This thesis examines and identifies the problems of shape collapse in large deformation image registration. Shape collapse occurs in image registration when a region in the moving image is transformed into a set of near zero volume in the target image space. Shape collapse may occur when the moving image has a structure that is either missing or does not sufficiently overlap the corresponding structure in the target image. We state that shape collapse is a problem in image registration because it may lead to the following consequences: (1) Incorrect pointwise correspondence between different coordinate systems; (2) Incorrect automatic image segmentation; (3) Loss of functional signal. The above three disadvantages of registration with shape collapse are illustrated in detail using several examples with both real and phantom data. Shape collapse problem is common in image registration algorithms with large degrees of freedom such as many diffeomorphic image registration algorithms. This thesis proposes a shape collapse measurement algorithm to detect the regions of shape collapse after image registration in pairwise and group-wise registrations. We further compute the shape collapse for a whole population of pairwise transformations such as occurs when registering many images to a common atlas coordinate system. Experiments are presented using the SyN diffeomorphic image registration algorithm and diffeomorphic demons algorithm. We show that shape collapse exists in both of the two large deformation registration methods. We demonstrate how changing the input parameters to the SyN registration algorithm can mitigate the collapse image registration artifacts.