Imperial College London

Professor Xiao Yun Xu

Faculty of EngineeringDepartment of Chemical Engineering

Professor, Biofluid Mechanics & Director of Graduate School



yun.xu Website




407ACE ExtensionSouth Kensington Campus





Publication Type

297 results found

Watson C, Saaid H, Vedula V, Cardenas JC, Henke PK, Nicoud F, Xu XY, Hunt BJ, Manning KBet al., 2024, Venous Thromboembolism: Review of Clinical Challenges, Biology, Assessment, Treatment, and Modeling., Ann Biomed Eng, Vol: 52, Pages: 467-486

Venous thromboembolism (VTE) is a massive clinical challenge, annually affecting millions of patients globally. VTE is a particularly consequential pathology, as incidence is correlated with extremely common risk factors, and a large cohort of patients experience recurrent VTE after initial intervention. Altered hemodynamics, hypercoagulability, and damaged vascular tissue cause deep-vein thrombosis and pulmonary embolism, the two permutations of VTE. Venous valves have been identified as likely locations for initial blood clot formation, but the exact pathway by which thrombosis occurs in this environment is not entirely clear. Several risk factors are known to increase the likelihood of VTE, particularly those that increase inflammation and coagulability, increase venous resistance, and damage the endothelial lining. While these risk factors are useful as predictive tools, VTE diagnosis prior to presentation of outward symptoms is difficult, chiefly due to challenges in successfully imaging deep-vein thrombi. Clinically, VTE can be managed by anticoagulants or mechanical intervention. Recently, direct oral anticoagulants and catheter-directed thrombolysis have emerged as leading tools in resolution of venous thrombosis. While a satisfactory VTE model has yet to be developed, recent strides have been made in advancing in silico models of venous hemodynamics, hemorheology, fluid-structure interaction, and clot growth. These models are often guided by imaging-informed boundary conditions or inspired by benchtop animal models. These gaps in knowledge are critical targets to address necessary improvements in prediction and diagnosis, clinical management, and VTE experimental and computational models.

Journal article

Manchester EL, Pirola S, Pirola S, Mastroiacovo G, Polvani G, Pontone G, Xu XYet al., 2024, Aortic valve neocuspidization and bioprosthetic valves: evaluating turbulence haemodynamics, Computers in Biology and Medicine, Vol: 171, ISSN: 0010-4825

Aortic valve disease is often treated with bioprosthetic valves. An alternative treatment is aortic valve neocuspidization which is a relatively new reparative procedure whereby the three aortic cusps are replaced with patient pericardium or bovine tissues. Recent research indicates that aortic blood flow is disturbed, and turbulence effects have yet to be evaluated in either bioprosthetic or aortic valve neocuspidization valve types in patient-specific settings. The aim of this study is to better understand turbulence production in the aorta and evaluate its effects on laminar and turbulent wall shear stress. Four patients with aortic valve disease were treated with either bioprosthetic valves (n=2) or aortic valve neocuspidization valvular repair (n=2). Aortic geometries were segmented from magnetic resonance images (MRI), and 4D flow MRI was used to derive physiological inlet and outlet boundary conditions. Pulsatile large-eddy simulations were performed to capture the full range of laminar, transitional and turbulence characteristics in the aorta. Turbulence was produced in all aortas with highest levels occurring during systolic deceleration. In the ascending aorta, turbulence production is attributed to a combination of valvular skew, valvular eccentricity, and ascending aortic dilation. In the proximal descending thoracic aorta, turbulence production is dependent on the type of arch-descending aorta connection (e.g., a narrowing or sharp bend) which induces flow separation. Laminar and turbulent wall shear stresses are of similar magnitude throughout late systolic deceleration and diastole, although turbulent wall shear stress magnitudes exceed laminar wall shear stresses between 27.3% and 61.1% of the cardiac cycle. This emphasises the significance of including turbulent wall shear stress to improve our comprehension of progressive arterial wall diseases. The findings of this study recommend that aortic valve treatments should prioritise minimising valvular

Journal article

Yang Y, Gu B, Xu XY, 2024, In silico study of combination thrombolytic therapy with alteplase and mutant pro-urokinase for fibrinolysis in ischemic stroke, Computers in Biology and Medicine, Vol: 171, ISSN: 0010-4825

The synergistic advantage of combining tissue plasminogen activator (tPA) with pro-urokinase (proUK) for thrombolysis has been demonstrated in several in vitro experiments, and a single site proUK mutant (m-proUK) has been developed for better stability in plasma. Based on these studies, combination thrombolytic therapy with intravenous tPA and m-proUK has been suggested as a promising treatment for patients with ischemic stroke. This paper evaluates the efficacy and safety of the dual therapy by computational simulations of pharmacokinetics and pharmacodynamics coupled with a local fibrinolysis model. Seven dose regimens are simulated and compared with the standard intravenous tPA monotherapy. Our simulation results provide more insights into the complementary reaction mechanisms of tPA and m-proUK during clot lysis and demonstrate that the dual therapy can achieve a similar recanalization time (about 50 min) to tPA monotherapy, while keeping the circulating fibrinogen level within a normal range. Specifically, our results show that for all dual therapies with a 5 mg tPA bolus, the plasma concentration of fibrinogen remains stable at around 7.5 μM after a slow depletion over 50 min, whereas a rapid depletion of circulating fibrinogen (to 5 μM) is observed with the standard tPA therapy, indicating the potential advantage of dual therapy in reducing the risk of intracranial hemorrhage. Through simulations of varying dose combinations, it has been found that increasing tPA bolus can significantly affect fibrinogen level but only moderately improves recanalization time. Conversely, m-proUK doses and infusion duration exhibit a mild impact on fibrinogen level but significantly affect recanalization time. Therefore, future optimization of dose regimen should focus on limiting the tPA bolus while adjusting m-proUK dosage and infusion rate. Such adjustments could potentially maximize the therapeutic advantages of this combination therapy for

