With the large amount of image data accumulated daily from medical imaging modalities and Picture Archiving and Communication Systems (PACS) in hospitals, we can take advantage of this resource to investigate innovative clinical service, research and education using the concept of imaging informatics. In this paper we describe three current PACS -based research agendas: medical imaging informatics, Data Grid for image backup and disaster recovery, and Computer-Assisted Detection and diagnosis (CAD). In addition, we also discuss the concept of combining image-guided diagnosis and treatment in a continuum. As an example, integrating innovative imaging technologies for diagnosis and treatment in Minimally Invasive Spine Surgery (MISS) is highlighted. The success of implementing these novel agendas and concepts will have tremendous impact to better present and future healthcare delivery.