A method of detecting defects in a patterned substrate includes positioning a charged-particle-beam optical column relative to a patterned substrate, the charged-particle-beam optical column having a field of view (FOV) with a substantially uniform resolution over the FOV; operating the charged-particle-beam optical column to acquire images of a region of the patterned substrate lying within the FOV by scanning the charged-particle beam over the patterned substrate; and comparing the acquired images to a reference to identify defects in the patterned substrate.