LAUSR

BACKGROUND Biomarkers estimating local lung ventilation have been derived from computed tomography (CT) imaging using various image acquisition and post-processing techniques. CT-ventilation biomarkers have potential clinical use in functional avoidance radiation therapy (RT), in which RT treatment plans are optimized to reduce dose delivered to highly-ventilated lung. Widespread clinical implementation of CT-ventilation biomarkers necessitates understanding of biomarker repeatability. Performing imaging within a highly controlled experimental design enables quantification of error associated with remaining variables. PURPOSE To characterize CT-ventilation biomarker repeatability and dependence on image acquisition and post-processing methodology in anesthetized and mechanically ventilated pigs. METHODS Five mechanically ventilated Wisconsin Miniature Swine (WMS) received multiple consecutive four-dimensional CT (4DCT) and maximum inhale and exhale breath-hold CT (BH-CT) scans on five dates to generate CT-ventilation biomarkers. Breathing maneuvers were controlled with an average tidal volume difference <200 cc. As surrogates for ventilation, multiple local expansion ratios (LERs) were calculated from the acquired CT scans using Jacobian-based post-processing techniques. LER2 measured local expansion between an image pair using either inhale and exhale BH-CT images or two 4DCT breathing phase images. LERN measured the maximum local expansion across the 4DCT breathing phase images. Breathing maneuver consistency, intra- and inter-day biomarker repeatability, image acquisition and post-processing technique dependence were quantitatively analyzed. RESULTS Biomarkers showed strong agreement with voxel-wise Spearman correlation ρ > 0.9 for intra-day repeatability and ρ > 0.8 for all other comparisons, including between image acquisition techniques. Intra- and inter-day repeatability were significantly different (p<0.01). LER2 and LERN post-processing did not significantly affect intra-day repeatability. CONCLUSIONS 4DCT and BH-CT ventilation biomarkers derived from consecutive scans show strong agreement in controlled experiments with non-human subjects. This article is protected by copyright. All rights reserved.