Simulation Of Blood Flow Research Articles

A highly parallel fully implicit domain decomposition method for the simulation of the hemodynamics of a patient-specific artery at the full-body scale

The numerical simulation of blood flows in the human body with a certain level of clinical accuracy is important for the understanding of the human physiology. The success of the modeling relies on a robust numerical method with the corresponding software that can handle the complex geometry, the complex fluid flows and run efficiently on a supercomputer. In this work, we introduce a highly parallel domain decomposition method to solve the three-dimensional incompressible Navier-Stokes equations on a patient-specific artery at the full-body scale from neck to feet with 222 outlets and a minimum diameter around 1.0 mm. A locally refined, unstructured mesh is used to resolve the complex fluid flow. Moreover, a two-level method is introduced to determine the model parameters in the Windkessel outlet boundary condition to guarantee clinically correct flow distributions to 14 major regions. A fully implicit Newton-Krylov-Schwarz method is used to solve the nonlinear algebraic system at each time step and numerical experiments show that the proposed method is robust with respect to the complex geometry, the graph-based partition of the complex mesh, the ill-conditioned sparse systems with locally dense blocks, and different model parameters and is scalable with up to 15,360 processor cores. With the proposed method, one simulation of the blood flow in a full-body arterial network can be obtained in about 8 hours per cardiac cycle, which enables its potential use in a wide range of clinical scenarios.

High Dose Rate and Fractionation to Reduce Radiation-Induced Lymphopenia: In Vivo Derivation of Lymphocyte Radiosensitivity Using Patient-Specific Blood Flow Simulations

<h3>Purpose/Objective(s)</h3> Radiation induced lymphopenia (RIL) has recently gained attention due to its correlation with outcome/survival in a range of indications, particularly when combining radiotherapy (RT) with immunotherapy. The purpose of this study is to use a dynamic blood circulation model combined with observed lymphocyte depletion in patients to derive the in vivo lymphocyte radiosensitivity and study the effect of fast delivery techniques. <h3>Materials/Methods</h3> We evaluated weekly Absolute Lymphocyte Counts (ALC) during RT and follow-up (median 7 measurements per patient) in 17 patients with hepatocellular carcinoma (HCC) treated with RT alone in 15 fractions (fx) using conventional dose rates. We utilized HEDOS, a time-dependent, whole-body, blood flow computational framework, in combination with explicit liver blood flow modeling, to calculate the dose volume histogram for circulating lymphocytes. We utilized linear-quadratic cell survival and an exponential recovery model optimized for lymphocyte radiation sensitivity, α (and β using α/β=2), and the daily recovery source term. We investigated the impact of using a 5-fx treatment regimen (currently investigated in a randomized trial – NCT03186898) and increasing the dose rate to delivery times <<1s (FLASH). The primary endpoints of interest were relative ALC depletion measured at nadir and time to recovery of 80% of baseline ALC. <h3>Results</h3> The <i>in-vivo</i> derived patient-specific lymphocyte radiation sensitivity has a mean of 0.7 <i>Gy⁻¹</i> (range 0.28 – 1.23) after optimal fitting using conventional fractionation and dose rate. Simulating a 5-fx treatment regimen at the conventional dose rate reduces ALC depletion by 8% on average, with an interquartile range (IQR) from 3% to 16% and mean reduction in number of days until recovery by 26% (IQR 21 – 31%) both caused by the varying patient-specific lymphocyte radiosensitivity. Simulating the 15-fx regimen with FLASH dose rates leads to a 13% reduction (IQR 3 – 23%) in ALC depletion and a mean reduction in number of days until recovery by 9% (IQR 2 – 116%). Combining the shorter, 5-fx, treatment regimen with FLASH dose rates leads to a mean reduction in ALC depletion by 45% (IQR 41 – 56%) and mean reduction in time to ALC recovery by 67% (IQR 54 – 80%). <h3>Conclusion</h3> We developed a patient-specific computational framework to simulate lymphocyte depletion in patients receiving RT depending on fractionation and dose rate. We observed that increasing dose rate at the same fractionation reduced ALC depletion more significantly than reducing the number of fractions. High dose rates led to an increased sparing of lymphocytes when shortening the fractionation regimen, particularly for patients with radiosensitive lymphocytes at elevated risk.

