SYSTEM AND METHOD FOR RECONSTRUCTING AND VIEWING CARDIAC ELECTRICAL ACTIVATION

Abstract
System and method for the reconstruction of cardiac electrical activation from cardiac electrical signals recorded by intracardiac catheters. The obtained signals are processed using a Support Vector Machine (SVM) algorithm to solve the dual signal problem. Visualization of the solution includes geometric information in such a way that the cardiac electrical activity can be identified and localized. The system and method are described as a preferential application for anti-arrhythmic therapies.
Description
OBJECT OF THE INVENTION

The object of the present invention is a new system for reconstruction of the cardiac electric activity from cardiac electric signals recorded with a vector (array) of intracardiac catheters and adequate processing media, for their visualization with position of the cardiac electrical activity. This invention is in the frame of technics for inverse problem in electrocardiography, consisting of estimating the endocardial or epicardial electric sources (transmembrane voltage or current) from remote measurements (intracardiac electrograms) in catheters or electrodes.


FIELD OF THE INVENTION

The field of the invention is that one of systems for generating and visualizing medical images, specifically, the graphical representation of the electric activity in medical systems used in electrocardiology and cardiac electrophysiology.


PRECEDENTS OF THE INVENTION

Cardiac arrhythmias are one of the main causes of mortality in the world. Current therapies have their foundamentals on a partial knowledge of the mechanisms of the most usual arrhythmias (atrial and ventricular tachicardias, atrial and ventricular fibrillation, and others), and thouth these therapies reach high levels of effectiveness, the detailed knowledge of a fast arrhythmia (tachyarrhythmia) is the key for creating new anti-arrhythmic therapies or for improving the actual ones.


Nevertheless, the knowledge of the arrhythmic mechanism in a given patient is limited by the fact that the physical magnitude involved is the electric impulse propagation throughout the cardiac cells. The visualization of electric activity in the internal surface of the heart (endocardium) is troublesome, given that current technology only gives indirect measurements, consisting of electric voltage measured in catheters inside the heart (electrograms). These measurements record the electric field that is induced by the cardiac currents at a given distance of atrial or ventricular walls, and hence, mathematical calculations are required for estimated the numerical values of the cardiac currents in the endocardial surface.


Intracardiac navigation systems allow the spacial reconstruction of one or several cardiac cavities and a representation of miocardiac electrical activity changes with time, using the electric signal recordings in diverse points and the detection of the spacial location of the catheter from different spatial location media. Currently, several cardiac navigation systems are used to reconstruct the cardiac electric activity in the myocardium from measurements in catheters. The most relevant are the following:

    • i. Carta System (Biosense, Cordis-Webster). It is probably the most widespread used. It allows to obtain an image (color-coded) of the relative activation time of the endocardium with respect to a reference signal during a stationary rhythm. Its main limitation is it only can be used in stationary rhythms, hence it can not be used in real time for analyzing the nature of non-periodic arrhythmias. More, it requires a time for mapping the electric activity in each patient, between one and three hours, which represents a high cost for the health system
    • ii. Localisa. This system is similar to the preceding one, and it was commertialized by Medtronic. It is no longer commertialized, and its succesor is Navex (n the sense that it uses the same system for spacial detection).
    • iii. Ensite. It is an advanced system allowing the reconstruction of the myocardial electric activation from the recordings in a catheter array. Theoretically, it allows this reconstruction in an instantaneous form, hene being potentially useful for any kind of arrhythmia (periodical or not).


Probably, the cause for Ensite not having a wider acceptation and use in practice, despite its theoretical advantages, is that it gives an estimation of bioelectrical currents with an associated uncertainty. Improvement of this uncertainty would make a system of this family having a widespread acceptation in the clinical practice. Other problems are the catheters dimensions, its complicated manipulation, its price, and the fact that the accurate information is limited to the proximal zone of the electrode.


In the current state of technique, several systems are described including the use of catheters for cardiac mapping. Among them, we can consider the patents U.S. Pat. No. 6,892,091, U.S. Pat. No. 5,297,549 y U.S. Pat. No. 5,311,866.


