Abstract: This paper proposes a novel extension to mutual information called regional mutual information.In the process of computing the image information entropy，this method not only considers the information of each pixel，but also considers the neighborhood of the pixel，thus increases the stable of registration，reduces the local optimization according by linear interpolation algorithm and partial volume interpolation，and effectively smoothes the curve of information entropy.Then uses the mixed optimization algorithm based on GA algorithm and Powell algorithm to optimize the function of information entropy.The results show that the modified MRI measure is very accuracy and effictive.