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 medical imaging is changing, and CAI2R has been at the forefront of that change. Tasks that were once the sole domain of meticulously-engineered hardware are increasingly being accomplished in software, aided by modern AI and informed by diverse arrays of inexpensive auxiliary sensors. The longstanding conviction that “bigger is better” in imaging technology is being supplanted, or at least supplemented, by a new “less is more” philosophy. It is a time of remarkable creative flux, with new technologies and new mathematical transforms causing long-held assumptions about the daily practice of imaging to be called into question. In short, imaging is in the process of being reimagined. Each of our three Technology Research and Development (TRD) projects will advance this project of reinvention, introducing new enabling technologies & transforms: 1. Reimagining the Future of Scanning: Intelligent image acquisition, reconstruction, and analysis. 2. Unshackling the Scanners of the Future: From rigid control to flexible sensor-rich navigation. 3. Revealing Microstructure: Biophysical modeling and validation for discovery and clinical care. Having pioneered the use of machine learning for accelerated image reconstruction, and having introduced new continuous comprehensive data acquisition methods, we will bring the two together for improved quantitative imaging. Based on our experience with use of shared information across time in dynamic imaging, we will also explore new ways to leverage prior information in longitudinal scanning over spans of months rather than milliseconds. In place of our early technology test beds of ultra-high-field MRI and MR-PET, we will explore new applications in low-field MRI and MR-guided radiotherapy. We will extend the “standard model” of microstructure originally conceived by our team, developing newly efficient and information-rich diffusion MRI methods. Our Center has an explicit translational focus, which is reflected in the day-to-day operation of TRD 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 ind...