Project Abstract/Summary Congenital heart disease (CHO) afflicts up to 2% of live births in the United States. Among the most severe CHO is single ventricle disease (SVD) where infants are born with only one sufficiently functional ventricle. SVD often requires a series of surgeries that is completed with the Fontan procedure. This results in a circulation that bypasses a right-heart-driven pulmonary circulation, instead, routing systemic venous return directly to the pulmonary arteries. While it is a life-saving procedure, a common complication later in life is failing Fontan physiology which often results in heart transplant, initiation of palliation, or death. Despite regular monitoring of these patients, the underlying mechanisms leading to Fontan failure are poorly understood. Several modes of Fontan failure are hypothesized to be secondary to changes in 3D blood flow dynamics inside the Fontan connection. Current standard-of care imaging methods (echocardiography and 2D phase contrast MRI) capture only 1D hemodynamics and have substantial user variability. 4D flow MRI, a technique pioneered by our lab, was developed to address these challenges, and enable volumetric, 3D velocity measurement over the cardiac cycle. While this technique has been used to study Fontan hemodynamics, among other CHDs, it is not optimal for thorough, life-long monitoring. 4D flow has long, unpredictable scan times which are not amenable to small children requiring anesthesia during cardiac MRI studies. Additionally, 4D flow has a limited velocity dynamic range, lacks flexible reconstruction for different temporal and spatial resolution, and does not capture respiratory driven flow, a hemodynamic feature known to be important in the Fontan connection. To address these limitations, we have developed a method termed 5D flow MRI, a free-running technique with flexible, compressed sensing reconstruction that captures 3D velocities along the cardiac and respiratory cycles. The first aim of this proposal is to develop an under 10 minutes dual-velocity encode (venc) 5D flow method along with a streamlined processing and analysis pipeline. This will enable accurate, simultaneous measurement of flow in veins and arteries while remaining sufficiently short for patients requiring general anesthesia. The second aim of this proposal is to validate this method and to optimize the reconstruction and acquisition parameters. This will be crucial for understanding the reliability of the metrics compared to clinical standards and to ensure that respiratory resolved flow is accurate. The third aim of this proposal is to apply the developed sequence in a cohort of patients with the Fontan connection. I hypothesize that: 1. Dual-venc 5D flow will be faster and simpler than clinically standard acquisitions, 2. Respiratory resolved flow measurements reveal additional hemodynamic information, 3. Voxel-wise parameters derived from 5D flow, such as respiratory driven peak velocities, correla...