Annals of Biomedical Engineering, Vol. 29, pp. 47–59, 2001
00
Printed in the USA. All rights reserved.
An Experimentalist’s Approach to Accurate Localization
of Phase Singularities during Reentry
ANAND N. IYER and RICHARD A. GRAY
Department of Biomedical Engineering, University of Alabama at Birmingham, 1670 University Blvd.,
Volker Hall B 140, Birmingham, AL
(Received 30 December 1999; accepted 27 October 2000)
Abstract—A phase variable that uniquely represents the time
course of the action potential has been used to study the
mechanisms of cardiac fibrillation. A spatial phase singularity
共PS兲 occurs during reentrant wave propagation and represents
the organizing center of the rotating wave. Here, we present an
error analysis to investigate how well PSs can be localized.
Computer simulations of rotating spiral waves scaled appropri-
ately for cardiac tissue were studied with various levels of
noise added. The accuracy in identifying and localizing singu-
larities depended on three factors: 共i兲 the point chosen as the
origin in state space used to calculate the phase variable; 共ii兲
signal to noise ratio; and 共iii兲 discretization 共number of levels
used to represent data兲. We found that for both simulation as
well as experimental data, there existed a wide range for the
choice of origin for which PSs could be identified. Discretiza-
tion coupled with noise affected this range adversely. However,
there always existed a range for choice of the origin that was
20% or more of the action potential amplitude within which the
accuracy of localizing PSs was better than 2 mm. Thus, a
precise determination of origin was not necessary for accurately
identifying PSs. © 2001 Biomedical Engineering Society.
关DOI: 10.1114/1.1335538兴
Keywords—Spiral wave, Computer simulations, Two state
variable model, BRDR, State space, Optical mapping.
INTRODUCTION
Sudden cardiac death is the major cause of fatalities
in the industrialized world.20 It is believed that ventricu-
lar fibrillation in the form of reentrant spiral waves is the
underlying cause of these deaths.15 Typically, spiral
waves in the whole heart are unstable, causing and sus-
taining fibrillation.16,17 In the past, the phenomenon of
fibrillation has been considered the result of primarily
random events. Only recently, investigators have been
able to show evidence that organization exists during
fibrillation.12,16,26 Still, the mechanisms underlying fibril-
lation remain poorly understood. One approach to under-
stand the mechanisms of cardiac fibrillation is the use of
a cardiac ‘‘phase’’ variable, ␪, which uniquely defines
Address correspondence to Anand N. lyer, 1670 University Blvd.,
Volker Hall B 140, Birmingham, AL 35294-0019. Electronic mail:
ani@crml.uab.edu
47
0090-6964/2001/29共1兲/47/13/$15.
Copyright © 2001 Biomedical Engineering Society
the ‘‘state’’ of a cell at any instant of time.16 Phase maps
关 ␪ (x,y,t) 兴 are obtained by calculating phase at each
instant of time for each recorded site on the heart. A
unique spatial pattern exists near the tip of rotating
waves. The phase at the exact center of rotation is un-
defined, but neighboring sites exhibit a continuous pro-
gression of phase equal to 2␲ around the center. In the
phase maps, this center corresponds to a phase singular-
ity 共PS兲. PSs are a necessary 共but not sufficient兲 condi-
tion for functional reentry in the heart and thus play a
significant role in sustaining cardiac arrhythmias.16,25 A
better understanding of phase and PSs may provide valu-
able insight into the mechanisms of cardiac fibrillation.
However, in order to analyze the phase variable appro-
priately during cardiac arrhythmias, it is necessary to
provide a formal analysis of the phase mapping tech-
nique. In addition, it is essential to quantify the errors
associated with the identification of PSs including the
effect of signal noise.
Here, we test the ‘‘robustness’’ of the accuracy in
localizing PSs using automated algorithms to calculate
phase and identify PSs. How the choice of origin for the
phase transformation, the effect of noise, and the level of
discretization affect the ability to localize PSs are stud-
ied. The algorithms are first applied to computer simu-
lations of stable rotating spiral waves using two state
variable models with parameters chosen such that the
results are appropriately scaled for cardiac tissue. The
algorithms are then tested on stationary and nonstation-
ary spiral waves generated using ionic models, as well as
data from rabbit hearts in tachyarrhythmias, recorded us-
ing current video-imaging technology.
THEORETICAL FORMULATION
Models of Cardiac Tissue
Complex ionic models6,10,19 and simpler two-state
variable models1,4,11,22 共TSVMs兲 of the cardiac cell have
been studied over the years by mathematicians and elec-
trophysiologists to provide a better understanding of the
electrical activity in the heart. Each of these models
48 A. N. IYER and R. A. GRAY

TABLE 1. Values of parameters used for the BAR model

computer simulations.

