Multiphasic modelling of human brain tissue for intracranial drug-infusion studies

A direct intracranial infusion of a therapeutic solution into the extra-vascular space of human brain tissue is a promising medical application for the effective treatment of malignant brain tumours [1]. The advantage of this method, compared to an intra-vascular medication, is the targeted delivery with the circumvention of the blood-brain barrier (BBB), which prohibits the passing of therapeutic macro-molecules across the vascular walls into the brain parenchyma. The prediction of the resulting therapeutical distribution by a numerical simulation is challenging, since the spreading is affected by the complex nature of living brain tissue. For this purpose, a macroscopic continuum-mechanical model is established within the Theory of Porous Media (TPM), proceeding from a homogenisation of the underlying micro-structure [5]. The ternary four-component model consists of an elastically deformable solid skeleton (composed of tissue cells and vascular walls), which is perfused by two mobile but separated liquid phases, the blood and the overall interstitial fluid (treated as a real two-component mixture of the liquid solvent and the dissolved therapeutic solute). The strongly coupled solid-liquid-transport problem is simultaneously approximated in all primary unknowns using mixed finite elements (uppc-formulation) and consequently solved in a monolithic manner with an implicit time-integration scheme. This numerical investigation allows the computational study of several circumstances influencing the irregular distribution of infused drugs, as observed in clinical studies. Therefore, the microstructural perfusion characteristics in the extra-cellular space of the white-matter tracts are considered by a spatial diversification of the anisotropic permeability tensors, provided by Diffusion Tensor Imaging (DTI). Furthermore, Magnetic Resonance Angiography (MRA) enables the in vivo location of blood vessels within the brain tissue. Finally, the selection of appropriate material parameters has a crucial influence on the drug distribution profile and further occurring effects beyond. (© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

A Porous Media Model to Describe the Behaviour of Brain Tissue

The human brain is a very sensitive organ. Even small changes in the cranium cavity can cause life–threatening effects. In case of medical intervention, biomechanics can assist the therapy decisions by simulating the physical behaviour of brain tissue, e.g., the coupled interaction of the fluid motion and the deformation of the brain tissue. In the context of the Theory of Porous Media (TPM), a convenient model of the brain is introduced, which is able to simulate essential mechanical effects in the porous structure of the brain material. The fluid–saturated brain can be treated as an immiscible binary mixture of constituents. In this macroscopic biphasic model, the mixture consists of a solid phase (brain tissue) and a fluid phase (interstitial fluid or blood plasma). Both constituents are assumed to be materially incompressible. The resulting set of coupled partial differential equations is then spatially discretised using mixed finite elements with a backward Euler time integration. Numerical examples are presented illustrating the fundamental effects on the brain tissue under heart–rate dependent pulsative pressure variations. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Continuum-Mechanical Analysis of Human Brain Tissue

The effective treatment of brain diseases, such as malignant brain tumours, is generally constricted by the controlled contribution of therapeutic agents. Novel brain tumour therapy proceeds from a direct infusion of the drug into the extra-vascular space of the nervous brain tissue (convection-enhanced delivery). This is carried out using catheter to bypass the blood-brain barrier, which effectively separates brain tissue from the intra-vascular space and hence hamper drug delivery through the bloodstream. The dilation of the target tissue, as response to the local pressure increase, initiates interstitial fluid flow and, thus, the distribution of the chemical agents. An adequate constitutive model of the complex tissue aggregate in the framework of the Theory of Porous Media is essential in order to assist modern clinical application via numerical simulations. The presented model consists of an elastically deformable solid skeleton, provided by the tissue cells, permeated by two viscous, materially incompressible pore-liquid phases, interstitial fluid and blood plasma. Both liquids are mobile within the solid skeleton and separated from each other. With regard to simulate a drug infusion process in the extra-vascular space, the interstitial fluid is treated as a solution of a liquid solvent and a dissolved therapeutic solute. The constitutive assumptions for the involved constituents are adjusted in order to describe the physical behaviour of human brain tissue. The presented numerical examples illustrate the fundamental effects during an infusion process. Therefore, the resulting set of coupled partial differential equations is spatially discretised using hexahedral mixed finite elements with an implicit (backward) Euler time integration scheme to solve the considered problem in a monolithic manner for the primary variables. (© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

A porous media approach for plantar tissue during gait

Recently a new computational model, based on the thermodynamically constrained averaging theory, has been proposed to predict tumor initiation and proliferation and afterwards to study plantar tissue mechanics. The foot tissue is modeled as an elastic porous medium, in large strain regime and completely filled by a fluid phase. By considering the interstitial fluid, it is possible to mimic the viscoelastic behavior of the plantar tissue observed experimentally. Being the global response of the bi-phase system viscoelastic, it is shown that the duration of stance as well as of each of gait cycle has an influence on tissue stress field. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Computational modelling of drug infusion into the anisotropic white-matter tracts of the human brain

