Magnitude Of Wall Shear Stress Research Articles

Assessment of abnormal transvalvular flow and wall shear stress direction for pediatric/young adults with bicuspid aortic valve: a cross-sectional 4D flow study

BackgroundAortic dilation is seen in pediatric/young adult patients with bicuspid aortic valve (BAV), and hemodynamic markers to predict aortic dilation are necessary for monitoring. Although promising hemodynamic metrics, such as abnormal wall shear stress (WSS) magnitude, have been proposed for adult BAV patients using 4D flow cardiovascular magnetic resonance, those for pediatric BAV patients have less frequently been reported, partly due to scarcity of data to define normal WSS range. To circumvent this challenge, this study aims to investigate if a recently proposed 4D flow-based hemodynamic measurement, abnormal flow directionality, is associated with aortic dilation in pediatric/young adult BAV patients. Methods4D flow scans for BAV patients (<20 years old) and age-matched controls were retrospectively enrolled. Static segmentation for the aorta and pulmonary arteries was obtained to quantify peak systolic hemodynamics and diameters in the proximal aorta. In addition to peak velocity, wall shear stress (WSS), vorticity, helicity, and viscous energy loss, direction of aortic velocity and WSS in BAV patients was compared with that of control atlas using registration technique; angle differences of >60deg and >120deg were defined as moderately and severely abnormal, respectively. Association between the obtained metrics and normalized diameters (Z-scores) were evaluated at the sinotubular junction, mid ascending aorta, and distal ascending aorta. ResultsFifty-three BAV patients, including eighteen with history of repaired aortic coarctation, and seventeen controls were enrolled. Correlation between moderately abnormal velocity/WSS direction and aortic Z-scores was moderate to strong at the sinotubular junction and mid ascending aorta (R=0.62-0.81; p<0.001) while conventional measurements exhibited weaker correlation (|R|=0.003-0.47, p=0.009-0.99) in all subdomains. Multivariable regression analysis found moderately abnormal velocity direction and existence of aortic regurgitation (only for isolated BAV group) were independently associated with mid ascending aortic Z-scores. ConclusionAbnormal velocity and WSS directionality in the proximal aorta was strongly associated with aortic Z-scores in pediatric/young adult BAV patients.

Patient-specific arterial wall generation for intracranial aneurysms with a variable and a near realistic vessel wall thickness for FSI studies

Background and ObjectiveImaging methodologies such as, computed tomography (CT) aid in three-dimensional (3D) reconstruction of patient-specific aneurysms. The radiological data is useful in understanding their location, shape, size, and disease progression. However, there are serious impediments in discerning the blood vessel wall thickness due to limitations in the current imaging modalities. This further restricts the ability to perform high-fidelity fluid structure interaction (FSI) studies for an accurate assessment of rupture risk. FSI studies would require the arterial wall mesh to be generated to determine realistic maximum allowable wall stresses by performing coupled calculations for the hemodynamic forces with the arterial walls. MethodsIn the present study, a novel methodology is developed to geometrically model variable vessel wall thickness for the lumen isosurface extracted from CT scan slices of patient-specific aneurysms based on clinical and histopathological inputs. FSI simulations are carried out with the reconstructed models to assess the importance of near realistic wall thickness model on rupture risk predictions. ResultsDuring surgery, clinicians often observe translucent vessel walls, indicating the presence of thin regions. The need to generate variable vessel wall thickness model, that embodies the wall thickness gradation, is closer to such clinical observations. Hence, corresponding FSI simulations performed can improve clinical outcomes. Considerable differences in the magnitude of instantaneous wall shear stresses and von Mises stresses in the walls of the aneurysm was observed between a uniform wall thickness and a variable wall thickness model. ConclusionIn the present study, a variable vessel wall thickness generation algorithm is implemented. It was shown that, a realistic wall thickness modeling is necessary for an accurate prediction of the shear stresses on the wall as well as von Mises stresses in the wall. FSI simulations are performed to demonstrate the utility of variable wall thickness modeling.

