230 results found
Johari NH, Wood NB, Cheng Z, et al., 2019, Disturbed flow in a stenosed carotid artery bifurcation: Comparison of RANS-based transitional model and LES with experimental measurements, International Journal of Applied Mechanics, Vol: 11, ISSN: 1758-8251
Blood flow in the carotid arteries is usually laminar, but can undergo laminar-turbulent transition in the presence of a high-grade stenosis. In this study, pulsatile flow in a patient-based stenosed carotid artery bifurcation was examined using both large eddy simulation (LES) with dynamic Smagorinsky eddy viscosity model, and a Reynolds-averaged Navier-Stokes (RANS) method with a transitional version of the shear stress transport (SST-Tran) model. In addition, an experimental phantom was built for the same bifurcation geometry and velocity measurements were made using particle image velocimetry (PIV). Comparisons with PIV measurements of axial velocity profiles demonstrated that both SST-Tran and LES predicted the experimental results fairly well, with LES being slightly superior. Furthermore, LES predicted cycle-to-cycle variations in the region where transition to turbulence occurred, indicating the unsteady nature of turbulence transition. On the other hand, the SST-Tran model was able to capture important flow features observed in the PIV experiment, demonstrating its potential as a cost-effective alternative to LES for haemodynamic analyses of highly disturbed flow in diseased arteries.
Su J, Chai G, Wang L, et al., 2019, Pore-scale direct numerical simulation of particle transport in porous media, Chemical Engineering Science, Vol: 199, Pages: 613-627, ISSN: 1873-4405
A computational platform for direct numerical simulation of fluid-particle two-phase flow in porous media is presented in this study. In the proposed platform, the Navier-Stokes equations are used to describe the motion of the continuous phase, while the discrete element method (DEM) is employed to evaluate particle-particle and particle-wall interactions, with a fictitious domain method being adopted to evaluate particle-fluid interactions. Particle-wall contact states are detected by the ERIGID scheme. Moreover, a new scheme, namely, base point-increment method is developed to improve the accuracy of particle tracking in porous media. In order to improve computationally efficiency, a time splitting strategy is applied to couple the fluid and DEM solvers, allowing different time steps to be used which are adaptively determined according to the stability conditions of each solver. The proposed platform is applied to particle transport in a porous medium with its pore structure being reconstructed from micro-CT scans from a real rock. By incorporating the effect of pore structure which has a comparable size to the particles, numerical results reveal a number of distinct microscopic flow mechanisms and the corresponding macroscopic characteristics. The time evolution of the inlet to outlet pressure-difference consists of large-scale spikes and small-scale fluctuations. Apart from the influence through direct contacts between particles, the motion of a particle can also be affected by particles without contact through blocking a nearby passage for fluid flow. Particle size has a profound influence on the macroscopic motion behavior of particles. Small particles are easier to move along the main stream and less dispersive in the direction perpendicular to the flow than large particles.
Huang Y, Yu L, Ren J, et al., 2019, An activated-platelet-sensitive nanocarrier enables targeted delivery of tissue plasminogen activator for effective thrombolytic therapy, Journal of Controlled Release, Vol: 300, Pages: 1-12, ISSN: 0168-3659
It remains a major challenge to develop a selective and effective fibrinolytic system for thrombolysis with minimal undesirable side effects. Herein, we report a multifunctional liposomal system (164.6 ± 5.3 nm in diameter) which can address this challenge through targeted delivery and controlled release of tissue plasminogen activator (tPA) at the thrombus site. The tPA-loaded liposomes were PEGylated to improve their stability, and surface coated with a conformationally-constrained, cyclic arginine-glycine-aspartic acid (cRGD) to enable highly selective binding to activated platelets. The in vitro drug release profiles at 37 °C showed that over 90% of tPA was released through liposomal membrane destabilization involving membrane fusion upon incubation with activated platelets within 1 h, whereas passive release of the encapsulated tPA in pH 7.4 PBS buffer was 10% after 6 h. The release of tPA could be readily manipulated by changing the concentration of activated platelets. The presence of activated platelets enabled the tPA-loaded, cRGD-coated, PEGylated liposomes to induce efficient fibrin clot lysis in a fibrin-agar plate model and the encapsulated tPA retained 97.4 ± 1.7% of fibrinolytic activity as compared with that of native tPA. Furthermore, almost complete blood clot lysis was achieved in 75 min, showing considerably higher and quicker thrombolytic activity compared to the tPA-loaded liposomes without cRGD labelling. These results suggest that the nano-sized, activated-platelet-sensitive, multifunctional liposomes could facilitate selective delivery and effective release of tPA at the site of thrombus, thus achieving efficient clot dissolution whilst minimising undesirable side effects.
