Electrical field application for irreversible electroporation single heart ablation

Abstract

Disclosed herein are devices, systems, and methods for ablating tissue in a patient by electroporation. Embodiments generally include an ablation catheter having a hand, a shaft, and an electroporation electrode arrangement. The shaft has a distal end and defines a longitudinal axis of the ablation catheter. The electroporation electrode arrangement is located at the distal end of the shaft and is configured to generate a multidirectional electric field when at least one pulse sequence is delivered thereto. The multidirectional electric field includes at least two of the following directions relative to the longitudinal axis: substantially axial, circumferential, and transverse. The electroporation electrode arrangement is configured to be operably coupled to an electroporation generator configured to generate the at least one pulse sequence and configured to receive the at least one pulse sequence from the electroporation generator.

Description

[0001] This application is a divisional application of patent application No. 202180060536.0, filed on July 21, 2021, entitled “Electric Field Application in Irreversible Electroporation Single Cardiac Ablation”.

[0002] Related applications

[0003] This application claims priority to Provisional Application No. 63 / 056,017, filed on July 24, 2020, the entire contents of which are incorporated herein by reference. Technical Field

[0004] This disclosure relates to medical devices, systems, and methods for ablating patient tissue. More specifically, this disclosure relates to medical devices, systems, and methods for tissue ablation via electroporation. Background Technology

[0005] Ablation procedures are used to treat a wide range of conditions in patients. Ablation can be used to treat arrhythmias, benign tumors, cancerous tumors, and to control bleeding during the procedure. Typically, ablation is performed using thermal ablation techniques, which include radiofrequency (RF) ablation and cryoablation. In RF ablation, a probe is inserted into the patient's body, and radiofrequency waves are delivered through the probe to the surrounding tissue. The RF waves generate heat that destroys the surrounding tissue and burns blood vessels. In cryoablation, a hollow needle or cryoprobe is inserted into the patient's body, and a cold, heat-conducting fluid circulates through the probe to freeze and kill the surrounding tissue. Both RF ablation and cryoablation techniques indiscriminately kill tissue through cell necrosis, which may damage or kill other healthy tissues, such as tissue in the esophagus, phrenic nerve cells, and tissue in the coronary arteries.

[0006] Another ablation technique uses electroporation. In electroporation, or electropermeabilization, an electric field is applied to the cell to increase the permeability of the cell membrane. Electroporation can be reversible or irreversible, depending on the strength of the electric field. If electroporation is reversible, the increased permeability of the cell membrane can be used to introduce chemicals, drugs, and / or deoxyribonucleic acid (DNA) into the cell before the cell heals and recovers. If electroporation is irreversible, the affected cells are killed through apoptosis.

[0007] Irreversible electroporation can be used as a non-thermal ablation technique. In irreversible electroporation, a short series of high-voltage pulses is used to generate a sufficiently strong electric field to kill cells through apoptosis. In the ablation of cardiac tissue, irreversible electroporation may be a safe and effective alternative to the indiscriminate killing of thermal ablation techniques such as RF ablation and cryoablation. Irreversible electroporation can be used to kill target tissues, such as cardiac tissue, by using the strength and duration of an electric field that kills the target tissue without permanently damaging other cells or tissues, such as non-targeted myocardial tissue, erythrocytes, vascular smooth muscle tissue, endothelial tissue, and nerve cells. However, the effectiveness of electroporation depends on exposing the target tissue to a critical electric field strength, which depends on the electrode geometry. This is because the effectiveness of irreversible electroporation depends on the cell geometry and / or orientation relative to the generated electric field. And typically, the electrode geometry results in a finite (e.g., single) orientation of the electric field generated by the electrode. Summary of the Invention

[0008] In Example 1, an electroporation ablation system for treating target tissue includes an ablation catheter and an electroporation generator. The ablation catheter includes an axis defining a longitudinal axis, and an electroporation electrode arrangement located at the distal end of the axis and including a plurality of electrodes. The plurality of electrodes are arranged to define a plurality of anode-cathode pairs, each anode-cathode pair being configured to generate an electric field when a sequence of electrical pulses is delivered thereto. The plurality of anode-cathode pairs includes a first anode-cathode pair arranged to generate a first electric field having a first orientation relative to the longitudinal axis when a first sequence of electrical pulses is delivered thereto.

[0009] The second anode-cathode pair is arranged to generate a second electric field having a second orientation relative to the longitudinal axis when a second electrical pulse sequence is delivered thereto. The electroporation generator is operatively coupled to the electroporation electrode arrangement and configured to selectively generate a first electrical pulse sequence and deliver it to the first anode-cathode pair, and selectively generate a second electrical pulse sequence and deliver it to the second anode-cathode pair.

[0010] In Example 2, the electroporation ablation system of Example 1 is used, wherein the first orientation is generally aligned with the longitudinal axis, and wherein the second orientation is circumferentially around the longitudinal axis.

[0011] In Example 3, the electroporation ablation system of Example 1 is used, wherein the first orientation is generally aligned with the longitudinal axis, and wherein the second orientation is transverse to the longitudinal axis.

[0012] In Example 4, the electroporation ablation system of Example 1 is used, wherein the first orientation is transverse to the longitudinal axis and the second orientation is generally circumferentially around the longitudinal axis.

