Initial findings and potential applicability of computational simulation of the aorta in acute type B dissection.

OBJECTIVE: Type B aortic dissection can be acutely complicated by rapid expansion, rupture, and malperfusion syndromes. Short-term adverse outcomes are associated with failure of the false lumen to thrombose. The reasons behind false lumen patency are poorly understood, and the objective of this pilot study was to use computational fluid dynamics reconstructions of aortic dissection cases to analyze the effect of aortic and primary tear morphology on flow characteristics and clinical outcomes in patients with acute type B dissections. METHODS: Three-dimensional patient-specific aortic dissection geometry was reconstructed from computed tomography scans of four patients presenting with acute type B aortic dissection and a further patient with sequential follow-up scans. The cases were selected based on their clinical presentation. Two were complicated by acute malperfusion that required emergency intervention. Three patients were uncomplicated and were managed conservatively. The patient-specific aortic models were used in computational simulations to assess the effect of aortic tear morphology on various parameters including flow, velocity, shear stress, and turbulence. RESULTS: Pulsatile flow simulation results showed that flow rate into the false lumen was dependent on both the size and position of the primary tear. Linear regression analysis demonstrated a significant relationship between percentage flow entering the false lumen and the size of the primary entry tear and an inverse relationship between false lumen flow and the site of the entry tear. Subjects complicated by malperfusion had larger-dimension entry tears than the uncomplicated cases (93% and 82% compared with 32% and 55%, respectively). Blood flow, wall shear stress, and turbulence levels varied significantly between subjects depending on aortic geometry. Highest wall shear stress (>7 Pa) was located at the tear edge, and progression of false lumen thrombosis was associated with prolonged particle residence times. CONCLUSIONS: Results obtained from this preliminary work suggest that aortic morphology and primary entry tear size and position exert significant effects on flow and other hemodynamic parameters in the dissected aorta in this preliminary work. Blood flow into the false lumen increases with increasing tear size and proximal location. Morphologic analysis coupled with computational fluid dynamic modeling may be useful in predicting acute type B dissection behavior allowing for selection of proper treatment modalities, and further confirmatory studies are warranted.

A computational study on the influence of catheter-delivered intravascular probes on blood flow in a coronary artery model.

Catheter-delivered intravascular probes are widely used in clinical practice to measure coronary arterial velocity and pressure, but the artefactual effect of the probe on the variables being measured is not well characterised. A coronary artery was simulated with a 180 degrees curved tube 3mm in diameter and the effect of catheters of different diameters was modelled numerically under pulsatile flow conditions. The presence of a catheter increased pressure by 1.3-4.3 mmHg depending on its diameter, and reduced velocity-pressure phase-lag. For an ultrasound sample volume 5mm downstream from the probe tip, the underestimation in velocity measurement attributed to catheter blockage is approximately 15-21% for an average inlet velocity of 0.1m/s. The velocity measurement error is lower at higher mean flow velocity. Accuracy of clinical velocity measurements could be improved by moving the sample volume farther downstream from the probe tip, because the centrifugal pressure gradient intrinsic to the curvature promotes re-development of flow.

3D geometric reconstruction of thoracic aortic aneurysms.

BACKGROUND: The thoracic aortic aneurysm (TAA) is a pathology that involves an expansion of the aortic diameter in the thoracic aorta, leading to risk of rupture. Recent studies have suggested that internal wall stress, which is affected by TAA geometry and the presence or absence of thrombus, is a more reliable predictor of rupture than the maximum diameter, the current clinical criterion. Accurate reconstruction of TAA geometry is a crucial step in patient-specific stress calculations. METHODS: In this work, a novel methodology was developed, which combines data from several sets of magnetic resonance (MR) images with different levels of detail and different resolutions. Two sets of images were employed to create the final model, which has the highest level of detail for each component of the aneurysm (lumen, thrombus, and wall). A reference model was built by using a single set of images for comparison. This approach was applied to two patient-specific TAAs in the descending thoracic aorta. RESULTS: The results of finite element simulations showed differences in stress pattern between the coarse and fine models: higher stress values were found with the coarse model and the differences in predicted maximum wall stress were 30% for patient A and 11% for patient B. CONCLUSION: This paper presents a new approach to the reconstruction of an aneurysm model based on the use of several sets of MR images. This enables more accurate representation of not only the lumen but also the wall surface of a TAA taking account of intraluminal thrombus.

