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In this paper, a new multi-modal non-rigid registration technique for medical images is presented. Firstly, the registration problem is outlined and some of the most common approaches reported, then, the proposed algorithm is presented. The proposed technique is based on mutual information maximization and computes a deformation field through a suitable globally smoothed affine piecewise transformation. The algorithm has been conceived with particular attention to computational load and accuracy of results. Experimental results involving intra-patient, inter-patients and atlas images on brain CT and MR (T1, T2 and PD modalities) are reported.