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DOI: 10.1007/s10439-009-9873-0
AbstractThis paper deals with the numerical simulation of Despite that, the clinical signicance of some ECG
electrocardiograms (ECG). Our aim is to devise a mathe- ndings is still not fully understood. Computer based
matical model, based on partial differential equations, which simulations of the ECG, linking models of the electri-
is able to provide realistic 12-lead ECGs. The main ingredi-
ents of this model are classical: the bidomain equations cal activity of the heart (in normal or pathological
coupled to a phenomenological ionic model in the heart, and condition) to the ECG signal, can therefore be a
a generalized Laplace equation in the torso. The obtention of valuable tool for improving this knowledge. Such an
realistic ECGs relies on other important featuresincluding ECG simulator can also be useful in building a virtual
hearttorso transmission conditions, anisotropy, cell hetero- data base of pathological conditions, in order to test
geneity and His bundle modelingthat are discussed in
detail. The numerical implementation is based on state- and train medical devices.16 Moreover, being able to
of-the-art numerical methods: domain decomposition tech- simulate realistic ECGs is a necessary step toward the
niques and second order semi-implicit time marching development of patient-specic models from clinical
schemes, offering a good compromise between accuracy, ECG data.
stability and efciency. The numerical ECGs obtained with The mathematical modeling of the ECG is known as
this approach show correct amplitudes, shapes and polarities,
in all the 12 standard leads. The relevance of every modeling the forward problem of electrocardiography.32 It relies
choice is carefully discussed and the numerical ECG sensi- on three main ingredients: a model for the electrical
tivity to the model parameters investigated. activity of the heart, a model for the torso (extracar-
diac regions) and some specic hearttorso coupling
Keywords12-Lead electrocardiogram, Mathematical mod- conditions. Within each of these components, several
eling, Numerical simulation, Bidomain equation, Ionic options are possible, with different levels of complexity
model, Hearttorso coupling, Monodomain equation, Sen- and realism (see Lines et al.32 for a recent compre-
sitivity analysis. hensive review).
Although many works have been devoted to the
numerical simulation of cardiac electrophysiology (see
INTRODUCTION e.g. the monographs44,47,51 and the references therein),
only a small number28,30,32,41,43,54 addresses the
The electrocardiogram (ECG) is a noninvasive numerical simulation of ECGs using a whole-heart
recording of the electrical activity of the heart, reaction-diffusion (i.e. bidomain or monodomain)
obtained from a standard set of skin electrodes and model. Among them, only a very few41,43 provide
presented to the physician as the 12-lead ECG: i.e., meaningful simulations of the complete 12-lead ECG.
12 graphs of the recorded voltage vs. time. The ECG These simulations rely on a monodomain description of
can be considered as the most widely used clinical tool the electrical activity of the heart, a decoupling of the
for the detection and diagnosis of a broad range of heart and the torso (isolated heart assumption) and a
cardiac conditions (see e.g. Aehlert,1 Goldberger24). multi-dipole approximation of the cardiac source within
the torso (see Sect. 4.2.4 in Lines et al.,32 and Gulra-
Address correspondence to Miguel A. Fernandez, INRIA, CRI
jani26). To the best of our knowledge, none of the
Paris-Rocquencourt, Rocquencourt BP 105, 78153 Le Chesnay existing approaches based on partial differential equa-
Cedex, France. Electronic mail: miguel.fernandez@inria.fr tions (PDE) and a fully coupled hearttorso formulation
(see e.g. Sect. 4.6 in Lines et al.,32 and Sundnes et al.51) and the coupled system of partial and ordinary dif-
have shown realistic 12-lead ECG simulations. ferential equations (PDE/ODE) involved in the refer-
The main ingredients of our mathematical ECG ence mathematical model considered in this paper.
model are standard (see e.g. Lines et al.,32 Pullan
et al.,44 Sundnes et al.51): bidomain equations and
Heart Tissue
phenomenological cell model for the heart, and a
generalized Laplace equation for the torso. Neverthe- Our reference model for the electrical activity of the
less, once these ingredients have been chosen, several heart is the so-called bidomain model.44,51,55 This
other critical aspects have to be elucidated: hearttorso macroscopic model is based on the assumption that, at
transmission conditions, cell heterogeneity, His bundle the cell scale, the cardiac tissue can be viewed as par-
modeling, anisotropy, etc. titioned into two ohmic conducting media, separated
The purpose of the present work is therefore twofold: by the cell membrane: intracellular, made of the car-
rst, provide realistic simulations of the 12-lead ECG diac cells, and extracellular which represents the space
based on a complete PDE model with a fully coupled between them. After an homogenization process (see
hearttorso formulation; second, discuss through Neu and Krassowska,37 Pennacchio et al.39), the intra-
numerical simulations the impact of various modeling and extracellular domains can be supposed to occupy
options and the sensitivity to the model parameters. the whole heart volume XH (this also applies to the cell
Note that the achievement of these two goals is a fun- membrane). Hence, the averaged intra- and extracel-
damental step prior to addressing the inverse problem of lular densities of current, ji and je ; conductivity tensors,
electrocardiography, which consists in identifying the ri and re ; and electric potentials, ui and ue, are dened
ECG model parameters from clinical ECG data. in XH. The electrical charge conservation becomes
The numerical methods proposed to solve the prob-
divji je 0; in XH ; 2:1
lem oer a good balance between eciency, stability
and accuracy. The PDE system made of the heart and and the homogenized equation of the electrical activity
torso models is solved using a nite element method and of the cell membrane is given by
a second order semi-implicit time marching scheme (see
e.g. Quarteroni et al.45). The coupling conditions at @Vm
Am Cm Iion Vm ; w divji Am Iapp ; in XH ;
the hearttorso interface are enforced by a Dirichlet- @t
Neumann domain decomposition algorithm (see e.g. 2:2
Quarteroni and Valli,46 Toselli and Widlund53).
complemented with the Ohms laws
The remainder of this paper is organized as follows.
