Abstract: An improved ROI segmentation image processing system substantially masks non-ROI image data from a digital image to produce a ROI segmented image for subsequent digital processing. The ROI segmentation image processing system is a computer-based system having a collimation subsystem configured to detect and mask out collimated regions within the image. Furthermore, a direct exposure (DE) subsystem is configured to detect and remove DE regions from the image. Holes generated in the image are filled-in to provide a resulting image with only ROI.