Aortic valve neocuspidization and bioprosthetic valves: Evaluating turbulence haemodynamics.

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 eccentricity and skew in order to mitigate turbulence generation.

In silico study of combination thrombolytic therapy with alteplase and mutant pro-urokinase for fibrinolysis in ischemic stroke.

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 ischemic stroke treatment.

A numerical study of the effect of thrombus breakdown on predicted thrombus formation and growth.

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.

Venous Thromboembolism: Review of Clinical Challenges, Biology, Assessment, Treatment, and Modeling.

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.

Towards biomechanics-based pre-procedural planning for thoracic endovascular aortic repair of aortic dissection.

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 simulation results are promising and demonstrate the feasibility of using the virtual SG deployment model to assist clinicians in pre-procedural planning.

Irregular anatomical features can alter hemodynamics in Takayasu arteritis.

Objective: Takayasu 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. Methods: Eleven 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. Results: Compared 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). Conclusions: CFD 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 warranted. Clinical Relevance: Based on patient-specific computational fluid dynamics simulations, the present retrospective study revealed significant difference in aortic hemodynamics between the patients with and without Takayasu arteritis (TA). To the best of our knowledge, this study is the first to evaluate hemodynamic conditions within TA, demonstrating the potential of computational flow modeling in capturing abnormal hemodynamic forces, such as high wall shear stress, resulted from irregular morphological changes. In the future, assessing the hemodynamic parameters within patients with TA during the prestenotic period, together with longitudinal computational fluid dynamics studies may allow better monitoring and management of TA.

A study of the proteomic expression in patients with complicated parapneumonic pleural effusion.

Introduction: The present study aimed to investigate the differences in the proteomic expression between uncomplicated parapneumonic pleural effusion (UPPE) and complicated parapneumonic pleural effusion (CPPE). Material and methods: There were 10 patients with UPPE and 10 patients with CPPE. These patients were combined due to the complication of pleural effusion and further divided into group A and group B. An LC-MS analysis was conducted with the extraction of high-abundance proteins, and proteins with 1.5-fold or higher difference multiples were identified as differential proteins. Then, gene ontology (GO) and KEGG analyses were conducted on the differential proteins between the groups. Results: Compared with the UPPE group, there were 38 upregulated proteins and 29 downregulated proteins in the CPPE group. The GO analysis revealed that the CPPE group had enhanced expressions in monosaccharide biosynthesis, glucose catabolism, fructose-6-phosphate glycolysis, glucose-6-phosphate glycolysis, and NADH regeneration as well as reduced expressions in fibrinogen complexes, protein polymerization, and coagulation. Moreover, the KEGG analysis showed that the CPPE group had enhanced expressions in amino acid synthesis, the HIF-1 signalling pathway, and glycolysis/glycoisogenesis and decreased expressions in platelet activation and complement activation. Conclusions: In pleural effusion in patients with CPPE, there are enhanced expressions of proteins concerning glucose and amino acid metabolism, NADH regeneration, and HIF-1 signalling pathways together with decreased expressions of proteins concerning protein polymerization, blood coagulation, platelet activation, and complement activation.

Haemodynamic changes in visceral hybrid repairs of type III and type V thoracoabdominal aortic aneurysms.

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 enhanced post-operative management, even in patients with complicated geometrical bypass configurations.

Hemodynamic parameters impact the stability of distal stent graft-induced new entry.

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.

Nonsurgical Repair of the Ascending Aorta: Why Less Is More.

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 aortic root after the placement of stent graft in the ascending aorta, whereas the free motion of aortic root was preserved with an occluder. The causality of erosion may however not be fully understood, as besides the stiffness and radial force of the stent graft, other factors such as the induced inflammatory reactions of aortic tissue and local adhesions within the chest may also play a role. With stent grafts failing to portend long-term success, they may still have a role as a temporizing solution for elective surgical conversion. Larger datasets from registries are needed to further explore this evolving field of interventions to the ascending aorta.

Aortic haemodynamics and wall stress analysis following arch aneurysm repair using a single-branched endograft.

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.

A computational study of the effects of size, location, and number of tears on haemodynamics in surgically repaired type A aortic dissection.