Numerical investigation on flow-induced wall shear stress variation of metastatic cancer cells in lymphatics with elastic valves

Hematogenous metastasis occurs when cancer cells detach from the extracellular matrix in the primary tumor into the bloodstream or lymphatic system. Elucidating the response of metastatic tumor cells in suspension to the flow conditions in lymphatics with valves from a mechanical/fluidic perspective is necessary. A physiologically relevant computational model of a lymphatic vessel with valves was constructed using fully coupled fluid–cell–vessel interactions to investigate the effects of lymphatic vessel contractility, valve properties, and cell size and stiffness on the variations in magnitude and gradient of the flow-induced wall shear stress (WSS) experienced by suspended tumor cells. Results indicated that the maximum WSSmax increased with the increments in cell diameter, vessel contraction amplitude, and valve stiffness. The decrease in vessel contraction period and valve aspect ratio also increased the maximum WSSmax. The influence of the properties of the valve on the WSS was more significant among the factors mentioned above. The maximum WSSmax acting on the cancer cell when the cell reversed the direction of its motion in the valve region increased by 0.5–1.4 times that before the cell entered the valve region. The maximum change in WSS was in the range of 0.004–0.028 Pa/µm depending on the factors studied. They slightly exceeded the values associated with breast cancer cell apoptosis. The results of this study provide biofluid mechanics-based support for mechanobiological research on the metastasis of metastatic cancer cells in suspension within the lymphatics.

Hemodynamic Characteristics of a Tortuous Microvessel Using High-Fidelity Red Blood Cell Resolved Simulations.

Tortuous microvessels are characteristic of microvascular remodeling associated with numerous physiological and pathological scenarios. Three-dimensional (3D) hemodynamics in tortuous microvessels influenced by red blood cells (RBCs), however, are largely unknown, and important questions remain. Is blood viscosity influenced by vessel tortuosity? How do RBC dynamics affect wall shear stress (WSS) patterns and the near-wall cell-free layer (CFL) over a range of conditions? The objective of this work was to parameterize hemodynamic characteristics unique to a tortuous microvessel. RBC-resolved simulations were performed using an immersed boundary method-based 3D fluid dynamics solver. A representative tortuous microvessel was selected from a stimulated angiogenic network obtained from imaging of the rat mesentery and digitally reconstructed for the simulations. The representative microvessel was a venule with a diameter of approximately 20 μm. The model assumes a constant diameter along the vessel length and does not consider variations due to endothelial cell shapes or the endothelial surface layer. Microvessel tortuosity was observed to increase blood apparent viscosity compared to a straight tube by up to 26%. WSS spatial variations in high curvature regions reached 23.6 dyne/cm2 over the vessel cross-section. The magnitudes of WSS and CFL thickness variations due to tortuosity were strongly influenced by shear rate and negligibly influenced by tube hematocrit levels. New findings from this work reveal unique tortuosity-dependent hemodynamic characteristics over a range of conditions. The results provide new thought-provoking information to better understand the contribution of tortuous vessels in physiological and pathological processes and help improve reduced-order models.

A fluid–structure interaction study to analyze the severity of carotid artery stenosis at different locations and its effect on various hemodynamic biomarkers

The study on arterial stenosis has gained rapid interest among researchers in the last decade because of its chronic consequences. Several researchers have tried to investigate stenosis and plaque progression in the carotid artery with different simulation models. In this study, a realistic 3-D geometry of the carotid artery has been used to analyze the effect of varying degrees of stenosis present at different locations of the carotid artery on various hemodynamic parameters. An extensive range of stenosis degrees, starting from a healthy artery(0 %stenosis) to 10%, 30%, 50%, 75%, and 90% stenosis, have been studied. These degrees of stenosis were planted at different locations of the artery grown simultaneously. The whole study was done under the realm of Fluid–Structure Interaction multiphysics. The change in velocity profiles at the areas of stenosis has been found along with the wall shear stress and arterial displacement. The magnitude of velocity and wall shear stress in the case of multiple stenosis locations has been found to be dependent on each other. The presence or absence of one stenosis affects the other, and given the regular and irregular patterns of the velocity profile, wall shear stress, and displacement, their inclusion in blood flow simulation studies having multiple stenoses should be considered.