[0013] In Example 5, the electroporation ablation system of any of Examples 1-4, wherein each of the first pulse sequence and the second pulse sequence includes multiple direct current (DC) pulses.

[0014] In Example 6, the electroporation ablation system of Example 5 is used, wherein the DC pulse is a single-phase pulse, a two-phase pulse, or a three-phase pulse.

[0015] In Example 7, the electroporation ablation system of Example 6 is provided, wherein the electroporation generator is configured to generate DC pulses for each electrical pulse sequence separated by an inter-pulse delay, and wherein at least some of the DC pulses of the second electrical pulse sequence are delivered during the respective inter-pulse delay of the first electrical pulse sequence.

[0016] In Example 8, the electroporation system of Example 6 is provided, wherein the electroporation generator is configured to generate a plurality of electrical pulse sequence sets with pauses therebetween, wherein each electrical pulse sequence set includes a first electrical pulse sequence and a second electrical pulse sequence.

[0017] In Example 9, the electroporation ablation system of Example 6 is provided, wherein the DC pulses are biphasic pulses, and the electroporation ablation generator is configured to alternate between delivering a first electrical pulse sequence to a first anode-cathode pair and delivering a second electrical pulse sequence to a second anode-cathode pair.

[0018] In Example 10, the electroporation ablation system of Example 6, wherein each DC pulse is a three-phase pulse defined by a first phase having a first phase voltage and a first phase length, a second phase having a second phase voltage and a second phase length, and a third phase having a third phase voltage and a third phase length, wherein the first and third phases have the same polarity and the second phase has the opposite polarity.

[0019] In Example 11, the electroporation ablation system of Example 10 is used, wherein the first phase voltage, the first phase length, the second phase voltage, the second phase length, the third phase voltage, and the third phase length are selected such that each DC pulse is charge and energy balanced.

[0020] In Example 12, the electroporation ablation system of Example 11 has a first phase voltage, a second phase voltage, and a third phase voltage that are equal to each other, and wherein the first phase length and the third phase length are equal to each other and have a duration of half the second phase length.

[0021] In Example 13, the electroporation ablation system of Example 11 is used, wherein the first phase voltage and the third phase voltage and phase length are equal to each other and are different from the second phase voltage and the second phase length, respectively.

[0022] In Example 14, the electroporation ablation system of Example 10, wherein the first phase length, the second phase length, and the third phase length, as well as the first phase voltage, the second phase voltage, and the third phase voltage, are selected such that each DC pulse is charge-disequilibrium in order to promote electrolysis of the target tissue.

[0023] In Example 15, the electroporation ablation system of Example 5, wherein each DC pulse of the first electrical pulse sequence has a first voltage and a first pulse length, which is selected to ablate the target tissue by irreversible electroporation, and wherein each DC pulse of the second pulse sequence has a second voltage and a second pulse length, which is selected to create an electrolytic byproduct at the target tissue near the second anode-cathode pairing.

[0024] In Example 16, an electroporation ablation system for treating target tissue includes an ablation catheter and an electroporation generator. The ablation catheter includes:

[0025] The device comprises a handle, an axis having a distal end and defining a longitudinal axis of an ablation catheter, and an electroporation electrode arrangement located at the distal end of the axis and including a plurality of spatially arranged electrodes to generate a plurality of electric fields when a sequence of electrical pulses is delivered to selected electrode pairs. The plurality of electric fields include a first electric field having a first orientation relative to the longitudinal axis and a second electric field having a second orientation relative to the longitudinal axis. An electroporation generator is operatively coupled to the electroporation electrode arrangement and configured to selectively generate and deliver a sequence of electrical pulses to each selected electrode pair.

[0026] In Example 17, the electroporation ablation system of Example 16 is shown, wherein a first orientation is generally aligned with the longitudinal axis, and wherein a second orientation is circumferentially oriented around the longitudinal axis.

[0027] In Example 18, the electroporation ablation system of Example 16 is shown, wherein a first orientation is generally aligned with the longitudinal axis, and wherein a second orientation is transverse to the longitudinal axis.

[0028] In Example 19, the electroporation ablation system of Example 16 is shown, wherein a first orientation is transverse to the longitudinal axis and a second orientation is generally circumferentially around the longitudinal axis.

[0029] In Example 20, the electroporation ablation system of Example 16, wherein each of the multiple electrical pulse sequences includes multiple direct current (DC) pulses.

[0030] In Example 21, the electroporation ablation system of Example 20 is used, wherein the DC pulse is a single-phase pulse, a bi-phase pulse, or a three-phase pulse.

[0031] In Example 22, the electroporation ablation system of Example 20, wherein the electroporation generator is configured to generate DC pulses for each pulse sequence separated by an inter-pulse delay, and wherein at least some of the DC pulses of the first electrical pulse sequence are delivered during the corresponding inter-pulse delay of the second electrical pulse sequence.

[0032] In Example 23, the electroporation system of Example 16 is provided, wherein the electroporation generator is configured to generate a set of multiple electrical pulse sequences with pauses therebetween, wherein each set of electrical pulse sequences comprises multiple electrical pulse sequences.

