Using unipolar configurations for irreversible electroporation (IRE)

Abstract

The invention discloses a pulse field ablation (PFA) system. The PFA system comprises a composite electrode, a body surface electrode, a PFA generator and a processor. The composite electrode is coupled to a distal end of a catheter configured for insertion into an organ of a patient. The body surface electrode is configured to be attached to the skin of a patient. The PFA generator is configured to be electrically connected to the composite electrode of the catheter and electrically connected to the body surface electrode, and to generate direct current (DC) PFA pulses. The processor is configured to control the PFA generator to apply a DC PFA pulse between the composite electrode and the body surface electrode when the composite electrode is placed in contact with a target tissue of the organ and the body surface electrode is in contact with a patient's skin.

Description

Technical Field

[0001] The present invention generally relates to invasive ablation and, more particularly, to irreversible electroporation (IRE) of cardiac tissue in monopolar mode. Background Art

[0002] The use of multi-electrode catheters for irreversible electroporation (IRE) has been previously proposed in the patent literature. For example, PCT International Publication WO 2018 / 191149 describes an electroporation system and method for energizing a catheter used to deliver electroporation. A catheter for delivering electroporation includes a distal segment and an electrode assembly. The distal segment is configured to be positioned in a vein within the body. The vein defines a central axis. The electrode assembly is coupled to the distal segment and includes a structure and a plurality of electrodes distributed around the structure. The structure is configured to at least partially contact the vein. Each of the electrodes is configured to be selectively energized to form a circumferential ring of energized electrodes that is concentric with the central axis of the vein. In one embodiment, each electrode is individually wired such that it can be selectively paired or combined with any other electrode to act as a bipolar or multipolar electrode.

[0003] As another example, U.S. Patent 8,295,902 describes a tissue electrode assembly that includes a septum configured to form an expandable, conformable body that can be deployed within a patient. The assembly also includes a flexible circuit positioned on a surface of the septum. Conductive electrodes cover at least a portion of the flexible circuit and a portion of the septum surface not covered by the flexible circuit, wherein the conductive electrodes are foldable on themselves with the septum into a delivery conformation having a diameter suitable for minimally invasive delivery of the assembly to a patient. In one embodiment, the pattern of a plurality of electrodes deposited on the septum can collectively form a large electrode array of an energy transfer element. Summary of the Invention

[0004] Embodiments of the present invention described below provide a pulsed field ablation (PFA) system that includes a composite electrode, a body surface electrode, a PFA generator, and a processor. The composite electrode is coupled to a distal end of a catheter configured for insertion into an organ of a patient. The body surface electrode is configured to be attached to the skin of the patient. The PFA generator is configured to: be electrically connected to the composite electrode of the catheter and electrically connected to the body surface electrode, and generate direct current (DC) PFA pulses. The processor is configured to: control the PFA generator to: apply a DC PFA pulse between the composite electrode and the body surface electrode when the composite electrode is placed in contact with target tissue of the organ and the body surface electrode is in contact with the skin of the patient.

[0005] In some embodiments, the catheter includes a plurality of electrodes and includes a switching assembly configured to electrically short the plurality of electrodes to each other to form a composite electrode.

[0006] In some embodiments, the catheter includes an expandable frame coupled to the distal end of the catheter, and the plurality of electrodes are disposed on the expandable frame.

[0007] In one embodiment, the catheter is a tip catheter having tip electrodes that serve as a composite electrode.

[0008] In another embodiment, the catheter includes a plurality of electrodes that are permanently shorted to each other by electrical connections disposed on the catheter to form a composite electrode.

[0009] In some embodiments, the PFA generator is configured to generate DC PFA pulses having voltage polarities that alternate between pulses.

[0010] In other embodiments, the PFA generator is configured to generate DC PFA pulses in a plurality of bursts separated by pause intervals.

[0011] In one embodiment, the DC PFA pulse is a bipolar DC PFA pulse.

