Bidomain Domain
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The bidomain model is a
mathematical model A mathematical model is a description of a system using mathematical concepts and language. The process of developing a mathematical model is termed mathematical modeling. Mathematical models are used in the natural sciences (such as physics, ...
to define the electrical activity of the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
. It consists in a continuum (volume-average) approach in which the cardiac mictrostructure is defined in terms of muscle fibers grouped in sheets, creating a complex
three-dimensional Three-dimensional space (also: 3D space, 3-space or, rarely, tri-dimensional space) is a geometric setting in which three values (called ''parameters'') are required to determine the position of an element (i.e., point). This is the informal ...
structure with anisotropical properties. Then, to define the electrical activity, two interpenetrating domains are considered, which are the
intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
and
extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
domains, representing respectively the space inside the cells and the region between them. The bidomain model was first proposed by Schmitt in 1969 before being formulated mathematically in the late 1970s. Since it is a continuum model, rather than describing each cell individually, it represents the average properties and behaviour of group of cells organized in complex structure. Thus, the model results to be a complex one and can be seen as a generalization of the
cable theory Classical cable theory uses mathematical models to calculate the electric current (and accompanying voltage) along passive neurites, particularly the dendrites that receive synaptic inputs at different sites and times. Estimates are made by model ...
to higher dimensions and, going to define the so-called bidomain equations. Many of the interesting properties of the bidomain model arise from the condition of unequal anisotropy ratios. The
electrical conductivity Electrical resistivity (also called specific electrical resistance or volume resistivity) is a fundamental property of a material that measures how strongly it resists electric current. A low resistivity indicates a material that readily allow ...
in anisotropic tissues is not unique in all directions, but it is different in parallel and perpendicular direction with respect to the fiber one. Moreover, in tissues with unequal anisotropy ratios, the ratio of conductivities parallel and perpendicular to the fibers are different in the intracellular and extracellular spaces. For instance, in cardiac tissue, the anisotropy ratio in the
intracellular space Intracellular space is the interior space of the plasma membrane. It contains about two-thirds of TBW. Cellular rupture may occur if the intracellular space becomes dehydrated, or if the opposite happens, where it becomes too bloated. Thus it ...
is about 10:1, while in the
extracellular space Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells. The compositi ...
it is about 5:2. Mathematically, unequal anisotropy ratios means that the effect of anisotropy cannot be removed by a change in the distance scale in one direction. Instead, the anisotropy has a more profound influence on the electrical behavior. Three examples of the impact of unequal anisotropy ratios are * the distribution of transmembrane potential during unipolar stimulation of a sheet of cardiac tissue, * the
magnetic field A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and to ...
produced by an action potential wave front propagating through cardiac tissue, * the effect of fiber curvature on the transmembrane potential distribution during an electric shock.


Formulation


Bidomain domain

The bidomain domain is principally represented by two main regions: the cardiac cells, called intracellular domain, and the space surrounding them, called extracellular domain. Moreover, usually another region is considered, called extramyocardial region. The intracellular and extracellular domains, which are separate by the
cellular membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
, are considered to be a unique physical space representing the heart (\mathbb H), while the extramyocardial domain is a unique physical space adjacent of them (\mathbb T). The extramyocardial region can be considered as a fluid bath, especially when one wants to simulate experimental conditions, or as a human torso to simulate physiological conditions. The boundary of the two principal physical domains defined are important to solve the bidomain model. Here the heart boundary is denoted as \partial\mathbb H while the torso domain boundary is \partial\mathbb T.


Unknowns and parameters

The unknowns in the bidomain model are three, the intracellular potential v_i, the extracellular potential v_e and the transmembrane potential v, which is defined as the difference of the potential across the cell membrane v=v_i-v_e. Moreover, some important parameters need to be taken in account, especially the intracellular conductivity tensor matrix \mathbf\Sigma_i, the extracellular conductivity tensor matrix \mathbf\Sigma_e. The transmembrane current flows between the intracellular and extracellular regions and it is in part described by the corresponding ionic current over the membrane per unit area I_. Moreover, the membrane capacitance per unit area C_m and the surface to volume ratio of the cell membrane \chi need to be considered to derive the bidomain model formulation, which is done in the following
section Section, Sectioning or Sectioned may refer to: Arts, entertainment and media * Section (music), a complete, but not independent, musical idea * Section (typography), a subdivision, especially of a chapter, in books and documents ** Section sign ...
.


