Tetralogy of Fallot (TOF) accounts for approximately 10 percent of congenital heart disease. Surgical techniques have improved survival such that TOF patients require follow-up for common post-operative complications, including pulmonary regurgitation (PR) and right ventricular (RV) dilatation, right and/or left ventricular dysfunction, atrial and ventricular arrhythmias and sudden death¹. MRI plays a central role in evaluating these abnormalities and determining indications for reintervention, however, risk assessment is based on simplified functional parameters (e.g. ejection fraction, indexed ventricular volumes) which measure late expression of underlying physiologic changes². In the repaired TOF patient with chronic PR, pulmonary valve replacement may reverse RV dilatation, but risk of arrhythmia and sudden death may not be avoided³. Consequently, early and more sensitive markers of deteriorating hemodynamics are needed. While emerging 4D MRI techniques promise new insights, published findings in TOF are largely descriptive characterizations of abnormal flow patterns^4,5 or comparisons to traditional 2D MR flow parameters⁶. In this study we explore newer quantitative 4D measures that may be alternative markers of hemodynamic efficiency in patients with repaired TOF.We compared pediatric patients who were status post TOF repair (n=24) with age-appropriate healthy control subjects (n=22) in accordance with a prospective IRB-approved protocol. All patients underwent standard-of-care MRI with bloodpool contrast administration, as well as ECG and respiratory navigator gated 4D flow MRI. Ventricular volumes and function were measured using standard cine post-processing techniques. All 4D flow MRI data were corrected for velocity aliasing, Maxwell terms and eddy currents⁷ from which time-averaged 3D PC-MR angiograms were calculated. Commercial software (Mimics, Materialise, Leuven, Belgium) was used to generate 3D segmentations of the thoracic aorta (Ao) and main and proximal branch pulmonary arteries (PA) (Figure 1A). A custom software tool developed in Matlab (The MathWorks, Natick, MA, USA) was used to derive energetic parameters from Ao and PA segmentations. For each voxel inside the Ao and PA segmentation volumes, maximum systolic flow acceleration, maximum diastolic deceleration, and kinetic energy (KE) were calculated. KE for a voxel of blood was calculated using the equation KE = 1/2 mv², where mass (m) is voxel volume multiplied by density of blood (1.05 g/mL) and velocity (v) determined from 4D flow . For each subject, average KE was calculated over 3 phases (systole, early diastole and late diastole) in order to compare changes across the cardiac cycle. Ao and PA KE maps were generated for each phase by projecting mean KE on a 2D plane transecting the Ao and PA, respectively (Figure 1B). Total KE_Ao and KE_PA were calculated as the sum over all voxels inside the Ao and PA segmentations and indexed to body surface area (BSA).Age and gender distribution were similar between TOF patients and controls, though TOF had smaller BSA, significant PR, increased ventricular size and diminished ventricular function, as expected. There were also significant differences in several calculated 4D energetic parameters (Table 1). Systolic KE_Ao was higher in controls while systolic KE_PA was increased in TOF. Patients with TOF had higher KE_PA throughout early and late diastole, a finding that remained true even when corrected for BSA. Figure 2 compares distribution of KE_PA across the cardiac cycle in a control subject and two TOF patients. Greater KE_PA is expended during systole in both TOF patients compared to the control, while KE_PA during late diastole is increased only in the patient with severe PR and RV dilatation. Interestingly, in a subgroup analysis comparing TOF patients with severe PR (>25% regurgitation fraction, 73% of whom underwent transannular patch repair) and those without severe PR (<25%, 75% of whom underwent valve sparing repair), we found that both absolute and indexed KE_PA during late diastole was significantly higher in the severe PR cohort (4.3±3.0 vs 1.3±2.8 mJ, p=0.02; 3.3±1.9 vs 1.0±1.9 mJ/m², p<0.01). In fact, KE_PA significantly correlated with RV end-diastolic volume (Figure 3). Additionally, maximum systolic acceleration in the PA correlated with RV ejection fraction (R=0.31).Conventional MRI assessment of patients with repaired TOF relies heavily on morphologic and simplified functional parameters. 4D flow offers whole heart, post-hoc derivation of additional quantitative metrics to assess disease progression in patients with chronic PR. Energetic measures such as KE and maximum systolic acceleration are abnormal in TOF compared to healthy controls. While these measures correlate modestly with routine measurements of ventricular efficiency, they may be earlier markers of disease progression. Additional comparison with ventricular KE may yield further insights into important ventricular-vascular coupling relationships, energy loss and deteriorating hemodynamics. Comparison to exercise capacity and clinical outcomes in a larger cohort is warranted.