Korean Journal of Cerebrovascular Surgery 2004;6(2):165-168.
Published online September 1, 2004.
Magnetic Resonance Imaging of the Ischemic Penumbra: Diffusion-Perfusion Mismatch in Acute Stroke Patients.
Joo, Jin Yang , Ahn, Jung Yong , Yoon, Pyeong Ho , Kim, Sang Heum
1Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea.
2Department of Neurosurgery, Pundang CHA Hospital, College of Medicine, Pochon CHA University, Sungnam, Korea.
3Department of Diagnostic Radiology, Pundang CHA Hospital, College of Medicine, Pochon CHA University, Sungnam, Korea. phyoon@cha.ac.kr
Abstract
The ischemic penumbra is defined as functionally impaired but salvageable ischemic brain tissue surrounding an irreversibly damaged core. Therefore, rapid and precise identification of the penumbra is of considerable interest for decision-making in acute stroke treatment. The region with perfusion abnormality but no diffusion lesion (the so-called diffusion-perfusion mismatch) identifies tissue that is hypoperfused but that not yet experienced advanced bioenergetic failure and represents the penumbra. Thus, diffusion-perfusion mismatch are predicted to have the most lesion growth and may benefit most from any perfusion-altering therapies. The time window available for salvage of the penumbra in selected patients may be much longer than the traditional, presumed 3- to 6-hour window and that diffusion-perfusion MRI has the ability to identify these patients. Multimodal MRI allows therapeutic decisions to be based on individual patient pathophysiological information, allowing the time window to be extended in appropriate patients.
Key Words: Ischemic penumbra, Magnetic resonance imaging, Diffusion, Perfusion, Stroke

Introduction


  
The ischemic penumbra is defined as functionally impaired but salvageable ischemic brain tissue surrounding an irreversibly damaged core.2) Penumbral tissue needs to be distinguished from the ischemic core(tissue that is already irreversibly injured even if blood flow is reestablished) and from tissue experiencing benign oligemia, in which the mild reductions in tissue perfusion do not actually place the tissue at risk. The promise of acute stroke therapies is anchored in the assumption that the penumbra tissue may be salvaged with restoration of blood flow or effective neuroprotective treatments. The penumbra changes rapidly with time and differs from patient to patient. Therefore, rapid and precise identification of the penumbra is of considerable interest for decision-making in acute stroke treatment.1)12)15)23) Direct visualization of the location and extent of the penumbra could greatly improve our ability to determine which patients may benefit from therapy and allow treatment decisions to be based on individualized pathophysiology rather than arbitrary chronological time windows. 
   In the past decade, diffusion- and perfusion-weighted MRI (DWI and PWI, respectively) techniques have revolutionized the role of MRI in the evaluation of patients with acute cerebrovascular disease.4) DWI provides a measure of tissue bioenergetic compromise and PWI a measure of hemodynamic compromise. This physiologic state may be characterized by parameters of tissue perfusion such as cerebral blood volume(CBV), cerebral blood flow(CBF), mean transit time(MTT), and time-to-peak(TTP). The combined data from these 2 modalities can delineate the pathophysiological state of ischemia and may provide a practical means to rapidly and precisely identify the ischemic penumbra in the acute stroke setting. In this review, we explored the role of diffusion- and perfusion-weighted MR image as a rapid method of defining ischemic penumbra and its clinical applications in acute stroke patients.

1. Diffusion and perfusion mismatch
  
According to mismatch model(Fig. 1), the diffusion abnormality represents core, irreversibly injured tissue, and the outer rim of the visualized perfusion abnormality defines the periphery of the penumbra. The region with perfusion abnormality but no diffusion lesion(the so-called PWI/DWI mismatch) identifies tissue that is hypoperfused but that not yet experienced advanced bioenergetic failure and represents the penumbra.21) The difference between a large abnormal area on PWI and a smaller bright area on DWI, is currently the most used index of the ischemic penumbra(Fig. 2).5)12)17)22)25) The most compelling data supporting the mismatch model come from observations in untreated patients is to grow over time into the area of the initial perfusion abnormality as the penumbra gradually fails.3) An analysis of data from placebotreated patients enrolled in 2 neuroprotective studies demonstrated that lesions grew on average by 144% to 180% from the baseline to the follow-up imaging studies.26) 
   Previously, it has not been clear which hemodynamic maps are most informative in predicting final infarct volume. Recently, there have been several reports of prediction of stroke volume with diffusion- and perfusion-weighted MRI.5)6)8)11)13)14)19)20)22) Schaefer et al.19) demonstrated that DWI continued to correlate highly with final infarct volume when there is a DWI-CBV, DWI-CBF, or DWI-MTT mismatch. Of the perfusion parameters, CBV(63%) appeared superior to CBF and MTT(approximately 20%) in predicting final infarct volume. Thus, DWI-CBV mismatch are predicted to have the most lesion growth and may benefit most from any perfusion-altering therapies. However, others found CBF was the most useful parameter in distinguishing hypoperfused tissue that progressed to infarction from hypoperfused tissue that remained viable in the operationally defined ischemic penumbra in patients not treated with thrombolysis.8)10)11)14)20)

