A multivariable study of deformable image registration evaluation metrics in 4DCT of thoracic cancer patients.

Deformable image registration (DIR) accuracy is often validated using manually identified landmarks or known deformations generated using digital or physical phantoms. In daily practice, the application of these approaches is limited since they are time-consuming or require additional equipment. An alternative is the use of metrics automatically derived from the registrations, but their interpretation is not straightforward. In this work we aim to determine the suitability of DIR-derived metrics to validate the accuracy of 4 commonly used DIR algorithms. First, we investigated the DIR accuracy using a landmark-based metric (target registration error (TRE)) and a digital phantom-based metric (known deformation recovery error (KDE)). 4DCT scans of 16 thoracic cancer patients along with corresponding pairwise anatomical landmarks (AL) locations were collected from two public databases. Digital phantoms with known deformations were generated by each DIR algorithm to test all other algorithms and compute KDE. TRE and KDE were evaluated at AL. KDE was additionally quantified in coordinates randomly sampled (RS) inside the lungs. Second, we investigated the associations of 5 DIR-derived metrics (distance discordance metric (DDM), inverse consistency error (ICE), transitivity (TE), spatial (SS) and temporal smoothness (TS)) with DIR accuracy through uni- and multivariable linear regression models. TRE values were found higher compared to KDE values and these varied depending on the phantom used. The algorithm with the best accuracy achieved average values of TRE = 1.1 mm and KDE ranging from 0.3 to 0.8 mm. DDM was the best predictor of DIR accuracy, with moderate correlations (R 2 < 0.61). Poor correlations were obtained at AL for algorithms with better accuracy, which improved when evaluated at RS. Only slight correlation improvement was obtained with a multivariable analysis (R 2 < 0.64). DDM can be a useful metric to identify inaccuracies for different DIR algorithms without employing landmarks or digital phantoms.