Plaque heterogeneity and the spatial distributions of its components dictate drug-coated balloon therapy.

Drug-coated balloon (DCB) angioplasty is one of the potential approaches to alleviating in-stent restenosis and treating peripheral artery disease. An in-silico model has been developed for sirolimus drug eluted from an inflated balloon in a patient-specific arterial cross-section consisting of fibrous tissue, fibrofatty tissue, dense calcium, necrotic core, and healthy tissue. The convection-diffusion-reaction equation represents the transport of drug, while drug binding, both specific and non-specific, can be modelled as a reaction process. The Brinkman equations describe the interstitial flow in porous tissue. An image processing technique is leveraged for reconstructing the computational domain. The Marker and Cell, and Immersed Boundary Methods are used to solve the set of governing equations. The no-flux interface condition and convection do amplify the tissue content, and the regions of dense calcium and necrotic core limited to or extremely close to the interface pose a clinical threat to DCB therapy. Simulations predict the effects of the positioning and clustering of plaque components in the domain. This study demands extensive intravascular ultrasound-derived virtual histology (VH-IVUS) imaging to understand the plaque morphology and determine the relative positions of different plaque compositions about the lumen-tissue interface, which have a significant impact on arterial pharmacokinetics.

Specific and nonspecific binding of drug eluted from a half-embedded stent in presence of atherosclerotic plaque.

This study is dealt with the two-phase binding (specific and nonspecific) of drug eluted from a half- embedded drug-eluting stent in presence of atherosclerotic plaque. The specific binding due to the interaction of drug molecules with specific receptors and nonspecific binding caused by the trapping of drug in the extra-cellular matrix have been paid due attention. An idealised wall consisting of a plaque and a healthy tissue region has been considered. Moreover, a Dirichlet release condition is imposed on the strut surface. In this investigation, a two-dimensional model governing drug transport and its two-phase binding in cylindrical polar coordinate system has been solved numerically by a finite-difference method. Our simulation predicts that plaque behaves like a physical barrier in two types of the binding process and there is an inverse relationship between bound drug concentration and plaque thickness. Simulations show that a single peak profile of drug is noted when the struts are situated one-strut radius apart and as the inter-strut distance increases, the peak concentration falls and distinct peak profiles over each strut are visualised. The model also reveals that in the region downstream of a strut, the concentration of both bound drug forms in the plaque and healthy regions increases, and eventually, the saturation length of binding sites increases. Predicted results show for smaller Damköhler number, the rapid saturation of binding sites takes place and the stent having thinner strut may perform well in terms of effectiveness as well as efficacy in the stent-based delivery.

Modelling the dynamics of Pine Wilt Disease with asymptomatic carriers and optimal control.

Pine wilt disease is a lethal tree disease caused by nematodes carried by pine sawyer beetles. Once affected, the trees are destroyed within a few months, resulting in significant environmental and economic losses. The role of asymptomatic carrier trees in the disease dynamics remains unclear. We developed a mathematical model to investigate the effect of asymptomatic carriers on the long-term outcome of the disease. We performed a stability and sensitivity analysis to identify key parameters and used optimal control to examine several intervention options. Our model shows that, with the application of suitable controls, the disease can be eliminated in the vector population and all tree populations except for asymptomatic carriers. Of the possible controls (tree injection, elimination of infected trees, insecticide spraying), we determined that elimination of infected trees is crucial. However, if the costs of insecticide spraying increase, it can be supplemented (although not replaced entirely) by tree injection, so long as some spraying is still undertaken.

Computational model of stent-based delivery from a half-embedded two-layered coating.

An attempt is made in the present investigation to develop a computational model for the purpose of studying the effect of interstitial flow in the porous media on the distribution of drug eluted from a half-embedded drug-eluting stent and its retention in the presence of two-layered coating of the stent. The transport of free drug inside the coatings is considered as an unsteady diffusion process while that in the tissue as an unsteady convection-diffusion-reaction process. The bound drug is governed by an unsteady reaction process only. Immersed boundary method (IBM) in the staggered grid formulation, popularly known as marker and cell (MAC) method, has been leveraged to tackle numerically the governing equations. This model highlights the benefits of consideration of two-layered coating and does predict underlying mechanism for better efficacy by tweaking the kinetics parameters. Comparisons are also made with the results available for stent-based delivery.

Effect of Interstitial Fluid Flow on Drug-Coated Balloon Delivery in a Patient-Specific Arterial Vessel with Heterogeneous Tissue Composition: A Simulation Study.