Standard formulation

The bidomain model is defined through two
partial differential equations In mathematics, a partial differential equation (PDE) is an equation which imposes relations between the various partial derivatives of a multivariable function. The function is often thought of as an "unknown" to be solved for, similarly to ...
(PDE) the first of which is a
reaction diffusion equation Reaction may refer to a process or to a response to an action, event, or exposure: Physics and chemistry *Chemical reaction *Nuclear reaction *Reaction (physics), as defined by Newton's third law *Chain reaction (disambiguation). Biology and me ...
in terms of the transmembrane potential, while the second one computes the extracellular potential starting from a given transmembran potential distribution. Thus, the bidomain model can be formulated as follows: : \begin &\nabla \cdot \left(\mathbf\Sigma_i \nabla v \right) + \nabla \cdot \left(\mathbf\Sigma_i \nabla v_e \right) = \chi \left( C_m \frac + I_\mathrm \right)- I_ \\ &\nabla \cdot \left( \left( \mathbf\Sigma_i + \mathbf\Sigma_e \right) \nabla v_e \right) = - \nabla \cdot \left( \mathbf\Sigma_i \nabla v \right) + I_ \end where I_ and I_ can be defined as applied external stimulus currents.


Ionic current equation

The ionic current is usually represented by an ionic model through a system of
ordinary differential equations In mathematics, an ordinary differential equation (ODE) is a differential equation whose unknown(s) consists of one (or more) function(s) of one variable and involves the derivatives of those functions. The term ''ordinary'' is used in contrast w ...
(ODEs). Mathematically, one can write I_ = I_(v,\mathbf w) where \mathbf w is called ionic variable. Then, in general, for all t > 0, the system reads :\begin \frac = \mathbf(v,\mathbf w) &\text \mathbb \\ \mathbf w(t = 0) = \mathbf_0 &\text \mathbb \end Different ionic models have been proposed: * phenomenological models, which are the simplest ones and used to reproduce macroscopic behavior of the cell. * physiological models, which take into account both macroscopic behaviour and cell physiology with a quite detailed description of the most important ionic current.


Model of an extramyocardial region

In some cases, an extramyocardial region is considered. This implies the addition to the bidomain model of an equation describing the potential propagation inside the extramyocardial domain. Usually, this equation is a simple generalized
Laplace equation In mathematics and physics, Laplace's equation is a second-order partial differential equation named after Pierre-Simon Laplace, who first studied its properties. This is often written as \nabla^2\! f = 0 or \Delta f = 0, where \Delta = \nab ...
of type : -\nabla \cdot (\mathbf \Sigma_0 \nabla v_0) = 0 \quad \mathbf x \in \mathbb where v_0 is the potential in the extramyocardial region and \mathbf \Sigma_0 is the corresponding conductivity tensor. Moreover, an isolated domain assuption is considered, which means that the following boundary conditions are added : (\mathbf \Sigma_0 \nabla v_0) \cdot \mathbf_0 = 0 \quad \mathbf x \in \partial \mathbb, \mathbf_0 being the unit normal directed outside of the extramyocardial domain. If the extramyocardial region is the human torso, this model gives rise to the
forward problem of electrocardiology The forward problem of electrocardiology is a computational and mathematical approach to study the electrical activity of the heart through the body surface. The principal aim of this study is to computationally reproduce an electrocardiogram (EC ...
.


