Validation of numerical flow simulations against in vitro phantom measurements in different type B aortic dissection scenarios

An aortic dissection (AD) is a serious condition defined by the splitting of the arterial wall, thus generating a secondary lumen [the false lumen (FL)]. Its management, treatment and follow-up are clinical challenges due to the progressive aortic dilatation and potentially severe complications during follow-up. It is well known that the direction and rate of dilatation of the artery wall depend on haemodynamic parameters such as the local velocity profiles, intra-luminal pressures and resultant wall stresses. These factors act on the FL and true lumen, triggering remodelling and clinical worsening. In this study, we aimed to validate a computational fluid dynamic (CFD) tool for the haemodynamic characterisation of chronic (type B) ADs. We validated the numerical results, for several dissection geometries, with experimental data obtained from a previous in vitro study performed on idealised dissected physical models. We found a good correlation between CFD simulations and experimental measurements as long as the tear size was large enough so that the effect of the wall compliance was negligible.     

Comparative analysis of realistic CT-scan and simplified human airway models in airflow simulation

Efforts to model the human upper respiratory system have undergone many phases. Geometrical proximity to the realistic shape has been the subject of many research projects. In this study, three different geometries of the trachea and main bronchus were modelled, which were reconstructed from computed tomography (CT) scan images. The geometrical variations were named realistic, simplified and oversimplified. Realistic refers to the lifelike image taken from digital imaging and communications in medicine format CT scan images, simplified refers to the reconstructed image based on natural images without realistic details pertaining to the rough surfaces, and oversimplified describes the straight wall geometry of the airway. The characteristics of steady state flows with different flow rates were investigated, simulating three varied physical activities and passing through each model. The results agree with previous studies where simplified models are sufficient for providing comparable results for airflow in human airways. This work further suggests that, under most exercise conditions, the idealised oversimplified model is not favourable for simulating either airflow regimes or airflow with particle depositions. However, in terms of immediate analysis for the prediction of abnormalities of various dimensions of human airways, the oversimplified techniques may be used.     

Numerical simulation of non-Newtonian blood flow dynamics in human thoracic aorta

Three non-Newtonian blood viscosity models plus the Newtonian one are analysed for a patient-specific thoracic aorta anatomical model under steady-state flow conditions via wall shear stress (WSS) distribution, non-Newtonian importance factors, blood viscosity and shear rate. All blood viscosity models yield a consistent WSS distribution pattern. The WSS magnitude, however, is influenced by the model used. WSS is found to be the lowest in the vicinity of the three arch branches and along the distal walls of the branches themselves. In this region, the local non-Newtonian importance factor and the blood viscosity are elevated, and the shear rate is low. The present study revealed that the Newtonian assumption is a good approximation at mid-and-high flow velocities, as the greater the blood flow, the higher the shear rate near the arterial wall. Furthermore, the capabilities of the applied non-Newtonian models appeared at low-flow velocities. It is concluded that, while the non-Newtonian power-law model approximates the blood viscosity and WSS calculations in a more satisfactory way than the other non-Newtonian models at low shear rates, a cautious approach is given in the use of this blood viscosity model. Finally, some preliminary transient results are presented.     

Numerical simulation of blood flow in the left ventricle and aortic sinus using magnetic resonance imaging and computational fluid dynamics

Understanding cardiac blood flow patterns has many applications in analysing haemodynamics and for the clinical assessment of heart function. In this study, numerical simulations of blood flow in a patient-specific anatomical model of the left ventricle (LV) and the aortic sinus are presented. The realistic 3D geometry of both LV and aortic sinus is extracted from the processing of magnetic resonance imaging (MRI). Furthermore, motion of inner walls of LV and aortic sinus is obtained from cine-MR image analysis and is used as a constraint to a numerical computational fluid dynamics (CFD) model based on the moving boundary approach. Arbitrary Lagrangian–Eulerian finite element method formulation is used for the numerical solution of the transient dynamic equations of the fluid domain. Simulation results include detailed flow characteristics such as velocity, pressure and wall shear stress for the whole domain. The aortic outflow is compared with data obtained by phase-contrast MRI. Good agreement was found between simulation results and these measurements.     

