## 4 Discussion  
The experiments performed in this study were designed to investigate the reproducibility of renal lesions' RFs across the different CECT phases when the remaining scanning parameters were kept similar. The experiments were further intended to examine the ability of ComBat harmonization method to remove the variations in renal lesions' RF values across the different phases of CECT scans. Differences in the CECT phase used to extract the RFs affected their reproducibility significantly. Aside from the first order total energy and shape features, all RFs were significantly impacted between the arterial phase RFs and the non and late phase RFs. Since the same mask was used to extract the RFs from the different imaging phases, the shape features were used as a control, indicating that a single feature is independent of the shape of the ROI. Nevertheless, some texture features (8, 7.5%) were found to be reproducible between the non-contrast enhanced phase and late phase RFs. These findings indicate that scans from different phases must be analyzed separately. Our results are in line with previous studies that investigated the reproducibility of RFs across different phases [19; 20]. In  
Figure 3: Boxplot comparison of the C-indices across the imaging phases. addition, ComBat harmonization technique has not statistically significantly increased the agreement in the values of RFs across the CECT phases. A single (1%) RF was found to be reproducible following ComBat harmonization across the arterial and late phase scans compared to before harmonization. The number of reproducible RFs has not changed in the remaining investigated scenarios. These results also align with previous studies that reported on the use of ComBat harmonization in radiomics [16; 17; 18; 19; 41]. Despite having all the other imaging parameters fixed across the different phases, the variation in the imaging phase significantly impacted almost all of the RFs. This is expected because of the nature of the renal lesions, their enhancement characteristics, and the differential regional enhancement of the kidneys across the different imaging phases. Yet, in the comparison between the non-contrast enhanced and late phases, some texture RFs remained reproducible, which could also be attributed to the similarity in lesion enhancement across those phases (or the lack thereof). In contrast, a previous study investigating the reproducibility of hepatocellular carcinoma-based RFs between the arterial and portal venous CECT phases reported a slightly higher percentage of reproducible RFs [19]. The variations in the rate of RFs between the study and our results could be attributed to several factors: (i) The difference in the anatomic nature of the lesions investigated; (ii) The previous study analyzed arterial and portal venous scans, which are taken at shorter time intervals following contrast injection compared to the phases analyzed in this study; (iii) The differences in imaging parameters across the patients were less compared to our data. Similar to the HCC study, our results signify the need for careful curation of the imaging datasets before performing radiomics analyses. Most publicly available datasets were collected retrospectively and included scans of different phases, as is the case with the data analyzed in this study. Careful curation of the imaging dataset is needed to ensure that RF values are meaningful and reproducible across the different imaging parameters to develop robust and generalizable radiomic signatures. Some possibilities could justify the lack of statistically significant increments in the number of reproducible RFs across the CECT phases: (i) ComBat harmonization was designed for variables that were calculated in the same manner (gene arrays), in contrast to the RFs, which have different definitions and levels of complexity; (ii) ComBat harmonization assumes that the effect of the batch is the same on all of the RFs to be harmonized [36].