Phase-locked µPIV analysis of flow dynamics in a simulated root canal with different laser-activated irrigations.

To measure the dynamic characteristics of the flow field in a complex root canal model activated by two laser-activated irrigation (LAI) modalities at different activation energy outputs: photon-induced photoacoustic streaming (PIPS) and microshort pulse (MSP). A phase-locked micro-scale Particle Image Velocimetry (µPIV) system was employed to characterise the temporal variations of LAI-induced velocity fields in the root canal following a single laser pulse. The wall shear stress (WSS) in the lateral root canal was subsequently estimated from the phase-averaged velocity fields. Both PIPS and MSP were able to generate the 'breath mode' of the irrigant current under all tested conditions. The transient irrigation flush in the root canal peaked at speeds close to 6 m/s. However, this intense flushing effect persisted for only about 2000 µs (or 3% of a single laser-pulse activation cycle). For MSP, the maximum WSS magnitude was approximately 3.08 Pa at an activation energy of E = 20 mJ/pulse, rising to 9.01 Pa at E = 50 mJ/pulse. In comparison, PIPS elevated the WSS to 10.63 Pa at E = 20 mJ/pulse. Elevating the activation energy can boost the peak flushing velocity and the maximum WSS, thereby enhancing irrigation efficiency. Given the same activation energy, PIPS outperforms MSP. Additionally, increasing the activation frequency may be an effective strategy to improve irrigation performance further.

Changes in aorta hemodynamics in Left-Right Type 1 bicuspid aortic valve patients after replacement with bioprosthetic valves: An in-silico study.

Bicuspid aortic valve (BAV) is the most common cardiac congenital abnormality with a high rate of concomitant aortic valve and ascending aorta (AAo) pathologic changes throughout the patient's lifetime. The etiology of BAV-related aortopathy was historically believed to be genetic. However, recent studies theorize that adverse hemodynamics secondary to BAVs also contribute to aortopathy, but their precise role, specifically, that of wall shear stress (WSS) magnitude and directionality remains controversial. Moreover, the primary therapeutic option for BAV patients is aortic valve replacement (AVR), but the role of improved post-AVR hemodynamics on aortopathy progression is also not well-understood. To address these issues, this study employs a computational fluid dynamics model to simulate personalized AAo hemodynamics before and after TAVR for a small cohort of 6 Left-Right fused BAV patients. Regional distributions of five hemodynamic metrics, namely, time-averaged wall shear stress (TAWSS) and oscillating shear index (OSI), divergence of wall shear (DWSS), helicity flux integral & endothelial cell activation potential (ECAP), which are hypothesized to be associated with potential aortic injury are computed in the root, proximal and distal ascending aorta. BAVs are characterized by strong, eccentric jets, with peak velocities exceeding 4 m/s and axially circulating flow away from the jets. Such conditions result in focused WSS loading along jet attachment regions on the lumen boundary and weaker, oscillating WSS on other regions. The jet attachment regions also show alternating streaks of positive and negative DWSS, which may increase risk for local tissue stretching. Large WSS magnitudes, strong helical flows and circumferential WSS have been previously implicated in the progression of BAV aortopathy. Post-intervention hemodynamics exhibit weaker, less eccentric jets. Significant reductions are observed in flow helicity, TAWSS and DWSS in localized regions of the proximal AAo. On the other hand, OSI increases post-intervention and ECAP is observed to be low in both pre- and post-intervention scenarios, although significant increases are also observed in this ECAP. These results indicate a significant alleviation of pathological hemodynamics post AVR.

Evaluation of the shrinkage process of a neck remnant after stent-coil treatment of a cerebral aneurysm using silent magnetic resonance angiography and computational fluid dynamics analysis: illustrative case.

