Identification of penumbra and infarct core on hyperacute non-contrast and perfusion CT. Neurology. 2007 March;68(3):730–6.Google Scholar
10. Davis, SM, Donnan, GA, Butcher, KS, Parsons, M. Selection of thrombolytic therapy beyond 3 h using magnetic resonance imaging. Curr Opin Neurol. 2005 Feb;18(1):47–52.Google Scholar
11. Schlaug, G, Benfield, A, Baird, AE, Siewert, B, Lovblad, KO, Parker, RA, et al. The ischemic penumbra: operationally defined by diffusion and perfusion MRI. Neurology. 1999;53(7):1528–37.CrossRefGoogle ScholarPubMed
12. Kidwell, CS, Alger, JR, Saver, JL. Beyond mismatch: evolving paradigms in imaging the ischemic penumbra with multimodal magnetic resonance imaging. Stroke. 2003;34 (11):2729–35.Google Scholar
13. Darby, DG, Barber, PA, Gerraty, RP, Desmond, PM, Yang, Q, Parsons, M, et al. Pathophysiological topography of acute ischemia by combined diffusion-weighted and perfusion MRI. Stroke. 1999;30(10):2043–52.Google Scholar
14. Barber, PA, Darby, DG, Desmond, PM, Yang, Q, Gerraty, RP, Jolley, D, et al. Prediction of stroke outcome with echoplanar perfusion- and diffusion-weighted MRI. Neurology. 1998 Aug;51(2): 418–26.Google Scholar
15. Warach, S, Dashe, JF, Edelman, RR. Clinical outcome in ischemic stroke predicted by early diffusion-weighted and perfusion magnetic resonance imaging: a preliminary analysis. J Cereb Blood Flow Metab. 1996;16(1):53–9.Google Scholar
16. Butcher, K, Parsons, M, Baird, T, Barber, A, Donnan, G, Desmond, P, et al. Perfusion thresholds in acute stroke thrombolysis. Stroke. 2003;34:2159–64.Google Scholar
17. Butcher, KS, Lee, SB, Parsons, MW, Allport, L, Fink, J, Tress, B, et al. Differential prognosis of isolated cortical swelling and hypoattenuation on CT in acute stroke. Stroke. 2007 Mar;38(3):941–7.Google Scholar
18. Barber, PA, Darby, DG, Desmond, PM, Gerraty, RP, Yang, Q, Li, T, et al. Identification of major ischemic change. Diffusion-weighted imaging versus computed tomography. Stroke. 1999;30(10):2059–65.Google Scholar
19. Eastwood, JD, Lev, MH, Azhari, T, Lee, TY, Barboriak, DP, Delong, DM, et al. CT perfusion scanning with deconvolution analysis: pilot study in patients with acute middle cerebral artery stroke. Radiology. 2002 Jan;222(1):227–36.Google Scholar
20. Smith, WS, Roberts, HC, Chuang, NA, Ong, KC, Lee, TJ, Johnston, SC, et al. Safety and feasibility of a CT protocol for acute stroke: combined CT, CT angiography, and CT perfusion imaging in 53 consecutive patients. AJNR Am J Neuroradiol. 2003 Apr;24(4):688–90.Google Scholar
21. Kudo, K, Terae, S, Katoh, C, Oka, M, Shiga, T, Tamaki, N, et al. Quantitative cerebral blood flow measurement with dynamic perfusion CT using the vascular-pixel elimination method: comparison with H2(15)O positron emission tomography. AJNR Am J Neuroradiol. 2003 Mar;24(3):419–26.Google Scholar
22. Murphy, BD, Fox, AJ, Lee, DH, Sahlas, DJ, Black, SE, Hogan, MJ, et al. Identification of penumbra and infarct in acute ischemic stroke using computed tomography perfusion-derived blood flow and blood volume measurements. Stroke. 2006 Jul;37(7):1771–7.Google Scholar
23. Parsons, MW, Pepper, EM, Chan, V, Siddique, S, Rajaratnam, S, Bateman, GA, et al. Perfusion computed tomography: prediction of final infarct extent and stroke outcome. Ann Neurol. 2005 Nov;58(5):672–9.Google Scholar
24. Wintermark, M, Reichhart, M, Cuisenaire, O, Maeder, P, Thiran, JP, Schnyder, P, et al. Comparison of admission perfusion computed tomography and qualitative diffusion- and perfusion-weighted magnetic resonance imaging in acute stroke patients. Stroke. 2002 Aug;33(8):2025–31.Google Scholar