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.

Experimental 61-partite entanglement on a three-dimensional photonic chip.

Multipartite entanglements are essential resources for proceeding tasks in quantum information science and technology. However, generating and verifying them present significant challenges, such as the stringent requirements for manipulations and the need for a huge number of building-blocks as the systems scale up. Here, we propose and experimentally demonstrate the heralded multipartite entanglements on a three-dimensional photonic chip. Integrated photonics provide a physically scalable way to achieve an extensive and adjustable architecture. Through sophisticated Hamiltonian engineering, we are able to control the coherent evolution of shared single photon in the multiple spatial modes, dynamically tuning the induced high-order W-states of different orders in a single photonic chip. Using an effective witness, we successfully observe and verify 61-partite quantum entanglements in a 121-site photonic lattice. Our results, together with the single-site-addressable platform, offer new insights into the accessible size of quantum entanglements and may facilitate the developments of large-scale quantum information processing applications.

In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke.

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.

Data-driven generation of 4D velocity profiles in the aneurysmal ascending aorta.

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 studies of blood flow. The proposed software system also allows to map any of the generated velocity profiles to the inlet plane of any virtual subject given its coordinate set.

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.

BACKGROUND: The geometrical characterization of ascending thoracic aortic aneurysms in clinical practice is limited to diameter measurements. Despite growing interest in hemodynamic assessment, its relationship with ascending thoracic aortic aneurysm pathogenesis is poorly understood. This study examines the relationship between geometry of the ventriculo-aortic junction and blood flow patterns in ascending thoracic aortic aneurysm disease. METHODS: Thirty-three patients with ascending thoracic aortic aneurysms (exclusions: bicuspid aortic valves, connective tissue disease) underwent 4-dimensional flow magnetic resonance imaging. After image segmentation, geometrical parameters were measured, including aortic curvature, tortuosity, length, and diameter. A unique angular measurement made by the trajectory of the left ventricular outflow tract axis and the proximal aorta was also conducted. Velocity profiles were quantitatively and qualitatively analyzed. In addition, 11 patients (33%) underwent wall shear stress mapping of the ascending thoracic aortic aneurysm region using computational fluid dynamics simulation. RESULTS: Greater left ventricular outflow tract aortic angles were associated with larger aortic diameters at the levels of the sinus (coefficient = 0.387, P = .014) and ascending aorta (coefficient = 0.284, P = .031). Patients with left ventricular outflow tract aortic angles greater than 60° had marked asymmetric flow acceleration on the outer curvature in the proximal aorta, ascertained from 4-dimensional flow analysis. For patients undergoing computational fluid dynamics assessment, regression analysis found that higher left ventricular outflow tract aortic angles were associated with significantly higher wall shear stress values in the outer curve of the aorta (coefficient 0.07, 95% confidence interval 0.04-0.11, P = .002): Angles greater than 50° yielded time-averaged wall shear stress values greater than 2.5 Pa, exhibiting a linear relationship. CONCLUSIONS: Our findings strengthen the hypothesis of flow-mediated ascending thoracic aortic aneurysm disease progression and that left ventricular outflow tract aortic angle may be a predictor of disease severity.

Multiscale Modelling of Nanoparticle Distribution in a Realistic Tumour Geometry Following Local Injection.

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.

Shear-driven modelling of thrombus formation in type B aortic dissection.

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. Such improvement means the new model is a significant step towards clinical applicability. Conclusion: The thrombosis model developed in this study is accurate and efficient at predicting FL thrombosis based on patient-specific data, and may assist clinicians in choosing individualized treatments in the future.

Evaluating the Haemodynamic Performance of Endografts for Complex Aortic Arch Repair.

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.

Modelling of Nanoparticle Distribution in a Spherical Tumour during and Following Local Injection.

Radio-sensitizing nanoparticles are a potential method to increase the damage caused to cancerous 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. In this study, a three-part mathematical model is shown to predict the distribution of nanoparticles after 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 onto cells are compared for different values of particle surface charges during and after injection. Our results 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 tumour volume compared to 8.8% for uncharged particles. This has implications for the future development of radiosensitizers and any associated trials.