One embodiment relates to an apparatus for detecting defects on a manufactured substrate. The apparatus includes an imaging tool arranged to obtain image frames from the manufactured substrate. The apparatus further includes a data processing system which includes computer-readable code configured to compute features for pixels in an image frame and divide the pixels in the image frame into feature-defined groups of pixels. The computer-readable code is further configured to select a feature-defined group, and generate a multi-dimensional feature distribution for the selected feature-defined group. Another embodiment relates to a method of detecting defects from a test images frame and multiple reference image frames. Other embodiments, aspects, and features are also disclosed.