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(1) To explore the potential impact of an AI dual-energy CT (DECT) prototype on decision making and workflows by investigating its capabilities to differentiate COVID-19 from immunotherapy-related pneumonitis. (2) Methods: From 3 April 2020 to 12 February 2021, DECT from biometrically matching patients with COVID-19, pneumonitis, and inconspicuous findings were selected from our clinical routine. Three blinded readers independently scored each pulmonary lobe analogous to CO-RADS. Inter-rater agreement was determined with an intraclass correlation coefficient (ICC). Averaged perfusion metrics per lobe (iodine uptake in mg, volume without vessels in ml, iodine concentration in mg/mL) were extracted using manual segmentation and an AI DECT prototype. A generalized linear mixed model was used to investigate metric validity and potential distinctions at equal CO-RADS scores. Multinomial regression measured the contribution “Reader”, “CO-RADS score”, and “perfusion metrics” to diagnosis. The time to diagnosis was measured for manual vs. AI segmentation. (3) Results: We included 105 patients (62 ± 13 years, mean BMI 27 ± 2). There were no significant differences between manually and AI-extracted perfusion metrics (p = 0.999). Regardless of the CO-RADS score, iodine uptake and concentration per lobe were significantly higher in COVID-19 than in pneumonitis (p &lt; 0.001). In regression, iodine uptake had a greater contribution to diagnosis than CO-RADS scoring (Odds Ratio (OR) = 1.82 [95%CI 1.10–2.99] vs. OR = 0.20 [95%CI 0.14–0.29]). The AI prototype extracted the relevant perfusion metrics significantly faster than radiologists (10 ± 1 vs. 15 ± 2 min, p &lt; 0.001). (4) Conclusions: The investigated AI prototype positively impacts decision making and workflows by extracting perfusion metrics that differentiate COVID-19 from visually similar pneumonitis significantly faster than radiologists.

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AI Lung Segmentation and Perfusion Analysis of Dual-Energy CT Can Help to Distinguish COVID-19 Infiltrates from Visually Similar Immunotherapy-Related Pneumonitis Findings and Can Optimize Radiological Workflows