DESCRIPTION OF THE INVENTION

The system for the reconstruction and visualization of cardiac electric activity, object of the present invention, includes, at least:

    • a. A set of intracardiac catheters.
    • b. Media for positioning and obtention of the location coordinates of said set.
    • c. Media for auxiliary image (resonance, TAC, ecography) that yields the geometrical coordinates of the cardiac wall, and eventually of some additional electric properties (for instance, necrosis regions).
    • d. Media for processing the signals from the catheters, where said processing methods include, at least, an algorithm based on SVM for the reconstruction of the dual signal problem.
    • e. Media for visualizing the processed signals.


Where the SVM subsystem includes a statistical learning algorithm that is derived from the structural risk minimization principle. Two of the main advantages of the SVM are regularization and robustness, ideal conditions for the requirements of the inverse problem in electrocardiography.


The said system generates a plurality of signals whose physical origin is in that system, and they are subsequently used in the method, hence we have that:

    • Signals v[k] are the voltages measured in the k-th electrode of the catheter set, and they are acquired in the same time instant for all the electrodes.
    • Signal ho[k] is the spacial transfer function, and it can be either estimated by conventional system identification techniques, or obtained from the volume conductor equation for a homogeneous media.
    • Spacial coordinates of each catheter are recorded by means of available media of catheter positioning.
    • Data of the cardiac cavity geometry are obtained with the auxiliar image subsystem, from image fusion techniques from previous medical images, such as magnetic resonance (and variants) or ultrasound echocardiography.


A second aspect of the present invention is the method for reconstruction and visualization of cardiac activity that includes, at least, the next stages:

    • (i) A first stage of registering the anatomical cardiac information (resonance, ultrasound) and storing it in digital format.
    • (ii) A second stage of electro-physiological procedure, where a set of catheters are placed inside the cavity, and the catheter locations are recorded with the dedicated subsystem.
    • (iii) A third stage of calculating the distance matrix, with the previous information, storing it in digital format.
    • (iv) A fourth stage of simultaneously recording of the voltages in the catheters v[k], for k successive time instants.
    • (v) For each voltage measurement v[k], the SVM is volved in a digital processing element as follows:
      • a. The quadratic problem given by measurements v[k] and by the distance matrix is solved in block, and transmembrane currents i[k] are estimated.
      • b. The signal of measurements of estimated voltages v[k] is interpolated, from estimated transmembrane currents in
      • c. Interpolated potentials are checked to correspond with quality to the recorded potentials.
    • (vi) A sixth stage (optional) of visualization of the reconstructed voltage (with increased resolution) or of the estimated transmembrane current (with increase resolution) for successive time instants.





SHORT DESCRIPTION OF THE FIGURES

We next describe (very briefly) a series of plots which aim to help to better understand the invention, and that are related with a realization of said invention that is presented as a non-limiting example.



FIG. 1. Block diagram of the system for reconstruction and visualization of cardiac electric activity, object of the present invention.



FIG. 2. Representation of a unidimensional simulation of the system for reconstruction and visualization of the cardiac electrical activity, object of the present invention.



FIG. 3. Reconstruction of the signal of the system for reconstruction and visualization of cardiac electric activity, object of the present invention.





PREFERENTIAL REALIZATION OF THE INVENTION

The system for reconstruction and visualization of cardiac electric activity, object of the present invention, includes at least:

    • a. A set of intracardiac catheters.
    • b. Media for positioning for obtention of the location coordinates of said set.
    • c. Metida for auxiliary image (resonance, TAC, echocardiography) yielding the location coordinates for the cardiac wall geometry, and eventually of some additional electrical properties (for instance, necrosed regions).
    • d. Media for processing the signals from the set of intracardiac catheters, where said media include at least an algorithm based on SVM for solving the dual signal problem.
    • e. Media for visualization of the processed signal.


Where the SVM subsystem consists of a statistical learning algorithm derived from the structural risk minimization principle. Two of the main advantages of the sVM are regularization and robustness, ideal conditions for the requirements of the inverse problem in electrocardiography.


Said system generates a plurality of signals with physical origin on that system, and they are subsequently used, hence, we have that:

    • Signals v[k] are the voltages measured in the k-th element of the set of catheters, and they are acquired at the same time instant for all the catheters.
    • Signal ho[k] is the spacial transfer function, and it can be either estimated from conventional system identification techniques, or given by the volume conductor equation for a homogeneous media.
    • Spacial coordinates of each catheter are recorded with the location media of the catheters.
    • Data about the cardiac cavity geometry are obtained with the auxiliar medical image media, thanks to fusion image techniques from previous medical images, such as given by magnetic resonance, or by ultrasound echocardiography.