Unfortunately, the human brain is compromised by an amount of brain diseases, such as strokes or cerebral tumours. In this contribution, special attention is paid to the constitutive modelling procedure and the numerical simulation of the so-called convection-enhanced delivery process, where an effective treatment of malignant brain tumours is achieved by bypassing the blood-brain barrier via a direct infusion of therapeutic agents into the extra-vascular space of the brain tissue using implanted catheters. The modelling approach of the complex brain-tissue aggregate proceeds from the Theory of Porous Media including an elastically deformable solid skeleton, provided by the tissue cells and the vascular walls. The tissue is permeated by two liquid phases, the blood and the interstitial fluid. In order to describe a distribution process of the inserted drugs, the interstitial fluid phase is treated as a chemical solution of two components, the liquid solvent and the dissolved therapeutic solute. The inhomogeneous anisotropic nature of the white-matter tracts is considered by spatially varying permeability tensors, obtained by diffusion-weighted magnetic resonance imaging. The strongly coupled solid-liquid transport problem is simultaneously approximated in all primary unknowns using mixed finite elements and solved in a monolithic manner with an implicit time-integration scheme. The numerical investigation is applied to un-bloody numerical studies. (© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Pulsatile flow of Herschel–Bulkley fluid through catheterized arteries – A mathematical model

The pulsatile flow of blood through catheterized artery has been studied in this paper by modeling blood as Herschel–Bulkley fluid and the catheter and artery as rigid coaxial circular cylinders. The Herschel–Bulkley fluid has two parameters, the yield stress θ and the power index n. Perturbation method is used to solve the resulting quasi-steady nonlinear coupled implicit system of differential equations. The effects of catheterization and non-Newtonian nature of blood on yield plane locations, velocity, flow rate, wall shear stress and longitudinal impedance of the artery are discussed. The existence of two yield plane locations is investigated and their dependence on yield stress θ, amplitude A, and time t are analyzed. The width of the plug core region increases with increasing value of yield stress at any time. The velocity and flow rate decrease, whereas wall shear stress and longitudinal impedance increase for increasing value of yield stress with other parameters held fixed. On the other hand, the velocity, flow rate and wall shear stress decrease but resistance to flow increases as the catheter radius ratio (ratio of catheter radius to vessel radius) increases with other parameters fixed. The results for power law fluid, Newtonian fluid and Bingham fluid are obtained as special cases from this model.     

Analysis of blood flow through a modelled artery with an aneurysm

The intention of the present work is to carry out a systematic analysis of flow features in a tube, modelled as artery, having a local aneurysm in presence of haematocrit. The arterial model is treated to be axi-symmetric and rigid. The blood, flowing through the modelled artery, is treated to be Newtonian and non-homogeneous. For a thorough quantitative analysis of the flow characteristics such as wall pressure, flow velocity, wall shear stress, the unsteady incompressible Navier-Stokes equations in cylindrical polar co-ordinates under the laminar flow conditions are solved by using the finite-difference method. Finally, the numerical illustrations presented in this paper provide an effective measure to estimate the combined influence of haematocrit and aneurysm on flow characteristics. It is found that the magnitude of wall shear stress and also the length of separation increase with increasing values of the haematocrit parameter. The length of flow separation increases but the peak value of wall shear stress decreases with the increasing length of aneurysm. The peak value of wall shear stress as well as the length of separation increases with the increasing height of the aneurysm.     

On predicting unsteady non-Newtonian blood flow

The influence of the non-Newtonian stress–strain relation of blood on the oscillatory shear index (OSI) and mean wall shear stress (WSS) are described. A mathematical non-dimensional model based on the momentum equation for a modified Casson’s fluid is formulated in terms of the dimensionless yield shear stress . An original direct numerical procedure is presented to predict the flow patterns. Results obtained by using a finite difference approach show a difference in OSI when blood is assumed to be a Newtonian fluid instead of a modified Casson’s fluid. The calculation of the OSI in human normal conditions under the Newtonian approach differs in 5% from the result obtained from using the Casson model.     

A non-Newtonian fluid flow model for blood flow through a catheterized artery—Steady flow

In this paper the effects catheterization and non-Newtonian nature of blood in small arteries of diameter less than 100 μm, on velocity, flow resistance and wall shear stress are analyzed mathematically by modeling blood as a Herschel–Bulkley fluid with parameters n and θ and the artery and catheter by coaxial rigid circular cylinders. The influence of the catheter radius and the yield stress of the fluid on the yield plane locations, velocity distributions, flow rate, wall shear stress and frictional resistance are investigated assuming the flow to be steady. It is shown that the velocity decreases as the yield stress increases for given values of other parameters. The frictional resistance as well as the wall shear stress increases with increasing yield stress, whereas the frictional resistance increases and the wall shear stress decreases with increasing catheter radius ratio k (catheter radius to vessel radius). For the range of catheter radius ratio 0.3–0.6, in smaller arteries where blood is modeled by Herschel–Bulkley fluid with yield stress θ = 0.1, the resistance increases by a factor 3.98–21.12 for n = 0.95 and by a factor 4.35–25.09 for n = 1.05. When θ = 0.3, these factors are 7.47–124.6 when n = 0.95 and 8.97–247.76 when n = 1.05.     

