Flow instability detected in ruptured versus unruptured cerebral aneurysms at the internal carotid artery

Flow instability has emerged as a new hemodynamic metric hypothesized to have potential value in assessing the rupture risk of cerebral aneurysms. However, diverse findings have been reported in the literature. In the present study, high-resolution hemodynamic simulations were performed retrospectively on 35 aneurysms (10 ruptured & 25 unruptured) located at the internal carotid artery (ICA). Simulated hemodynamic parameters were statistically compared between the ruptured and unruptured aneurysms, with emphasis on examining the correlation of flow instability with the status of aneurysm rupture. Pronounced flow instability was detected in 20% (2 out of 10) of the ruptured aneurysms, whereas in 44% (11 out of 25) of the unruptured aneurysms. Statistically, the flow instability metric (quantified by the temporally and spatially averaged fluctuating kinetic energy over the aneurysm sac) did not differ significantly between the ruptured and unruptured aneurysms. In contrast, low wall shear stress area (LSA) and pressure loss coefficient (PLC) exhibited significant correlations with the status of aneurysm rupture. In conclusion, the present study suggests that the presence of flow instability may not correlate closely with the status of aneurysm rupture, at least for ICA aneurysms. On the other hand, the retrospective nature of the study and the small sample size may have to some extent compromised the reliability of the conclusion, and therefore large-scale prospective studies would be needed to further address the issue.     

Flow patterns in the jugular veins of pulsatile tinnitus patients

Pulsatile Tinnitus (PT) is a pulse-synchronous sound heard in the absence of an external source. PT is often related to abnormal flow in vascular structures near the cochlea. One vascular territory implicated in PT is the internal jugular vein (IJV). Using computational fluid dynamics (CFD) based on patient-specific Magnetic Resonance Imaging (MRI), we investigated the flow within the IJV of seven subjects, four symptomatic and three asymptomatic of PT. We found that there were two extreme anatomic types classified by the shape and position of the jugular bulbs: elevated and rounded. PT patients had elevated jugular bulbs that led to a distinctive helical flow pattern within the proximal internal jugular vein. Asymptomatic subjects generally had rounded jugular bulbs that neatly redirected flow from the sigmoid sinus directly into the jugular vein. These two flow patterns were quantified by calculating the length-averaged streamline curvature of the flow within the proximal jugular vein: 130.3±8.1 m⁻¹ for geometries with rounded bulbs, 260.7±29.4 m⁻¹ for those with elevated bulbs (P<0.005). Our results suggest that variations in the jugular bulb geometry lead to distinct flow patterns that are linked to PT, but further investigation is needed to determine if the vortex pattern is causal to sound generation.     

A reduced-order model for wall shear stress in abdominal aortic aneurysms by proper orthogonal decomposition

In this paper, we introduce a method to construct a Reduced-Order Model (ROM) to study the physiological flow and the Wall Shear Stress (WSS) conditions in Abdominal Aortic Aneurysms (AAA). We start the process by running a training case using Computational Fluid Dynamics (CFD) simulations with time-varying flow parameters, such that these parameters cover the range of parameters that we would like to consider in our ROM. We use the inflow angle as the variable parameter in the current study. Then we use the snapshot Proper Orthogonal Decomposition (POD) to construct the reduced-order bases, which are subsequently enhanced using a QR-factorization technique to satisfy the relevant fluid boundary conditions. The resulting ROM enables us to study the flow pattern and the WSS distribution over a range of system parameters computationally very efficiently. We have used this method to show how the WSS varies significantly for an AAA with a simplified geometry, over a range of inflow angles usually considered mild in clinical terms. We have validated the ROM results with CFD results. This approach enables comprehensive analysis of the model system across a range of inflow angles and frequencies without the need to re-compute the simulation for small changes.     

A study of wall shear stress in 12 aneurysms with respect to different viscosity models and flow conditions

Recent computational fluid dynamics (CFD) studies relate abnormal blood flow to rupture of cerebral aneurysms. However, it is still debated how to model blood flow with sufficient accuracy. Common assumptions made include Newtonian behaviour of blood, traction free outlet boundary conditions and inlet boundary conditions based on available literature. These assumptions are often required since the available patient specific data is usually restricted to the geometry of the aneurysm and the surrounding vasculature. However, the consequences of these assumptions have so far been inadequately addressed.     