Hemodynamic evaluation of endarterectomy and stenting treatments for carotid web.

A carotid web is a thin, shelf-like luminal protrusion in the internal carotid artery that might cause carotid stenosis and stroke by inducing disturbed flow patterns, thrombosis, and abnormal biomechanical stimulus to the endothelial cells. This study simulated and evaluated how the two main treatments (endarterectomy and stenting) influence hemodynamic environments in the carotid artery and distal carotid siphon arteries, aiming to provide more references for the selection of clinical treatment. The carotid web, endarterectomy, and stenting models were reconstructed based on CT images. The blood flow simulations were conducted, and critical parameters related to thrombosis formation and artery remodeling, including swirling strength, wall shear stress (WSS), vortex Q-criterion, and oscillating shear index (OSI), were analyzed. In the model of the carotid web, obvious recirculation formed distal to the web, accompanied by lower velocity, lower WSS, higher relative resident time (RRT), and higher Q value. While in both two treatment models, the velocity increased and the Q value and RRT decreased at the carotid bifurcation. In addition, both treatments provide more kinetic energy to the distal carotid siphon artery, especially the stenting model. The carotid web can significantly influence the flow environments in the carotid artery. Both endarterectomy and stenting treatments could significantly diminish the side effects of the web and are feasible choices for web patients in terms of hemodynamics. Besides, the treatments for the carotid web would also influence the flow patterns at the distal carotid siphon, especially for the stenting treatment. But more innovational designs are needed to make the minimally invasive stenting treatment more beneficial.

A computational study of aortic insufficiency in patients supported with continuous flow left ventricular assist devices: Is it time for a paradigm shift in management?

De novo aortic insufficiency (AI) following continuous flow left ventricular assist device (CF-LVAD) implantation is a common complication. Traditional early management utilizes speed augmentation to overcome the regurgitant flow in an attempt to augment net forward flow, but this strategy increases the aortic transvalvular gradient which predisposes the patient to progressive aortic valve pathology and may have deleterious effects on aortic shear stress and right ventricular (RV) function. We employed a closed-loop lumped-parameter mathematical model of the cardiovascular system including the four cardiac chambers with corresponding valves, pulmonary and systemic circulations, and the LVAD. The model is used to generate boundary conditions which are prescribed in blood flow simulations performed in a three-dimensional (3D) model of the ascending aorta, aortic arch, and thoracic descending aorta. Using the models, impact of various patient management strategies, including speed augmentation and pharmacological treatment on systemic and pulmonary (PA) vasculature, were investigated for four typical phenotypes of LVAD patients with varying degrees of RV to PA coupling and AI severity. The introduction of mild/moderate or severe AI to the coupled RV and pulmonary artery at a speed of 5,500 RPM led to a reduction in net flow from 5.4 L/min (no AI) to 4.5 L/min (mild/moderate) to 2.1 L/min (severe). RV coupling ratio (Ees/Ea) decreased from 1.01 (no AI) to 0.96 (mild/moderate) to 0.76 (severe). Increasing LVAD speed to 6,400 RPM in the severe AI and coupled scenario, led to a 42% increase in net flow and a 16% increase in regurgitant flow (RF) with a nominal decrease of 1.6% in RV myocardial oxygen consumption (MVO2). Blood pressure control with the coupled RV with severe AI at 5,500 RPM led to an 81% increase in net flow with a 15% reduction of RF and an 8% reduction in RV MVO2. With an uncoupled RV, the introduction of mild/moderate or severe AI at a speed of 5,500 RPM led to a reduction in net flow from 5.0 L/min (no AI) to 4.0 L/min (mild/moderate) to 1.8 L/min (severe). Increasing the speed to 6,400 RPM with severe AI and an uncoupled RV increased net flow by 45%, RF by 15% and reduced RV MVO2 by 1.1%. For the uncoupled RV with severe AI, blood pressure control alone led to a 22% increase in net flow, 4.2% reduction in RF, and 3.9% reduction in RV MVO2; pulmonary vasodilation alone led to a 18% increase in net flow, 7% reduction in RF, and 26% reduction in RV MVO2; whereas, combined BP control and pulmonary vasodilation led to a 113% increase in net flow, 20% reduction in RF and 31% reduction in RV MVO2. Compared to speed augmentation, blood pressure control consistently resulted in a reduction in WSS throughout the proximal regions of the arterial system. Speed augmentation to overcome AI in patients supported by CF-LVAD appears to augment flow but also increases RF and WSS in the aorta, and reduces RV MVO2. Aggressive blood pressure control and pulmonary vasodilation, particularly in those patients with an uncoupled RV can improve net flow with more advantageous effects on the RV and AI RF.

