Project Summary: Revolutionary advances in imaging drive discovery in the biological sciences and medicine. These advances in imaging sciences depend on innovations in technology throughout the physical and biological sciences. In recent decades, a number of significant breakthroughs have underscored the fundamental importance of this interdependent relationship between technology and biomedical science. One important discovery that culminated in the 2008 Nobel Prize was the work on fluorescent proteins in the laboratories of Shimomura, Chalfie, Inoue, Tsien and many others. “Live cell microscopy would have remained in the hands of a small number of skilled cell biologists had not these groups devised a simple way to use molecular biology to tag vital proteins in living cells. Gene products can be localized not only structurally, as with antibody technology, but also dynamically within living cells. With this technology, it is now possible to place virtually any biomolecule in the context of structure and dynamics; that is, within space and time.” From the current perspective, where are the frontiers of imaging sciences in the 21st century, and what are its biggest challenges? Challenges in basic and translational sciences, often define the imaging science challenges, as illustrated in the following examples. (1) Optogenetic and Chemogenetic techniques have revolutionized the way brain circuitry is probed, and now enable dissection of complex neuromodulatory circuits related to reward, aversion and anxiety. Novel Sonogenetic methods are also just now emerging. Yet these technologies for “writing” information into the brain require advances in imaging to “read” the responses. (2) Computational imaging has experienced a revolution over the last 5 years with the incredible growth in machine learning and deep learning techniques. However, as these methods are translated into clinical applications the challenges in optimizing and validating implementation loom large. (3) Tremendous progress is anticipated in the area of cell therapy and tissue engineering. Yet, these advanced therapeutics are asking for advancements in imaging for personalized therapeutic optimization. (4) Major advances in multimodal imaging technologies have recently been made, most prominently the development of PET/MR hybrid systems. New hybrid imaging systems that combine PET and optical or photoacoustic imaging, for example, advance only through solving imaging science challenges. A new educational and creative paradigm is required to prepare future imaging scientists for solving these problems. Interdisciplinary teams of engineers, physicists, computer scientists, mathematicians, chemists, biologists, and physicians working together at the interfaces between biology, technology, and medicine are needed to collaborate in the development of new imaging technologies and strategies. With these needs and goals in mind, Washington University created the Imaging Sciences Pathway (ISP)...