Over the past decade, innovations in the field of pediatric imaging have been based largely on single-center and retrospective studies, which provided limited advances for the benefit of pediatric patients. To identify opportunities for potential "quantum-leap" progress in the field of pediatric imaging, the ACR-Pediatric Imaging Research (PIR) Committee has identified high-impact research directions related to the P4 concept of predictive, preventive, personalized, and participatory diagnosis and intervention. Input from 237 members of the Society for Pediatric Radiology was clustered around 10 priority areas, which are discussed in this article. Needs within each priority area have been analyzed in detail by ACR-PIR experts on these topics. By facilitating work in these priority areas, we hope to revolutionize the care of children by shifting our efforts from unilateral reaction to clinical symptoms, to interactive maintenance of child health.