Pirola S, Guo B, Menichini C, et al., 2019, 4D flow MRI-based computational analysis of blood flow in patient-specific aortic dissection, IEEE Transactions on Biomedical Engineering, ISSN: 0018-9294
OBJECTIVE: Computational hemodynamics studies of aortic dissections usually combine patient-specific geometries with idealized or generic boundary conditions. In this study we present a comprehensive methodology for simulations of hemodynamics in type B aortic dissection (TBAD) based on fully patient-specific BCs. METHODS: Pre-operative 4D flow magnetic resonance imaging (MRI) and Doppler-wire pressure measurements (pre- and post-operative) were acquired from a TBAD patient. These data were used to derive boundary conditions for computational modelling of flow before and after thoracic endovascular repair (TEVAR). Validations of the computational results were performed by comparing predicted flow patterns with pre-TEVAR 4D flow MRI, as well as pressures with in vivo measurements. RESULTS AND CONCLUSION: Comparison of instantaneous velocity streamlines showed a good qualitative agreement with 4D flow MRI. Quantitative comparison of predicted pressures with pressure measurements revealed a maximum difference of 11 mmHg (-9.7%). Furthermore, our model correctly predicted the reduction of true lumen pressure from 74/115 mmHg pre-TEVAR to 64/107 mmHg post-TEVAR (diastolic/systolic pressures at entry tear level), compared to the corresponding measurements of 72/118 mmHg and 64/114 mmHg. This demonstrates that pre-TEVAR 4D flow MRI can be used to tune boundary conditions for post-TEVAR hemodynamic analyses.
Gu B, Piebalgs A, Huang Y, et al., 2019, Mathematical modelling of intravenous thrombolysis in acute ischaemic stroke: Effects of dose regimens on levels of fibrinolytic proteins and clot lysis time, Pharmaceutics, Vol: 11, ISSN: 1999-4923
Thrombolytic therapy is one of the medical procedures in the treatment of acute ischaemic stroke (AIS), whereby the tissue plasminogen activator (tPA) is intravenously administered to dissolve the obstructive blood clot. The treatment of AIS by thrombolysis can sometimes be ineffective and it can cause serious complications, such as intracranial haemorrhage (ICH). In this study, we propose an efficient mathematical modelling approach that can be used to evaluate the therapeutic efficacy and safety of thrombolysis in various clinically relevant scenarios. Our model combines the pharmacokinetics and pharmacodynamics of tPA with local clot lysis dynamics. By varying the drug dose, bolus-infusion delay time, and bolus-infusion ratio, with the FDA approved dosing protocol serving as a reference, we have used the model to simulate 13 dose regimens. Simulation results are compared for temporal concentrations of fibrinolytic proteins in plasma and the time that is taken to achieve recanalisation. Our results show that high infusion rates can cause the rapid degradation of plasma fibrinogen, indicative of increased risk for ICH, but they do not necessarily lead to fast recanalisation. In addition, a bolus-infusion delay results in an immediate drop in plasma tPA concentration, which prolongs the time to achieve recanalisation. Therefore, an optimal administration regimen should be sought by keeping the tPA level sufficiently high throughout the treatment and maximising the lysis rate while also limiting the degradation of fibrinogen in systemic plasma. This can be achieved through model-based optimisation in the future.
Zhan W, Gedroyc W, Xu X, 2019, Towards a multiphysics modelling framework for thermosensitive liposomal drug delivery to solid tumour combined with ultrasound hyperthermia, Biophysics Reports, Vol: 5, Pages: 43-59, ISSN: 2364-3439
Systemic toxicity and insufficient drug accumulation at the tumour site are main barriers in chemotherapy. Thermosensitive liposomes (TSL) combined with high intensity focused ultrasound (HIFU) has emerged as a potential solution to overcome these barriers through targeted drug delivery and localised release. Owing to the multiple physical and biochemical processes involved in this combination therapy, mathematical modelling becomes an indispensable tool for detailed analysis of the transport processes and prediction of tumour drug uptake. To this end, a multiphysics model has been developed to simulate the transport of chemotherapy drugs delivered through a combined HIFU-TSL system. All key delivery processes are considered in the model; these include interstitial fluid flow, HIFU acoustics, bioheat transfer, drug release and transport, as well as tumour drug uptake. The capability of the model is demonstrated through its application to a 2-D prostate tumour model reconstructed from magnetic resonance images. Our results not only demonstrate the feasibility of the model to simulate this combination therapy, but also confirm the advantage of HIFU-TSL drug delivery system with enhancement of drug accumulation in tumour regions and reduction of drug availability in normal tissue. This multiphysics modelling framework can serve as a useful tool to assist in the design of HIFU-TSL drug delivery systems and treatment regimen for improved anticancer efficacy.
