Prospective study on the mismatch concept in acute stroke patients within the first 24 h after symptom onset - 1000Plus study

Benjamin Hotter, Sandra Pittl, Martin Ebinger, Gabriele Oepen, Kati Jegzentis, Kohsuke Kudo, Michal Rozanski, Wolf U Schmidt, Peter Brunecker, Chao Xu, Peter Martus, Matthias Endres, Gerhard J Jungehülsing, Arno Villringer, Jochen B Fiebach, Benjamin Hotter, Sandra Pittl, Martin Ebinger, Gabriele Oepen, Kati Jegzentis, Kohsuke Kudo, Michal Rozanski, Wolf U Schmidt, Peter Brunecker, Chao Xu, Peter Martus, Matthias Endres, Gerhard J Jungehülsing, Arno Villringer, Jochen B Fiebach

Abstract

Background: The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months.

Methods and design: 1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up.

Discussions: The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task.

Trial registration: clinicaltrials.gov NCT00715533.

Figures

Figure 1
Figure 1
Study Design.

References

    1. Von Kummer R, Bourquain H, Bastianello S, Bozzao L, Manelfe C, Meier D, Hacke W. Early prediction of irreversible brain damage after ischemic stroke at CT. Radiology. 2001;219:95–100.
    1. Fiebach JB, Schellinger PD, Gass A, Kucinski T, Siebler M, Villringer A, Olkers P, Hirsch JG, Heiland S, Wilde P. et al.Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage: a multicenter study on the validity of stroke imaging. Stroke. 2004;35:502–506. doi: 10.1161/01.STR.0000114203.75678.88.
    1. Kidwell CS, Chalela JA, Saver JL, Starkman S, Hill MD, Demchuk AM, Butman JA, Patronas N, Alger JR, Latour LL. et al.Comparison of MRI and CT for detection of acute intracerebral hemorrhage. Jama. 2004;292:1823–1830. doi: 10.1001/jama.292.15.1823.
    1. Jansen O, Schellinger P, Fiebach J, Hacke W, Sartor K. Early recanalisation in acute ischaemic stroke saves tissue at risk defined by MRI. Lancet. 1999;353:2036–2037. doi: 10.1016/S0140-6736(99)01146-0.
    1. Rother J, Schellinger PD, Gass A, Siebler M, Villringer A, Fiebach JB, Fiehler J, Jansen O, Kucinski T, Schoder V. et al.Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours. Stroke. 2002;33:2438–2445. doi: 10.1161/01.STR.0000030109.12281.23.
    1. Schellinger PD, Fiebach JB, Jansen O, Ringleb PA, Mohr A, Steiner T, Heiland S, Schwab S, Pohlers O, Ryssel H. et al.Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia. Ann Neurol. 2001;49:460–469. doi: 10.1002/ana.95.
    1. Furlan AJ, Eyding D, Albers GW, Al-Rawi Y, Lees KR, Rowley HA, Sachara C, Soehngen M, Warach S, Hacke W. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke. 2006;37:1227–1231. doi: 10.1161/01.STR.0000217403.66996.6d.
    1. Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR. 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;36:66–73. doi: 10.1161/01.STR.0000149938.08731.2c.
    1. 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. doi: 10.1002/ana.10067.
    1. Kohrmann M, Juttler E, Fiebach JB, Huttner HB, Siebert S, Schwark C, Ringleb PA, Schellinger PD, Hacke W. MRI versus CT-based thrombolysis treatment within and beyond the 3 h time window after stroke onset: a cohort study. Lancet Neurol. 2006;5:661–667. doi: 10.1016/S1474-4422(06)70499-9.
    1. Thomalla G, Schwark C, Sobesky J, Bluhmki E, Fiebach JB, Fiehler J, Zaro Weber O, Kucinski T, Juettler E, Ringleb PA. et al.Outcome and symptomatic bleeding complications of intravenous thrombolysis within 6 hours in MRI-selected stroke patients: comparison of a German multicenter study with the pooled data of ATLANTIS, ECASS, and NINDS tPA trials. Stroke. 2006;37:852–858. doi: 10.1161/01.STR.0000204120.79399.72.
