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Background: Although the spot sign is a strong predictor of hematoma expansion, there is no accepted consensus on the timing of CTA acquisition, mainly because its pathophysiologic significance is uncertain. We investigated the yield of the spot sign in the prediction of hematoma expansion and its pathophysiological underpinnings using multiphase CTA.Methods: Single-center prospective observational cohort study of 123 consecutive patients with acute (<6 hours) ICH. Patients underwent multiphase CTA performed in 3 automated phases after contrast dye injection (delay of 8, 4, and 15 seconds, respectively). According to spot sign positivity in the 3 phases, patients were categorized into 1 of 4 patterns: A (+/+/-), B (+/+/+), C (-/+/+), and D (-/-/+). Outcomes included frequency of the spot sign, significant hematoma expansion at 24 hours (>33% or >6 mL, primary outcome), and absolute hematoma growth.Results: The frequency of the spot sign was higher the later the phase of CTA was: 29.3% in phase 1, 43.1% in 2, and 46.3% in 3 (P<0.001). The presence of the spot sign in phase 1, 2, 3, or any phase was related to significant hematoma expansion (P<0.001 for all comparisons). Predictive values varied depending on the CTA phase, with highest PPV observed in phase 1 (63%) and highest NPV in phase 2 (88.9%). Onset to imaging time was not significantly lower the more arterial the pattern of spot sign presentation was (Figure). The frequency of significant hematoma expansion was higher the earlier the pattern of spot sign presentation: A 100%, B 59.1%, C 40%, and D 0% (P=0.013). Absolute hematoma growth analysis showed a hierarchical distribution of patterns of spot sign presentation: A > B > C > D > no spot sign (P=0.003, Figure).Conclusions: Multiphase CTA improves hematoma expansion prediction and might provide additional information on the pathophysiology of the spot sign. Arterial spot signs may represent the point of active hemorrhage, and venous spot signs the site of resolved bleeding.