[0033] In Example 24, the electroporation ablation system of Example 20, wherein the electroporation generator is configured to generate DC pulses for each electrical pulse sequence separated by an inter-pulse delay, and wherein at least some of the DC pulses of the second electrical pulse sequence are delivered during the respective inter-pulse delay of the first electrical pulse sequence.

[0034] In Example 25, the electroporation ablation system of Example 20, wherein the DC pulses are biphasic pulses, and the electroporation ablation generator is configured to alternate between delivering a first electrical pulse sequence to a first anode-cathode pair and delivering a second electrical pulse sequence to a second anode-cathode pair.

[0035] In Example 26, an electroporation ablation system for treating target tissue includes an ablation catheter comprising a handle, an axis having a distal end and defining a longitudinal axis of the ablation catheter, and an electroporation electrode arrangement located at the distal end of the axis and including a plurality of electrodes arranged to define a plurality of electrode pairs, each electrode pair being configured to generate an electric field when a sequence of electrical pulses is delivered thereto. The plurality of electrode pairs includes: a first electrode pair arranged to generate a first electric field having a first orientation relative to the longitudinal axis when a first sequence of electrical pulses is delivered thereto; and

[0036] A second electrode pair is arranged to generate a second electric field having a second orientation relative to a longitudinal axis when a second electrical pulse sequence is delivered thereto. An electroporation generator is operatively coupled to the electroporation electrode arrangement and configured to selectively generate a first electrical pulse sequence and deliver it to the first electrode pair, and selectively generate a second electrical pulse sequence and deliver it to the second electrode pair.

[0037] In Example 27, the electroporation ablation system of Example 26 is shown, wherein a first orientation is generally aligned with the longitudinal axis, and wherein a second orientation is circumferentially circumferentially around the longitudinal axis.

[0038] In Example 28, the electroporation ablation system of Example 26 is shown, wherein a first orientation is generally aligned with the longitudinal axis, and wherein a second orientation is transverse to the longitudinal axis.

[0039] In Example 29, the electroporation ablation system of Example 26 has a first orientation transverse to the longitudinal axis and a second orientation generally circumferentially around the longitudinal axis.

[0040] In Example 30, the electroporation ablation system of Example 26, wherein each of the first and second electrical pulse sequences comprises a plurality of biphasic DC pulses, and wherein the electroporation ablation generator is configured to alternate between delivering the first electrical pulse sequence to the first electrode pair and delivering the second electrical pulse sequence to the second electrode pair.

[0041] In Example 31, a method for generating a signal and delivering it to an electrode in an electroporation ablation system includes: delivering a first electrical pulse sequence to a first electrode pair of an electroporation catheter having a longitudinal axis to generate a first electric field having a first orientation relative to the longitudinal axis, and delivering a second electrical pulse sequence to a second electrode pair of the electroporation catheter to generate a second electric field having a second orientation relative to the longitudinal axis.

[0042] In Example 32, the method of Example 31, wherein delivering a first electrical pulse sequence to a first electrode pair and delivering a second electrical pulse sequence to a second electrode pair comprises: alternately delivering the first electrical pulse sequence to the first electrode pair and the second electrical pulse sequence to the second electrode pair over a time period to generate a dynamic rotating electric field, the dynamic rotating electric field comprising a pattern that varies over the time period.

[0043] In Example 33, the method of Example 32 is used, wherein the first orientation is generally aligned with the longitudinal axis, and wherein the second orientation is circumferentially around the longitudinal axis.

[0044] In Example 34, the method of Example 32 is used, wherein the first orientation is generally aligned with the longitudinal axis, and wherein the second orientation is transverse to the longitudinal axis.

[0045] In Example 35, the method of Example 32 is used, wherein the first orientation is transverse to the longitudinal axis and the second orientation is generally circumferentially around the longitudinal axis.

[0046] While several embodiments have been disclosed, other embodiments of the invention will become apparent to those skilled in the art from the following detailed description illustrating and describing illustrative embodiments of the invention. Therefore, the drawings and detailed description should be considered illustrative in nature and not restrictive. Attached Figure Description

[0047] Figure 1 This is a diagram illustrating an exemplary clinical setup for treating a patient and treating the patient's heart using an electrophysiological system according to an embodiment of the subject matter of this disclosure.

[0048] Figure 2AThis is a diagram illustrating the interaction between the distal end of a shaft included in a catheter and an electrode pair according to an embodiment of the subject matter of this disclosure.

[0049] Figure 2B This is a diagram illustrating the axial electric field generated by the interaction between electrode pairs according to an embodiment of the subject matter of this disclosure.

[0050] Figure 2C This is a diagram illustrating the circumferential electric field generated by the interaction between electrode pairs in a conduit according to an embodiment of the subject matter of this disclosure.

[0051] Figure 3A This is a diagram illustrating two pulse sequence series according to an embodiment of the subject matter of this disclosure, the two pulse sequence series comprising two sets of pulse sequences having interleaved monophase pulses to be delivered to electrodes in an electroporation electrode arrangement of a catheter.

[0052] Figure 3B This is a diagram illustrating two pulse sequence series according to an embodiment of the subject matter of this disclosure, the two pulse sequence series comprising two sets of pulse sequences having interleaved biphasic pulses to be delivered to electrodes in an electroporation electrode arrangement of a catheter.