In FIG. 1 we can observe the block diagram of the system, where it has been included an interpolation/decimation stage for obtaining an increment in resolution given by a number of sensing catheters.


A second aspect of the present invention is the method of reconstruction and visualization of the cardiac activity, which includes, at least, the following stages:

    • (i) A first stage of registering the anatomical cardiac information (resonance, ultrasound, or others) and storing it in digital format.
    • (ii) A second stage of electro-physiological procedure, where a set of catheters are placed inside the cavity, and the catheter locations are recorded with the dedicated subsystem.
    • (iii) A third stage of calculating the distance matrix, with the previous information, storing it in digital format, and building the SVM kernel from it.
    • (iv) A fourth stage of simultaneously recording of the voltages in the catheters v[k], for k successive time instants.
    • (v) For each voltage measurement v[k], the SVM is volved in a digital processing element as follows:
      • a. The quadratic problem given by measurements v[k] and by the distance matrix is solved in block, and transmembrane currents i[k] are estimated.
      • b. The signal of measurements of estimated voltages v[k] is interpolated, from estimated transmembrane currents i[k].
      • c. Interpolated potentials are checked to correspond with quality to the recorded potentials.
    • (vi) A sixth stage (optional) of visualization of the reconstructed voltage (with increased resolution) or of the estimated transmembrane current (with increase resolution) for successive time instants.


The SVM stage, which is the responsible of restoring the electric cardiac activity, is described more in detail with a set of equations which are necessary for defining said stage.


i. Signal Model.


The voltage sensing in catheters, for a given time instant, can be written as:






text missing or illegible when filedlif.fm(text missing or illegible when filed)


where M represents the distance matrix relating (according to the volume conductor model) the transmembrane current (im) with the voltage that is recorded in different points of the cardiac substrate (egm). In matrix form:






text missing or illegible when filed(N)w isvwft.11Ppywir. If text missing or illegible when filed


where v is a [K×1] matrix, i is a [L×1] matrix, and H is a [L×K] matrix, with L≧K. Explicitely, we have:







[





?

0











?




]

=



[


?



?



t

ɛ
-
1



]

P

·

[


h

0

r




h

1

r




?



h

K
-
1



]









?



indicates text missing or illegible when filed





In FIG. 2 we show the unidimensional representation of the electrode measurements recording, where hk is distance matrix M (expressed in vector form) that relates the transmembrane current in each myocite with the voltage measured in the k-th electrode. For electrode k, the captation model can be written as:








?

k

=





t
=
0


L
-
1





t
l



h
lk



=



t
T

·


h
k

.





?





indicates text missing or illegible when filed







where (.) denotes the dot product. This function is also depicted in FIG. 2. This equation, in conventional notation for signal processing, is defined as:








?



[
k
]


=




n
=
0


K
-
1






t


[
n
]


·



h
k



[
n
]


.





?





indicates text missing or illegible when filed







Given that hk[n] can be expressed as h0[n−k], and by defining the impulse response as h[n]=hg[n], the system is perfectly characterized by the convolution between the current and transfer function h[n]:








?



[
k
]


-




n
=
0


K
-
1





t


[
n
]


·


h
k



[
n
]




-




n
=
0


K
-
1





t


[
n
]


·

k


[

n
-
k

]




-

t


[
k
]


+

h


[
k
]









?



indicates text missing or illegible when filed





The problem of cardiac activity reconstruction, as shown next, consists then in finding that current text missing or illegible when filed([text missing or illegible when filed] better approximating the voltage measured in the exterior points of the volume conductor v[k].


ii. Signal Model in the Primal Problem


Be the truncated time series (vk, k=0, . . . , K−1) the set of values of voltage observed as a result of convolving the unknown time series of the myocites currents (lk,k=0, . . . , K−1) with the known transfer function (htext missing or illegible when filedk=0, . . . , K−1) so that the next model is obtained:







?

=




?



?



h
k


+

?


=





n
=
0


K
-
1





?



h

n
-
k




+

?










?



indicates text missing or illegible when filed





Where the problem of current estimation can be expressed as the minimization of:







?

=



1
2






?



2
2


+




k
=
0


K
-
1





?



(

?

