Overall Project Summary The Center for Advanced Imaging Innovation and Research (CAI2R) pursues a mission of bringing people together to create new ways of seeing. The work of our Center has been focused on creating new paradigms for the acquisition, reconstruction, and interpretation of biomedical images, and on implementing new collaboration models in order to translate these developments rapidly into clinical practice. The world of biomedical imaging is changing, and CAI2R has been at the forefront of that change. Tasks that were once the sole domain of meticulously-engineered imaging hardware are now beginning to be accomplished in software, increasingly informed by diverse arrays of inexpensive auxiliary sensors. Information once pursued through the laborious acquisition of carefully separated image datasets is now being derived from newly integrated, and richly quantitative, data streams. In keeping with these themes, our Center will be organized around the following four Technology Research and Development (TR&D) projects going forward: 1. Reimagining the Future of Scanning: Intelligent image acquisition, reconstruction, and analysis. 2. Unshackling the Scanners of the Future: Flexible, self-correcting, multisensor machines. 3. Enriching the Data Stream: MRI and PET in concert. 4. Revealing Microstructure: Biophysical modeling and validation for discovery and clinical care. In each of these projects, we aim to push medical imaging technology to the next level, both in hardware and in software. Having made great strides in developing rapid, continuous imaging data streams, we will next aim to add key new information to those streams, both from physics-driven microstructural modeling and from data- driven machine learning. Having focused on the development of robust tools for image acquisition and reconstruction, we will extend the pipeline to image interpretation, using the results of human- or machine- derived evaluations of image content as feedback for the further improvement of acquisition strategies and sensor designs. We will also aim to close the loop between diagnostic sensing and therapeutic intervention, exploring new ways to guide therapy with continuously-acquired information about tissue bioeffects. Our Center has an explicit translational focus, which is reflected in the day-to-day operation of TR&D projects as well as in the topics of Collaborative Projects (CPs) and Service Projects (SPs), which are focused on three general areas of high public health impact: cancer, musculoskeletal disease, and neurologic disease. In keeping with this translational emphasis, CAI2R is also be driven by an embedded collaboration model in which basic scientists, clinicians, and industry developers sit down together regularly at the scanners for interactive technology development and assessment. With early involvement of clinical stakeholders and industry partners, we aim to make CAI2R technologies widely available, for the advancement of ...