Multi-parametric MR image registration combines different imaging sequences to enhance visualisation and analysis. However, alignment of the different acquisitions is challenging, due to contrast-dependent anatomical information and abundant artefacts. For two decades, voxel-based registration has been dominated by methods based on mutual information, calculated from the joint image histogram. In this paper, we propose a modified framework - based on an asymmetric cluster-to-image mutual information metric - that increases registration speed and robustness. A new parameter, the homogeneous dynamic intensity range, is used to determine to which image clustering is applied. The framework also includes a semi-automatic 3D region of interest, multi-resolution wavelet decomposition, and particle swarm optimization. Performance of the framework, and its individual components, were evaluated on two diverse datasets, comprising cardiac and neonatal brain datasets. The results demonstrated the method was more robust and accurate than mutual information alone.