Publications
297 results found
Li Z, Xu H, Armour CH, et al., 2022, The necessity to seal the re-entry tears of aortic dissection after TEVAR: a hemodynamic indicator, Frontiers in Bioengineering and Biotechnology, Vol: 10, Pages: 1-11, ISSN: 2296-4185
Thoracic endovascular aortic repair (TEVAR) is a common treatment for Stanford type B aortic dissection (TBAD). However, re-entry tears might be found distal to the stented region which transports blood between the true and false lumens. Sealing the re-entry tears, especially for the thoracic tears, could further reduce blood perfusion to the false lumen; however, it might also bring risks by re-intervention or surgery. Wise determination of the necessity to seal the re-entry tears is needed. In this study, patient-specific models of TBAD were reconstructed, and the modified models were established by virtually excluding the thoracic re-entries. Computational hemodynamics was investigated, and the variation of the functional index and first balance position (FBP) of the luminal pressure difference, due to the sealing of the re-entries, was reported. The results showed that the direction of the net flow through the unstented thoracic re-entries varied among cases. Excluding the re-entries with the net flow toward the false lumen may induce the FBP moving distally and the relative particle residence time increasing in the false lumen. This study preliminarily demonstrated that the hemodynamic status of the re-entry tears might serve as an indicator to the necessity of sealing. By quantifying the through-tear flow exchange and shift of FBP, one can predict the hemodynamic benefit by sealing the thoracic re-entries and thus wisely determine the necessity of further interventional management.
Manchester E, Pirola S, Salmasi MY, et al., 2022, Evaluation of computational methodologies for accurate prediction of wall shear stress and turbulence parameters in a patient-specific aorta, Frontiers in Bioengineering and Biotechnology, Vol: 10, ISSN: 2296-4185
Background: Recent studies suggest that blood flow in main arteries is intrinsically disturbed, even under healthy conditions. Despite this, many computational fluid dynamics (CFD) analyses of aortic haemodynamics make the assumption of laminar flow, and best practices surroundingappropriate modelling choices are lacking. This study aims to address this gap by evaluating different modelling and post-processing approaches in simulations of a patient-specific aorta. Methods: Magnetic resonance imaging (MRI) and 4D flow MRI from a patient with aortic valve stenosis were used to reconstruct the aortic geometry and derive patient-specific inlet and outlet boundary conditions. Three different computational approaches were considered based on assumed laminar or assumed disturbed flow states including low-resolution laminar (LR-laminar),high-resolution laminar (HR-Laminar) and large-eddy simulation (LES). Each simulation was ran for 30 cardiac cycles and post-processing was conducted on either the final cardiac cycle, or using a phase-averaged approach which utilised all 30 simulated cycles. Model capabilities were evaluated in terms of mean and turbulence-based parameters. Results: All simulation types, regardless of post-processing approach could correctly predict velocity values and flow patterns throughout the aorta. Lower resolution simulations could not accurately predict gradient-derived parameters including wall shear stress and viscous energy loss (largest differences up to 44.6% and 130.3%, respectively), although phase-averagingthese parameters improved predictions. The HR-Laminar simulation produced more comparable results to LES with largest differences in wall shear stress and viscous energy loss parameters up to 5.1% and 11.6%, respectively. Laminar-based parameters were better estimated thanturbulence-based parameters.Conclusions: Our findings suggest that well-resolved laminar simulations can accurately predict many laminar-based parameters in disturbed flo
Zhu Y, Xu XY, Rosendahl U, et al., 2022, Prediction of aortic dilatation in surgically repaired type A dissection: a longitudinal study using computational fluid dynamics, JTCVS Open, Vol: 9, Pages: 11-27, ISSN: 2666-2736
Objective:This study aimed to examine the role of a key hemodynamic parameter, namely the true and false lumen pressure difference to predict progressive aortic dilatation following type A aortic dissection (TAAD) repair.Methods:Four surgically repaired TAAD patients with multiple follow-up computed tomography (CT) angiography scans (4-5 scans per patient; N =18) were included. Through-plane diameter of the residual native thoracic aorta was measured in various aortic segments during the follow up period (mean follow up: 49.6±31.2 months;). Computational flow analysis was erformedto estimate true and false lumen pressure difference at the same locations and the correlation with aortic size change was studied using a linear mixed effects model.Results:Higher pressure difference between the true and false lumen was consistent with greater aortic diameter expansion during the follow up period (linear mixed effects analysis; coefficient 0.26, 95% confidence interval 0.15 – 0.37; P < 0.001). Based on our limited data points, a pressure difference higher than 5 mmHg might cause unstable aortic growth.Conclusions:Computational fluid dynamic assessment of standard aortic CT angiography offers a non-invasive technique that predicts the risk of aortic dilatation following TAAD. The technique may be used to plan closer observation or intervention in high-risk patients.
