BackgroundThe aim of this work was to assess the robustness of cardiac SPECT radiomic features against changes in imaging settings, including acquisition, and reconstruction parameters. MethodsFour commercial SPECT and SPECT/CT cameras were used to acquire images of a static cardiac phantom mimicking typical myorcardial perfusion imaging using 185 MBq of 99mTc. The effects of different image acquisition and reconstruction parameters, including number of views, view matrix size, attenuation correction, as well as image reconstruction related parameters (algorithm, number of iterations, number of subsets, type of post-reconstruction filter, and its associated parameters, including filter order and cut-off frequency) were studied. In total, 5,063 transverse views were reconstructed by varying the aforementioned factors. Eighty-seven radiomic features including first-, second-, and high-order textures were extracted from these images. To assess reproducibility and repeatability, the coefficient of variation (COV), as a widely adopted metric, was measured for each of the radiomic features over the different imaging settings. ResultsThe Inverse Difference Moment Normalized (IDMN) and Inverse Difference Normalized (IDN) features from the Gray Level Co-occurrence Matrix (GLCM), Run Percentage (RP) from the Gray Level Co-occurrence Matrix (GLRLM), Zone Entropy (ZE) from the Gray Level Size Zone Matrix (GLSZM), and Dependence Entropy (DE) from the Gray Level Dependence Matrix (GLDM) feature sets were the only features that exhibited high reproducibility (COV ≤ 5%) against changes in all imaging settings. In addition, Large Area Low Gray Level Emphasis (LALGLE), Small Area Low Gray Level Emphasis (SALGLE) and Low Gray Level Zone Emphasis (LGLZE) from GLSZM, and Small Dependence Low Gray Level Emphasis (SDLGLE) from GLDM feature sets turned out to be less reproducible (COV > 20%) against changes in imaging settings. The GLRLM (31.88%) and GLDM feature set (54.2%) had the highest (COV < 5%) and lowest (COV > 20%) number of the reproducible features, respectively. Matrix size had the largest impact on feature variability as most of the features were not repeatable when matrix size was modified with 82.8% of them having a COV > 20%. ConclusionThe repeatability and reproducibility of SPECT/CT cardiac radiomic features under different imaging settings is feature-dependent. Different image acquisition and reconstruction protocols have variable effects on radiomic features. The radiomic features exhibiting low COV are potential candidates for future clinical studies.