Parameter Value

a0 ⫺0.84
a1 0.15
a2 0
a3 0
b0 1
b1 ⫺6.75
b2 13.5
b3 ⫺6.75
␶e 1
␶g 33

reproduces some 共but not all兲 features of cardiac cells.

TSVM dynamics are entirely described using two state
variables and thus allow a formal analysis of phase
共which is computed using two variables兲 using the
‘‘true’’ state space. Using TSVMs is also important in
order to form a link between calculating phase from the
true and ‘‘reconstructed’’ state spaces 共described later兲.
TSVMs consist of two differential equations that de-
scribe the dynamics of a fast variable 共e兲, analogous to
the transmembrane potential (V m ) and a slow variable
共g兲, representing recovery. We use a generic representa-
tion of TSVMs. The equations for a single cell are as
follows:
de/dt⫽ 关 F 共 e 兲 ⫺g 兴 / ␶ e ,
共1兲
dg/dt⫽ 关 H 共 e 兲 ⫺g 兴 / ␶ g ,
where F(e)⫽a 0 ⫹a 1 e⫹a 2 e 2 ⫹a 3 e 3 and H(e)⫽b 0
⫹b 1 e⫹b 2 e 2 ⫹b 3 e 3 , ␶ e and ␶ g are the time constants for
the fast and slow variables, respectively.
In the present study, we chose a TSVM by Bär and
Eisworth 共BAR model兲4 and modified the equations to fit
Eq. 共1兲. The parameter values were scaled appropriately
共see Table 1兲 for cardiac tissue. This was done by choos-
ing the diffusion coefficient 共0.6 cm2/s兲 to match that of
cardiac tissue and ensuring that the rotation period of the
spiral wave 共150 ms兲 was within the range observed in
the heart. The time constant of the fast variable was set
to 1 ms so that the conduction speed was appropriate and
the full range of the action potential amplitude was
scaled to range from ⫺80 to 20 mV.
Detailed mathematical models of the ionic currents in
cardiac tissue have been developed. In order to ensure
that the method of calculating phase and localizing PSs
can be applied to cardiac data, we will analyze reentrant
waves generated with an ionic model. In this paper, we
use the Drouhard–Roberge modification9 of the Beeler–
Reuter model6 共BRDR model兲 to generate stationary as
well as nonstationary spiral waves.
FIGURE 1. Representation of one action potential cycle. „a…
State space representation of the action potential „solid line…
using two variables, e and g. The dotted lines are the
nullclines for the FitzHugh model „a TSVM…. The intersection
of the nullclines is called the fixed point. In this case, the
fixed point is stable and is equal to the resting potential.
Phase, ␪, is measured with respect to an origin „ e * , g * … cho-
sen in the state space. Inset shows the fast variable, analo-
gous to transmembrane potential, which is used to represent
the action potential cycle. „b… The true state space „nullclines
denoted by dotted lines… for the BAR model, which has three
fixed points „denoted by diamonds…, only one of which is
stable. Inset shows an action potential obtained using this
model.
True State Space and Phase
Transmembrane potential or e alone is not a unique
measure of the state of the heart. For example, during
one action potential, the transmembrane potential has a
value of ⫺20 mV twice, during both depolarization and
repolarization. However, using two variables to represent
the time course in the true state space diagram 共see Fig.
1兲 can eliminate this duality; each point on the trajectory
has a unique value in state space. In order to utilize a
single variable that can uniquely define the phase of each
action potential, we use a cardiac phase variable, ␪,
which is calculated from two variables. A detailed de-
scription of the calculation of phase is given later.
In the past, phase has most often been defined as the
time elapsed since the last activation or event.25 During
cardiac fibrillation, however, all sites do not undergo
‘‘full-blown’’ action potentials, which makes proper
picking of activation times very difficult. In this work,
 ACCURATE LOCALIZATION
we use a definition for phase that does not depend on
activation time, but instead uses two variables to calcu-
late phase.16 In the case of TSVMs, the two true vari-
ables, e and g, can be used to calculate phase for any site
at any instant of time. To calculate phase, we choose a
point in state space as the origin, denoted by (e * ,g * ),
and make a transformation to a polar coordinate system
in true state space. Phase is calculated as follows:
␪ 共 t 兲 ⫽arctan 2 关 g 共 t 兲 ⫺g * , e 共 t 兲 ⫺e * 兴 . 共2兲
The arctan 2 function returns a value of phase between
⫺␲ and ␲ depending upon the value and signs 共⫹/⫺兲 of
the two input variables.
In order to study the TSVM in two dimensions, we
incorporate a spatial diffusion term to account for the
coupling between cells.21 In the heart, only the fast vari-
able diffuses. Thus, the diffusion term, Dⵜ 2 e 共where D
is the diffusion coefficient in cm2/s and ⵜ 2 is the La-