4D Biofabrication of T‐Shaped Vascular Bifurcation

Abstract4D Biofabrication – a pioneering biofabrication technique – involves the automated fabrication of 3D constructs that are dynamic and show shape‐transformation capability. Although current 4D biofabrication methods are highly promising for the fabrication of vascular elements such as tubes, the fabrication of tubular junctions is still highly challenging. Here, for the first time, a 4D biofabrication‐based concept for the fabrication of a T‐shaped vascular bifurcation using 3D printed shape‐changing layers based on a mathematical model is reported. The formation of tubular structures with various diameters is achieved by precisely controlling the parameters (e.g. crosslinking time). Consequently, the 3D printed films show self‐transformation into a T‐junction upon immersion in water with a diameter of a few millimeters. Perfusion of the tubular T‐junction with an aqueous medium simulating blood flow through vessels shows minimal leakages with a maximum flow velocity of 0.11 m s–1. Furthermore, human umbilical vein endothelial cells seeded on the inner surface of the plain T‐junction show outstanding growth properties and excellent cell viability. The achieved diameters are comparable to the native blood vessels, which is still a challenge in 3D biofabrication. This approach paves the way for the fabrication of fully automatic self‐actuated vascular bifurcations as vascular grafts.

Quantifying the Effect of Body Habitus on Cardiac Auscultation Via Computational Hemoacoustics.

The effect of body habitus on auscultation of heart murmurs is investigated via computational hemoacoustic modeling. The source of the heart murmur is first obtained from a hemodynamic simulation of blood flow through a stenosed aortic valve. This sound source is then placed at the aortic valve location in four distinct human thorax models, and the propagation of the murmur in each thorax model is simulated by solving the elastic wave equations in the time-domain. Placing the same sound source in different thorax models allows for the disambiguation of the effect of body habitus on cardiac auscultation. The surface acceleration resulting from the murmur on each subject's chest surface shows that subjects with higher body-mass index and thoracic cross-sectional area yield smaller acceleration values for the S1 sound. Moreover, the spectral analysis of the signal shows that slope from linear regression in the normal heart sound frequency range (10-150 Hz) is larger for children at the aortic, pulmonic, and mitral auscultation points compared to that for adults. The slope in the murmur frequency range (150-400 Hz) was larger for female subjects at the mitral point compared to that for male subjects. The trends from the results show the potential of the proposed computational method to provide quantitative insights regarding the effect of various anatomical factors on cardiac auscultation.

