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This paper presents a new3-D image registration method based on principal component analysis (PCA) and mutual information (MI), named as PCA-MI algorithm. First, principal component analysis is applied to align the volumes roughly. Second, registration is refined via maximizing the MI. We evaluate the effectiveness of the PCA-MI approach by applying it to the real image data. The experimental results indicate that the algorithm is effective in reducing computation time as well as in helping to avoid local minima.