Project Summary Congenital heart disease (CHD) is the most common defect affecting approximately 1% of live births. Initially developed and optimized for adults, cardiac magnetic resonance imaging (CMR) is increasingly used in pediatric CHD patients to complement echocardiography and invasive angiography for anatomical and functional evaluation of the heart and blood vessels. For children, the non-invasiveness, unrestricted field of view, and absence of ionizing radiation make MRI an attractive imaging modality because many will need sequential imaging and long-term follow-up evaluations. However, current CMR for very young children requires general anesthesia and invasive intubation for acquisition of images that are of acceptable diagnostic quality. In the past 5 years, we pioneered ferumoxytol-enhanced CMR techniques that provide unprecedented image quality and diagnostic value; this technique has changed how CMR for pediatric CHD is clinically performed at our center. Our diagnostic application of ferumoxytol obviates any concerns about gadolinium accumulation in biologic tissues, In this renewal R01, we aim to develop next-generation CMR that can be performed without invasive intubation, and potentially with reduced anesthesia/sedation exposure. We further propose to build upon our improved CMR framework to develop advanced anatomical and hemodynamic modeling techniques for complex CHD. Together, these tools provide a CMR image-based strategy to help inform the patient's surgical plan and to ultimately predict surgical outcome. We will expand our multi-center collaborations to pool data and enable larger scale studies. Completion of the project will result in clinical deployment of new MRI pulse sequences, image acquisition and reconstruction strategies, and experimental and computational modeling methods.