Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

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Background and Purpose-We sought to assess whether the volume of the ischemic penumbra can be estimated more accurately by altering the threshold selected for defining perfusion-weighting imaging (PWI) lesions. Methods-DEFUSE is a multicenter study in which consecutive acute stroke patients were treated with intravenous tissue-type plasminogen activator 3 to 6 hours after stroke onset. Magnetic resonance imaging scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Baseline and posttreatment PWI volumes were defined according to increasing Tmax delay thresholds (Ͼ2, Ͼ4, Ͼ6, and Ͼ8 seconds). Penumbra salvage was defined as the difference between the baseline PWI lesion and the final infarct volume (30-day fluid-attenuated inversion recovery sequence). We hypothesized that the optimal PWI threshold would provide the strongest correlations between penumbra salvage volumes and various clinical and imaging-based outcomes. Results-Thirty-three patients met the inclusion criteria. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by Tmax Ͼ6 seconds versus Tmax Ͼ2 seconds, as was the difference in median penumbra salvage volume in patients with a favorable versus an unfavorable clinical response. Among patients who did not experience early reperfusion, the Tmax Ͼ4 seconds threshold provided a more accurate prediction of final infarct volume than the Ͼ2 seconds threshold. Conclusions-Defining PWI lesions based on a stricter Tmax threshold than the standard Ͼ2 seconds delay appears to provide more a reliable estimate of the volume of the ischemic penumbra in stroke patients imaged between 3 and 6 hours after symptom onset. A threshold between 4 and 6 seconds appears optimal for early identification of critically hypoperfused tissue.

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Diffusion-weighted imaging (DWI) is commonly used to assess irreversibly infarcted tissue but its accuracy is challenged by reports of diffusion lesion reversal (DLR). We investigated the frequency and implications for mismatch classification of DLR using imaging from the EPITHET (Echoplanar Imaging Thrombolytic Evaluation Trial) and DEFUSE (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) studies. In 119 patients (83 treated with IV tissue plasminogen activator), follow-up images were coregistered to acute diffusion images and the lesions manually outlined to their maximal visual extent in diffusion space. Diffusion lesion reversal was defined as voxels of acute diffusion lesion that corresponded to normal brain at follow-up (i.e., final infarct, leukoaraiosis, and cerebrospinal fluid (CSF) voxels were excluded from consideration). The appearance of DLR was visually checked for artifacts, the volume calculated, and the impact of adjusting baseline diffusion lesion volume for DLR volume on perfusion-diffusion mismatch analyzed. Median DLR volume reduced from 4.4 to 1.5 mL after excluding CSF/leukoaraiosis. Visual inspection verified 8/119 (6.7%) with true DLR, median volume 2.33 mL. Subtracting DLR from acute diffusion volume altered perfusion-diffusion mismatch (T max > 6 seconds, ratio > 1.2) in 3/119 (2.5%) patients. Diffusion lesion reversal between baseline and 3 to 6 hours DWI was also uncommon (7/65, 11%) and often transient. Clinically relevant DLR is uncommon and rarely alters perfusion-diffusion mismatch. The acute diffusion lesion is generally a reliable signature of the infarct core.

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Background MRI-based selection of patients for acute stroke interventions requires rapid accurate estimation of the infarct core on diffusion-weighted MRI (DWI). Typically used manual methods to delineate DWI lesions are subjective and time-consuming. These limitations would be overcome by a fully automated method that can rapidly and objectively delineate the ischemic core. An automated method would require pre-defined criteria to identify the ischemic core. Aim To determine Apparent Diffusion Coefficient (ADC) based criteria that can be implemented in a fully automated software solution for identification of the ischemic core. Methods Imaging data from patients enrolled in the DEFUSE study who had early revascularization following tPA treatment, was included. The patients’ baseline DWI and 30-day FLAIR lesions were manually delineated after co-registration. Parts of the DWI lesion that corresponded with 30-day infarct were considered ischemic core, whereas parts that corresponded with normal brain parenchyma at 30 days were considered non-core. The optimal ADC threshold to discriminate core from non-core voxels was determined by voxel-based ROC analysis using the Youden index. Results 51045 DWI positive voxels from 14 patients who met eligibility criteria were analyzed. The mean DWI lesion volume was 24(±23) mL. Of this, 18(±22) mL was ischemic core and 3(±5) mL was non-core. The remainder corresponded to pre-existing gliosis, CSF, or was lost to post-infarct atrophy. The ADC of core was lower than that of non-core voxels (p<0.0001). The optimal threshold for identification of ischemic core was an ADC ≤620 ×10−6 mm2/s (sensitivity 69% and specificity 78%). Conclusions Our data suggests the ischemic core can be identified with an absolute ADC threshold. This threshold can be implemented in image analysis software for fully automated segmentation of the ischemic core.

Objectives: Stroke risk immediately after TIA defined by time-based criteria is high, and prognostic scores (ABCD2 and ABCD3-I) have been developed to assist management. The American Stroke Association has proposed changing the criteria for the distinction between TIA and stroke from time-based to tissue-based. Research using these definitions is lacking. In a multicenter observational cohort study, we have investigated prognosis and performance of the ABCD2 score in TIA, subcategorized as tissue-positive or tissue-negative on diffusion-weighted imaging (DWI) or CT imaging according to the newly proposed criteria.Methods: Twelve centers provided data on ABCD2 scores, DWI or CT brain imaging, and follow-up in cohorts of patients with TIA diagnosed by time-based criteria. Stroke rates at 7 and 90 days were studied in relation to tissue-positive or tissue-negative subcategorization, according to the presence or absence of brain infarction. The predictive power of the ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses.Results: A total of 4,574 patients were included. Among DWI patients (n ϭ 3,206), recurrent stroke rates at 7 days were 7.1% (95% confidence interval 5.5-9.1) after tissue-positive and 0.4% (0.2-0.7) after tissue-negative events (p diff Ͻ 0.0001). Corresponding rates in CT-imaged patients were 12.8% (9.3-17.4) and 3.0% (2.0-4.