Abstract: Defects in a patterned substrate are detected by positioning a charged-particle-beam optical column relative to a patterned substrate, the charged-particle imaging system having a field of view (FOV) with a substantially uniform resolution over the FOV; operating the charged-particle-beam optical column to acquire images over multiple subareas of the patterned substrate lying within the FOV by scanning a charged-particle beam over the patterned substrate while maintaining the charged-particle-beam optical column fixed relative to the patterned substrate; and comparing the acquired images to a reference to identify defects in the patterned substrate. The use of a large-FOV imaging system with substantially uniform resolution over the FOV allows acquisition of images over a wide area of the patterned substrate without requiring mechanical stage moves, thereby reducing the time overhead associated with mechanical stage moves. Multiple columns can be ganged together to further improve throughput.