Piebalgs A, Gu B, Roi D, et al., 2018, Computational simulations of thrombolytic therapy in acute ischaemic stroke, Scientific Reports, Vol: 8, ISSN: 2045-2322
Ischaemic stroke can occur when an artery to the brain is blocked by a blood clot. The use of thrombolytic agents, such as tissue plasminogen activator (tPA), to dissolve the occluding clot is limited by the risk of intracerebral haemorrhage (ICH), a known side effect associated with tPA. We developed a computational thrombolysis model for a 3D patient-specific artery coupled with a compartmental model for temporal concentrations of tPA and lysis proteins during intravenous infusion of tPA, in order to evaluate the effects of tPA dose on the efficacy of thrombolytic therapy and the risk of ICH. The model was applied to a 3-mm-long fibrin clot with two different fibrin fibre radii in the middle cerebral artery (MCA) – a setting relevant to ischaemic stroke, and results for different tPA dose levels and fibrin fibre radii were compared. Our simulation results showed that clot lysis was accelerated at higher tPA doses at the expense of a substantial increase in the risk of ICH. It was also found that a fine clot with a smaller fibre radius dissolved much slowly than a coarse clot due to a slower tPA penetration into the clots.
Menichini C, Pirola S, Guo B, et al., 2018, High wall stress may predict the formation of stent-graft-induced new entries after thoracic endovascular aortic repair, Journal of Endovascular Therapy, Vol: 25, Pages: 571-577, ISSN: 1526-6028
PURPOSE: To explore the potential role of morphological factors and wall stress in the formation of stent-graft-induced new entries (SINE) based on computed tomography (CT) images after thoracic endovascular aortic repair (TEVAR). CASE REPORT: Two female patients aged 59 years (patient 1) and 44 years (patient 2) underwent TEVAR for type B dissection in the chronic (patient 1) or subacute (patient 2) phase. CT scans at 3-month follow-up showed varying degrees of false lumen thrombosis in both patients. At 14-month follow-up, a SINE was observed in patient 1 while the dissected aorta in the other patient remained stable. Morphological and finite element analyses were performed based on the first follow-up CT images. The computational results showed that the SINE patient had higher stent-graft tortuosity than the non-SINE patient and much higher wall stress in the region close to the distal SINE. CONCLUSION: This case study suggests that high stent-graft tortuosity can lead to high wall stress, which is potentially linked to the formation of SINE. Further large population-based studies are needed to confirm this preliminary finding.
Zhan W, Alamer M, Xu XY, 2018, Computational modelling of drug delivery to solid tumour: Understanding the interplay between chemotherapeutics and biological system for optimised delivery systems, Advanced Drug Delivery Reviews, Vol: 132, Pages: 81-103, ISSN: 0169-409X
Drug delivery to solid tumour involves multiple physiological, biochemical and biophysical processes taking place across a wide range of length and time scales. The therapeutic efficacy of anticancer drugs is influenced by the complex interplays among the intrinsic properties of tumours, biophysical aspects of drug transport and cellular uptake. Mathematical and computational modelling allows for a well-controlled study on the individual and combined effects of a wide range of parameters on drug transport and therapeutic efficacy, which would not be possible or economically viable through experimental means. A wide spectrum of mathematical models has been developed for the simulation of drug transport and delivery in solid tumours, including PK/PD-based compartmental models, microscopic and macroscopic transport models, and molecular dynamics drug loading and release models. These models have been used as a tool to identify the limiting factors and for optimal design of efficient drug delivery systems. This article gives an overview of the currently available computational models for drug transport in solid tumours, together with their applications to novel drug delivery systems, such as nanoparticle-mediated drug delivery and convection-enhanced delivery.