Divergence of the normalized wall shear stress as an effective computational template of low-density lipoprotein polarization at the arterial blood-vessel wall interface

Background and ObjectiveNear-wall transport of low-density lipoproteins (LDL) in arteries plays a relevant role in the initiation of atherosclerosis. Although it can be modelled in silico by coupling the Navier–Stokes equations with the 3D advection-diffusion (AD) equation, the associated computational cost is high. As wall shear stress (WSS) represents a first-order approximation of the near-wall velocity in arteries, we aimed at identifying computationally convenient WSS-based quantities to infer LDL near-wall transport based on the underlying near-wall hemodynamics in five models of three human arterial districts (aorta, carotid bifurcations, coronary arteries). The simulated LDL transport and its WSS-based surrogates were qualitatively compared with in vivo longitudinal measurements of wall thickness growth on the coronary artery models. MethodsNumerical simulations of blood flow coupled with AD equations for LDL transport and blood-wall transfer were performed. The co-localization of the simulated LDL concentration polarization patterns with luminal surface areas characterized by low cycle-average WSS, near-wall flow stagnation and WSS attracting patterns was quantitatively assessed by the similarity index (SI). In detail, the latter two represent features of the WSS topological skeleton, obtained respectively through the Lagrangian tracking of surface-born particles, and the Eulerian analysis of the divergence of the normalized cycle-average WSS vector field. ResultsConvergence of the solution of the AD problem required the simulation of 3 (coronary artery) to 10 (aorta) additional cardiac cycles with respect to the Navier-Stokes problem. Co-localization results underlined that WSS topological skeleton features indicating near-wall flow stagnation and WSS attracting patterns identified LDL concentration polarization profiles more effectively than low WSS, as indicated by higher SI values (SI range: 0.17–0.50 for low WSS; 0.24–0.57 for WSS topological skeleton features). Moreover, the correspondence between the simulated LDL uptake and WSS-based quantities profiles with the in vivo measured wall thickness growth in coronary arteries appears promising. ConclusionsThe recently introduced Eulerian approach for identifying WSS attracting patterns from the divergence of normalized WSS provides a computationally affordable template of the LDL polarization at the arterial blood-wall interface without simulating the AD problem. It thus candidates as an effective biomechanical tool for elucidating the mechanistic link amongst LDL transfer at the arterial blood-wall interface, WSS and atherogenesis.

КОНТРОЛЬ ПАРАМЕТРОВ ТЕМПЕРАТУРНОГО РАСПРЕДЕЛЕНИЯ В ПРЕДПЛЕЧЬЕ ЧЕЛОВЕКА ПРИ ПРОЦЕДУРЕ УВЧ-ГИПЕРТЕРМИИ МЕТОДАМИ ПАССИВНОЙ АКУСТИЧЕСКОЙ ТЕРМОМЕТРИИ И ИНФРАКРАСНОЙ ТЕРМОГРАФИИ

In this work we performed UHF heating with an electromagnetic field of frequency 40.68 MHz and power of 30 W on human forearms and phantoms made of plastisol with simulated blood flow at physiotherapeutic doses of 10, 15 and 20 minutes. Thermal acoustic radiation of heated objects measured with a multichannel acoustothermograph with a bandwidth of 1.6-2.5 MHz, an integration time of 10 C, and a threshold sensitivity of 0.2 K. Additionally, the surface temperature of the forearm measured by infrared thermometry and the internal temperature of the phantom by an electronic thermometer. We obtained data about temperature distribution patterns in the human forearm and in the plastisol phantom. Blood flow in the phantoms was simulated by copper, aluminum and polyvinyl chloride tubes, through which water from a thermostat was passed. Comparison of cooling rates of different types of phantoms showed that the thermal properties of the phantom with aluminum tubes were the closest to the soft tissues of the human forearm. The data of objective control do not agree with the subjective sensations of the subjects, but agree well with each other, which confirms the necessity and shows the possibility of objective assessment of temperature distribution parameters in the soft tissues of the human body during hyperthermia during UHF-physiotherapy.

