Deep Learning–based Segmentation of Computed Tomography Scans Predicts Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis

<b>Rationale:</b> Despite evidence demonstrating a prognostic role for computed tomography (CT) scans in idiopathic pulmonary fibrosis (IPF), image-based biomarkers are not routinely used in clinical practice or trials. <b>Objectives:</b> To develop automated imaging biomarkers using deep learning-based segmentation of CT scans. <b>Methods:</b> We developed segmentation processes for four anatomical biomarkers, which were applied to a unique cohort of treatment-naive patients with IPF enrolled in the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study and tested against a further United Kingdom cohort. The relationships among CT biomarkers, lung function, disease progression, and mortality were assessed. <b>Measurements and Main Results:</b> Data from 446 PROFILE patients were analyzed. Median follow-up duration was 39.1 months (interquartile range, 18.1-66.4 mo), with a cumulative incidence of death of 277 (62.1%) over 5 years. Segmentation was successful on 97.8% of all scans, across multiple imaging vendors, at slice thicknesses of 0.5-5 mm. Of four segmentations, lung volume showed the strongest correlation with FVC (<i>r</i> = 0.82; <i>P</i> < 0.001). Lung, vascular, and fibrosis volumes were consistently associated across cohorts with differential 5-year survival, which persisted after adjustment for baseline gender, age, and physiology score. Lower lung volume (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.96-0.99]; <i>P</i> = 0.001), increased vascular volume (HR, 1.30 [95% CI, 1.12-1.51]; <i>P</i> = 0.001), and increased fibrosis volume (HR, 1.17 [95% CI, 1.12-1.22]; <i>P</i> < 0.001) were associated with reduced 2-year progression-free survival in the pooled PROFILE cohort. Longitudinally, decreasing lung volume (HR, 3.41 [95% CI, 1.36-8.54]; <i>P</i> = 0.009) and increasing fibrosis volume (HR, 2.23 [95% CI, 1.22-4.08]; <i>P</i> = 0.009) were associated with differential survival. <b>Conclusions:</b> Automated models can rapidly segment IPF CT scans, providing prognostic near and long-term information, which could be used in routine clinical practice or as key trial endpoints.