Imperial College London

Professor Xiao Yun Xu

Faculty of EngineeringDepartment of Chemical Engineering

Professor, Biofluid Mechanics & Director of Graduate School
 
 
 
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Contact

 

yun.xu Website

 
 
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Location

 

407ACE ExtensionSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

234 results found

Gu B, Piebalgs A, Huang Y, Roi D, Lobotesis K, Longstaff C, Hughes AD, Chen R, Thom SA, Xu XYet al., 2019, Computational simulations of thrombolysis in acute stroke: Effect of clot size and location on recanalisation, Medical Engineering & Physics, Vol: 73, Pages: 9-17, ISSN: 1350-4533

Acute ischaemic stroke can be treated by intravenous thrombolysis whereby tissue plasminogen activator (tPA) is infused to dissolve clots that block blood supply to the brain. In this study, we aim to examine the influence of clot location and size on lysis pattern and recanalisation by using a recently developed computational modelling framework for thrombolysis under physiological flow conditions. An image-based patient-specific model is reconstructed which consists of the internal carotid bifurcation with the A1 segment of anterior cerebral arteries and M1 segment of middle cerebral arteries, and the M1 bifurcation containing the M2 segments. By varying the clot size and location, 7 scenarios are simulated mimicking thrombolysis of M1 and M2 occlusions. Our results show that initial breakthrough always occurs along the inner curvature of the occluded cerebral artery, due to prolonged tPA residence time in the recirculation zone. For a given occlusion site, lysis completion time appears to increase almost quadratically with the initial clot volume; whereas for a given clot volume, the simulated M2 occlusions take up to 30% longer for complete lysis compared to the corresponding M1 occlusions.

Journal article

Jarral OA, Tan MKH, Salmasi MY, Pirola S, Pepper JR, O'Regan DP, Xu XY, Athanasiou Tet al., 2019, Phase-contrast magnetic resonance imaging and computational fluid dynamics assessment of thoracic aorta blood flow: a literature review, European Journal of Cardio-Thoracic Surgery, ISSN: 1010-7940

The death rate from thoracic aortic disease is on the rise and represents a growing global health concern as patients are often asymptomatic before acute events, which have devastating effects on health-related quality of life. Biomechanical factors have been found to play a major role in the development of both acquired and congenital aortic diseases. However, much is still unknown and translational benefits of this knowledge are yet to be seen. Phase-contrast cardiovascular magnetic resonance imaging of thoracic aortic blood flow has emerged as an exceptionally powerful non-invasive tool enabling visualization of complex flow patterns, and calculation of variables such as wall shear stress. This has led to multiple new findings in the areas of phenotype-dependent bicuspid valve flow patterns, thoracic aortic aneurysm formation and aortic prosthesis performance assessment. Phase-contrast cardiovascular magnetic resonance imaging has also been used in conjunction with computational fluid modelling techniques to produce even more sophisticated analyses, by allowing the calculation of haemodynamic variables with exceptional temporal and spatial resolution. Translationally, these technologies may potentially play a major role in the emergence of precision medicine and patient-specific treatments in patients with aortic disease. This clinically focused review will provide a systematic overview of key insights from published studies to date.

Journal article

Saitta S, Pirola S, Piatti F, Votta E, Lucherini F, Pluchinotta F, Carminati M, Lombardi M, Geppert C, Cuomo F, Figueroa C, Xu X, Redaelli Aet al., 2019, Evaluation of 4D Flow MRI-based non-invasive pressure assessment in aortic coarctations, Journal of Biomechanics, Vol: 94, Pages: 13-21, ISSN: 0021-9290

Severity of aortic coarctation (CoA) is currently assessed by estimating trans-coarctation pressure drops through cardiac catheterization or echocardiography. In principle, more detailed information could be obtained non-invasively based on space- and time-resolved magnetic resonance imaging (4D flow) data. Yet the limitations of this imaging technique require testing the accuracy of 4D flow-derived hemodynamic quantities against other methodologies.With the objective of assessing the feasibility and accuracy of this non-invasive method to support the clinical diagnosis of CoA, we developed an algorithm (4DF-FEPPE) to obtain relative pressure distributions from 4D flow data by solving the Poisson pressure equation. 4DF-FEPPE was tested against results from a patient-specific fluid-structure interaction (FSI) simulation, whose patient-specific boundary conditions were prescribed based on 4D flow data. Since numerical simulations provide noise-free pressure fields on fine spatial and temporal scales, our analysis allowed to assess the uncertainties related to 4D flow noise and limited resolution.4DF-FEPPE and FSI results were compared on a series of cross-sections along the aorta. Bland-Altman analysis revealed very good agreement between the two methodologies in terms of instantaneous data at peak systole, end-diastole and time-averaged values: biases (means of differences) were +0.4 mmHg, −1.1 mmHg and +0.6 mmHg, respectively. Limits of agreement (2 SD) were ±0.978 mmHg, ±1.06 mmHg and ±1.97 mmHg, respectively. Peak-to-peak and maximum trans-coarctation pressure drops obtained with 4DF-FEPPE differed from FSI results by 0.75 mmHg and −1.34 mmHg respectively. The present study considers important validation aspects of non-invasive pressure difference estimation based on 4D flow MRI, showing the potential of this technology to be more broadly applied to the clinical practice.

