Robust quantification of CT-ventilation biomarker techniques and repeatability in a porcine model

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. (Figure presented.) measured local expansion between an image pair using either inhale and exhale BH-CT images or two 4DCT breathing phase images. (Figure presented.) measured the maximum local expansion across the 4DCT breathing phase images. Breathing maneuver consistency, intra- and interday biomarker repeatability, image acquisition and post-processing technique dependence were quantitatively analyzed. Results: Biomarkers showed strong agreement with voxel-wise Spearman correlation (Figure presented.) for intraday repeatability and (Figure presented.) for all other comparisons, including between image acquisition techniques. Intra- and interday repeatability were significantly different (p < 0.01). LER₂ and LER_N post-processing did not significantly affect intraday repeatability. Conclusions: 4DCT and BH-CT ventilation biomarkers derived from consecutive scans show strong agreement in controlled experiments with nonhuman subjects.