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      Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment

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          Abstract

          Introduction

          The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned.

          Methods

          62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded.

          Results

          Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome.

          Conclusions

          Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.

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          Most cited references23

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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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            The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. TIMI Study Group.

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              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.

              Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3-9 h after the onset of the symptoms of stroke in patients with presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI). In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (1:1:1) to 90 microg/kg desmoteplase, 125 microg/kg desmoteplase, or placebo within 3-9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0-2 points, and a Barthel index of 75-100. Secondary endpoints included change in lesion volume between baseline and day 30, rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT00111852. Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 microg/kg desmoteplase; 66 received 125 microg/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6-14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10.6 cm(3) and 52.5 cm(3), respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 microg/kg desmoteplase, 36% (24 of 66) for 125 microg/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 microg/kg desmoteplase 14.0% (0.5 cm(3)); 125 microg/kg desmoteplase 10.8% (0.3 cm(3)); placebo -10.0% (-0.9 cm(3)). The rates of symptomatic intracranial haemorrhage were 3.5% (2 of 57) for 90 microg/kg desmoteplase, 4.5% (3 of 66) for 125 microg/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% [3 of 57] for 90 microg/kg desmoteplase; 21% [14 of 66] for 125 microg/kg desmoteplase; and 6% [4 of 63] for placebo). The DIAS-2 study did not show a benefit of desmoteplase given 3-9 h after the onset of stroke. The high response rate in the placebo group could be explained by the mild strokes recorded (low baseline NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase. PAION Deutschland GmbH; Forest Laboratories.
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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, CA USA )
                1932-6203
                29 January 2016
                2016
                : 11
                : 1
                : e0147910
                Affiliations
                [1 ]Section of Neurology, Department of Biological, Psychiatric and Psychological Science, University of Ferrara, Ferrara, Italy
                [2 ]Section of Diagnostic Imaging, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
                [3 ]Neuroradiology Unit, Department of Neuroscience and Rehabilitation, Azienda Ospedaliera Universitaria, Ferrara, Italy
                [4 ]Neurology Unit, Department of Neuroscience and Rehabilitation, Azienda Ospedaliera Universitaria, Ferrara, Italy
                [5 ]Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
                [6 ]Imaging Research Lab, Robarts Research Institute, Western Ontario University, London, Ontario, Canada
                [7 ]Imaging program, Lawson Health Research Institute, Western Ontario University, London, Ontario, Canada
                National Cheng Kung University, TAIWAN
                Author notes

                Competing Interests: TYL licenses CT Perfusion software to and receives funding from GE Healthcare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: MP EF. Performed the experiments: MP AB CT EF. Analyzed the data: MP EF. Contributed reagents/materials/analysis tools: GR MB AS AD CA LB OM SC IC. Wrote the paper: MP CD TYL EF.

                Article
                PONE-D-15-28275
                10.1371/journal.pone.0147910
                4732987
                26824672
                923eded0-b62f-425b-8893-d01984e94841
                © 2016 Padroni et al

                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
                : 29 June 2015
                : 10 January 2016
                Page count
                Figures: 4, Tables: 5, Pages: 16
                Funding
                This work has been supported by Italian National Health System- Research Program entitled “Nuove conoscenze e problematiche assistenziali nell’ictus cerebrale: un Programma Strategico di Ricerca e Sviluppo” ex art. 12-12bis/D.Lgs n. 502/92, PG/2007/0293184. The authors would also like to thank the Canadian Stroke Network and European Stroke Network, Canadian Institutes of Health Research, Ontario Research Fund and GE Healthcare for partial support of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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