[0053] Figures 3C-3D This is a schematic diagram illustrating an exemplary biphasic electrical pulse sequence to be delivered to an electrode arrangement according to an embodiment of the subject matter of this disclosure.

[0054] Figure 3E This is a diagram illustrating two pulse sequences of symmetrical three-phase pulses representing the charge and energy balance of electrodes in an electroporation electrode arrangement to be delivered to a catheter, according to an embodiment of the subject matter of this disclosure. One pulse sequence is non-alternating and the other is alternating.

[0055] Figure 3F This is a diagram illustrating two pulse sequences of asymmetric three-phase pulses representing the charge and energy balance of electrodes in an electroporation electrode arrangement to be delivered to a catheter, according to an embodiment of the subject matter of this disclosure. One pulse sequence is non-alternating and the other is alternating.

[0056] Figure 3G-Figure 3I This is a schematic diagram illustrating an exemplary sequence of charge-imbalanced pulses to be delivered to an electrode arrangement according to an embodiment of the subject matter of this disclosure.

[0057] Figure 4 This is a diagram illustrating the steps of a method for generating a signal and delivering it to an electrode in an electroporation ablation system.

[0058] While the invention may be modified and alternatively implemented in various ways, specific embodiments have been illustrated by way of example in the accompanying drawings and are described in detail below. However, it is not intended to limit the invention to the specific embodiments described. Rather, the invention is intended to cover all modifications, equivalents, and alternatives that fall within the scope of the invention as defined by the appended claims. Detailed Implementation

[0059] The following detailed description is exemplary in nature and is not intended to limit the scope, applicability, or configuration of the invention in any way. Rather, the following description provides some practical illustrations for carrying out exemplary embodiments of the invention. Examples of structures, materials, and / or dimensions are provided for selected elements. Those skilled in the art will recognize that many of the mentioned examples have a wide variety of suitable alternatives.

[0060] Figure 1 This is a diagram illustrating an exemplary clinical setup 10 for treating a patient 20 and the heart 30 of the patient 20 using an electrophysiology system 50 according to an embodiment of the subject matter of this disclosure. The electrophysiology system 50 includes an electroporation catheter system 60 and an electroanatomical mapping (EAM) system 70, the latter including a positioning field generator 80, a mapping and navigation controller 90, and a display 92. Furthermore, the clinical setup 10 includes additional devices such as an imaging device 94 (represented by a C-arm) and various controller elements, such as a foot controller 96, configured to allow an operator to control various aspects of the electrophysiology system 50. As those skilled in the art will understand, the clinical setup 10 may have… Figure 1 Other components and component arrangements not shown.

[0061] The electroporation catheter system 60 includes an electroporation catheter 105, a guide sheath 110, and an electroporation generator 130. Additionally, the electroporation catheter system 60 includes various connecting elements (e.g., cables, umbilical cables, and the like) that operate to functionally interconnect the components of the electroporation catheter system 60 and connect to the components of the EAM system 70. This arrangement of the connecting elements is not significant to this disclosure, and those skilled in the art will recognize that the various components described herein can be interconnected in a wide variety of ways.

[0062] In one embodiment, the electroporation catheter system 60 is configured to deliver electric field energy to target tissue in a patient's heart 30 to induce tissue cell apoptosis, thereby preventing the tissue from conducting electrical signals. The electroporation generator 130 is configured to control functional aspects of the electroporation catheter system 60. In another embodiment, the electroporation generator 130 is operable as an electroporation pulse generator for generating and supplying pulse sequences to the electroporation catheter 105, as described in more detail herein.

[0063] In one embodiment, the electroporation generator 130 includes one or more controllers, microprocessors, and / or computers that execute off-memory code to control and / or perform functional aspects of the electroporation catheter system 60. In another embodiment, the memory may be part of one or more controllers, microprocessors, and / or computers, and / or a portion of memory capacity accessible via a network such as the World Wide Web.

[0064] In one embodiment, the guide sheath 110 is operable to provide a delivery catheter through which the electroporation catheter 105 can be deployed to a specific target site within the patient's heart 30. However, it should be understood that the guide sheath 110 is illustrated and described herein to provide context for the overall electrophysiological system 50, but it is not critical to the novel aspects of the various embodiments described herein.

[0065] The EAM system 70 is operable to track the positioning of various functional components of the electroporation catheter system 60 and generate high-fidelity three-dimensional anatomical and electroanatomical mappings of the cardiac chambers of interest. In an embodiment, the EAM system 70 may be a RHYTHMIA product sold by Boston Scientific Corporation. TM HDx mapping system. Furthermore, in embodiments, the mapping and navigation controller 90 of the EAM system 70 includes one or more controllers, microprocessors, and / or computers that execute off-memory code to control and / or perform functional aspects of the EAM system 70, wherein in embodiments, the memory may be part of one or more controllers, microprocessors, and / or computers, and / or part of a memory capacity accessible via a network such as the World Wide Web.

[0066] As those skilled in the art will understand, Figure 1 The depiction of the electrophysiological system 50 shown is intended to provide a general overview of the various components of the system 50 and is not in any way intended to imply that this disclosure is limited to any set of components or arrangement of components. For example, those skilled in the art will readily recognize that additional hardware components (e.g., junction boxes, workstations, and the like) may and are likely to be included in the electrophysiological system 50.