The ECG model equations are presented in Model- ji ri rui ; je re rue : 2:3
ing section. The section Numerical Methods is
devoted to the description of the numerical algorithm. Here, Vm stands for the transmembrane potential,
The numerical ECGs obtained with the resulting dened as
computational model, under a healthy and a patho- def
V m ui ue ; 2:4
logical (bundle branch block) condition, are presented
and discussed in Numerical Results section. The Am is a constant representing the rate of membrane
section Impact of Some Modeling Assump- area per volume unit and Cm the membrane capaci-
tions investigates the impact, on the ECG, of various tance per area unit. The term Iion(Vm, w) represents the
modeling assumptions: hearttorso uncoupling, mon- ionic current across the membrane and Iapp a given
odomain approximation, isotropy, cell homogeneity, applied current stimulus. Both currents are measured
resistancecapacitance behavior of the pericardium. In per membrane area unit.
Numerical Investigations with Weak HeartTorso In general, the ionic variable w (possibly vector
Coupling section, we present a time and space con- valued) satises a system of ODE of the type:
vergence study in terms of the ECG. The sensitivity of
@w
the ECG to the main model parameters is also inves- gVm ; w 0; in XH : 2:5
tigated. At last, conclusions and some lines of forth- @t
coming research are drawn in Conclusion section. The denition of the functions g and Iion depends on the
considered cell ionic model (see Pullan et al.,44 Sundnes
et al.,51 Tung,55 and the references therein). According
MODELING to their degree of complexity and realism, the ionic
models typically fall into one of the following categories
This section contains standard material (see e.g. (see Chapter 3 in Pullan et al.44): phenomenological
Chapter 2 in Sundnes et al.51). It introduces notation (e.g. Fenton and Karma,18 Fitzhugh,19 Mitchell and
Mathematical Modeling of Electrocardiograms
Schaeffer,36 and van Capelle and Durrer56) or physio- Neu,31 Pullan et al.,44 Sundnes et al.,51 and Tung55)
logical (e.g. Beeler and Reuter,4 Djabella and Sorine,15 that the intracellular current does not propagate out-
Luo and Rudy,33,34 and Noble et al.38). side the heart. Consequently,
In this study, the phenomenological two-variable
ji n ri rui n 0; on R;
model proposed by Mitchell and Schaeer36 is con-
sidered (rescaled version). The functions g and Iion are where n stands for the outward unit normal to XH.
then given by Equivalently, and owing to the divergence structure of
(2.7)1, this condition can be enforced as
w Vm Vmin 2 Vmax Vm
Iion Vm ; w ri rVm n ri rue n 0; on R: 2:9
sin Vmax Vmin
1 Vm Vmin
;
sout Vmax Vmin
( w Coupling with Torso
1
sopen s V V 2
if Vm <Vgate ;
gVm ; w w
open max min
To set up boundary conditions on the extracellular
sclose if Vm >Vgate ; potential ue, a perfect electric transmission between the
2:6 heart and the torso domains is generally assumed (see
e.g. Krassowska and Neu,31 Pullan et al.,44 Sundnes
where sin, sout, sopen, sclose, Vgate are given parameters et al.,51 and Tung55):
and Vmin, Vmax scaling constants (typically 80 and
20 mV, respectively). ue uT ; on R;
2:10
Despite its reduced complexity (2 state variables, 5 re $ue n rT $uT n; on R:
free parameters), the Mitchell-Schaeer model inte-
Here, uT and rT stand respectively for the potential
grates relevant physiological properties of the cell mem-
and conductivity tensor of the torso tissue, denoted by
brane: transmembrane potential, activation dynamics
XT (see Fig. 1). Note that, with (2.9), the current conti-
and two currents (inward and outward) leading to
nuity condition (2.10)2 is consistent with the divergence
depolarization and repolarization. Moreover, owing to
structure of (2.7)2. Other possible hearttorso trans-
its planar character, the model can be understood ana-
mission conditions will be discussed in HeartTorso
lytically (see e.g. Mitchell and Schaeer36), which allows
to identify how the free parameters affect its behavior
(see Cell Heterogeneity section).
The gate variable w depends on the change-over
voltage Vgate and on the time constants for opening,
sopen, and closing, sclose. The time constants sin and
sclose are respectively related to the length of the
depolarization and repolarization (nal stage) phases.
Typically, these constants are such that sin
sout sopen, sclose.
To sum up, the system of equations modeling the
electrical activity within the heart is
8
>
> Am Cm @V m
Iion Vm ; w
< @t
divri $Vm divri $ue Am Iapp ; in XH ;
> divri re $ue divri $Vm 0; in XH ;
>
: @w
@t gVm ; w 0; in XH ;
2:7
with g and Iion given by (2.6). This system has to be
complemented with appropriate initial and boundary
conditions. Denoting by V0m and w0 given initial data
for the transmembrane potential and the gate variable,
the following initial condition must be enforced
Vm x; 0 V0m x; wx; 0 w0 x 8x 2 XH : 2:8
def
As regards the boundary conditions on R @XH (see FIGURE 1. Geometry description: the heart domain XH and
Fig. 1), it is widely assumed (see e.g. Krassowska and the torso domain XT (extramyocardial regions).
