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Background: CT perfusion imaging (CTP) is used in the diagnostic workup of acute ischemic stroke (AIS). CTP may be performed within the angio suite using flat detector CT (FDCT) to help reduce patient management time. Purpose: In order to significantly improve FDCT perfusion (FDCTP) imaging, data‐processing algorithms need to be able to compensate for the higher levels of noise, slow rotation speed, and a lower frame rate of current FDCT devices. Methods: We performed a realistic simulation of FDCTP acquisition based on CTP data from seven subjects. We used the time separation technique (TST) as a model‐based approach for FDCTP data processing. We propose a novel dimension reduction in which we approximate the time attenuation curves by a linear combination of trigonometric functions. Our goal was to show that the TST can be used even without prior assumptions on the shape of the attenuation profiles. Results: We first demonstrated that a trigonometric basis is suitable for dimension reduction of perfusion data. Using simulated FDCTP data, we have shown that a trigonometric basis in the TST provided better results than the classical straightforward processing even with additional noise. Average correlation coefficients of perfusion maps were improved for cerebral blood flow (CBF), cerebral blood volume, mean transit time (MTT) maps. In a moderate noise scenario, the average Pearson's coefficient for the CBF map was improved using the TST from 0.76 to 0.81. For the MTT map, it was improved from 0.37 to 0.45. Furthermore, we achieved a total processing time from the reconstruction of FDCTP data to the generation of perfusion maps of under 5 min. Conclusions: In our study cohort, perfusion maps created from FDCTP data using the TST with a trigonometric basis showed equivalent perfusion deficits to classic CT perfusion maps. It follows, that this novel FDCTP technique has potential to provide fast and accurate FDCTP imaging for AIS patients. [ABSTRACT FROM AUTHOR]