25. Wintermark, M, Reichhart, M, Thiran, JP, Maeder, P, Chalaron, M, Schnyder, P, 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 Apr;51(4):417–32.Google Scholar
26. Silvennoinen, HM, Hamberg, LM, Lindsberg, PJ, Valanne, L, Hunter, GJ. CT perfusion identifies increased salvage of tissue in patients receiving intravenous recombinant tissue plasminogen activator within 3 hours of stroke onset. AJNR Am J Neuroradiol. 2008 Jun;29(6):1118–23.Google Scholar
27. Parsons, MW, Pepper, EM, Bateman, GA, Wang, Y, Levi, CR. Identification of the penumbra and infarct core on hyperacute noncontrast and perfusion CT. Neurology. 2007 Mar 6;68(10):730–6.CrossRefGoogle ScholarPubMed
28. Schellinger, PD, Thomalla, G, Fiehler, J, Kohrmann, M, Molina, CA, Neumann-Haefelin, T, et al. MRI-based and CT-based thrombolytic therapy in acute stroke within and beyond established time windows: an analysis of 1210 patients. Stroke. 2007 Oct;38(10):2640–5.Google Scholar
29. Hacke, W, Donnan, G, Fieschi, C, Kaste, M, von Kummer, R, Broderick, JP, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004 Mar 6;363(9411):768–74.Google Scholar
30. Schellinger, PD, Jansen, O, Fiebach, JB, Heiland, S, Steiner, T, Schwab, S, et al. Monitoring intravenous recombinant tissue plasminogen activator thrombolysis for acute ischemic stroke with diffusion and perfusion MRI. Stroke. 2000;31(6):1318–28.Google Scholar
31. Parsons, MW, Barber, PA, Chalk, J, Darby, DG, Rose, S, Desmond, PM, et al. Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke. Ann Neurol. 2002 Jan;51(1):28–37.Google Scholar
32. Albers, GW, Thijs, VN, Wechsler, L, Kemp, S, Schlaug, G, Skalabrin, E, et al. Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol. 2006 Nov;60(5):508–17.Google Scholar
33. Davis, SM, Donnan, GA, Parsons, MW, Levi, C, Butcher, KS, Peeters, A, et al. Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurol. 2008 Apr;7(4):299–309.Google Scholar
34. Furlan, AJ, Eyding, D, Albers, GW, Al-Rawi, Y, Lees, KR, Rowley, HA, et al. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke. 2006 May;37(5):1227–31.CrossRefGoogle ScholarPubMed
35. Hacke, W, Albers, G, Al-Rawi, Y, Bogousslavsky, J, Davalos, A, Eliasziw, M, et al. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke. 2005 Jan;36(1):66–73.Google Scholar
36. Hacke, W, Furlan, AJ, Al-Rawi, Y, Davalos, A, Fiebach, JB, Gruber, F, et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2009 Feb;8(2):141–50.Google Scholar
37. Parsons, MW. Perfusion CT: is it clinically useful? Int J Stroke. 2008 Feb;3(1):41–50.Google Scholar
38. Gasparotti, R, Grassi, M, Mardighian, D, Frigerio, M, Pavia, M, Liserre, R, et al. Perfusion CT in patients with acute ischemic stroke treated with intra-arterial thrombolysis: predictive value of infarct core size on clinical outcome. AJNR Am J Neuroradiol. 2009 Apr; 30(4):722–7.CrossRefGoogle ScholarPubMed
39. Parsons, MW, Miteff, F, Bateman, GA, Spratt, N, Loiselle, A, Attia, J, et al. Acute ischemic stroke: imaging-guided tenecteplase treatment in an extended time window. Neurology. 2009 Mar 10;72(10):915–21.CrossRefGoogle Scholar
40. Hjort, N, Butcher, K, Davis, S, Kidwell, CS, Koroshetz, WJ, Rother, J, et al. Magnetic resonance imaging criteria for thrombolysis in acute cerebral infarct. Stroke. 2005;36(2):388–97.Google Scholar