BOULAKIA et al.
Uncoupling and Capacitive and Resistive Effect of setting ue ujXH and uT ujXT : Note that this weak
the Pericardium sections. formulation (3.13) integrates, in a natural way, the
Under the quasi-static assumption,35 the torso can coupling conditions (2.10).
be viewed as a passive conductor. Therefore, the The space semi-discretized formulation is based
potential uT satises the generalized Laplace equation: on (3.13) and obtained by replacing the functional
spaces by nite dimensional spaces of continu-
divrT ruT 0; in XT : 2:11
ous piecewise afne functions, Vh H1 XH and
This equation is complemented with a boundary Wh H1 X:
def
condition on the external boundary Cext @XT n R The resulting system is discretized in time by com-
(see Fig. 1). Moreover, assuming that no current can bining a second order implicit scheme (backward dif-
ow from the torso across Cext, we enforce ferentiation formulae, see e.g. Quarteroni et al.45) with
an explicit treatment of the ionic current. We refer to
rT ruT nT 0; on Cext ; 2:12
Ethier and Bourgault17 for a recent review which
where nT stands for the outward unit normal to XT. suggests the use of second order schemes. Let N 2 N
In summary, our reference model for the ECG is be a given integer and consider a uniform partition
def
based on the coupled solution of systems (2.7), (2.6) and ftn ; tn1 g0nN1 ; with tn ndt; of the time interval of
def
(2.11), completed with the boundary conditions (2.9) interest [0, T], with a time-step dt T=N: Denote by
n n n
and (2.12), the interface conditions (2.10) and the initial Vm ; u ; w the approximated solution obtained at
condition (2.8). Throughout this study, this system of time tn. Then, Vn1 m ;u
n1
; wn1 is computed as fol-
equations will be termed RM (reference model), which is lows: For 0 n N 1
also known in the literature as full bidomain model (see en1 def n
1. Second order extrapolation: V m 2Vm
e.g. Clements et al.9). The interested reader is referred to n1
Vm ;
Boulakia et al.7 for a recent study on the mathematical 2. Solve for wn+1 2 Vh:
well-posedness of this system, under appropriate
assumptions on the structure of Iion and g. 1 3 n1 n 1 n1 en1 ; wn1 0;
w 2w w gVm
Although additional complexity and realism can dt 2 2
still be introduced through the ionic model (see e.g. (nodal-wise);
Beeler and Reuter,4 Djabella and Sorine,15 Luo and
Rudy,33,34 and Noble et al.38), this coupled system can 3. Ionic current evaluation: I en1 ; wn1 ;
V
be considered as the state-of-the-art in the PDE/ODE n1 n1 ion m
4. Solve
R for Vm ; u 2 Vh Wh ; with
modeling of the ECG (see e.g. Lines et al.32). u n1
0:
XH
8 R Cm 3 n1 n 1 n1
NUMERICAL METHODS >
> A m V m 2V m Vm /
>
>
XRH dt 2 n1 n1
2
>
> XH ri $ Vm u $/
This section is devoted to a brief presentation of the < R
Am XH Iapp tn1 Iion V en1 ; wn1 /;
numerical method used to solve the coupled problem RM. >
> R R
m
>
> $u n1
n1
>
> ri r e $w XH ri $Vm $w
: XRH
Space and Time Discretization XT rT $un1 $w 0;
un1;k1
T un1;k
e ; on R; Anatomical Model and Computational Meshes
R n1;k1
XT rT ruT rwT 0; 8wT 2 Zh;0 : The torso computational geometry (see Fig. 2),
including the lung and main bone regions, was
Heart-bidomain solution (Neumann):
obtained starting from the Zygote (http://www.
8 R Cm 3 n1;k1
> Am XH dt 2 Vm 2Vnm 12 Vn1 / 3dscience.com) modela geometric model based on
>
> m
>
> R d actual anatomical datausing the 3-matic (http://
>
> XH ri $ Vn1;k1 uen1;k1
$/
>
> m www.materialise.com) software to obtain computa-
<
R tionally-correct surface meshes. The heart geometry is
A I t I en1 ;wn1 /;
V
>
>
m XH app n1 ion m simplied, based on intersecting ellipsoids, so that the
>
> R R
>
> d
n1;k1 bers orientation can be parametrized in terms of
>
> XH ri re $ue $we XH ri $Vn1;k1
m $we
>
: R n1;k1 analytical functions. We refer to Sermesant et al.49 for
XT rT $uT $Lwe ; the details of the geometrical denition of the heart.