placian operator兲, is added to the equation for the fast
variable in Eq. 共1兲. This gives us the following equation
for the two-dimensional case:
⳵ e/ ⳵ t⫽ 关 F 共 e 兲 ⫺g 兴 / ␶ e ⫹Dⵜ 2 e,
共3兲
⳵ g/ ⳵ t⫽ 关 H 共 e 兲 ⫺g 兴 / ␶ g .
For a perfectly stable spiral wave 共i.e., rotational sym-
metry兲 the time derivatives of both e and g will be zero
at the exact center of rotation. By setting the left-hand
side of Eq. 共3兲 to zero, one can solve for the values of e
* ,g ideal
and g at the center (e ideal * ); these values will be
different than the fixed point for a single cell due to the
diffusion term. We denote these values as ‘‘ideal’’ be-
cause this is the state we wish to use as the origin for the
transformation to polar coordinates and calculating
phase.
Each site on the heart 共physical space兲 has a value of
e 共activation兲 and g 共recovery兲 at each instant of time.
Over time, the values of e and g for each site go through
a periodic cycle. A single trajectory in state space is
obtained by plotting the ‘‘e’’ and ‘‘g’’ values for each
site/pixel through time. Figure 5共a兲 was obtained by plot-
ting several such trajectories 共from several different sites/
pixels兲. Any point in this state space can be used as the
origin (e * ,g * ) to calculate the instantaneous phase ac-
cording to Eq. 共2兲. But, we cannot pick just any point if
we want an accurate phase map. Why? For stable reen-
try, the phase for each site should progress through ex-
actly 2␲ during each complete rotation, in order to define
phase uniquely. The action potential amplitude of sites
near the center of rotation in a spiral wave is smaller
than those in the periphery. If we pick a random point in
the state space as the origin, this origin may lie within
OF PHASE SINGULARITIES 49
some trajectories and outside others. If any trajectory
does not traverse around the origin, then the phase for
that site does not change by 2␲ during one rotation.
Therefore, for stable reentry, the ideal point for comput-
ing phase should be the one such that all trajectories
traverse around it exactly once during each rotation, i.e.,
* ,g ideal
(e ideal * ). We approximated this ideal state by choos-
ing a state within the smallest trajectory 共i.e., smallest
amplitude oscillations兲 during stable reentry. For a stable
rotating spiral in a TSVM, the state for each site is
defined by a closed loop trajectory in the true state space
diagram during one complete rotation and Fig. 5共a兲
shows trajectories plotted on state space from every site
of the array during stable reentry for the BAR model.
* ,g ideal
The ideal origin (e ideal * ) is within the smallest tra-
jectory, denoted by an arrow.
Calculation of Phase using One Variable
For numerical simulations of TSVMs, we can calcu-
late phase directly from the two state variables, e and g.
However, for experimental data, typically only one vari-
able is recorded. Accordingly, the calculation of phase
and the identification of PSs have been carried out using
one variable.16 This is accomplished using a ‘‘recon-
structed’’ state space, that is topologically equivalent to
the true state space.23 The reconstructed variables can be
obtained for the original time series e(t) as e(t),
⳵ e(t)/ ⳵ (t), ⳵ 2 e(t)/ ⳵ t 2 ... or e(t), e(t⫹ ␶ ), e(t⫹2 ␶ ),...
Here, we use a time delay-embedding technique to cal-
culate phase from a two-dimensional reconstructed state
space. Phase can be calculated as follows:
␪ 共 t 兲 ⫽arctan 2 关 e 共 t⫹ ␶ 兲 ⫺e * ,e 共 t 兲 ⫺e * 兴 . 共4兲
It can easily be seen that the ideal origin in the recon-
* ,e ideal
structed state space will then be (e ideal * ).
Time Delay-Embedding
The reconstructed state space is obtained by plotting
e(t) against a recreated variable, in this case, e(t⫹ ␶ ).
The choice of time-delay 共␶兲 should be such that the
phase trajectories in state space uniquely define the time
course of the action potential. One method is to pick ␶
such that the autocorrelation between e(t) and e(t⫹ ␶ ) is
zero, ensuring that the variables are linearly independent.
In our analysis for the BAR model and for the experi-
mental data, we used this method to choose ␶. However,
Gray and Jalife have shown14 that if the value of ␶ is
greater than the upstroke of the action potential, the
phase loops cross over in state space. For the BRDR
model, using the ‘‘zero autocorrelation method’’ resulted
in a value of ␶ ( ␶ ⫽14 ms) that was larger than the up-
stroke which resulted in phase loops crossing over as
50 A. N. IYER and R. A. GRAY

shown in Fig. 2共a兲. When this occurs, phase cannot be

defined uniquely. Figure 2共b兲 shows the phase loop for
the same data for ␶ ⫽2. Thus, we chose a value of ␶ that
was equal to the upstroke 共␶ ⫽2 ms for the BRDR
model兲.

