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Introduction: Assessment of tissue viability, usually performed by multimodal neuroimaging, allows the use of reperfusion therapies in selected patients, even out of the therapeutic time-window. However, multimodal imaging is still a scarce and expensive tool. The availability of blood biomarkers reflecting tissue viability could be a useful tool to manage reperfusion therapies. We aimed to test whether selected candidate biomarkers may reflect tissue viability in relation to Alberta Stroke Program Early CT score (ASPECTS) and multimodal imaging.Methods: The StrokeChip was a prospective, observational study, conducted at six Hospitals in Catalonia. Patients with suspected stroke were enrolled at Emergency Departments. Blood samples were obtained within the first six hours after symptoms onset to measure a 21-biomarker panel. Acute brain neuroimaging was dichotomized into normal (ASPECTS=10) or pathological (ASPECTS<10). For those patients with perfusion imaging, comparison was performed between patients with and without significant mismatch (>20%).Results: From August-2012 to December-2013, 941 out of 1308 patients were ischemic strokes. ASPECTS was obtained in admission neuroimaging in 927 patients. Among them, 25% displayed pathological neuroimaging. Levels of Apo-CIII disclosed a positive correlation with ASPECTS, while negative correlations were found for D-dimer, IL-6, GroA, NT-proBNP and IGFBP-3. In logistic regression analysis, Apo-CIII [OR=0.52(0.36-0.75)], D-dimer [OR=2.47(1.39-4.39)] and IGFBP-3 [OR=2.28(1.51-3.43)] were independently associated with ASPECTS <10, after adjustment by age, sex and NIHSS. Moreover, in 103 patients with baseline perfusion imaging (70% with mismatch >20%), Apo-CIII was an independent predictor of the presence of mismatch after adjustment by age, sex and NIHSS [OR=0.27(0.10-0.75)].Conclusions: Assessment of tissue viability with blood biomarkers seems feasible. Apo-CIII might represent a surrogate marker for tissue viability assessment.