Multi-site imaging research has several specialized needs that are substantially different from what is commonly available in clinical imaging systems. An attempt to address these concerns is being led by several institutes including the National Institutes of Health and the National Cancer Institute. With the exception of results reporting (which has an infrastructure for standard reports, albeit with several competing lexicons), medical imaging has been largely standardized by the efforts of DICOM, HL7, and IHE. What are not well developed in this area are the tools required for multi-site imaging collaboration and data mining. The goal of this paper is to identify existing clinical interoperability methods that can be used to harmonize the research and clinical worlds, and identify gaps where they exist. To do so, we will detail the approaches of a specific multi-site trial, point out the current deficiencies and workarounds developed in that trial, and finally point to work that seeks to address multi-site imaging challenges.