Bipolar organization ablation method and system according to predetermined periodic time slot groups

Abstract

The invention is entitled "Bipolar Organized Ablation According to Predetermined Periodic Sets of Time Slots". A method for applying bipolar ablation pulses, the method comprising positioning a plurality of electrodes of a catheter in contact with tissue of an organ. The tissue is ablated using the plurality of electrodes according to a predetermined pattern comprising periodic sets of time slots. Each of the time slots defines (i) a pair of electrodes (EP), (ii) a waveform of one or more bipolar ablation pulses (BAP) applied to the tissue by the EP, and (iii) a duration of the time slot. The time slots are applied sequentially, and the pattern further comprises at least one empty time slot.

Description

TECHNICAL FIELD

[0001] The present invention relates generally to medical devices, and in particular to methods and systems for bipolar tissue ablation. BACKGROUND

[0002] Various techniques for ablating an extended region of heart tissue by applying irreversible electroporation (IRE) pulses are known in the art.

[0003] For example, U.S. Patent 10470822 describes a system for estimating a three-dimensional treatment volume of a device for applying treatment energy through a plurality of electrodes that define a treatment region, the system including a memory, a display device, a processor coupled to the memory and the display device, and a treatment planning module stored in the memory and executable by the processor.

[0004] U.S. Patent Application Publication 2019 / 0336207 describes a system including a pulse waveform generator and an ablation device coupled to the pulse waveform generator. The ablation device includes at least one electrode configured for delivering ablation pulses to tissue during use. The pulse waveform generator is configured to deliver voltage pulses to the ablation device in a pulse waveform. The pulse waveform can include multiple tiers, and multiple groups of electrodes can be activated so that their pulse delivery is interleaved with one another. SUMMARY

[0005] Embodiments of the invention described herein provide a method for applying bipolar ablation pulses, the method including positioning a plurality of electrodes of a catheter in contact with tissue of an organ. The tissue is ablated using the plurality of electrodes according to a predetermined pattern including a set of periodic time slots. Each of the time slots defines: (i) an electrode pair (EP), (ii) a waveform of one or more bipolar ablation pulses (BAPs) applied by the EP to the tissue, and (iii) a duration of the time slot. The time slots are applied sequentially, and the pattern further includes at least one empty time slot.

[0006] In some embodiments, a first electrode of a first EP is positioned between a second electrode and a third electrode of a second EP. In other embodiments, each of the time slots includes a time gap scheduled before or after the one or more BAPs. In other embodiments, the BAPs include irreversible electroporation (IRE) BAPs.

[0007] In one embodiment, the EPs of the time slots have the same inter-electrode distance. In another embodiment, a first EP of a first time slot of the predetermined pattern includes a first electrode and a second electrode, and a second EP of a second time slot of the predetermined pattern includes the first electrode and a third electrode.

[0008] In some embodiments, the predetermined pattern includes at least one time slot positioned between the first time slot and the second time slot. In other embodiments, the positioning catheter includes a positioning lasso catheter.

[0009] According to embodiments of the present application, there is additionally provided a system comprising a catheter, a pulse generator, and a processor. The catheter comprises a plurality of electrodes configured to contact tissue of an organ. The pulse generator is configured to generate one or more bipolar ablation pulses (BAPs). The processor is configured to ablate the tissue according to a predetermined pattern comprising a periodic set of time slots, which are sequentially applied to the tissue, using the plurality of electrodes. Each of the time slots defines: (i) a pair of electrodes (EP) selected from the plurality of electrodes, (ii) a waveform of one or more BAPs applied to the tissue by the EP, and (iii) a duration of the time slot, and the pattern further comprises at least one empty time slot. BRIEF DESCRIPTION OF DRAWINGS

[0010] The present application will be more fully understood from the following detailed description of the embodiments thereof, taken together with the drawings in which:

[0011] Figure 1 schematic illustration of a catheter-based positioning-tracking and irreversible electroporation (IRE) ablation system according to exemplary embodiments of the present application;

[0012] Figure 2 schematic illustration of a distal segment of an IRE catheter having a plurality of electrodes, and a configuration for applying IRE pulses to selected electrodes thereof, according to exemplary embodiments of the present application; and