[0012] According to another embodiment of the present invention, there is also provided a pulsed field ablation (PFA) method, which includes inserting a composite electrode coupled to the distal end of a catheter into an organ of a patient. Body surface electrodes are attached to the skin of the patient. When the composite electrode of the catheter is placed in contact with the target tissue of the organ and the body surface electrodes are in contact with the skin of the patient, a direct current (DC) PFA pulse is applied between the composite electrode and the body surface electrodes. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The present invention will be more fully understood from the following detailed description of embodiments of the invention in conjunction with the accompanying drawings, in which:

[0014] Figure 1 is a schematic illustration of a catheter-based irreversible electroporation (IRE) system according to an embodiment of the present invention;

[0015] Figure 2 is according to an embodiment of the present invention Figure 1 schematic illustration of an IRE catheter using bursts of unipolar pulsed field ablation (PFA) pulses to ablate a pulmonary vein (PV) ostium; and

[0016] Figure 3 schematically shows the use of a system according to an embodiment of the present invention Figure 1 flowchart of a method of applying unipolar PFA pulses. Detailed implementation mode

[0017] Overview

[0018] Irreversible electroporation (IRE), also known as pulsed field ablation (PFA), can be used as an invasive treatment modality to kill tissue cells by subjecting them to high voltage pulses. Specifically, IRE pulses can be used to kill myocardial tissue cells to treat arrhythmias. Cell disruption occurs when the transmembrane potential exceeds a threshold, leading to cell death and thus the development of tissue lesions. Therefore, particular attention is paid to using high voltage bipolar electrical pulses (e.g., using a selected pair of electrodes in contact with the tissue) to generate a high electric field (e.g., an electric field above a certain threshold) to kill the tissue cells between the electrodes.

[0019] IRE is typically performed by applying high voltage pulses between pairs of electrodes that are relatively close to each other, because the generated field strength must be high. In other words, IRE is typically a bipolar operation and is achieved over a relatively small area. However, if IRE is to be applied to a large tissue area, such as to ablate the entire circumference of the pulmonary vein (PV) ostium using bipolar pulses, then the ablation must be repeatedly applied to multiple individual portions of the area, which is time-consuming and may result in inconsistent results due to, for example, cardiac motion that makes the contact of the catheter with the ostium unstable.

[0020] The embodiments of the present invention described below use a multi-electrode catheter, such as a balloon catheter, a basket catheter, or a loop catheter, and connect multiple (e.g., all) electrodes together to effectively form a composite catheter electrode. The catheter is inserted into a patient, and the composite electrode is connected to one lead of the output of a PFA generator. Body surface electrodes ("skin electrodes") such as back patches are used as the return electrode for the generator. Typically, the skin electrodes are relatively large (e.g., 10 cm × 20 cm). The PFA generator generates PFA pulses between the composite electrode of the catheter and the skin electrode, thereby performing IRE on the tissue contacted by the composite electrode. The PFA pulses are typically direct current (DC) voltage pulses, such as rectangular voltage pulses. The parameters of the PFA pulses (e.g., pulse width, duty cycle, and amplitude) are typically selected according to a protocol that has been shown to kill the expected target tissue with little or no damage to other tissues. In some embodiments, the PFA generator generates a burst of PFA pulses, where the voltage polarity of the pulses in each burst alternates between pulses.

[0021] When using the techniques disclosed in the present invention to apply PFA pulses, the current density near the composite electrode is higher than the current density at the external back patch because the surface area of the composite electrode is smaller than the surface area of the back patch. The higher current density causes ablation to occur near the composite electrode rather than near the back patch.

[0022] Multiple electrodes of the catheter can be connected in different ways to form a composite electrode. The connection can be formed, for example, using a switching circuit in a PFA generator. In another embodiment, the composite electrode is formed by using an electrical connection at the distal end of the catheter, which creates a permanent short circuit between the electrodes disposed on the catheter.

[0023] In some embodiments, catheters typically used in monopolar radiofrequency (RF) ablation (such as catheters having a single large electrode, e.g., a tip catheter having a tip electrode) can be used with the techniques disclosed herein for monopolar PFA ablation. The sinusoidal RF ablation waveform typically has a maximum amplitude of 200 volts, and the RF energy destroys tissue by heating the tissue. On the other hand, IRE / PFA pulses are typically square wave DC pulses with a voltage amplitude higher than 500V (peak-to-peak value 1000V) and up to 2000V, with the aim of obtaining a strong electric field to kill tissue cells without heating.

[0024] The techniques disclosed herein generally use an optimized protocol to overcome muscle contraction, such as skeletal muscle contraction, which is a side effect of DC monopolar IRE. To this end, PFA pulses with a high repetition rate (e.g., >100KHz) are generated, where the alternating voltage polarities provide a substantially zero DC average voltage.