)











?



indicates text missing or illegible when filed





Where text missing or illegible when filed=[t, . . . lk-1]text missing or illegible when filedand:








L

ε





H




(

e
k

)


=

{




0
,







e
k




ɛ








1

2

δ





(




e
k



-
ɛ

)

2


,




ɛ




e
k





e
C









C


(




e
k



-
ɛ

)


-


1
2


δ






C
2



,







e
k





e
C










Therefore, the previous functional can be expressed as:







J
PSM

=





k
=
0


K
-
1





i
k
2

2


+


1

2

δ







k


I
1





(


ξ
k
2

+

ξ
k

*
2



)



+

C





k


I
2





(


ξ
k

+

ξ
k
*


)



-


1
2






k


I
2





δ






C
2









Which has to be minimized with respect to (lk) and (text missing or illegible when filed(text missing or illegible when filed)k), constrained to:








υ
k

-




j
=
0


K
-
1





i
j



h

k
-
j







ɛ
+

ξ
k





-

υ
k

+




j
=
0


K
-
1





i
j



h

k
-
j







ɛ
+

ξ
k
*









ξ
k

,


ξ
k
*


0





For k=0, . . . , k=1 and where (text missing or illegible when filed(h)k) are slack variables or losses, and I1, (I2) are the indices of the residuals that can be found in the quadratic (linear) cost zone.


The solution to the previous optimization problem is given by the saddle point of the corresponding Lagrangian function:






L
=





k
=
0


K
-
1





i
k
2

2


+


1

2

δ







k


I
1





(


ξ
k
2

+

E
k

*
2



)



+

C





k


I
2





(


ξ
k

+

ξ
k
*


)



-


1
2






k


I
3





δ







C
2

--






k
=
0


K
-
1






(


?

+

?


)

++






k
=
0


K
-
1





α
k



(


υ
k

-




j
=
0


K
-
1





i
j



h

k
-
j




-
ɛ
-

ξ
k


)








+




k
=
0


K
-
1





α
k
*



(


-

υ
k


+




j
=
0


K
-
1





i
j



h

k
-
j




-
ɛ
-

ξ
k
*


)











?



indicates text missing or illegible when filed





subject to the following constraints:







α
k

(*
)


,

β
k

(*
)


,


ξ
k

(*
)



0











L




i
n



=
0

;









L




ξ
n

(*
)




=
0




together with Karush-Kuhn-Tucker conditions:






{







α
k



(


υ
k

-




j
=
0


K
-
1





i
j



h

k
-
j




-
ɛ
-

ξ
k


)


=
0








α
k
*



(


-

υ
k


+




j
=
0


K
-
1





i
j



h

k
-
j




-
ɛ
-

ξ
k
*


)


=
0










{






β
k



ξ
k


=
0








β
k
*



ξ
k
*


=
0










Since (text missing or illegible when filedktext missing or illegible when filed; are slack variables, then text missing or illegible when filed=text missing or illegible when filed, and therefore text missing or illegible when filedktext missing or illegible when filedk=text missing or illegible when filed. By deriving the Lagrangian with respect to the primal variables, we can obtain the dual problem, which is the next stage of the method.


iii. Signal Model in the Dual Problem


For the optimization of









ɛ




i
n



=

0


:












i
n

-




[




k
=
0


K
-
1





(


α
k

-

α
k
*


)



(




n
=
0


K
-
1





i
n



h

k
-
n




)



]





i
n




=


0


i
n


=




k
=
0


K
-
1





(


α
k

-

α
k
*


)



h

k
-
n









Using a change of variables and having njj−αj*′, we have:








i
^

k

=





j
=
0


K
-
1





h

j
-
k




(


α
j

-

α
j
*


)



=


h

-
k


*

η
k







which can be expressed in matrix form as:







i
^

=




j
=
0


K
-
1





h

j
-
k




(


α
j

-

α
j
*


)







where hj-k=[1×K], and hence






î=H(α−α′)


where H(m,p)=hform with indices {m,p=1, . . . ,K} and hence:








[





h
0

,





h
1

,







h

K
-
1








h

-
1


,





h
0

,







h

K
-
2






















h

1
-
K


,





h

2
-
K


,







h
0




]





Moreover, given that





i∥2=iTicustom-character∥i∥2=(α−α*)THTH(α−α*)





i∥2=(α−α*)TK(α−α*)





K=HTH


Explicitly,





K
=


[





h
0

,





h

-
1


,







h

1
-
K








h
1

,





h
0

,







h

2
-
K






















h

K
-
1


,





h

K
-
2


,







h
0




]