3:15 Note that this simplied geometry only includes the
BOULAKIA et al.
ventricles. We therefore cannot simulate the P-wave of conductivity coefcients in the intra- and extra-cellular
the ECG. media measured along the bers direction and in the
The 3D computational meshes of the torso and the transverse direction. Different conductivities values are
heart are displayed in Figs. 2 and 3. They have been available in the literature (see e.g. Clements et al.,9
obtained by processing the surface meshes with the Malmivuo and Plonsey,35 Sundnes et al.51). The values
softwares Yams21 and GHS3D.22 used in our simulations, originally reported in Potse
et al.,42 are given in Table 1. As mentioned above, the
Heart Conductivity bers directions have been set as in Sermesant et al.49
Cardiac muscle is made of bers. The electrical
Torso Conductivity
conductivity is higher along the ber direction than
along the cross-ber direction. The intracellular and We assume that the torso has isotropic conductivity,
extracellular media are therefore anisotropic. This i.e. rT is diagonal rT rT I; and that the scalar het-
anisotropy is included in our model dening the con- erogeneous conductivity rT takes three different
ductivity tensors ri and re by: values:
8
def
ri;e x rti;e I rli;e rti;e ax ax; 4:16 < rlT lungs;
rT rbT ; bone;
: t
where ax is a unit vector parallel to the local ber rT ; remaining regions,
direction (Fig. 3) and rli;e and rti;e are respectively the
given in Table 2.
FIGURE 3. Computational heart mesh (left) and heart fiber directions (right).
Mathematical Modeling of Electrocardiograms
rise to the thin Purkinje bers in the ventricular mus- instance: between base and apex, between septal and
cle. The activation travels from the His bundle to the posterior sides, and transmurally (see e.g. Franz
ventricular muscle in about 40 ms. Interesting attempts et al.20). Although not yet fully explained (see e.g.
at modeling the His bundle and the Purkinje bers Conrath and Opthof,13 for a review), experimental
have been presented in the literature (see e.g. Vigmond evidence2,20,27,59 suggests that transmural APD heter-
and Clements57). But a physiological model of this fast ogeneity is likely to be the most important factor in the
conduction network coupled to a 3D model of the genesis of the normal ECG T-wave shape and polarity.
myocardium raises many modeling and computational A number of simulation studies5,14,30,40,41 conrm also
difculties: the ber network has to be manually this (still debated) postulate. Interestingly, the numer-
dened whereas it cannot be non-invasively obtained ical investigations recently reported in Colli Franzone
from classical imaging techniques; the results are et al.11 (using a highly idealized geometry) indicate that
strongly dependent on the density of bers which is a the polarity of the T-wave (for unipolar ECG leads)
quantity difcult to determine; the time and the space may be mainly driven by the cardiac tissue anisotropy.
scales are quite different in the fast conduction net- In the present work, cell heterogeneity is only
work and in the rest of the tissue which can be chal- considered as transmural variation of APD in the left
lenging from the computational standpoint. ventricle. Hence, we assume that epicardial cells have
To circumvent these issues, we propose to roughly the shortest APD and that endocardial cells have an
model the Purkinje system by initializing the activation intermediate APD between mid-myocardial cells
with a (time-dependent) external volume current, acting (M-cells) and epicardial cells (see e.g. Yan and
on a thin subendocardial layer (both left and right Antzelevitch59). From the analysis reported in Sect.
parts). The propagation speed of this initial activation is 3.1 in Mitchell and Schaeffer,36 the leading order of
a parameter of the model (see the details in Appendix). the maximum APD provided by the Mitchell-Scha-
Although this approach involves a strong simplication effer ionic model (2.6) is proportional to the param-
of the reality, it allows a simple and quite accurate eter sclose. Thus, the APD heterogeneity is modeled
control of the activation initialization, which is a fun- with a parameter sclose varying across the left ven-
damental aspect in the simulation of correct ECGs. tricle transmural direction: sendo close near the endocar-
dium, smcell
close in the mid-myocardium (M-cells) and
sepi
close near the epicardium (see Fig. 4). For simplicity,
Cell Heterogeneity we take a constant value of sRV in the whole right
close
Action potential duration (APD) heterogeneity ventricle. The values of the parameters are given in
may be found at dierent myocardium locations, for Table 3.
FIGURE 4. Transmural APD heterogeneity: comparison of the simulated transmembrane potentials for endocardial cells (green),
M-cells (red) and epicardial cells (blue). Snapshots of the transmembrane potential at times t 5 60 and 300 ms.
Results
The ECGs are computed according to the standard
12-lead ECG denition (see Malmivuo and Plonsey,35
for instance):
def def
I uT L uT R; II uT F uT R;
def
III uT F uT L;
def 3 def 3
aVR uT R uW ; aVL uT L uW ; 4:17
2 2
def 3
aVF uT F uW ;
2
def
Vi uT Vi uW i 1; . . . ; 6;
def
where uW uT L uT R uT F=3 and the body
surface electrode locations L, R, F, fVi gi1;...;6 are
indicated in Fig. 5.
The simulated ECG obtained from RS is reported in
Fig. 6. Some snapshots of the corresponding body
surface potential are depicted in Fig. 7. Compared to a
physiological ECG, the computed ECG has some minor
aws. First, the T-wave amplitude is slightly lower than
expected. Second, the electrical heart axis (i.e. the mean
FIGURE 5. Torso domain: ECG leads locations. frontal plane direction of the depolarization wave
FIGURE 6. Reference simulation: 12-lead ECG signals obtained by a strong coupling with the torso, including anisotropy and
APD heterogeneity. As usual, the units in the x- and y-axis are ms and mV, respectively.
Mathematical Modeling of Electrocardiograms
FIGURE 7. Reference simulation: some snapshots of the body surface potentials at times t 5 10, 47, 70, 114, 239 and 265 ms
(from left to right and top to bottom).
traveling through the ventricles during ventricular cavity. Third, in the precordial leads, the R-wave pre-
activation) is about 40 whereas it should be between sents abnormal (low) amplitudes in V1 and V2 and the
0 and 90 (see e.g. Aehlert1). This is probably due to a QRS complex shows transition from negative to posi-
too horizontal position of the heart in the thoracic tive polarity in V4 whereas this could be expected in V3.
