Machine learning-based texture analysis for differentiation of radiologically indeterminate small adrenal tumors on adrenal protocol CT scans

Goal: To evaluate the ability of radiomic feature extraction and a machine learning algorithm to differentiate between benign and malignant indeterminate adrenal lesions on contrast-enhanced computed tomography (CT) studies. Background: Adrenal “incidentalomas” are adrenal lesions that are accidentally discovered during workup not related to the adrenal glands; they have an incidence as high as 5%. Small adrenal incidentalomas (< 4 cm) with high attenuation values on pre-contrast CT(> 10 HU) need further evaluation to calculate the absolute percentage of washout (APW). If the APW is < 60%, these lesions are considered non-adenomas and commonly classified as indeterminate adrenal lesions. Further workup for indeterminate lesions includes more complicated and expensive radiological studies or invasive procedures like biopsy or surgical resection. Methods: We searched our institutional database for indeterminate adrenal lesions with the following characteristics: < 4 cm, pre-attenuation value > 10 HU, and APW < 60%. Exclusion criteria included pheochromocytoma and no histopathological examination. CT images were converted to Nifti format, and adrenal tumors were segmented using Amira software. Radiomic features from the adrenal mask were extracted using PyRadiomics software after removing redundant features (highly pairwise correlated features and low-variance features) using recursive feature extraction to select the final discriminative set of features. Lastly, the final features were used to build a binary classification model using a random forest algorithm, which was validated and tested using leave-one-out cross-validation, confusion matrix, and receiver operating characteristic curve. Results: We found 40 indeterminate adrenal lesions (21 benign and 19 malignant). Feature extraction resulted in 3947 features, which reduced down to 62 features after removing redundancies. Recursive feature elimination resulted in the following top 4 discriminative features: gray-level size zone matrix-derived size zone non-uniformity from pre-contrast and delayed phases, gray-level dependency matrix-derived large dependence high gray-level emphasis from venous-phase, and gray-level co-occurrence matrix-derived cluster shade from delayed-phase. A binary classification model with leave-one-out cross-validation showed AUC = 0.85, sensitivity = 84.2%, and specificity = 71.4%. Conclusion: Machine learning and radiomic features extraction can differentiate between benign and malignant indeterminate adrenal tumors and can be used to direct further workup with high sensitivity and specificity.