Rationale: The computed tomography (CT) pattern of definite or probable usual interstitial pneumonia (UIP) can be diagnostic of idiopathic pulmonary fibrosis and may obviate the need for invasive surgical biopsy. Few machine-learning studies have investigated the classification of interstitial lung disease (ILD) on CT imaging, but none have used histopathology as a reference standard.Objectives: To predict histopathologic UIP using deep learning of high-resolution computed tomography (HRCT).Methods: Institutional databases were retrospectively searched for consecutive patients with ILD, HRCT, and diagnostic histopathology from 2011 to 2014 (training cohort) and from 2016 to 2017 (testing cohort). A blinded expert radiologist and pulmonologist reviewed all training HRCT scans in consensus and classified HRCT scans based on the 2018 American Thoracic Society/European Respriatory Society/Japanese Respiratory Society/Latin American Thoracic Association diagnostic criteria for idiopathic pulmonary fibrosis. A convolutional neural network (CNN) was built accepting 4 × 4 × 2 cm virtual wedges of peripheral lung on HRCT as input and outputting the UIP histopathologic pattern. The CNN was trained and evaluated on the training cohort using fivefold cross validation and was then tested on the hold-out testing cohort. CNN and human performance were compared in the training cohort. Logistic regression and survival analyses were performed.Results: The CNN was trained on 221 patients (median age 60 yr; interquartile range [IQR], 53-66), including 71 patients (32%) with UIP or probable UIP histopathologic patterns. The CNN was tested on a separate hold-out cohort of 80 patients (median age 66 yr; IQR, 58-69), including 22 patients (27%) with UIP or probable UIP histopathologic patterns. An average of 516 wedges were generated per patient. The percentage of wedges with CNN-predicted UIP yielded a cross validation area under the curve of 74% for histopathological UIP pattern per patient. The optimal cutoff point for classifying patients on the training cohort was 16.5% of virtual lung wedges with CNN-predicted UIP and resulted in sensitivity and specificity of 74% and 58%, respectively, in the testing cohort. CNN-predicted UIP was associated with an increased risk of death or lung transplantation during cross validation (hazard ratio, 1.5; 95% confidence interval, 1.1-2.2; P = 0.03).Conclusions: Virtual lung wedge resection in patients with ILD can be used as an input to a CNN for predicting the histopathologic UIP pattern and transplant-free survival.

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