Journal article

Wang K, Armour CH, Gibbs RGJ, Xu XYet al., 2024, A numerical study of the effect of thrombus breakdown on predicted thrombus formation and growth, Biomechanics and Modeling in Mechanobiology, Vol: 23, Pages: 61-71, ISSN: 1617-7940

Thrombosis is a complex biological process which involves many biochemical reactions and is influenced by blood flow. Various computational models have been developed to simulate natural thrombosis in diseases such as aortic dissection (AD), and device-induced thrombosis in blood-contacting biomedical devices. While most hemodynamics-based models consider the role of low shear stress in the initiation and growth of thrombus, they often ignore the effect of thrombus breakdown induced by elevated shear stress. In this study, a new shear stress-induced thrombus breakdown function is proposed and implemented in our previously published thrombosis model. The performance of the refined model is assessed by quantitative comparison with experimental data on thrombus formation in a backward-facing step geometry, and qualitative comparison with in vivo data obtained from an AD patient. Our results show that incorporating thrombus breakdown improves accuracy in predicted thrombus volume and captures the same pattern of thrombus evolution as measured experimentally and in vivo. In the backward-facing step geometry, thrombus breakdown impedes growth over the step and downstream, allowing a stable thrombus to be reached more quickly. Moreover, the predicted thrombus volume, height and length are in better agreement with the experimental measurements compared to the original model which does not consider thrombus breakdown. In the patient-specific AD, the refined model outperforms the original model in predicting the extent and location of thrombosis. In conclusion, the effect of thrombus breakdown is not negligible and should be included in computational models of thrombosis.

Journal article

Armour C, Guo B, Saitta S, Guo D, Liu Y, Fu W, Dong Z, Xu Xet al., 2024, The role of multiple re-entry tears in type B aortic dissection progression: a longitudinal study using a controlled swine model, Journal of Endovascular Therapy, Vol: 31, Pages: 104-114, ISSN: 1074-6218

Purpose: False lumen (FL) expansion often occurs in type B aortic dissection (TBAD) and hasbeen associated with the presence of re-entry tears. This longitudinal study aims to elucidatethe role of re-entry tears in the progression of TBAD using a controlled swine model, byassessing aortic hemodynamics through combined imaging and computational modelling.Materials and Methods: A TBAD swine model with a primary entry tear at 7 cm distal to theleft subclavian artery was created in a previous study. In the current study, re-interventionwas carried out in this swine model to induce two additional re-entry tears of approximately5 mm in diameter. CT and 4D-flow MRI scans were taken at multiple follow-ups before andafter re-intervention. Changes in aortic volume were measured on CT scans, andhemodynamic parameters were evaluated based on dynamic data acquired with 4D-flow MRIand computational fluid dynamics simulations incorporating all available in-vivo data.Results: Morphological analysis showed FL growth of 20% following the initial TBAD – growthstabilised after the creation of additional tears and eventually FL volume reduced by 6%.Increasing the number of re-entry tears from one to two caused flow redistribution, with thepercentage of true lumen (TL) flow increasing from 56% to 78%, altered local velocities,reduced wall shear stress surrounding the tears, and led to a reduction in FL pressure andpressure difference between the two lumina.Conclusion: This study combined extensive in-vivo imaging data with sophisticatedcomputational methods to show that additional re-entry tears can alter dissectionhemodynamics through redistribution of flow between the TL and FL. This helps to reduce FLpressure, which could potentially stabilise aortic growth and lead to reversal of FL expansion.This work provides a starting point for further study into the use of fenestration in controllingundesirable FL expansion.

Journal article

Kan X, Ma T, Jiang X, Holzapfel GA, Dong Z, Xu XYet al., 2024, Towards biomechanics-based pre-procedural planning for thoracic endovascular aortic repair of aortic dissection, Computer Methods and Programs in Biomedicine, Vol: 244, ISSN: 0169-2607

BACKGROUND AND OBJECTIVE: Although thoracic aortic endovascular repair (TEVAR) has shown promising outcomes in the treatment of patients with complicated type B aortic dissection, complications still occur after TEVAR that can lead to catastrophic events. Biomechanical interactions between the stent-graft (SG) and the local aortic tissue play a critical role in determining the outcome of TEVAR. Different SG design may cause different biomechanical responses in the treated aorta, but such information is not known at the time of pre-procedural planning. By developing patient-specific virtual stent-graft deployment tools, it is possible to analyse and compare the biomechanical impact of different SGs on the local aorta for individual patients. METHODS: A finite element based virtual SG deployment model was employed in this study. Computational simulations were performed on a patient-specific model of type B aortic dissection, accounting for details of the SG design and the hyperelastic behaviour of the aortic wall. Based on the geometry reconstructed from the pre-TEVAR CTA scan, the patient-specific aortic dissection model was created and pre-stressed. Parametric models of three different SG products (SG1, SG2 and SG3) were built with two different lengths for each design. The SG models incorporated different stent and graft materials, stent strut patterns, and assembly approaches. Using our validated SG deployment simulation framework, virtual trials were performed on the patient-specific aortic dissection model using different SG products and varying SG lengths. CONCLUSION: Simulation results for different SG products suggest that SG3 with a longer length (SG3-long) would be the most appropriate device for the individual patient. Compared to SG1-short (the SG deployed in the patient), SG3-long followed the true lumen tortuosity closely, resulted in a more uniform true lumen expansion and a significant reduction in peak stress in the distal landing zone. These simulat