Chong MY, Gu B, Armour C, et al., 2022, An integrated fluid-structure interaction and thrombosis model for type B aortic dissection, Biomechanics and Modeling in Mechanobiology, Vol: 21, Pages: 261-275, ISSN: 1617-7940
False lumen thrombosis (FLT) in type B aortic dissection has been associated with theprogression of dissection and treatment outcome. Existing computational models mostlyassume rigid wall behaviour which ignores the effect of flap motion on flow and thrombusformation within the FL. In this study, we have combined a fully coupled fluid-structureinteraction (FSI) approach with a shear-driven thrombosis model described by a series ofconvection-diffusion reaction equations. The integrated FSI-thrombosis model has beenapplied to an idealised dissection geometry to investigate the interaction between vessel wallmotion and growing thrombus. Our simulation results show that wall compliance and flapmotion can influence the progression of FLT. The main difference between the rigid and FSImodels is the continuous development of vortices near the tears caused by drastic flap motionup to 4.45 mm. Flap-induced high shear stress and shear rates around tears help to transportactivated platelets further to the neighbouring region, thus speeding up thrombus formationduring the accelerated phase in the FSI models. Reducing flap mobility by increasing theYoung’s modulus of the flap slows down the thrombus growth. Compared to the rigid model,the predicted thrombus volume is 25 % larger using the FSI-thrombosis model with a relativelymobile flap. Furthermore, our FSI-thrombosis model can capture the gradual effect of thrombusgrowth on the flow field, leading to flow obstruction in the FL, increased blood viscosity andreduced flap motion. This model is a step closer towards simulating realistic thrombus growthin aortic dissection, by taking into account the effect of intimal flap and vessel wall motion.
Gu B, Huang Y, Manchester E, et al., 2022, Multiphysics modelling and simulation of thrombolysis via activated platelet-targeted nanomedicine, Pharmaceutical Research, Vol: 39, Pages: 41-56, ISSN: 0724-8741
Purpose:This study establishes a multiphysics simulation platform for both conventional and targeted thrombolysis using tissue plasminogen activator (tPA). Based on our computational results, the effects of therapeutic parameters on the dynamics of thrombolysis and the risk of side effects are investigated.Methods:The model extends our previously developed one-dimensional(1D) mathematical models for fibrinolysis by incorporating targeted thrombolysis. It consists of two parts: (i) a coupled mathematical model of systemic pharmacokinetics (PK) and pharmacodynamics (PD) and local PD in a 1D occluded artery, and (ii) a mechanistic model for a targeted thrombolytic system via activated platelet-targeted tPA-loaded nanovesicles (tPA-NV), with model parameters derived from our in vitro experiments. A total of 16 therapeutic scenarios are simulated by varying the clot location and composition as well as the dosing regimen with free tPA or tPA-NV.Results:Our simulation results indicate that tPA-NV offers several advantages over free tPA for thrombolysis. It reduces systemic exposure of tPA, thereby minimising the risk of bleeding complications. Simulations with different tPA-NV doses reveal that tPA-NV at 10% of the recommended dose can be as effective as the standard regimen with the full recommended dose of free tPA, demonstrating the potential of our tPA-NV as a new thrombolytic strategy with a reduced tPA dose. Moreover, faster recanalisation can be achieved with tPA-NV, especially for platelet-rich(or fibrin-poor) clots.Conclusions:Our simulation platform for thrombolysis with well-tuned model parameters can be used to evaluate and optimise treatment regimens of existing and new thrombolytic therapies via benefit/risk assessment under various therapeutic scenarios.
Sengupta S, Hamady M, Xu X-Y, 2022, Haemodynamic analysis of branched endografts for complex aortic arch repair, Bioengineering, Vol: 9, Pages: 1-17, ISSN: 2306-5354
This study aims to investigate the haemodynamic response induced by implantation of a double-branched endograft used in thoracic endovascular aortic repair (TEVAR) of the aortic arch. Anatomically realistic models were reconstructed from CT images obtained from patients who underwent TEVAR using the RelayPlus double-branched endograft implanted in the aortic arch. Two cases (Patient 1, Patient 2) were included here, both patients presented with type A aortic dissection before TEVAR. To examine the influence of inner tunnel branch diameters on localised flow patterns, three tunnel branch diameters were tested using the geometric model reconstructed for Patient 1. Pulsatile blood flow through the models was simulated by numerically solving the Navier–Stokes equations along with a transitional flow model. The physiological boundary conditions were imposed at the model inlet and outlets, while the wall was assumed to be rigid. Our simulation results showed that the double-branched endograft allowed for the sufficient perfusion of blood to the supra-aortic branches and restored flow patterns expected in normal aortas. The diameter of tunnel branches in the device plays a crucial role in the development of flow downstream of the branches and thus must be selected carefully based on the overall geometry of the vessel. Given the importance of wall shear stress in vascular remodelling and thrombus formation, longitudinal studies should be performed in the future in order to elucidate the role of tunnel branch diameters in long-term patency of the supra-aortic branches following TEVAR with the double-branched endograft.
Armour CH, Guo B, Saitta S, et al., 2022, Evaluation and verification of patient-specific modelling of type B aortic dissection, Computers in Biology and Medicine, Vol: 140, Pages: 1-11, ISSN: 0010-4825
Quantitative assessment of the complex hemodynamic environment in type B aortic dissection (TBAD) through computational fluid dynamics (CFD) simulations can provide detailed insights into the disease and its progression. As imaging and computational technologies have advanced, methodologies have been developed to increase the accuracy and physiological relevance of CFD simulations. This study presents a patient-specific workflow to simulate blood flow in TBAD, utilising the maximum amount of in vivo data available in the form of CT images, 4D-flow MRI and invasive Doppler-wire pressure measurements, to implement the recommended current best practice methodologies in terms of patient-specific geometry and boundary conditions. The study aimed to evaluate and verify this workflow through detailed qualitative and quantitative comparisons of the CFD and in vivo data. Based on data acquired from five TBAD patients, a range of essential model inputs was obtained, including inlet flow waveforms and 3-element Windkessel model parameters, which can be utilised in further studies where in vivo flow data is not available. Local and global analysis showed good consistency between CFD results and 4D-MRI data, with the maximum velocity in the primary entry tear differing by up to 0.3 m/s, and 80% of the analysed regions achieving moderate or strong correlations between the predicted and in vivo velocities. CFD predicted pressures were generally well matched to the Doppler-wire measurements, with some deviation in peak systolic values. Overall, this study presents a validated comprehensive workflow with extensive data for CFD simulation of TBAD.