[0067] EAM system 70 generates a positioning field via field generator 80 to define a positioning volume around heart 30, and one or more positioning sensors or sensing elements on one or more tracked devices (e.g., electroporation catheter 105) generate an output that can be processed by mapping and navigation controller 90 to track the positioning of the sensors and thus the corresponding devices within the positioning volume. In the illustrated embodiment, device tracking is achieved using magnetic tracking technology, whereby field generator 80 is a magnetic field generator that generates a magnetic field defining the positioning volume, and the positioning sensors on the tracked devices are magnetic field sensors.

[0068] In other embodiments, impedance tracking methods can be used to track the positioning of various devices. In such embodiments, the positioning field is an electric field generated, for example, by an external field generator (e.g., surface electrodes), an in vivo or intracardiac device (e.g., an intracardiac catheter), or both. In these embodiments, positioning sensing elements can form electrodes on the tracked device, generating outputs received and processed by the mapping and navigation controller 90 to track the positioning of various positioning sensing electrodes within the positioning volume.

[0069] In this embodiment, the EAM system 70 is equipped with both magnetic and impedance tracking capabilities. In such embodiments, in some cases, impedance tracking accuracy can be improved by first creating a mapping of the electric field induced by an electric field generator within the cardiac chamber of interest using a probe equipped with a magnetic positioning sensor, as is possible with the RHYTHMIA HDx™ mapping system described above. An exemplary probe is the INTELLAMAPORION, sold by Boston Scientific Corporation. TM Mapping catheter.

[0070] Regardless of the tracking method used, the EAM system 70 utilizes the location information of various tracked devices, along with cardiac electrical activity acquired by, for example, the electroporation catheter 105 or another catheter or probe equipped with sensing electrodes, to generate and display via the display 92 a detailed three-dimensional geometric anatomy map or representation of the heart chambers, as well as an electroanatomical map of the cardiac electrical activity of interest superimposed on the geometric anatomy map. Furthermore, the EAM system 70 can generate graphical representations of various tracked devices within the geometric anatomy map and / or the electroanatomical map.

[0071] Although the EAM system 70 is shown in combination with the electroporation catheter system 60 to provide a comprehensive depiction of an exemplary clinical setting 10, the EAM system 70 is not essential to the operation and function of the electroporation catheter system 60. That is, in embodiments, the electroporation catheter system 60 may be used independently of the EAM system 70 or any similar electroanatomical mapping system.

[0072] In the illustrated embodiment, the electroporation catheter 105 includes a handle 105a, a shaft 105b, and an electroporation electrode arrangement 150, which will be further described below. The handle 105a is configured to be operated by a user to position the electroporation electrode arrangement 150 at a desired anatomical location. The shaft 105b has a distal end 105c and generally defines the longitudinal axis of the electroporation catheter 105. As shown, the electroporation electrode arrangement 150 is located at or near the distal end 105c of the shaft 105b. In an embodiment, the electroporation electrode arrangement 150 is electrically coupled to an electroporation generator 130 to receive a sequence or series of electrical pulses to selectively generate an electric field for the target tissue to be ablated by irreversible electroporation.

[0073] As described above and also in more detail elsewhere in this document, the electroporation catheter system 60 is operable to generate a multidirectional electric field to ablate target tissue via irreversible electroporation. Such procedures include one-shot ablation procedures, such as pulmonary vein isolation (PVI) procedures and focal cardiac ablation procedures.

[0074] Figures 2A-2C Features of an electroporation conduit 105 including an electroporation electrode arrangement 150 according to an embodiment are shown. Figure 2A In the embodiment illustrated, the electroporation electrode arrangement 150 includes a plurality of electrodes 201a, 201b, 201c, 201d, 201e, and 201f arranged in a three-dimensional electrode array, such that the respective electrodes 201a, 201b, 201c, 201d, 201e, and 201f are axially (i.e., in the direction of the longitudinal axis LA), circumferentially around the longitudinal axis LA, and / or radially spaced from the longitudinal axis LA. In this embodiment, each of electrodes 201a, 201b, 201c, 201d, 201e, and 201f can be transmitted via an electroporation generator 130 (… Figure 1 It can be independently and selectively addressed to define multiple anode-cathode electrode pairs, each capable of receiving a sequence of electrical pulses from the electroporation generator 130, and thus generating an electric field capable of selectively ablating target tissue via irreversible electroporation. Figure 2A The diagram schematically illustrates the interactions (e.g., currents forming an electric field) between electrode pairs formed between electrodes 201 (e.g., 201a, 201b, 201c, 201d, 201e, and 201f) included in the electroporation conduit 105. In this diagram, the interactions are shown as paired arrows (e.g., ad, be, and df) indicating the currents between the electrodes 201. Furthermore, the electrode pairs (e.g., 201a and 201d, 201b and 201e, and 201d and 201f) are shown labeled with their corresponding currents (e.g., ad, be, and df).

[0075] Figure 2B This is a diagram illustrating the electric field 210 generated by the interaction between electrode pairs in the electroporation catheter 105. In this diagram, the axially oriented electric field 210 is shown as being located at an orifice 221 between the left atrium 223 and the left inferior pulmonary vein 225. In an embodiment, the axially oriented electric field 210 is generated by delivering electrical pulses to axially spaced anodes and cathodes.