[0025] For example, the PFA pulses can include positive and negative pulses applied between the composite electrode and the patch, with a pulse width of 0.5 μs to 5 μs, and an interval between the positive and negative pulses of 0.5 μs to 5 μs. The terms "positive" and "negative" used herein refer to arbitrarily selected polarities between the two electrodes. The pulses can be grouped into pulse trains, each pulse train including between two and one hundred DC PFA pulses, where the PFA pulse-to-PFA pulse period is 0.1 μs to 0.7 μs, and the interval between PFA pulse trains is 10 μs to 100 μs. Such trains of pure ultra-short AC pulses ensure that only a minimal amount of muscle activation will occur in the monopolar configuration disclosed herein.

[0026] By providing a monopolar PFA configuration as an alternative to a bipolar PFA configuration, the IRE ablation procedure in the mouth of the PV using a catheter, for example, can be made easier while maintaining clinical efficacy.

[0027] System Description

[0028] Figure 1Schematic illustration of a catheter-based irreversible electroporation (IRE) system 20 according to an embodiment of the present invention. System 20 includes a catheter 21, wherein the shaft 22 of the catheter is inserted by a physician 30 through a sheath 23 into the vascular system of a patient 28. The physician then navigates the distal end 22a of the shaft 22 to a target location (inset 25) within the heart 26 of the patient 28.

[0029] Once the distal end 22a of the shaft 22 has reached the target location, the physician 30 generally retracts the sheath 23 by pumping saline into the balloon 40 and inflates the balloon 40. The physician 30 then manipulates the shaft 22 such that the electrodes 50 disposed on the balloon 40 catheter engage the inner wall of the PV ostium 51 to apply a high-voltage PFA pulse to the ostium 51 tissue via the electrodes 50.

[0030] As shown in inset 25, the distal end 22a is equipped with an expandable balloon 40 that includes a plurality of equally spaced IRE electrodes 50. Since the distal portion of the balloon 40 has a flat shape, the distance between adjacent electrodes 50 can remain substantially constant even when the electrodes 50 cover the distal portion. Thus, the configuration of the balloon 40 allows for more effective electroporation (e.g., with a substantially uniform electric field strength) between adjacent electrodes 50.

[0031] Certain aspects of the inflatable balloon are addressed in, for example, U.S. Patent Application 16 / 993,092, filed August 13, 2020, entitled "Applying Bipolar Ablation Energy Between Shorted Electrode Groups", which is assigned to the assignee of the present patent application and the disclosure of which is incorporated herein by reference.

[0032] In the embodiments described herein, the catheter 21 can be used for any suitable diagnostic and / or therapeutic purpose, such as electrophysiological sensing and / or the aforementioned IRE isolation of the PV ostium 51 tissue in the left atrium 45 of the heart 26.

[0033] The proximal end of the catheter 21 is connected to a switch assembly 48 included in a console 24, wherein a circuit forms an effective composite electrode 250 by shorting the electrodes 50 to each other (e.g., using the switches of the assembly 48). The electrodes 50 are connected to the assembly 48PFA by wires (shown in Figure 2 ) that extend through the shaft 22 of the catheter 21. The console 24 also includes a PFA pulse generator 38 to which the assembly 48 is connected, wherein the generator 38 is configured to apply a PFA pulse between the composite electrode 250 and a skin patch electrode (in Figure 2A PFA pulse is applied between the (shown in). An IRE pulse generator similar to the PFA pulse generator 38 is described in U.S. Patent Application No. 16 / 701,989, filed on December 3, 2019, entitled "Pulse Generator for Irreversible Electroporation", which is assigned to the assignee of the present patent application and the disclosure of which is incorporated herein by reference.

[0034] The memory 34 of the console 24 stores an IRE protocol including PFA pulse parameters such as the inter-peak voltage and the pulse width, as Figure 2 described.

[0035] The console 24 includes a processor 41, typically a general-purpose computer, which has suitable front-end and interface circuitry 37 for receiving signals from the catheter 21 and from external electrodes 49 that are typically placed around the chest of the patient 28. To this end, the processor 41 is connected to the external electrodes 49 through wires extending through the cable 39.

[0036] During the procedure, the system 20 can use the Active Current Location (ACL) method provided by Biosense-Webster (Irvine, California) to track the corresponding positions of the electrodes 50 within the heart 26, which is described in U.S. Patent No. 8,456,182, the disclosure of which is incorporated herein by reference.

[0037] In some embodiments, the physician 30 can modify any of the parameters of the monopolar IRE protocol used with the composite electrode 250 from the user interface 47. The user interface 47 can include any suitable type of input device, such as a keyboard, a mouse, or a trackball, etc.

[0038] The processor 41 is typically programmed in software to perform the functions described herein. The software can be downloaded electronically to the computer through a network, for example, or alternatively or additionally it can be set and / or stored on a non-transitory tangible medium (such as a magnetic memory, an optical memory, or an electronic memory).

