Background:Compared with chest X-ray (CXR) imaging, which is a single image projected from the front of the patient, chest digital tomosynthesis (CDTS) imaging can be more advantageous for lung lesion detection because it acquires multiple images projected from multiple angles of the patient. Various clinical comparative analysis and verification studies have been reported to demonstrate this, but there is no artificial intelligence (AI)-based comparative analysis studies. Existing AI-based computer-aided detection (CAD) systems for lung lesion diagnosis have been developed mainly based on CXR images; however, CAD-based on CDTS, which uses multi-angle images of patients in various directions, has not been proposed and verified for its usefulness compared to CXR-based counterparts.Background and objective:This study develops and tests a CDTS-based AI CAD system to detect lung lesions to demonstrate performance improvements compared to CXR-based AI CAD.Methods:We used multiple (e.g., five) projection images as input for the CDTS-based AI model and a single-projection image as input for the CXR-based AI model to compare and evaluate the performance between models. Multiple/single projection input images were obtained by virtual projection on the three-dimensional (3D) stack of computed tomography (CT) slices of each patient’s lungs from which the bed area was removed. These multiple images result from shooting from the front and left and right 30/60∘. The projected image captured from the front was used as the input for the CXR-based AI model. The CDTS-based AI model used all five projected images. The proposed CDTS-based AI model consisted of five AI models that received images in each of the five directions, and obtained the final prediction result through an ensemble of five models. Each model used WideResNet-50. To train and evaluate CXR- and CDTS-based AI models, 500 healthy data, 206 tuberculosis data, and 242 pneumonia data were used, and three three-fold cross-validation was applied.Results:The proposed CDTS-based AI CAD system yielded sensitivities of 0.782 and 0.785 and accuracies of 0.895 and 0.837 for the (binary classification) performance of detecting tuberculosis and pneumonia, respectively, against normal subjects. These results show higher performance than the sensitivity of 0.728 and 0.698 and accuracies of 0.874 and 0.826 for detecting tuberculosis and pneumonia through the CXR-based AI CAD, which only uses a single projection image in the frontal direction. We found that CDTS-based AI CAD improved the sensitivity of tuberculosis and pneumonia by 5.4% and 8.7% respectively, compared to CXR-based AI CAD without loss of accuracy.Conclusions:This study comparatively proves that CDTS-based AI CAD technology can improve performance more than CXR. These results suggest that we can enhance the clinical application of CDTS. Our code is available at https://github.com/kskim-phd/CDTS-CAD-P.