[0076] Figure 2C This is also a diagram illustrating the electric field 210 generated by the interaction between the electrode pairs in the electroporation conduit 105. However, here, the electric field 210 is circumferentially oriented. In an embodiment, the circumferentially oriented electric field 210 is generated by delivering electrical pulses to circumferentially spaced anodes (“A”) and cathodes (“C”).

[0077] exist Figures 2A-2C It is evident that multiple electric fields 210 can be generated simultaneously and / or sequentially, and in both axial and circumferential orientations. For example, in an embodiment, by selectively controlling the timing of delivering electrical pulses to the respective electrodes 201, axial and circumferential electric fields 210 can be generated non-simultaneously in a predefined sequence. Furthermore, it should be understood that the intermittent generation of electric fields 210 caused by the staggered interactions between sets of electrode pairs, as well as electric field orientations other than axial and circumferential, are not beyond the scope of this disclosure and are indeed described in detail below.

[0078] like Figure 2A As can be seen, the electroporation electrode arrangement 150 may include a plurality of independently addressable electrodes 201 (e.g., anodes or cathodes) arranged to selectively define a plurality of electrode pairs (e.g., anode-cathode pairs). Each anode-cathode pair may be configured to generate an electric field when a pulse sequence is delivered thereto. The plurality of anode-cathode pairs may include at least two of a first anode-cathode pair, a second anode-cathode pair, and a third anode-cathode pair. The first anode-cathode pair may be arranged to generate a first electric field oriented generally circumferentially relative to the longitudinal axis when a first pulse sequence is delivered thereto. The second anode-cathode pair may be arranged to generate a second electric field oriented generally in the same direction as the longitudinal axis when a second pulse sequence is delivered thereto. The third anode-cathode pair may be arranged to generate a third electric field oriented generally transversely to the longitudinal axis when a third pulse sequence is delivered thereto. In embodiments, any combination of the first, second, and third pulse sequences may be delivered simultaneously or intermittently and may take various forms as described below.

[0079] In an embodiment, the electroporation electrode arrangement 150 can be configured to structurally arrange electrodes 201a, 201b, 201c, 201d, 201e, and 201f in a first region located distally and a second region located more proximally. In this way, electrode pairs can be formed across various electrodes 201 in the electroporation electrode arrangement 150 between the first and second regions. For example, electrodes 201d and 201f can be configured to form an electrode pair. Similarly, electrodes 201a and 201d, or electrodes 201b and 201e, or combinations thereof, can be selected to form a corresponding electrode pair. Thus, electrode pairs can include axially spaced electrodes, laterally spaced electrodes, or circumferentially spaced electrodes. Additionally, in an embodiment, a given electrode (e.g., 201d) can be used as a common electrode in at least two electrode pairs to generate an electric field 210.

[0080] Figure 2B A diagram illustrating an exemplary electric field 210 that can be generated by an electroporation electrode arrangement 150 is shown. The electroporation electrode arrangement 150 can be configured to generate a multidirectional electric field 210 when at least one pulse sequence is delivered thereto. The multidirectional electric field 210 can include at least two of the following directions relative to a longitudinal axis: generally axial, circumferential, and transverse. As used herein, transverse can mean any non-parallel angle relative to the longitudinal axis. As described elsewhere herein, the electroporation electrode arrangement 150 can be configured to be operatively coupled to an electroporation generator configured to generate at least one pulse sequence. The electroporation electrode arrangement 150 can be configured to receive at least one pulse sequence from the electroporation generator. Thus, the electroporation electrode arrangement 150 and the electroporation generator can operate in communication with each other. In this disclosure, such communication can be used to generate an electric field 210 that is at least substantially gapless.

[0081] Undesirable gaps in the electric field 210 generated by the electroporation electrode arrangement 150 can be limited or at least substantially eliminated. Such gaps can potentially lead to damage gaps and thus require, for example, multiple repositioning of the catheter. Overlapping electric fields 210 can at least substantially limit the number of such gaps. In embodiments, at least some of the electric fields 210 generated in the first pulse sequence set can at least partially overlap each other. For example, adjacent electric fields 210 (e.g., axial, transverse, and / or circumferential) in the combined electric field 211 can intersect each other, such that gaps are limited in the combined electric field 211. Overlap may occur at or near the periphery of adjacent electric fields 210, or may occur over the body or majority of one or more adjacent electric fields 210. In this disclosure, adjacent means adjacent electrodes 201 or electrodes 201 close to each other. The electroporation generator can be configured to generate a pulse sequence for generating overlapping electric fields.

[0082] The configuration of the electroporation electrode arrangement 150 in various embodiments can take any form suitable for a three-dimensional electrode structure, whether now known or developed later. In an exemplary embodiment, the electroporation electrode arrangement 150 may be in the form of a spline basket conduit, wherein the respective electrodes 201a, 201b, 201c, 201d, 201e, and 201f are positioned on a plurality of splines in any manner known in the art. In an embodiment, the electroporation electrode arrangement 150 may be formed on an expandable balloon, for example, wherein the electrodes are formed on flexible circuit branches or individual traces are arranged on the surface of the balloon. In other embodiments, the electroporation electrode arrangement 150 may be in the form of an expandable mesh. In short, the specific structure used to form the electroporation electrode arrangement 150 is not important to the embodiments of this disclosure.