41. Butcher, KS, Parsons, M, MacGregor, L, Barber, PA, Chalk, J, Bladin, C, et al. Refining the perfusion-diffusion mismatch hypothesis. Stroke. 2005 May 12, 2005:1153–9.Google Scholar
42. Hossman, K. Viability thresholds and the penumbra of focal ischemia. Ann Neurol. 1994;36:557–65.Google Scholar
43. Arakawa, S, Wright, PM, Koga, M, Phan, TG, Reutens, DC, Lim, I, et al. Ischemic thresholds for gray and white matter: a diffusion and perfusion magnetic resonance study. Stroke. 2006 May;37(5):1211–6.Google Scholar
44. Kakuda, W, Lansberg, MG, Thijs, VN, Kemp, SM, Bammer, R, Wechsler, LR, et al. Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients. J Cereb Blood Flow Metab. 2008 May;28(5):887–91.Google Scholar
45. Donnan, GA, Baron, JC, Ma, H, Davis, SM. Penumbral selection of patients for trials of acute stroke therapy. Lancet Neurol. 2009 Mar;8(3):261–9.CrossRefGoogle ScholarPubMed
46. Christensen, S, Parsons, M, DeSilva, D, Ebinger, M, Butcher, K, Fink, J, et al. Optimal mismatch definitions for detecting treatment response in acute stroke. Cerebrovascular Dis. 2008;25 Suppl 2:33.Google Scholar
47. Coutts, SB, Simon, JE, Tomanek, AI, Barber, PA, Chan, J, Hudon, ME, et al. Reliability of assessing percentage of diffusion-perfusion mismatch. Stroke. 2003 Jul;34(7):1681–3.Google Scholar
48. Butcher, KS, Parsons, MW, Davis, S, Donnan, G. PWI/DWI mismatch: better definition required. Stroke. 2003 Nov;34(11):e215–6; author reply e-6.Google Scholar
49. Pexman, JHW, Barber, PA, Hill, MD, Sevick, RJ, Demchuk, AM, Hudon, ME, et al. Use of the Alberta Stroke Program Early CT Score (ASPECTS) for assessing CT Scans in patients with acute stroke. AJNR Am J Neuroradiol. 2001; 22(8):1534–42.Google Scholar
50. Butcher, K, Parsons, M, Allport, L, Lee, SB, Barber, PA, Tress, B, et al. Rapid assessment of perfusion-diffusion mismatch. Stroke. 2008 Jan;39(1):75–81.Google Scholar
51. Aviv, RI, Mandelcorn, J, Chakraborty, S, Gladstone, D, Malham, S, Tomlinson, G, et al. Alberta Stroke Program Early CT Scoring of CT perfusion in early stroke visualization and assessment. AJNR Am J Neuroradiol. 2007 Nov-Dec;28(10):1975–80.Google Scholar
52. Kothari, RU, Brott, T, Broderick, JP, Barsan, WG, Sauerbeck, LR, Zuccarello, M, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996;27:1304–5.Google Scholar
53. Kwak, R, Kadoya, S, Suzuki, T. Factors affecting the prognosis in thalamic hemorrhage. Stroke. 1983 Jul-Aug;14(4):493–500.CrossRefGoogle ScholarPubMed
54. Gomez-Marino, R, Andre, C, Novis, SA. [Volumetric determination of cerebral infarction in the acute phase using skull computed tomography without contrast: comparative study of 3 methods]. Arq Neuropsiquiatr. 2001 Jun;59(2-B):380–3.Google Scholar
55. Lev, MH. CT versus MR for acute stroke imaging: is the “obvious” choice necessarily the correct one? AJNR Am J Neuroradiol. 2003 Nov-Dec;24(10):1930–1.Google Scholar
56. Lansberg, MG, Albers, GW, Beaulieu, C, Marks, MP. Comparison of diffusion-weighted MRI and CT in acute stroke. Neurology. 2000 Apr 25;54(8):1557–61.Google Scholar
57. Schellinger, PD, Jansen, O, Fiebach, JB, Hacke, W, Sartor, K. A standardized MRI stroke protocol: comparison with CT in hyperacute intracerebral hemorrhage. Stroke. 1999;30(4):765–8.Google Scholar
58. Kidwell, CS, Chalela, JA, Saver, JL, Starkman, S, Hill, MD, Demchuk, AM, et al. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. JAMA. 2004 Oct;292(15):1823–30.Google Scholar
59. Mnyusiwalla, A, Aviv, RI, Symons, SP. Radiation dose from multidetector row CT imaging for acute stroke. Neuroradiology. Epub 2009 Jun 9.Google Scholar