Myocardial bridging and endothelial dysfunction – Computational fluid dynamics study

Myocardial bridging (MB) is associated with endothelial dysfunction in patients with angina and non-obstructive coronary artery disease. This study aims to determine if there is a link between abnormal blood flow patterns and endothelial dysfunction in patients with MB. Ten patients with MB in their left anterior descending (LAD) artery were selected, 5 of whom had endothelial dysfunction and 5 had no endothelial dysfunction based on their response to acetylcholine. Similarly, 10 patients without MB in their LAD, 5 of whom had endothelial dysfunction and 5 of whom had no endothelial dysfunction, were studied as a control group. Transient computational fluid dynamics simulations were performed to derive wall shear stress (WSS) over the entire vessel including proximal, middle and distal segments. Patients with MB and endothelial dysfunction had lower WSS in the proximal LAD and greater WSS in the mid-LAD than patients with MB but without endothelial dysfunction. When comparing patients with endothelial dysfunction, those with MB had significantly lower shear stress in the proximal LAD (0.32 ± 0.14 Pa (with MB) vs 0.71 ± 0.38 Pa (without MB), p = 0.01) and greater shear stress in the mid-LAD (2.81 ± 1.20 Pa (with MB) vs 1.66 ± 0.31 Pa (without MB), p = 0.014) than patients without MB. Our findings demonstrated that the presence of MB significantly contributes to low WSS and endothelial dysfunction relationship.     

A computational model for prediction of clot platelet content in flow-diverted intracranial aneurysms

Treatment of intracranial aneurysms with flow-diverting stents is a safe and minimally invasive technique. The goal is stable embolisation that facilitates stent endothelialisation, and elimination of the aneurysm. However, it is not fully understood why some aneurysms fail to develop a stable clot even with sufficient levels of flow reduction. Computational prediction of thrombus formation dynamics can help predict the post-operative response in such challenging cases. In this work, we propose a new model of thrombus formation and platelet dynamics inside intracranial aneurysms. Our novel contribution combines platelet activation and transport with fibrin generation, which is key to characterising stable and unstable thrombus. The model is based on two types of thrombus inside aneurysms: red thrombus (fibrin- and erythrocyte-rich) can be found in unstable clots, while white thrombus (fibrin- and platelet-rich) can be found in stable clots. The thrombus generation model is coupled to a CFD model and the flow-induced platelet index (FiPi) is defined as a quantitative measure of clot stability. Our model is validated against an in vitro phantom study of two flow-diverting stents with different sizing. We demonstrate that our model accurately predicts the lower thrombus stability in the oversized stent scenario. This opens possibilities for using computational simulations to improve endovascular treatment planning and reduce adverse events, such as delayed haemorrhage of flow-diverted aneurysms.     

The effect of inlet waveforms on computational hemodynamics of patient-specific intracranial aneurysms

Due to the lack of patient-specific inlet flow waveform measurements, most computational fluid dynamics (CFD) simulations of intracranial aneurysms usually employ waveforms that are not patient-specific as inlet boundary conditions for the computational model. The current study examined how this assumption affects the predicted hemodynamics in patient-specific aneurysm geometries. We examined wall shear stress (WSS) and oscillatory shear index (OSI), the two most widely studied hemodynamic quantities that have been shown to predict aneurysm rupture, as well as maximal WSS (MWSS), energy loss (EL) and pressure loss coefficient (PLc). Sixteen pulsatile CFD simulations were carried out on four typical saccular aneurysms using 4 different waveforms and an identical inflow rate as inlet boundary conditions. Our results demonstrated that under the same mean inflow rate, different waveforms produced almost identical WSS distributions and WSS magnitudes, similar OSI distributions but drastically different OSI magnitudes. The OSI magnitude is correlated with the pulsatility index of the waveform. Furthermore, there is a linear relationship between aneurysm-averaged OSI values calculated from one waveform and those calculated from another waveform. In addition, different waveforms produced similar MWSS, EL and PLc in each aneurysm. In conclusion, inlet waveform has minimal effects on WSS, OSI distribution, MWSS, EL and PLc and a strong effect on OSI magnitude, but aneurysm-averaged OSI from different waveforms has a strong linear correlation with each other across different aneurysms, indicating that for the same aneurysm cohort, different waveforms can consistently stratify (rank) OSI of aneurysms.     