左侧大肠癌和右侧大肠癌蛋白质差异表达谱的建立及质谱分析

目的:初步探索左侧大肠癌和右侧大肠癌中蛋白质表达的差异,为左右侧大肠癌生物学特性上的差别提供功能基因组学上的依据。方法:以左右侧大肠癌组织为研究对象,提取组织总蛋白,依次进行二维凝胶电泳,凝胶图象分析,质谱及生物信息学分析。结果:成功建立了左侧大肠癌和右侧大肠癌的二维电泳图谱,进行质谱和生物信息学分析比较得到左侧大肠癌与右侧大肠癌的差异表达蛋白共有16个,其中左侧大肠癌中表达增加的蛋白有10个包括蛋白质二硫化异构酶A1,78 kDa葡萄糖调节蛋白,抑制素,热休克蛋白60,含硫氧还蛋白域的蛋白5,T-复合蛋白1ε亚单位,应急蛋白70,异柠檬酸脱氢酶,蛋白质二硫化异构酶A3,巨噬细胞加帽蛋白;左侧大肠癌表达降低的蛋白6个包括ATP合成酶β亚单位,延伸因子1-delta,热休克蛋白β1,载脂蛋白A-Ⅰ,转甲状腺素蛋白,热休克蛋白β6。结论:左侧大肠癌和右侧大肠癌中存在差异表达蛋白,这些差异表达蛋白可能是左右侧大肠癌生物学性质差异的分子遗传学基础。     

A family-based association study of congenital left-sided heart malformations and 5,10 methylenetetrahydrofolate reductase

BACKGROUND: Aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS) are obstructive malformations of the left ventricular outflow tract that account for a significant proportion of infant mortality. Two previous small case-control studies suggested methylenetetrahydrofolate reductase (MTHFR) polymorphisms may be associated with this group of malformations. METHODS: We used a family-based association design with inclusion criteria of nonsyndromic diagnosis of AVS, CoA, and HLHS, powered to detect an odds ratio for the heterozygote of <1.5. A total of 207 affected offspring-parent trios were genotyped by restriction fragment length polymorphisms at the two common polymorphic loci C677T and A1298C. RESULTS: Error rate estimation based on replicate samples was 0.76%. Mendelian inconsistency at either polymorphism was noted in 10 trios, for a calculated undetected error rate of 1.95%. A total of 197 trios were analyzed using the transmission disequilibrium test. Significant association was not found between both the C677T or A1298C polymorphisms and presence of a heart defect, whether analyzed as a group, or by sex, ethnicity, or specific diagnosis. A log-linear analysis did not find increased relative risk based on the maternal genotype. CONCLUSIONS: We were unable to replicate previous association studies and concluded that neither the affected nor the maternal MTHFR genotype, by itself, is a major risk factor for congenital left ventricular outflow tract malformations.     

Evaluation of dentinal fluid flow behaviours: a fluid-structure interaction simulation

This study uses the fluid-structure interaction (FSI) method to investigate the fluid flow in dental pulp. First, the FSI method is used for the biomechanical simulation of dental intrapulpal responses during force loading (50, 100 and 150 N) on a tooth. The results are validated by comparison with experimental outcomes. Second, the FSI method is used to investigate an intact tooth subjected to a mechanical stimulus during loading at various loading rates. Force loading (0–100 N) is applied gradually to an intact tooth surface with loading rates of 125, 62.5, 25 and 12.5 N/s, respectively, and the fluid flow changes in the pulp are evaluated. FSI analysis is found to be suitable for examining intrapulpal biomechanics. An external force applied to a tooth with a low loading rate leads to a low fluid flow velocity in the pulp chamber, thus avoiding tooth pain.     

A numerical analysis of the aortic blood flow pattern during pulsed cardiopulmonary bypass

In the modern era, stroke remains a main cause of morbidity after cardiac surgery despite continuing improvements in the cardiopulmonary bypass (CPB) techniques. The aim of the current work was to numerically investigate the blood flow in aorta and epiaortic vessels during standard and pulsed CPB, obtained with the intra-aortic balloon pump (IABP). A multi-scale model, realized coupling a 3D computational fluid dynamics study with a 0D model, was developed and validated with in vivo data. The presence of IABP improved the flow pattern directed towards the epiaortic vessels with a mean flow increase of 6.3% and reduced flow vorticity.     

