Actually, one more thought on this...

It is usually better to use padding in the reference than in the floating image. That's because then the number of padded pixels and their relative weights do not change dependent on the transformation between the images.

When you compute a nonrigid transformation, you don't usually have a choice what image to select as the fixed image, but if/when you are computing an affine or rigid transformation, you can select its direction to work well with padding, then later use its inverse for reslicing etc. (Better to do this with "registrationx" rather than "registration" because by default the latter will switch reference and floating image to optimize speed.)

TR