Silent magnetic resonance angiography (MRA) mitigates metal artifacts, facilitating clear visualization of neck remnants after stent and coil embolization of cerebral aneurysms. This study aims to scrutinize hemodynamics at the neck remnant by employing silent MRA and computational fluid dynamics. The authors longitudinally tracked images of a partially thrombosed anterior communicating artery aneurysm's neck remnant, which had been treated with stent-assisted coil embolization, using silent MRA over a decade. Computational fluid dynamics delineated the neck remnant's reduction process, evaluating hemodynamic parameters such as flow rate, wall shear stress magnitude and vector, and streamlines. The neck remnant exhibited diminishing surface area, volume, neck size, dome depth, and aspect ratio. Its reduction correlated with a decline in the flow rate ratio of the remnant dome to the inflow parent artery. Analysis delineated regions within the contracting neck remnant characterized by consistently low average wall shear stress magnitude and variation, accompanied by notable variations in wall shear stress vector directionality. Evaluation of neck remnants after stent-coil embolization is possible through silent MRA and computational fluid dynamics. Predicting the neck remnant reduction may be achievable through hemodynamic parameter analysis.

Shear Stress Quantification in Tissue Engineering Bioreactor Heart Valves: A Computational Approach.

Tissue-engineered heart valves can grow, repair, and remodel after implantation, presenting a more favorable long-term solution compared to mechanical and porcine valves. Achieving functional engineered valve tissue requires the maturation of human cells seeded onto valve scaffolds under favorable growth conditions in bioreactors. The mechanical stress and strain on developing valve tissue caused by different pressure and flow conditions in bioreactors are currently unknown. The aim of this study is to quantify the wall shear stress (WSS) magnitude in heart valve prostheses under different valve geometries and bioreactor flow rates. To achieve this, this study used fluid-structure interaction simulations to obtain the valve's opening geometries during the systolic phase. These geometries were then used in computational fluid dynamics simulations with refined near-wall mesh elements and ranges of prescribed inlet flow rates. The data obtained included histograms and regression curves that characterized the distribution, peak, and median WSS for various flow rates and valve opening configurations. This study also found that the upper region of the valve near the commissures experienced higher WSS magnitudes than the rest of the valve.

Pulsatile pressure-driven non-Newtonian blood flow through a porous stenotic artery: A computational analysis

Blood flow through a narrowed artery, such as those caused by plaque buildup, can lead to various cardiovascular diseases. Therefore, studying this phenomenon is essential for developing better treatments and understanding the underlying mechanisms. In this study, a mathematical model is developed to simulate blood flow through stenotic arteries with porous walls. The familiar Navier-Stokes equations are executed to simulate flow, whereas the Carreau fluid model is employed to quantify blood rheology. This model illustrates both Newtonian and non-Newtonian characteristics depending on the shear rate. Other than that, the blood vessel is assumed to have a moderate level of stenosis with porous saturated walls. The solution of the governed partial differential equations is carried out using a finite difference scheme. Our research addresses the impacts of permeability and rheological parameters, stenosis size, Brinkman number, and Prandtl number on blood velocity, flow rate, resistance to flow, wall shear stress, and temperature distribution. The findings demonstrate that while flow resistance reduces, the velocity, shear stress, and flow rate increase with high permeability values. Conversely, as the stenosis amplitude increases, the magnitude of wall shear stresses, velocity, and flow rates decrease. In addition, blood rheology also has the potential to transfigure the aforementioned factors. We also found that the temperature distribution increases with the Brinkman number, stenosis size, permeability, and power law exponent. It drives down, however, by raising the values of Weissenberg number and Prandtl number. Collectively, our findings contribute to a better understanding of the complicated phenomena of blood flow in stenotic vessels with porous saturated walls. The findings of this study may be valuable in establishing improved therapies for cardiovascular disorders and formulating more precise mathematical models to forecast blood flow in vivo.

Predicting Lipid-Rich Plaque Progression in Coronary Arteries Using Multimodal Imaging and Wall Shear Stress Signatures.