[0039] Specifically, the processor 41 runs a dedicated protocol as disclosed herein, which is included in Figure 3 such that the processor 41 can perform the steps disclosed in the present invention, as further described below.

[0040] IRE Using a Monopolar Configuration

[0041] Figure 2 For an embodiment in accordance with the present invention Figure 1Schematic illustration of an irreversible electroporation (IRE) catheter 40 using a train of monopolar pulsed - field ablation (PFA) pulses 100 to ablate the pulmonary vein (PV) ostium 51. Figure 2 The composite electrode 250 is shown in contact with the ostium 51 around its entire circumference. The composite electrode is connected via a cable 60 to a switching assembly 48, where individual wires of the cable 60 connected to the electrodes 50 are short - circuited to each other in the assembly 48 to form an effective composite electrode 250. A single conductor 62 connects the switching assembly 48 to one end of a PFA generator 38. The other lead of the PFA generator 38 is connected to a back - patch electrode 66 attached to the patient's skin.

[0042] As described above, implementing monopolar PFA using the electrode 250 requires applying a dedicated IRE protocol with appropriate PFA pulses to the patient. In some embodiments, the provided PFA protocol divides (segments) the delivery of PFA pulses of a selected protocol into a plurality of pulse trains (“pulse bursts”) 204, with a pause 202 between the pulse trains. This pause allows the muscle to relax in case any contraction occurs.

[0043] Figure 2 Illustration 222 is a schematic diagram of the waveform 200 of a PFA pulse according to an embodiment of the present invention. In an IRE procedure, the PFA signal is delivered to the electrode 50 as a waveform 200 having one or more pulse trains 204. The waveform 200 includes N T pulse trains 204, where each train includes N P bipolar DC pulses 100. The shape of the bipolar pulse is described below. The length of the pulse train 204 is labeled as t T . The period of the bipolar pulses 100 within the pulse train 204 is labeled as t PP , and the interval between consecutive trains 204 is labeled as Δ T , during which no signal is applied. Typical values of the parameters of the waveform 200 are given in Table 1 below.

[0044] A schematic diagram of the PFA pulse 100 is depicted in Illustration 222. As shown, the curve 102 shows the variation of the voltage of the PFA pulse 100 with time during a PFA ablation procedure. The bipolar PFA pulse includes a positive pulse 104 and a negative pulse 106, where the terms “positive” and “negative” refer to an arbitrarily chosen polarity of the electrodes 50 and 66 between which the PFA pulse is applied. The amplitude of the positive pulse 104 is labeled as V +, and the time - width of the DC pulse is labeled as t +. Similarly, the amplitude of the negative pulse 106 is labeled as V -, and the time - width of the DC pulse is labeled as t -. The time - width between the positive pulse 104 and the negative pulse 106 is labeled as t 间隔 . Typical values of the parameters of the bipolar pulse 100 are given in Table 1 below.

[0045]

[0046] Table 1: Typical Values of Parameters of Monopolar PFA Signals

[0047] As shown in Table 1, the PFA pulse is different from the RF signal. Among them, the voltage amplitude of the optional RF signal is at most 200V, while the PFA voltage amplitude is higher than 1000V.

[0048] Figure 3 To schematically show the method of using Figure 1 system 20 according to an embodiment of the present invention to apply a monopolar pulsed field ablation (PFA) pulse. The algorithm according to an embodiment of the present invention executes a process starting from the catheter insertion step 300, in which the physician 30 inserts the balloon 40 into the patient's heart 26, and the balloon has a plurality of electrodes 50 arranged in a radial geometry on the balloon. In the electrode placement step 302, the electrodes 50 are placed in contact with the target tissue of the heart 26 (for example, at the orifice 51), as described above with respect to Figure 1 and Figure 2 stated.

[0049] In the IRE protocol selection step 304, the physician 30 selects a protocol having parameters suitable for pulsed monopolar PFA, such as the parameters provided in Table 1.

[0050] In the electrode short - circuit step 306, the processor 41 controls the switch assembly 48 to electrically short - circuit between the electrodes 50 to form the composite electrode 250, as described with respect to Figure 1 and Figure 2 stated.

[0051] Finally, in the monopolar PFA ablation step 308, the processor 41 controls the RF generator 38 to apply a monopolar PFA pulse between the composite electrode 250 placed in contact with the target tissue and the patch electrode 66, as described above with respect to Figure 2 stated.

