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I haven't tried it with DT data, but I've used the method you've described with some success. Are you sure you have the right expression in image calc? Say, for example, your images are i1=grey matter i2=white matter i3=csf i4=image you are stripping where i1, i2, and i3 are NOT normalized (to get these images, you need to change the writing options in the segment routine) Your expression should look something like ((i1+i2)>0).*i4 If you want to include CSF, use i1+i2+i3 instead of i1+i2 Hope that helps.