There is a pressing need to establish novel biomarkers to predict the progression of thoracic aortic aneurysm (TAA) dilatation. Aside from hemodynamics, the roles of oxygen (O₂) and nitric oxide (NO) in TAA pathogenesis are potentially significant. As such, it is imperative to comprehend the relationship between aneurysm presence and species distribution in both the lumen and aortic wall. Given the limitations of existing imaging methods, we propose the use of patient-specific computational fluid dynamics (CFD) to explore this relationship. We have performed CFD simulations of O₂ and NO mass transfer in the lumen and aortic wall for two cases: a healthy control (HC) and a patient with TAA, both acquired using 4D-flow magnetic resonance imaging (MRI). The mass transfer of O₂ was based on active transport by hemoglobin, while the local variations of the wall shear stress (WSS) drove NO production. Comparing hemodynamic properties, the time-averaged WSS was considerably lower for TAA, while the oscillatory shear index and endothelial cell activation potential were notably elevated. O₂ and NO showed a non-uniform distribution within the lumen and an inverse correlation between the two species. We identified several locations of hypoxic regions for both cases due to lumen-side mass transfer limitations. In the wall, NO varied spatially, with a clear distinction between TAA and HC. In conclusion, the hemodynamics and mass transfer of NO in the aorta exhibit the potential to serve as a diagnostic biomarker for TAA. Furthermore, hypoxia may provide additional insights into the onset of other aortic pathologies.

OBJECTIVES: To date, it is not known if 16–20-mm extracardiac conduits are outgrown during somatic growth from childhood to adolescence. This study aims to determine total cavopulmonary connection (TCPC) haemodynamics in adolescent Fontan patients at rest and during simulated exercise and to assess the relationship between conduit size and haemodynamics. METHODS: Patient-specific, magnetic resonance imaging-based computational fluid dynamic models of the TCPC were performed in 51 extracardiac Fontan patients with 16–20-mm conduits. Power loss, pressure gradient and normalized resistance were quantified in rest and during simulated exercise. The cross-sectional area (CSA) (mean and minimum) of the vessels of the TCPC was determined and normalized for flow rate (mm²/l/min). Peak (predicted) oxygen uptake was assessed. RESULTS: The median age was 16.2 years (Q1–Q3 14.0–18.2). The normalized mean conduit CSA was 35–73% smaller compared to the inferior and superior vena cava, hepatic veins and left/right pulmonary artery (all P < 0.001). The median TCPC pressure gradient was 0.7 mmHg (Q1–Q3 0.5–0.8) and 2.0 (Q1–Q3 1.4–2.6) during rest and simulated exercise, respectively. A moderate–strong inverse nonlinear relationship was present between normalized mean conduit CSA and TCPC haemodynamics in rest and exercise. TCPC pressure gradients of >_1.0 at rest and >_3.0 mmHg during simulated exercise were observed in patients with a conduit CSA <_ 45 mm²/l/min and favourable haemodynamics (<1 mmHg during both rest and exercise) in conduits >_125 mm²/l/min. Normalized TCPC resistance correlated with (predicted) peak oxygen uptake. CONCLUSIONS: Extracardiac conduits of 16–20 mm have become relatively undersized in most adolescent Fontan patients leading to suboptimal haemodynamics.

Aortic aneurysm is associated with aberrant blood flow and wall shear stress (WSS). This can be studied by coupling magnetic resonance imaging (MRI) with computational fluid dynamics (CFD). For patient-specific simulations, extra attention should be given to the variation in segmentation of the MRI data-set and its effect on WSS. We performed CFD simulations of blood flow in the aorta for ten different volunteers and provided corresponding WSS distributions. The aorta of each volunteer was segmented four times. The same inlet and outlet boundary conditions were applied for all segmentation variations of each volunteer. Steady-state CFD simulations were performed with inlet flow based on phase-contrast MRI during peak systole. We show that the commonly used comparison of mean and maximal values of WSS, based on CFD in the different segments of the thoracic aorta, yields good to excellent correlation (0.78–0.95) for rescan and moderate to excellent correlation (0.64–1.00) for intra- and interobserver reproducibility. However, the effect of geometrical variations is higher for the voxel-to-voxel comparison of WSS. With this analysis method, the correlation for different segments of the whole aorta is poor to moderate (0.43–0.66) for rescan and poor to good (0.48–0.73) for intra- and interobserver reproducibility. Therefore, we advise being critical about the CFD results based on the MRI segmentations to avoid possible misinterpretation. While the global values of WSS are similar for different modalities, the variation of results is high when considering the local distributions.