Spatial Phase Singularities

A phase map shows the instantaneous value of phase
at each site of the spiral wave. Phase maps 关 ␪ (x,y,t) 兴
can be obtained by using Eqs. 共2兲 or 共4兲 to calculate
phase at every site 共x,y兲 of the spiral wave for each
instant of time. A snapshot of the spiral wave generated
using the BAR model and its corresponding phase map
are shown in Fig. 3; phase was computed using the ideal
origin from reconstructed state space.
A spatial PS occurs at a site where all phase values
converge. Specifically, a PS occurs when the line integral
of the change of phase around a site equals ⫾2␲ where
the sign indicates chirality. The mathematical definition
of a PS is

冖 “ ␪"dr⫽⫾2 ␲ . 共5兲

This definition of the PS is used in an automated algo-

rithm that identifies the locations of PSs from a phase
map. A schematic representation of the algorithm for
identifying a PS is given in Fig. 4. The PS-finding algo-
rithm evaluates the difference in phase over a discrete
path. If the phase difference is equal to ⫾2␲, the path
encloses a PS. The path length can be varied, however,
smaller path lengths are desirable for precision in local-
izing PSs. Here, we used a path length of eight pixels,
which will identify 4 pixels that satisfy the condition for
a PS 关Eq. 共5兲兴 if one exists, and the PS lies at the
common junction of these four pixels 共‘‘䊉’’ in Fig. 4兲.
METHODS
Model Simulations
The algorithms and software were implemented using
PV-Wave version 6.10 共Visual Numerics兲 software. A
100⫻100-element array was used for the TSVM simu-
lations. A 200⫻200-element array was used to simulate
spiral waves using the BRDR model, but the data was
spatially averaged to result in a 100⫻100 array. A spa-
tial discretization 共dx兲 of 0.25 mm and a temporal dis-
cretization 共dt兲 of 0.01 ms were used for all simulations
and the data were sampled every 1 ms. The diffusion
coefficient 共D兲 for all models was 0.6 cm2/s. No-flux
boundary conditions were imposed. For the BAR model
parameters were chosen to ensure stable rotation 共values
are given in Table 1兲; the rotation period was 152 ms
similar to that observed in cardiac tissue.2,17,22 For the
FIGURE 2. Choice of ␶. „a… For a value of ␶ Ä14 ms, three
phase loops, drawn for the BRDR model, crossover in recon-
structed state space. When this occurs, phase does not
uniquely define every portion of the action potential cycle.
v „ t … denotes time course of transmembrane potential and
v „ t ¿ ␶ … denotes the recreated variable. „b… For a value of ␶
Ä2 ms, which is equal to the upstroke time, phase trajecto-
ries for the same data are full loops. In this case, phase is
unique for every portion of the action potential cycle.
BRDR model, the time constants of the d and f gates
were reduced compared to their original values to obtain
stable 共50% reduction兲 and unstable 共67% reduction兲 spi-
ral waves as done previously.8 Spiral waves were gener-
ated by imposing a linear gradient of two variables 共e
and g for the BAR model, and V m and h for the BRDR
model兲 on the x and y axes, respectively,18 which al-
lowed the system to evolve into a spiral wave. In all
cases, the spiral waves were allowed to go through a few
rotations before performing analyses, to ensure stability.
Henceforth, the term e * will represent the origin cho-
sen using the BAR model. The comparable origins for
the BRDR model and experimental data will be denoted
by v * and f * , respectively. These terms can be used
interchangeably in Eq. 共4兲.
Methods of Analysis
Method of Calculating the Actual Locations of PSs. The
method of calculating the actual locations of the PSs
 ACCURATE LOCALIZATION OF PHASE SINGULARITIES 51

FIGURE 3. Snapshot from a spiral wave simulation and the corresponding phase map. „a… Snapshot from a spiral wave obtained
using the BAR model. Color bar indicates values in millivolts. „b… Snapshot from a phase map for the same instant of time as
in „a…. Phase is calculated from reconstructed state space. Color bar indicates values of phase in radians.