Wang C-H, Xu XY, Zhan W, et al., 2018, 3D-Bioprinting and Micro-/Nano-Technology: Emerging Technologies in Biomedical Sciences Preface, ADVANCED DRUG DELIVERY REVIEWS, Vol: 132, Pages: 1-2, ISSN: 0169-409X
Centelles MN, Wright M, So P-W, et al., 2018, Image-guided thermosensitive liposomes for focused ultrasound drug delivery: Using NIRF-labelled lipids and topotecan to visualise the effects of hyperthermia in tumours, JOURNAL OF CONTROLLED RELEASE, Vol: 280, Pages: 87-98, ISSN: 0168-3659
Xu XY, Pirola S, Jarral O, et al., 2018, Computational study of aortic hemodynamics for patients with an abnormal aortic valve: the importance of secondary flow at the ascending aorta inlet, APL Bioengineering, Vol: 2, Pages: 026101-1-026101-14, ISSN: 2473-2877
Blood flow in the aorta is helical, but most computational studies ignore the presence of secondary flow components at the ascending aorta (AAo) inlet. The aim of this study is to ascertain the importance of inlet boundary conditions (BCs) in computational analysis of flow patterns in the thoracic aorta based on patient-specific images, with a particular focus on patients with an abnormal aortic valve. Two cases were studied: one presenting a severe aortic valve stenosis and the other with a mechanical valve. For both aorta models, three inlet BCs were compared; these included the flat profile and 1D through-plane velocity and 3D phase-contrast magnetic resonance imaging derived velocity profiles, with the latter being used for benchmarking. Our results showed that peak and mean velocities at the proximal end of the ascending aorta were underestimated by up to 41% when the secondary flow components were neglected. The results for helical flow descriptors highlighted the strong influence of secondary velocities on the helical flow structure in the AAo. Differences in all wall shear stress (WSS)-derived indices were much more pronounced in the AAo and aortic arch (AA) than in the descending aorta (DAo). Overall, this study demonstrates that using 3D velocity profiles as inlet BC is essential for patient-specific analysis of hemodynamics and WSS in the AAo and AA in the presence of an abnormal aortic valve. However, predicted flow in the DAo is less sensitive to the secondary velocities imposed at the inlet; hence, the 1D through-plane profile could be a sufficient inlet BC for studies focusing on distal regions of the thoracic aorta.
Ma T, Dong ZH, Fu WG, et al., 2018, Incidence and risk factors for retrograde type A dissection and stent graft-induced new entry after thoracic endovascular aortic repair, JOURNAL OF VASCULAR SURGERY, Vol: 67, Pages: 1026-+, ISSN: 0741-5214
Izgi C, Mohiaddin R, Xu XY, et al., 2018, Aortic Leaflet Stress in Surgery for Genetically Determined Root Aneurysms: Biomechanical Insights, ANNALS OF THORACIC SURGERY, Vol: 105, Pages: 984-984, ISSN: 0003-4975
Guo B, Pirola S, Guo D, et al., 2018, Hemodynamic evaluation using four-dimensional flow magnetic resonance imaging for a patient with multichanneled aortic dissection, Journal of Vascular Surgery Cases and Innovative Techniques, Vol: 4, Pages: 67-71, ISSN: 2468-4287
The hemodynamic function of multichanneled aortic dissection (MCAD) requires close monitoring and effective management to avoid potentially catastrophic sequelae. This report describes a 47-year-old man who underwent endovascular repair based on findings from four-dimensional (4D) flow magnetic resonance imaging of an MCAD. The acquired 4D flow data revealed complex, bidirectional flow patterns in the false lumens and accelerated blood flow in the compressed true lumen. The collapsed abdominal true lumen expanded unsatisfactorily after primary tear repair, which required further remodeling with bare stents. This case study demonstrates that hemodynamic analysis using 4D flow magnetic resonance imaging can help understand the complex pathologic changes of MCAD.
Menichini C, Cheng Z, Gibbs RGJ, et al., 2017, A computational model for false lumen thrombosis in type B aortic dissection following thoracic endovascular repair, Journal of Biomechanics, Vol: 66, Pages: 36-43, ISSN: 0021-9290
Thoracic endovascular repair (TEVAR) has recently been established as the preferred treatment option for complicated type B dissection. This procedure involves covering the primary entry tear to stimulate aortic remodelling and promote false lumen thrombosis thereby restoring true lumen flow. However, complications associated with incomplete false lumen thrombosis, such as aortic dilatation and stent graft induced new entry tears, can arise after TEVAR. This study presents the application and validation of a recently developed mathematical model for patient-specific prediction of thrombus formation and growth under physiologically realistic flow conditions. The model predicts thrombosis through the evaluation of shear rates, fluid residence time and platelet distribution, based on convection-diffusion-reaction transport equations. The model was applied to 3 type B aortic dissection patients: two TEVAR cases showing complete and incomplete false lumen thrombosis respectively, and one medically treated dissection with no signs of thrombosis. Predicted thrombus growth over time was validated against follow-up CT scans, showing good agreement with in vivo data in all cases with a maximum difference between predicted and measured false lumen reduction below 8%. Our results demonstrate that TEVAR-induced thrombus formation in type B aortic dissection can be predicted based on patient-specific anatomy and physiologically realistic boundary conditions. Our model can be used to identify anatomical or stent graft related factors that are associated with incomplete false lumen thrombosis following TEVAR, which may help clinicians develop personalised treatment plans for dissection patients in the future.
