(1) Background: To test the accuracy of a fully automated stroke tissue estimation algorithm (FASTER) to predict final lesion volumes in an independent dataset in patients with acute stroke; (2) Methods: Tissue-at-risk prediction was performed in 31 stroke patients presenting with a proximal middle cerebral artery occlusion. FDA-cleared perfusion software using the AHA recommendation for the Tmax threshold delay was tested against a prediction algorithm trained on an independent perfusion software using artificial intelligence (FASTER). Following our endovascular strategy to consequently achieve TICI 3 outcome, we compared patients with complete reperfusion (TICI 3) vs. no reperfusion (TICI 0) after mechanical thrombectomy. Final infarct volume was determined on a routine follow-up MRI or CT at 90 days after the stroke; (3) Results: Compared to the reference standard (infarct volume after 90 days), the decision forest algorithm overestimated the final infarct volume in patients without reperfusion. Underestimation was observed if patients were completely reperfused. In cases where the FDA-cleared segmentation was not interpretable due to improper definitions of the arterial input function, the decision forest provided reliable results; (4) Conclusions: The prediction accuracy of automated tissue estimation depends on (i) success of reperfusion, (ii) infarct size, and (iii) software-related factors introduced by the training sample. A principal advantage of machine learning algorithms is their improved robustness to artifacts in comparison to solely threshold-based model-dependent software. Validation on independent datasets remains a crucial condition for clinical implementations of decision support systems in stroke imaging.
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