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      Reliability of Visual Assessment of Non-Contrast CT, CT Angiography Source Images and CT Perfusion in Patients with Suspected Ischemic Stroke


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          Background and Purpose

          Good reliability of methods to assess the extent of ischemia in acute stroke is important for implementation in clinical practice, especially between observers with varying experience. Our aim was to determine inter- and intra-observer reliability of the 1/3 middle cerebral artery (MCA) rule and the Alberta Stroke Program Early CT Score (ASPECTS) for different CT modalities in patients suspected of acute ischemic stroke.


          We prospectively included 105 patients with acute neurological deficit due to suspected acute ischemic stroke within 9 hours after symptom onset. All patients underwent non-contrast CT, CT perfusion and CT angiography on admission. All images were evaluated twice for presence of ischemia, ischemia with >1/3 MCA involvement, and ASPECTS. Four observers evaluated twenty scans twice for intra-observer agreement. We used kappa statistics and intraclass correlation coefficient to calculate agreement.


          Inter-observer agreement for the 1/3 MCA rule and ASPECTS was fair to good for non-contrast CT, poor to good for CT angiography source images, but excellent for all CT perfusion maps (cerebral blood volume, mean transit time, and predicted penumbra and infarct maps). Intra-observer agreement for the 1/3 MCA rule and ASPECTS was poor to good for non-contrast CT, fair to moderate for CT angiography source images, and good to excellent for all CT perfusion maps.


          Between observers with a different level of experience, agreement on the radiological diagnosis of cerebral ischemia is much better for CT perfusion than for non-contrast CT and CT angiography source images, and therefore CT perfusion is a very reliable addition to standard stroke imaging.

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          Most cited references 23

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          Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke.

          Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra. One hundred and thirty patients with symptoms suggesting hemispheric stroke < or =12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard. The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml x 100 g(-1). In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.
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            Acute stroke: usefulness of early CT findings before thrombolytic therapy.

            To determine whether the extent of subtle parenchymal hypoattenuation detected on computed tomographic (CT) scans obtained within 6 hours of ischemic stroke is a factor in predicting patients' response to thrombolytic treatment. The baseline CT scans of 620 patients, who received either recombinant tissue plasminogen activator (rt-PA) or a placebo, in a double-blind, randomized multicenter trial were prospectively evaluated and assigned to one of three categories according to the extent of parenchymal hypoattenuation: none, 33% or less (small), or more than 33% (large) of the middle cerebral artery territory. The association between the extent of hypoattenuation on the baseline CT scans and the clinical outcome in the placebo-treated and the rt-PA-treated groups after 3 months was analyzed. In 215 patients with a small hypoattenuating area, treatment increased the chance of good outcome. In 336 patients with a normal CT scan and in 52 patients with a large hypoattenuating area, rt-PA had no beneficial effect but increased the risk for fatal brain hemorrhage. The response to rt-PA in patients with ischemic stroke can be predicted on the basis of initial CT findings of the extent of parenchymal hypoattenuation in the territory of the middle cerebral artery.
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              Systematic comparison of perfusion-CT and CT-angiography in acute stroke patients.

              To systematically evaluate the accuracy of noncontrast computed tomography (NCT), perfusion computed tomography (PCT), and computed tomographic angiography (CTA) in determining site of occlusion, infarct core, salvageable brain tissue, and collateral flow in a large series of patients suspected of acute stroke. We retrospectively identified all consecutive patients with signs and symptoms suggesting hemispheric stroke of < 48 hours in duration who were evaluated on admission by NCT, PCT, and CTA, and underwent a follow-up CT/CTA or magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) within 6 months of initial imaging. Two neuroradiologists evaluated NCT for hypodensity, PCT for infarct core and salvageable brain tissue, and CTA source images and maximal intensity projections for site of occlusion, infarct core, and collateral flow. Follow-up CTA and MRA were assessed for persistent arterial occlusion or recanalization. Follow-up CT and MRI were reviewed for final infarct location and volume, and used as a gold standard to calculate sensitivity (SE) and specificity (SP) of initial imaging. A total of 113 patients were considered for analysis, including 55 patients with a final diagnosis of stroke. CTA source images were the most accurate technique in the detection of the site of occlusion (SE = 95%; SP = 100%). Decreased cerebral blood volume on PCT was the most accurate predictor of final infarct volume (SE = 80%; SP = 97%), Increased mean transit time on PCT was predictive of the tissue at risk for infarction in patients with persistent arterial occlusion. CTA maximal intensity projections was the best technique to quantify the degree of collateral circulation. The most accurate assessment of the site of occlusion, infarct core, salvageable brain tissue, and collateral circulation in patients suspected of acute stroke is afforded by a combination of PCT and CTA.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                8 October 2013
                : 8
                : 10
                [1 ]Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
                [2 ]Department of Neurology, Utrecht Stroke Center, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
                [3 ]Department of Radiology, Rijnstate Hospital, Arnhem, The Netherlands
                [4 ]Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
                University of Cambridge, United Kingdom
                Author notes

                ¶ Membership of the DUST Investigators is provided in the Acknowledgments

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: TvS GJB WPTMM LJK YvdG BKV. Performed the experiments: TvS JMN ICvdS JWD ADH BKV. Analyzed the data: TvS YvdG BKV. Contributed reagents/materials/analysis tools: WPTMM YvdG BKV. Wrote the paper: TvS GJB LJK YvdG BKV.


                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.

                Page count
                Pages: 6
                This study was supported by a grant from the Dutch Heart Foundation (grant 2008T034; http://www.hartstichting.nl) and the NutsOhra Foundation (grant 0903-012; http://www.stichtingnutsohra.nl). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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