Manchester E, Roi D, Gu B, et al., 2021, Modelling combined intravenous thrombolysis and mechanical thrombectomy in acute ischaemic stroke: Understanding the relationship between stent retriever configuration and clot lysis mechanisms, Life, Vol: 11, ISSN: 2075-1729
Background: Combined intravenous thrombolysis and mechanical thrombectomy (IVT-MT) is a common treatment in acute ischaemic stroke, however the interaction between IVT and MT from a physiological standpoint is poorly understood. In this pilot study, we conduct numerical simulations of combined IVT-MT with various idealised stent retriever configurations to evaluate performance in terms of complete recanalisation times and lysis patterns. Methods: A 3D patient-specific geometry of a terminal internal carotid artery with anterior and middle cerebral arteries is reconstructed, and a thrombus is artificially implanted in the MCA branch. Various idealised stent retriever configurations are implemented by varying stent diameter and stent placement, and a configuration without a stent retriever provides a baseline for comparison. A previously validated multi-level model of thrombolysis is used, which incorporates blood flow, drug transport, and fibrinolytic reactions within a fibrin thrombus. Results: Fastest total recanalisation was achieved in the thrombus without a stent retriever, with lysis times increasing with stent retriever diameter. Two mechanisms of clot lysis were established: axial and radial permeation. Axial permeation from the clot front was the primary mechanism of lysis in all configurations, as it facilitated increased protein binding with fibrin fibres. Introducing a stent retriever channel allowed for radial permeation, which occurred at the fluid-thrombus interface, although lysis was much slower in the radial direction because of weaker secondary velocities. Conclusions: Numerical models can be used to better understand the complex physiological relationship between IVT and MT. Two different mechanisms of lysis were established, providing a basis towards improving the efficacy of combined treatments.
Salmasi MYB, Pirola S, Sasidharan S, et al., 2021, High wall shear stress can predict wall degradation in ascending aorticaneurysms: an integrated biomechanics study, Frontiers in Bioengineering and Biotechnology, Vol: 9, Pages: 1-13, ISSN: 2296-4185
Background: Blood flow patterns can alter material properties of ascending thoracic aortic aneurysms (ATAA) via vascular wall remodeling. This study examines the relationship between wall shear stress (WSS) obtained from image-based computational modelling with tissue-derived mechanical and microstructural properties of the ATAA wall using segmental analysis.Methods: Ten patients undergoing surgery for ATAA were recruited. Exclusions: bicuspid aortopathy, connective tissue disease. All patients had pre-operative 4-dimensional flow magnetic resonance imaging (4D-MRI), allowing for patient-specific computational fluid dynamics (CFD) analysis and anatomically precise WSS mapping of ATAA regions (6–12 segments per patient). ATAA samples were obtained from surgery and subjected to region-specific tensile and peel testing (matched to WSS segments). Computational pathology was used to characterize elastin/collagen abundance and smooth muscle cell (SMC) count.Results: Elevated values of WSS were predictive of: reduced wall thickness [coef −0.0489, 95% CI (−0.0905, −0.00727), p = 0.022] and dissection energy function (longitudinal) [−15,0, 95% CI (−33.00, −2.98), p = 0.048]. High WSS values also predicted higher ultimate tensile strength [coef 0.136, 95% CI (0 0.001, 0.270), p = 0.048]. Additionally, elevated WSS also predicted a reduction in elastin levels [coef −0.276, 95% (CI −0.531, −0.020), p = 0.035] and lower SMC count ([oef −6.19, 95% CI (−11.41, −0.98), p = 0.021]. WSS was found to have no effect on collagen abundance or circumferential mechanical properties.Conclusions: Our study suggests an association between elevated WSS values and aortic wall degradation in ATAA disease. Further studies might help identify threshold values to predict acute aortic events.
Saitta S, Guo B, Pirola S, et al., 2021, Qualitative and quantitative assessments of blood flow on tears in type B aortic dissection with different morphologies, Frontiers in Bioengineering and Biotechnology, Vol: 9, ISSN: 2296-4185
Objective: The interactions between aortic morphology and hemodynamics play a key role in determining type B aortic dissection (TBAD) progression and remodeling. The study aimed to provide qualitative and quantitative hemodynamic assessment in four different TBAD morphologies based on 4D flow MRI analysis.Materials and Methods: Four patients with different TBAD morphologies underwent CT and 4D flow MRI scans. Qualitative blood flow evaluation was performed by visualizing velocity streamlines and flow directionality near the tears. Quantitative analysis included flow rate, velocity and reverse flow index (RFI) measurements. Statistical analysis was performed to evaluate hemodynamic differences between the true lumen (TL) and false lumen (FL) of patients.Results: Qualitative analysis revealed blood flow splitting near the primary entry tears (PETs), often causing the formation of vortices in the FL. All patients exhibited clear hemodynamic differences between TL and FL, with the TL generally showing higher velocities and flow rates, and lower RFIs. Average velocity magnitude measurements were significantly different for Patient 1 (t = 5.61, p = 0.001), Patient 2 (t = 3.09, p = 0.02) and Patient 4 (t = 2.81, p = 0.03). At follow-up, Patient three suffered from left renal ischemia because of FL collapse. This patient presented a complex morphology with two FLs and marked flow differences between TL and FLs. In Patient 4, left renal artery malperfusion was observed at the 32-months follow-up, due to FL thrombosis growing after PET repair.Conclusion: The study demonstrates the clinical feasibility of using 4D flow MRI in the context of TBAD. Detailed patient-specific hemodynamics assessment before treatment may provide useful insights to better understand this pathology in the future.