Assessment of Hemodynamic Conditions in the Aorta Following Root Replacement with Composite Valve-Conduit Graft.

This paper presents the analysis of detailed hemodynamics in the aortas of four patients following replacement with a composite bio-prosthetic valve-conduit. Magnetic resonance image-based computational models were set up for each patient with boundary conditions comprising subject-specific three-dimensional inflow velocity profiles at the aortic root and central pressure waveform at the model outlet. Two normal subjects were also included for comparison. The purpose of the study was to investigate the effects of the valve-conduit on flow in the proximal and distal aorta. The results suggested that following the composite valve-conduit implantation, the vortical flow structure and hemodynamic parameters in the aorta were altered, with slightly reduced helical flow index, elevated wall shear stress and higher non-uniformity in wall shear compared to normal aortas. Inter-individual analysis revealed different hemodynamic conditions among the patients depending on the conduit configuration in the ascending aorta, which is a key factor in determining post-operative aortic flow. Introducing a natural curvature in the conduit to create a smooth transition between the conduit and native aorta may help prevent the occurrence of retrograde and recirculating flow in the aortic arch, which is particularly important when a large portion or the entire ascending aorta needs to be replaced.

A viscoelastic fluid-structure interaction model for carotid arteries under pulsatile flow.

In this study, a fluid-structure interaction model (FSI) incorporating viscoelastic wall behaviour is developed and applied to an idealized model of the carotid artery under pulsatile flow. The shear and bulk moduli of the arterial wall are described by Prony series, where the parameters can be derived from in vivo measurements. The aim is to develop a fully coupled FSI model that can be applied to realistic arterial geometries with normal or pathological viscoelastic wall behaviour. Comparisons between the numerical and analytical solutions for wall displacements demonstrate that the coupled model is capable of predicting the viscoelastic behaviour of carotid arteries. Comparisons are also made between the solid only and FSI viscoelastic models, and the results suggest that the difference in radial displacement between the two models is negligible.

Geometric and flow features of type B aortic dissection: initial findings and comparison of medically treated and stented cases.

Uncomplicated acute type B aortic dissections are usually treated medically, but they can become acutely complicated by rapid expansion, rupture and malperfusion syndromes and in the longer term by chronic dilatation and aortic aneurysm formation. The objective of this study is to use computational fluid dynamics reconstructions of type B aortic dissections to compare geometric and haemodynamic factors between the cases selected for medical treatment and the cases selected for thoracic endovascular aortic repair (TEVAR), and to examine whether any of these factors are associated with the outcome of the medically treated group. This study includes eight type B dissection cases, with four in each group. Aortic flow analyses were carried out based on patient-specific anatomy at initial presentation before treatment. Comparisons between the two groups show that the false lumen to true lumen volume ratio is considerably higher in patients selected for TEVAR. Results from the four medically treated cases indicate that the size of the primary entry tear is the key determinant of the false lumen flow rate, which may influence the long-term outcome of medically treated patients. Potential relations between flow related parameters based on initial anatomy and subsequent anatomical changes in the medically treatment group were examined. Our initial findings based on the limited cases are that high relative residence time is a strong predictor of subsequent false lumen thrombosis, whereas pressure difference between the true and false lumen as well as the location of the largest pressure difference may be associated with the likelihood of subsequent aortic expansion.

Flow pattern analysis in a highly stenotic patient-specific carotid bifurcation model using a turbulence model.

The aim of this study is to investigate the blood flow pattern in carotid bifurcation with a high degree of luminal stenosis, combining in vivo magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). A newly developed two-equation transitional model was employed to evaluate wall shear stress (WSS) distribution and pressure drop across the stenosis, which are closely related to plaque vulnerability. A patient with an 80% left carotid stenosis was imaged using high resolution MRI, from which a patient-specific geometry was reconstructed and flow boundary conditions were acquired for CFD simulation. A transitional model was implemented to investigate the flow velocity and WSS distribution in the patient-specific model. The peak time-averaged WSS value of approximately 73 Pa was predicted by the transitional flow model, and the regions of high WSS occurred at the throat of the stenosis. High oscillatory shear index values up to 0.50 were present in a helical flow pattern from the outer wall of the internal carotid artery immediately after the throat. This study shows the potential suitability of a transitional turbulent flow model in capturing the flow phenomena in severely stenosed carotid arteries using patient-specific MRI data and provides the basis for further investigation of the links between haemodynamic variables and plaque vulnerability. It may be useful in the future for risk assessment of patients with carotid disease.