2. Role of recanalization therapy in diffusion-perfusion mismatch model
  
Intra-arterial thrombolysis is a particularly powerful technique for acute stroke patients. Some of patients were guaranteed to recover neurologically from thrombolysis, but others were not. Diffusion- and perfusion-weighted MRI can give powerful information for proper indication of recanalization therapies(Fig. 3). Several analyses of patients experiencing reperfusion have shown inhibition of diffusion lesion growth, suggesting actual salvage of the mismatch region. For example, Jansen and colleagues12) demonstrated inhibition of lesion growth in patients experiencing reperfusion compared with patients with persistent perfusion deficits or vessel occlusions. More recently, Parsons and colleagues18) compared MRI signatures in patients treated with intravenous tissue plasminogen activator within 6 hours of onset compared with a group of matched controls. They found a significant decrease in the amount of mismatch tissue that proceeded to infarction in the thrombolysis-treated group. 
   While recent trials have demonstrated that thrombolytic therapies are successful in the early time windows,24) there remains a crucial need to identify patients with existing salvageable tissue over longer time periods since these patients may benefit from late recanalization therapies. Most of acute stroke trials showed a benefit of reperfusion therapies when delivered within 3 hours of symptom onset. However, there are two problems in practice. First, few patients are currently being treated within the 3-hour window, and second, identification of effective therapies beyond 3 hours from symptoms onset remains elusive. In the presented case, the patient underwent the recanalization procedures at 2 days after symptom onset, usually not indicated for aggressive therapy due to time window. In terms of critical time window, the most exciting potential application of MRI is its use as a selection tool for acute and subacute stroke treatments.10) Significant diffusion-perfusion mismatch may be present up to 24 hours or more from symptom onset.7)16) Darby and colleagues7) demonstrated that while the presence and volume of mismatch progressively decreases over time, approximately 60% to 70% of patients up to 24 hours will still have substantial regions of mismatch. This finding is supported by studies previously performed in stroke patients employing positron emission tomography demonstrating penumbral tissue present in up to 16 to 48 hours after symptom onset.9)16) This finding suggests that the time window available for salvage of the penumbra in selected patients may be much longer than the traditional, presumed 3- to 6-hour window and that diffusion-perfusion MRI has the ability to identify these patients. 

Conclusions

   MRI is a very practical method for acute stroke imaging and therapeutic salvage of the ischemic penumbra has been demonstrated in patients with the use of diffusion-perfusion MRI. Multimodal MRI allows therapeutic decisions to be based on individual patient pathophysiological information, allowing the time window to be extended in appropriate patients.


REFERENCES


  1. Albers GW. Expanding the window for thrombolytic therapy in acute stroke: the potential role of acute MRI for patient selection. Stroke 30:2230-7, 1999

  2. Astrup J, Siesjo B, Symon L. Threshold in cerebral ischemia: the ischemic penumbra. Stroke 12:723-5, 1981

  3. Baird AE, Benfield A, Schlaug G, Siewert B, Lovblad KO, Edelman RR, Warach S. Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging. Ann Neurol 41:581-9, 1997

  4. Baird AE, Warach S. Magnetic resonance imaging of acute stroke. J Cereb Blood Flow Metab 18:583-609, 1998

  5. Barber PA, Darby DG, Desmond PM, Yang Q, Gerraty RP, Jolley D, Donnan GA, Tress BM, Davis SM. Prediction of stroke outcome with echoplanar perfusion- and diffusion-weighted MRI. Neurology 51:418-26, 1998

  6. Beaulieu C, de Crespigny A, Tong DC, Moseley ME, Albers GW, Marks MP. Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: evolution of lesion volume and correlation with clinical outcome. Ann Neurol 46:568-78, 1999

  7. Darby DG, Barber PA, Gerraty RP, Desmond PM, Yang Q, Parsons M, Li T, Tress BM, Davis SM. Pathophysiological topography of acute ischemia by combined diffusion-weighted and perfusion MRI. Stroke 30:2043-52, 1999

  8. Fiehler J, von Bezold M, Kucinski T, Knab R, Eckert B, Wittkugel O, Zeumer H, Rother J. Cerebral blood flow predicts lesion growth in acute stroke patients. Stroke 33:2421-5, 2002

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

  10. Hillis AE, Wityk RJ, Beauchamp NJ, Ulatowski JA, Jacobs MA, Barker PB. Perfusion-weighted MRI as a marker of response to treatment in acute and subacute stroke. Neuroradiology 46:31-9, 2004

  11. Igarashi H, Hamamoto M, Yamaguchi H, Ookubo S, Nagashima J, Nagayama H, Amemiya S, Katayama Y. Cerebral blood flow index: dynamic perfusion MRI delivers a simple and good predictor for the outcome of acute-stage ischemic lesion. J Comput Assist Tomogr 27:874-81, 2003

