Fetal 4D Flow CMR for Advanced Diagnostics of Congenital Heart Disease: Clinical Feasibility

Background: Fetal circulation undergoes complex changes in congenital heart disease (CHD) that are challenging to assess with fetal echocardiography. As fetal cardiovascular magnetic resonance (CMR) emerges as an adjunct imaging modality, 4D flow imaging could provide previously unattainable diagnostic information for advanced evaluation of fetal circulation. This study aimed to assess clinical feasibility and diagnostic value of 4D flow imaging in fetal CMR of CHD.

Methods: Pregnant women in advanced third trimester pregnancy with suspected fetal CHD were prospectively recruited for fetal CMR between 08/2021 and 11/2024. CMR protocol included cine and 4D time-resolved phase-contrast acquisitions. 4D flow data were analyzed and evaluated for additional diagnostic information beyond cine imaging. Postnatal examination reports were used to confirm CMR findings. Net flow was quantified in the ascending aorta, distal aortic arch, main pulmonary artery, ductus arteriosus, and descending aorta, and normalized to combined ventricular output (CVO). Student’s t-test and analysis of variance (ANOVA) with Tukey post-hoc test was applied.

Results: Among 77 participants (mean gestational age: 35.8 ± 1.2 weeks), 4D flow was of diagnostic quality in 62 (81%) fetuses (11/62 [18%] without CHD, 51/62 [82%] with CHD). Comparison of net flow distributions revealed significant differences between fetuses without CHD and those with hypoplastic left heart complex (HLHC), dextro-transposition of the great arteries, and coarctation of the aorta. CVO was higher in normal fetal circulation compared to CHD (6.4 ± 1.5 ml vs. 5.1 ± 1.9 ml, p = 0.049). 4D flow provided diagnostic findings beyond cine imaging in 26 of 51 (51%) fetuses with CHD (e.g., retrograde aortic perfusion in HLHC, circular shunting in Ebstein anomaly, or adverse stream patterns in truncus arteriosus communis with oxygenated blood directed to the lungs instead of the brain) that were confirmed postnatally.

Conclusion: Fetal 4D flow CMR characterizes flow patterns and provides relevant diagnostic information beyond cine imaging for CHD assessment. As barriers for clinical translation and integration into routine protocols are minimal, 4D flow CMR could improve prenatal assessment and diagnosis of CHD.

Box-whisker plots of combined ventricular output (CVO) and antegrade net blood flow volumes in the ascending aorta (AAo), distal aortic arch (AA), main pulmonary artery (MPA), ductus arteriosus (DA), and descending aorta (DAo) in fetuses without congenital heart disease (CHD) and major CHD subgroups. Schematic illustrations show relative net flows normalized to the CVO for visual comparison of flow redistribution patterns across conditions. In fetuses without CHD, the right ventricle contributes the majority of the CVO, a pattern amplified hypoplastic left heart complex. In d-transposition of the great arteries, this pattern reverses due to discordant ventricular-arterial connections. In coarctation of the aorta, left ventricular contribution to the CVO remains normal, but only 6% of the CVO passes through the distal aortic arch, reflecting the hemodynamic impact of the narrowing. These characteristic distribution patterns are consistent with previous measurement in animal models and 2D flow CMR; however, 4D flow uniquely enables comprehensive assessment of the entire fetal circulation within a single acquisition.
Fetal 4D flow pathline visualizations with time-velocity curves in a fetus without congenital heart disease (CHD) and in fetuses with the two most common cyanotic heart defects: tetralogy of Fallot (TOF) and d-transposition of the great arteries (d-TGA). In the fetus without CHD, most descending aorta (Dao) flow passes through the main pulmonary artery (MPA) and ductus arteriosus (DA), with a smaller portion via the ascending aorta (AAo) and distal aortic arch (AA). Conversely, in TOF, pulmonary obstruction directs most combined ventricular output (CVO) through the AA, while in d-TGA, discordant ventricular-arterial connections cause a similar pattern. A key advantage of 4D flow over other flow imaging techniques is its ability to simultaneously depict anatomical features throughout the entire circulation: in the fetus without CHD, the AA and DA are nearly equal in size, whereas in TOF, reduced pulmonary blood flow is reflected in the smaller DA compared to the AA. Normal crossing pattern of the AAo and MPA is evident in the fetus without CHD and in TOF, while in d-TGA, the great arteries are parallel, obscuring the inferior DA and left pulmonary artery (LPA) from cranial views, while the right pulmonary artery (RPA) to the right remains visible.
Images from a fetus with severe Ebstein anomaly and a circular shunt at 36 weeks of gestation (fetus 31). Diastole: (Top) 4D flow pathline visualization and axial cine overlay shows filling of the left ventricle (LV) and the enlarged right ventricle (RV). (Bottom) An anterior 4D flow pathline view highlights blood flow distribution from the right atrium (RA) across the anteriorly displaced tricuspid valve (TV), primarily directed cranially toward the right ventricular outflow tract. Systole: (Top left) The LV ejects blood into the ascending aorta (AAo), while RV blood predominantly regurgitates back into the RA via the insufficient TV, crossing the foramen ovale into the left heart. (Top right) Pathline visualization reveals absent antegrade flow in the main pulmonary artery and retrograde perfusion of the hypoplastic ductus arteriosus (DA) from the aortic arch, forming a circular shunt pathway (AAo → DA → RA → foramen ovale → LV → AAo). (Bottom left) Pathline visualization and (bottom right) velocity vectors depict massive retrograde flow from the RV into the RA through the insufficient TV, generating a prominent vortical flow pattern within the RA. The ability to visualize complex, multidirectional flow patterns enabled the identification of the circular shunt in this fetus, which would likely have been missed using 2D flow imaging alone.