Derivation

The bidomain equations are derived from the
Maxwell's equations Maxwell's equations, or Maxwell–Heaviside equations, are a set of coupled partial differential equations that, together with the Lorentz force law, form the foundation of classical electromagnetism, classical optics, and electric circuits. ...
of the electromagnetism, considering some simplifications. The first assumption is that the intracellular current can flow only between the intracellular and extracellular regions, while the intracellular and extramyocardial regions can comunicate between them, so that the current can flow into and from the extramyocardial regions but only in the extracellular space. Using
Ohm's law Ohm's law states that the current through a conductor between two points is directly proportional to the voltage across the two points. Introducing the constant of proportionality, the resistance, one arrives at the usual mathematical equat ...
and a quasi-static assumption, the gradient of a scalar potential field \varphi can describe an electrical field \mathbf, which means that : \mathbf = - \nabla \varphi. Then, if J represent the current density of the electric field \mathbf, two equations can be obtained : \begin J_i & = -\mathbf\Sigma_i \nabla v_i \\ J_e & = -\mathbf\Sigma_e \nabla v_e. \end where the subscript i and e represent the intracellular and extracellular quantities respectively. The second assumption is that the heart is isolated so that the current that leaves one region need to flow into the other. Then, the current density in each of the intracellular and extracellular domain must be equal in magnitude but opposite in sign, and can be defined as the product of the surface to volume ratio of the cell membrane and the transmembrane ionic current density I_m per unit area, which means that : -\nabla \cdot J_i = \nabla \cdot J_e = \chi I_m. By combining the previous assumptions, the conservation of current densities is obtained, namely from which, summing the two equations : \nabla \cdot (\mathbf\Sigma_i \nabla v_i) = - \nabla \cdot (\mathbf\Sigma_e \nabla v_e). This equation states exactly that all currents exiting one domain must enter the other. From here, it is easy to find the second equation of the bidomain model subtracting \nabla \cdot (\mathbf\Sigma_i \nabla v_e) from both sides. In fact, : \nabla \cdot (\mathbf\Sigma_i \nabla v_i) - \nabla \cdot (\mathbf\Sigma_i \nabla v_e) = - \nabla \cdot (\mathbf\Sigma_e \nabla v_e) -\nabla \cdot (\mathbf\Sigma_i \nabla v_e) and knowing that the transmembral potential is defined as v = v_i - v_e : \nabla \cdot (\mathbf\Sigma_i \nabla v) = - \nabla \cdot ((\mathbf\Sigma_i + \mathbf\Sigma_e) \nabla v_e). Then, knowing the transmembral potential, one can recover the extracellular potential. Then, the current that flows across the cell membrane can be modelled with the
cable equation Classical cable theory uses mathematical models to calculate the electric current (and accompanying voltage) along passive neurites, particularly the dendrites that receive synapse, synaptic inputs at different sites and times. Estimates are made ...
, Combining equations () and () gives : \nabla \cdot \left( \mathbf\Sigma_i \nabla v_i \right) = \chi \left( C_m \frac + I_ \right) . Finally, adding and subtracting \nabla \cdot (\mathbf\Sigma_i \nabla v_e) on the left and rearranging v = v_i - v_e, one can get the first equation of the bidomain model : \nabla \cdot \left( \mathbf\Sigma_i \nabla v \right) + \nabla \cdot \left( \mathbf\Sigma_i \nabla v_e \right) = \chi \left( C_m \frac + I_\mathrm \right) , which describes the evolution of the transmembrane potential in time. The final formulation described in the
standard formulation Standard may refer to: Symbols * Colours, standards and guidons, kinds of military signs * Standard (emblem), a type of a large symbol or emblem used for identification Norms, conventions or requirements * Standard (metrology), an object th ...
section is obtained through a generalization, considering possible external stimulus which can be given through the external applied currents I_ and I_.


