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The purpose of this study was to evaluate the impact of ultralow radiation dose single-energy computed tomographic (CT) acquisitions with Sn prefiltration and third-generation iterative reconstruction on density-based quantitative measures of growing interest in phenotyping pulmonary disease.The effects of both decreasing dose and different body habitus on the accuracy of the mean CT attenuation measurements and the level of image noise (SD) were evaluated using the COPDGene 2 test object, containing 8 different materials of interest ranging from air to acrylic and including various density foams. A third-generation dual-source multidetector CT scanner (Siemens SOMATOM FORCE; Siemens Healthcare AG, Erlangen, Germany) running advanced modeled iterative reconstruction (ADMIRE) software (Siemens Healthcare AG) was used.We used normal and very large body habitus rings at dose levels varying from 1.5 to 0.15 mGy using a spectral-shaped (0.6-mm Sn) tube output of 100 kV(p). Three CT scans were obtained at each dose level using both rings. Regions of interest for each material in the test object scans were automatically extracted. The Hounsfield unit values of each material using weighted filtered back projection (WFBP) at 1.5 mGy was used as the reference value to evaluate shifts in CT attenuation at lower dose levels using either WFBP or ADMIRE. Statistical analysis included basic statistics, Welch t tests, multivariable covariant model using the F test to assess the significance of the explanatory (independent) variables on the response (dependent) variable, and CT mean attenuation, in the multivariable covariant model including reconstruction method.Multivariable regression analysis of the mean CT attenuation values showed a significant difference with decreasing dose between ADMIRE and WFBP. The ADMIRE has reduced noise and more stable CT attenuation compared with WFBP. There was a strong effect on the mean CT attenuation values of the scanned materials for ring size (P < 0.0001) and dose level (P < 0.0001). The number of voxels in the region of interest for the particular material studied did not demonstrate a significant effect (P > 0.05). The SD was lower with ADMIRE compared with WFBP at all dose levels and ring sizes (P < 0.05).The third-generation dual-source CT scanners using third-generation iterative reconstruction methods can acquire accurate quantitative CT images with acceptable image noise at very low-dose levels (0.15 mGy). This opens up new diagnostic and research opportunities in CT phenotyping of the lung for developing new treatments and increased understanding of pulmonary disease.