Image registration is an important task in medical image analysis. Whereas most methods are designed for the registration of two images (pairwise registration), there is an increasing interest in simultaneously aligning more than two images using groupwise registration. Multimodal registration in a groupwise setting remains difficult, due to the lack of generally applicable similarity metrics. In this work, a novel similarity metric for such groupwise registration problems is proposed. The metric calculates the sum of the conditional entropy between each image in the group and a representative template image constructed iteratively using principal component analysis. The proposed metric is validated in extensive experiments on synthetic and intrasubject clinical image data. These experiments showed equivalent or improved registration accuracy compared to other state-of-the-art (dis)similarity metrics and improved transformation consistency compared to pairwise mutual information.

Multimodal groupwise registration has been of growing interest to the image processing community due to developments in scanner technologies (e.g. multiparametric MRI, DCE-CT or PET-MR) that increased both the number of modalities and number of images under consideration. In this work a novel methodology is presented for multimodal groupwise registration that is based on Laplacian eigenmaps, a nonlinear dimensionality reduction technique. Compared to recently proposed dissimilarity metrics based on principal component analysis, the proposed metric should enable a better capture of the intensity relationships between different images in the group. The metric is constructed to be the second smallest eigenvalue from the eigenvector problem defined in Laplacian eigenmaps. The method was validated in three distinct experiments: a non-linear synthetic registration experiment, the registration of quantitative MRI data of the carotid artery, and the registration of multimodal data of the brain (RIRE). The results show increased accuracy and robustness compared to other state-of-the-art groupwise registration methodologies.