  12. Jansen O, Schellinger P, Fiebach J, Hacke W, Sartor K. Early recanlization in acute ischaemic stroke saves tissue at risk defined by MRI. Lancet 353:2036-7, 1999

  13. Karonen JO, Vanninen RL, Liu Y, Ostergaard L, Kuikka JT, Nuutinen J, Vanninen EJ, Partanen PL, Vainio PA, Korhonen K, Perkio J, Roivainen R, Sivenius J, Aronen HJ. Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke. Ischemic penumbra predicts infarct growth. Stroke 30:1583-90, 1999

  14. Lev MH, Segal AZ, Farkas J, Hossain ST, Putman C, Hunter GJ, Budzik R, Harris GJ, Buonanno FS, Ezzeddine MA, Chang Y, Koroshetz WJ, Gonzalez RG, Schwamm LH. 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 32:2021-8, 2001

  15. Liu Y, Karonen JO, Vanninen RL, Ostergaard L, Roivainen R, Nuutinen J, Perkio J, Kononen M, Hamalainen A, Vanninen EJ, Soimakallio S, Kuikka JT, Aronen HJ. Cerebral hemodynamics in human acute ischemic stroke: a study with diffusion- and perfusion-weighted magnetic resonance imaging and SPECT. J Cereb Blood Flow Metab 20:910-20, 2000

  16. Marchal G, Beaudouin V, Rioux P, de la Sayette V, Le Doze F, Viader F, Derlon JM, Baron JC. Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke: a correlative PET-CT study with voxel-based data analysis. Stroke 27:599-606, 1996

  17. Neumann-Haefelin T, Wittsack HJ, Wenserski F, Siebler M, Seitz RJ, Modder U, Freund HJ. Diffusion- and perfusion-weighted MRI: the DWI/PWI mismatch region in acute stroke. Stroke 30:1591-7, 1999

  18. Parsons MW, Barber PA, Chalk J, Darby DG, Rose S, Desmond PM, Gerraty RP, Tress BM, Wright PM, Donnan GA, Davis SM. Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke. Ann Neurol 51:28-37, 2002

  19. Schaefer PW, Hunter GJ, He J, Hamberg LM, Sorensen AG, Schwamm LH, Koroshetz WJ, Gonzalez RG. Predicting cerebral ischemic infarct volume with diffusion and perfusion MR imaging. AJNR Am J Neuroradiol 23:1785-94, 2002

  20. Schaefer PW, Ozsunar Y, He J, Hamberg LM, Hunter GJ, Sorensen AG, Koroshetz WJ, Gonzalez RG. Assessing tissue viability with MR diffusion and perfusion imaging. AJNR Am J Neuroradiol 24:436-43, 2003

  21. Schlaug G, Benfield A, Baird AE, Siewert B, Lovblad KO, Parker RA, Edelman RR, Warach S. The ischemic penumbra: operationally defined by diffusion and perfusion MRI. Neurology 53:1528-37, 1999

  22. Sorensen AG, Copen WA, Ostergaard L, Buonanno FS, Gonzalez RG, Rordorf G, Rosen BR, Schwamm LH, Weisskoff RM, Koroshetz WJ. Hyperacute stroke: simultaneous measurement of relative cerebral blood volume, relative cerebral blood flow, and mean tissue transit time. Radiology 210:519-27, 1999

  23. Sunshine JL, Tarr RW, Lanzieri CF, Landis DM, Selman WR, Lewin JS. Hyperacute stroke: ultrafast MR imaging to triage patients prior to therapy. Radiology 212:325-32, 1999

  24. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 333:1581-7, 1995

  25. Tong DC, Yenari MA, Albers GW, O'Brien M, Marks MP, Moseley ME. Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute(<6.5 hour) ischemic stroke. Neurology 50:864-70, 1998

  26. Warach S, Pettigrew LC, Dashe JF, Pullicino P, Lefkowitz DM, Sabounjian L, Harnett K, Schwiderski U, Gammans R. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators. Ann Neurol 48:713-22, 2000

TOOLS
METRICS Graph View
  • 812 View
  • 4 Download
Related articles


ABOUT
BROWSE ARTICLES
EDITORIAL POLICY
FOR CONTRIBUTORS
Editorial Office
The Journal of Cerebrovascular and Endovascular Neurosurgery (JCEN), Department of Neurosurgery, Wonkwang University
School of Medicine and Hospital, 895, Muwang-ro, Iksan-si, Jeollabuk-do 54538, Korea
Tel: +82-2-2279-9560    Fax: +82-2-2279-9561    E-mail: editor.jcen@the-jcen.org                

Copyright © 2024 by Korean Society of Cerebrovascular Surgeons and Korean NeuroEndovascular Society.

Developed in M2PI

Close layer
prev next