In contrast to the more common Diffusion Tensor Imaging (DTI), High Angular Resolution Diffusion Imaging (HARDI) allows superior delineation of angular microstructures of brain white matter, and makes possible multiple-fiber modeling of each voxel for better characterization of brain connectivity. However, the complex orientation information afforded by HARDI makes registration of HARDI images more complicated than scalar images. In particular, the question of how much orientation information is needed for satisfactory alignment has not been sufficiently addressed. Low order orientation representation is generally more robust than high order representation, although the latter provides more information for correct alignment of fiber pathways. However, high order representation, when naïvely utilized, might not necessarily be conducive to improving registration accuracy since similar structures with significant orientation differences prior to proper alignment might be mistakenly taken as non-matching structures. We present in this paper a HARDI registration algorithm, called SPherical Harmonic Elastic REgistration (SPHERE), which in a principled means hierarchically extracts orientation information from HARDI data for structural alignment. The image volumes are first registered using robust, relatively direction invariant features derived from the Orientation Distribution Function (ODF), and the alignment is then further refined using spherical harmonic (SH) representation with gradually increasing orders. This progression from non-directional, single-directional to multi-directional representation provides a systematic means of extracting directional information given by diffusion-weighted imaging. Coupled with a template-subject-consistent soft-correspondence-matching scheme, this approach allows robust and accurate alignment of HARDI data. Experimental results show marked increase in accuracy over a state-of-the-art DTI registration algorithm
