Here are my tips as someone who routinely registers longitudinal studies.

You do not need to play with the interpolation, use tri-linear (or spline if you want sharp edges)

1) Skull strip - this always helps (if your looking at the brain)
2) If it is a single subject, you may want to play with the DOF (generally 6 DOF for single subject multiple scans and single visit, 7 for longitudinal, i.e. multi-visit registrations).
3) Cost function, I always use normalized mutual information (normmi). My experience has taught me that this always provides the best registration. Feel free to try a variety of them, just be consistent.
4) Register to a template image (I use freesurfers mri_robust_template)
5) Worst case scenario, truncate one of the images z-axis to say 20 slices mid-brain. Then register this to the other image (care must be taken to then apply transform to original - non ROI image)

I have more tricks, but cannot think of them. I am not an expert, just someone who registers many brains.

Cheers,

Bryson

On Sun, Mar 1, 2015 at 11:26 AM, Subscribe FSL Chris <[log in to unmask]> wrote:
Dear fsl-ers, I’m aligning two different T2 images from a single subject, each of which has its own manually drawn ROI, and need advice on how to improve alignment.  Using tri-linear interpolation gives good registration but of course blurs the ROI.  Nearest neighbor keeps the ROI’s integrity but changes the T2 non-uniformly, e.g., changing the pitch of the anterior 2/3 of the image while separately effectively moving the occipital lobe superiorly.  Skull stripping does not help.  Any advice on the best way to address this within FSL would be great.  Thanks, Chris