Plaque composition and wall shear stress (WSS) magnitude act as well-established players in coronary plaque progression. However, WSS magnitude per se does not completely capture the mechanical stimulus to which the endothelium is subjected, since endothelial cells experience changes in the WSS spatiotemporal configuration on the luminal surface. This study explores WSS profile and lipid content signatures of plaque progression to identify novel biomarkers of coronary atherosclerosis. Thirty-seven patients with acute coronary syndrome underwent coronary computed tomography angiography, near-infrared spectroscopy intravascular ultrasound, and optical coherence tomography of at least 1 nonculprit vessel at baseline and 1-year follow-up. Baseline coronary artery geometries were reconstructed from intravascular ultrasound and coronary computed tomography angiography and combined with flow information to perform computational fluid dynamics simulations to assess the time-averaged WSS magnitude (TAWSS) and the variability in the contraction/expansion action exerted by WSS on the endothelium, quantifiable in terms of topological shear variation index (TSVI). Plaque progression was measured as intravascular ultrasound-derived percentage plaque atheroma volume change at 1-year follow-up. Plaque composition information was extracted from near-infrared spectroscopy and optical coherence tomography. Exposure to high TSVI and low TAWSS was associated with higher plaque progression (4.00±0.69% and 3.60±0.62%, respectively). Plaque composition acted synergistically with TSVI or TAWSS, resulting in the highest plaque progression (≥5.90%) at locations where lipid-rich plaque is exposed to high TSVI or low TAWSS. Luminal exposure to high TSVI, solely or combined with a lipid-rich plaque phenotype, is associated with enhanced plaque progression at 1-year follow-up. Where plaque progression occurred, low TAWSS was also observed. These findings suggest TSVI, in addition to low TAWSS, as a potential biomechanical predictor for plaque progression, showing promise for clinical translation to improve patient prognosis.

Evaluating the efficacy of the punch-out technique in systemic-to-pulmonary shunts: A computational fluid dynamics approach.

Systemic-to-pulmonary shunt is a palliative procedure used to decrease pulmonary blood flow in congenital heart diseases. Shunt stenosis or occlusion has been reported to be associated with mortality; therefore, the management of thrombotic complications remains a challenge for most congenital cardiovascular surgeons. Despite its importance, the optimal method for shunt anastomosis remains unclear. The study investigates the clinical benefits of the punch-out technique over conventional methods in the anastomosis process of Systemic-to-pulmonary shunt, focusing on its potential to reduce shunt-related complications. Anastomotic models were created by two different surgeons employing both traditional slit and innovative punch-out techniques. Computational tomography was performed to construct three-dimensional models for computational fluid dynamics (CFD) analysis. We assessed the flow pattern, helicity, magnitude of wall shear stress, and its gradient. The anastomotic flow area was larger in the model using the punch-out technique than in the slit model. In CFD simulation, we found that using the punch-out technique decreases the likelihood of establishing a high wall shear stress distribution around the anastomosis line in the model. The punch-out technique emerges as a promising method in SPS anastomosis, offering a reproducible and less skill-dependent alternative that potentially diminishes the risk of shunt occlusion, thereby enhancing patient outcomes.

Influence of Fluid Rheology on Blood Flow Haemodynamics in Patient-Specific Arterial Networks of Varied Complexity – In-Silico Studies

Abstract Results obtained with computational fluid dynamics (CFD) rely on assumptions made during a pre-processing stage, including a mathematical description of a fluid rheology. Up to this date there is no clear answer to several aspects, mainly related to the question of whether and under what conditions blood can be simplified to a Newtonian fluid during CFD analyses. Different research groups present contradictory results, leaving the question unanswered. Therefore, the objective of this research was to perform steady-state and pulsatile blood flow simulations using eight different rheological models in geometries of varying complexity. A qualitative comparison of shear- and viscosity-related parameters showed no meaningful discrepancies, but a quantitative analysis revealed significant differences, especially in the magnitudes of wall shear stress (WSS) and its gradient (WSSG). We suggest that for the large arteries blood should be modelled as a non-Newtonian fluid, whereas for the cerebral vasculature the assumption of blood as a simple Newtonian fluid can be treated as a valid simplification.