Journal article

Guo B, Dong Z, Pirola S, Liu Y, Menichini C, Xu XY, Guo D, Fu Wet al., 2019, Dissection level within aortic wall layers is associated with propagation of type B aortic dissection: a swine model study, European Journal of Vascular and Endovascular Surgery, Vol: 58, Pages: 415-425, ISSN: 1078-5884

OBJECTIVE: Haemodynamic and geometric factors play pivotal roles in the propagation of acute type B aortic dissection (TBAD). The aim of this study was to evaluate the association between dissection level within all aortic layers and the propagation of acute TBAD in porcine aorta. METHODS: Twelve pig acute TBAD models were created. In model A, the aortic wall tear was superficial and close to the intima (thin intimal flap), whereas in model B it was deep and close to the adventitia (thick intimal flap). Dissection propagation was evaluated using angiography or computed tomography scans, and the haemodynamic measurements were acquired using Doppler wires. Most pigs were followed up at 1, 3, 6, 12, 18, and up to 24 months; four animals were euthanised at three and six months, respectively (two from each group). RESULTS: Both models were successfully created. No statistical difference was observed for the median antegrade propagation distance intra-operatively between the two models (p = .092). At 24 months, the longitudinal propagation distance was significantly greater in model B than in model A (p = .016). No statistical difference in retrograde propagation was noted (p = .691). Over time, aortic wall dissection progressed most notably over the first three months in model A, whereas it continued over the first 12 months in model B. Flow velocity was significantly greater in the true lumen than in false lumen at the level of the primary tear (p = .001) and in the middle of the dissection (p = .004). The histopathological images at three and six months demonstrated the fibres were stretched linearly at the outside wall of false lumen in both models, while the depth of intimal tears developed to be superficial and similar at the distal dissection. CONCLUSION: In this swine model of TBAD, a deeper intimal tear resulted in greater dissection propagation.

Journal article

Su J, Chai G, Wang L, Cao W, Gu Z, Chen C, Xu Xet 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.

Journal article

Johari NH, Wood NB, Cheng Z, Torii R, Oishi M, Oshima M, Xu XYet 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.

Journal article

Huang Y, Yu L, Ren J, Gu B, Longstaff C, Hughes AD, Thom SA, Xu XY, Chen Ret 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.

Journal article

Pirola S, Guo B, Menichini C, Saitta S, Fu W, Dong Z, Xu XYet 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.

Journal article

Gu B, Piebalgs A, Huang Y, Longstaff C, Hughes A, Chen R, Thom S, Xu Xet 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.

Journal article

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.

Journal article

Piebalgs A, Gu B, Roi D, Lobotesis K, Thom S, Xu Xet 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.

Journal article

Menichini C, Pirola S, Guo B, Fu W, Dong Z, Xu XYet 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.

Journal article

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.

Journal article

Wang C-H, Xu XY, Zhan W, Davoodi Pet 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

Journal article

Centelles MN, Wright M, So P-W, Amrahli M, Xu XY, Stebbing J, Miller AD, Gedroyc W, Thanou Met 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

Journal article

Xu XY, Pirola S, Jarral O, O'Regan D, Asimakopoulos G, Anderson JR, Pepper J, Athanasiou Tet 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.

Journal article

Ma T, Dong ZH, Fu WG, Guo DQ, Xu X, Chen B, Jiang JH, Yang J, Shi ZY, Zhu T, Shi Y, Jiang BH, Xu XYet 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

Journal article

Izgi C, Mohiaddin R, Xu XY, Pepper J, Treasure Tet 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

Journal article

Guo B, Pirola S, Guo D, Dong Z, Xu XY, Fu Wet 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.

Journal article

Menichini C, Cheng Z, Gibbs RGJ, Xu XYet 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.

Journal article

Pirola S, Cheng Z, Jarral OA, O'Regan DP, Pepper JR, Athanasiou T, Xu XYet 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.

Journal article

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

Conference paper

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.

Journal article

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.

Journal article

Menichini C, Cheng Z, Gibbs R, Xu XYet 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.

Journal article

Pirola S, Cheng Z, Jarral OA, O’Regan DP, Athanasiou T, Xu Xet al., 2016, Aortic flow hemodynamics after surgical aortic valve replacement: comparison with a healthy subject, Virtual Physiological Human 2016 Conference

Conference paper

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.

Journal article

Su J, Huang C, Gu Z, Chen C, Xu Xet 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.

Journal article

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.

Journal article

Carallo C, Tripolino C, De Franceschi MS, Irace C, Xu XY, Gnasso Aet 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.

Journal article

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