[0083] Figures 3A-3I Various sequences of electrical pulses, which can be delivered to an electroporation electrode arrangement, for example, via an electroporation generator, according to embodiments of the subject matter of this disclosure, are illustrated. Figures 3A-3I As can be seen in the text and as described herein, various exemplary pulse sequences that can be delivered to the multiple anode-cathode pairs described above may include single-phase pulses, two-phase pulses, three-phase pulses, and four-phase pulses. The time-based characteristics of each pulse include orientation (e.g., axial, circumferential, or transverse) and polarity (e.g., positive (+) or negative (-)) as indicated on the axis.

[0084] Figure 3AThe illustration shows two pulse sequence series 301a and 302a, each pulse sequence series having two pulse sequence sets 310a and 320a therein. As shown, pulse sequence set 310a consists of single-phase direct current (DC) pulses 311a, 312a, 313a, and 314a. In the illustrated embodiment, pulses 311a and 313a are delivered to an anode-cathode pair that is generally axially oriented relative to the longitudinal axis of the electroporation conduit, while pulses 312a and 314a are delivered to an anode-cathode pair that is circumferentially arranged relative to the longitudinal axis. As shown, adjacent axially oriented pulses 311a and 313a are single-phase DC pulses separated by a predetermined inter-pulse delay in time and have opposite polarities. Similarly, adjacent circumferentially oriented pulses 312a and 314a are single-phase DC pulses separated by a predetermined inter-pulse delay in time and have opposite polarities. It should be understood that, in the embodiments, electrical pulses 311a and 313a may have the same (e.g., positive) polarity, and similarly, electrical pulses 312a and 314a may also have the same polarity. As shown, the series of electrical pulses 311a, 313a, 312a, and 314a are grouped into two sets 310a of electrical pulse sequences separated in time by pauses of predetermined length. In the illustrated embodiment, corresponding circumferentially oriented electrical pulses 312a and 314a are generated and delivered during the inter-pulse delay between adjacent axially oriented electrical pulses 311a and 313a.

[0085] In the illustrated embodiment, the pulse sequence series 302a and the corresponding pulse sequence set 320a differ from the pulse sequence series 301a and pulse sequence set 310a in that the electrical pulses 312a and 314a are opposite in polarity.

[0086] Further reference Figure 3AInterleaved pulses within a pulse sequence set (e.g., 310a, 320a) can be implemented using delays in the pulse sequences within the pulse sequence set. As described elsewhere herein, multiple pulse sequence sets may have a first pulse sequence set 310a, which includes both a first generated pulse sequence and a second generated pulse sequence. Each of the first generated pulse sequence (e.g., two pulses 311a) and the second generated pulse sequence (e.g., two pulses 312a) may include multiple pulses. The first generated pulse sequence may have a first inter-pulse delay between at least two pulses (e.g., between each pulse 311a in pulse sequence set 310a). The first generated pulse sequence and the second generated pulse sequence may be alternately arranged within the first pulse sequence set 310a such that at least one pulse in the second generated pulse sequence (e.g., the leftmost pulse 312a) occurs within the first inter-pulse delay. The second generated pulse sequence may have a second inter-pulse delay between at least two pulses (e.g., between each pulse 312a in pulse sequence set 310a). At least one pulse in the first generated pulse sequence (e.g., the rightmost pulse 311a) may occur within a second inter-pulse delay. Multiple pulse sequence sets may include second pulse sequence sets 310a, 320a, which are separate from the first pulse sequence sets 310a, 320a (respectively) and have pauses between the first and second pulse sequence sets. In embodiments, as shown herein, the inter-pulse delay between any two pulse sequences (e.g., between 311a and 312a) may be less than the pause between any two pulse sequence sets. However, this disclosure should not be limited to such a configuration, as, for example, in embodiments, the inter-pulse delay may be less than or equal to the inter-pulse-set delay if desired. The delay may facilitate the formation of an interleaved pulse sequence set 310a and / or the timing between pulse sequences. As will be understood by one skilled in the art, these concepts can be extended to any number of pulse sequences or post-sequence sets and any type of pulse.

[0087] It should be understood that, although Figure 3A Electrical pulses for delivery to axially and circumferentially oriented electrode pairs are depicted, but in other embodiments, one of these orientations may be replaced by a transversely oriented electrode pair.

[0088] Figure 3BThe diagram illustrates two pulse sequence series 301b and 302b, each pulse sequence series having two pulse sequence sets 310b and 320b. Each pulse sequence set consists of multiple pulse sequences, wherein interleaved biphasic DC pulses (e.g., 311b and 312b) are delivered to axially and circumferentially oriented electrode pairs in an electroporation electrode arrangement of an electroporation conduit, respectively. As shown, pulse sequence set 310b includes axially oriented biphasic pulses 311b separated in time by inter-pulse delays, and circumferentially oriented biphasic electrical pulses 312b interleaved in time with the axially oriented biphasic pulses. As further shown, in a given pulse sequence set 310b, a first circumferentially oriented electrical pulse 312b is generated during the inter-pulse delay between adjacent axially oriented electrical pulses 311b. However, it should be understood that this order may be reversed in other embodiments. In the illustrated embodiment, the pulse sequence series 320b is substantially the same as the pulse sequence series 310b, except that in the pulse sequence series 320b, the polarity of the circumferentially oriented electrical pulses 312b is reversed from one pulse to the next.

