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The objective of this study was to assess the feasibility and safety of krypton ventilation imaging with intraindividual comparison to xenon ventilation computed tomography (CT).In a first step, attenuation of different concentrations of xenon and krypton was analyzed in a phantom setting. Thereafter, 7 male New Zealand white rabbits (4.4–6.0 kg) were included in an animal study. After orotracheal intubation, an unenhanced CT scan was obtained in end-inspiratory breath-hold. Thereafter, xenon- (30%) and krypton-enhanced (70%) ventilation CT was performed in random order. After a 2-minute wash-in of gas A, CT imaging was performed. After a 45-minute wash-out period and another 2-minute wash-in of gas B, another CT scan was performed using the same scan protocol. Heart rate and oxygen saturation were measured. Unenhanced and krypton or xenon data were registered and subtracted using a nonrigid image registration tool. Enhancement was quantified and statistically analyzed.One animal had to be excluded from data analysis owing to problems during intubation. The CT scans in the remaining 6 animals were completed without complications. There were no relevant differences in oxygen saturation or heart rate between the scans. Xenon resulted in a mean increase of enhancement of 35.3 ± 5.5 HU, whereas krypton achieved a mean increase of 21.9 ± 1.8 HU in enhancement (P = 0.0055).The use of krypton for lung ventilation imaging appears to be feasible and safe. Despite the use of a markedly higher concentration of krypton, enhancement is significantly worse when compared with xenon CT ventilation imaging, but sufficiently high for CT ventilation imaging studies.