Xu X, Kan X, Ma T, et al., 2021, Patient-specific simulation of stent-graft deployment in type B aortic dissection: model development and validation, Biomechanics and Modeling in Mechanobiology, Vol: 20, Pages: 2247-2258, ISSN: 1617-7940
Thoracic endovascular aortic repair (TEVAR) has been accepted as the mainstream treatment for type B aortic dissection, but post-TEVAR biomechanical-related complications are still a major drawback. Unfortunately, the stent-graft (SG) configuration after implantation and biomechanical interactions between the SG and local aorta are usually unknown prior to a TEVAR procedure. The ability to obtain such information via personalized computational simulation would greatly assist clinicians in pre-surgical planning. In this study, a virtual SG deployment simulation framework was developed for the treatment for a complicated aortic dissection case. It incorporates patient-specific anatomical information based on pre-TEVAR CT angiographic images, details of the SG design, and the mechanical properties of the stent wire, graft and dissected aorta. Hyperelastic material parameters for the aortic wall were determined based on uniaxial tensile testing performed on aortic tissue samples taken from type B aortic dissection patients. Pre-stress conditions of the aortic wall and the action of blood pressure were also accounted for. The simulated post-TEVAR configuration was compared with follow-up CT scans, demonstrating good agreement with mean deviations of 5.8% in local open area and 4.6 mm in stent strut position. Deployment of the SG increased the maximum principal stress by 24.30 KPa in the narrowed true lumen but reduced the stress by 31.38 KPa in the entry tear region where there was an aneurysmal expansion. Comparisons of simulation results with different levels of model complexity suggested that pre-stress of the aortic wall and blood pressure inside the stent-graft should be included in order to accurately predict the deformation of the deployed SG
Tan WT, Liew YM, Mokhtarudin MJM, et al., 2021, Effect of Vessel Tortuosity on Stress Concentration at the Distal Stent-Vessel Interface: Possible Link With New Entry Formation Through Biomechanical Simulation, JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, Vol: 143, ISSN: 0148-0731
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Kan X, Ma T, Dong Z, et al., 2021, Patient-specific virtual stent-graft deployment for Type B aortic dissection: a pilot study of the impact of stent-graft length, Frontiers in Physiology, Vol: 12, ISSN: 1664-042X
Thoracic endovascular aortic repair (TEVAR) has been accepted as a standard treatment option for complicated type B aortic dissection. Distal stent-graft induced new entry (SINE) is recognized as one of the main post-TEVAR complications, which can lead to fatal prognosis. Previous retrospective cohort studies suggested that short stent-graft (SG) length (<165 mm) might correlate with increased risk of distal SINE. However, the influence of SG length on changes in local biomechanical conditions before and after TEVAR is unknown. In this paper, we aim to address this issue using a virtual SG deployment simulation model developed for application in type B aortic dissection. Our model incorporates detailed SG design and hyperelastic behaviour of the aortic wall. By making use of patient-specific geometry reconstructed from pre-TEVAR computed tomography angiography (CTA) scan, our model can predict post-TEVAR SG configuration and wall stress. Virtual SG deployment simulations were performed on a patient who underwent TEVAR with a short SG (158 mm in length), mimicking the actual clinical procedure. Further simulations were carried out on the same patient geometry but with different SG lengths (183 mm and 208 mm) in order to evaluate the effect of SG length on changes in local stress in the treated aorta.
Kan X, Yuan X, Salmasi MYB, et al., 2021, Comprehensive Mechanical Modelling of Thoracic Endovascular Aortic Repair in Type A Aortic Dissection, Publisher: The Japanese Circulation Society, ISSN: 0047-1828
Huang Y, Gu B, Salles II, et al., 2021, Fibrinogen-mimicking, multi-arm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy, Science Advances, Vol: 7, ISSN: 2375-2548
Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and hemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multi-arm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This novel system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our experiments with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. Furthermore, we report a purpose-built computational model capable of simulating targeted thrombolysis of the tPA-loaded nanovesicle and with potential in predicting the dynamics of thrombolysis in physiologically realistic scenarios. This combined experimental and computational work presents a promising platform for development of thrombolytic nanomedicines.
