Medical image registration (IR) is the systematic process of aligning spate images, often involving different modalities with common reference framework, so complementary information can be combined and compared. This paper presents a new similarity measure which uses Expectation Maximization for Principal Component Analysis allied with mutual information (EMPCA-MI) for medical IR. The new measure has been analysed on multimodal, three band magnetic resonance images (MRI) T1, T2 and PD weighted, in the presence of both intensity non-uniformities (INU) and noise. Both quantitative and qualitative experimental results clearly demonstrate both improved robustness and lower computational complexity of the new EMPCA-MI paradigm compared with existing MI-based similarity measures, for various MRI test datasets. (6 pages)