Journal article

Pirola S, Pirola S, Mastroiacovo G, Bonomi A, Manchester EL, Fisichella SM, Maragna R, Baggiano A, Mushtaq S, Muscogiuri G, Guglielmo M, Yun Xu X, Pontone G, Polvani Get al., 2023, Does the AVNeo valve reduce wall stress on the aortic wall? A cardiac magnetic resonance analysis with 4D-flow for the evaluation of aortic valve replacement with the Ozaki technique., Eur J Cardiothorac Surg, Vol: 64

OBJECTIVES: Aortic valve neocuspidalization aims to replace the 3 aortic cusps with autologous pericardium pre-treated with glutaraldehyde, and it is a surgical alternative to the classical aortic valve replacement (AVR). Image-based patient-specific computational fluid dynamics allows the derivation of shear stress on the aortic wall [wall shear stress (WSS)]. Previous studies support a potential link between increased WSS and histological alterations of the aortic wall. The aim of this study is to compare the WSS of the ascending aorta in patients undergoing aortic valve neocuspidalization versus AVR with biological prostheses. METHODS: This is a prospective nonrandomized clinical trial. Each patient underwent a 4D-flow cardiac magnetic resonance scan after surgery, which informed patient-specific computational fluid dynamics models to evaluate WSS at the ascending aortic wall. The adjusted variables were calculated by summing the residuals obtained from a multivariate linear model (with ejection fraction and left ventricle outflow tract-aorta angle as covariates) to the mean of the variables. RESULTS: Ten patients treated with aortic valve neocuspidalization were enrolled and compared with 10 AVR patients. The aortic valve neocuspidalization group showed a significantly lower WSS in the outer curvature segments of the proximal and distal ascending aorta as compared to AVR patients (P = 0.0179 and 0.0412, respectively). WSS levels remained significantly lower along the outer curvature of the proximal aorta in the aortic valve neocuspidalization population, even after adjusting the WSS for the ejection fraction and the left ventricle outflow tract-aorta angle [2.44 Pa (2.17-3.01) vs 1.94 Pa (1.72-2.01), P = 0.02]. CONCLUSIONS: Aortic valve neocuspidalization hemodynamical features are potentially associated with a lower WSS in the ascending aorta as compared to commercially available bioprosthetic valves.

Journal article

Johari NH, Menichini C, Hamady M, Xu XYet al., 2023, Computational modeling of low-density lipoprotein accumulation at the carotid artery bifurcation after stenting, International Journal for Numerical Methods in Biomedical Engineering, Vol: 39, ISSN: 1069-8299

Restenosis typically occurs in regions of low and oscillating wall shear stress, which also favor the accumulation of atherogenic macromolecules such as low-density lipoprotein (LDL). This study aims to evaluate LDL transport and accumulation at the carotid artery bifurcation following carotid artery stenting (CAS) by means of computational simulation. The computational model consists of coupled blood flow and LDL transport, with the latter being modeled as a dilute substance dissolved in the blood and transported by the flow through a convection-diffusion transport equation. The endothelial layer was assumed to be permeable to LDL, and the hydraulic conductivity of LDL was shear-dependent. Anatomically realistic geometric models of the carotid bifurcation were built based on pre- and post-stent computed tomography (CT) scans. The influence of stent design was investigated by virtually deploying two different types of stents (open- and closed-cell stents) into the same carotid bifurcation model. Predicted LDL concentrations were compared between the post-stent carotid models and the relatively normal contralateral model reconstructed from patient-specific CT images. Our results show elevated LDL concentration in the distal section of the stent in all post-stent models, where LDL concentration is 20 times higher than that in the contralateral carotid. Compared with the open-cell stents, the closed-cell stents have larger areas exposed to high LDL concentration, suggesting an increased risk of stent restenosis. This computational approach is readily applicable to multiple patient studies and, once fully validated against follow-up data, it can help elucidate the role of stent strut design in the development of in-stent restenosis after CAS.

Journal article

Ong CW, Wee IJY, Toma M, Cui F, Xu XY, Richards AM, Leo HL, Choong AMTLet al., 2023, Haemodynamic changes in visceral hybrid repairs of type III and type V thoracoabdominal aortic aneurysms, Scientific Reports, Vol: 13, ISSN: 2045-2322