Recent advances in the application of computational fluid dynamics in the development of rotary blood pumps

In recent years, ventricular assist devices (VADs, also known as blood pumps) have gradually entered clinical practice and provide effective treatment for heart failure patients. However, adverse events related to mechanical blood damage in patients receiving the VAD treatment, were often reported and have become a major concern during the development of VADs, limiting their clinical and economic benefits. Compared with bench and in-vivo testing, computational fluid dynamics (CFD) is flexible and inexpensive, offering the possibility to predict hemodynamics and mechanical blood damage in a purely numerical manner. Thus, CFD has become an important tool for the design, optimization and evaluation of blood pumps. The stringent requirements of blood pumps require high fidelity simulations. Thus, this article reviews the current state of the art in high-fidelity methodologies for simulating blood flow and blood damage for the development and evaluation of rotary blood pumps; design and optimization methods of rotatory blood pumps using CFD, as well as future challenges.

Development and performance of a HemeLB GPU code for human-scale blood flow simulation

In recent years, it has become increasingly common for high performance computers (HPC) to possess some level of heterogeneous architecture - typically in the form of GPU accelerators. In some machines these are isolated within a dedicated partition, whilst in others they are integral to all compute nodes - often with multiple GPUs per node - and provide the majority of a machine's compute performance. In light of this trend, it is becoming essential that codes deployed on HPC are updated to execute on accelerator hardware. In this paper we introduce a GPU implementation of the 3D blood flow simulation code HemeLB that has been developed using CUDA C++. We demonstrate how taking advantage of NVIDIA GPU hardware can achieve significant performance improvements compared to the equivalent CPU only code on which it has been built whilst retaining the excellent strong scaling characteristics that have been repeatedly demonstrated by the CPU version. With HPC positioned on the brink of the exascale era, we use HemeLB as a motivation to provide a discussion on some of the challenges that many users will face when deploying their own applications on upcoming exascale machines. Program summaryProgram Title: HemeLB (HemePure_GPU)CPC Library link to program files:https://doi.org/10.17632/jhdv4drxbx.1Developer's repository link:https://github.com/UCL-CCS/HemePure-GPULicensing provisions: LGPLv3Programming language: CUDA C++Nature of problem: The geometric characteristics of arteries and veins throughout the human body can vary considerably between individuals. This is particularly true for patients with cardiovascular disease. Accurately resolving the dynamics of blood flow within such domains requires a three-dimensional technique that can replicate such variations at high fidelity. The study of full human-scale domains for physiologically relevant timeframes further demands a tool that can be executed efficiently on the advancing technological frameworks available on modern high performance computers.Solution method: HemeLB uses the lattice Boltzmann method [1,2,3,4] to simulate blood flow in complex, three-dimensional sparse vasculatures. A single relaxation time approximation is used [5]. Solid boundaries are modelled using simple bounce-back boundary conditions [6]. Blood flow is driven by applying either velocity or pressure boundary conditions [7]. The localised solution kernels of the algorithm allow for efficient parallelisation of the method to very high core counts. This version of HemeLB outlines the conversion of the code to allow execution on NVIDIA GPUs, currently the most widely used architecture in ultra high performance computers, whilst retaining its capacity for strong scaling to very large core counts.

Experience of Patient-Specific CFD Simulation of Blood Flow in Proximal Anastomosis for Femoral-Popliteal Bypass

Femoral artery bypass surgery needs postoperative monitoring due to the high complication risks after bypass. Numerical simulation is an effective tool to help solve this task. This work presents the experience of patient-specific CFD simulation of blood flow in proximal anastomosis for femoral-popliteal bypass, including patient follow-up after bypass surgery. Six cases of proximal anastomosis of femoral-popliteal bypass 3–30 months after surgery were studied. A repeated study was performed for four patients to monitor geometric and hemodynamic changes. The blood flow structure variety in proximal anastomoses and the blood flow dynamics during the cardiac cycle are described in detail using CFD simulation. Special attention is paid to time-average wall shear stresses (TAWSS) and oscillatory shear index (OSI) distributions. Low and oscillatory wall shear stresses were registered in the graft downstream from the suture, especially in case of low inlet flow. It was shown that the postoperative geometry changes led to significant hemodynamic changes; thereby, neointima has grown in areas with initially low and oscillatory wall shear stresses.