[0013] Figure 3 flowchart schematically illustrating a method for applying bipolar IRE ablation pulses to tissue, according to exemplary embodiments of the present application. DETAILED DESCRIPTION

[0014] SUMMARY

[0015] Irreversible electroporation (IRE) can be used to treat cardiac arrhythmias, for example, by using high-voltage pulses applied to tissue to ablate tissue cells. Cell destruction occurs when the transmembrane potential exceeds a threshold value, resulting in cell death and lesion formation. In an IRE-based ablation procedure (also referred to herein for brevity as IRE ablation), high-voltage bipolar electrical pulses are applied to a pair of electrodes, for example, in contact with tissue to be ablated, in order to form a lesion between the electrodes, thereby treating a cardiac arrhythmia in a patient's heart.

[0016] Sometimes, lasso catheters having multiple electrodes can be used to perform IRE ablation over an extended area. Due to the lasso shape of the catheter, when bipolar IRE pulses are applied to pairs of electrodes sequentially or simultaneously, one or more electrodes not intended to be energized can undesirably contact the energized electrodes and thus can compromise the results of the IRE ablation and in severe cases can be harmful to the patient.

[0017] Embodiments of the present invention described below provide improved techniques for applying IRE bipolar pulses using an ablation protocol that improves patient safety.

[0018] In some embodiments, in an IRE ablation procedure using a lasso catheter, a physician positions multiple electrodes of the catheter in contact with a target tissue, such as a pulmonary vein of a patient's heart. Subsequently, the physician can use a processor that controls an IRE ablation system for ablating the tissue using the multiple electrodes according to a predetermined pattern comprising a set of periodic time slots.

[0019] In some embodiments, the time slots are applied sequentially and each of the time slots defines: (i) a pair of electrodes (EP) selected from the multiple electrodes, (ii) a waveform of one or more bipolar ablation pulses (BAPs) applied by the EP to the tissue, also referred to herein as "IRE ablation pulses", and (iii) a duration of the time slot. Note that the term "periodic" refers to one or more repetitions of the same predetermined pattern. For example, a given predetermined pattern can have three time slots in which one or more BAPs are sequentially applied to a first EP, a second EP, and a third EP during a first time slot, a second time slot, and a third time slot, respectively. Subsequently, the given predetermined pattern is repeated by applying one or more BAPs to the first EP of the first time slot, and so on.

[0020] In some embodiments, the electrodes of different EPs are interleaved such that a first electrode of a first EP is positioned between a second electrode and a third electrode of a second EP. Each of the time slots includes a time gap scheduled before or after the one or more BAPs such that during the time gap, IRE ablation pulses are not applied to the target tissue.

[0021] In some embodiments, the pattern can also include at least one empty time slot, in other words, during the duration of the empty time slot, IRE ablation pulses are not applied to any EP.

[0022] The disclosed techniques improve safety in various bipolar ablation procedures that apply bipolar pulses to a target tissue having a wide area by controlling the location of the bipolar ablation pulses applied to the target tissue.

[0023] System Description

[0024] Figure 1 Schematic illustration of a catheter 21 -based location-tracking and irreversible electroporation (IRE) ablation system 20, in accordance with an exemplary embodiment of the present application.

[0025] In some embodiments, system 20 includes a deflectable tip segment 40 that fits over a distal end 22a of a shaft 22 of catheter 21, where tip segment 40 includes a plurality of electrodes 50 (inset 25). In the present example, tip segment 40 includes a CARTO® tip segment produced by Biosense Webster, Inc. (Irvine, Calif.) that includes 16 electrodes 50. In other embodiments, tip segment 40 can include any other suitable type of deflectable catheter having electrodes 50. Catheter, also referred to herein for brevity as "lariat." Lariat and electrodes 50 are described in detail below with reference to Figure 2 DETAILED DESCRIPTION.

[0026] In other embodiments, tip segment 40 can include any other suitable type of deflectable catheter having electrodes 50.

[0027] In the embodiments described herein, electrodes 50 are configured to apply IRE ablation pulses to tissue of left atrium 26, such as IRE ablation of ostia 51 of pulmonary veins in heart 26. Electrodes 50 can also be used to sense intracardiac electrocardiogram (ECG) signals. Note that the technology disclosed herein can be applied to other segments of heart 26 (e.g., atria or ventricles) with necessary modifications in details, and to other organs of patient 28.