The visceral hybrid procedure combining retrograde visceral bypass grafting and completion endovascular stent grafting is a feasible alternative to conventional open surgical or wholly endovascular repairs of thoracoabdominal aneurysms (TAAA). However, the wide variability in visceral hybrid configurations means that a priori prediction of surgical outcome based on haemodynamic flow profiles such as velocity pattern and wall shear stress post repair remain challenging. We sought to appraise the clinical relevance of computational fluid dynamics (CFD) analyses in the setting of visceral hybrid TAAA repairs. Two patients, one with a type III and the other with a type V TAAA, underwent successful elective and emergency visceral hybrid repairs, respectively. Flow patterns and haemodynamic parameters were analysed using reconstructed pre- and post-operative CT scans. Both type III and type V TAAAs showed highly disturbed flow patterns with varying helicity values preoperatively within their respective aneurysms. Low time-averaged wall shear stress (TAWSS) and high endothelial cell action potential (ECAP) and relative residence time (RRT) associated with thrombogenic susceptibility was observed in the posterior aspect of both TAAAs preoperatively. Despite differing bypass configurations in the elective and emergency repairs, both treatment options appear to improve haemodynamic performance compared to preoperative study. However, we observed reduced TAWSS in the right iliac artery (portending a theoretical risk of future graft and possibly limb thrombosis), after the elective type III visceral hybrid repair, but not the emergency type V repair. We surmise that this difference may be attributed to the higher neo-bifurcation of the aortic stent graft in the type III as compared to the type V repair. Our results demonstrate that CFD can be used in complicated visceral hybrid repair to yield potentially actionable predictive insights with implications on surveillance and enha

Journal article

Wang K, Armour C, Ma T, Dong Z, Xu Xet al., 2023, Hemodynamic parameters impact the stability of distal stent graft-induced new entry, Scientific Reports, Vol: 13, Pages: 1-11, ISSN: 2045-2322

Stent graft-induced new entry tear (SINE) is a serious complication in aortic dissection patients caused by the stent-graft itself after thoracic endovascular aortic repair (TEVAR). The stability of SINE is a key indicator for the need and timing of reinterventions. This study aimed to understand the role of hemodynamics in SINE stability by means of computational fluid dynamics (CFD) analysis based on patient-specific anatomical information. Four patients treated with TEVAR who developed a distal SINE (dSINE) were included; two patients had a stable dSINE and two patients experienced expansion of the dSINE upon follow-up examinations. CFD simulations were performed on geometries reconstructed from computed tomography scans acquired upon early detection of dSINE in these patients. Computational results showed that stable dSINEs presented larger regions with low time-averaged wall shear stress (TAWSS) and high relative residence time (RRT), and partial thrombosis was observed at subsequent follow-ups. Furthermore, significant systolic antegrade flow was observed in the unstable dSINE which also had a larger retrograde flow fraction (RFF) on the SINE plane. In conclusion, this pilot study suggested that high RRT and low TAWSS may indicate stable dSINE by promoting thrombosis, whereas larger RFF and antegrade flows inside dSINE might be associated with its expansion.

Journal article

Yuan X, Kan X, Dong Z, Xu Y, Nienaber Cet al., 2023, Nonsurgical repair of the ascending aorta: why less is more, Journal of Clinical Medicine, Vol: 12, Pages: 1-11, ISSN: 2077-0383

Objective: Advanced endovascular options for acute and chronic pathology of the ascending aorta are emerging; however, several problems with stent grafts placed in the ascending aorta have been identified in patients unsuitable for surgical repair, such as migration and erosion at aorta interface. Method: Among the six cases analysed in this report, three were treated with a stent graft in the ascending aorta to manage chronic dissection in the proximal aorta; dimensions of those stent grafts varied between 34 and 45 mm in diameter, and from 77 to 100 mm in length. Three patients, matched by age, sex and their nature of pathology, were subjected to the focal closure of a single communicating entry by the use of an occluding device (Amplatzer ASD and PFO occluders between 14 and 18 mm disc diameter) with similar Charlson comorbidity score. Results: Both conceptually different nonsurgical management strategies were technically feasible; however, with stent grafts, an early or delayed erosion to full re-dissection was documented with stent grafts, in contrast to complete seal, with an induced remodelling and a long-term survival after the successful placing of coils and occluder devices. Moreover, aortic root motion was not impaired by the focal occlusion of a communication with an occluder, while free motion was impeded after stent graft placement. Conclusions: The intriguing observation in our small series was that stent grafts placed in the ascending aorta portends the risk of an either early (post-procedural) or delayed migration and erosion of aortic tissues at the landing site or biological interface between 12 and 16 months after the procedure, a phenomenon not seen with the use of focal occluding devices up to 5 years of follow-up. Obviously, the focal approach avoids the erosion of the aortic wall as the result of minimal interaction with the biological interface, such as a diseased aortic wall. Potential explanations may be related to a reduced motion of the

Journal article

Salmasi MY, Pirola S, Mahuttanatan S, Fisichella SM, Sengupta S, Jarral OA, Oo A, O'Regan D, Xu XY, Athanasiou Tet al., 2023, Geometry and flow in ascending aortic aneurysms are influenced by left ventricular outflow tract orientation: Detecting increased wall shear stress on the outer curve of proximal aortic aneurysms, JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, Vol: 166, Pages: 11-+, ISSN: 0022-5223

Journal article

Hanna L, Gibbs RGJ, London Aortic Mechanobiology Working Group, 2023, Type II Endoleaks and Culprit Vessels: Will 4D MRI Change the Paradigm?, Eur J Vasc Endovasc Surg, Vol: 66

Journal article

Motoki K, Zhu Y, Mirsadraee S, Rosendahl U, Pepper J, Xu Xet al., 2023, A computational study of the effects of size, location, and number of tears on haemodynamics in surgically repaired type A aortic dissection, Frontiers in Cardiovascular Medicine, Vol: 10, Pages: 1-14, ISSN: 2297-055X