Angioplasty with drug-coated balloons (DCBs) using excipients as drug carriers is emerging as a potentially viable strategy demonstrating clinical efficacy and proposing additional compliance for the treatment of obstructive vascular diseases. An attempt is made to develop an improved computational model where attention has been paid to the effect of interstitial flow, that is, plasma convection and internalization of bound drug. The present model is capable of capturing the phenomena of the transport of free drug and its retention, and also the internalization of drug in the process of endocytosis to atherosclerotic vessel of heterogeneous tissue composition comprising of healthy tissue, as well as regions of fibrous cap, fibro-fatty, calcified and necrotic core lesions. Image processing based on an unsupervised clustering technique is used for color-based segmentation of a patient-specific longitudinal image of atherosclerotic vessel obtained from intravascular ultrasound derived virtual histology. As the residence time of drug in a stent-based delivery within the arterial tissue is strongly influenced by convective forces, effect of interstitial fluid flow in case of DCB delivery can not be ruled out, and has been investigated by modeling it through unsteady Navier-Stokes equations. Transport of free drug is modeled by considering unsteady advection-reaction-diffusion process, while the bound drug, assuming completely immobilized in the tissue, by unsteady reaction process. The model also takes into account the internalization of drug through the process of endocytosis which gets degraded by the lysosomes and finally recycled into the extracellular fluid. All the governing equations representing the flow of interstitial fluid, the transport of free drug, the metabolization of free drug into bound phase and the process of internalization along with the physiologically realistic boundary and initial conditions are solved numerically using marker and cell method satisfying necessary stability criteria. Simulated results obtained predict that faster drug transfer promotes rapid saturation of binding sites despite perivascular wash out and the concentrations of all drug forms are modulated by the presence of interstitial flow. Such premier attempt of its kind would certainly be of great help in the optimization of therapeutic efficacy of drug.

Dynamical behaviour of a two-predator model with prey refuge.

A three-component model consisting on one-prey and two-predator populations is considered with a Holling type II response function incorporating a constant proportion of prey refuge. We also consider the competition among predators for their food (prey) and shelter. The essential mathematical features of the model have been analyzed thoroughly in terms of stability and bifurcations arising in some selected situations. Threshold values for some parameters indicating the feasibility and stability conditions of some equilibria are determined. The range of significant parameters under which the system admits different types of bifurcations is investigated. Numerical illustrations are performed in order to validate the applicability of the model under consideration.

Analysis of a competitive prey-predator system with a prey refuge.

Gauss's competitive exclusive principle states that two competing species having analogous environment cannot usually occupy the same space at a time but in order to exploit their common environment in a different manner, they can co-exist only when they are active in different times. On the other hand, several studies on predators in various natural and laboratory situations have shown that competitive coexistence can result from predation in a way by resisting any one prey species from becoming sufficiently abundant to outcompete other species such that the predator makes the coexistence possible. It has also been shown that the use of refuges by a fraction of the prey population exerts a stabilizing effect in the interacting population dynamics. Further, the field surveys in the Sundarban mangrove ecosystem reveal that two detritivorous fishes, viz. Liza parsia and Liza tade (prey population) coexist in nature with the presence of the predator fish population, viz. Lates calcarifer by using refuges. In view of such observations in mind, a three-component model consisting of two prey and one predator population is considered in the present investigation with the inclusion of Holling type-II response function incorporating a constant proportion of prey refuge. The essential mathematical features of the present model have been analyzed thoroughly in terms of the local and the global stability and the bifurcations arising in some selected situations as well. The threshold values for some parameters indicating the feasibility and the stability conditions of some equilibria are also determined. The ranges of the significant parameters under which the system admits a Hopf bifurcation are investigated. The explicit formulae for determining the stability, direction and other properties of bifurcating periodic solutions are also derived with the use of both the normal form and the central manifold theory. Numerical illustrations are performed finally in order to validate the applicability of the model under consideration.

Unsteady magnetohydrodynamic blood flow through irregular multi-stenosed arteries.

Flow of an electrically conducting fluid characterizing blood through the arteries having irregular shaped multi-stenoses in the environment of a uniform transverse magnetic-field is analysed. The flow is considered to be axisymmetric with an outline of the irregular stenoses obtained from a three-dimensional casting of a mild stenosed artery, so that the physical problem becomes more realistic from the physiological point of view. The marker and cell (MAC) and successive-over-relaxation (SOR) methods are respectively used to solve the governing unsteady magnetohydrodynamic (MHD) equations and pressure-Poisson equation quantitatively and to observe the flow separation. The results obtained show that the flow separates mostly towards the downstream of the multi-stenoses. However, the flow separation region keeps on shrinking with the increasing intensity of the magnetic-field which completely disappears with sufficiently large value of the Hartmann number. The present observations certainly have some clinical implications relating to magnetotherapy which help reducing the complex flow separation zones causing flow disorder leading to the formation and progression of the arterial diseases.