Pirola S, Cheng Z, Jarral OA, et al., 2017, On the choice of outlet boundary conditions for patient-specific analysis of aortic flow using computational fluid dynamics, Journal of Biomechanics, Vol: 60, Pages: 15-21, ISSN: 1873-2380
Boundary conditions (BCs) are an essential part in computational fluid dynamics (CFD) simulations of blood flow in large arteries. Although several studies have investigated the influence of BCs on predicted flow patterns and hemodynamic wall parameters in various arterial models, there is a lack of comprehensive assessment of outlet BCs for patient-specific analysis of aortic flow. In this study, five different sets of outlet BCs were tested and compared using a subject-specific model of a normal aorta. Phase-contrast magnetic resonance imaging (PC-MRI) was performed on the same subject and velocity profiles extracted from the in vivo measurements were used as the inlet boundary condition. Computational results obtained with different outlet BCs were assessed in terms of their agreement with the PC-MRI velocity data and key hemodynamic parameters, such as pressure and flow waveforms and wall shear stress related indices. Our results showed that the best overall performance was achieved by using a well-tuned three-element Windkessel model at all model outlets, which not only gave a good agreement with in vivo flow data, but also produced physiological pressure waveforms and values. On the other hand, opening outlet BCs with zero pressure at multiple outlets failed to reproduce any physiologically relevant flow and pressure features.
Zhan W, Gedroyc W, Xu X, Numerical Simulation of Thermosensitive Liposome-mediated Delivery of Doxorubicin to Solid Tumour under High Intensity Focused Ultrasound Heating, International Conference on Computational and Mathematical Biomedical Engineering
Zhan W, Gedroyc W, Xu XY, 2017, The effect of tumour size on drug transport and uptake in 3-D tumour models reconstructed from magnetic resonance images, PLOS ONE, Vol: 12, ISSN: 1932-6203
Drug transport and its uptake by tumour cells are strongly dependent on tumour properties, which vary in different types of solid tumours. By simulating the key physical and biochemical processes, a numerical study has been carried out to investigate the transport of anti-cancer drugs in 3-D tumour models of different sizes. The therapeutic efficacy for each tumour is evaluated by using a pharmacodynamics model based on the predicted intracellular drug concentration. Simulation results demonstrate that interstitial fluid pressure and interstitial fluid loss vary non-linearly with tumour size. Transvascular drug exchange, driven by the concentration gradient of unbound drug between blood and interstitial fluid, is more efficient in small tumours, owing to the low spatial-mean interstitial fluid pressure and dense microvasculature. However, this has a detrimental effect on therapeutic efficacy over longer periods as a result of enhanced reverse diffusion of drug to the blood circulation after the cessation of drug infusion, causing more rapid loss of drug in small tumours.
Gu B, Adjiman CS, Xu XY, 2016, The effect of feed spacer geometry on membrane performance and concentration polarisation based on 3D CFD simulations, Journal of Membrane Science, Vol: 527, Pages: 78-91, ISSN: 1873-3123
Feed spacers are used in spiral wound reverse osmosis (RO) membrane modules to keep the membrane sheets apart as well as to enhance mixing. They are beneficial to membrane performance but at the expense of additional pressure loss. In this study, four types of feed spacer configurations are investigated, with a total of 20 geometric variations based on commercially available spacers and selected filament angles. The impact of feed spacer design on membrane performance is investigated by means of three-dimensional (3D) computational fluid dynamics (CFD) simulations, where the solution-diffusion model is employed for water and solute transport through RO membranes. Numerical simulation results show that, for the operating and geometric conditions examined, fully woven spacers outperform other spacer configurations in mitigating concentration polarisation (CP). When designed with a mesh angle of 60°, fully woven spacers also deliver the highest water flux, although the associated pressure drops are slightly higher than their nonwoven counterparts. Middle layer geometries with a mesh angle of 30° produce the lowest water flux. On the other hand, spacers with a mesh angle of 90° show the lowest pressure drop among all the filament arrangements examined. Furthermore, the computational model presented here can also be used to predict membrane performance for a given feed spacer type and geometry.