Objective: This study aimed to comprehensively examine the roles of size, location, and number of tears in the progression of surgically repaired type A aortic dissection (TAAD) by assessing haemodynamic changes through patient-specific computational fluid dynamic (CFD) simulations.Methods: Two patient-specific TAAD geometries with replaced ascending aorta were reconstructed based upon computed 15 tomography (CT) scans, after which 10 hypothetical models (5 per patient) with different tear configurations were artificially created. CFD simulations were performed on all the models under physiologically realistic boundary conditions.Results: Our simulation results showed that increasing either the size or number of the re-entry tears reduced the luminal pressure difference (LPD) and maximum time-averaged wall shear stress (TAWSS), as well as areas exposed to abnormally high or low TAWSS values. Models with a large re-entry tear outperformed the others by reducing the maximum LPD by 1.88 mmHg and 7.39 mmHg, for patients 1 and 2, respectively. Moreover, proximally located re-entry tears in the descending aorta were more effective at reducing LPD than distal re-entry tears.Discussion: These computational results indicate that the presence of a relatively large re-entry tear in the proximal descending aorta might help stabilize post-surgery aortic growth. This finding has important implications for the management and risk stratification of surgically repaired TAAD patients. Nevertheless, further validation in a large patient cohort is needed.

Journal article

Zhu Y, Xu XY, Rosendahl U, Pepper J, Mirsadraee Set al., 2023, A simplified computational workflow for evaluation of aortic hemodynamics after frozen elephant trunk intervention in type A aortic dissection, International Journal of Applied Mechanics, Vol: 15, ISSN: 1758-8251

This study aimed to predict the hemodynamic performance of frozen elephant trunk (FET) intervention in surgically repaired type A aortic dissection (TAAD) patients through computational simulations of post-operative scenarios. Patient-specific geometries of a single patient were reconstructed from pre- and post-FET intervention computed tomography angiography (CTA) images. The pre-FET geometry was used to create post-FET geometry through anatomical modifications and a simplified finite element simulation to inflate the stented true lumen (TL) segment. Computational fluid dynamics (CFD) simulations were then performed on the virtually created post-FET geometry, and the results were compared with those obtained with the actual post-FET geometry. Various intervention scenarios with different stent-graft (SG) lengths and TL volume expansion were also simulated and compared to study their impacts on hemodynamic performance. A good overall agreement was achieved between the virtual and real post-FET models, with the maximum difference in true and false lumen (FL) pressures along the dissected aorta being 4.2%. Simulation results for the actual intervention revealed high wall shear stress (WSS) and pressure around a distal tear that was found to have expanded on post-FET scan. Extending the SG length dramatically reduced the maximum WSS and pressure around the distal tear. This pilot study demonstrates the feasibility of using the simplified simulation workflow for personalized assessment of aortic hemodynamics following FET intervention in repaired TAAD. Further studies in a large patient cohort are warranted.

Journal article

Sengupta S, Yuan X, Maga L, Pirola S, Nienaber C, Xu Xet al., 2023, Aortic haemodynamics and wall stress analysis following arch aneurysm repair using a single-branched endograft, Frontiers in Cardiovascular Medicine, Vol: 10, Pages: 1-15, ISSN: 2297-055X

Introduction: Thoracic endovascular aortic repair (TEVAR) of the arch is challenging given its complex geometry and the involvement of supra-aortic arteries. Different branched endografts have been designed for use in this region, but their haemodynamic performance and the risk for post-intervention complications are not yet clear. This study aims to examine aortic haemodynamics and biomechanical conditions following TVAR treatment of an aortic arch aneurysm with a two-component single-branched endograft.Methods: Computational fluid dynamics and finite element analysis were applied to a patient-specific case at different stages: pre-intervention, post-intervention and follow-up. Physiologically accurate boundary conditions were used based on available clinical information.Results: Computational results obtained from the post-intervention model confirmed technical success of the procedure in restoring normal flow to the arch. Simulations of the follow-up model, where boundary conditions were modified to reflect change in supra-aortic vessel perfusion observed on the follow-up scan, predicted normal flow patterns but high levels of wall stress (up to 1.3M MPa) and increased displacement forces in regions at risk of compromising device stability. This might have contributed to the suspected endoleaks or device migration identified at the final follow up.Discussion: Our study demonstrated that detailed haemodynamic and biomechanical analysis can help identify possible causes for post-TEVAR complications in a patient-specific setting. Further refinement and validation of the computational workflow will allow personalised assessment to aid in surgical planning and clinical decision making.

Journal article

Xu X, Sengupta S, Yuan X, Pirola Set al., 2023, Aortic haemodynamics and wall stress analysis following arch aneurysm repair using a single-branched endograft, Frontiers in Cardiovascular Medicine, ISSN: 2297-055X

Journal article

Saitta S, Maga L, Armour C, Votta E, O'Regan DP, Salmasi MY, Athanasiou T, Weinsaft JW, Xu XY, Pirola S, Redaelli Aet al., 2023, Data-driven generation of 4D velocity profiles in the aneurysmal ascending aorta., Computer Methods and Programs in Biomedicine, Vol: 233, Pages: 1-8, ISSN: 0169-2607

