Objectives: Accurate registration of lung CT images is inevitable for numerous clinical applications. Usually, nonlinear intensity-based methods are used. Their accuracy is typically evaluated using corresponding anatomical points (landmarks; e.g. bifurcations of bronchial and vessel trees) annotated by medical experts in the images to register. As image registration can be interpreted as correspondence finding problem, these corresponding landmarks can also be used in feature-based registration techniques. Recently, approaches for automated identification of such landmark correspondences in lung CT images have been presented. In this work, a novel combination of variational nonlinear intensity-based registration with an approach for automated landmark correspondence detection in lung CT pairs is presented and evaluated.

Methods: The main blocks of the proposed hybrid intensity- and feature-based registration scheme are a two-step landmark correspondence detection and the so-called CoLD (Combining Landmarks and Distance Measures) framework. The landmark correspondence identification starts with feature detection in one image followed by a block-matching-based transfer of the features to the other image. The established correspondences are used to compute a thin-plate spline (TPS) transformation. Within CoLD, the TPS transformation is improved by minimization of an objective function consisting of a Normalized Gradient Field distance measure and a curvature regularizer; the landmark correspondences are guaranteed to be preserved by optimization on the kernel of the discretized landmark constraints.

Results: Based on ten publicly available end-inspiration/expiration CT scan pairs with anatomical landmark sets annotated by medical experts from the DIR-Lab database, it is shown that the hybrid registration approach is superior in terms of accuracy: The mean distance of expert landmarks is decreased from 8.46 mm before to 1.15 mm after registration, outperforming both the TPS transformation (1.68 mm) and a nonlinear registration without usage of automatically detected landmarks (2.44 mm). The improvement is statistically significant in eight of ten datasets in comparison to TPS and in nine of ten datasets in comparison to the intensity-based registration. Furthermore, CoLD globally estimates the breathing-induced lung volume change well and results in smooth and physiologically plausible motion fields of the lungs.

Conclusions: We demonstrated that our novel landmark-based registration pipeline outperforms both TPS and the underlying nonlinear intensity-based registration without landmark usage. This highlights the potential of automatic landmark correspondence detection for improvement of lung CT registration accuracy.