    1. Hacke W, Furlan AJ, Al-Rawi Y, Davalos A, Fiebach JB, Gruber F, Kaste M, Lipka LJ, Pedraza S, Ringleb PA. 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;8:141–150. doi: 10.1016/S1474-4422(08)70267-9.
    1. Hill MD. Desmoteplase and imaging science. Lancet Neurol. 2009;8:126–128. doi: 10.1016/S1474-4422(08)70268-0.
    1. Albers GW, Thijs VN, Wechsler L, Kemp S, Schlaug G, Skalabrin E, Bammer R, Kakuda W, Lansberg MG, Shuaib A. 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;60:508–517. doi: 10.1002/ana.20976.
    1. Davis SM, Donnan GA, Parsons MW, Levi C, Butcher KS, Peeters A, Barber PA, Bladin C, De Silva DA, Byrnes G. 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;7:299–309. doi: 10.1016/S1474-4422(08)70044-9.
    1. Marks MP, Olivot JM, Kemp S, Lansberg MG, Bammer R, Wechsler LR, Albers GW, Thijs V. Patients with acute stroke treated with intravenous tPA 3-6 hours after stroke onset: correlations between MR angiography findings and perfusion- and diffusion-weighted imaging in the DEFUSE study. Radiology. 2008;249:614–623. doi: 10.1148/radiol.2492071751.
    1. 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. 1999;30:2043–2052.
    1. Frayne R, Goodyear BG, Dickhoff P, Lauzon ML, Sevick RJ. Magnetic resonance imaging at 3.0 Tesla: challenges and advantages in clinical neurological imaging. Invest Radiol. 2003;38:385–402. doi: 10.1097/00004424-200307000-00003.
    1. Takahashi M, Uematsu H, Hatabu H. MR imaging at high magnetic fields. Eur J Radiol. 2003;46:45–52. doi: 10.1016/S0720-048X(02)00331-5.
    1. Yamada K, Wu O, Gonzalez RG, Bakker D, Ostergaard L, Copen WA, Weisskoff RM, Rosen BR, Yagi K, Nishimura T, Sorensen AG. Magnetic resonance perfusion-weighted imaging of acute cerebral infarction: effect of the calculation methods and underlying vasculopathy. Stroke. 2002;33:87–94. doi: 10.1161/hs0102.101893.
    1. Fiehler J, Foth M, Kucinski T, Knab R, von Bezold M, Weiller C, Zeumer H, Rother J. Severe ADC decreases do not predict irreversible tissue damage in humans. Stroke. 2002;33:79–86. doi: 10.1161/hs0102.100884.
    1. Kidwell CS, Saver JL, Mattiello J, Starkman S, Vinuela F, Duckwiler G, Gobin YP, Jahan R, Vespa P, Kalafut M, Alger JR. Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging. Ann Neurol. 2000;47:462–469. doi: 10.1002/1531-8249(200004)47:4<462::AID-ANA9>;2-Y.
    1. Fiehler J, Knudsen K, Kucinski T, Kidwell CS, Alger JR, Thomalla G, Eckert B, Wittkugel O, Weiller C, Zeumer H, Rother J. Predictors of apparent diffusion coefficient normalization in stroke patients. Stroke. 2004;35:514–519. doi: 10.1161/01.STR.0000114873.28023.C2.
    1. Kane I, Carpenter T, Chappell F, Rivers C, Armitage P, Sandercock P, Wardlaw J. Comparison of 10 different magnetic resonance perfusion imaging processing methods in acute ischemic stroke: effect on lesion size, proportion of patients with diffusion/perfusion mismatch, clinical scores, and radiologic outcomes. Stroke. 2007;38:3158–3164. doi: 10.1161/STROKEAHA.107.483842.
    1. Parsons MW, Yang Q, Barber PA, Darby DG, Desmond PM, Gerraty RP, Tress BM, Davis SM. Perfusion magnetic resonance imaging maps in hyperacute stroke: relative cerebral blood flow most accurately identifies tissue destined to infarct. Stroke. 2001;32:1581–1587.
    1. Tomanek AI, Coutts SB, Demchuk AM, Hudon ME, Morrish WE, Sevick RJ, Simon JE, Frayne R, Buchan AM, Hill MD. MR angiography compared to conventional selective angiography in acute stroke. Can J Neurol Sci. 2006;33:58–62.

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