[0028] In some embodiments, a proximal end of catheter 21 is connected to a control console 24 (also referred to herein as console 24) that includes an ablation power source, in the present example an IRE pulse generator (IPG) 45 that is configured to deliver peak power in the tens of kW range. Console 24 includes a switching box 46 that is configured to switch power applied by IPG 45 to a selected one or more pairs of electrodes 50. A sequence IRE ablation protocol (also referred to herein as an ablation plan or predetermined pattern) can be pre-defined by physician 30, or by processor 41, or by a combination thereof, and stored in a memory 48 of console 24.

[0029] In some embodiments, processor 41 and / or physician 30 can select the most suitable predetermined pattern for obtaining a desired result of an IRE ablation procedure, e.g., based on electrical mapping of activation pulses generated in heart 26. The selection of a predetermined pattern is described below with reference to Figure 2 The configuration of tip segment 40 with IPG 45 and switching box 46 is described in detail below, and the predetermined pattern is described in detail in Figure 2 and Figure 3

[0030] ​In some embodiments, physician 30 inserts distal end 22a of shaft 22 through sheath 23 into heart 26 of patient 28 lying on table 29. Physician 30 navigates distal end 22a of shaft 22 to a target location in heart 26 by manipulating shaft 22 using a manipulator 32 located, for example, proximate to the proximal end of catheter 21. During insertion of distal end 22a, deflectable tip segment 40 is held in an extended configuration by sheath 23. By including tip segment 40 in an extended configuration, sheath 23 also serves to minimize vascular trauma as physician 30 moves catheter 21 through the vasculature of patient 28 to a target location, such as an ablation site in heart 26.

[0031] Once distal end 22a of shaft 22 has reached the ablation site, physician 30 retracts sheath 23 and manipulates shaft 22 to place electrode 50 disposed above lasso of tip segment 40 in contact with the wall of ostium 51 at the ablation site. In the present example, the ablation site comprises a pulmonary vein, but in other embodiments, physician 30 can select any other suitable ablation site.

[0032] In some embodiments, electrode 50 is connected to processor 41 by wiring extending through shaft 22, which is configured to control switching box 46 of interface circuit 44 in console 24.

[0033] As further shown in inset 25, distal end 22a includes a position sensor 39 of a position tracking system, which is coupled to distal end 22a, for example, at tip segment 40. In the present example, position sensor 39 comprises a magnetic position sensor, but in other embodiments, any other suitable type of position sensor can be used (e.g., other than magnetic-based). During navigation of distal end 22a in heart 26, processor 41 of console 24 receives signals from magnetic position sensor 39, for example, for measuring the position of tip segment 40 in heart 26, in response to magnetic fields from external magnetic field generator 36, and optionally, displays a tracked position superimposed on an image of heart 26 on display 27 of console 24. Magnetic field generator 36 is placed at a known location outside of patient 28, for example, under table 29. Console 24 also includes drive circuit 34 configured to drive magnetic field generator 36.

[0034] The position sensing method using external magnetic fields is implemented in various medical application scenarios, for example, in CARTO® systems produced by Biosense Webster, Inc. (Irvine, Calif.). TMThe system is implemented in, and described in detail in, U.S. Patents 5,391,199, 6,690,963, 6,484,118, 6,239,724, 6,618,612, and 6,332,089, as well as PCT Patent Publication WO 96 / 05768, and U.S. Patent Application Publications 2002 / 0065455 Al, 2003 / 0120150 Al, and 2004 / 0068178 Al, the disclosures of which are all incorporated herein by reference in their entirety.

[0035] Typically, the processor 41 of the console 24 comprises a general purpose processor of a general purpose computer, with a suitable front end and interface circuitry 44 for receiving signals from the catheter 21, and for applying ablation energy to the left atrium of the heart 26 via the catheter 21, and for controlling other components of the system 20. The processor 41 typically comprises software in the memory 48 of the system 20, which is programmed to perform the functions described herein. The software can be downloaded to the computer in electronic form, over a network, for example, or it can alternatively or additionally be provided and / or stored on non-transitory tangible media, such as magnetic or optical storage media or an electronic memory.

