Makes sense, but (as I mentioned in my email): still be mindful of the response function selection, and whether it has gone well, so the response functions make sense; since the result of your CSD outcome and its interpretation depend crucially on it. I’ll add another reply to your other forum post about that, briefly mentioning some details I also emailed, for future reference for people that may be looking into analysing challenging data.
Yeah, that sucks. …well, especially with a voxel- or fixel-wise analysis in mind, because everything has to align if you want to compare like with like. If this fails, most studies would just suffer of increased variance, without the risk of false positive findings (if anything more likely to lose results due to lack of power). However, since these deformations are in this case specific to one group, there is effectively a risk of detecting false positive differences that have nothing to do with the pathology (but with the consistent misalignment).
Makes sense again, but if you want, you can make this more specific by making that not just a voxel-ROI using the WM FD scalar values (“total voxel-wise FD”), but effectively a fixel-ROI. You can first use tractography on your template itself to find the bundles of interest. The next step would be tck2fixel, which essentially generates a fixel-wise track density image (i.e. equivalent of track count, but counted per specific fixel rather than just per voxel). Using mrthreshold or mrcalc you can then threshold the fixel folder’s datafile that resulting from tck2fixel, which would leave you with a binary fixel-wise mask (the equivalent of what a ROI/mask is in voxel space, but then for fixels). And then extract FD values only for these fixels.
This would essentially be slightly more specific (and hence potentially sensitive to just the bundle of interest). But if you’ve got success with just voxel-ROIs in the way you describe, that would be useful as well of course. So in conclusion: yep, the approach you suggest sounds like it makes sense. As always, take great care at each individual step, especially in a challenging case like yours.