The influence of artery wall curvature on the anatomical assessment of stenosis severity derived from fractional flow reserve: a computational fluid dynamics study

This study aims to investigate the influence of artery wall curvature on the anatomical assessment of stenosis severity and to identify a region of misinterpretation in the assessment of per cent area stenosis (AS) for functionally significant stenosis using fractional flow reserve (FFR) as standard. Five artery models of different per cent AS severity (70, 75, 80, 85 and 90%) were considered. For each per cent AS severity, the angle of curvature of the arterial wall varied from straight to an increasingly curved model (0°, 30°, 60°, 90° and 120°). Computational fluid dynamics was performed under transient physiologic hyperemic flow conditions to investigate the influence of artery wall curvature on the pressure drop and the FFR. The findings in this study may be useful in in vitro anatomical assessment of functionally significant stenosis. The FFR decreased with increasing stenosis severity for a given curvature of the artery wall. Moreover, a significant decrease in FFR was found between straight and curved models discussed for a given severity condition. These findings indicate that the curvature effect was included in the FFR assessment in contrast to minimum lumen area (MLA) or per cent AS assessment. The MLA or per cent AS assessment may lead to underestimation of stenosis severity. From this numerical study, an uncertainty region could be evaluated using the clinical FFR cutoff value of 0.8. This value was observed at 81.98 and 79.10% AS for arteries with curvature angles of 0° and 120° respectively. In conclusion, the curvature of the artery should not be neglected in in vitro anatomical assessment.     

Computer modelling of maximal displacement forces in endoluminal thoracic aortic stent graft

The objective of this study was to determine the orientation and magnitude of maximal displacement forces (DFs) in the thoracic aortic aneurysm endograft (TAA endograft) in three-dimensional (3D) space. Theoretical computer model representing the anatomically worst-case scenario with respect to DF magnitude was used to calculate the magnitude and orientation of maximal DF. A patient-specific anatomical computer model of typically seen, average size anatomy was used to analyse the progression of DF throughout the cardiac cycle. Maximal DFs were 35.01 and 37.32 N in standing and supine position, respectively, in 46-mm diameter TAA graft with 90° bend. A patient-specific model shows that a maximal DF magnitude is achieved at the peak systolic flow. In both models, the orientation of the DF vector was perpendicular to the greater curvature of the aorta, with upward (cranial) and sideways components. The effect of shearing force on the total DF that acts on the TAA endograft was found negligible due to the several orders of magnitude stronger contribution of pressure forces to the total DF relative to the wall shear stress contribution, resulting in aortic diameters and angulation being the main drivers of DF. It was discovered that the TAA endografts can be subjected to much stronger DF than previously suspected. The magnitude of maximal DF in thoracic aorta in the worst-case scenario could be as high as 35.01 N (standing) and 37.32 N (supine). This new information should be used in the process of designing new generations of TAA endografts with better migration resistance properties.     

Direct numerical simulation of transitional flow in a patient-specific intracranial aneurysm

In experiments turbulence has previously been shown to occur in intracranial aneurysms. The effects of turbulence induced oscillatory wall stresses could be of great importance in understanding aneurysm rupture. To investigate the effects of turbulence on blood flow in an intracranial aneurysm, we performed a high resolution computational fluid dynamics (CFD) simulation in a patient specific middle cerebral artery (MCA) aneurysm using a realistic, pulsatile inflow velocity. The flow showed transition to turbulence just after peak systole, before relaminarization occurred during diastole. The turbulent structures greatly affected both the frequency of change of wall shear stress (WSS) direction and WSS magnitude, which reached a maximum value of 41.5Pa. The recorded frequencies were predominantly in the range of 1-500Hz. The current study confirms, through properly resolved CFD simulations that turbulence can occur in intracranial aneurysms.     