[0036] Applying irreversible electroporation pulses to tissue

[0037] Irreversible electroporation (IRE), also known as pulsed field ablation (PFA), can be used as a minimally invasive treatment means for creating lesions (e.g., killing tissue cells) at an ablation site by applying high voltage pulses to the tissue. In the present example, IRE pulses can be used to kill myocardial tissue cells in order to treat cardiac arrhythmias in the heart 26. Cell destruction occurs when the transmembrane potential exceeds a threshold value, resulting in cell death and, thus, development of a tissue lesion. Thus, particular attention is paid to using high voltage bipolar electrical pulses (e.g., using a pair of electrodes 50 in contact with tissue at the ablation site) to create a high electric field (e.g., above a certain threshold) to create lesions by killing tissue cells located between the electrodes.

[0038] In the context of the present disclosure, a “bipolar” voltage pulse means a voltage pulse applied between two electrodes 50 of the catheter 21 (as opposed to, for example, a monopolar pulse applied during radiofrequency ablation by a catheter electrode relative to some common ground electrode not located on the catheter). Moreover, the terms “IRE pulse” and “bipolar ablation pulse” are used interchangeably and refer to one or more bipolar pulses applied by the IPG 45 to ablate tissue of the heart 26 via the switch box 46 and a pair of electrodes (EP) selected from the electrodes 50.

[0039] To perform IRE ablation on a relatively large tissue region of the heart 26, such as the ostium of a pulmonary vein (PV) or the periphery of any other suitable organ, it is necessary to use multiple pairs of electrodes 50 of the catheter 21 having multiple electrodes 50 in the tip segment 40. To make the generated electric field as spatially uniform as possible over the large tissue region, it is preferable to have the selected pairs of electrodes 50 have overlapping fields or at least fields that are adjacent to each other. However, there are components of Joule heating that occur with the field generated by IRE, and this heating can cause uncontrolled damage to the tissue and undesirable damage to the electrodes when multiple pairs of electrodes 50 are used in succession to apply predetermined IRE pulses according to a time-slot pattern.

[0040] In some embodiments, based on a pre-mapping of activation signals generated in the heart 26, the processor 41 is configured to assist the physician 30 in defining an IRE ablation plan. The pre-mapping can be performed using the electrodes 50 shown in the example of FIG. 1 and / or using surface electrodes 38 attached as by wires extending through the cable 37 to the chest and shoulders of the patient 28. Figure 1

[0041] In some embodiments, the surface electrodes 38 are configured to sense body surface (BS) ECG signals in response to the beating of the heart 26. The acquisition of the BS ECG signals can be performed using conductive pads attached to the body surface or any other suitable technique. As shown in FIG. 1, the surface electrodes 38 are attached to the chest and shoulders of the patient 28, however, additional surface electrodes 38 can be attached to other organs of the patient 28, such as the limbs. Figure 1

[0042] In some embodiments, the electrodes 50 are configured to sense intracardiac (IC) ECG signals and (e.g., simultaneously) the surface electrodes 38 are sensing BS ECG signals. In other embodiments, sensing IC ECG signals can be sufficient to perform IRE ablation, such that the surface electrodes 38 can be applied to other instances.

[0043] In some embodiments, the physician 30 can couple the multiple electrodes 50 to target tissue at an ablation site in the heart 26. The target tissue is intended to be ablated by applying one or more IRE pulses via the pairs of electrodes 50. It is noted that the IRE pulses can be applied to the target tissue multiple times using any suitable pattern during the IRE ablation procedure.

[0044] ​​For conceptual clarity, this particular configuration of system 20 is simplified and shown by way of example to illustrate certain problems addressed by embodiments of the present application and to demonstrate the application of these embodiments in enhancing the performance of such IRE ablation systems. Embodiments of the present application are in no way limited to this particular class of exemplary systems, however, and the principles described herein can be similarly applied to other classes of ablation systems.

[0045] Applying irreversible electroporation pulses to tissue according to a predetermined pattern

[0046] Figure 2 Schematic illustration of end segment 40 according to an exemplary embodiment of the present application, and the configuration for applying IRE pulses to selected electrodes 50.

