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(Stroke. 2005;36:1098.)
© 2005 American Heart Association, Inc.

Controversies in Stroke

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

Peter D. Schellinger, MD Jochen B. Fiebach, MD

From the Departments of Neurology (P.D.S.), and Neuroradiology (J.B.F.), University of Heidelberg, Germany.

Correspondence to Peter D. Schellinger, MD, Neurologische Universitatsklinik, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. E-mail Peter-Schellinger{at}med.uni-heidelberg.de

Section Editors: Geoffrey A. Donnan MD, FRACP Stephen M. Davis MD, FRACP

Key Words: diffusion magnetic resonance imaging • magnetic resonance imaging

"It’s now or never. I was caught in a dead end street. A look (into your eyes) can heal me. And after this moment, you gave me something (back). What I really need."

— Primal Fear, "Nuclear Fire," 2001

Of course, the "dead end street" refers to computed tomography (CT), "the healing look" to reading a stroke MRI, and being "given something that one really needs" to thrombolytic therapy.

What do we need to establish that a new methodology is ready to be put to use instead of an older one? We need to show that it is at least as good, if not better, than the old modality with regard to safety, feasibility, cost efficiency, and diagnostic and prognostic power. Over the last years, a growing number of reports on the use of multiparametric MRI protocols including diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) for guiding treatment in acute stroke patients have been published.¹

MRI is safe in acute stroke patients; side effects such as allergic reactions to contrast agent and x-ray load virtually do not exist. Feasibility of stroke MRI is estimated between 75% and 95%,^2–4 granted, somewhat lower than that of CT. The feasibility of stroke MRI depends in part on how patient instability, and therefore safety concerns, is defined in different centers. When compared with noncontrast CT alone, the cost of stroke MRI is higher; as soon as CT angiography and perfusion CT are added to the CT protocol, the difference in cost is marginal. Again, we admit that cost effectiveness of stroke MRI has not been proven yet.

However, it has been shown beyond doubt that the diagnostic accuracy of stroke MRI for ischemic stroke is significantly higher than that of CT, and for intracerebral hemorrhage, it is equally as good as CT.^5,6 On the other hand, time to treatment is a very strong prognostic variable within the first 90 to 180 minutes after stroke onset.⁷ All recombinant tissue plasminogen activator trials with a time window exceeding 3 hours were negative, suggesting that thereafter, patient selection may be more important than time in combination with an insensitive diagnostic tool.

Several open controlled studies used the PWI/DWI mismatch concept to extend the therapeutic time window for thrombolytic therapy and showed that selected patients profit from treatment.^8,9 Another series showed that patients who are treated on the basis of stroke MRI criteria within 3 to 6 hours fare at least as well as those being treated on the basis of CT within 3 hours.¹⁰ Finally, the recently presented Desmoteplase In Acute Ischemic Stroke phase II trial illustrated 3 important things.¹¹ First, it demonstrated that thrombolysis beyond 3 hours works if an appropriate tool (ie, stroke MRI) for patient selection is applied. Second, reperfusion on stroke MRI paralleled clinical outcome, showing that stroke MRI may be used as a surrogate parameter for outcome. Third, the therapeutic effect on clinical and MRI outcomes did not depend on time to treatment, illustrating that patient selection may be more important than time. To prevent time loss where it really counts, CT should be the primary diagnostic tool within 3 hours if a center is not able to provide stroke MRI as fast as CT. In keeping with the times, stroke MRI can and should be applied to guide stroke therapy within institutional protocols outside the 3-hour time window if inclusion in a randomized controlled trial is not possible.

Conclusion

"Who all need it—who. Who all need it—you. Who all need it, who all need it (yes you do). You all breathe it, we all need it. Are you ready for a good time? Are you ready?"

— Taken from AC/DC, "The Razors Edge", 1990

Yes, we are ready for stroke MRI!

Received October 21, 2004; accepted October 22, 2004.

References

1. Schellinger PD, Fiebach JB, Hacke W. Imaging-based decision making in thrombolytic therapy for ischemic stroke: present status. Stroke. 2003; 34: 575–583.[Abstract/Free Full Text]
2. Buckley BT, Wainwright A, Meagher T, Briley D. Audit of a policy of magnetic resonance imaging with diffusion-weighted imaging as first-line neuroimaging for in-patients with clinically suspected acute stroke. Clin Radiol. 2003; 58: 234–237.[CrossRef][Medline] [Order article via Infotrieve]
3. Schellinger PD, Jansen O, Fiebach JB, Pohlers O, Ryssel H, Heiland S, Steiner T, Hacke W, Sartor K. Feasibility and practicality of MR imaging of stroke in the management of hyperacute cerebral ischemia. AJNR. 2000; 21: I184–I189.
4. Singer OC, Sitzer M, du Mesnil de Rochemont R, Neumann-Haefelin T. Practical limitations of acute stroke MRI due to patient-related problems. Neurology. 2004; 62: 1848-l 849.[Free Full Text]
5. Fiebach JB, Schellinger PD, Jansen O, Meyer M, Wilde P, Bender J, Schramm P, JuttIer E, Ghler J, Hartmann M, Hahnel S, Knauth M, Hacke W, Sartor K. CT and diffusion-weighted MR-imaging in randomized order: DWI results in higher accuracy and lower interrater variability in the diagnosis of hyperacute ischemic stroke. Stroke. 2002; 33: 2206–2210.[Abstract/Free Full Text]
6. Fiebach JB, Schellinger PD, Gass A, Kucinski T, Siebler M, Villringer A, Olkers P, Hirsch JG, Heiland S, Wilde, Jansen O, Rother J, Hacke W, Sartor K. Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage. A multicenter study on the validity of stroke imaging. Stroke. 2004; 35: 502–507.[Abstract/Free Full Text]
7. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S; ATLANTIS Trials Investigators; ECASS Trials Investigators; NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004; 363: 768–774[CrossRef][Medline] [Order article via Infotrieve]
8. Rother J, Schellinger PD, Gass A, Siebler M, Villringer A, Fiebach JB, Fiehler J, Jansen O, Kucinski T, Schoder V, Szabo K, Junge-Hiilsing GJ, Hennerici M, Zeumer H, Sartor K, Weiller C, Hacke W. Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke c6h. Stroke. 2002; 33: 2438–2445.[Abstract/Free Full Text]
9. 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. 2002; 51: 28–37.[CrossRef][Medline] [Order article via Infotrieve]
10. Kulkens S, Schwark C, Schellinger PD, Fiebach JB, Ringleb PA, Hacke W. Thrombolysis in ischemic stroke 3 to 6 hours after symptom onset using an MR-based algorithm. International Stroke Conference, Phoenix, Ariz. February 5, 2003.
11. Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fisher M, Furland A, Kaste M, Lees KR, Soehngen M, Warach S. 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; 36: 66–73.[Abstract/Free Full Text]

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This Article Full Text (PDF) All Versions of this Article: 36/5/1098    most recent 01.STR.0000162388.67745.8dv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schellinger, P. D. Articles by Fiebach, J. B. Search for Related Content PubMed PubMed Citation Articles by Schellinger, P. D. Articles by Fiebach, J. B. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Stroke Related Collections Fibrinolysis Computerized tomography and Magnetic Resonance Imaging Thrombolysis Related Articles