Previously, we developed an "activity painting" tool for PET image simulation; however, it could simulate heterogeneous patterns only in the air. We aimed to improve this phantom technique to simulate arbitrary lesions in a radioactive background to perform relevant multi-center radiomic analysis. We conducted measurements moving a 22Na point source in a 20-liter background volume filled with 5 kBq/mL activity with an adequately controlled robotic system to prevent the surge of the water. Three different lesion patterns were "activity-painted" in five PET/CT cameras, resulting in 8 different reconstructions. We calculated 46 radiomic indeces (RI) for each lesion and imaging setting, applying absolute and relative discretization. Reproducibility and reliability were determined by the inter-setting coefficient of variation (CV) and the intraclass correlation coefficient (ICC). Hypothesis tests were used to compare RI between lesions. By simulating precisely the same lesions, we confirmed that the reconstructed voxel size and the spatial resolution of different PET cameras were critical for higher order RI. Considering conventional RIs, the SUVpeak and SUVmean proved the most reliable (CV<10%). CVs above 25% are more common for higher order RIs, but we also found that low CVs do not necessarily imply robust parameters but often rather insensitive RIs. Based on the hypothesis test, most RIs could clearly distinguish between the various lesions using absolute resampling. ICC analysis also revealed that most RIs were more reproducible with absolute discretization. The activity painting method in a real radioactive environment proved suitable for precisely detecting the radiomic differences derived from the different camera settings and texture characteristics. We also found that inter-setting CV is not an appropriate metric for analyzing RI parameters’ reliability and robustness. Although multicentric cohorts are increasingly common in radiomics analysis, realistic texture phantoms can provide indispensable information on the sensitivity of an RI and how an individual RI parameter measures the texture.