Flow rates in perfusion bioreactors to maximise mineralisation in bone tissue engineering in vitro

In bone tissue engineering experiments, fluid-induced shear stress is able to stimulate cells to produce mineralised extracellular matrix (ECM). The application of shear stress on seeded cells can for example be achieved through bioreactors that perfuse medium through porous scaffolds. The generated mechanical environment (i.e. wall shear stress: WSS) within the scaffolds is complex due to the complexity of scaffold geometry. This complexity has so far prevented setting an optimal loading (i.e. flow rate) of the bioreactor to achieve an optimal distribution of WSS for stimulating cells to produce mineralised ECM. In this study, we demonstrate an approach combining computational fluid dynamics (CFD) and mechano-regulation theory to optimise flow rates of a perfusion bioreactor and various scaffold geometries (i.e. pore shape, porosity and pore diameter) in order to maximise shear stress induced mineralisation. The optimal flow rates, under which the highest fraction of scaffold surface area is subjected to a wall shear stress that induces mineralisation, are mainly dependent on the scaffold geometries. Nevertheless, the variation range of such optimal flow rates are within 0.5–5 mL/min (or in terms of fluid velocity: 0.166–1.66 mm/s), among different scaffolds. This approach can facilitate the determination of scaffold-dependent flow rates for bone tissue engineering experiments in vitro, avoiding performing a series of trial and error experiments.     

Hemodynamic analysis of a novel stent graft design with slit perforations in thoracic aortic aneurysm

Thoracic endovascular aortic repair (TEVAR) has been introduced as a less invasive approach to the treatment of thoracic aortic aneurysm (TAA). However, the effectiveness of TEVAR in the treatment of TAA is often limited due to the complex anatomy of aortic arch. Flow preservation at the three supra-aortic branches further increases the overall technical difficulty. This study proposes a novel stent graft design with slit perforations that can positively alter the hemodynamics at the aortic arch while maintaining blood flow to supra-aortic branches. We carried out a computational fluid dynamic (CFD) analysis to evaluate flow characteristics near stented aortic arch in simplified TAA models, followed by in-vitro experiments using particle image velocimetry (PIV) in a mock circulatory loop. The hemodynamics result was studied in terms of time-averaged wall shear stress (TAWSS), oscillating shear index (OSI), and endothelial cell action potential (ECAP). The results showed that the stent graft with slit perforations can reduce the disturbed flow region considerably. Furthermore, the effect of the slits on flow preservation to the supra-aortic branches was simulated and compared with experimental results. The effectiveness of the stent graft with slit perforations in preserving flow to the branches was demonstrated by both simulated and experimental results. Low TAWSS and elevated ECAP were observed in the aortic arch aneurysm after the placement of the stent graft with slits, implying the potential of thrombus formation in the aneurysm. On the other hand, the effects of the stent grafts with full-slit design and half-slit design on the shear stress did not differ significantly. The present analysis indicated that not only could the stent graft with slit perforations shield the aneurysm from rupture, but also it resulted in a favorable environment for thrombus that can contribute to the shrinkage of the aneurysm.     

Direct numerical simulation of transitional flow in a patient-specific intracranial aneurysm

In experiments turbulence has previously been shown to occur in intracranial aneurysms. The effects of turbulence induced oscillatory wall stresses could be of great importance in understanding aneurysm rupture. To investigate the effects of turbulence on blood flow in an intracranial aneurysm, we performed a high resolution computational fluid dynamics (CFD) simulation in a patient specific middle cerebral artery (MCA) aneurysm using a realistic, pulsatile inflow velocity. The flow showed transition to turbulence just after peak systole, before relaminarization occurred during diastole. The turbulent structures greatly affected both the frequency of change of wall shear stress (WSS) direction and WSS magnitude, which reached a maximum value of 41.5Pa. The recorded frequencies were predominantly in the range of 1-500Hz. The current study confirms, through properly resolved CFD simulations that turbulence can occur in intracranial aneurysms.     

Magnetic resonance imaging based modeling of microvascular perfusion in patients with peripheral artery disease

Peripheral artery disease (PAD) is associated with an increased risk of adverse cardiovascular events, impaired lower extremity blood flow and microvascular perfusion abnormalities in the calf muscles which can be determined with contrast-enhanced magnetic resonance imaging (CE-MRI). We developed a computational model of the microvascular perfusion in the calf muscles. We included 20 patients (10 PAD, 10 controls) and utilized the geometry, mean signal intensity and arterial input functions from CE-MRI calf muscle perfusion scans. The model included the microvascular pressure (p_v), outflow filtration coefficient (OFC), transfer rate constant (k^t), porosity (φ), and the interstitial permeability (K_tissue). Parameters were fitted and the simulations were compared across PAD patients and controls. Intra-observer reproducibility of the simulated mean signal intensities was excellent (intraclass correlation coefficients >0.995). k^t and K_tissue were higher in PAD patients compared with controls (4.72 interquartile range (IQR) 3.33, 5.56 vs. 2.47 IQR 2.10, 2.85; p = 0.003; and 3.68 IQR 3.18, 4.41 vs. 1.81 IQR 1.81, 1.81; p < 0.001). Conversely, porosity (φ) was lower in PAD patients compared with controls (0.52 IQR 0.49, 0.54 vs. 0.61 IQR 0.58, 0.64; p = 0.016). Porosity (φ) was correlated with the ankle brachial index (r = 0.64, p = 0.011). The proposed computational microvascular model is robust and reproducible, and essential model parameters differ significantly between PAD patients and controls.     

