This invention relates generally to cardiology, and specifically to cardiac arrythmia.
Atrial fibrillation (AF) is the most common arrythmia, projected to affect 6-12 million people in the United States by 2050 and 17.9 million people in Europe by 2060. Radiofrequency (RF) or irreversible electroporation (IRE) or pulsed field (PF) ablation is a treatment option for AF which acts to change the path of an electric wave in the heart. However, in order to apply the ablation effectively, it is important to locate the source or driver of the AF, and methods for implementing this are known.
An embodiment of the present invention provides a method, consisting of:
acquiring, from a plurality of electrodes in contact with heart tissue undergoing atrial fibrillation, respective signals;
calculating from the signals respective mutual information metrics between multiple pairs of the electrodes;
generating a graph with the electrodes as nodes, and edges as connections therebetween for which the respective mutual information metrics exceed a selected mutual information metric threshold;
calculating a respective local efficiency metric for each node, indicating an efficiency of information exchange between the node and other nodes connected to the node, based on path lengths between the connected nodes;
averaging respective local efficiency metrics of the nodes to formulate a resultant local efficiency for the selected mutual information metric threshold; and
analyzing the resultant local efficiency and the selected mutual information metric threshold to classify the atrial fibrillation.
The signals may be unipolar or bipolar voltage or action potential voltage vs. time signals.
Typically, calculating from the signals includes estimating local activation times (LATs) from the signals.
In a disclosed embodiment the heart tissue is part of an atrium, and classifying the atrial fibrillation includes estimating a percentage of remodeling of the atrium.
In a further disclosed embodiment the method includes presenting to a user of the method a classification of the atrial fibrillation.
The plurality of electrodes may be located on a catheter having a multiplicity of spines.
Typically, the nearest-neighbor electrodes in the plurality of electrodes are separated by less than 3 mm.
In another embodiment, averaging respective local efficiency metrics of the nodes consists of generating subgraphs of nodes connected directly to a given node, calculating local efficiency metrics for each of the subgraphs, and averaging the calculated local efficiency metrics.
In yet another embodiment, the method includes reiterating the steps of generating the graph, and averaging the respective local efficiency metrics while incrementing the selected mutual information metric threshold, so as to produce a set of ordered pairs of resultant local efficiency and mutual information threshold.
The set of ordered pairs may be analyzed to classify the atrial fibrillation. Typically, analyzing the set of ordered pairs consists of fitting a polynomial to the set, and classifying the atrial fibrillation in response to a first derivative of the polynomial.
In a yet further embodiment, calculating from the signals includes calculating from the signals respective mutual information metrics between all pairs of the electrodes.
There is also provided, according to an embodiment of the invention, apparatus, including:
a probe, having a plurality of electrodes configured to contact heart tissue undergoing atrial fibrillation; and
a processor, configured to:
receive signals from the electrodes and calculate from the signals mutual information metrics between multiple pairs of the electrodes;
generate a graph with the electrodes as nodes, and edges as connections therebetween for which the respective mutual information metrics exceed a selected mutual information metric threshold;
calculate a respective local efficiency metric for each node, indicating an efficiency of information exchange between the node and other nodes connected to the node, based on path lengths between the connected nodes;
average respective local efficiency metrics of the nodes to formulate a resultant local efficiency for the selected mutual information metric threshold; and
analyze the resultant local efficiency and the selected mutual information metric threshold to classify the atrial fibrillation.
The present disclosure will be more fully understood from the following detailed description of the embodiments thereof, taken together with the drawings, in which:
While, for atrial fibrillation (AF), it is important to locate the driver of the AF, it is also important to classify the atrial fibrillation to identify an optimal strategy for RF (radiofrequency) or IRE (irreversible electroporation)/pulsed field (PF) ablation. Areas with significant remodeling, i.e., electrophysiological and/or structural changes in the atrium, may be important in atrial fibrillation maintenance mechanisms. Consequently, knowing whether or not an atrium has been remodeled leads to improvement in the mapping and ablation strategy.
The present disclosure develops a novel strategy for estimating how much remodeling is present in a fibrillating atrium.
In an embodiment of the present invention, a probe, comprising a plurality of electrodes, is inserted into a human patient so that the electrodes contact heart tissue that is undergoing atrial fibrillation. A processor acquires signals from the electrodes, and calculates a mutual information metric between each pair of electrodes of the probe. For a given pair of electrodes, the mutual information metric provides a numerical value of the mutual dependence of the signals of the pair. (e.g., if the signals are independent of each other, the metric is close to zero.)
The processor generates a graph with the electrodes as nodes, and with edges, as connections between the nodes, that exceed a selected mutual information metric threshold. In one embodiment the threshold is selected so that at least 50% of the electrodes have connections.
The processor calculates a local efficiency metric for each of the nodes, the local efficiency metric for a given node being a measure of how efficiently nodes connected to the given node exchange information. The processor then averages the local efficiency metric for the graph to generate a resultant local efficiency metric for the selected mutual information metric threshold.
