Objective: Advanced neuroimaging has proved to be pivotal in the management of acute ischemic stroke. The use of CT perfusion (CTP) core and penumbra parameters to predict the outcome in wake-up stroke (WUS) patients in everyday clinical scenarios has not yet been investigated. The aim of our study was to investigate the predictive power of CTP parameters on functional and morphological outcomes in WUS patients treated with recombinant tissue plasminogen activator (rTPA). Approach: We analyzed clinical data and processed CTP images of 83 consecutive WUS patients treated with rTPA. The predictive power of whole-brain CTP features and of the clinical stroke-related parameters to predict the National Institutes of Health Stroke Scale (NIHSS) score at the seventh day and ischemic lesion volume outcome was investigated by means of multivariate regression analysis as well as least absolute shrinkage and selection operator (LASSO) modeling. Main results: Multivariate analysis showed that CTP core volume (β = 0.403, p = 0.000), NIHSS at admission (β = 0.323, p = 0.005) and Alberta Stroke Program Early CT (ASPECT) score (β = -0.224, p = 0.012) predict NIHSS at 7 days, while total hypoperfused volume (β = 0.542, p = 0.000) and core volume on CTP (β =0.441, p = 0.000) predict infarct lesion volume at follow-up CT. The LASSO modeling approach confirmed the significant predictive power of CTP core volume, total hypoperfused CTP volume, NIHSS at baseline and ASPECT score, producing a sparse model with adequate reliability (the root mean square error on a previously unseen testing dataset was 3.68). Significance: Our findings highlight the importance of CT multimodal imaging features for decision-making and prediction in the hyperacute phase of WUS. The predictive model supports the hypothesis that an irreversible necrotic core rather than the extent of the penumbra is the main prognostic factor in WUS patients treated with rTPA.