Construction of hybrid 1D‐0D networks for efficient and accurate blood flow simulations

AbstractThe one‐dimensional (1D) modeling of blood flow in complex networks of vessels and cardiovascular models can result in computationally expensive simulations. The complexity of such networks has significantly increased in the last years, in terms of both enhanced anatomical detail and modeling of physiological mechanisms and mechanical characteristics. To address such issue, the main goal of this work is to present a novel methodology to construct hybrid networks of coupled 1D and 0D vessels and to perform computationally efficient and accurate blood flow simulations in such networks. Departing from both the 1D and lumped‐parameter (0D) nonlinear models for blood flow, we propose high‐order numerical coupling strategies to solve the 1D, 0D, and hybrid coupling of vessels at junctions. To effectively construct hybrid networks, we explore different a‐priori model selection criteria focusing in obtaining the best possible trade‐off between computational cost of the simulations and accuracy of the computed solutions for the hybrid network with respect to the 1D network. The achievement of the expected order of accuracy is verified in several test cases. The novel methodology is applied to two different arterial networks, the 37‐artery network and the reduced ADAN56 model, where, in order to identify the best performinga‐priorimodel selection criteria, the quantitative assessment of CPU times and errors and the qualitative comparison between results are carried out and discussed.

Impact of atrial fibrillation on left atrium haemodynamics: A computational fluid dynamics study

We analyse the haemodynamics of the left atrium, highlighting differences between healthy individuals and patients affected by atrial fibrillation. The computational study is based on patient-specific geometries of the left atria to simulate blood flow dynamics. We design a novel procedure to compute the boundary data for the 3D haemodynamic simulations, which are particularly useful in absence of data from clinical measurements. With this aim, we introduce a parametric definition of atrial displacement, and we use a closed-loop lumped parameter model of the whole cardiovascular circulation conveniently tuned on the basis of the patient’s characteristics. We evaluate several fluid dynamics indicators for atrial haemodynamics, validating our numerical results in terms of clinical measurements; we investigate the impact of geometric and clinical characteristics on the risk of thrombosis. To highlight the correlation of thrombus formation with atrial fibrillation, according to medical evidence, we propose a novel indicator: age stasis. It arises from the combination of Eulerian and Lagrangian quantities. This indicator identifies regions where slow flow cannot properly rinse the chamber, accumulating stale blood particles, and creating optimal conditions for clots formation.

Quantifying Shear-induced Margination and Adhesion of Platelets in Microvascular Blood Flow

Platelet margination and adhesion are two critical and closely related steps in thrombus formation. Using dissipative particle dynamics (DPD) method that seamlessly models blood cells, blood plasma, and vessel walls with functionalized surfaces, we quantify the shear-induced margination and adhesion of platelets in microvascular blood flow. The results show that the occurrence of shear-induced RBC-platelet collisions has a remarkable influence on the degree of platelet margination. We characterize the lateral motion of individual platelets by a mean square displacement analysis of platelet trajectories, and find that the wall-induced lift force and the shear-induced displacement in wall-bounded flow cause the variation in near-wall platelet distribution. We then investigate the platelet adhesive dynamics under different flow conditions, by conducting DPD simulations of blood flow in a microtube with fibrinogen-coated wall surfaces. We find that the platelet adhesion is enhanced with the increase of fibrinogen concentration level but decreased with the increase of shear rate. These results are consistent with available experimental results. In addition, we demonstrate that the adherent platelets have a negative impact on the margination dynamics of the circulating platelets, which is mainly due to the climbing effect induced by the adherent ones. Taken together, these findings provide useful insights into the platelet margination and adhesion dynamics, which may facilitate the understanding of the predominant processes governing the initial stage of thrombus formation.