The processor reiterates the steps of generating the graph, and averaging the respective local efficiency metrics while incrementing the selected mutual information metric threshold, so as to produce a set of ordered pairs of resultant local efficiency and mutual information threshold. The processor then analyzes the set of ordered pairs so as to classify the atrial fibrillation.
The analysis typically comprises estimating a percentage of remodeling of the heart tissue.
In the following description, like elements in the drawings are identified by like numerals, and like elements are differentiated as necessary by appending a letter to the identifying numeral.
Reference is now made to
Electrodes 32 are coupled, via conductors in catheter 24 and an interface 34, to a processor 36. Processor 36 comprises a processing unit 42, typically a central processing unit (CPU) and also referred to herein as CPU 42, which is coupled to a memory 46. Memory 46 comprises a number of modules: an ECG module 50, a tracking module 58, and an AF analysis module 54. The functions of the modules are described below.
CPU 42 typically comprises a general-purpose processor with software programmed to carry out the functions described herein. The software may be downloaded in electronic form, over a network, for example, or it may, alternatively or additionally, be provided and/or stored on non-transitory tangible media, such as magnetic, optical, or electronic memory.
Physician 22 communicates with processor 36 via an input device 70, such as a keypad or a pointing unit, as well as a screen 74, and the processor 36 may present results of procedures performed by the processor on the screen.
In system 20 CPU 42 may track the locations of electrodes 32 using tracking module 58. In one embodiment the CPU and the module are configured to implement an Advanced Current Location (ACL) system in system 20. The ACL system is described in U.S. Pat. No. 8,456,182. In the ACL system, a processor estimates the respective locations of the distal electrodes based on impedances or currents measured between each of distal electrodes 32 and a plurality of surface electrodes 66 that are coupled to the skin of patient 28. For ease of illustration, only one surface-electrode 66 is shown in
Alternatively or additionally, the CPU and module 58 are configured to track the locations of electrodes 32 using an electromagnetic tracking system, such as is used in the Carto® System produced by Biosense Webster of Irvine Calif., and as is described in U.S. Pat. Nos. 5,391,199 5,433,489 and 6,198,963. In this case, one or more magnetic sensors 38, typically single, double, or triple axis coils, are attached to distal end 31. In addition, a set 60 of alternating magnetic field radiators are located in proximity to, typically beneath, patient 28. Currents generated in sensors 38, in response to the fields from set 60, are registered by module 58, and the module and the CPU analyze the currents to determine the location of the distal end as well as the locations of electrodes 32, since the geometry of the distal end is known or may be estimated.
Typically the tracking within the atrium is presented to the physician by processor 36 overlaying an icon of the probe on a pre-acquired map 78 of the atrium that is presented on screen 74. In addition to using the tracking provided by module 58, the physician may use processor 36 to measure impedances between electrodes 32 and a return electrode 80 attached to the skin of patient 28, and from the impedances confirm the contact of the electrodes with atrium tissue.
Once in position, physician 22 operates probe 24 to acquire and record sets of unipolar signals, i.e., sets of voltages measured with respect to electrode 80, for each electrode 32. Typically the sets of signals are acquired over a time period of approximately 2 minutes, i.e., for approximately 150 heartbeats, but embodiments of the invention may acquire signals for shorter or longer periods. Typically, a minimum of 30 seconds of AF should be recorded. CPU 42 stores the acquired signals in memory 46, and for each signal the CPU uses ECG module 50 to calculate the local activations times (LATs). It will be understood that since patient 28 has atrial fibrillation, then, unlike a heart in sinus rhythm, the LAT values for one electrode, at a fixed position in the heart, have changing values, i.e., for the 150 heartbeats there may be 150 different LAT values.
In a first analysis step 104, CPU 42 uses AF analysis module 54 to sort the set of LAT values for each electrode into bins of a histogram. Typically, to simplify the calculations described hereinbelow, the histograms have equal-width bins. Embodiments of the invention may use the histograms to represent a distribution of the LAT values In one embodiment the number of bins is approximately
where L is the number of LAT values in the set.
Returning to step 104 of the flowchart of
where N represents the number of bins in the histograms,
X is a first given electrode,
Y is a second given electrode,
and xi is the number of LAT values in the ith bin of electrode X's histogram,
and yi is the number of LAT values in the ith bin of electrode Y's histogram,
L is the total number of values in each histogram,
In the description hereinbelow, except where otherwise stated, the mutual information metric is estimated, using equation (1), for all pairs of electrodes 32. However, those having ordinary skill in the art will be able to adapt the description, mutatis mutandis, for embodiments where the metric is estimated for fewer than all pairs of electrodes 32, for example if some of the electrodes are not coupled to processor 36, and all such embodiments are assumed to be comprised within the scope of the present invention.
