At last year’s SPIE, we presented a multiple sclerosis (MS) eFolder as an integrated imaging-informatics based system to provide several functionalities to both clinical and research environments. The eFolder system combines patients’ clinical data, radiological images and computer-aided lesion detection and quantification results to aid in longitudinal tracking, data mining, decision support, and other clinical and research needs. To demonstrate how this system can be integrated in an existing imaging environment such as a large-scale multi-site MS clinical trial, we present a system infrastructure to streamline imaging and clinical data flow with postprocessing (CAD) steps. The system stores clinical and imaging data, provides CAD postprocessing algorithm and data storage, and a web-based graphical user interface (GUI) to view clinical trial data and monitor workflow. To evaluate the system infrastructure, the MS eFolder is set up in a simulated environment with workflow scenarios, including DICOM store, query, and retrieve, automatic CAD steps, and data mining based on CAD results. This project aims to discuss the methodology of setting up eFolder system simulation with a connection to a CAD server component, simulation performance and test results, and discussion of eFolder system deployment results.