BOULAKIA et al.
Despite that, the main features of a physiological The results are reported in Fig. 8 (RBBB) and 9
ECG can be observed. For example, the QRS-complex (LBBB). As in the healthy case, an expert would
has a correct orientation and a realistic amplitude in detect some aws in these ECGs. For example, he
each of the 12 leads. In particular, it is negative in lead V1 would expect a larger QRS and a lead V1 without
and becomes positive in lead V6. Moreover, its duration Q-wave. Nevertheless, he would also recognize the
is between 80 and 120 ms, which is the case of a healthy main features that indicate the bundle branch blocks
subject. The orientation and the duration of the T-wave (see e.g. Malmivuo and Plonsey35). First, the QRS-
are also satisfactory. To the best of our knowledge, this complex exceeds 120 ms in both cases. Second, it can
12-lead ECG is the most realistic ever published from a be seen in Fig. 8 that the duration between the
fully based PDE/ODE 3D computational model. beginning of the QRS complex and its last positive
wave in V1 exceeds 40 ms which is a sign of RBBB.
Third, it can be seen in Fig. 9 that the duration
Pathological Simulations
between the beginning of the QRS complex and its
In this paragraph, we modify the reference simula- last positive wave in V6 exceeds 40 ms which is a sign
tion that provided the healthy ECG (Fig. 6) in order of LBBB. It is noticeable that these results have been
to simulate a right or a left bundle branch block obtained without any recalibration of the RS, besides
(RBBB or LBBB). The purpose is to test whether the the above mentioned (natural) modications needed
ECG produced by our model possesses the main to model the disease.
characteristics that allow a medical doctor to detect
these pathologies.
In the RS, the right and the left ventricle are acti- IMPACT OF SOME MODELING ASSUMPTIONS
vated simultaneously. Now, in order to simulate a
LBBB (resp. a RBBB) the initial activation is blocked In this section, the impact of some alternative
in the left (resp. right) ventricle. modeling assumptions on the simulated ECG is
investigated. This allows to assess to what extent the Thereafter, the torso potential uT is recovered by
modeling assumptions involved in the RS are necessary solving (2.11) with
to obtain a meaningful ECG.
uT ue ; on R;
: 5:20
rT $uT nT 0; on Cext ;
HeartTorso Uncoupling as boundary conditions. In other words, the uncoupled
A common approach to reduce the computational heart potential ue is transferred, from XH to XT,
complexity of the RM consists in uncoupling the through the interface R (see Barr et al.,3 Shahidi
computation of (Vm, ue) and uT. This can be achieved et al.50).
by neglecting, in (2.10), the electrical torso feedback on
the cardiac region. That is, by replacing the coupling Remark 5.1 Rather than interface based, as (5.20),
condition (2.10)2 by most of the uncoupled approaches reported in the
literature are volume based (see Sect. 4.2.4 in Lines
re rue n 0; on R; 5:18 et al.,32 for a review). Thus, the torso potentials are
generated by assuming a (multi-)dipole representation
which amounts to work with an isolated heart domain
of the cardiac source, typically based on the
(see e.g. Clements et al.,9 Potse et al.42).
transmembrane potential gradient rVm (see e.g.
As a result, the intracardiac quantities (Vm, ue)
Gulrajani,26 Pullan et al.44).
can be obtained, independently of uT, by solving
From the numerical point of view, the hearttorso
(2.7) with initial condition (2.8) and insulating con-
uncoupling amounts to replace Step 4, in Space and
ditions
Time Discretization section, by:
ri $Vm n ri $ue n 0; on R;
Solving Vn1 n1
5:19 R for m ; ue 2 Vh Vh ; with
re $ue n 0; on R: n1
0:
X H ue
BOULAKIA et al.
8 R
> Am XH Cdtm 32 Vn1 2Vnm 12 Vn1 / substantial increasing in epicardial potentials magni-
>
> R m
n1 m
>
< n1 tude were observed when the heart surface was exposed
i $ Vm u
XH r $/
R to insulating air. Thus, considering an uncoupled for-
>
> Am XH Iapp tn1 Iion V en1 ; wn1 /;
> m mulation can be reasonable to get a qualitatively correct
>R
: n1
R
XH ri re $ue $we XH ri $Vn1 m $we 0;
ECGs, in the sense that some important features of the
R ECGsfor example, the QRS or the QT intervalsare
for all /; we 2 Vh Vh ; with XH we 0: the same as in the fully coupled case. This observation is
Then, once fun1 the basis of the numerical study reported in Numerical
e g0nN1 are available, the torso
potential is obtained by solving, for un1 2 Zh ; Investigations with Weak HeartTorso Coupling sec-
T
tion using hearttorso uncoupling. Nevertheless,
un1
T un1
e ; on R; Fig. 11 shows that both amplitude and shape can differ
Z in some cases. The uncoupling assumption has therefore
5:21
rT run1
T rwT 0; 8wT 2 Zh;0 : to be considered with caution. Similar conclusions are
XT
given in Page 315 in Pullan et al.44 (see also Sect. 4.3 in
The remainder of this section discusses the impact of Lines et al.32), by comparing the surface potentials, on a
the uncoupled approach on ECG accuracy and com- 2D torso slice, obtained with a multi-dipole represen-
putational cost. tation of the cardiac source (see Remark 5.1).