Healthy and diseased coronary bifurcation geometries influence near-wall and intravascular flow: A computational exploration of the hemodynamic risk

Local hemodynamics has been identified as one main determinant in the onset and progression of atherosclerotic lesions at coronary bifurcations. Starting from the observation that atherosensitive hemodynamic conditions in arterial bifurcation are majorly determined by the underlying anatomy, the aim of the present study is to investigate how peculiar coronary bifurcation anatomical features influence near-wall and intravascular flow patterns. Different bifurcation angles and cardiac curvatures were varied in population-based, idealized models of both stenosed and unstenosed bifurcations, representing the left anterior descending (LAD) coronary artery with its diagonal branch. Local hemodynamics was analyzed in terms of helical flow and exposure to low/oscillatory shear stress by performing computational fluid dynamics simulations.Results show that bifurcation angle impacts lowly hemodynamics in both stenosed and unstenosed cases. Instead, curvature radius influences the generation and transport of helical flow structures, with smaller cardiac curvature radius associated to higher helicity intensity. Stenosed bifurcation models exhibit helicity intensity values one order of magnitude higher than the corresponding unstenosed cases. Cardiac curvature radius moderately affects near-wall hemodynamics of the stenosed cases, with smaller curvature radius leading to higher exposure to low shear stress and lower exposure to oscillatory shear stress. In conclusion, the proposed controlled benchmark allows investigating the effect of various geometrical features on local hemodynamics at the LAD/diagonal bifurcation, highlighting that cardiac curvature influences near wall and intravascular hemodynamics, while bifurcation angle has a minor effect.     

Stratification of a population of intracranial aneurysms using blood flow metrics

Indices of the intra-aneurysm hemodynamic environment have been proposed as potentially indicative of their longitudinal outcome. To be useful, the indices need to be used to stratify large study populations and tested against known outcomes. The first objective was to compile the diverse hemodynamic indices reported in the literature. Furthermore, as morphology is often the only patient-specific information available in large population studies, the second objective was to assess how the ranking of aneurysms in a population is affected by the use of steady flow simulation as an approximation to pulsatile flow simulation, even though the former is clearly non-physiological. Sixteen indices of aneurysmal hemodynamics reported in the literature were compiled and refined where needed. It was noted that, in the literature, these global indices of flow were always time-averaged over the cardiac cycle. Steady and pulsatile flow simulations were performed on a population of 198 patient-specific and 30 idealised aneurysm models. All proposed hemodynamic indices were estimated and compared between the two simulations. It was found that steady and pulsatile flow simulations had a strong linear dependence (r ≥ 0.99 for 14 indices; r ≥ 0.97 for 2 others) and rank the aneurysms in an almost identical fashion (ρ ≥ 0.99 for 14 indices; ρ ≥ 0.96 for other 2). When geometry is the only measured piece of information available, stratification of aneurysms based on hemodynamic indices reduces to being a physically grounded substitute for stratification of aneurysms based on morphology. Under such circumstances, steady flow simulations may be just as effective as pulsatile flow simulation for estimating most key indices currently reported in the literature.     

Magnetic particle imaging for artifact-free imaging of intracranial flow diverter stents: A phantom study

PurposeMagnetic Particle Imaging (MPI) is a new, background- and radiation-free tomographic imaging method that enables near real-time imaging of superparamagnetic iron-oxide nanoparticles (SPIONs) with high temporal and spatial resolution. This phantom study aims to investigate the potential of MPI for visualization of the stent lumen in intracranial flow diverters (FD).MethodsNitinol FD of different dimensions (outer diameter: 3.5 mm, 4.0 mm, 5.5 mm; total length: 22–40 mm) were scanned in vascular phantoms in a custom-built MPI scanner (in-plane resolution: ~ 2 mm, field of view: 65 mm length, 29 mm diameter). Phantoms were filled with diluted (1:50) SPION tracer agent Ferucarbotran (10 µmol (Fe)/ml; NaCL). Each phantom was measured in 32 different projections (overall acquisition time per image: 3200 ms, 5 averages). After image reconstruction from raw data, two radiologists assessed image quality using a 5-point Likert scale. The signal intensity profile was measured using a semi-automatic evaluation tool.ResultsMPI visualized the lumen of all FD without relevant differences between the stented vessel phantom and the reference phantom. At 3.5 mm image quality was slightly inferior to the larger diameters. The FD themselves neither generated an MPI signal nor did they lead to relevant imaging artifacts. Ratings of both radiologists showed no significant difference, interrater reliability was good (ICC 0.84). A quantitative evaluation of the signal intensity profile did not reveal any significant differences (p > 0.05) either.ConclusionMPI visualizes the lumen of nitinol FD stents in vessel phantoms without relevant stent-induced artifacts.     

