Abstract:Abstract Background: Pulmonary function tests (PFTs) and computed tomography (CT) imaging are vital in diagnosing, managing, and monitoring lung diseases. A common issue in practice is the lack of access to recorded pulmonary functions despite available chest CT scans. Purpose: To develop and validate a deep learning algorithm for predicting pulmonary function directly from chest CT scans. Methods: The development cohort came from the Pittsburgh Lung Screening Study (PLuSS) (n=3619). The validation cohort came from the Specialized Centers of Clinically Oriented Research (SCCOR) in COPD (n=662). A deep learning model called BeyondCT, combining a three-dimensional (3D) convolutional neural network (CNN) and Vision Transformer (ViT) architecture, was used to predict forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) from non-contrasted inspiratory chest CT scans. A 3D CNN model without ViT was used for comparison. Subject demographics (age, gender, smoking status) were also incorporated into the model. Performance was compared to actual PFTs using mean absolute error (MAE, L), percentage error, and R square. Results: The 3D-CNN model achieved MAEs of 0.395 L and 0.383 L, percentage errors of 13.84% and 18.85%, and R square of 0.665 and 0.679 for FVC and FEV1, respectively. The BeyondCT model without demographics had MAEs of 0.362 L and 0.371 L, percentage errors of 10.89% and 14.96%, and R square of 0.719 and 0.727, respectively. Including demographics improved performance (p<0.05), with MAEs of 0.356 L and 0.353 L, percentage errors of 10.79% and 14.82%, and R square of 0.77 and 0.739 for FVC and FEV1 in the test set. Conclusion: The BeyondCT model showed robust performance in predicting lung function from non-contrast inspiratory chest CT scans.