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In the field of medical imaging, image registration methods are useful for many applications such as inter- and intra-subject morphological comparisons, creation of population atlases, delivery of precision therapies, etc. A user may want to know which is the most suitable registration algorithm that would work best for the intended application, but the vastness of medical image registration applications makes evaluation and comparison of image registration performance a non-trivial task. In general, evaluating image registration performance is not straightforward because in most image registration applications there is an absence of “Gold Standard” or ground truth correspondence map to compare against. It is therefore the primary goal of this thesis work to provide a means for recommending the most appropriate registration algorithm for a given task. One of the contributions of this thesis is to examine image registration algorithm performance at the component level. Another contribution of this thesis is to catalog the benefits and limitations of many of the most commonly used image registration evaluation approaches. One incremental contribution of this thesis was to demonstrate how existing evaluation methods can be applied in the midpoint coordinate system to evaluate some symmetric image registration algorithms such as the SyN registration algorithm. Finally, a major contribution of this thesis was to develop tools to evaluate and visualize 2D and 3D image registration shape collapse. This thesis demonstrates that many current diffeomorphic image registration algorithms suffer from the collapse problem, provides the first visualizations of the collapse problem in 3D for simple shapes and real human brain MR images, and provides the first experiments that demonstrate how adjusting image registration parameters can mitigate the collapse problem to some extent.

This dissertation provides the foundations of computer-based automated phenotyping methods for analyzing 3D images of mouse embryos. A group-wise registration technique was utilized and optimized and computerized methods were employed for analysis of 3D MRI images of mouse embryos. The assumption that embryo anatomy is highly conserved among genetically identical specimens was verified. The group-wise registration approach was used to align a group of embryos from the 129S1/SvImJ (129Sv) strain as well as a group of C57BL/6J (C57) embryos. Finally, we shed some light on some of the morphological differences between the 129Sv and C57 strains using automated techniques.