60. Klingebiel, R, Siebert, E, Diekmann, S, Wiener, E, Masuhr, F, Wagner, M, et al. 4-D Imaging in cerebrovascular disorders by using 320-slice CT: feasibility and preliminary clinical experience. Acad Radiol. 2009 Feb;16(2):123–9.CrossRefGoogle ScholarPubMed
61. Siebert, E, Bohner, G, Dewey, M, Masuhr, F, Hoffmann, KT, Mews, J, et al. 320-slice CT neuroimaging: initial clinical experience and image quality evaluation. Br J Radiol. 2009 Jul;82(979):561–70.Google Scholar
62. Hopyan, JJ, Gladstone, DJ, Mallia, G, Schiff, J, Fox, AJ, Symons, SP, et al. Renal safety of CT angiography and perfusion imaging in the emergency evaluation of acute stroke. AJNR Am J Neuroradiol. 2008 Nov;29(10):1826–30.Google Scholar
63. Benko, A, Fraser-Hill, M, Magner, P, Capusten, B, Barrett, B, Myers, A, et al. Canadian Association of Radiologists: consensus guidelines for the prevention of contrast-induced nephropathy. Can Assoc Radiol J. 2007 Apr;58(2):79–87.Google ScholarPubMed
64. Pedersen, M. Safety update on the possible causal relationship between gadolinium-containing MRI agents and nephrogenic systemic fibrosis. J Magn Reson Imaging. 2007 May;25(5): 881–3.Google Scholar
65. Barber, PA, Davis, SM, Darby, DG, Desmond, PM, Gerraty, RP, Yang, Q, et al. Absent middle cerebral artery flow predicts the presence and evolution of the ischemic penumbra. Neurology. 1999 Apr 12;52(6):1125–32.Google Scholar
66. Lansberg, MG, Thijs, VN, Bammer, R, Olivot, JM, Marks, MP, Wechsler, LR, et al. The MRA-DWI mismatch identifies patients with stroke who are likely to benefit from reperfusion. Stroke. 2008 Sep;39(9):2491–6.Google Scholar
67. Hill, MD. Desmoteplase and imaging science. Lancet Neurol. 2009 Feb;8(2):126–8.Google Scholar
68. Ezzeddine, MA, Lev, MH, McDonald, CT, Rordorf, G, Oliveira-Filho, J, Aksoy, FG, et al. CT angiography with whole brain perfused blood volume imaging: added clinical value in the assessment of acute stroke. Stroke. 2002 Apr;33(4):959–66.Google Scholar
69. Lev, MH, Segal, AZ, Farkas, J, Hossain, ST, Putman, C, Hunter, GJ, et al. Utility of perfusion-weighted CT imaging in acute middle cerebral artery stroke treated with intra-arterial thrombolysis: prediction of final infarct volume and clinical outcome. Stroke. 2001 Sep;32(9):2021–8.Google Scholar
70. Hunter, GJ, Hamberg, LM, Ponzo, JA, Huang-Hellinger, FR, Morris, PP, Rabinov, J, et al. Assessment of cerebral perfusion and arterial anatomy in hyperacute stroke with three-dimensional functional CT: early clinical results. AJNR Am J Neuroradiol. 1998;19:29–37.Google Scholar
71. Davalos, A, Blanco, M, Pedraza, S, Leira, R, Castellanos, M, Pumar, JM, et al. The clinical-DWI mismatch: a new diagnostic approach to the brain tissue at risk of infarction. Neurology. 2004 Jun 22;62(12):2187–92.Google Scholar
72. Tei, H, Uchiyama, S, Usui, T. Clinical-diffusion mismatch defined by NIHSS and ASPECTS in non-lacunar anterior circulation infarction. J Neurol. 2007 Mar;254(3):340–6.Google Scholar
73. Prosser, J, Butcher, K, Allport, L, Parsons, M, MacGregor, L, Desmond, P, et al. Clinical-diffusion mismatch predicts the putative penumbra with high specificity. Stroke. 2005 Aug;36(8):1700–4.CrossRefGoogle ScholarPubMed
74. Buchan, AM, Barber, PA, Newcommon, N, Karbalai, HG, Demchuk, AM, Hoyte, KM, et al. Effectiveness of t-PA in acute ischemic stroke: outcome relates to appropriateness. Neurology. 2000 Feb 8;54(3):679–84.Google Scholar