Zhu Y, Mirsadraee S, Asimakopoulos G, et al., 2021, Association of hemodynamic factors and progressive aortic dilatation following type A aortic dissection surgical repair, Scientific Reports, Vol: 11, ISSN: 2045-2322
Type A aortic dissection (TAAD) involves the ascending aorta or the arch. Acute TAAD usually requires urgent replacement of the ascending aorta. However, a subset of these patients develops aortic rupture due to further dilatation of the residual dissected aorta. There is currently no reliable means to predict the risk of dilatation following TAAD repair. In this study, we performed a comprehensive morphological and hemodynamic analysis for patients with and without progressive aortic dilatation following surgical replacement of the ascending aorta. Patient-specific models of repaired TAAD were reconstructed from post-surgery computed tomography images for detailed computational fluid dynamic analysis. Geometric and hemodynamic parameters were evaluated and compared between patients with stable aortic diameters (N = 9) and those with aortic dilatation (N = 8). Our results showed that the number of re-entry tears and true/false lumen pressure difference were significantly different between the two groups. Patients with progressive aortic dilatation had higher luminal pressure difference (6.7 [4.6, 10.9] vs. 0.9 [0.5, 2.3] mmHg; P = 0.001) and fewer re-entry tears (1.5 [1, 2.8] vs. 5 [3.3, 7.5]; P = 0.02) compared to patients with stable aortic diameters, suggesting that these factors may serve as potential predictors of aneurysmal dilatation following surgical repair of TAAD.
Yuan X, Kan X, Xu XY, et al., 2021, Identifying and quantifying the 4D motion of aortic root, 70th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: Elsevier, Pages: 1832-1832, ISSN: 0735-1097
BackgroundThe motion of aortic root due to heart traction was previously suggested to contribute to proximal aortic dissection. The 4D motion of the aorta is recognisable with dynamic image acquisition (multiphase ECG-gated contrast-enhanced CT). However, both displacement and rotation in quantitative terms still remain unknown. The objective is to investigate the motion of aortic root from dynamic CT images in quantitative terms.Methods40 patients’ dynamic CT images for coronary assessment have been identified from PACS at Royal Brompton and Harefield hospital. All images were acquired under the same scanning protocol and no aortopathy had been identified. The scans were triggered by ECG and consist of 10 evenly spaced phases (0%-90%) in a cardiac cycle. The end diastolic phase (0%) was used as reference phase and the three commissures of leaflets were manually marked to identify the plane of sinotubular junction (STJ) by image post-processing software. A patient-specific coordinate system was created at the centre of STJ with the Z-axis parallel to the local longitudinal direction. Both the ostia of the left and right coronary were chosen as landmarks and traced at each phase. The coordinates of the two coronary ostia were transferred to the patient-specific coordinate system to quantify the motion normal to STJ plane (out-plane), the motion within STJ plane (in-plane) and the twist motion.ResultsA total of 40 patients enrolled for this study with a mean age 65±12, and 14 patients were male (35%). The out-plane motion was recorded the largest displacement with 10.03±2.90 and 9.30±2.36 mm referenced by the left and right coronary ostium, respectively. The mean downward movement of aortic root is 9.10±2.38 mm. The STJ in-plane motion was 7.56±3.01 and 6.65±2.74 mm for left coronary ostium, compared with 6.65±2.74 and 6.54±2.51 mm for right coronary ostium. The twisting of the aortic root is 10.78±4
Gu B, Adjiman C, Xu X, 2021, Correlations for concentration polarisation and pressure drop in spacer-filled RO membrane modules based on CFD simulations, Membranes, Vol: 11, ISSN: 2077-0375
Empirical correlations for mass transfer coefficient and friction factor are often used in process models for reverse osmosis (RO) membrane systems. These usually involve four dimensionless groups, namely Reynolds number (Re), Sherwood number (Sh), friction factor (f), and Schmidt number (Sc), with the associated coefficients and exponents being obtained by fitting to experimental data. However, the range of geometric and operating conditions covered by the experiments is often limited. In this study, new dimensionless correlations for concentration polarization (CP) modulus and friction factor are presented, which are obtained by dimensional analysis and using simulation data from computational fluid dynamics (CFD). Two-dimensional CFD simulations are performed on three configurations of spacer-filled channels with 76 combinations of operating and geometric conditions for each configuration, covering a broad range of conditions encountered in RO membrane systems. Results obtained with the new correlations are compared with those from existing correlations in the literature. There is good consistency in the predicted CP with mean discrepancies less than 6%, but larger discrepancies for pressure gradient are found among the various friction factor correlations. Furthermore, the new correlations are implemented in a process model with six spiral wound modules in series and the predicted recovery, pressure drop, and specific energy consumption are compared with a reference case obtained by ROSA (Reverse Osmosis System Analysis, The Dow Chemical Company). Differences in predicted recovery and pressure drop are up to 5% and 83%, respectively, highlighting the need for careful selection of correlations when using predictive models in process design. Compared to existing mass transfer correlations, a distinct advantage of our correlations for CP modulus is that they can be directly used to estimate the impact of permeate flux on CP at a membrane surface without having to r
Manchester E, Pirola S, Salmasi M, et al., 2021, Analysis of turbulence effects in a patient-specific aorta with aortic valve stenosis, Cardiovascular Engineering and Technology, Vol: 12, Pages: 438-453, ISSN: 1869-408X
Blood flow in the aorta is often assumed laminar, however aortic valve pathologies may induce transition to turbulence and our understanding of turbulence effects is incomplete. The aim of the study was to provide a detailed analysis of turbulence effects in aortic valve stenosis (AVS).Methods:Large-eddy simulation (LES) of flow through a patient-specific aorta with AVS was conducted. Magnetic resonance imaging (MRI) was performed and used for geometric reconstruction and patient-specific boundary conditions. Computed velocity field was compared with 4D flow MRI to check qualitative and quantitative consistency. The effect of turbulence was evaluated in terms of fluctuating kinetic energy, turbulence-related wall shear stress (WSS) and energy loss.Results:Our analysis suggested that turbulence was induced by a combination of a high velocity jet impinging on the arterial wall and a dilated ascending aorta which provided sufficient space for turbulence to develop. Turbulent WSS contributed to 40% of the total WSS in the ascending aorta and 38% in the entire aorta. Viscous and turbulent irreversible energy losses accounted for 3.9 and 2.7% of the total stroke work, respectively.Conclusions:This study demonstrates the importance of turbulence in assessing aortic haemodynamics in a patient with AVS. Neglecting the turbulent contribution to WSS could potentially result in a significant underestimation of the total WSS. Further work is warranted to extend the analysis to more AVS cases and patients with other aortic valve diseases.
