A microscope comprising an illumination assembly, an image capture device and a processor can be configured to selectively identify regions of a sample comprising artifacts or empty space. By selectively identifying regions of the sample that have artifacts or empty space, the amount of time to generate an image of the sample and resources used to generate the image can be decreased substantially while providing high resolution for appropriate regions of the computational image. The processor can be configured to change the imaging process in response to regions of the sample that comprises artifacts or empty space. The imaging process may comprise a higher resolution process to output higher resolution portions of the computational image for sample regions comprising valid sample material, and a lower resolution process to output lower resolution portions of the computational image for sample regions comprising valid sample material.