In image registration, a similarity measure is computed of first and second images (4, 6) offset at a plurality of relative axial offsets (30). A starting relative axial offset (40) between the first and second images is identified based on the computed similarity measures. An iterative image registration process is performed to relatively register the first and second images (4, 6) using the identified starting relative axial offset between the first and second images as an initial condition for the iterative image registration process. A starting relative in-slice offset (42) may also be identified as an in-slice offset effective to align corresponding slices of the first and second images (4, 6) offset at the starting relative axial offset (40), the identified starting relative in-slice offset also being used as an initial condition for the iterative image registration process.