described later uses only one variable, e(t) 共or trans- actual location of the PS was calculated and plotted
membrane potential兲; the second variable was obtained graphically as a function of the chosen e * . However,
using the time delay technique discussed before. We beyond a certain range of e * , PSs were not identified by
wanted to use the same method for all calculations so the algorithm.
that we could compare results quantitatively. Phase for
every pixel was calculated using Eq. 共4兲 关replacing e * The Effective Range. We consider the PS-finding algo-
* in Eq. 共4兲兴 with e pixel
with e pixel * equal to the mean am- rithm to have failed if it did not identify any PSs for
plitude of that pixel over approximately 500 ms. Next, more than two of the eight instants in one rotation. For
phase maps were generated and the PS-finding algorithm all models there existed a range of e * beyond which the
was used to determine the positions of the PS for eight PS-finding algorithm failed. We call this range the ‘‘ef-
intervals of one complete rotation. These are the actual fective range.’’
positions of the PSs during the rotation, denoted by
(x 1 ,y 1 ),(x 2 ,y 2 ),...,(x 8 ,y 8 ). For the BAR model, this Addition of Noise. Levels of noise in experimental data
method of identifying PSs was identical to that using depend on several factors. Cinelli et al.7 have found that
e * ⫽e ideal
* 共see method described under ‘‘Calculation of
Phase using One Variable’’兲. For the nonstationary spiral
wave, another step was added to the earlier method in
order to locate a single pixel as the organizing center of
the spiral wave for each rotation. One pixel was identi-
fied as the average location 关 (x 1 ⫹x 2 ⫹....⫹x 8 )/8,(y 1
⫹y 2 ⫹....⫹y 8 )/8兴 of these eight positions and the mean
amplitude of this pixel for one rotation was obtained.
This mean value was used as the reference origin
*
(e reference) to calculate phase maps for the entire record-
ing area and then the ‘‘actual’’ positions of the PSs were
located.

