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Dear Sasha, I am sorry to hear that you are having such trouble. Are you correcting for bias fields in your images? If they are 7T images then that might be a problem. If that is not the case then I think I'd need to see an example in order to help - and so please upload an example to our upload site (see the Support webpage in the FSL website for details). All the best, Mark On 5 Feb 2013, at 17:24, Alejandro Vicente Grabovetsky <[log in to unmask]<mailto:[log in to unmask]>> wrote: Dear FSLers, I have been attempting to run sub-cortical segmentation using FIRST, using a (large) variety of methods on set of high-resolution, brain extracted 7T MP2RAGE images. Some examples: run_first_all first_flirt followed by run_first on each structure flirt followed by run_first The whole procedure appears to fail at the FLIRT stage, which misaligns the brains very badly (often inverting them, or shrinking them to the size of a walnut). This appears to be due to FLIRT being less robust when the reference image is lower resolution/contrast than the input image, but this does not seem to be the whole story. Namely, the best results I achieved have been using the last method, where I back-normalise the (BETted) T1 template to the (BETted) individual brain, and then re-flirt using the sub-cortical weighting mask. This gives a significant, but not sufficient improvement: it fails in 20-30% of brains, rather than 40% when simply using run_first_all. One suggested option of using robustfov from fsl_anat to crop the individual brains unfortunately does not help at all (if anything it makes things worse). Suggestions to make this work robustly are very welcome! Sasha -- Vicente Grabovetsky, Alejandro (Sasha) Postdoctoral researcher Donders Centre for Cognitive Neuroimaging http://www.doellerlab.com<http://www.doellerlab.com/>