BACKGROUND AND OBJECTIVE: Numerical simulations of blood flow are a valuable tool to investigate the pathophysiology of ascending thoratic aortic aneurysms (ATAA). To accurately reproduce in vivo hemodynamics, computational fluid dynamics (CFD) models must employ realistic inflow boundary conditions (BCs). However, the limited availability of in vivo velocity measurements, still makes researchers resort to idealized BCs. The aim of this study was to generate and thoroughly characterize a large dataset of synthetic 4D aortic velocity profiles sampled on a 2D cross-section along the ascending aorta with features similar to clinical cohorts of patients with ATAA. METHODS: Time-resolved 3D phase contrast magnetic resonance (4D flow MRI) scans of 30 subjects with ATAA were processed through in-house code to extract anatomically consistent cross-sectional planes along the ascending aorta, ensuring spatial alignment among all planes and interpolating all velocity fields to a reference configuration. Velocity profiles of the clinical cohort were extensively characterized by computing flow morphology descriptors of both spatial and temporal features. By exploiting principal component analysis (PCA), a statistical shape model (SSM) of 4D aortic velocity profiles was built and a dataset of 437 synthetic cases with realistic properties was generated. RESULTS: Comparison between clinical and synthetic datasets showed that the synthetic data presented similar characteristics as the clinical population in terms of key morphological parameters. The average velocity profile qualitatively resembled a parabolic-shaped profile, but was quantitatively characterized by more complex flow patterns which an idealized profile would not replicate. Statistically significant correlations were found between PCA principal modes of variation and flow descriptors. CONCLUSIONS: We built a data-driven generative model of 4D aortic inlet velocity profiles, suitable to be used in computational stu

Journal article

Zhu Y, Xu XY, Rosendahl U, Pepper J, Mirsadraee Set al., 2023, Advanced risk prediction for aortic dissection patients using imaging-based computational flow analysis, Clinical Radiology, Vol: 78, Pages: e155-e165, ISSN: 0009-9260

Patients with either a repaired or medically managed aortic dissection have varying degrees of risk of developing late complications. High-risk patients would benefit from earlier intervention to improve their long-term survival. Currently serial imaging is used for risk stratification, which is not always reliable. On the other hand, understanding aortic haemodynamics within a dissection is essential to fully evaluate the disease and predict how it may progress. In recent decades, computational fluid dynamics (CFD) has been extensively applied to simulate complex haemodynamics within aortic diseases, and more recently, four-dimensional (4D)-flow magnetic resonance imaging (MRI) techniques have been developed for in vivo haemodynamic measurement. This paper presents a comprehensive review on the application of image-based CFD simulations and 4D-flow MRI analysis for risk prediction in aortic dissection. The key steps involved in patient-specific CFD analyses are demonstrated. Finally, we propose a workflow incorporating computational modelling for personalised assessment to aid in risk stratification and treatment decision-making.

Journal article

Yang Y, Gu B, Xu X, 2023, In silico study of different thrombolytic agents for fibrinolysis in acute ischemic stroke, Pharmaceutics, Vol: 15, Pages: 1-14, ISSN: 1999-4923

Alteplase is the only FDA-approved drug for thrombolysis in acute ischemic stroke (AIS). Meanwhile, several thrombolytic drugs are deemed to be promising candidates to substitute alteplase. This paper evaluates the efficacy and safety of urokinase, ateplase, tenecteplase, and reteplase for intravenous AIS therapy by computational simulations of the pharmacokinetics and pharmacodynamics combined with a local fibrinolysis model. The performances of the drugs are evaluated by comparing clot lysis time, plasminogen activator inhibitor (PAI) inhibition resistance, intracranial hemorrhage (ICH) risk, and activation time from drug administration to clot lysis. Our results reveal that urokinase has the quickest lysis completion but the highest ICH risk due to excess fibrinogen depletion in systemic plasma. While tenecteplase and alteplase have very similar thrombolysis efficacy, tenecteplase has a lower risk of ICH and better resistance to PAI-1. Among the four simulated drugs, reteplase has the slowest fibrinolysis rate, but fibrinogen concentration in systemic plasma is unaffected during thrombolysis.

Journal article

Zhu Y, 2023, Irregular anatomical features can alter hemodynamics in Takayasu arteritis, JVS - Vascular Science, Vol: 4, ISSN: 2666-3503

ObjectiveTakayasu arteritis (TA) is a difficult disease to deal with because there are neither reliable clinical signs, laboratory biomarkers, nor a single noninvasive imaging technique that can be used for early diagnosis and disease activity monitoring. Knowledge of aortic hemodynamics in TA is lacking. This study aimed to fill this gap by assessing hemodynamics in patients with TA using image-based computational fluid dynamics (CFD) simulations.MethodsEleven patients with TA were included in the present study. Patient-specific geometries were reconstructed from either clinical aortic computed tomography angiography or magnetic resonance angiography studies and coupled with physiological boundary conditions for CFD simulations. Key anatomical and hemodynamic parameters were compared with a control group consisting of 18 age- and sex-matched adults without TA who had healthy aortas.ResultsCompared with controls, patients with TA had significantly higher aortic velocities (0.9 m/s [0.7, 1.1 m/s] vs 0.6 m/s [0.5, 0.7 m/s]; P = .002), maximum time-averaged wall shear stress (14.2 Pa [9.8, 20.9 Pa] vs 8.0 Pa [6.2, 10.3 Pa]; P = .004), and maximum pressure drops between the ascending and descending aorta (36.9 mm Hg [29.0, 49.3 mm Hg] vs 28.5 mm Hg [25.8, 31.5 mm Hg]; P = .004). These significant hemodynamic alterations in patients with TA might result from abnormal anatomical features including smaller arch diameter (20.0 mm [13.8, 23.3 mm] vs 25.2 mm [23.3, 26.8 mm]; P = .003), supra-aortic branch diameters (21.9 mm [18.5, 24.6 mm] vs 25.7 mm [24.3, 28.3 mm]; P = .003) and descending aorta diameter (14.7 mm [12.2, 16.8 mm] vs 22.5 mm [19.8, 24.0 mm]; P < .001).ConclusionsCFD analysis reveals hemodynamic changes in the aorta of patients with TA. The applicability of CFD technique coupled with standard imaging assessments in predicting disease progression of such patients will be explored in future studies. Future large cohort study with outcome correlation is also w

