Systems and methods that acquire digital slides and other large images and store these images into commercially available PACS systems using DICOM-standard messaging are provided. A digital slide or other large two-dimensional image is acquired and each separate resolution level of the digital slide or large image is divided into a series of regions that are each identified as a DICOM image. All of the regions at the same resolution in the digital slide or other large image are collectively identified as a DICOM series. A plurality of DICOM series, representing multiple resolution levels in a digital slide are collectively identified and stored as a DICOM study.