Error Due to Choice of Origin. In order to ascertain the
sensitivity of accurately localizing PSs on the choice of
origin, the choice of the origin (e * ) was varied in incre-
ments of 5 mV. This is equivalent to introducing an error
in the choice of origin which is equal to the difference
between the chosen e * and e ideal* 共or e reference
* for the
nonstationary case兲. Phase maps were recalculated and
PSs were computed for the same eight intervals. The
average distance of the location of these PSs from the
FIGURE 4. Schematic representation of the algorithm that
identifies a PS. „a… Using a path length of eight pixels, the
line integral or change in phase around a site „along the
arrows… is computed, and four pixels „stars… are identified by
the PS-finding algorithm. The PS exists at the intersection of
these four pixels. The diagram denotes the algorithm applied
to the center pixel. This path length of eight pixels is applied
to each pixel in the data array to search for a PS. „b… The
change in phase between two adjacent points with values
‘‘a’’ and ‘‘b’’ is calculated according to the flowchart. This
algorithm ensures that the value of the result is within the
range À␲ to ␲.
52 A. N. IYER and R. A. GRAY
for acquisition of voltage-sensitive dye fluorescence sig-
nals using video imaging techniques, the ‘‘distribution of
noise across the pixels of a frame was Gaussian, indicat-
ing that pixel variability was randomly distributed.’’ In
order to study the effect of noise on localizing PSs in
model simulations, a normally distributed random data
set, n(x,y,t), was used to simulate experimental noise.
The mean value was zero and the standard deviation was
set to different levels to simulate various signal to noise
ratios 共SNRs兲. This noise was added to the fast variable
data as follows:
e n 共 x,y,t 兲 ⫽e 共 x,y,t 兲 ⫹n 共 x,y,t 兲 /SNR. 共6兲
We define SNR as SNR⫽1/␣ , where ␣ is fraction of
action potential amplitude. The resulting data, e n (x,y,t),
was then filtered using a spatio-temporal boxcar filter of
width five. Localization of PSs was done for SNRs of 5,
10, 20, and ⬁ 共no noise兲.
Discretization. The precision of experimental data is lim-
ited by the number of levels used for the analog-to-
digital 共A/D兲 conversion. To study if discretization itself
had an effect on the accuracy of localizing PSs, all of
our model simulation data, except for the BRDR station-
ary case, were discretized to 4096 levels 共12 bits兲.
Analyses were performed on the original and discretized
data.
RESULTS
Error Analysis
Phase Calculated from True State Space Versus
Reconstructed State Space. The effect of the choice of
origin in localizing PSs was studied for the BAR model
by computing phase using true state space 关i.e., two
variables e and g; i.e., Eq. 共2兲 with e * ⫽e ideal* and g *
⫽g ideal兴 and reconstructed state space 关i.e., one variable
* data. Figures 8共a兲 and 8共b兲 shows a snapshot from the
e; Eq. 共4兲兴. The trajectories for reconstructed state space
for the BAR model are shown in Fig. 5共b兲. For this
* was ⫺35.5 mV. The results are shown in
model, e ideal
Fig. 5共c兲. It can be seen that there is very little difference
between the two plots. The effective range is also the
same for both cases. This suggests that using a recon-
structed variable is an effective method to obtain phase
data when only one variable is available.
BAR Model (Stable Spiral). The results for the BAR
model for float data type 共before discretization兲 and in-
teger data type 共after discretization兲 are shown in Figs.
6共a兲 and 6共b兲. For float data, there was very little effect
of increase in noise level 共decreased SNR兲 on the ability
to localize PSs. An increase in error in picking the origin
led to a gradual increase in the error in localizing PSs
and the effective range was not affected by SNR. For the
discretized data, however, the addition of noise caused a
decrease in the effective range. For increasing noise lev-
els, the error in localizing PSs increased more abruptly
with error in choice of origin than the float data. Using
discretized data, for 20% added noise (SNR⫽5), the
effective range reduced by 35 mV as compared to no
noise. For SNR⫽10, the effective range was ⫺55 to
⫺20 mV.
BRDR Model (Stable and Unstable Spirals). The results
of the error analysis for the BRDR model were similar
for both the stationary and nonstationary cases as seen in
Figs. 7共b兲 and 7共e兲. The trajectories in reconstructed state
space for both cases are shown in Figs. 7共a兲 and 7共c兲.
The trajectory of the PS for the nonstationary case is
plotted in Fig. 7共d兲. Using float data type, noise had little
effect on the ability to localize PSs and there was a wide
effective range over which PSs could be identified 共over
75% of action potential amplitude for the stationary and
85% for the nonstationary case, with an SNR of 10兲.
However, discretization had a profound effect on the
ability to localize PSs 关Fig. 7共f兲兴 as seen in the case of
the BAR model simulations. The effective range for dis-
cretized data, obtained from the nonstationary spiral
wave using BRDR model, was 40 mV for SNR⫽10.
Experimental Data. Experimental data was obtained from
four rabbit hearts mapped using video imaging technol-
ogy 共for details see Ref. 3兲. Data was sampled at 480 Hz
using a charge coupled device 共CCD兲 camera with a
spatial resolution of 0.31⫾0.03 mm. We chose only
those episodes of tachyarrhythmias that were terminated
successfully by application of an electric shock to ensure
proper normalization. The data were passed through a
five-point median temporal filter followed by a spa-
tiotemporal conical filter (3⫻3⫻3 mask). The SNR for
our experimental data was approximately 9.0 for the raw
experimental data and the corresponding phase map at
the same instant of time. The effect of varying the origin
for the four sets of experimental data are summed to-
gether in Fig. 8共c兲. The effective range for all four ani-
mals was very similar 共approximately 40% of the action
*
potential amplitude兲, while the f reference varied from
⫺56.3 to ⫺42.9 mV.
Comparison with Other Algorithms
As the method of calculating phase and identifying
PSs is relatively new, it is necessary to compare the
results with previous methods of locating the tip of re-
entrant waves. In order to do this, we calculated isoch-
rones for the stationary cases using the BAR and BRDR
models, and isopotential maps and for the BRDR non-
stationary case. The isochrones were computed from
 ACCURATE LOCALIZATION OF PHASE SINGULARITIES 53

FIGURE 5. One variable versus two variables for the BAR model. „a… Trajectories from every element in the array for stable,
stationary spiral waves. Trajectories are plotted onto true state space for the BAR model. Note that there is a central area
„indicated by arrow…, around which all trajectories traverse. „b… Trajectories in reconstructed state space. Trajectories from every
element in the array are plotted onto recreated state space for a stable spiral wave simulation using the BAR model. Note that
there exists a central area, around which all trajectories traverse. „c… Results from the BAR model simulations, comparing the
use of only one variable to identify PSs against the ‘‘gold’’ standard method of using two variables. Note that the results for
both cases are very similar in PS error as well as effective range.