Positive Pressure and Negative Pressure Irrigation Dynamics with Different Needle Designs Using Computational Fluid Dynamics

This study aimed to investigate the irrigation dynamics of the positive pressure side-vented (SV) needle, EndoVac (micropores) needle and modified apical negative pressure (mANP) open-ended needle using computational fluid dynamics (CFD). A simulation of a prepared root canal (conical frustum) of 15 mm length with an apical diameter of 0.40 mm following Protaper F4 apical preparation was created using three-dimensional (3D) CAD software. The 3D simulated needle of SV 30G needle, EndoVac with micropores needle and mANP, 30G flat open-ended needle were also created. The irrigation dynamics were evaluated through transient CFD simulations. In addition, the irrigation dynamics of mANP at 0.2 mm, 0.5 mm, and 1.0 mm short from the working length were also assessed. The EndoVac and mANP showed negative apical static pressure and streamline patterns able to reach the apical region, thus indicating negligible extrusion. Meanwhile, SV showed positive apical static pressure and almost nonexistent streamlines beyond the needle tip. The SV showed the highest wall shear stress (WSS) magnitude of 1030Pa whereas Endovac (161 Pa) and mANP1 (258 Pa). However, SV revealed lower average WSS (10 Pa) compared to mANP1 (13 Pa) and mANP2 (11 Pa). This is due to SV developed a localised maximum WSS opposite the open vent area only therefore, uneven distribution of WSS. The EndoVac system developed a localised maximum WSS in the pair of micropores furthest away from the apical. CFD analysis of the EndoVac, mANP and SV showed different technique approach, needle design and needle depths insertion affect the irrigation dynamics pattern and magnitude.

Pulsatile blood plasma flow over an endothelial cell monolayer

We present a microfluidic cell culture platform for studying the responses of Endothelial Cells (ECs) under pulsatile flow conditions of blood plasma. Through numerical investigations, we explore the dynamic behaviors of the Endothelial Cell Monolayer under both physiological and extreme conditions, including the formation of recirculation zones. Furthermore, we conduct a quantitative analysis of the Wall Shear Stress (WSS) magnitude on the EC surface and evaluate the Oscillatory Shear Index (OSI) to gain insights into the extent of WSS reversal within a single cycle across different spatial locations. Our findings reveal that the ECs deform in the direction of the flow, periodically returning to their initial position, with slight vertical deformation in the nanometer scale. In contrast to our previous observations for startup rheometry, cell membrane thinning is found to be more prominent at the lateral points of the cell protrusion, where fluid detachment from the cell surface initiates, rather than at the top. We further note that negative shear stresses emerge within the cytoplasm. Moreover, the shear stresses within the nucleus remain consistent for both rheometric protocols, while the normal stresses are slightly lower during pulsatile experiments. Finally, the model provides insight into the actual phenomena that arise in vivo as well as the expected behaviors in the vicinity of the endothelium of a vessel.

On-Chip Reconstitution of Uniformly Shear-Sensing 3D Matrix-embedded Multicellular Blood Microvessel.

Preclinical human-relevant modeling of organ-specific vasculature offers a unique opportunity to recreate pathophysiological intercellular, tissue-tissue, and cell-matrix interactions for a broad range of applications. Here, we present a reliable, and simply reproducible process for constructing user-controlled long rounded extracellular matrix (ECM)-embedded vascular microlumens on-chip for endothelization and co-culture with stromal cells obtained from human lung. We demonstrate the critical impact of microchannel cross-sectional geometry and length on uniform distribution and magnitude of vascular wall shear stress, which is key when emulating in vivo-observed blood flow biomechanics in health and disease. In addition, we provide an optimization protocol for multicellular culture and functional validation of the system. Moreover, we show the ability to finely tune rheology of the three-dimensional natural matrix surrounding the vascular microchannel to match pathophysiological stiffness. In summary, we provide the scientific community with a matrix-embedded microvasculature on-chip populated with all-primary human-derived pulmonary endothelial cells and fibroblasts to recapitulate and interrogate lung parenchymal biology, physiological responses, vascular biomechanics, and disease biogenesis in vitro. Such a mix-and-match synthetic platform can be feasibly adapted to study blood vessels, matrix, and ECM-embedded cells in other organs and be cellularized with additional stromal cells.