MR image-based geometric and hemodynamic investigation of the right coronary artery with dynamic vessel motion.

The aim of this study was to develop a fully subject-specific model of the right coronary artery (RCA), including dynamic vessel motion, for computational analysis to assess the effects of cardiac-induced motion on hemodynamics and resulting wall shear stress (WSS). Vascular geometries were acquired in the right coronary artery (RCA) of a healthy volunteer using a navigator-gated interleaved spiral sequence at 14 time points during the cardiac cycle. A high temporal resolution velocity waveform was also acquired in the proximal region. Cardiac-induced dynamic vessel motion was calculated by interpolating the geometries with an active contour model and a computational fluid dynamic (CFD) simulation with fully subject-specific information was carried out using this model. The results showed the expected variation of vessel radius and curvature throughout the cardiac cycle, and also revealed that dynamic motion of the right coronary artery consequent to cardiac motion had significant effects on instantaneous WSS and oscillatory shear index. Subject-specific MRI-based CFD is feasible and, if scan duration could be shortened, this method may have potential as a non-invasive tool to investigate the physiological and pathological role of hemodynamics in human coronary arteries.

Computational modeling of LDL and albumin transport in an in vivo CT image-based human right coronary artery.

Low wall shear stress (WSS) is implicated in endothelial dysfunction and atherogenesis. The accumulation of macromolecules is also considered as an important factor contributing to the development of atherosclerosis. In the present study, a fluid-wall single-layered model incorporated with shear-dependent transport parameters was used to investigate albumin and low-density lipoprotein (LDL) transport in an in vivo computed tomographic image-based human right coronary artery (RCA). In the fluid-wall model, the bulk blood flow was modeled by the Navier-Stokes equations, Darcy's law was employed to model the transmural flow in the arterial wall, mass balance of albumin and LDL was governed by the convection-diffusion mechanism with an additional reaction term in the wall, and the Kedem-Katchalsky equations were applied at the endothelium as the interface condition between the lumen and wall. Shear-dependent models for hydraulic conductivity and albumin permeability were derived from experimental data in literature to investigate the influence of WSS on macromolecular accumulation in the arterial wall. A previously developed so-called lumen-free time-averaged scheme was used to approximate macromolecular transport under pulsatile flow conditions. LDL and albumin accumulations in the subendothelial layer were found to be colocalized with low WSS. Two distinct mechanisms responsible for the localized accumulation were identified: one was insufficient efflux from the subendothelial layer to outer wall layers caused by a weaker transmural flow; the other was excessive influx to the subendothelial layer from the lumen caused by a higher permeability of the endothelium. The comparison between steady flow and pulsatile flow results showed that the dynamic behavior of the pulsatile flow could induce a wider and more diffuse macromolecular accumulation pattern through the nonlinear shear-dependent transport properties. Therefore, it is vital to consider blood pulsatility when modeling the shear-dependent macromolecular transport in large arteries. In the present study, LDL and albumin accumulations were observed in the low WSS regions of a human RCA using a fluid-wall mass transport model. It was also found that steady flow simulation could overestimate the magnitude and underestimate the area of accumulations. The association between low WSS and accumulation of macromolecules leading to atherosclerosis may be mediated through effects on transport properties and mass transport and is also influenced by flow pulsatility.

Stress phase angle depicts differences in coronary artery hemodynamics due to changes in flow and geometry after percutaneous coronary intervention.