Menichini C, Cheng Z, Gibbs R, et al., 2016, Predicting false lumen thrombosis in patient-specific models of aortic dissection, Journal of the Royal Society Interface, Vol: 13, ISSN: 1742-5689
Aortic dissection causes splitting of the aortic wall layers, allowing blood to enter a ‘false lumen’ (FL). For type B dissection, a significant predictor of patient outcomes is patency or thrombosis of the FL. Yet, no methods are currently available to assess the chances of FL thrombosis. In this study, we present a new computational model that is capable of predicting thrombus formation, growth and its effects on blood flow under physiological conditions. Predictions of thrombus formation and growth are based on fluid shear rate, residence time and platelet distribution, which are evaluated through convection–diffusion–reaction transport equations. The model is applied to a patient-specific type B dissection for which multiple follow-up scans are available. The predicted thrombus formation and growth patterns are in good qualitative agreement with clinical data, demonstrating the potential applicability of the model in predicting FL thrombosis for individual patients. Our results show that the extent and location of thrombosis are strongly influenced by aortic dissection geometry that may change over time. The high computational efficiency of our model makes it feasible for clinical applications. By predicting which aortic dissection patient is more likely to develop FL thrombosis, the model has great potential to be used as part of a clinical decision-making tool to assess the need for early endovascular intervention for individual dissection patients.
Pirola S, Cheng Z, Jarral OA, et al., 2016, Aortic flow hemodynamics after surgical aortic valve replacement: comparison with a healthy subject, Virtual Physiological Human 2016 Conference
Gu B, Xu XY, Adjiman CS, 2016, A predictive model for spiral wound reverse osmosis membrane modules: The effect of winding geometry and accurate geometric details, Computers and Chemical Engineering, Vol: 96, Pages: 248-265, ISSN: 1873-4375
A new one-dimensional predictive model for spiral wound modules (SWMs) applied to reverse osmosis membrane systems is developed by incorporating a detailed description of the geometric features of SWMs and considering flow in two directions. The proposed model is found to capture existing experimental data well, with similar accuracy to the widely-used plate model in which the SWM is assumed to consist of multiple thin rectangular channels. However, physical parameters that should in principle be model-independent, such as membrane permeability, are found to differ significantly depending on which model is used, when the same data sets are used for parameter estimation. Conversely, when using the same physical parameter values in both models, the water recovery predicted by the plate-like model is 12–20% higher than that predicted by the spiral model. This discrepancy is due to differences in the description of geometric features, in particular the active membrane area and the variable channel heights through the module, which impact on predicted performance and energy consumption. A number of design variables – the number of membrane leaves, membrane dimensions, centre pipe radius and the height of feed and permeate channels – are varied and their effects on performance, energy consumption and calculated module size are analysed. The proposed spiral model provides valuable insights into the effects of complex geometry on the performance of the SWM as well as of the overall system, at a low computational cost.
Su J, Huang C, Gu Z, et al., 2016, An Efficient RIGID Algorithm and Its Application to the Simulation of Particle Transport in Porous Medium, Transport in Porous Media, Pages: 1-33, ISSN: 1573-1634
RIGID algorithm was recently proposed to identify the contact state between spherical particles and arbitrary-shaped walls, demonstrating significantly improved robustness, accuracy and efficiency compared to existing methods. It is an important module when coupling computational fluid dynamics with discrete element model to simulate particle transport in porous media. The procedure to identify particle and surface contact state is usually time-consuming and takes a large part of the CPU time for discrete element simulations of dense particle flow in complex geometries, especially in cases with a large number of particle–wall collisions (e.g. particle transport in porous media). This paper presents a new version of RIGID algorithm, namely ERIGID, which further improves the efficiency of the original algorithm through a number of new strategies including the recursive algorithm for particle-face pair selection, angle-testing algorithm for determining particle-face relations and the smallest index filter for fast rejection and storage of time invariant. Several specially designed numerical experiments have been carried out to test the performance of ERIGID and verify the effectiveness of these strategies. Finally, the improved algorithm is used to simulate particle transport in a rock treated as a porous medium. Our numerical results reveal several important flow phenomena and the primary reason for particle trapping inside the rock.