Influence of morphological characteristics on the deposition of low-density lipoprotein in intracranial bifurcation aneurysms

The increasingly demonstrated association of wall enhancement (WE) measured by vascular wall imaging with the instability/rupture of intracranial aneurysms (IAs) implies the significance of investigating the transport and accumulation of blood substances [e.g., low-density lipoprotein (LDL), lipoprotein (a)] related to WE in IAs. In the present study, we perform numerical simulations to explore the relationships between the distribution/severity of LDL deposition on the lumen surface and the morphological characteristics of aneurysm and its adjacent arteries as well as the underlying fluid dynamic mechanisms. Bifurcation aneurysms located at the middle cerebral artery are selected as the subject of investigation and for which both idealized and patient-specific models are built. Studies on the idealized models reveal that the aneurysm–parent (AP) artery angle is more powerful than other morphological parameters [e.g., daughter–parent (DP) artery angle, nonsphericity index (NI) of aneurysm] in determining the severity of LDL deposition. A bleb (i.e., secondary sac) can enhance local LDL deposition, especially when located in an LDL deposition-prone aneurysm wall region. In patient-specific models, the dominant effect on the LDL deposition of the AP angle remains identifiable, whereas the effects of the DP angle and NI are overwhelmed by confounding factors. Enhanced LDL deposition prefers to appear in wall regions perpendicular to the intra-aneurysmal vortex centerline. In comparison with wall shear stress magnitude, the normal-to-tangential near-wall velocity ratio and particle residence time can better predict the localization of enhanced LDL deposition.

Fluid dynamics by 4D flow CMR in Marfan and Loeys-Dietz patients before and after valve sparing aortic root replacement

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III (Spain), Sociedad Española de Cardiología Introduction Patients with Marfan or Loeys-Dietz syndrome present abnormal aortic flow patterns in the arch and the proximal descending aorta that may contribute to aortic dilation (1,2). Valve sparing aortic root replacement, which is effective in reducing the risk of aortic dissection in case of severe dilation, may also normalize flow patterns beyond the replaced aorta and potentially slow its progressive aortic dilation. Purpose To assess aortic flow dynamics in these patients with Marfan or Loeys-Dietz by 4D flow cardiovascular magnetic resonance (CMR) before and after valve sparing aortic root replacement (David surgery), and to compare the results with those of healthy volunteers (HV). Methods Patients with Marfan or Loeys-Dietz syndrome underwent two non-contrast enhanced 4D flow CMR, one before and another after undergoing David surgery. Healthy volunteers matched for age, sex and BSA were also included for comparison. Maximum velocity, in-plane rotational flow (IRF), systolic flow reversal ratio (SFRR) and wall shear stress (WSS) magnitude and its axial and circumferential components were obtained at 24 planes covering the thoracic aorta from the sinotubular junction to the descending aorta at the diaphragmatic level (3–5). Results Sixteen patients and 21 healthy volunteers were included. Demographic and clinical data is presented in Table. The mean time between the CMR prior and posterior to surgery was 15 months. Compared to HV, patients with CTD before intervention presented lower maximum velocity at the proximal ascending aorta (Figure 1A), lower IRF and circumferential WSS at the arch and the proximal descending aorta (Figure 1B and F), lower magnitude and axial WSS at the proximal ascending and descending aorta (Figure 1E and D), and increased SFRR at the proximal descending aorta (Figure 1C). The intervention completely restored maximum velocity and partially-restored physiological helical flow and circumferential WSS, but barely improved axial WSS and SFRR. Conclusion Valve sparing aortic root replacement in patients with Marfan or Loeys-Dietz syndrome partially restore to physiological level both in-plane rotational flow and circumferential wall shear stress in the descending aorta.

The Influence of Aortic Valve Disease on Coronary Hemodynamics: A Computational Model-Based Study.

Aortic valve disease (AVD) often coexists with coronary artery disease (CAD), but whether and how the two diseases are correlated remains poorly understood. In this study, a zero-three dimensional (0-3D) multi-scale modeling method was developed to integrate coronary artery hemodynamics, aortic valve dynamics, coronary flow autoregulation mechanism, and systemic hemodynamics into a unique model system, thereby yielding a mathematical tool for quantifying the influences of aortic valve stenosis (AS) and aortic valve regurgitation (AR) on hemodynamics in large coronary arteries. The model was applied to simulate blood flows in six patient-specific left anterior descending coronary arteries (LADs) under various aortic valve conditions (i.e., control (free of AVD), AS, and AR). Obtained results showed that the space-averaged oscillatory shear index (SA-OSI) was significantly higher under the AS condition but lower under the AR condition in comparison with the control condition. Relatively, the overall magnitude of wall shear stress was less affected by AVD. Further data analysis revealed that AS induced the increase in OSI in LADs mainly through its role in augmenting the low-frequency components of coronary flow waveform. These findings imply that AS might increase the risk or progression of CAD by deteriorating the hemodynamic environment in coronary arteries.