The effects of changes in flow velocity waveform and arterial geometry before and after percutaneous coronary intervention (PCI) in the right coronary artery (RCA) were investigated using computational fluid dynamics. An RCA from a patient with a stenosis was reconstructed based on multislice computerized tomography images. A nonstenosed model, simulating the same RCA after PCI, was also constructed. The blood flows in the RCA models were simulated using pulsatile flow waveforms acquired with an intravascular ultrasound-Doppler probe in the RCA of a patient undergoing PCI. It was found that differences in the waveforms before and after PCI did not affect the time-averaged wall shear stress and oscillatory shear index, but the phase angle between pressure and wall shear stress on the endothelium, stress phase angle (SPA), differed markedly. The median SPA was -63.9 degrees (range, -204 degrees to -10.0 degrees ) for the pre-PCI state, whereas it was 10.4 degrees (range, -71.1 degrees to 25.4 degrees ) in the post-PCI state, i.e., more asynchronous in the pre-PCI state. SPA has been reported to influence the secretion of vasoactive molecules (e.g., nitric oxide, PGI(2), and endothelin-1), and asynchronous SPA ( approximately -180 degrees ) is proposed to be proatherogenic. Our results suggest that differences in the pulsatile flow waveform may have an important influence on atherogenesis, although associated with only minor changes in the time-averaged wall shear stress and oscillatory shear index. SPA may be a useful indicator in predicting sites prone to atherosclerosis.

Low wall shear stress predicts subsequent development of wall hypertrophy in lower limb bypass grafts.

BACKGROUND: Venous grafts commonly develop myointimal hyperplasia, which can lead to stenoses and, ultimately, with expression of adhesion molecules, lumenal occlusion. The aim of the present study was to investigate whether wall shear stress measured post-operatively would predict subsequent myointimal hypertrophy in lower limb venous bypass grafts. METHODS: Magnetic resonance imaging and ultrasound were performed in a cohort of patients following lower limb venous bypass graft surgery for peripheral arterial disease at baseline (1-2 weeks) and at follow-up (9-12 months). Wall shear stress was determined at baseline using computational fluid dynamics techniques and intima-media thickness along the length of the graft was measured by ultrasound at baseline and follow up. RESULTS: Complete follow-up was possible in eight patients, in whom low wall shear stress at baseline predicted high intima-media thickness. The relationship between wall shear stress (WSS) and intima-media thickness (IMT) was curvilinear with IMT increasing sharply at lower levels of WSS (IMT >1.0 mm at <0.3 Pa). CONCLUSIONS: Low wall shear stress is associated with subsequent increase in myointimal thickness in lower limb venous bypass grafts. This is believed to be the first prospective study in humans to demonstrate the relationship between low wall shear stress and myointimal thickening and indicates a likely causative role for low wall shear stress in the development of myointimal hyperplasia.

Effects of elastic compression stockings on wall shear stress in deep and superficial veins of the calf.

The purpose of this study was to estimate wall shear stress (WSS) in individual vessels of the venous circulation of the calf and quantify the effects of elastic compression based on change of vessel geometry and velocity waveform. The great saphenous vein and either a peroneal or posterior tibial vein have been imaged in four healthy subjects using magnetic resonance imaging, with and without the presence of a grade 1 medical stocking. Flow through image-based reconstructed geometries was numerically simulated for both a range of steady flow rates and ultrasound-derived transient velocity waveforms, scaled to give a standardized time averaged flow rate. For steady flow, the stocking produced an average percentage increase in mean WSS of approximately 100% in the great saphenous vein across a range of 0.125-1.25 ml/s. The percentage increase in the peroneal/posterior tibial veins varied from 490 to 650% across a range of 0.5-5 ml/s. In addition, application of the stocking eliminated periods of very low or zero flow from the transient waveforms. The average minimum value of WSS in all vessels without the stocking was <0.1 Pa. With the stocking, this was increased to 0.7 Pa in the great saphenous and 0.9 Pa in the peroneal/posterior tibial veins. The pathophysiological effects of these changes are discussed. In conclusion, the flight stocking was effective in raising venous WSS levels in prone subjects, and this effect was much more pronounced in the deep vessels. The stocking also tended to prevent cessation of flow during periods of increased downstream pressure produced by respiration.

Influence of pulsatile flow on LDL transport in the arterial wall.