Armour C, Guo B, Pirola S, et al., 2021, The influence of inlet velocity profile on predicted flow in type B aortic dissection, Biomechanics and Modeling in Mechanobiology, Vol: 20, Pages: 481-490, ISSN: 1617-7940
In order for computational fluid dynamics to provide quantitative parameters to aid in the clinical assessment of type B aortic dissection, the results must accurately mimic the hemodynamic environment within the aorta. The choice of inlet velocity profile (IVP) therefore is crucial; however, idealised profiles are often adopted, and the effect of IVP on hemodynamics in a dissected aorta is unclear. This study examined two scenarios with respect to the influence of IVP—using (a) patient-specific data in the form of a three-directional (3D), through-plane (TP) or flat IVP; and (b) non-patient-specific flow waveform. The results obtained from nine simulations using patient-specific data showed that all forms of IVP were able to reproduce global flow patterns as observed with 4D flow magnetic resonance imaging. Differences in maximum velocity and time-averaged wall shear stress near the primary entry tear were up to 3% and 6%, respectively, while pressure differences across the true and false lumen differed by up to 6%. More notable variations were found in regions of low wall shear stress when the primary entry tear was close to the left subclavian artery. The results obtained with non-patient-specific waveforms were markedly different. Throughout the aorta, a 25% reduction in stroke volume resulted in up to 28% and 35% reduction in velocity and wall shear stress, respectively, while the shape of flow waveform had a profound influence on the predicted pressure. The results of this study suggest that 3D, TP and flat IVPs all yield reasonably similar velocity and time-averaged wall shear stress results, but TP IVPs should be used where possible for better prediction of pressure. In the absence of patient-specific velocity data, effort should be made to acquire patient’s stroke volume and adjust the applied IVP accordingly.
Alamer M, Xu X, 2021, The influence of tumour vasculature on fluid flow in solid tumours: a mathematical modelling study, Biophysics Reports, Vol: 7, Pages: 35-54, ISSN: 2364-3439
Tumour vasculature is known to be aberrant, tortuous and erratic which can have significant implications for fluid flow. Fluid dynamics in tumour tissue plays an important part in tumour growth, metastasis and the delivery of therapeutics. Mathematical models are increasingly employed to elucidate the complex interplay between various aspects of the tumour vasculature and fluid flow. Previous models usually assume a uniformly distributed vasculature without explicitly describing its architecture or incorporate the distribution of vasculature without accounting for real geometric features of the network. In this study, an integrated computational model is developed by resolving fluid flow at the single capillary level across the whole tumour vascular network. It consists of an angiogenesis model and a fluid flow model which resolves flow as a function of the explicit vasculature by coupling intravascular flow and interstitial flow in tumour tissue. The integrated model has been used to examine the influence of microvascular distribution, necrosis and vessel pruning on fluid flow, as well as the effect of heterogeneous vessel permeability. Our results reveal the level of nonuniformity in tumour interstitial fluid pressure (IFP), with large variations in IFP profile between necrotic and non-necrotic tumours. Changes in microscopic features of the vascular network can significantly influence fluid flow in the tumour where removal of vessel blind ends has been found to reduce IFP and promote interstitial fluid flow. Our results demonstrate the importance of incorporating microscopic properties of the tumour vasculature and intravascular flow when predicting fluid flow in tumour tissue.
