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Nonrigid registration of medical images is especially critical in clinical treatment. Mutual information is a popular similarity measure for medical image registration; however, only the intensity statistical characteristics of the global consistency of image are considered in MI, and the spatial information is ignored. In this paper, a novel intensity‐based similarity measure combining normalized mutual information with spatial information for nonrigid medical image registration is proposed. The different parameters of Gaussian filtering are defined according to the regional variance, the adaptive Gaussian filtering is introduced into the local structure tensor. Then, the obtained adaptive local structure tensor is used to extract the spatial information and define the weighting function. Finally, normalized mutual information is distributed to each pixel, and the discrete normalized mutual information is multiplied with a weighting term to obtain a new measure. The novel measure fully considers the spatial information of the image neighborhood, gives the location of the strong spatial information a larger weight, and the registration of the strong gradient regions has a priority over the small gradient regions. The simulated brain image with single‐modality and multimodality are used for registration validation experiments. The results show that the new similarity measure improves the registration accuracy and robustness compared with the classical registration algorithm, reduces the risk of falling into local extremes during the registration process.

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