Hello FSL-experts,

While working with SIENAX on a cross-sectional study I ran into the following:

If I understand correctly, SIENAX uses the exterior skull surface as a scaling constraint in the registration by determining the boundary between the low skull intensity and bright scalp.

My first question is what happens if in between these two, abnormally large temporal muscles are present. Will it still be able to reliably determine the outline of the outer skull or is there a chance that the muscle will be included?

My second question relates more to the normalization to skull size, with respect to atrophy estimates. I understand that there is a close relationship between normal skull and brain growth, making the skull size a reliable marker, but what if there is a diseased state disrupting normal skull growth? How does one dissect for example different skull thickness (low intensity) from more CSF (also low intensity)?

I appreciate any and all advice in this matter.

Nathalie