Journal article

Caddy G, Stebbing J, Wakefield G, Adair M, Xu XYet al., 2022, Multiscale modelling of nanoparticle distribution in a realistic tumour geometry following local injection, Cancers, Vol: 14, ISSN: 2072-6694

Radiosensitizers have proven to be an effective method of improving radiotherapy outcomes, with the distribution of particles being a crucial element to delivering optimal treatment outcomes due to the short range of effect of these particles. Here we present a computational model for the transport of nanoparticles within the tumour, whereby the fluid velocity and particle deposition are obtained and used as input into the convection-diffusion equation to calculate the spatio-temporal concentration of the nanoparticles. The effect of particle surface charge and injection locations on the distribution of nanoparticle concentration within the interstitial fluid and deposited onto cell surfaces is assessed. The computational results demonstrate that negatively charged particles can achieve a more uniform distribution throughout the tumour as compared to uncharged or positively charged particles, with particle volume within the fluid being 100% of tumour volume and deposited particle volume 44.5%. In addition, varying the injection location from the end to the middle of the tumour caused a reduction in particle volume of almost 20% for negatively charged particles. In conclusion, radiosensitizing particles should be negatively charged to maximise their spread and penetration within the tumour. Choosing an appropriate injection location can further improve the distribution of these particles.

Journal article

Jafarinia A, Armour CH, Gibbs RGJ, Xu XY, Hochrainer Tet al., 2022, Shear-driven modelling of thrombus formation in type B aortic dissection, Frontiers in Bioengineering and Biotechnology, Vol: 10, Pages: 1-12, ISSN: 2296-4185

Background: Type B aortic dissection (TBAD) is a dangerous pathological condition with a high mortality rate. TBAD is initiated by an intimal tear that allows blood to flow between the aortic wall layers, causing them to separate. As a result, alongside the original aorta (true lumen), a false lumen (FL) develops. TBAD compromises the whole cardiovascular system, in the worst case resulting in complete aortic rupture. Clinical studies have shown that dilation and rupture of the FL are related to the failure of the FL to thrombose. Complete FL thrombosis has been found to improve the clinical outcomes of patients with chronic TBAD and is the desired outcome of any treatment. Partial FL thrombosis has been associated with late dissection-related deaths and the requirement for re-intervention, thus the level of FL thrombosis is dominant in classifying the risk of TBAD patients. Therefore, it is important to investigate and understand under which conditions complete thrombosis of the FL occurs.Method: Local FL hemodynamics play an essential role in thrombus formation and growth. In this study, we developed a simplified phenomenological model to predict FL thrombosis in TBAD under physiological flow conditions. Based on an existing shear-driven thrombosis model, a comprehensive model reduction study was performed to improve computational efficiency. The reduced model has been implemented in Ansys CFX and applied to a TBAD case following thoracic endovascular aortic repair (TEVAR) to test the model. Predicted thrombus formation based on post-TEVAR geometry at 1-month was compared to actual thrombus formation observed on a 3-year follow-up CT scan.Results: The predicted FL status is in excellent agreement with the 3-year follow-up scan, both in terms of thrombus location and total volume, thus validating the new model. The computational cost of the new model is significantly lower than the previous thrombus model, with an approximate 65% reduction in computational time. Su

Journal article

Sengupta S, Zhu Y, Hamady M, Xu Xet al., 2022, Evaluating the haemodynamic performance of endografts for complex aortic arch repair, Bioengineering, Vol: 9, ISSN: 2306-5354

Thoracic endovascular aortic repair (TEVAR) of aortic aneurysms and dissections involving the arch has evolved over the last two decades. Compared to conventional surgical methods, endovascular repair offers a less invasive treatment option with lower risk and faster recovery. Endografts used in TEVAR vary in design depending on the procedure and application. Novel endografts (e.g., branched stent-graft) were developed to ensure perfusion of blood to the supra-aortic vessels, but their haemodynamic performance and long-term durability have not been adequately studied. This review focuses on the use of computational modelling to study haemodynamics in commercially available endografts designed for complex aortic arch repair. First, we summarise the currently adopted workflow for computational fluid dynamics (CFD) modelling, including geometry reconstruction, boundary conditions, flow models, and haemodynamic metrics of interest. This is followed by a review of recently (2010-present) published CFD studies on complex aortic arch repair, using both idealized and patient-specific models. Finally, we introduce some of the promising techniques that can be potentially applied to predict post-operative outcomes.