[0047] In Figure 2 In the example shown, end segment 40 includes ten electrodes 50, referred to herein as electrodes 50A, 50B, 50C, 50D, 50E, 50F, 50G, 50H, 50I, and 50J, which are coupled to end segment 40 along the lasso described above. Figure 1

[0048] In some embodiments, IPG 45 applies BAPs to switch box 46, which is electrically coupled to each of electrodes 50A-50J via respective wires 55 or using any other suitable connection.

[0049] In some embodiments, based on the aforementioned mapping of heart 26, processor 41 and / or physician 30 can select the most appropriate predetermined pattern from the aforementioned one or more predetermined patterns of IRE ablation protocols stored in memory 48 for treating the arrhythmia detected in heart 26.

[0050] An example of a predetermined pattern is shown in Table 1 below:

[0051]

[0052]

[0053] Table 1 - Predetermined Patterns of EPs by Time Slot

[0054] As shown in Table 1, each time slot defines an electrode pair (EP) that receives a bipolar ablation pulse (BAP) generated by IPG 45 and routed to the respective EP via switch box 46.

[0055] ​In some embodiments, all EPs have the same inter-electrode distance. For example, the distance between electrodes 50E and 50G of time slot 1 is similar to the distance between electrodes 50F and 50H of time slot 2, and similar to the distance between electrodes 50C and 50E of time slot 9.

[0056] In some embodiments, at least some of the electrodes 50 are used more than once in different time slots of the same predetermined pattern, but are paired with different electrodes in the different time slots. For example, electrode 50C is paired with electrode 50A in time slot 1, and with electrode 50E in time slot 9. Moreover, as shown in Table 1, at least one time slot is positioned between two time slots having a common electrode in the predetermined pattern.

[0057] In some embodiments, the time slots are applied to the ablated tissue sequentially, but in other embodiments, two or more time slots can be applied simultaneously or with some overlap in timing.

[0058] In some embodiments, each time slot defines a waveform of one or more BAPs applied to the tissue by the respective EP in a burst. In the present example, the waveform includes ten pulses each of about 5 microseconds, applied at a frequency of 200 KHz, and the time slot ends with a time gap of about 0.5 milliseconds (msec), which is typically but not necessarily scheduled after the tenth pulse. Moreover, all time slots of Table 1 use the same waveform as the above-described waveform.

[0059] In the context of the present disclosure and claims, the term “about” or “approximately” with respect to any numerical or range of values indicates suitable dimensional tolerances that allow for a part or assembly to function for its intended purpose as described herein.

[0060] In some embodiments, the predetermined pattern includes a periodic set of time slots. In other words, the predetermined pattern is repeated one or more times after the end time slot 10 and the time gap, so as to complete the required amount of ablation energy applied to the ablated tissue. Note that the number of repetitions can be calculated based on the electrical mapping and the aforementioned ablation protocol. As noted above, the total duration of each time slot is slightly longer than about 0.5 msec, and therefore, the total duration of the predetermined pattern (also referred to herein as the cycle length) is slightly longer than 5 msec.

[0061] In such embodiments, each electrode pair of the predetermined pattern has a duration for cooling slightly longer than 5 msec before receiving the next waveform of ten BAPs, thereby preventing overheating of the respective electrodes, and also preventing uncontrolled damage to the segment of tissue located between the electrodes of the respective pair.

[0062] In some embodiments, the predetermined pattern of Table 1 has slots 5 and 6 empty. In the context and claims of the present disclosure, the term“empty” means that no BAP is applied to any EP of the electrode 50 of the tip segment 40. Note that in the present example, a time gap of 0.5 milliseconds is also preserved in the empty slots.

[0063] Note that the EPs of the predetermined pattern are interleaved between slots. For example, electrode 50F (along the tip segment 40) of slot 2 is positioned between electrodes 50E and 50G of slot 1.

[0064] In other embodiments, the ablation protocol can include a predetermined pattern that has all slots filled with respective EPs that receive one or more BAPs from the IPG 45. In other words, there are no empty slots.

[0065] In other embodiments, the physician 30 and / or the processor 41 can skip slots, e.g., by leaving the EPs defined in the slots unenergized, whereby the length of the cycle of the predetermined pattern can be shortened.

