Hybrid discrete-continuum model of tumor growth considering capillary points

A hybrid discrete-continuum model of tumor growth in the avascular phase considering capillary points is established. The influence of the position of capillary points on tumor growth is also studied by simulation. The results of the dynamic tumor growth and the distribution of oxygen, matrix-degrading enzymes, and extracellular matrixconcentration in the microenvironment with respect to time are shown by graphs. The relationships between different oxygenated environments and the numbers of surviving, dead, proliferative, and quiescent tumor cells are also investigated.     

THE DISPLACEMENT WAVE THEORY OF BLOOD VESSEL

On the basis of the medical and mechanical analysis and explanations in this paper thevisco-elastic simply supported beam model is proposed to treat the displacement wave of theblood vessels.The relationships between the displacement wave and blood vessel elasticityas well as the viscous dissipation of the blood and blood vessel are obtained.Thecorresponding relations of such kinds of pulses in the traditional Chinese medicine assmooth pulse,surface pulse and deep pulse to the displacement waves of blood vessels arealso found.The computational results are in good agreement with those acquired in theexperiments with ultrasonic wave.     

NONLINEAR MOTION MECHANICS MODEL OF CURVED BLOOD VESSEL

A geometric model of curved blood vessels is established based on some reason-able hypotheses;the nonlinear motion mechanics model of the curved blood vessel is establishedaccording to basic mechanics laws.This model includes much more physiological factors.It cou-ples the interaction of blood flow with mechanical factors such as the displacement,deformation,strain and stress etc.of the curved blood vessel.It is of great importance for investigating thecirculation rules of the cardiovascular system and the nonlinear pulse wave propagation in curvedblood vessels.     

3D numerical study of tumor blood perfusion and oxygen transport during vascular normalization

The changes of blood perfusion and oxygen transport in tumors during tumor vascular normalization are studied with 3-dimensional mathematical modeling and numerical simulation. The models of tumor angiogenesis and vascular-disrupting are used to simulate "un-normalized" and "normalized" vasculatures. A new model combining tumor hemodynamics and oxygen transport is developed. In this model, the intravasculartransvascular-interstitial flow with red blood cell(RBC) delivery is tightly coupled, and the oxygen resource is produced by heterogeneous distribution of hematocrit from the flow simulation. The results show that both tumor blood perfusion and hematocrit in the vessels increase, and the hypoxia microenvironment in the tumor center is greatly improved during vascular normalization. The total oxygen content inside the tumor tissue increases by about 67%, 51%, and 95% for the three approaches of vascular normalization,respectively. The elevation of oxygen concentration in tumors can improve its metabolic environment, and consequently reduce malignancy of tumor cells. It can also enhance radiation and chemotherapeutics to tumors.     

Exact analytical solution to three-dimensional phase change heat transfer problems in biological tissues subject to freezing

Analytically solving a three-dimensional （3-D） bioheat transfer problem with phase change during a freezing process is extremely difficult but theoretically important. The moving heat source model and the Green function method are introduced to deal with the cryopreservation process of in vitro biomaterials. Exact solutions for the 3-D temperature transients of tissues under various boundary conditions, such as totally convective cooling, totally fixed temperature cooling and a hybrid between them on tissue surfaces, are obtained. Furthermore, the cryosurgical process in living tissues subject to freezing by a single or multiple cryoprobes is also analytically solved. A closed-form analytical solution to the bioheat phase change process is derived by considering contributions from blood perfusion heat transfer, metabolic heat generation, and heat sink of a cryoprobe. The present method is expected to have significant value for analytically solving complex bioheat transfer problems with phase change.     

Analysis of coupled flow-reaction with heat transfer in heap bioleaching processes

A mathematical model for heap bioleaching is developed to analyze heat transfer, oxygen flow, target ion distribution and oxidation leaching rate in the heap. The model equations are solved with Comsol Multiphysics software. Numerical simulation results show the following facts： Concentration of oxygen is relatively high along the boundary of the slope, and low in the center part where leaching rate is slow. Temper- ature is relatively low along the slope and reaches the highest along the bottom region near the slope, with difference being more than 6℃. Concentration of target mental ions is the highest in the bottom region near the slope. Oxidation leaching rate is relatively large in the bottom and slope part with a fast reaction rate, and small in the other part with low oxygen concentration.     