Discussion of Different Model Approaches for the Flow Behavior of Ice

Ice of Antarctic ice shelves is assumed to behave on long-term as an incompressible viscous fluid, which is dominated on short time scales by the elastic response. Hence, a viscoelastic material model is required. The thermodynamic pressure is treated differently in elastic and viscous models. For small deformations, the elastic isometric stress for ν → 0.5 gives similar results to those solving for pressure in an incompressible laminar flow model. A viscous model, in which the thermodynamic pressure is approximated by an elastic isometric stress, can be easily extended to viscoelasticity. (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Peripheral layer viscosity effects on periodic blood flow through rigid tube of thin diameter

A mathematical model has been presented for periodic blood flow in a rigid circular tube of thin diameter. Blood is presented as a 3-layered fluid by considering core fluid as a casson fluid which is covered by a thin layer of Newtonian fluid (plasma). The energy integral method has been used to obtain the unsteady pressure gradients as suggested by Elkouh [2]. The results obtained for velocity profiles have been compared with the experimental results of Bugliarello and Sevilla (Biorheology 7 (1970), 85). The effects of various parameters on wall shearing stress has also been brought out and discussed.     

Homogenization approach to the multi-compartment model of perfusion

The paper deals with modelling of the coupled diffusion-deformation processes in biological tissues with potential applications in describing the blood perfusion, or fluid filtration phenomena in general. The micromodel to be homogenized is based on the Biot type model for the incompressible medium. Due to the strong heterogeneity in the permeability coefficients associated with three compartments of the representative microstructural cell (RMC), the homogenization of the model leads to the double diffusion phenomena. The resulting homogenized equations, involving the stress-equilibrium equation and other two equations governing the mass redistribution, describe the parallel diffusion in two high-conducting compartments (arterial and venous sectors) separated by the low conducting matrix which represents the perfused tissue. To obtain the homogenized model, the method of two scale convergence is applied. The homogenized coefficients are defined in terms of the characteristic response of the RMC. It is possible to identify the instantaneous and fading memory viscoelastic coefficients; other effective parameters, controlling the fluid redistribution between the compartments, are involved also in time convolutions. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Helical flow arising from the yielded annular flow of a Bingham fluid

The Bingham fluid model was developed to represent viscoplastic materials that change from rigid bodies at low stress to viscous fluids at high stress – a process termed yielding. Such a fluid model is used in the modeling of slurries, which occur frequently in food processing and other engineering applications.     

Asymptotic stability of the human respiratory system with multiple state‐dependent delays

We extend the Grodins model of human cardiovascular‐respiratory system with multiple blood transport time delays into a model with four threshold type state‐dependent delays, in order to investigate the asymptotic stability of carbon dioxide concentrations in the lung, brain, cerebrospinal fluid, and tissue compartments. We show that the extended model can be transformed into a model with four discrete time delays and obtain sufficient conditions for local and global asymptotic stabilities of the extended model by constructing Lyapunov functionals. Numerical simulations are presented to illustrate the general results.     

A micropolar fluid model of blood flow through a tapered artery with a stenosis

A nonlinear two‐dimensional micropolar fluid model for blood flow in a tapered artery with a single stenosis is considered. This model takes into account blood rheology in which blood consists of microelements suspended in plasma. The classical Navier–Stokes theory is inadequate to describe the microrotations or particles' spin of such suspension in a viscous medium. The governing equations involving unsteady nonlinear partial differential equations are solved using a finite difference scheme. A quantitative analysis performed through numerical computation shows that the axial velocity profile and the flow rate decrease and the wall shear stress increases once the artery is narrower in the presence of the polar effect. Furthermore, the taper angle certainly bears the potential to influence the velocity and the flow characteristics to considerable extent. Copyright © 2010 John Wiley & Sons, Ltd.     

A model of fluid injection into the spinal disc

This paper presents an analytical model of the stress–strain response of intervertebral disc to fluid injection. The disc has nonlinear properties and collagen fibres play a significant role in sustaining strain. Each fibre is modeled as a flexible, helical string inclined at ∼30° to the horizontal plane. The tensile stress in the fibres is obtained from a nonlinear stress–strain law that has been determined by experiment. An asymptotic approximation of the model equations based on the ratio of the fluid injected to the initial volume of fluid in the disc is developed and its solution obtained. Some quantitative predictions are made by considering a hypothetical value of the amount of fluid injected and some material values of discs at different levels of the spine. Numerical simulations show that the model compare reasonably well with some experimental observations for discs of the lumbar region.