Effect of Reynolds number and blood viscosity models on the left coronary artery with multiple stenoses

This study aims to identify the significance of different blood viscosity models along with different Reynolds numbers in the simulation of blood flow in a multi-stenosed Left Coronary Artery (LCA) model. Computational fluid dynamics techniques were implemented to derive the hemodynamic outcomes of the diseased three-dimensional Left Coronary Artery (LCA) models comprising of multiple stenoses. The three-dimensional LCA model was reconstructed using the angiographic images of a healthy person, and three viscosity models, i.e., Carreau, Quemada, and Modified Cross, were considered for carrying out blood flow simulation through it. In this work, the behavior of blood velocity was analyzed by increasing the level of blockage in each of the considered blood viscosity model. It is noticed that the increase in velocity is in proportion with the rise in Reynolds number. This study shows that the Quemada model records the maximum velocity magnitude with the other two rheological models for higher Reynolds numbers. In this work, the area-averaged wall shear stress (AAWSS) along the left anterior descending segment between the areas of double stenoses for different Reynolds numbers was also analyzed. Two peaks of AAWSS were seen for all the Reynolds numbers indicating the two sections of constrictions. The obtained highest peak reflects the primary blockage. Also, an emphasis is laid to prefer the Carreau model over the Quemada and Modified Cross model. This work is purely computational based that might be helpful in providing an insightful understanding of blood flow conduct at the diseased stage in the cardiovascular system.

Spatiotemporal multi-scale modeling of radiopharmaceutical distributions in vascularized solid tumors

We present comprehensive mathematical modeling of radiopharmaceutical spatiotemporal distributions within vascularized solid tumors. The novelty of the presented model is at mathematical level. From the mathematical viewpoint, we provide a general modeling framework for the process of radiopharmaceutical distribution in the tumor microenvironment to enable an analysis of the effect of various tumor-related parameters on the distribution of different radiopharmaceuticals. We argue that partial differential equations (PDEs), beyond conventional methods, including ODE-based kinetic compartment modeling, can be used to evaluate radiopharmaceutical distribution in both time and space. In addition, we consider the spatially-variable dynamic structure of tumor microvascular networks to simulate blood flow distribution. To examine the robustness of the model, the effects of microvessel density (MVD) and tumor size, as two important factors in tumor prognosis, on the radiopharmaceutical distribution within the tumor are investigated over time (in the present work, we focus on the radiopharmaceutical [18F]FDG, yet the framework is broadly applicable to radiopharmaceuticals). Results demonstrate that the maximum total uptake of [18F]FDG at all time frames occurs in the tumor area due to the high capillary permeability and lack of a functional lymphatic system. As the MVD of networks increases, the mean total uptake in the tumor is also enhanced, where the rate of diffusion from vessel to tissue has the highest contribution and the rate of convection transport has the lowest contribution. The results of this study can be used to better investigate various phenomena and bridge a gap among cancer biology, mathematical oncology, medical physics, and radiology.

Development and evaluation of a bovine lung-on-chip (bLOC) to study bovine respiratory diseases

PurposeCurrent air-liquid interface (ALI) models of bovine proximal airways have their limitations. They do not simulate blood flow necessary to mimic systemic drug administration, and repeated sampling requires multiple, independent cultures. A bovine lung-on-chip (bLOC) would overcome these limitations, providing a convenient and cost-effective model for pharmacokinetic or pathogenicity studies.MethodsBovine pulmonary arterial endothelial cells seeded into the endothelial channel of an Emulate Lung-Chip were interfaced with bovine bronchial epithelial cells in the epithelial channel. Cells were cultured at ALI for up to 21 days. Differentiation was assessed by mucin quantification, phase-contrast light microscopy and immunofluorescence of cell-specific markers in fixed cultures. Barrier integrity was determined by FITC-labelled dextran 3–5 kDa permeability. To evaluate the model, endothelial-epithelial transport of the antibiotic drug, danofloxacin, was followed using liquid chromatography-mass spectrometry, with the aim of replicating data previously determined in vivo.ResultsbLOC cultures secreted quantifiable mucins, whilst cilia formation was evident in the epithelial channel. Barrier integrity of the model was demonstrated by resistance to FITC-Dextran 3–5 kDa permeation. Bronchial epithelial and endothelial cell-specific markers were observed. Close to plasma, representative PK data for danofloxacin was observed in the endothelial channel; however, danofloxacin in the epithelial channel was mostly below the limit of quantification.ConclusionA co-culture model of the bovine proximal airway was successfully generated, with potential to replace in vivo experimentation. With further optimisation and characterisation, the bLOC may be suitable to perform drug pharmacokinetic studies for bovine respiratory disease (BRD), and other applications.