·

[





h
0

,





h
1

,







h

K
-
1








h

-
1


,





h
0

,







h

K
-
2






















h

1
-
K


,





h

2
-
K


,







h
0




]






which can be expressed in a compressed form as







K


(

m
,
p

)


=




z
=
1

K




h

m
-
z




h

p
-
z








where m, p, z are indices taking values in {1, . . . , K}, and taking n=m−p, previous equation can be written as:







K


(

n
,
p

)


=




z
=
1

K




h

p
+
n
-
z




h

p
-
z








so that signal R can be defined as







R
k

=





n
=
0


K
-
1





h
k



h

k
+
n




=


h
k

*

h

-
k








which is the autocorrelation of hk.


On the other hand, in the optimization of














L




?



=
0








?



indicates text missing or illegible when filed





we have that:


1−k∈I1:cuadratic zone:









1
δ



(


ξ
k

+

ξ
k
*


)


-

(


β
k

+

β
k
*


)

-

(


α
k

+

α
k
*


)


=
0




k(•)=0 according to KKT, since in the cuadratic zone ξk(•)=0


*either ξk or ξk*; are different than zero, but not at the same time. Therefore:





ξk(•)=δαk(•)


It can be demonstrated that (using αkαk=0)











1

2

δ







k


I
1





(


ξ
k
2

+

ξ
k

*
2



)



=



1

2

δ







k


I
1





(



δ
2



α
k
2


+


δ
2



α
k

*
2




)



=







=



δ
2






k


I
1





(


α
k
2

+

α
k

*
2



)



=



δ
2






k


I
1






(


α
k

-

α
k
*


)

2



=








=


δ
2




(

α
-

α
*


)

T




I

I
1




(

α
-

α
*


)










2.−k∈I2: linear zone. As in the previous case we have:





βk(•)=0 por ξk(•)≠0





then,





αk(•)=C


iv. Solution for the Primal Signal Model


The solution of the primal signal model is depicted in FIG. 1, where given the initial model:






v
k

k
*h
k
+e
k
={circumflex over (v)}
k
+e
k





whose solution is






î
kk*{tilde over (h)}kk*h−k





we get that






{circumflex over (v)}
k

k
*h
kk*Rkh


v. Dual Signal Model


Be the set of measurements {vk}, modeled by a nonlinear regression from a set of given locations (k). This regression uses a nonlinear transformation text missing or illegible when filedH→H, which maps the set of locations (real scalars) to a Reproducing Hilbert Kernel Space (RKSH) H, or feature space. By choosing an adequate φ, we can build a linear regression model in H, given by:






v
k
=
custom-character
w,φ(k)custom-character+ek


where w∈H is the weight vector.


vi. Primal Problem for the Dual Signal Model


By developing the primal problem, functional is given by:







J
DSM

=





k
=
0


K
-
1





w
k
2

2


+


1

2

δ







k


I
1





(


ξ
k
2

+

ξ
k

*
2



)



+

C





k


I
2





(


ξ
k

+

ξ
k
*


)



-


1
2






k


I
2





δ






C
2









To be minimized with respect to (ωi) β(text missing or illegible when filedkh), and constrained to:





υ1custom-characterw,φ(l)custom-character≦ε+ξ1





υ−v1custom-characterw,φ(l)custom-character≦ε+ξ1*


By obtaining the Lagrangian and taking the derivatives with respect to primal variables, we get to:






w
=




k
=
0


K
-
1





η
k



φ


(
k
)








Hence, voltage can be expressed as







v
k

=








j
=
0


K
-
1





η
j



φ


(
j
)




,

φ


(
k
)





=




j
=
0


K
-
1





η
j






φ


(
j
)


,

φ


(
k
)












And by using the kernel trick,







v
k

=





j
=
0


K
-
1





η
j






(

j
,
k

)




=




j
=
0


K
-
1





η
j






(

j
-
k

)









This last equality is fulfilled as far as K is given by a suitable Mercer kernel.


vi. Dual Problem for the Dual Signal Model


By defining





G(j,k)=custom-characterφ(j),φ(k)custom-character=k(j,k)


where the following functional has to be maximized:







L
D

=



-

1
2





(

α
-

α
*


)

T



(

G
+

δ





I


)



(

α
-

α
*


)


+


v
T



(

α
-

α
*


)


-

ɛ






1
T



(

α
+

α
*


)









0


α

(*
)



C




and taking into account the convolutional model, then the voltage recorded in different K points {k=0, . . . , K−1} is







v
k

=




j
=
0


K
-
1





i
j



h

j
-
k








Comparing the equations of vk, and identifying terms, we can express





K(j−k)=hj-k





îkk





and then,





{circumflex over (v)}kk*kk*hk


Therefore, taking text missing or illegible when filed we find that the convolutive model emerges naturally for the relationship between the impulse response and the sparse signal (some few samples are different from zero).