Vascular wall flow-induced forces in a progressively enlarged aneurysm model

The current study is focused on the numerical investigation of the flow field induced by the unsteady flow in the vicinity of an abdominal aortic aneurysm model. The computational fluid dynamics code used is based on the finite volume method, and it has already been used in various bioflow studies. For modelling the rheological behaviour of blood, the Quemada non-Newtonian model is employed, which is suitable for simulating the two-phase character of blood namely a suspension of blood cells in plasma. For examining its non-Newtonian effects a comparison with a corresponding Newtonian flow is carried out. Furthermore, the investigation is focused on the distribution of the flow-induced forces on the interior wall of the aneurysm and in order to study the development of the distribution with the gradual enlargement of the aneurysm, three different degrees of aneurysm-growth have been assumed. Finally and for examining the effect of the distribution on the aneurysm growth, a comparison is made between the pressure and wall shear-stress distributions at the wall for each growth-degree.     

Numerical simulation of two-phase non-Newtonian blood flow with fluid-structure interaction in aortic dissection

The behavior of blood cells and vessel compliance significantly influence hemodynamic parameters, which are closely related to the development of aortic dissection. Here the two-phase non-Newtonian model and the fluid-structure interaction (FSI) method are coupled to simulate blood flow in a patient-specific dissected aorta. Moreover, three-element Windkessel model is applied to reproduce physiological pressure waves. Important hemodynamic indicators, such as the spatial distribution of red blood cells (RBCs) and vessel wall displacement, which greatly influence the hemodynamic characteristics are analyzed. Results show that the proximal false lumen near the entry tear appears to be a vortex zone with a relatively lower volume fraction of RBCs, a low time-averaged wall shear stress (TAWSS) and a high oscillatory shear index (OSI), providing a suitable physical environment for the formation of atherosclerosis. The highest TAWSS is located in the narrow area of the distal true lumen which might cause further dilation. TAWSS distributions in the FSI model and the rigid wall model show similar trend, while there is a significant difference for the OSI distributions. We suggest that an integrated model is essential to simulate blood flow in a more realistic physiological environment with the ultimate aim of guiding clinical treatment.     

Rotating cylindrical filters used in perfusion cultures: CFD simulations and experiments

The particle and fluid dynamics in a rotating cylindrical filtration (RCF) system used for animal cell retention in perfusion processes was studied. A validated CFD model was used and the results gave numerical evidence of phenomena that had been earlier claimed, but not proven for this kind of application under turbulent and high mesh permeability conditions, such as bidirectional radial exchange flow (EF) through the filter mesh and particle (cells) lateral migration. Taylor vortices were shown to cause EF 10‐100 times higher than perfusion flow, indicating that EF is the main drag source, at least in early stages of RCF operation. Particle lateral migration caused a cell concentration reduction (CCR) near the filter surface of approximately 10%, contributing significantly to cell separation in RCF systems and giving evidence that the mesh sieving effect is not the sole phenomenon underlying cell retention in RCF systems. Filter rotation rate was shown to significantly affect both EF and CCR. A higher separation efficiency (measured experimentally at 2,000‐L bioreactor scale) and an enhanced CCR (predicted by the numerical simulations) were found for the same rotation rate range, indicating that there is an optimal operational space with practical consequences on RCF performance. Experimental data of a large‐scale perfusion run employing the simulated RCF showed high cell viabilities for over 100 days, which is probably related to the fact that the computed shear stress level in the system was shown to be relatively low (below 20 Pa under all tested conditions). © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1093–1102, 2014     

Homogeneous non-equilibrium molecular dynamics simulations of viscous flow: techniques and applications

We provide a review of the literature for non-equilibrium molecular dynamics (NEMD) simulations of homogeneous fluids. Our review focuses on techniques for simulations of shear and elongational flows in viscous fluids and covers the formulation and application of NEMD algorithms for atomic and molecular fluids. We provide a set of expositions that can be effectively used as guidelines to formulate the relevant equations of motion, periodic boundary conditions and thermostats. We also provide a survey of applications in a convenient tabular form as an aid to researchers who wish to use NEMD to study transport phenomena.