If your images have consistent rotation scale etc you can reuse an existing registration. However if e.g. the rotation can vary then you may need to compute that but it might be quite efficient to do so if you know e.g. that brains are always mounted on their posterior surface with 360 degrees around the Z axis but say only +/-15 around the X axis (chin up or chin down). We used two strategies for initial registrations a Hough transform implemented in Amira. This was very handy but sadly I'm not sure it ever made it out of the Academic version from the Zuse Institute in Berlin. Or surface based mesh transforms in Amira. There are many other surface mesh registrations you could potentially use. So a fancy pipeline might do a marching cubes on a heavily downsampled version of the image. Other ideas would be identifying the plane of symmetry and then using that to define +/- 180 the rotation around the Z axis. You can use the mat2dof tool to convert a general affine transform into CMTK's format.

All the best, Greg.