Wall Shear Stress (WSS) topological skeleton, composed by fixed points and the manifolds linking them, reflects the presence of blood flow features associated to adverse vascular response. However, the influence of WSS topological skeleton on vascular pathophysiology is still underexplored. This study aimed to identify direct associations between the WSS topological skeleton and markers of vascular disease from real-world clinical longitudinal data of long-term restenosis after carotid endarterectomy (CEA). Personalized computational hemodynamic simulations were performed on a cohort of 13 carotid models pre-CEA and at 1 month after CEA. At 60 months after CEA, intima-media thickness (IMT) was measured to detect long-term restenosis. The analysis of the WSS topological skeleton was carried out by applying a Eulerian method based on the WSS vector field divergence. To provide objective thresholds for WSS topological skeleton quantitative analysis, a computational hemodynamic dataset of 46 ostensibly healthy carotid bifurcation models was considered. CEA interventions did not completely restore physiological WSS topological skeleton features. Significant associations emerged between IMT at 60 months follow-up and the exposure to (1) high temporal variation of WSS contraction/expansion (R² = 0.51, p < 0.05), and (2) high fixed point residence times, weighted by WSS contraction/expansion strength (R² = 0.53, p < 0.05). These WSS topological skeleton features were statistically independent from the exposure to low WSS, a previously reported predictor of long-term restenosis, therefore representing different hemodynamic stimuli and potentially impacting differently the vascular response. This study confirms the direct association between WSS topological skeleton and markers of vascular disease, contributing to elucidate the mechanistic link between flow disturbances and clinical observations of vascular lesions.

The combination of medical imaging and computational hemodynamics is a promising technology to diagnose/prognose coronary artery disease (CAD). However, the clinical translation of in silico hemodynamic models is still hampered by assumptions/idealizations that must be introduced in model-based strategies and that necessarily imply uncertainty. This study aims to provide a definite answer to the open question of how to properly model blood rheological properties in computational fluid dynamics (CFD) simulations of coronary hemodynamics. The geometry of the right coronary artery (RCA) of 144 hemodynamically stable patients with different stenosis degree were reconstructed from angiography. On them, unsteady-state CFD simulations were carried out. On each reconstructed RCA two different simulation strategies were applied to account for blood rheological properties, implementing (i) a Newtonian (N) and (ii) a shear-thinning non-Newtonian (non-N) rheological model. Their impact was evaluated in terms of wall shear stress (WSS magnitude, multidirectionality, topological skeleton) and helical flow (strength, topology) profiles. Additionally, luminal surface areas (SAs) exposed to shear disturbances were identified and the co-localization of paired N and non-N SAs was quantified in terms of similarity index (SI). The comparison between paired N vs. shear-thinning non-N simulations revealed remarkably similar profiles of WSS-based and helicity-based quantities, independent of the adopted blood rheology model and of the degree of stenosis of the vessel. Statistically, for each paired N and non-N hemodynamic quantity emerged negligible bias from Bland-Altman plots, and strong positive linear correlation (r > 0.94 for almost all the WSS-based quantities, r > 0.99 for helicity-based quantities). Moreover, a remarkable co-localization of N vs. non-N luminal SAs exposed to disturbed shear clearly emerged (SI distribution 0.95 [0.93, 0.97]). Helical flow topology resulted to be unaffected by blood rheological properties. This study, performed on 288 angio-based CFD simulations on 144 RCA models presenting with different degrees of stenosis, suggests that the assumptions on blood rheology have negligible impact both on WSS and helical flow profiles associated with CAD, thus definitively answering to the question "is Newtonian assumption for blood rheology adequate in coronary hemodynamics simulations?".

The degeneration of the arterial wall at the basis of the ascending thoracic aortic aneurysm (ATAA) is a complex multifactorial process, which may lead to clinical complications and, ultimately, death. Individual genetic, biological or hemodynamic factors are inadequate to explain the heterogeneity of ATAA development/progression mechanisms, thus stimulating the analysis of their complex interplay. Here the disruption of the hemodynamic environment in the ATAA is investigated integrating patient-specific computational hemodynamics, CT-based in vivo estimation of local aortic stiffness and advanced fluid mechanics methods of analysis. The final aims are (1) deciphering the ATAA spatiotemporal hemodynamic complexity and its link to near-wall topological features, and (2) identifying the existing links between arterial wall degeneration and hemodynamic insult. Technically, two methodologies are applied to computational hemodynamics data, the wall shear stress (WSS) topological skeleton analysis, and the Complex Networks theory. The same analysis was extended to the healthy aorta. As main findings of the study, we report that: (1) different spatiotemporal heterogeneity characterizes the ATAA and healthy hemodynamics, that markedly reflect on their WSS topological skeleton features; (2) a link (stronger than canonical WSS-based descriptors) emerges between the variation of contraction/expansion action exerted by WSS on the endothelium along the cardiac cycle, and ATAA wall stiffness. The findings of the study suggest the use of advanced methods for a deeper understanding of the hemodynamics disruption in ATAA, and candidate WSS topological skeleton features as promising indicators of local wall degeneration.

Patient-specific computational fluid dynamics is a powerful tool for investigating the hemodynamic risk in coronary arteries. Proper setting of flow boundary conditions in computational hemodynamic models of coronary arteries is one of the sources of uncertainty weakening the findings of in silico experiments, in consequence of the challenging task of obtaining in vivo 3D flow measurements within the clinical framework. Accordingly, in this study we evaluated the influence of assumptions on inflow velocity profile shape on coronary artery hemodynamics. To do that, (1) ten left anterior descending coronary artery (LAD) geometries were reconstructed from clinical angiography, and (2) eleven velocity profiles with realistic 3D features such as eccentricity and differently shaped (single- and double-vortex) secondary flows were generated analytically and imposed as inflow boundary conditions. Wall shear stress and helicity-based descriptors obtained prescribing the commonly used parabolic velocity profile were compared with those obtained with the other velocity profiles. Our findings indicated that the imposition of idealized velocity profiles as inflow boundary condition is acceptable as long the results of the proximal vessel segment are not considered, in LAD coronary arteries. As a pragmatic rule of thumb, a conservative estimation of the length of influence of the shape of the inflow velocity profile on LAD local hemodynamics can be given by the theoretical entrance length for cylindrical conduits in laminar flow conditions.