Kandail HS, Hamady M, Xu XY, 2016, Hemodynamic Functions of Fenestrated Stent Graft under Resting, Hypertension, and Exercise Conditions., Frontiers in Surgery, Vol: 3, ISSN: 2296-875X
The aim of this study was to assess the hemodynamic performance of a patient-specific fenestrated stent graft (FSG) under different physiological conditions, including normal resting, hypertension, and hypertension with moderate lower limb exercise. A patient-specific FSG model was constructed from computed tomography images and was discretized into a fine unstructured mesh comprising tetrahedral and prism elements. Blood flow was simulated using Navier-Stokes equations, and physiologically realistic boundary conditions were utilized to yield clinically relevant results. For a given cycle-averaged inflow of 2.08 L/min at normal resting and hypertension conditions, approximately 25% of flow was channeled into each renal artery. When hypertension was combined with exercise, the cycle-averaged inflow increased to 6.39 L/min but only 6.29% of this was channeled into each renal artery, which led to a 438.46% increase in the iliac flow. For all the simulated scenarios and throughout the cardiac cycle, the instantaneous flow streamlines in the FSG were well organized without any notable flow recirculation. This well-organized flow led to low values of endothelial cell activation potential, which is a hemodynamic metric used to identify regions at risk of thrombosis. The displacement forces acting on the FSG varied with the physiological conditions, and the cycle-averaged displacement force at normal rest, hypertension, and hypertension with exercise was 6.46, 8.77, and 8.99 N, respectively. The numerical results from this study suggest that the analyzed FSG can maintain sufficient blood perfusion to the end organs at all the simulated conditions. Even though the FSG was found to have a low risk of thrombosis at rest and hypertension, this risk can be reduced even further with moderate lower limb exercise.
Carallo C, Tripolino C, De Franceschi MS, et al., 2016, Carotid endothelial shear stress reduction with aging is associated with plaque development in twelve years, Atherosclerosis, Vol: 251, Pages: 63-69, ISSN: 1879-1484
BACKGROUND AND AIMS: Atherosclerosis is associated with clinical, biochemical and haemodynamic risk factors. In a group of subjects studied twelve years apart, we evaluated carotid plaque development in relation to baseline and to changes at follow-up in common carotid haemodynamic profile. METHODS: Forty-eight participants were recruited to a cardiovascular disease prevention programme. Atherosclerotic plaques were evaluated and scored by echography. Endothelial shear stress, circumferential wall tension, and Peterson's elastic modulus as an index of arterial stiffness, were computed by echo-Doppler, along with blood viscosity data. Binary logistic regression analyses were used to test the association among the development of atherosclerosis, cardiovascular risk factors and haemodynamic variations. Analyses were also performed on participants who presented at the follow-up with carotid haemodynamic variations in the left or right common carotid only. RESULTS: Participants (69% male) were aged 64.5 ± 9.7 years at follow-up. Peak and mean endothelial shear stress was significantly lower at follow-up as previously reported; circumferential wall tension and arterial stiffness were significantly higher. Carotid plaque scores increased after 12 years (0.39 ± 0.72 vs. 0.67 ± 0.86, p < 0.01). Of the 96 common carotids analysed, shear stress reduction with aging was an independent predictor of carotid atherosclerosis (B = -0.063; odds ratio = 0.94; p = 0.01). Out of 48 participants, 21 (44%) showed shear stress reduction with aging in only one side of the body and, on this side, the plaque score increased (0.52 ± 0.98 vs. 0.90 ± 0.94, p < 0.05), remaining unchanged in the contralateral carotid tree. CONCLUSIONS: Aging-related shear stress reduction is an independent predictor of atherosclerosis development.
Xu XY, Kandail H, Hamady M, 2016, Effect of a Flared Renal Stent on the Performance of Fenestrated Stent-Grafts at Rest and Exercise Conditions, Journal of Endovascular Therapy, Vol: 23, Pages: 809-820, ISSN: 1526-6028
Purpose: To quantify the hemodynamic impact of a flared renal stent on the performance of fenestrated stent-grafts (FSGs) by analyzing flow patterns and wall shear stress–derived parameters in flared and nonflared FSGs in different physiologic scenarios. Methods: Hypothetical models of FSGs were created with and without flaring of the proximal portion of the renal stent. Flared FSGs with different dilation angles and protrusion lengths were examined, as well as a nonplanar flared FSG to account for lumbar curvature. Laminar and pulsatile blood flow was simulated by numerically solving Navier-Stokes equations. A physiologically realistic flow rate waveform was prescribed at the inlet, while downstream vasculature was modeled using a lumped parameter 3-element windkessel model. No slip boundary conditions were imposed at the FSG walls, which were assumed to be rigid. While resting simulations were performed on all the FSGs, exercise simulations were also performed on a flared FSG to quantify the effect of flaring in different physiologic scenarios. Results: For cycle-averaged inflow of 2.94 L/min (rest) and 4.63 L/min (exercise), 27% of blood flow was channeled into each renal branch at rest and 21% under exercise for all the flared FSGs examined. Although the renal flow waveform was not affected by flaring, flow within the flared FSGs was disturbed. This flow disturbance led to high endothelial cell activation potential (ECAP) values at the renal ostia for all the flared geometries. Reducing the dilation angle or protrusion length and exercise lowered the ECAP values for flared FSGs. Conclusion: Flaring of renal stents has a negligible effect on the time dependence of renal flow rate waveforms and can maintain sufficient renal perfusion at rest and exercise. Local flow patterns are, however, strongly dependent on renal flaring, which creates a local flow disturbance and may increase the thrombogenicity at the renal ostia. Smaller dilation angles, shorter protr
