A wafer pattern inspection system using scanning electron microscopy (SEM) is desirable because electron probing makes it possible to inspect not only surface defects, but also internal electric properties. However, the detection rate of SEM is typically about 100 mega pixels per second (Mpps) due to the effect of shot noise on a signal caused by improving the detection rate.To reduce the cost of ownership of the inspection system, improving throughput of SEM is imperative. Unfortunately, the detection rate remains at 200 Mpps due to physical limitations of the resolution caused by the Coulomb effect and the increasing effect of shot noise. To overcome these limitations, projection electron microscopy systems [1,2] have been proposed.We created a novel image processing method that reliably detects defects images obtained at a 400 Mpps detection rate without increasing the beam current. By using the periodicity of circuit patterns in a memory mat area, the method generates the reference image of a high signal-to-noise ratio by averaging the periodic pattern and detects defects by comparing a defect image with the generated reference image. The theoretical study on the signal-to-noise ratio and the experimental results on the defect detection performance for various sizes of artificial pattern defects are presented.