The process of imaging medicine today is dominated by optical devices which are used at the point of care. These procedure-based tools are used together with radiologic devices to capture unique contrast features that help guide medical decisions. In the developments in the Optics in Medicine cluster at Dartmouth, there have been decades of development in image-guided spectroscopy for cancer, as well as surgical guidance tools, and now radiologic guidance tools. Examples from each will be used to highlight innovations in translational research that have gone from concept through to clinical trials, and now through to multicenter trial use. Translation beyond the trial phase involves the type of R&D which only companies can accomplish, and so partnerships with companies in translational research has been paramount, and examples in surgical guidance can show this. Translation through start up company, DoseOptics LLC, will be highlighted in which this pathway has enabled testing and deployment of a fundamentally new technology to image radiation dose delivery in real time. Taken as a whole, the Center for Imaging Medicine initiative supported by Thayer school of Engineering now consists of a dozen engineering faculty, collaborating with two dozen Geisel faculty, working on 42 clinical trials, sponsored by $11 million/year in extramural support, and resulting in 13 company collaborations and 5 startup companies to date. The stages and innovations needed to keep this enterprise going will be the topic of this discussion.