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      DWI Intensity Values Predict FLAIR Lesions in Acute Ischemic Stroke

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          Abstract

          Background and Purpose

          In acute stroke, the DWI-FLAIR mismatch allows for the allocation of patients to the thrombolysis window (<4.5 hours). FLAIR-lesions, however, may be challenging to assess. In comparison, DWI may be a useful bio-marker owing to high lesion contrast. We investigated the performance of a relative DWI signal intensity (rSI) threshold to predict the presence of FLAIR-lesions in acute stroke and analyzed its association with time-from-stroke-onset.

          Methods

          In a retrospective, dual-center MR-imaging study we included patients with acute stroke and time-from-stroke-onset ≤12 hours (group A: n = 49, 1.5T; group B: n = 48, 3T). DW- and FLAIR-images were coregistered. The largest lesion extent in DWI defined the slice for further analysis. FLAIR-lesions were identified by 3 raters, delineated as regions-of-interest (ROIs) and copied on the DW-images. Circular ROIs were placed within the DWI-lesion and labeled according to the FLAIR-pattern (FLAIR+ or FLAIR−). ROI-values were normalized to the unaffected hemisphere. Adjusted and nonadjusted receiver-operating-characteristics (ROC) curve analysis on patient level was performed to analyze the ability of a DWI- and ADC-rSI threshold to predict the presence of FLAIR-lesions. Spearman correlation and adjusted linear regression analysis was performed to assess the relationship between DWI-intensity and time-from-stroke-onset.

          Results

          DWI-rSI performed well in predicting lesions in FLAIR-imaging (mean area under the curve (AUC): group A: 0.84; group B: 0.85). An optimal mean DWI-rSI threshold was identified (A: 162%; B: 161%). ADC-maps performed worse (mean AUC: A: 0.58; B: 0.77). Adjusted regression models confirmed the superior performance of DWI-rSI. Correlation coefficents and linear regression showed a good association with time-from-stroke-onset for DWI-rSI, but not for ADC-rSI.

          Conclusion

          An easily assessable DWI-rSI threshold identifies the presence of lesions in FLAIR-imaging with good accuracy and is associated with time-from-stroke-onset in acute stroke. This finding underlines the potential of a DWI-rSI threshold as a marker of lesion age.

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          Most cited references20

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          Index for rating diagnostic tests.

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            DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4·5 h of symptom onset (PRE-FLAIR): a multicentre observational study.

            Many patients with stroke are precluded from thrombolysis treatment because the time from onset of their symptoms is unknown. We aimed to test whether a mismatch in visibility of an acute ischaemic lesion between diffusion-weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI (DWI-FLAIR mismatch) can be used to detect patients within the recommended time window for thrombolysis. In this multicentre observational study, we analysed clinical and MRI data from patients presenting between Jan 1, 2001, and May 31, 2009, with acute stroke for whom DWI and FLAIR were done within 12 h of observed symptom onset. Two neurologists masked to clinical data judged the visibility of acute ischaemic lesions on DWI and FLAIR imaging, and DWI-FLAIR mismatch was diagnosed by consensus. We calculated predictive values of DWI-FLAIR mismatch for the identification of patients with symptom onset within 4·5 h and within 6 h and did multivariate regression analysis to identify potential confounding covariates. This study is registered with ClinicalTrials.gov, number NCT01021319. The final analysis included 543 patients. Mean age was 66·0 years (95% CI 64·7-67·3) and median National Institutes of Health Stroke Scale score was 8 (IQR 4-15). Acute ischaemic lesions were identified on DWI in 516 patients (95%) and on FLAIR in 271 patients (50%). Interobserver agreement for acute ischaemic lesion visibility on FLAIR imaging was moderate (κ=0·569, 95% CI 0·504-0·634). DWI-FLAIR mismatch identified patients within 4·5 h of symptom onset with 62% (95% CI 57-67) sensitivity, 78% (72-84) specificity, 83% (79-88) positive predictive value, and 54% (48-60) negative predictive value. Multivariate regression analysis identified a longer time to MRI (p<0·0001), a lower age (p=0·0009), and a larger DWI lesion volume (p=0·0226) as independent predictors of lesion visibility on FLAIR imaging. Patients with an acute ischaemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomised trial of thrombolysis in patients with unknown time of symptom onset. Else Kröner-Fresenius-Stiftung, National Institutes of Health. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Acute human stroke studied by whole brain echo planar diffusion-weighted magnetic resonance imaging.

