Mid-space-independent deformable image registration

•A new mid-space-independent method for deformable image registration is proposed.•The need for enforcing artificial anti-drift constraints are alleviated.•The proposed MSI method is validated on brain magnetic resonance image datasets.•The toolbox has been made publicly available.

Aligning images in a mid-space is a common approach to ensuring that deformable image registration is symmetric - that it does not depend on the arbitrary ordering of the input images. The results are, however, generally dependent on the mathematical definition of the mid-space. In particular, the set of possible solutions is typically restricted by the constraints that are enforced on the transformations to prevent the mid-space from drifting too far from the native image spaces. The use of an implicit atlas has been proposed as an approach to mid-space image registration. In this work, we show that when the atlas is aligned to each image in the native image space, the data term of implicit-atlas-based deformable registration is inherently independent of the mid-space. In addition, we show that the regularization term can be reformulated independently of the mid-space as well. We derive a new symmetric cost function that only depends on the transformation morphing the images to each other, rather than to the atlas. This eliminates the need for anti-drift constraints, thereby expanding the space of allowable deformations. We provide an implementation scheme for the proposed framework, and validate it through diffeomorphic registration experiments on brain magnetic resonance images.