Depending on the computations you intend to perform, the ROI selection could be performed "on the fly" using the i,j, and k variables (or x,y,and z variables) in 3dcalc. This way you would only have to store the i,j,k (or x,y,z) values for each ROI center and loop through those.
e.g. the 3dcalc expression could incorporate
step(((i-i0)*(i-i0)+(j-j0)*(j-j0)+(k-k0)*(k-k0))-(R*R))
where R is the radius of the sphere, and
i0, j0, and k0 are the locations of the ROI (looping through all the voxels in the brain).
This would save on disk space, but the speed may be fairly slow (I haven't tested this).
-Rasmus