COMPREHENSIVE MATHEMATICAL MODEL OF MICROCIRCULATORY DYNAMICS (Ⅰ)——BASIC THEORY

Under the basis of physiological data, a nonlinear and unsteady comprehensive mathematical model of microcirculatory dynamics with distributed parameters is developed. Hemodynamics, interstitium dynamics, lymph dynamics, dynamics of protein transport, oxygen dynamics, dynamics of heat transfer, and myogenic and metabolic regulation procedures are included. The interactions between these factors were comprehensively exhibited. The influences of arteriolar vasomotion and nonlinear viscoelasticity of blood in arteriole are considered. A simplified vessel network consisting of arteriole, open and reserved capillaries, venule, initial lymphatics and arteriole-venule anastomose is adopted as the geometrical model. This kind of comprehensive mathematical model is helpful in analyzing clinical data and developing a “numerical experiment method” in microcirculation research.     

A CALCULATION METHOD FOR BLOOD FLOW VELOCITY DISTRIBUTION IN SMALLER BLOOD VESSELS

The calculative method presented in this paper is based on animprovement of boundary conditions for a micro-continuum fluidmodel with blood flow assuming that the blood cell velocity atblood vessel wall is unequal to zero.As for steady state floodflow equation (flow in vitre-a rigid circular tube) presentedby Exingen,the magnitude of the blood cell gyroscopic velocityat blood vessel wall and the slope of the blood cell gyroscopicvelocity distribution curve at the axis of the blood vessel areassumed.From the above-mentioned assumptions the calculatingmethod of velocity distribution curve in blood vessel is deri.ved.The curve calculated by this method is compared with thetest curve measured by Bugliarello and Hayden.The results ob-tained by Turk,Sylvester and Ariman as well as with this me-thod are compared with each other,too.     

Multidimensional modeling of the stenosed carotid artery: A novel CAD approach accompanied by an extensive lumped model

This study describes a multidimensional 3D/lumped parameter(LP) model which contains appropriate inflow/outflow boundary conditions in order to model the entire human arterial trees. A new extensive LP model of the entire arterial network(48 arteries) was developed including the effect of vessel diameter tapering and the parameterization of resistance, conductor and inductor variables. A computer aided-design(CAD) algorithm was proposed to effciently handle the coupling of two or more 3D models with the LP model, and substantially lessen the coupling processing time. Realistic boundary conditions and Navier–Stokes equations in healthy and stenosed models of carotid artery bifurcation(CAB) were used to investigate the unsteady Newtonian blood flow velocity distribution in the internal carotid artery(ICA). The present simulation results agree well with previous experimental and numerical studies. The outcomes of a pure LP model and those of the coupled 3D healthy model were found to be nearly the same in both cases. Concerning the various analyzed 3D zones, the stenosis growth in the ICA was not found as a crucial factor in determining the absorbing boundary conditions.This paper demonstrates the advantages of coupling local and systemic models to comprehend physiological diseases of the cardiovascular system.     

A dynamic cellular vertex model of growing epithelial tissues

Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphome-chanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tis-sue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercel-lular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.     

Numerical simulation of avascular tumor growth based on p27 gene regulation

A multi-scale continuous-discrete model based on the effects of the p27 gene control is built to simulate the avascular tumor growth. At the tissue level, the continuous Eulerian model is adopted to determine the distribution of the concentration of oxygen, the extracellular matrix (ECM), and the matrix-degradative enzyme (MDE). At the cellular level, the discrete Lagrangien model is adopted to determine the movement, the proliferation, and the death of single tumor cells (TCs). At the genetic level, whether a cell is committed to mitosis is determined by solving a set of equations modeling the effects of the p27 gene control. The avascular morphological evolution of the solid tumor growth is simulated, including the radius of the solid tumor, the number of the TCs, the oxygen distribution over time, and the inhibiting effect of the up-regulating p27 gene expression.     

Coupled modeling of tumour angiogenesis,tumour growth,and blood perfusion

This paper proposes a more realistic mathematical simulation method to investigate the dynamic process of tumour angio-genesis by fully coupling the vessel growth, tumour growth and associated blood perfusion. The tumour growth and angiogenesis are coupled by the chemical microenvironment and the cell-matrix interaction. The haemodynamic calculation is carried out on the new vasculature, and an estimation of vessel collapse is made according to the wall shear stress criterion. The results are consistent with physiological observations, and further confirm the application of the coupled model feedback mechanism. The model is available to examine the interactions between angiogenesis and tumour growth, to study the change in the dynamic process of chemical environment and the vessel remodeling.     