FIGURE 10. Comparison of the simulated healthy ECGs obtained using hearttorso uncoupling (top) and fully hearttorso
coupling (bottom).
Mathematical Modeling of Electrocardiograms
FIGURE 11. Comparison of the simulated RBBB ECGs obtained using hearttorso uncoupling (top) and fully hearttorso cou-
pling (bottom).
def
potential are partitioned as xT xT;I ; xT;R 2 RnI nR ; evaluating Tei for i = 1, , nR, where ei denotes the i-th
where xT;R denotes the hearttorso interface DOF and canonical vector of RnR : But each of these evaluations
xT;I the remaining DOF. We denote by xejR 2 RnR the involve the solution of system (5.23) with xejR ei ; and
extracellular potential DOF at the hearttorso inter- therefore the overall computational cost is proportional
face R. Finally, we assume that the 9 potential values to nR, which can be rather expensive (remember that nR
generating the ECG (see Results section), say is the number of nodes on the hearttorso interface, and
xECG 2 R9 ; are obtained from the discrete torso is therefore of the order of several thousands). In con-
potential xT in terms of an interpolation operator trast, a computation by row is much more efcient since
P 2 R9nI ; so that it is only needed to evaluate TT ei for i = 1, , 9, where
ei stands for the i-th canonical vector of R9 : From the
xECG PxT;I ; 5:22
symmetry of the nite element matrix,
for instance, P can be a nodal value extraction of xT;I :
On the other hand, from (5.21), the discrete torso TT ATIR AT T 1 T
II P ARI AII P :
potential xT is solution to the following nite element Therefore, the matrix-vector product evaluation
linear system:
TT ei ARI A1 T
5:24
AII AIR xT;I 0 II P ei ;
: 5:23 |
{z}
0 IRR xT;R xejR xT;I
Hence, by Gaussian elimination, we have that xT;I can be performed in two steps as follows. First, solve
A1
II AIR xejR ; and by inserting this expression in (5.22),
for xT;I ; xT;R the discrete source problem (depending
we obtain on the linear operator P), with homogeneous Dirichlet
boundary condition on R:
xECG PA1 II AIR xejR :
t
def T xT;I
with T PA1 II AIR :
T ei ARI xT;I ARI ARR
xT;R
:
There are dierent solutions to compute T: The naive
idea consisting of computing the matrix A1 II is of course Note that, TT ei is nothing but the discrete current ux
ruled out. A reasonable and natural option is to com- through the hearttorso interface R, associated to the
pute matrix T by column (see Shahidi et al.50), i.e. by homogeneous Dirichlet condition in (5.25).
BOULAKIA et al.
In this paper, all the numerical ECGs based on et al.,12 without any assumptions on the anisotropy
the uncoupling conditions (5.19)(5.20) have been ratio of the intra- and extracellular conductivities. The
obtained using the matrix T presented in this para- impact of this approximation on the simulated ECG is
graph (and this matrix has been computed by row). then illustrated in Numerical Results with Heart
Torso Uncoupling section, using the hearttorso
Remark 5.2 If the operator P is a simple extraction uncoupling simplication.
of nodal values from the torso potential DOF, xT ; each
evaluation TT ei ; for i = 1, , 9, can be (formally) The Monodomain Approximation
interpreted at the continuous level as a current ux
evaluation at R of the problem We assume that the intra- and extracellular local
8 conductivities rl;t l;t
i and re are homogeneous (constant
< divrT $v dxi ; in XT ; def
v 0; on R; in space). Let j ji je be the total current, owing
: def
rT $v nT 0; on Cext ; into XH, and r ri re be the bulk conductivity
tensor of the medium.
with dxi the Diracs delta function at the i-th point, xi ;
From (2.3) and (2.4), j ri $ui re $ue
of torso potential recording on Cext.
ri $Vm r$ue ; or, equivalently,
Remark 5.3 Note that the transfer matrix T can be $ue r1 ri $Vm r1 j: 5:26
computed off-line, since it depends neither on time
nor on solution in the heart. Nevertheless, this matrix By inserting this expression in (2.7)1 and (2.9), we
has to be recomputed when the torso conductivities are obtain
8
modied or when dealing with dynamic torso meshes. < Am Cm @V Vm ; w div ri I r1 ri $Vm
@t Iion1
m
FIGURE 12. Simulated normal ECG with hearttorso uncoupling: monodomain (top) and bidomain (bottom) models.
FIGURE 13. Simulated ECG for a RBBB pathology with hearttorso uncoupling: monodomain (top) and bidomain (bottom)
models.
much more striking when dealing with pathological Meaningful ECG simulations have therefore to incor-
activations. In Fig. 16, for instance, the simulated porate this modeling feature (see also Colli Franzone
ECG signals for a RBBB pathology have been et al.11).
reported with anisotropic and isotropic conductivities.
