ABSTRACT: Four-dimensional computed tomography (4DCT) can be used to make measurements of pulmonary function longitudinally. The sensitivity of such measurements to identify change depends on measurement uncertainty. Previously, intrasubject reproducibility of Jacobian-based measures of lung tissue expansion was studied in two repeat prior-RT 4DCT human acquisitions. Difference in respiratory effort such as breathing amplitude and frequency may affect longitudinal function assessment. In this study, the authors present normalization schemes that correct ventilation images for variations in respiratory effort and assess the reproducibility improvement after effort correction.Repeat 4DCT image data acquired within a short time interval from 24 patients prior to radiation therapy (RT) were used for this analysis. Using a tissue volume preserving deformable image registration algorithm, Jacobian ventilation maps in two scanning sessions were computed and compared on the same coordinate for reproducibility analysis. In addition to computing the ventilation maps from end expiration to end inspiration, the authors investigated the effort normalization strategies using other intermediated inspiration phases upon the principles of equivalent tidal volume (ETV) and equivalent lung volume (ELV). Scatter plots and mean square error of the repeat ventilation maps and the Jacobian ratio map were generated for four conditions: no effort correction, global normalization, ETV, and ELV. In addition, gamma pass rate was calculated from a modified gamma index evaluation between two ventilation maps, using acceptance criterions of 2 mm distance-to-agreement and 5% ventilation difference.The pattern of regional pulmonary ventilation changes as lung volume changes. All effort correction strategies improved reproducibility when changes in respiratory effort were greater than 150 cc (p < 0.005 with regard to the gamma pass rate). Improvement of reproducibility was correlated with respiratory effort difference (R = 0.744 for ELV in the cohort with tidal volume difference greater than 100 cc). In general for all subjects, global normalization, ETV and ELV significantly improved reproducibility compared to no effort correction (p = 0.009, 0.002, 0.005 respectively). When tidal volume difference was small (less than 100 cc), none of the three effort correction strategies improved reproducibility significantly (p = 0.52, 0.46, 0.46 respectively). For the cohort (N = 13) with tidal volume difference greater than 100 cc, the average gamma pass rate improves from 57.3% before correction to 66.3% after global normalization, and 76.3% after ELV. ELV was found to be significantly better than global normalization (p = 0.04 for all subjects, and p = 0.003 for the cohort with tidal volume difference greater than 100 cc).All effort correction strategies improve the reproducibility of the authors' pulmonary ventilation measures, and the improvement of reproducibility is highly correlated with the changes in respiratory effort. ELV gives better results as effort difference increase, followed by ETV, then global. However, based on the spatial and temporal heterogeneity in the lung expansion rate, a single scaling factor (e.g., global normalization) appears to be less accurate to correct the ventilation map when changes in respiratory effort are large.