Pulsatile non-Newtonian haemodynamics in a 3D bifurcating abdominal aortic aneurysm model

Numerical prediction of non-Newtonian blood flow in a 3D abdominal aortic aneurysm bifurcating model is carried out. The non-Newtonian Carreau model is used to characterise the shear thinning behaviour of the human blood. A physical inlet velocity waveform incorporating a radial velocity distribution reasonably representative of a practical case configuration is employed. Case studies subject to both equal and unequal outlet pressures at iliac bifurcations are presented to display convincingly the downstream pressure influences on the flow behaviour within the aneurysm. Simulations indicate that the non-Newtonian aspects of the blood cannot at all be neglected or given a cursory treatment. The wall shear stress (WSS) is found to change significantly at both the proximal and distal ends of the aneurysm. At the peak systole, the WSS is peak around the bifurcation point, whereas the WSS becomes zero in the bifurcation point. Differential downstream pressure fields display significant effects regarding the flow evolution in the iliac arteries, whereas little or no effects are observed directly on the flow details in the aneurysm.     

Computational fluid dynamics study of common stent models inside idealised curved coronary arteries

The haemodynamic behaviour of blood inside a coronary artery after stenting is greatly affected by individual stent features as well as complex geometrical properties of the artery including tortuosity and curvature. Regions at higher risk of restenosis, as measured by low wall shear stress (WSS < 0.5 Pa), have not yet been studied in detail in curved stented arteries. In this study, three-dimensional computational modelling and computational fluid dynamics methodologies were used to analyse the haemodynamic characteristics in curved stented arteries using several common stent models. Results in this study showed that stent strut thickness was one major factor influencing the distribution of WSS in curved arteries. Regions of low WSS were found behind struts, particularly those oriented at a large angle relative to the streamwise flow direction. These findings were similar to those obtained in studies of straight arteries. An uneven distribution of WSS at the inner and outer bends of curved arteries was observed where the WSS was lower at the inner bend. In this study, it was also shown that stents with a helical configuration generated an extra swirling component of the flow based on the helical direction; however, this extra swirl in the flow field did not cause significant changes on the distribution of WSS under the current setup.     

Optimizing a rotor‐stator filter matrix for high‐gradient magnetic separation of functionalized magnetic particles

The processing of wines with enzymes is a process chain in which losses of biocatalyst are unavoidable. A promising technique for the minimization of these losses and for the reduction of processing time is the high‐gradient magnetic separation in combination with enzymes, which are immobilized onto functionalized magnetic particles. When magnetizable particles are used and magnetic separation is applied to separate these particles from nonmagnetizable particles and solutes, the enzymes can be recycled and used for several production batches. The magnetic filter used in this study had a filter matrix with concentrically stacked circular rotor and stator plates which are arranged in an alternating order. Different geometries of the filter plate notches were examined to optimize the reproducibility of particle retention. In computational fluid dynamic studies, the influence of the notch geometries on the shear rate generation was analyzed for the rinsing procedure. Separation experiments with an optimized geometry of the filter plates were carried out in water and white wine suspensions.     

Development of a general method for designing microvascular networks using distribution of wall shear stress

In the present study, theoretical formulations for calculation of optimal bifurcation angle and relationship between the diameters of mother and daughter vessels using the power law model for non-Newtonian fluids are developed. The method is based on the distribution of wall shear stress in the mother and daughter vessels. Also, the effect of distribution of wall shear stress on the minimization of energy loss and flow resistance is considered. It is shown that constant wall shear stress in the mother and daughter vessels provides the minimum flow resistance and energy loss of biological flows. Moreover, the effects of different wall shear stresses in the mother and daughter branches, different lengths of daughter branches in the asymmetric bifurcations and non-Newtonian effect of biological fluid flows on the bifurcation angle and the relationship between the diameters of mother and daughter branches are considered. Using numerical simulations for non-Newtonian models such as power law and Carreau models, the effects of optimal bifurcation angle on the pressure drop and flow resistance of blood flow in the symmetric bifurcation are investigated. Numerical simulations show that optimal bifurcation angle decreases the pressure drop and flow resistance especially for bifurcations at large Reynolds number.