Enhancing Radiomic Feature Robustness Through Voxel Spacing-Aware Extraction in Anisotropic CT Data

This study aimed to evaluate whether voxel spacing-aware radiomic feature extraction improves reproducibility, variability, and discriminative performance compared to conventional preprocessing methods in anisotropic CT data. A curated cohort of 685 pulmonary nodules from the LIDC-IDRI dataset was analyzed. Three preprocessing strategies-no resampling, isotropic resampling, and voxel spacing-aware extraction-and one postprocessing approach, voxel spacing weighting, were systematically compared. A modified version of PyRadiomics was developed to compute texture and shape features directly from native images while incorporating physical voxel dimensions without interpolation. Among the 94 extracted features, spacingaware preprocessing improved reproducibility in 58 features, reduced variability in 48, and enhanced univariate discrimination in 37. An ensemble feature selection combining six statistical and machine learning methods identified between 18 and 20 robust features per method. Logistic Regression models trained with spacing-aware features achieved the highest composite performance score (1.498), balancing discrimination and generalizability. SHAP interpretability analysis confirmed the clinical relevance of selected geometric and texture features. Overall, voxel spacing-aware preprocessing preserved native spatial structure and mitigated the effects of voxel geometry and interpolation artifacts, yielding stable and clinically interpretable radiomic features. These findings support the adoption of spacing-aware pipelines in heterogeneous and multi-center CT radiomics studies to enhance feature robustness and reproducibility.