Semi-implicit fluid–structure interaction in biomedical applications

Fluid–structure interaction (FSI) incorporates effects of fluid flows on deformable solids and vice versa. Complex biomedical problems in clinical applications continue to challenge numerical algorithms, as incorporating the underlying mathematical methods can impair the solvers’ performance drastically. In this regard, we extend a semi-implicit, pressure Poisson-based FSI scheme for non-Newtonian fluids to incorporate several models crucial for biomechanical applications. We consider Windkessel outlets to account for neglected downstream flow regions, realistic material fibre orientation and stressed reference geometries reconstructed from medical image data. Additionally, we incorporate vital numerical aspects, namely, stabilisations to counteract dominant convective effects and instabilities triggered by re-entrant flow, while a major contribution of this work is combining interface quasi-Newton methods with Robin coupling conditions to accelerate the partitioned (semi-)implicit coupling scheme. The numerical examples presented herein aim to finally bridge the gap to real-world applications, considering state-of-the-art modelling aspects and physiological parameters. FSI simulations of blood flow in an iliac bifurcation derived from medical images and vocal folds deforming in the process of human phonation demonstrate the versatility of the framework.

Influence of right coronary artery motion, flow pulsatility and non-Newtonian rheology on wall shear stress metrics.

The patchy distribution of atherosclerosis within the arterial system is consistent with a controlling influence of hemodynamic wall shear stress (WSS). Patterns of low, oscillatory and transverse WSS have been invoked to explain the distribution of disease in the aorta. Disease of coronary arteries has greater clinical importance but blood flow in these vessels may be complicated by their movement during the cardiac cycle. Previous studies have shown that time average WSS is little affected by the dynamic geometry, and that oscillatory shear is influenced more. Here we additionally investigate effects on transverse WSS. We also investigate the influence of non-Newtonian blood rheology as it can influence vortical structure, on which transverse WSS depends; Carreau-Yasuda models were used. WSS metrics were derived from numerical simulations of blood flow in a model of a moving right coronary artery which, together with a subject-specific inflow waveform, was obtained by MR imaging of a healthy human subject in a previous study. The results confirmed that time average WSS was little affected by dynamic motion and that oscillatory WSS was more affected. They additionally showed that transverse WSS and its non-dimensional analogue, the Cross Flow Index, were affected still further. This appeared to reflect time-varying vortical structures caused by the changes in curvature. The influence of non-Newtonian rheology was significant with some physiologically realistic parameter values, and hence may be important in certain subjects. Dynamic geometry and non-Newtonian rheology should be incorporated into models designed to produce maps of transverse WSS in coronary arteries.

Validation of lattice Boltzmann based software for blood flow simulations in complex patient-specific arteries against traditional CFD methods

Detailed and accurate evaluation of blood flow through stenotic arteries is important and can provide better clinical care for patients. Lattice Boltzmann method (LBM) represents an alternative approach to study blood flow and the main goal of this study is to validate its accuracy against traditional CFD methods. The validation was performed for blood flow through complex geometries of coronary arteries, by comparing the results with traditional CFD methods. The good agreement of results demonstrates that LBM can be considered as an efficient alternative that can produce fast results of the same quality as traditional CFD methods.