Role of response to changes in flow rate in the regulation of vessel radius and blood flow

Estimates are presented for the effect of susceptibility of the inner surface of the blood vessel wall to shear stress on changes in diameter and volume blood flow rate. The model of thin-walled vessel with radius controlled by two parameters is used. The effect of rheological factors, hematocrit, and oxygen content in blood on the value of vessel response to a change in shear stress is considered. The estimates showed that the contribution of the vessel response in question to a change in blood volume flow rate amounts tens per cent. The influence of rheological (Fahraeus and Fahraeus-Lindqvist) effects on flow rate lies within several per cent. The role of the vessel response considered increases with anaemia: at low hematocrit its contribution to increase in flow rate exceeds 10%. Variation of oxygen concentration within the normal range has almost no effect on the hemodynamic parameters. With hypoxia, on the contrary, the participation of this response on changes in flow rate weakens: in severe hypoxia decrease in blood flow rate owing to a change in oxygen concentration equals approximately 9%.     

Numerical simulation of inhibiting effects on solid tumour cells in anti-angiogenic therapy: application of coupled mathematical model of angiogenesis with tumour growth

To investigate the inhibiting effects of the anti-angiogenic factor andostatin and the anti-angiogenic drug endostatin on tumour angiogenesis and tumour cells, a coupled mathematical model of tumor angiogenesis with tumour growth and blood perfusion is developed. Simulation results show that angiostatin and endostatin can improve the abnormal microenvironment inside the tumour tissue by effectively inhibiting the process of tumor angiogenesis and decreasing tumour cells. The present model can be used as a valid theoretical method in the investigation of the tumour anti-angiogenic therapy.     

The interplay between stress and growth in solid tumors

A number of biological phenomena are interlaced with classical mechanics. In this review we discuss the role of mechanics in tumor growth, namely the avascular phase of solid tumors. While a growing mass produces a traction of the surrounding tissues, a feedback mechanism controls the proliferation of the malignant cells depending on the tensional state. The formalism of continuum mechanics, possibly accompanied by numerical simulations, is able to shed light on biological controversial subjects. The converse is also true: non-standard mechanical problems suggest new challenging theoretical questions.     

Why do we have a bronchial tree with 23 levels of bifurcation?

A simple one-dimensional mass transfer model has been proposed for the oxygen transport through a bronchial tree to alveolar tissues as well as the carbon dioxide removal from the tissues in the human respiratory system. The proposed model mathematically describes the mass transfer between the airway inlet and the red blood cell interior in the pulmonary capillaries. The quasi steady one-dimensional analysis based on the model reveals that the bronchial tree is constructed such that it promotes the easiest access to the external air. Naturally, there exists the optimal number of the bifurcation levels, namely, 23, that yields the minimum overall mass transfer resistance for the mass transport from the external air to the red blood cells.     

Exploring the potential of blood flow network data

To gain a better understanding of the role of haemodynamic forces during the development of the cardiovascular system, a series of studies have been reported recently that describe flow fields in the vasculature of model systems. Such data sets, in particular those reporting networks at multiple stages, mark a transition in the focus from single blood vessels to large parts of vascular networks. It becomes possible to investigate the behaviour of a blood vessel in the context of its surroundings, rather than as an isolated entity. In this study, a framework is presented that facilitates the analysis of such data sets. The blood vessel data is represented as a graph, with each node connected by a vessel segment with known properties. Using this framework the pressure distribution and other parameters of interest can then be estimated. Two examples are given that make use of this scheme: (1) a method to detect and reduce measurement errors in the network and (2) a method that allows the testing of various haemorheological models. For both examples a proof-of-principle result is shown.     

血流动力学数值模拟与动脉粥样硬化研究进展

血流动力学因素被认为与动脉粥样硬化等病理改变密切相关。目前血流动力学数值模拟的对象,主要集中于分支动脉、弯曲动脉以及因血管内膜增生而导致的局部狭窄动脉,这些都是动脉粥样硬化多发的病灶部位。精确的血流动力学数值模拟,必须依赖于解剖精确的血管几何模型和生理真实的血流与管壁有限变形的非线性瞬态流－固耦合。只有在“虚拟血液流动”的基础上,综合考虑血管内的壁面剪应力、粒子滞留时间和氧气的跨血管壁传输等多种因素,血流动力学的数值模拟才能真正有助于人们理解动脉粥样硬化的血流动力学机理,才有可能应用于有关动脉疾病的外科手术规划中。