[0052] Although the embodiments described herein mainly relate to cardiac applications, the methods and systems described herein can also be used in other medical applications, such as the treatment of lung cancer and liver cancer.

[0053] Accordingly, it should be understood that the embodiments described above are cited by way of example, and the present invention is not limited to what has been specifically shown and described above. On the contrary, the scope of the present invention includes combinations and sub-combinations of the various features described above, as well as their variations and modifications, which will occur to those skilled in the art upon reading the above description and which are not disclosed in the prior art. Documents incorporated by reference into this patent application are considered an integral part of this application, except that any terms defined in these incorporated documents that conflict with the definitions expressly or implicitly given in this specification shall be considered only in light of the definitions in this specification.

Claims

1. A pulsed field ablation (PFA) system, comprising: A plurality of electrodes coupled to a distal end of a catheter configured to be inserted into an organ of a patient; A body surface electrode configured to be attached to the skin of the patient; A PFA generator configured to: be electrically connected to the plurality of electrodes of the catheter and electrically connected to the body surface electrode, and generate a direct current (DC) PFA pulse, wherein the DC PFA pulse is configured to ablate target tissue of the organ; A processor configured to: control the PFA generator to: apply the DC PFA pulse between the plurality of electrodes and the body surface electrode when the plurality of electrodes are placed in contact with the target tissue of the organ and the body surface electrode is in contact with the skin of the patient; And A switch assembly connected between a proximal end of the catheter and the PFA generator, wherein the switch assembly is only configured to connect all of the plurality of electrodes to a single lead of the PFA generator output before ablating the target tissue using the DC PFA pulse, and wherein connecting all of the plurality of electrodes to a single lead is based on electrically shorting the plurality of electrodes.

2. The PFA system according to claim 1, wherein electrically shorting the plurality of electrodes is configured to form a single composite electrode configured to simultaneously ablate an entire circumference of a pulmonary vein (PV) ostium.

3. The PFA system according to claim 1, wherein the catheter comprises an expandable frame coupled to the distal end of the catheter, and wherein the plurality of electrodes are disposed on the expandable frame.

4. The PFA system according to claim 1, wherein the PFA generator is configured to generate the DC PFA pulse having a voltage polarity that alternates between pulses.

5. The PFA system according to claim 1, wherein the PFA generator is configured to generate the DC PFA pulse in a plurality of bursts separated by pause intervals.

6. The PFA system according to claim 1, wherein the DC PFA pulse is a bipolar DC PFA pulse.

7. The PFA system according to claim 1, wherein the processor is configured to perform at least one of the following operations: capture a signal based on the switch assembly disconnecting the applied electrical short and track a respective position of each of the plurality of electrodes within the heart.

8. A pulsed field ablation (PFA) device, comprising: Means for inserting a plurality of electrodes into an organ of a patient, the plurality of electrodes being coupled to a distal end of a catheter; Means for attaching a body surface electrode to the skin of the patient; Means for applying a direct current (DC) PFA pulse between the plurality of electrodes and the body surface electrode when the plurality of electrodes of the catheter are placed in contact with the target tissue of the organ and the body surface electrode is in contact with the skin of the patient, the DC PFA pulse being configured to ablate the target tissue of the organ; A component for connecting a switch assembly between the proximal end of the catheter and a PFA generator, wherein the switch assembly is only configured to switch between connecting all of the plurality of electrodes to one lead of the PFA generator output and disconnecting all of the plurality of electrodes from one lead of the PFA generator output; And A component for operating the switch assembly to electrically short-circuit all of the plurality of electrodes before applying the DC PFA pulse to deliver a monopolar DC PFA ablation signal for ablating the target tissue.

9. The PFA device according to claim 8, wherein electrically short-circuiting the plurality of electrodes is configured to form a single composite electrode, and the single composite electrode is configured to simultaneously ablate the entire circumference of the pulmonary vein (PV) ostium.

10. The PFA device according to claim 8, wherein the component for applying the DC PFA pulse comprises a component for applying the DC PFA pulse having a voltage polarity that alternates between pulses.

11. The PFA device according to claim 8, wherein the component for applying the DC PFA pulse comprises a component for applying the DC PFA pulse in a plurality of bursts separated by pause intervals.

12. The PFA device according to claim 8, wherein the DC PFA pulse is a bipolar DC PFA pulse.

13. The PFA device according to claim 8, comprising a component for performing at least one of the following operations: capturing a signal based on the switch assembly disconnecting the applied electrical short-circuit and tracking the respective positions of each of the plurality of electrodes within the heart.

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