Amrahli M, Centelles M, Cressey P, et al., 2021, MR-labelled liposomes and focused ultrasound for spatiotemporally controlled drug release in triple negative breast cancers in mice., Nanotheranostics, Vol: 5, Pages: 125-142, ISSN: 2206-7418
Rationale: Image-guided, triggerable, drug delivery systems allow for precisely placed and highly localised anti-cancer treatment. They contain labels for spatial mapping and tissue uptake tracking, providing key location and timing information for the application of an external stimulus to trigger drug release. High Intensity Focused Ultrasound (HIFU or FUS) is a non-invasive approach for treating small tissue volumes and is particularly effective at inducing drug release from thermosensitive nanocarriers. Here, we present a novel MR-imageable thermosensitive liposome (iTSL) for drug delivery to triple-negative breast cancers (TNBC). Methods: A macrocyclic gadolinium-based Magnetic Resonance Imaging (MRI) contrast agent was covalently linked to a lipid. This was incorporated at 30 mol% into the lipid bilayer of a thermosensitive liposome that was also encapsulating doxorubicin. The resulting iTSL-DOX formulation was assessed for physical and chemical properties, storage stability, leakage of gadolinium or doxorubicin, and thermal- or FUS-induced drug release. Its effect on MRI relaxation time was tested in phantoms. Mice with tumours were used for studies to assess both tumour distribution and contrast enhancement over time. A lipid-conjugated near-infrared fluorescence (NIRF) probe was also included in the liposome to facilitate the real time monitoring of iTSL distribution and drug release in tumours by NIRF bioimaging. TNBC (MDA-MB-231) tumour-bearing mice were then used to demonstrate the efficacy at retarding tumour growth and increasing survival. Results: iTSL-DOX provided rapid FUS-induced drug release that was dependent on the acoustic power applied. It was otherwise found to be stable, with minimum leakage of drug and gadolinium into buffers or under challenging conditions. In contrast to the usually suggested longer FUS treatment we identified that brief (~3 min) FUS significantly enhanced iTSL-DOX uptake to a targeted tumour and triggered near-total rele
Yuan X, Kan X, Xu XY, et al., 2020, Finite element modeling to predict procedural success of thoracic endovascular aortic repair in type A aortic dissection, JTCVS Techniques, Vol: 4, Pages: 40-47, ISSN: 2666-2507
ObjectiveThoracic endovascular aortic repair (TEVAR) is recommended for type B aortic dissection and recently has even been used in selected cases of proximal (Stanford type A) aortic dissections in scenarios of prohibitive surgical risk. However, mechanical interactions between the native aorta and stent-graft are poorly understood, as some cases ended in failure. The aim of this study is to explore and better understand biomechanical changes after TEVAR and predict the result via virtual stenting.MethodsA case of type A aortic dissection was considered inoperable and selected for TEVAR. The procedure failed due to stent-graft migration even with precise deployment. A novel patient-specific virtual stent-graft deployment model based on finite element method was employed to analyze TEVAR-induced changes under such conditions. Two landing positions were simulated to investigate the reason for stent-graft migration immediately after TEVAR and explore options for optimization.ResultsSimulation of the actual procedure revealed that the proximal bare metal stent pushed the lamella into the false lumen and led to further stent-graft migration during the launch phase. An alternative landing position has reduced the local deformation of the dissection lamella and avoided stent-graft migration. Higher maximum principal stress (>20 KPa) was found on the lamella with deployment at the actual position, while the alternative strategy would have reduced the stress to <5 KPa.ConclusionsVirtual stent-graft deployment simulation based on finite element model could be helpful to both predict outcomes of TEVAR and better plan future endovascular procedures.
Chong MY, Gu B, Chan BT, et al., 2020, Effect of intimal flap motion on flow in acute type B aortic dissection by using fluid-structure interaction., International Journal for Numerical Methods in Biomedical Engineering, Vol: 36, Pages: 1-22, ISSN: 1069-8299
A monolithic, fully coupled fluid-structure interaction (FSI) computational framework was developed to account for dissection flap motion in acute type B aortic dissection (TBAD). Analysis of results included wall deformation, pressure, flow, wall shear stress (WSS), von. Mises stress and comparison of hemodynamics between rigid wall and FSI models. Our FSI model mimicked realistic wall deformation that resulted in maximum compression of the distal true lumen (TL) by 21.4%. The substantial movement of intimal flap mostly affected flow conditions in the false lumen (FL). Flap motion facilitated more flow entering the FL at peak systole, with the TL to FL flow split changing from 88:12 in the rigid model to 83:17 in the FSI model. There was more disturbed flow in the FL during systole (5.8% FSI vs. 5.2% rigid) and diastole (13.5% FSI vs. 9.8% rigid), via a λ2 -criterion. The flap-induced disturbed flow near the tears in the FSI model caused an increase of local WSS by up to 70.0% during diastole. This resulted in a significant reduction in the size of low time-averaged WSS (TAWSS) regions in the FL (113.11 cm2 FSI vs. 177.44 cm2 rigid). Moreover, the FSI model predicted lower systolic pressure, higher diastolic pressure, and hence lower pulse pressure. Our results provided new insights into the possible impact of flap motion on flow in aortic dissections, which are particularly important when evaluating hemodynamics of acute TBAD. This article is protected by copyright. All rights reserved.
Salmasi M, Jarral OA, Pirola S, et al., 2020, In-vivo blood flow parameters can predict at-risk aortic aneurysms and dissection: a comprehensive biomechanics model, EUROPEAN HEART JOURNAL, Vol: 41, Pages: 2339-2339, ISSN: 0195-668X
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Xu X, Manchester E, 2020, The effect of turbulence on transitional flow in the FDA’s benchmark nozzle model using large-eddy simulation, International Journal for Numerical Methods in Biomedical Engineering, Vol: 36, Pages: 1-15, ISSN: 1069-8299
The Food and Drug Administration's (FDA) benchmark nozzle model has been studied extensively both experimentally and computationally. Although considerable efforts have been made on validations of a variety of numerical models against available experimental data, the transitional flow cases are still not fully resolved, especially with regards to detailed comparison of predicted turbulence quantities with experimental measurements. This study aims to fill this gap by conducting large‐eddy simulations (LES) of flow through the FDA's benchmark model, at a transitional Reynolds number of 2000. Numerical results are compared to previous interlaboratory experimental results, with an emphasis on turbulence characteristics. Our results show that the LES methodology can accurately capture laminar quantities throughout the model. In the pre‐jet breakdown region, predicted turbulence quantities are generally larger than high resolution experimental data acquired with laser Doppler velocimetry. In the jet breakdown regions, where maximum Reynolds stresses occur, Reynolds shear stresses show excellent agreement. Differences of up to 4% and 20% are observed near the jet core in the axial and radial normal Reynolds stresses, respectively. Comparisons between viscous and Reynolds shear stresses show that peak viscous shear stresses occur in the nozzle throat reaching a value of 18 Pa in the boundary layer, whilst peak Reynolds shear stresses occur in the jet breakdown region reaching a maximum value of 87 Pa. Our results highlight the importance in considering both laminar and turbulent contributions towards shear stresses and that neglecting the turbulence effect can significantly underestimate the total shear force exerted on the fluid.
