Abstract
Tumor heterogeneity has been postulated as a hallmark of treatment resistance and a cure constraint in cancer patients. Conventional quantitative medical imaging (radiomics) can be extended to computing voxel-wise features and aggregating tumor subregions with similar radiological phenotypes (imaging habitats) to elucidate the distribution of tumor heterogeneity within and among tumors. Despite the promising applications of imaging habitats, they may be affected by variability of radiomics features, preventing comparison and generalization of imaging habitats techniques. We performed a comprehensive repeatability and reproducibility analysis of voxel-wise radiomics features in more than 500 lung cancer patients with computed tomography (CT) images and demonstrated the effect of voxel-wise radiomics variability on imaging habitats computation in 30 lung cancer patients with test-retest images. Repeatable voxel-wise features characterized texture heterogeneity and were reproducible regardless of the applied feature extraction parameters. Imaging habitats computed using robust radiomics features were more stable than those computed using all features in test-retest CTs from the same patient. Nine voxel-wise radiomics features (joint energy, joint entropy, sum entropy, maximum probability, difference entropy, Imc1, Imc2, Idn and Idmn) were repeatable and reproducible. This supports their application for computing imaging habitats in lung tumors towards the discovery of previously unseen tumor heterogeneity and the development of novel non-invasive imaging biomarkers for precision medicine.