This chapter summarizes regional cardiac functional studies using MRI that span the past 25 years. In addition to the comparison of the three major MRI techniques that achieve detailed studies of myocardial mechanics, an extensive reference to DENSE-MRI and its imaging and image-processing features is presented. The mouse paradigm, as a direct manifestation of international efforts for image-based phenotyping in health, disease and post-transgenetic modification, is also introduced. The appropriateness of extrapolations of inferences drawn from mouse studies to man are well-justified from presented evidence on isometric and allometric scaling of global and regional cardiac functional indices, however, noted mismatches of the fiber structure, force-frequency and energetic/metabolic reserves exist between the two species. While such arguments limit the range of possible pathological models that can associate human and murine disease, the mouse still remains a potentially attractive animal model for cardiovascular research today.