Notice that the electrical signal is signicantly dis-
Cell Homogeneity
torted. In particular, the amplitude of the QRS com-
plex is larger in the isotropic case (this observation also As mentioned in Cell Heterogeneity section, an
holds in the healthy case). heterogeneous coefcient sclose has been considered in
These numerical simulations show that anisotropy RS to incorporate an APD gradient across the left
has a major impact on the accuracy of ECG signals. ventricle transmural direction. In this paragraph, the
Mathematical Modeling of Electrocardiograms
myocardium is assumed to have homogeneous cells. present a similar polarity, irrespectively of the ADP
The ECG signals corresponding to a constant APD in heterogeneity (see also Colli Franzone et al.11).
the whole heart, obtained with sclose = 140 ms, are As a result, as also noticed in Boulakia et al.,5 Keller
reported in Fig. 17. et al.,30 and Potse et al.,40,41 transmural APD hetero-
Note that now, in the bipolar lead (I), the T-wave geneity is a major ingredient in the simulation of a
has an opposite polarity with respect to the RS and to complete 12-lead ECG with physiological T-wave
what is usually observed in normal ECGs. Indeed, polarities.
without transmural APD heterogeneity, the repolari-
zation and the depolarization waves travel in the same
Capacitive and Resistive Eect of the Pericardium
direction, which leads to the discordant polarity,
between the QRS and the T waves, observed in lead I. The coupling conditions (2.10) are formally
On the contrary, the unipolar leads (aVR, V1 and V4) obtained in Krassowska and Neu31 using an homoge-
nization procedure. In that reference, a perfect elec-
trical coupling is assumed between the heart and the
surrounding tissues.
It might be interesting to consider more general
coupling conditions. For instance, by assuming that
the pericardium (the double-walled sac containing the
heart) might induce a resistorcapacitor eect. This
can be a way to model pathological conditions
e.g. pericarditis, when the pericardium becomes
inamedor to take into account the fact that, even in
a healthy situation, the hearttorso coupling can be
more complex. Thus, we propose to generalize (2.10),
by introducing the following resistorcapacitor (RC)
coupling conditions:
Rp rT $uT n Rp Cp @ue@tuT ue uT ; on R;
re $ue n rT $uT n; on R;
5:37
where Cp and Rp stand for the capacitance and resis-
FIGURE 14. First ECG lead: bidomain and monodomain tance of the pericardium, respectively. Note that, the
models with hearttorso uncoupling. classical relations (2.10) can be recovered from (5.37)
FIGURE 15. ECG signals: isotropic conductivities (top), anisotropic conductivities (bottom).
BOULAKIA et al.
FIGURE 16. Isotropic (top) and anisotropic (bottom) conductivities in a pathological case (RBBB).
FIGURE 17. ECG signals: homogeneous action potential duration (top), heterogeneous action potential duration (bottom).
by setting Rp = 0. To the best of our knowledge, the In order to illustrate the resistor eect, we have
resistorcapacitor behavior (5.37) of the pericardium is reported in Fig. 19 the ECG obtained with Cp = 0 mF
not documented in the literature, so we propose to cm2 and Rp = 104 X cm2. We clearly observe that the
study its effect on ECGs through numerical simula- amplitude of the signals is smaller than in the RS.
tions. More generally, this amplitude decreases when Rp
Numerical tests showed that for Rp small (Rp < increases, as expected.
103 X cm2 approximately) or Cp large (Cp > 1 We now focus on the capacitor eect by taking
mF cm2 approximately) the simulated ECG is very Rp very large. Figure 20 presents the ECG sig-
close to the RS. Figure 18, for instance, presents the nals obtained with Rp = 1020 X cm2 and Cp =
ECG signals obtained with Rp = 102 X cm2 and 102 mF cm2. We observe that the capacitive
Cp = 0 mF cm2. term induces a relaxation effect and distorts the signal.
Mathematical Modeling of Electrocardiograms
FIGURE 18. Simulated 12-lead ECG signals: RC hearttorso coupling conditions with Rp 102 X cm2 ; Cp 0 mF cm2 .
In particular, the T-wave is inverted in all the ECG Time and Space Convergence
leads and the S-wave duration is larger than for the
In this section, we are not interested in the conver-
RS. At last, Fig. 21 shows that for very small values of
gence of the whole solution of the RM with respect
Cp the amplitude of the ECG is also very small. This
to the space and time discretization parameters, but
can be formally explained by the fact that, in this
rather in the convergence of the ECG which is here
case, condition (5.37)1 approximately becomes
considered as the quantity of interest.
rT ruT n 0 on R: no heart information is trans-
ferred to the torso, leading to very low ECG signals.
Time Convergence
In Fig. 22, we present the rst ECG lead (lead I)
obtained for three different time-step sizes dt = 0.25,
NUMERICAL INVESTIGATIONS WITH WEAK 0.5 and 2 ms. The l2-norm of the relative difference
HEARTTORSO COUPLING with the result obtained with dt = 0.25 ms is 10%
when dt = 2 ms and 2.0% when dt = 0.5 ms.
In this section, we investigate the ECG sensitivity
to the time and space discretizations and to the heart
Space Convergence
and torso model parameters. To carry out these
studies at a reasonable computational cost, we con- Three dierent levels of renements are considered
sider the hearttorso uncoupling. Although we have for the heart and the torso meshes, as shown in
noticed (in HeartTorso Uncoupling section) that Table 5. The nite element meshes used in the RS are
uncoupling may affect the ECG accuracy in some the R2. In Fig. 23, we report the rst lead of the ECGs
cases, we can expect that the conclusions of the obtained for these simulations.
sensitivity analysis remain still valid under this sim- Although the whole solution might not be fully
plication. converged within the heart, we can observe that the
BOULAKIA et al.