The accumulation of low-density lipoprotein (LDL) is one of the important factors in atherogenesis. Two different time scales may influence LDL transport in vivo: (1) LDL transport is coupled to blood flow with a pulse cycle of around 1 s in humans; (2) LDL transport within the arterial wall is mediated by transmural flow in the order of 10(-8) m/s. Most existing models have assumed steady flow conditions and overlooked the interactions between physical phenomena with different time scales. The objective of this study was to investigate the influence of pulsatile flow on LDL transport and examine the validity of steady flow assumption. The effect of pulsatile flow on transmural transport was incorporated by using a lumen-free cyclic (LFC) and a lumen-free time-averaged (LFTA) procedures. It is found that the steady flow simulation predicted a focal distribution in the post-stenotic region, differing from the diffuse distribution pattern produced by the pulsatile flow simulation. The LFTA procedure, in which time-averaged shear-dependent transport properties calculated from instantaneous wall shear stress (WSS) were used, predicted a similar distribution pattern to the LFC simulations. We conclude that the steady flow assumption is inadequate and instantaneous hemodynamic conditions have important influence on LDL transmural transport in arterial geometries with disturbed and complicated flow patterns.

Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model.

The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers.

Role of MRI in investigating the effects of elastic compression stockings on the deformation of the superficial and deep veins in the lower leg.

PURPOSE: To evaluate the potential of MRI to investigate the mechanical effects of compression stockings on the veins of the lower limb. MATERIALS AND METHODS: The right calves of eight healthy volunteers were imaged in the prone position, with and without the presence of a compression stocking. Cross-sectional areas of all peroneal and posterior tibial veins, both saphenous veins, and any sufficiently large superficial veins were segmented in all subjects at mid-calf level in both cases. Variation in cross-sectional area along the axis of the great saphenous vein and a peroneal vein was also examined in three subjects. RESULTS: The mean cross-sectional area reduction was found to be greater in the deep veins (64%) than in the superficial veins (39%). Deep-vein cross-sections were generally elliptical, while superficial veins were approximately circular. Significant axial fluctuations were found in the cross-sectional areas. CONCLUSION: MRI offers a precise source of data on the mechanical effects of lower-limb compression. Ultrasound (US) may be more cost-effective, but the data acquired are less comprehensive. Future biomechanical studies of lower-limb compression should make use of MRI.

Fluid-wall modelling of mass transfer in an axisymmetric stenosis: effects of shear-dependent transport properties.

Mechanical forces, such as low wall shear stress (WSS), are implicated in endothelial dysfunction and atherogenesis. The accumulation of low density lipoprotein (LDL) and hypoxia are also considered as main contributing factors in the development of atherosclerosis. The objective of this study was to investigate the influences of WSS on arterial mass transport by modelling the flow of blood and solute transport in the lumen and arterial wall. The Navier-Stokes equations and Darcy's Law were used to describe the fluid dynamics of the blood in the lumen and wall respectively. Convection-diffusion-reaction equations were used to model LDL and oxygen transport. The coupling of fluid dynamics and solute dynamics at the endothelium was achieved by the Kedem-Katchalsky equations. A shear-dependent hydraulic conductivity relation extracted from experimental data in the literature was employed for the transport of LDL and a shear-dependent permeability was used for oxygen. The integrated fluid-wall model was implemented in Comsol Multiphysics 3.2 and applied to an axisymmetric stenosis. The results showed elevated LDL concentration and reduced oxygen concentration in the subendothelial layer of the arterial wall in areas where WSS is low, suggesting that low WSS might be responsible for lipid accumulation and hypoxia in the arterial wall.

Progress towards patient-specific computational flow modeling of the left heart via combination of magnetic resonance imaging with computational fluid dynamics.

A combined computational fluid dynamics (CFD) and magnetic resonance imaging (MRI) methodology has been developed to simulate blood flow in a subject-specific left heart. The research continues from earlier experience in modeling the human left ventricle using time-varying anatomical MR scans. Breathing artifacts are reduced by means of a MR navigator echo sequence with feedback to the subject, allowing a near constant breath-hold diaphragm position. An improved interactive segmentation technique for the long- and short-axis anatomical slices is used. The computational domain is extended to include the proximal left atrium and ascending aorta as well as the left ventricle, and the mitral and aortic valve orifices are approximately represented. The CFD results show remarkable correspondence with the MR velocity data acquired for comparison purposes, as well as with previously published in vivo experiments (velocity and pressure). Coherent vortex formation is observed below the mitral valve, with a larger anterior vortex dominating the late-diastolic phases. Some quantitative discrepancies exist between the CFD and MRI flow velocities, owing to the limitations of the MR dataset in the valve region, heart rate differences in the anatomical and velocity acquisitions, and to certain phenomena that were not simulated. The CFD results compare well with measured ranges in literature.