Impact of Patient-Specific Inflow Boundary Conditions and Concentration Initialization on Hemodynamics and Low-Density Lipoproteins Transport in the Thoracic Aorta

The complex hemodynamics observed in the human aorta make this district a site of election for an in depth investigation of the relationship between fluid structures, transport and patho-physiology. In fact, it is well known that hemodynamics play an important role in the mass transport of blood specimen, and in turn, in their transfer to the vascular wall and ultimately in the localization of vascular disease in areas of complex arterial flow. In particular, the accumulation of lipoproteins in the arterial intima is a hallmark of atherosclerosis. Low-density lipoproteins (LDL) are the most abundant atherogenic lipoproteins in plasma and high plasma levels of LDL are causally related to the development of atherosclerosis. Advanced computational fluid dynamics coupled with medical imaging allows to combine the anatomical and hemodynamic inputs to realistic, fully personalized flow simulations to study local hemodynamics in arteries. Such an approach represents an effective way when addressing the still open questions about the role of blood-side LDL transfer to the arterial wall in atherogenesis. In particular, personalized computational models have been proposed to study LDL blood-to-wall transfer in the aorta, a district of election for the study of the relationships between the intricate local hemodynamics, LDL transport and disease. However, computational hemodynamics requires some assumptions that could affect the solutions of the equations governing blood flow and the aortic LDL transport and wall transfer. In previous studies of my research group, has been demonstrated that different strategies in applying boundary conditions (BCs) derived from phase-contrast MRI (PC-MRI) measurements could lead to different results in terms of distribution of near-wall and intravascular flow quantities. Additionally, a paucity of data characterizes the literature concerning the BCs and initial conditions (ICs) adopted to model LDL transport. In this contest, my thesis project have been focalized in analysing the impact that different possible strategies of applying (1) PC-MRI measured data as inflow BCs, and (2) LDL concentration profiles as ICs, have on LDL blood-to-wall transfer modelling in the human aorta. Technically, two different inflow BCs are generated, by imposing at the ascending aorta inflow PC-MRI measured 3D velocity profiles or idealized (flat) velocity profiles. In this way, the sensitivity of blood-to-wall LDL transfer to the inflow BC is explored, as the inflow BC influences LDL advective transport. The impact of applied BC-IC strategies on LDL blood-to-wall transfer has been evaluated in terms of computational costs and LDL polarization profiles at the luminal surface. Moreover, by virtue of the reported high LDL concentration in correspondence of disturbed shear regions, here a co-localization analysis with areas exposed to atheroprone wall shear stress (WSS) phenotype has been conducted as a “physics consistency check”. The results of my research would contribute to clarify which is (1) the level of detail obtained from measured flow data to be used as inflow BC, and (2) the plausibility of hypotheses on LDL concentration to be used as IC strategy, to satisfactorily simulate mass transport/transfer in personalized complex hemodynamic models of human aorta

Smartphone-based particle tracking velocimetry for the in vitro assessment of coronary flows

The present study adopts a smartphone-based approach for the experimental characterization of coronary flows. Technically, Particle Tracking Velocimetry (PTV) measurements were performed using a smartphone camera and a low-power continuous wave laser in realistic healthy and stenosed phantoms of left anterior descending artery with inflow Reynolds numbers approximately ranging from 20 to 200. A Lagrangian-Eulerian mapping was performed to convert Lagrangian PTV velocity data to a Eulerian grid. Eulerian velocity and vorticity data obtained from smartphone-based PTV measurements were compared with Particle Image Velocimetry (PIV) measurements performed with a smartphone-based setup and with a conventional setup based on a high-power double-pulsed laser and a CMOS camera. Smartphone-based PTV and PIV velocity flow fields substantially agreed with conventional PIV measurements, with the former characterized by lower average percentage differences than the latter. Discrepancies emerged at high flow regimes, especially at the stenosis throat, due to particle image blur generated by smartphone camera shutter speed and image acquisition frequency. In conclusion, the present findings demonstrate the feasibility of PTV measurements using a smartphone camera and a low-power light source for the in vitro characterization of cardiovascular flows for research, industrial and educational purposes, with advantages in terms of costs, safety and usability

Modeling methodology for defining a priori the hydrodynamics of a dynamic suspension bioreactor. Application to human induced pluripotent stem cell culture

Three-dimensional dynamic suspension is becoming an effective cell culture method for a wide range of bioprocesses, with an increasing number of bioreactors proposed for this purpose. The complex hydrodynamics establishing within these devices affects bioprocess outcomes and efficiency, and usually expensive in vitro trial-and-error experiments are needed to properly set the working parameters. Here we propose a methodology to define a priori the hydrodynamic working parameters of a dynamic suspension bioreactor, selected as a test case because of the complex hydrodynamics characterizing its operating condition. A combination of computational and analytical approaches was applied to generate operational guideline graphs for defining a priori specific working parameters. In detail, 43 simulations were performed under pulsed flow regime to characterize advective transport within the device depending on different operative conditions, i.e., culture medium flow rate and its duty cycle, cultured particle diameter, and initial particle suspension volume. The operational guideline graphs were then used to set specific hydrodynamic working parameters for an in vitro proof-of-principle test, where human induced pluripotent stem cell (hiPSC) aggregates were cultured for 24 h within the bioreactor. The in vitro findings showed that, under the selected pulsed flow regime, sedimentation was avoided, hiPSC aggregate circularity and viability were preserved, and culture heterogeneity was reduced, thus confirming the appropriateness of the a priori method. This methodology has the potential to be adaptable to other dynamic suspension devices to support experimental studies by providing in silico-based a priori knowledge, useful to limit costs and to optimize culture bioprocesses

Wall shear stress topological skeleton independently predicts long-term restenosis after carotid bifurcation endarterectomy

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

Wall shear stress topological skeleton analysis in cardiovascular flows: Methods and applications

A marked interest has recently emerged regarding the analysis of the wall shear stress (WSS) vector field topological skeleton in cardiovascular flows. Based on dynamical system theory, the WSS topological skeleton is composed of fixed points, i.e., focal points where WSS locally vanishes, and unstable/stable manifolds, consisting of contraction/expansion regions linking fixed points. Such an interest arises from its ability to reflect the presence of near-wall hemodynamic features associated with the onset and progression of vascular diseases. Over the years, Lagrangian-based and Eulerianbased post-processing techniques have been proposed aiming at identifying the topological skeleton features of the WSS. Here, the theoretical and methodological bases supporting the Lagrangian- and Eulerian-based methods currently used in the literature are reported and discussed, highlighting their application to cardiovascular flows. The final aim is to promote the use of WSS topological skeleton analysis in hemodynamic applications and to encourage its application in future mechanobiology studies in order to increase the chance of elucidating the mechanistic links between blood flow disturbances, vascular disease, and clinical observations

Modelling blood flow in coronary arteries: Newtonian or shear-thinning non-Newtonian rheology?

BACKGROUND 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. METHODS 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). RESULTS 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. CONCLUSIONS 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?"