Claims
  • 1. System for reconstruction and visualization of cardiac electrical activity, comprising: a set of catheters configured to measure cardiac voltages with a plurality of electrodes;position means configured for calculating the coordinates of the location of said array;auxiliary image means for auxiliary image acquisition, configured for giving anatomical geometric information of the cardiac walls;signal processing means for processing the signals obtained from the set of catheters, where said processing means implement an algorithm based on Support Vector Machines (SVM) for the resolution of the signal problem, incorporating information about the transfer function of the electrical activity from the cardiac cells to the catheters systems, by the SVM kernelthe signal processing means being coupled to interpolating means, configured for making use of spatial redundancy and improving the resolution without needing matrix inversions, from signals recorded in the catheters., andvisualization means for visualizing of the processed signal.
  • 2. System of reconstruction of the cardiac activity according to claim 1, wherein the auxiliary image media are at least one selected among: resonance;axial computerized tomography;echography;scopy.
  • 3. System for reconstruction of the cardiac activity according to claim 1, wherein the auxiliar image media detect additional cardiac electric properties
  • 4. System for reconstruction of the cardiac activity according to claim 1, wherein the system detects regions of necrosis.
  • 5. System for reconstruction of the cardiac activity according to claim 1, wherein the SVM includes a statistical learning algorithm, derived from the structural risk minimization principle.
  • 6. System for reconstruction of the cardiac electric activity according to claim 1, wherein signals are the voltages measured in the k-th electrode of the plurality of catheters, and are acquired in the same time instant for all the catheters.
  • 7. System for reconstruction of the cardiac activity, according to claim 1, wherein the signal is the spatial transfer function.
  • 8. System for reconstruction of cardiac activity according to claim 7, wherein signal is estimated by system identification techniques.
  • 9. System for reconstruction of cardiac activity, according to claim 1, wherein signal is calculated by using the volume conductor equation for a homogeneous media.
  • 10. System for reconstruction of cardiac activity according to claim 1, wherein the media for catheter location record the spatial coordinates of each catheter.
  • 11. System for reconstruction of cardiac activity, according to claim 1, wherein the media for auxiliary image of the system obtain the data of the geometry of the cardiac cavity.
  • 12. System for reconstruction of cardiac activity, according to claim 1, wherein the system includes interpolation and decimation media, for yielding an increment in the accuracy given by a given number of sensing catheters.
  • 13. Method for reconstruction and visualization of cardiac activity, comprising: (i) a first stage for registering the anatomical cardiac information (resonance or ultrasounds);(ii) a second stage for the electrophysiological procedure, where the catheter is placed inside the cavity, and the positions of the catheters are recorded with the dedicated subsystem;(iii) a third stage calculating the distance matrix, with the preceding information;(iv) a fourth stage simultaneously recording of the voltages in catheters, for successive time instants;(v) a fifth stage calculating the SVM algorithm for each voltage measurement.
  • 14. Method for reconstruction of the signals, according to claim 13, wherein the method includes an optional visualization stage for the reconstructed voltage.
  • 15. Method for reconstruction of the signals, according to claim 13, wherein the method includes an optional visualization stage for the transmembrane current estimated for successive time instants.
  • 16. Method for reconstruction of the signals, according to claim 13, wherein the SVM algorithm includes: (i) a first stage for block solving of the quadratic programming problem given by measurements and by distance matrix, and hence for estimating transmembrane currents;(ii) a second stage for signal interpolation of estimated voltages, from estimated transmembrane currents; and(iii) a third stage of verification that the voltages interpolated from the transmembrane currents correspond to the measured voltages with enough quality.
Priority Claims (1)
Number Date Country Kind
P200801074 Apr 2008 ES national
PCT Information
Filing Document Filing Date Country Kind 371c Date
PCT/ES2009/000194 4/14/2009 WO 00 4/1/2011