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Simple Summary  Handcrafted radiomic features (HRFs) are quantitative features extracted from medical images, and they are mined for associations with different clinical endpoints. While many studies reported on the potential of HRFs to unravel clinical endpoints, the sensitivity of HRFs to variations in scanning parameters is affecting the inclusion of radiomic signatures in clinical decision-making. In this study, we investigated the effects of variations in the in-plane resolution of scans, while all other scanning parameters were fixed. Moreover, we investigated the effects of ten different image resampling methods and ComBat harmonization on the reproducibility of HRFs. Our results show that the majority of HRFs are significantly and variably affected by the differences in in-plane resolution. The majority of image resampling methods resulted in a higher number of reproducible HRFs compared to ComBat harmonization. Our developed framework guides identifying the reproducible and harmonizable HRFs in different scenarios.    Abstract  While handcrafted radiomic features (HRFs) have shown promise in the field of personalized medicine, many hurdles hinder its incorporation into clinical practice, including but not limited to their sensitivity to differences in acquisition and reconstruction parameters. In this study, we evaluated the effects of differences in in-plane spatial resolution (IPR) on HRFs, using a phantom dataset (n = 14) acquired on two scanner models. Furthermore, we assessed the effects of interpolation methods (IMs), the choice of a new unified in-plane resolution (NUIR), and ComBat harmonization on the reproducibility of HRFs. The reproducibility of HRFs was significantly affected by variations in IPR, with pairwise concordant HRFs, as measured by the concordance correlation coefficient (CCC), ranging from 42% to 95%. The number of concordant HRFs (CCC > 0.9) after resampling varied depending on (i) the scanner model, (ii) the IM, and (iii) the NUIR. The number of concordant HRFs after ComBat harmonization depended on the variations between the batches harmonized. The majority of IMs resulted in a higher number of concordant HRFs compared to ComBat harmonization, and the combination of IMs and ComBat harmonization did not yield a significant benefit. Our developed framework can be used to assess the reproducibility and harmonizability of RFs.

The Effects of In-Plane Spatial Resolution on CT-Based Radiomic Features’ Stability with and without ComBat Harmonization