The mutual information metric is known in the art, and is a measure of dependence between two signals: i.e., the amount of information obtained about one signal based on the observation of another. Thus, if one signal is a deterministic function of another their mutual information is maximized; but if two signals are completely independent of each other, their mutual information is close to 0.
In a graph preparation step 108, CPU 42 uses module 54 to set a mutual information threshold such that a set percentage of electrode pairs have mutual information values above that value, and then prepares a graph, herein also termed a regional information graph, where nodes of the graph represent electrodes 32 and edges between the nodes represent connections that equal or exceed the threshold. Typically, the threshold is initially set to include 50% of electrode pairs.
In a subgraph step 112, for each given node in the regional information graph module 54 generates a subgraph, comprising a set of nodes that are connected to the given node being considered. CPU 42 calculates the shortest path between each pair of nodes in the set as the least number of connections between the pair, and for the calculation the CPU considers any given connection to have a unit length. The shortest path lengths are stored in memory 46.
As shown in
As shown in
In step 112 the inverse of the shortest path lengths is used to calculate a local efficiency metric, Elocal, for each node, according to equation (2):
where NGi is the number of nodes in a subgraph Gi, and
Lij is the shortest path length between nodes i and j in the subgraph Gi.
Local efficiency has been used in evaluating brains. It signifies fault tolerance, indicating how well each subgraph exchanges information when the central node is eliminated.
CPU 42 uses equation (2) to calculate a local efficiency metric for each node in the regional information graph. Thus, for node 84A equation (2), using the values for the path lengths of Table I, gives Elocal as 0.0972.
For node 84H, since there are no paths between nodes of the subgraph Elocal is 0.
In an averaging step 116 the calculated local efficiencies are averaged to provide a resultant local efficiency for the graph at the set mutual information threshold. CPU 42 stores the resultant local efficiency and the corresponding mutual information threshold as an ordered pair in memory 46.
As shown in a decision step 120 and an increment step 124, CPU 42 reiterates steps 108, 112, and 116, incrementing the mutual information metric threshold at each iteration, until a maximum value of the metric, typically approximately 95%, is reached. At each iteration the CPU stores the resultant local efficiency and the corresponding mutual information threshold as an ordered pair, so that when the iteration terminates, there is a set of ordered pairs available to CPU 42.
In a results step 128, from the set of ordered pairs produced in step 116, CPU 42 generates a graph of the resultant local efficiency vs. mutual information thresholds.
As is illustrated in graph 200, there is a plateau 202 where the slope of the graph decreases, compared to the slopes on either side of the plateau. There is no such plateau in graph 204. Graphs 200 and 204 illustrate that when electrodes are spaced by less than 3 mm, there is a plateau region in the graph when signals are rotational. This plateau is not present when the electrode spacing is 3 mm or greater.
To illustrate the existence of a plateau more clearly, in step 128 CPU 42 fits a polynomial, typically a third degree polynomial to the generated graph, calculates the first derivative of the polynomial, and plots a graph of the first derivative vs. the information threshold.
A graph 224 is the first derivative local efficiency vs. mutual information thresholds for the 10% remodeling graph 210;
A graph 228 is the first derivative local efficiency vs. mutual information thresholds for the 50% remodeling graph 214; and
A graph 232 is the first derivative local efficiency vs. mutual information thresholds for the 90% remodeling graph 218.
As seen in the graphs, the presence of a minimum in the graph indicates large or very large remodeling, whereas there is no minimum in the graph for small amounts, e.g., 10% remodeling. Furthermore, the “sharpness” of the minimum, e.g., the radius of curvature at the minimum, is indicative of the degree of remodeling, and embodiments of the invention may measure the radius of curvature, or some other metric of sharpness, to evaluate the degree of modeling.
In step 128 the first derivative graph may be presented to physician 22 on screen 74. Alternatively or additionally, CPU 42 may determine whether or not there is a minimum in the first derivative graph, and if there is the CPU may measure its sharpness. From the determination the CPU may present a conclusion such as “no significant remodeling,” “intermediate remodeling,” or “high remodeling” on screen 74.
It will be appreciated that in step 128, there may be no requirement for CPU 42 to generate all the physical graphs described, and that the CPU may generate data corresponding to some of the graphs. In other words, the CPU may just use the ordered pairs from step 116, and from the ordered pairs may present the first derivative graph and/or the conclusion described above.
The description above has, for simplicity, assumed that the signals acquired by the electrodes are used to form LATs. Those having ordinary skill in the art will be able to adapt the description, mutatis mutandis, using voltages, typically unipolar or bipolar voltages, or action potential voltages, of the signals, rather than LATs.
It will be appreciated that the embodiments described above are cited by way of example, and that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof which would occur to persons skilled in the art upon reading the foregoing description and which are not disclosed in the prior art.
This application claims the benefit of U.S. Provisional Patent Application 63/133,723, filed 4 Jan. 2021, which is incorporated herein by reference.
Number | Date | Country | |
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63133723 | Jan 2021 | US |