Osteogenic Activity on NaOH-Etched Three-Dimensional-Printed Poly-ɛ-Caprolactone Scaffolds in Perfusion or Spinner Flask Bioreactor.

Bioreactor systems, for example, spinner flask and perfusion bioreactors, and cell-seeded three-dimensional (3D)-printed scaffolds are used in bone tissue engineering strategies to stimulate cells and produce bone tissue suitable for implantation into the patient. The construction of functional and clinically relevant bone graft using cell-seeded 3D-printed scaffolds within bioreactor systems is still a challenge. Bioreactor parameters, for example, fluid shear stress and nutrient transport, will crucially affect cell function on 3D-printed scaffolds. Therefore, fluid shear stress induced by spinner flask and perfusion bioreactors might differentially affect osteogenic responsiveness of pre-osteoblasts inside 3D-printed scaffolds. We designed and fabricated surface-modified 3D-printed poly-ɛ-caprolactone (PCL) scaffolds, as well as static, spinner flask, and perfusion bioreactors to determine fluid shear stress and osteogenic responsiveness of MC3T3-E1 pre-osteoblasts seeded on the scaffolds in the bioreactors using finite element (FE)-modeling and experiments. FE-modeling was used to quantify wall shear stress (WSS) distribution and magnitude inside 3D-printed PCL scaffolds within spinner flask and perfusion bioreactors. MC3T3-E1 pre-osteoblasts were seeded on NaOH surface-modified 3D-printed PCL scaffolds, and cultured in customized static, spinner flask, and perfusion bioreactors up to 7 days. The scaffolds' physicochemical properties and pre-osteoblast function were assessed experimentally. FE-modeling showed that spinner flask and perfusion bioreactors locally affected WSS distribution and magnitude inside the scaffolds. The WSS distribution was more homogeneous inside scaffolds in perfusion than in spinner flask bioreactors. The average WSS on scaffold-strand surfaces ranged from 0 to 6.5 mPa for spinner flask bioreactors, and from 0 to 4.1 mPa for perfusion bioreactors. Surface modification of scaffolds by NaOH resulted in a surface with a honeycomb-like pattern and increased surface roughness (1.6-fold), but decreased water contact angle (0.3-fold). Both spinner flask and perfusion bioreactors increased cell spreading, proliferation, and distribution throughout the scaffolds. Perfusion, but not spinner flask bioreactors more strongly enhanced collagen (2.2-fold) and calcium deposition (2.1-fold) throughout the scaffolds after 7 days compared with static bioreactors, likely due to uniform WSS-induced mechanical stimulation of the cells revealed by FE-modeling. In conclusion, our findings indicate the importance of using accurate FE models to estimate WSS and determine experimental conditions for designing cell-seeded 3D-printed scaffolds in bioreactor systems. Impact Statement The success of cell-seeded three-dimensional (3D)-printed scaffolds depends on cell stimulation by biomechanical/biochemical factors to produce bone tissue suitable for implantation into the patient. We designed and fabricated surface-modified 3D-printed poly-ɛ-caprolactone (PCL) scaffolds, as well as static, spinner flask, and perfusion bioreactors to determine wall shear stress (WSS) and osteogenic responsiveness of pre-osteoblasts seeded on the scaffolds using finite element (FE)-modeling and experiments. We found that cell-seeded 3D-printed PCL scaffolds within perfusion bioreactors more strongly enhanced osteogenic activity than within spinner flask bioreactors. Our results indicate the importance of using accurate FE-models to estimate WSS and determine experimental conditions for designing cell-seeded 3D-printed scaffolds in bioreactor systems.