Johari NH, Hamady M, Xu XY, 2020, A computational study of the effect of stent design on local hemodynamic factors at the carotid artery bifurcation, Artery Research, Vol: 26, Pages: 161-169, ISSN: 1872-9312
Background: Previous clinical studies have shown that the incidence of restenosis after carotid and coronary stenting varies with stent design and deployment configuration. This study aims to determine how stent design may affect in-stent hemodynamics in stented carotid arteries by means of Computational Fluid Dynamics (CFD).Methods: A robust computational method was developed to integrate detailed stent strut geometry in a patient-specific carotid artery reconstructed from medical images. Three stent designs, including two closed-cell stents and one open-cell stent, were reproduced and incorporated into the reconstructed post-stent carotid bifurcation. CFD simulations were performed under patient-specific flow conditions. Local hemodynamic parameters were evaluated and compared in terms of Wall Shear Stress (WSS), Oscillatory Shear Index (OSI) and Relative Residence Time (RRT).Results: All simulated stent designs induced some degree of flow disruption as manifested through flow separation and recirculation zones downstream of stent struts and quantified by WSS-related indices. Compared to the simulated open-cell stent, closed-cell stents created slightly larger areas of low WSS, elevated OSI and high RRT, due to a greater number of stent struts protruding into the lumen.Conclusion: Detailed stent design and patient-specific geometric features of the stented vessel have a strong influence on the evaluated hemodynamic parameters. Our limited computational results suggest that closed-cell stents may pose a higher risk for in-stent restenosis (ISR) than open-cell stent design. Further large-scale prospective studies are warranted to elucidate the role of stent design in the development of ISR after CAS.
Zadrazil I, Corzo C, Voulgaropoulos V, et al., 2020, A combined experimental and computational study of the flow characteristics in a Type B aortic dissection: effect of primary and secondary tear size, Chemical Engineering Research and Design, Vol: 160, Pages: 240-253, ISSN: 0263-8762
Aortic dissection is related to the separation of the tunica intima from the aortic wall, which can cause blood to flow through the newly formed lumen, thereby further damaging the torn vessel. This type of pathology is the most common catastrophic event that affects the aorta and is associated with complications such as malperfusion. In this work, an idealised, simplified geometric model of Type B aortic dissection is investigated experimentally using particle image velocimetry (PIV) and numerically using computational fluid dynamic (CFD) simulations. The flow characteristics through the true and false lumina are investigated parametrically over a range of tear sizes. Specifically, four different tear sizes and size ratios are considered, each representing a different dissection case or stage, and the experimental and numerical results of the flow-rate profiles through the two lumina in each case, along with the phase-averaged velocity vector maps at mid-acceleration, mid-deceleration, relaminarisation and peak systole, and their corresponding velocity profiles are compared. The experimental and numerical results are in good qualitative as well as quantitative agreement. The flow characteristics found here provide insight into the importance of the re-entry tear. We observe that an increase in the re-entry tear size increases considerably the flow rate in the false lumen, decreases significantly the wall shear stress (WSS) and decreases the pressure difference between the false and the true lumen. On the contrary, an increase in the entry tear, increases the flow rate through the false lumen, increases slightly the WSS and increases the pressure difference between the false and the true lumen. These are crucial findings that can help interpret medical diagnosis and accelerate prevention and treatment, especially in high-risk patients.
Armour C, Menichini C, Milinis K, et al., 2020, The location of re-entry tears affects false lumen thrombosis in aortic dissection following TEVAR, Journal of Endovascular Therapy, Vol: 27, Pages: 396-404, ISSN: 1074-6218
Purpose. Thoracic endovascular aortic repair (TEVAR) has been shown to be an effective treatment method for acute type B aortic dissection. However, it remains unclear which factors determine false lumen thrombosis (FLT) after TEVAR. In this study we assess the influence of the distance between the distal end of the stent graft and first re-entry tear (SG-FET)on the progression of FLT.Methods.Three post-operative patient-specific models were reconstructed from computed tomography scans. Two additional models were created byartificially changing the SG-FET distance in patient 1 and 2. In all five models, computational fluid dynamics simulations coupled with thrombus formation modelling were performed at physiological flow conditions.Predicted FLT was compared with follow-up scans.Results.Ourresults showed reduced false lumen flow and low time-averaged wall shear stress (TAWSS) inpatients withlarge SG-FET distances. Predicted thrombus formation and growth were consistent with follow-up scansfor all patients. Reducingthe SG-FET distanceby 30 mm in patient 1 increased flowandTAWSS in the upper abdominal false lumen, reducing the thrombus volume by 9.6%. Increasingthe SG-FET distance inpatient 2 resulted in fasterthoracic thrombosis and increased total thrombus volume.Conclusion.The location of re-entry tears can influencethe progression of FLT following TEVAR. The more distal the re-entry tear in the aorta the more likely FLTis. Hence, the distal landing zone of the stent graft should be chosen carefully to ensure a sufficient SG-FET distance.
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