Abstract Positron emission tomography (PET) is a standard of care to molecularly characterize cancer and heart disease. It is also a well-used research tool to visualize and quantify molecular pathways of disease in neurological disorders. We propose to develop a metamaterial to create a “super-scintillator” for time-of-flight (ToF) PET. If successful, this technology will substantially enhance the image quality and quantitative accuracy of PET and open new roles for the modality in the management of disease. PET employs a radiolabeled molecular contrast agent that is injected into the patient to probe the biological mechanisms of disease. This tracer accumulates in the cells that express certain molecular signatures, enabling 3-dimensional visualization and quantification of disease biomarkers. The tracer molecule is labeled by a positron emitter that for every decay results in the emission of two oppositely directed 511 kilo-electron-volt (keV) annihilation photons. ToF-PET uses the arrival time difference between the two photons in each pair to more accurately position the emission location along PET system detector response lines, enhancing the reconstructed image signal-to-noise ratio (RISNR). RISNR is an image quality metric that strongly correlates with lesion detection sensitivity and accuracy. The more precise this time difference measurement, known as the coincidence time resolution (CTR), the better the RISNR. Any boosts in RISNR can also be employed to reduce injected radioactive dose or scanning duration, increasing patient safety or throughput in the clinic, respectively. The long-term goal for the proposed new scintillation technology is <10 picosecond (ps) CTR, which is over 20-fold better than the best CTR (214 ps) achieved for a state-of-the-art clinical ToF-PET system, enabling ~5-fold higher RISNR or ~25-fold lower injected dose or scan time compared to that system. If successful, this capability would enable new applications for PET. Current PET systems employ scintillation crystals, which are materials that convert 511 keV photon interactions in the crystal into flashes of visible light. We propose to use nanophotonic techniques to create a metamaterial “super” scintillator with vastly shorter rise time and decay time and greater light yield than all known PET scintillators, enabling the >20-fold reduction in CTR proposed. The emergence of nanophotonics and metamaterials has revolutionized photonics. Nanostructured materials provide considerable control over internal electromagnetic fields, enabling highly unusual optical properties not found in standard materials. This exciting investigation will have tremendous impact by both introducing a new technology, metamaterials, to the field of biomedical imaging, and by achieving breakthrough performance levels in PET imaging, that, if successful, will greatly expand PET’s capabilities for characterizing disease, as well as enable new roles for PET in disease management.