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We propose a voxel-based nonrigid registration algorithm for temporal subtraction of two-dimensional thorax X-ray computed radiography images of the same subject. The deformation field is represented by a B-spline with a limited number of degrees of freedom, that allows global rib alignment to minimize subtraction artifacts within the lung field without obliterating interval changes of clinically relevant soft-tissue abnormalities. The spline parameters are constrained by a statistical deformation model that is learned from a training set of manually aligned image pairs using principal component analysis. Optimization proceeds along the transformation components rather then along the individual spline coefficients, using pattern intensity of the subtraction image within the automatically segmented lung field region as the criterion to be minimized and applying a simulated annealing strategy for global optimization in the presence of multiple local optima. The impact of different transformation models with varying number of deformation modes is evaluated on a training set of 26 images using a leave-one-out strategy and compared to the manual registration result in terms of criterion value and deformation error. Registration quality is assessed on a second set of validation images by a human expert rating each subtraction image on screen. In 85% of the cases, the registration is subjectively rated to be adequate for clinical use. [ABSTRACT FROM AUTHOR]