              Our purpose was to use whole brain echo planar magnetic resonance imaging (MRI) to identify and characterize diffusion abnormalities in acute cerebral ischemia. We studied 40 patients as early as 3 hours after onset of signs and symptoms of cerebral ischemia. Diffusion-weighted imaging (DWI) of the entire brain could be completed in 3 seconds or, using seven different diffusion sensitivities (maximum b = 1,271 sec/mm2), in 48 seconds. Measurements and synthetic maps were made of apparent diffusion coefficients (ADC), a physiological parameter that characterizes the self-diffusion of water in tissue. Early ischemic lesions were identified with DWI as hyperintense regions of decreased ADC in all patients who subsequently developed infarction, before changes were evident on conventional MRI in cases studied earlier than 6 hours after onset of ischemic symptoms. Lesions as small as 4 mm in diameter were identified. The extent of lesions within white matter was best defined by controlling for the anisotropic effect of axonal orientation. The mean ADC (+/- SD) for control regions in the 36 patients was 9.15 (+/- 2.91) x 10(-4) mm2/sec. Mean ADC of ischemic regions was 56% of control values at 6 hours or less and stayed significantly reduced for 3 to 4 days after onset of ischemia. The relative ADC increased progressively over time to be pseudonormalized at 5 to 10 days and elevated in the chronic state, making the distinction of acute lesions adjacent to chronic infarcts readily apparent. DWI with echo planar imaging measures a unique physiological parameter that is sensitive to ischemic changes before conventional MRI. Its potential role in the quantitative study of human stroke pathophysiology and therapeutics is the subject of further investigation.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                21 March 2014
                : 9
                : 3
                : e92295
                Affiliations
                [1 ]Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin, Berlin, Germany
                [2 ]Max-Planck-Institute for Neurological Research, Cologne, Germany
                [3 ]Fraunhofer MEVIS, Bremen, Germany
                [4 ]Department of Radiology, Krankenhaus Ludmillenstift, Meppen, Germany
                [5 ]Department of Neurology, Charité-Universtitätsmedizin, Berlin, Germany
                [6 ]Department for Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany
                INSERM U894, Centre de Psychiatrie et Neurosciences, Hopital Sainte-Anne and Université Paris 5, France
                Author notes

                Competing Interests: The authors have read the journal's policy and make the following disclosures: JBF reports the following board memberships, consultancies and/or payments for lectures including service on speakers bureaus: Boehringer-Ingelheim, Lundbeck, Siemens, Sygnis, and Synarc. JS reports the following board memberships, consultancies and/or payments for lectures including service on speakers bureaus: Boehringer-Ingelheim, Bayer, Pfizer and Maquet. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: VIM IG WM ME JBF JS. Performed the experiments: VIM IG OZW JBF JS. Analyzed the data: VIM IG UG AS SZM FCvS KLS MAM. Wrote the paper: VIM IG OZW FCvS WM ME JBF JS UG.

                Article
                PONE-D-13-25670
                10.1371/journal.pone.0092295
                3962388
                24658092
                4c9207cf-550d-49f6-b41b-fc25dfad2bc3
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 June 2013
                : 21 February 2014
                Page count
                Pages: 9
                Funding
                The research leading to these results has received funding from the German Federal Ministry of Education and Research via the grant “Center for Stroke Research Berlin” (01 EO 0801; http://www.bmbf.de). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Medicine and Health Sciences
                Vascular Medicine
                Stroke
                Ischemic Stroke
                Cardiology
                Acute Cardiovascular Problems
                Critical Care and Emergency Medicine
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Neurology
                Cerebrovascular Diseases
                Radiology and Imaging

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                Uncategorized

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