Singh SD, Xu XY, Pepper JR, et al., 2016, Effects of aortic root motion on wall stress in the Marfan aorta before and after personalised aortic root support (PEARS) surgery, Journal of Biomechanics, Vol: 49, Pages: 2076-2084, ISSN: 1873-2380
Aortic root motion was previously identified as a risk factor for aortic dissection due to increased longitudinal stresses in the ascending aorta. The aim of this study was to investigate the effects of aortic root motion on wall stress and strain in the ascending aorta and evaluate changes before and after implantation of personalised external aortic root support (PEARS). Finite element (FE) models of the aortic root and thoracic aorta were developed using patient-specific geometries reconstructed from pre- and post-PEARS cardiovascular magnetic resonance (CMR) images in three Marfan patients. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Cardiovascular MR cine images were used to quantify aortic root motion, which was imposed at the aortic root boundary of the FE model, with zero-displacement constraints at the distal ends of the aortic branches and descending aorta. Measurements of the systolic downward motion of the aortic root revealed a significant reduction in the axial displacement in all three patients post-PEARS compared with its pre-PEARS counterparts. Higher longitudinal stresses were observed in the ascending aorta when compared with models without the root motion. Implantation of PEARS reduced the longitudinal stresses in the ascending aorta by up to 52%. In contrast, the circumferential stresses at the interface between the supported and unsupported aorta were increase by up to 82%. However, all peak stresses were less than half the known yield stress for the dilated thoracic aorta.
Xu XY, Menichini C, 2016, Mathematical modeling of thrombus formation in idealized models of aortic dissection: Initial findings and potential applications, Journal of Mathematical Biology, Vol: 73, Pages: 1205-1226, ISSN: 1432-1416
Aortic dissection is a major aortic catastrophe with a high morbidity and mortality risk caused by the formation of a tear in the aortic wall. The development of a second blood filled region defined as the “false lumen” causes highly disturbed flow patterns and creates local hemodynamic conditions likely to promote the formation of thrombus in the false lumen. Previous research has shown that patient prognosis is influenced by the level of thrombosis in the false lumen, with false lumen patency and partial thrombosis being associated with late complications and complete thrombosis of the false lumen having beneficial effects on patient outcomes. In this paper, a new hemodynamics-based model is proposed to predict the formation of thrombus in Type B dissection. Shear rates, fluid residence time, and platelet distribution are employed to evaluate the likelihood for thrombosis and to simulate the growth of thrombus and its effects on blood flow over time. The model is applied to different idealized aortic dissections to investigate the effect of geometric features on thrombus formation. Our results are in qualitative agreement with in-vivo observations, and show the potential applicability of such a modeling approach to predict the progression of aortic dissection in anatomically realistic geometries.
Xu XY, Piebalgs A, 2015, Towards a Multi-Physics Modelling Framework for Thrombolysis under the Influence of Blood Flow, Journal of the Royal Society Interface, ISSN: 1742-5689
Thrombolytic therapy is an effective means of treating thromboembolic diseases but can also give rise to life-threatening side-effects. The infusion of a high drug concentration can provoke internal bleeding while an insufficient dose can lead to artery reocclusion. It is hoped that mathematical modelling of the process of clot lysis can lead to a better understanding and improvement of thrombolytic therapy. To this end, a multi-physics continuum model has been developed to simulate the dissolution of clot over time upon the addition of tissue plasminogen activator (tPA). The transport of tPA and other lytic proteins is modelled by a set of reaction-diffusion-convection equations, while blood flow is described by volume-averaged continuity and momentum equations. The clot is modelled as a fibrous porous medium with its properties being determined as a function of the fibrin fibre radius and voidage of the clot. A unique feature of the model is that it is capable of simulating the entire lytic process from the initial phase of lysis of an occlusive thrombus (diffusion-limited transport), the process of recanalization, to post-canalization thrombolysis under the influence of convective blood flow. The model has been used to examine the dissolution of a fully occluding clot in a simplified artery at different pressure drops. Our predicted lytic front velocities during the initial stage of lysis agree well with experimental and computational results reported by others. Following canalisation, clot lysis patterns are strongly influenced by local flow patterns which are symmetric at low pressure drops, but asymmetric at higher pressure drops which give rise to larger recirculation regions and extended areas of intense drug accumulation.
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