FIGURE 19. Simulated 12-lead ECG signals: RC hearttorso coupling conditions with Rp = 104 X cm2 ; Cp = 0 mF cm2 .
quantity of interestnamely the ECGis almost where e is a small parameter, in our case 106
unaected by the last renement. Therefore, in a goal- e 104 gives a good approximation. Instead of
oriented renement framework, the solution may @ai ECG a1 ; a2 ; . . . ; ap we consider
the normalized
indeed be considered as converged. value ai @ai ECG a1 ; a2 ; . . . ; ap , which allows to com-
pare the sensitivity irrespectively of the parameter
scales. In the next paragraphs, we provide time evo-
Sensitivity to Model Parameters
lution of this scaled derivative, evaluated around the
In this section, we study the sensitivity of ECG to parameters used in the RS. Once more, for the sake of
some model parameters. This is fundamental step prior conciseness, we focus on the rst ECG lead.
to addressing its estimation (see e.g. Boulakia et al.6)
using data assimilation techniques. Ionic Model Parameters
Suppose that a1, a2, , ap are parameters the ECG
depends upon, i.e. In this paragraph, we investigate the sensitivity of
the ECG to the Mitchell-Schaeer parameters. In
ECG ECG a1 ; a2 ; . . . ; ap : Fig. 24, we have reported the normalized derivatives
The ECG sensitivity to parameter ai can then be with respect to sin, sout, sopen or sclose. The high ECG
approximated as sensitivity to sin is clearly visible, particularly during
the QRS-complex. The sensitivity to sout is moderate
both during the depolarization and depolarization
@ai ECG a1 ;a2 ;...;ap
phases. As expected, the sensitivity to sclose is only
ECGa1 ;a2 ;...;1eai ;...;ap ECGa1 ;a2 ;...;ap relevant during repolarization. Interestingly, the sen-
;
eai sitivity to sopen is relatively small. Therefore, this
Mathematical Modeling of Electrocardiograms
FIGURE 20. Simulated 12-lead ECG signals: RC hearttorso coupling conditions with Rp 1020 X cm2 ; Cp 102 mF cm2 .
parameter may be removed (i.e. keep xed) within an At last, we investigate the sensitivity of the ECG to
inverse estimation procedure. the initial activation in the heart (see Appendix). More
precisely, we focus on the sensitivity to the activation
angular velocity 2tpact . The corresponding normalized
Bidomain Model Parameters derivative is reported Fig. 27. As expected, the ECG is
strongly sensitive to this parameter, particularly during
We rst focus on the ECG sensitivity to the local
the depolarization phase.
myocardium conductivities: rte, rle, rti and rli. The
corresponding normalized derivatives are given in
Torso Parameters
Fig. 25. During depolarization (QRS-complex), the
ECG is mainly sensitive to transverse conductivity We nally consider the sensitivity of the ECG to the
(rte, rti ). This can be due to the dominating trans- torso conductivities rlT, rbT and rtT. Note that, in a
mural propagation of the depolarization wave in the hearttorso uncoupling framework, the corresponding
left ventricle (see Fig. 4, left). During repolarization three normalized derivatives are linked by a linear
(T-wave), on the contrary, the ECG shows approxi- relation. Indeed, from (2.11) and (5.20), we have that,
mately the same sensitivity to all the local conduc- for all k 2 R; uT solves
tivities. 8
< divkrT $uT 0; in XT ;
We now pursue our sensitivity analysis, by consid-
u ue ; on R;
ering the parameters Am and Cm. The corresponding : T
krT $uT nT 0; on Cext :
normalized derivatives are given in Fig. 26. We
observe a strong sensitivity to both parameters during In other words,
depolarization. Whereas, during the repolarization
phase, the sensitivity is reduced. uT krlT ; krbT ; krtT uT rlT ; rbT ; rtT : 6:38
BOULAKIA et al.
FIGURE 21. Simulated 12-lead ECG signals: RC hearttorso coupling conditions with Rp 5 1020 X cm2, Cp 5 1024 mF cm22.
Total number
Meshes Heart nodes Torso nodes of tetrahedra
rti and rte. As regards the ECG sensitivity to the with iapp the amplitude of the external applied
ionic model parameters, we have noticed a stimulus,
extreme sensitivity of the QRS-complex to
def 1 if x; y; z 2 S;
the parameter sin and a high sensitivity of the vS x; y; z
T-wave to the parameter sclose. Moreover, we 0 if x; y; z 2j S;
have also observed that the ECG sensitivity to def 1 if t 2 0; tact ;
v0;tact t
the torso conductivity parameters is less sig- 0 if t 2j 0; tact ;
nicant than to the heart model parameters. 8
>
< 1 if atan xx 0
at;
def zz 0
To conclude, our main concern during this study wx; z; t
was to build a model rich enough to provide realistic >
: 0 if atan xx zz0 >at;
0
ACKNOWLEDGMENTS
APPENDIX: EXTERNAL STIMULUS This work was partially supported by INRIA
through its large scope initiative CardioSense3D. The
In order to initiate the spread of excitation within the authors wish to thank Elsie Phe (INRIA) for her work
myocardium, we apply a given volume current density to on the anatomical models and meshes, and Michel
a thin subendocardial layer of the ventricles during a Sorine (INRIA) for valuable discussions regarding, in
small period of time tact. In the left ventricle, this thin particular, the hearttorso transmission conditions.
layer (1.6 mm) of external activation is given by
def
S fx; y; z 2 XH =c1 ax2 by2 cz2 c2 g;
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