maps of activation times 共defined as the time of crossing
50% of the height of the action potential兲.3 The PSs
identified for each model are plotted onto the resulting
graphs 共Fig. 9兲. From Fig. 9共a兲, one can see that for the
BAR model the PS is located at the exact center of
rotation as indicated by the isochrones. For the stationary
spiral wave with the BRDR model, there is a central
‘‘core’’ area 关Fig. 9共b兲兴 that does not activate during the
rotation and the PS was exactly in the center of this
inactivated area. For the BRDR nonstationary case, a
series of isopotential maps are shown instead of iso-
chrone maps due to the limitation of isochrone maps in
showing subsequent positions of the wave front. Isopo-
tential maps for eight equal intervals of one rotation and
the corresponding PSs are plotted on the maps in Fig.
9共c兲. The PSs are very close to these isopotential lines
and their exact location corresponds to where the local
curvature of the isopotential changes sign. Thus it ap-
pears that our method of calculating PSs is consistent
with other methods of identifying the tip of the spiral
wave.
DISCUSSION
Recently developed video imaging technology has
made it possible to record the transmembrane potential
from thousands of sites over the whole heart with high
spatial and temporal resolution.5 This provides new av-
enues of research to explore. The method of using a
phase variable to study cardiac activity is a direct off-
spring of the advancements in video imaging and a rela-
tively new concept. This ‘‘phase mapping’’ technique is
54 A. N. IYER and R. A. GRAY
based on certain fundamental properties of ‘‘excitable’’
cells and nonlinear wave propagation.24 Here, we show
that the localization of PSs is the same whether phase is
computed from the true state space or a reconstructed
one. This result ensures that analyzing PSs computed
from the dynamical patterns of transmembrane potential
共only兲 is sound. In addition, we show that although noise
level, discretization, and choice of origin affect the abil-
ity to localize PSs, they can be localized with an accu-
racy of 2 mm over a wide range of these parameters
even for unstable spiral waves.
Perhaps the most applicable result for experimentalists
is that, for data recorded with a video imaging system
with SNR ⬃10, there exists a range of over 20 mV,
which is over 20% of action potential amplitude, for
picking the origin such that the error in localizing PSs is
less than 2 mm. For example, if one were to pick an
origin of ⫺50 mV 共for example兲 for all four data sets,
PSs could still be identified with an accuracy of 2 mm.
The magnitude of this accuracy is within the range of
values reported for the central core area during reentry in
cardiac tissue. Pertsov et al.22 calculated the core size to
be 17 mm2 for canine and sheep ventricular myocardium,
FIGURE 6. BAR model results. Results
from the BAR model simulations of stable
spiral waves, showing the effects of
choice of origin, discretization and noise
on the accuracy in localizing phase sin-
gularities. ‘‘n’’ indicates noise level in
percentage of action potential amplitude.
SNRÄ100Õn . „a… BAR model with float
data type. „b… BAR model for discretized
data. Comparing panels „a… and „b… shows
the effect of discretization.
while Ikeda et al.17 have calculated the area of the core
to be 12 mm2 in canine atria.
Method of Calculating the Cardiac Phase Variable
Previously, the core of a rotating spiral wave has been
calculated by identifying the region of low amplitude
variation of potential during one complete rotation.17,22
The method of choosing an ideal origin for the BAR
model used in this paper is similar to previous work by
Winfree24 who plotted trajectories in true state space to
track the tip of rotating waves in TSVMs. However, this
method 共using true state space兲 cannot be extrapolated to
experimental data where only one variable is recorded.
In this work we calculate a second reconstructed variable
using the time-delay embedding method. An advantage
of our method 共also shared by Winfree’s technique, but
not by Pertsov’s22 method兲 is that PSs can be identified
within a very short time interval 共as little as two video
frames兲. This enables a description of rotating waves on
a time scale much shorter than the period of rotation.
 ACCURATE LOCALIZATION OF PHASE SINGULARITIES 55

FIGURE 7. BRDR model results. „a… Trajectories plotted onto reconstructed state space for the stationary BRDR model. „b… Error
analysis for the stationary spiral wave showing the effect of choice of origin and noise on the ability to localize phase
singularities using float data type. „c… Trajectories plotted onto reconstructed state space for the nonstationary BRDR model. „d…
The movements of the PS of the nonstationary spiral wave over 450 ms for the BRDR model. „e… Results of the error analysis
for the nonstationary spiral wave using float data type and „f… integer data type „discretized data…. Note that for no noise „ n
Ä0…, discretization has little effect on the PS error. However, discretization coupled with noise tends to cause shortening of the
effective range as well as increase in the PS error.

Identifying PSs for Nonstationary Rotating Waves should be noted that this step is not absolutely necessary
In the section ‘‘Method of Calculating Actual Loca- to identify instantaneous PSs for the nonstationary case.
tions of PSs,’’ we have added a second step for the The second step was added to be consistent with the
nonstationary case for defining an organizing center. It stationary case. For the nonstationary case, f * 共or e * 兲
56 A. N. IYER and R. A. GRAY

