Open Access Highly Accessed Study protocol

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

Benjamin Hotter1, Sandra Pittl1, Martin Ebinger1, Gabriele Oepen1, Kati Jegzentis1, Kohsuke Kudo2, Michal Rozanski1, Wolf U Schmidt1, Peter Brunecker1, Chao Xu1, Peter Martus3, Matthias Endres1, Gerhard J Jungehülsing1, Arno Villringer1 and Jochen B Fiebach1*

Author Affiliations

1 Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany

2 Advanced Medical Research Center, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan

3 Institute of Biometrics and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany

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BMC Neurology 2009, 9:60  doi:10.1186/1471-2377-9-60

Published: 8 December 2009



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.


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 NCT00715533