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Introduction: Alberta Stroke Program Early CT Score (ASPECTS) is a validated clinical tool to predict early ischemic changes in acute ischemic stroke (AIS). In addition to scoring of non-contrast brain CT images (CT), head CT angiogram source images (CTA) have also been demonstrated as useful for scoring. We hypothesized that CTA ASPECTS would show superior inter-rater reliability as compared to CT ASPECTS, and that both would perform better in the setting of the favorable target mismatch (TM) profile on CT perfusion imaging (CTP).Methods: We reviewed AIS patients from 2010-2014 with an acute M1 middle cerebral artery occlusion that underwent CT, CTA, and CTP imaging at hospital admission. CT and CTA were independently scored by two experienced physician raters using the standard ASPECTS methodology. Inter-rater agreement was calculated with a weighted kappa. The cohort was then further stratified into either favorable or non-favorable TM profiles using volumetric measurements from the Olea Sphere software and the DEFUSE-3 definition of TM.Results: We included 68 patients. The mean±SD age was 62±18 years. 60% were men. The mean NIH stroke scale was 14.5±7.9. The median (IQR) follow-up modified Rankin Scale (mRS) was 3 (1,6). 37 of 68 (54%) patients had the TM profile and were significantly more likely to have lower follow-up mRS scores (z=3.5, p<0.001). Inter-rater agreement of CTA ASPECTS (kappa=0.82) was superior to CT ASPECTS (kappa=0.76). Patients with the TM profile demonstrated more reliable agreement on both CTA and CT ASPECTS scoring systems (kappa=0.79, 0.78), compared to those without the TM profile (kappa=0.71, 0.75).Discussion: We found that inter-rater agreement was higher for CTA ASPECTS as compared to CT ASPECTS and that both performed better in patents with the TM profile. Clinically this is important because it reaffirms the utility of CTA ASPECTS in this population of patients in which high reliability is paramount, as ASPECTS is often used in medical decision making when determining eligibility for medical and/or endovascular thrombolytic therapies.