Journal article

Johari NH, Hamady M, Xu XY, 2022, Fluid-Structure Interaction Study of The Effect of Stent on Local Hemodynamics Parameters at The Stented Carotid Artery Bifurcation, Journal of Advanced Research in Applied Sciences and Engineering Technology, Vol: 28, Pages: 247-255

Previous fluid-structure interaction (FSI) studies on carotid bifurcation focused on the effect of wall compliance on the predicted hemodynamic features in normal or atherosclerotic carotid arteries. However, FSI study on patient-specific post-stent carotid model is still lacking, and to the authors knowledge no such a study has been reported so far. This study attempts to simulate the full-scale patient-specific post-stent carotid bifurcation geometry with the hope to understand the effect of wall compliance on hemodynamic quantities. The FSI model was based on patient-specific geometry consisting of three components i.e., the carotid artery wall and stent as the solid domain, and blood in the fluid domain. Full FSI simulations incorporating patient-specific boundary conditions at the inlet and outlets, and realistic homogenous incompressible carotid wall and stent were completed to evaluate the flow patterns and wall shear stress. The FSI simulation results were compared with the corresponding rigid-wall model. The quantitative difference in time-averaged wall shear stress (TAWSS) distribution between the FSI and rigid-wall models shows that FSI model predicted 8% less of the area in the low TAWSS band (<0.4%) compared 0.4-1.2 Pa. The results suggest that although the effect of wall compliance on flow patterns in the patient-specific post-stent carotid model is negligible, its quantitative effect on wall shear stress may not be trivial and should be considered in future studies.

Journal article

Caddy G, Stebbing J, Wakefield G, Xu Xet al., 2022, Modelling of nanoparticle distribution in a spherical tumour during and following local injection, Pharmaceutics, Vol: 14, ISSN: 1999-4923

Radio-sensitizing nanoparticles are a potential method to increase the damage caused tocancerous cells during the course of radiotherapy. The distribution of these particles in a given targeted tumour is a relevant factor in determining the efficacy of nanoparticle enhanced treatment. Inthis study a three-part mathematical model is shown to predict the distribution of nanoparticlesafter direct injection into a tumour. In contrast with previous studies, here a higher value of diffusivity for charged particles was used and the concentration profile of deposited particles was studied. Simulation results for particle concentrations both in the interstitial fluid and deposited ontocells are compared for different values of particle surface charges during and after injection. Ourresults show that particles with a negative surface charge can spread farther from the injection location as compared to uncharged particles with charged particles occupying 100% of the tumourvolume compared to 8.8% for uncharged particles. This has implications for the future developmentof radiosensitizers and associated trials.

Journal article

Yang QZC, Hanna L, Statton B, Armour C, ORegan D, Xu Y, Gibbs Ret al., 2022, O024 Prognostic value of haemodynamic parameters in predicting adverse clinical events in type B aortic dissection, Annual Scientific Meeting of the Surgical-Research-Society, Publisher: OXFORD UNIV PRESS, ISSN: 0007-1323

Conference paper

Armour C, Menichini C, Hanna L, Gibbs R, Xu Xet al., 2022, Computational Modeling of Flow and Thrombus Formation in Type B Aortic Dissection: The Influence of False Lumen Perfused Side Branches, Solid (Bio)mechanics: Challenges of the Next Decade., Publisher: Springer

Book chapter

Zhu Y, Mirsadraee S, Rosendahl U, Pepper J, Xu Xet al., 2022, Fluid-structure interaction simulations of repaired type A aortic dissection: a comprehensive comparison with rigid wall models, Frontiers in Physiology, Vol: 13, ISSN: 1664-042X

This study aimed to evaluate the effect of aortic wall compliance on intraluminal hemodynamics within surgically repaired type A aortic dissection (TAAD). Fully coupled two-way fluid-structure interaction (FSI) simulations were performed on two patient-specific post-surgery TAAD models reconstructed from computed tomography angiography images. Our FSI model incorporated prestress and different material properties for the aorta and graft. Computational results, including velocity, wall shear stress (WSS) and pressure difference between the true and false lumen, were compared between the FSI and rigid wall simulations. It was found that the FSI model predicted lower blood velocities and WSS along the dissected aorta. In particular, the area exposed to low time-averaged WSS (≤0.2 Pa) was increased from 21 cm2 (rigid) to 38 cm2 (FSI) in patient 1 and from 35 cm2 (rigid) to 144 cm2 (FSI) in patient 2. FSI models also produced more disturbed flow where much larger regions presented with higher turbulence intensity as compared to the rigid wall models. The effect of wall compliance on pressure difference between the true and false lumen was insignificant, with the maximum difference between FSI and rigid models being less than 0.25 mmHg for the two patient-specific models. Comparisons of simulation results for models with different Young’s moduli revealed that a more compliant wall resulted in further reduction in velocity and WSS magnitudes because of increased displacements. This study demonstrated the importance of FSI simulation for accurate prediction of low WSS regions in surgically repaired TAAD, but a rigid wall computational fluid dynamics simulation would be sufficient for prediction of luminal pressure difference.

Journal article

Hanna L, Armour C, Xu X, Gibbs Ret al., 2022, The haemodynamic and pathophysiological mechanisms of calcific aortic valve disease, Biomedicines, Vol: 10, ISSN: 2227-9059

Calcific aortic valve disease (CAVD) describes a chronic and slowly progressive condition that results in impaired functioning of the aortic valves due to pathological calcification of the valve leaflets. Recent epidemiological studies suggest a rising incidence and mortality from this condition making this a global health problem. CAVD shares many risk factors for atherosclerosis and early lesions of CAVD resemble atherosclerotic plaques. However, it is now apparent that CAVD is a distinct disease entity. The complex and harsh haemodynamic environment to which the aortic valve is exposed may act as the initial trigger for a cascade of downstream cellular and molecular pathways including lipid deposition, inflammation, extracellular matrix degradation and remodeling, and finally calcification. The effectors of calcification are two heterogenic cell types integral to the normal functioning of the aortic valve, the valvular endothelial and interstitial cells that develop an osteogenic phenotype. This review draws a summary of the pathophysiological mechanisms thought to be involved in CAVD.

Journal article

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