FIGURE 8. Experimental data results. „a… Snapshot from optically recorded data from rabbit heart in stable tachyarrhythmia.
Data is scaled from À80 to 20 mV. Thin white lines show the movement of the PS over one rotation. „b… Snapshot from the
corresponding phase map for the same instant of time as in „a…. The phase singularity exists at the region where all colors
converge. Note that it is also easier to visually identify the general location of the tip of the rotating wave from the phase data
rather than transmembrane potential. The movement of the PS over one complete rotation †same as in „a…‡ is shown in thin
black lines. „c… The results from four sets of experimental data are pooled together. There is a range of origin greater than 20%
of action potential amplitude, for which the error in identifying PSs is less than 2 mm.

can be obtained by calculating the mean amplitude of all
pixels over time.16 The optimal time interval 共window兲 to
compute f * 共or e * 兲 deserves to be studied in greater
detail. Here, we averaged the amplitudes of all pixels for
two full rotations to obtain f * .
Effects of Discretization
A comparison of the graphs in Figs. 6 and 7 for float
and integer data types show that, in the presence of
noise, discretization had a large effect on the ability to
localize PSs. The results using the float data type showed
increased effective range and little effect due to noise
compared to those obtained with integer data. It is inter-
esting to note that discretization by itself had little effect
with no added noise. However, discretization coupled
with noise produced a shortening of the effective range
and an increase in the error in localizing PSs. But where
does the discretization error come from? In order to find
the source of this error, we performed the following
analysis on the same set of float data from computer
simulations with added noise. First, the float data was
used to calculate phase in floats, which was then used to
 ACCURATE LOCALIZATION OF PHASE SINGULARITIES 57

FIGURE 9. Comparison with alternative method. „a… Isochrones for one complete rotation of the spiral wave using the BAR
model. Arrow shows the position of the PSs calculated. „b… Isochrones for one complete rotation of the stationary spiral wave
using the BRDR model. „c… Isopotential maps „50% of maximum APA… at eight equal intervals of one rotation of the non-
stationary spiral wave using the BRDR model. PSs calculated using the PS-finding algorithm are denoted by ‘‘*.’’

localize PSs 关see Figs. 6共a兲, 7共b兲, and 7共e兲兴. Second, the
float data was used to calculate phase in floats, but the
phase map was discretized and PSs were identified 共not
shown兲. In the third case, the float data was discretized
before calculating phase 关Figs. 6共b兲 and 7共d兲兴. The re-
sults from the first two cases were very similar and
showed almost no effect of discretization whereas there
was a marked effect on the third case. This leads us to
believe that the precision of the data used to calculate the
phase variable plays an important role in the accurate
localization of PSs. Although discretization cannot be
avoided during data acquisition, newer, more sensitive
共i.e., lower noise levels and more A/D bits兲 CCD
cameras13 will increase the effective range and reduce
the effect of noise in localizing PSs accurately. Our re-
sults suggest that investigators carrying out simulations
may want to save transmembrane potential maps as float
data 共or calculate phase ‘‘on-the-fly’’兲 in order to pre-
cisely localize PSs.
Limitations
Many different problems can occur during the identi-
fication of PSs. First, a PS can be identified when none
existed. Second, a PS could exist and not be identified.
Third, a PS that existed could be identified, but at a
nearby location. The first two cases usually occur near
the extremities of the effective range and their frequency
increased with noise and discretization. However, these
cases were infrequent enough that the affect of these
58 A. N. IYER and R. A. GRAY
factors could be considered minimal in our analysis. For
example, for the nonstationary BRDR case with SNR of
10 using discretized data, multiple PSs were identified 5
times, and no PSs were identified twice 共out of 72 cal-
culations兲 within the effective range. The goal of our
study was to study only the third case in detail 共we
studied the affect of three parameters兲. Further work is
required to study the first two issues as well as extending
our results to the situation where multiple PSs exist.
SUMMARY
The objective of this work was to quantify the accu-
racy of localizing PSs in heart tissue and the factors that
affect this accuracy. The results obtained from the dis-
cretized BRDR with a SNR of 10 are very similar to
those obtained from our experimental data and suggest
that a considerable amount of noise and discretization is
tolerable in the localization of PSs. During fibrillation,
multiple rotating waves are often observed on the heart.
Our results suggest that it may be possible to identify
two PSs which are as close as 2 mm. Here, we felt it was
necessary to analyze the case in which we know that one
and only one PS exists, by which we can ascertain the
capabilities and limitations of the method of calculating
phase and identifying PSs. Here we show that it is pos-
sible to accurately localize PSs in TSVMs, ionic models,
and experimental data and the accuracy is similar for
both stationary and nonstationary spiral waves.
ACKNOWLEDGMENTS
The authors would like to thank Frederick Evans and
Isabelle Banville for the experimental data and Kyle Jus-
tice for the graphical user interface in the data analysis
software. This work was supported in part by grants
from the Whitaker Foundation 共RAG兲 and the American
Heart Association 共RAG兲.
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