[0066] In alternative embodiments, each slot can include more than one waveform, with a time gap between adjacent waveforms.

[0067] This particular slot configuration and order of the predetermined pattern of Table 1 is shown by way of example in order to illustrate certain problems addressed by embodiments of the present application, and to demonstrate the application of these embodiments in enhancing the performance of such IRE ablation protocols. However, embodiments of the present application are by no means limited to this specific category of example predetermined patterns, and the principles described herein can be similarly applied to other categories of predetermined patterns and / or ablation protocols.

[0068] Figure 3 To schematically show a flowchart of a method for applying bipolar IRE ablation pulses to ablated tissue according to embodiments of the present application. The method starts with an ablation protocol definition step 100, in which a pattern of an ablation protocol having a periodic set of slots is defined. Each slot includes an electrode pair (EP), a waveform of one or more bipolar ablation pulses (BAPs), and a duration of the slot. As described above Figure 2 in the context of the present disclosure, a slot can include a time gap scheduled before or after the one or more BAPs of the waveform.

[0069] At a catheter insertion step 102, the physician 30 inserts the tip segment 40 of the catheter 21 into the heart 26 and positions the plurality of electrodes 50 in contact with the target tissue, as described above Figure 1 .

[0070] At a tissue ablation step 104 that ends the method, the predetermined pattern of the ablation protocol as described in step 100 above is applied to the target tissue, and in the present example, the ablation protocol is a bipolar IRE ablation protocol.Figure 2 In more detail, irreversible electroporation (IRE) bipolar ablation pulses (BAPs) are applied to the target tissue. Note that the predetermined pattern is periodic, such that the set of time slots defined in the end pattern repeats after the cycle of time slots is completed. The number of repetitions is defined based on the ablation protocol and the electrical mapping of the heart 26, such that in the case of multiple repetitions, the method terminates after the end of the last repetition, and the physician 30 retracts the tip segment 40 from the patient 28.

[0071] While the embodiments described herein primarily address irreversible electroporation of a patient's heart, the methods and systems described herein can also be used for other applications, such as, but not limited to, renal ablation, liver ablation, lung cancer treatment, or ablation of any other suitable organ.

[0072] It should therefore be understood that the embodiments described above are cited by way of example, and that the present application is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present application includes both combinations and sub-combinations of the various features described hereinabove, as well as variations and modifications thereof which would occur to persons of skill in the art upon reading the foregoing description and which are not disclosed in the prior art. Documents incorporated by reference in the present patent application are to be considered an integral part of the application except that to the extent any terms are defined in such incorporated documents in a manner inconsistent with the definitions expressly set forth in the present specification, the terms as expressly used in the present specification take precedence.

Claims

1. A system for applying bipolar ablation pulses, the system comprising: a catheter comprising a plurality of electrodes configured to be in contact with tissue of an organ; a pulse generator configured to generate one or more bipolar ablation pulses (BAPs); and a processor configured to ablate the tissue using the plurality of electrodes according to a predetermined pattern comprising a periodic set of time slots applied to the tissue, wherein two or more time slots are applied sequentially, and wherein each of the time slots defines: (i) a pair of electrodes (EP) selected from the plurality of electrodes, (ii) a waveform of the one or more BAPs applied to the tissue by the EP, and (iii) a duration of the time slot, and wherein the predetermined pattern further comprises at least one empty time slot, wherein a first EP of a first time slot of the predetermined pattern comprises a first electrode and a second electrode, and wherein a second EP of a second time slot of the predetermined pattern comprises the first electrode and a third electrode, wherein the predetermined pattern comprises at least one time slot positioned between the first time slot and the second time slot.

2. The system of claim 1, wherein the first electrode of the first EP is positioned between the second electrode and the third electrode of the second EP.

3. The system of claim 1, wherein each of the time slots comprises a time gap scheduled before or after the one or more BAPs.

4. The system of claim 1, wherein the BAPs comprise irreversible electroporation BAPs.

5. The system of claim 1, wherein the EPs have the same inter-electrode distance.

6. The system of claim 1, wherein the catheter comprises a lasso catheter.

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