Boundary conditions

In order to solve the model, boundary conditions are needed. The more classical boundary conditions are the following ones, formulated by Tung. First of all, as state before in the derive section, there ca not been any flow of current between the intracellular and extramyocardial domains. This can be mathematically described as : (\mathbf\Sigma_i \nabla v_i ) \cdot \mathbf n = 0 \quad \mathbf x \in \partial \mathbb H where \mathbf n is the vector that represents the outwardly unit normal to the myocardial surface of the heart. Since the intracellular potential is not explicitily presented in the bidomain formulation, this condition is usually described in terms of the transmembrane and extracellular potential, knowing that v = v_i - v_e , namely : (\mathbf\Sigma_i \nabla v) \cdot \mathbf n = - (\mathbf\Sigma_i \nabla v_e) \cdot \mathbf n \quad \mathbf x \in \partial \mathbb H. For the extracellular potential, if the myocardial region is presented, a balance in the flow between the extracellular and the extramyocardial regions is considered : \left( \mathbf\Sigma_e \nabla v_e \right) \cdot \mathbf n_e= -\left( \mathbf\Sigma_0 \nabla v_0 \right) \cdot \mathbf n_0 \quad \mathbf x \in \partial \mathbb H . Here the normal vectors from the perspective of both domains are considered, thus the negative sign are necessary. Moreover, a perfect transmission of the potential on the cardiac boundary is necessary, which gives : v_e = v_0 \quad \mathbf x \in \partial \mathbb H. Instead, if the heart is considered as isoleted, which means that no myocardial region is presented, a possible boundary condition for the extracellular problem is : \left( \mathbf\Sigma_i \nabla v \right) \cdot \mathbf n= -\left( (\mathbf\Sigma_i + \mathbf\Sigma_e) \nabla v_e \right) \cdot \mathbf n \quad \mathbf x \in \partial \mathbb H .


Reduction to monodomain model

By assuming equal anisotropy ratios for the intra- and extracellular domains, i.e. \mathbf\Sigma_i = \lambda\mathbf\Sigma_e for some scalar \lambda, the model can be reduced to one single equation, called monodomain equation : \nabla \cdot (\mathbf \Sigma \nabla v ) = \chi \left( C_m \frac + I_\mathrm\right) - I_s where the only variable is now the transmembrane potential, and the conductivity tensor \mathbf\Sigma is a combination of \mathbf\Sigma_i and \mathbf \Sigma_e.


Formulation with boundary conditions in an isolated domain

If the heart is considered as an isolated tissue, which means that no current can flow outside of it, the final formulation with boundary conditions reads : \begin \nabla \cdot \left(\mathbf\Sigma_i \nabla v \right) + \nabla \cdot \left(\mathbf\Sigma_i \nabla v_e \right) = \chi \left( C_m \frac + I_\mathrm \right) - I_ & \mathbf x \in \mathbb H \\ \nabla \cdot \left( \left( \mathbf\Sigma_i + \mathbf\Sigma_e \right) \nabla v_e \right) = -\nabla \cdot \left( \mathbf\Sigma_i \nabla v \right) + I_ & \mathbf x \in \mathbb H \\ \mathbf \Sigma_i(\nabla v + \nabla v_e) \cdot \mathbf n = 0 &\mathbf x \in \partial\mathbb H\\ \left \mathbf \Sigma_i(\nabla v + \nabla v_e) + \mathbf \Sigma_e \nabla v_e\right\cdot \mathbf n = 0 &\mathbf x \in \partial\mathbb H \end


Numerical solution

There are various possible techniques to solve the bidomain equations. Between them, one can find finite difference schemes, finite element schemes and also finite volume schemes. Special considerations can be made for the numerical solution of these equations, due to the high time and space resolution needed for numerical convergence.


See also

*
Monodomain model The monodomain model is a reduction of the bidomain model of the electrical propagation in myocardial tissue. The reduction comes from assuming that the intra- and extracellular domains have equal anisotropy ratios. Although not as physiologically ...
*
Forward problem of electrocardiology The forward problem of electrocardiology is a computational and mathematical approach to study the electrical activity of the heart through the body surface. The principal aim of this study is to computationally reproduce an electrocardiogram (EC ...


References

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External links


Scholarpedia article about the bidomain model
Cardiac electrophysiology Electrophysiology Differential equations Partial differential equations Mathematical modeling Numerical analysis