[0089] Further reference Figure 3B Different electrode pairs in an electroporation electrode arrangement can execute different pulse sequence series. A first electrode pair set can receive a first pulse sequence series 301b, and a second electrode pair set can receive a second pulse sequence series 302b. The first pulse sequence series 301b may differ from the second pulse sequence series 302b. In this way, for example, the electroporation electrode arrangement can have dedicated electrode pairs for generating electric fields in certain orientations. The first electrode pair set can generate an electric field in one of the axial, lateral, or circumferential orientations, and the second electrode pair set can generate any orientation that the first electrode set does not generate. For example, as illustrated herein, the first pulse sequence series 301b includes non-alternating pulses within the pulse sequence (e.g., 312b within 301b), while the second pulse sequence series 302b includes alternating pulses within the pulse sequence (e.g., 312b within 302b). The first pulse sequence series 301b and the second pulse sequence series 302b can be generated and / or delivered to the electroporation electrode arrangement synchronously or asynchronously. As further described below, these concepts can generate an electric field with dynamic gyration if executed over time. Both the first and second electrode pairs can receive either a first pulse sequence series or a second pulse sequence series (e.g., 301b or 302b). In this way, the magnitude of the electric field in a given orientation can be increased when only the first or second electrode pair generates the first or second pulse sequence series (e.g., 301b or 302b). Other pulse manipulation techniques can help improve the efficiency of electric field-driven electroporation.

[0090] Figures 3C-3D This is a schematic diagram illustrating alternative pulse sequence series 301c, 301d according to embodiments of the present disclosure. Figure 3C As shown, the pulse sequence series 301c comprises multiple alternating pulse sequences 305c, 306c, which are separated by corresponding pauses in time. As illustrated, each pulse sequence 305c, 306c consists of biphase DC pulse series 311c, 312c, respectively. In the illustrated embodiment, pulse sequence 305c is delivered to an axially oriented electrode pair to generate a generally axially oriented electric field, while pulse sequence 306c is delivered to a circumferentially oriented electrode pair to generate a circumferentially oriented electric field. As discussed elsewhere herein, in embodiments, the above order may be reversed, and / or one of the pulse sequences 305c, 306c may be delivered to a laterally oriented electrode pair.

[0091] exist Figure 3D In one embodiment, the pulse sequence series 301d includes two electrical pulse sequences 305d separated by a predetermined pause, which are delivered to an axially oriented electrode pair, followed by two electrical pulse sequences 306d separated by a predetermined pause and delivered to a circumferentially oriented electrode pair. Figure 3D As with the embodiments described above, the order can be reversed, and / or one of the pulse sequences 305d and 306d can be delivered to the laterally oriented electrode pair.

[0092] It should be emphasized that this disclosure should not be limited to Figures 3A-3D The orientations shown in the figures are different. Although depicted in these figures as having axial and circumferential orientations, the pulse sequences in this disclosure may include other combinations of orientations. For example, pulse sequences may include axial and lateral orientations, circumferential and lateral orientations, or each of axial, circumferential, and lateral orientations. Regardless of their form, pulse sequences may be arranged as a set of pulse sequences, and a set of pulse sequences may be arranged as a series of pulse sequences.

[0093] As discussed elsewhere herein, each generated pulse sequence delivered to multiple anode-cathode pairs can be charge and energy balanced, for example, to prevent the accumulation of electrolytic and ionic byproducts and to aid muscle stimulation. Although described and discussed using a specific number, orientation, or arrangement of pulse sequences, sets of pulse sequences, or series of pulse sequences, this disclosure should not be limited thereto, as will be understood by those skilled in the art. Likewise, it should be understood that pulse sequences may contain the same or different pulses, and sets of pulse sequences may contain the same or different pulse sequences.

[0094] Figure 3EIt is a diagram of two pulse sequences 305e of a symmetrical three-phase pulse (311t) for the charge and energy balance of the electrodes in the electroporation electrode arrangement to be delivered to the catheter, one non-alternating (301e) and the other alternating (302e). Figure 3F It is a diagram of two pulse sequences 305f of the asymmetric three-phase pulse (311t) of the electrodes in the electroporation electrode arrangement to be delivered to the catheter, one non-alternating (301f) and the other alternating (302f).

[0095] refer to Figure 3E According to embodiments of this disclosure, the voltage offset and amplitude can vary for a given pulse or between pulses. A rapid voltage offset may open more pores in the cell membrane. To generate such a voltage offset, one or more pulses in the pulse sequence may have alternating polarities. For example, in pulse sequence series 302e and pulse sequence set 310e, one or more pulses may include a first pulse 311t1 and a second pulse 311t2. The second pulse 311t2 may follow the first pulse 311t1, and the first pulse 311t1 and the second pulse 311t2 may have alternating polarities. Triphasic pulses, such as those shown in this figure, generate rapid voltage offsets within the pulse and may also generate this between two pulses. For example, as shown, the first pulse 311t1 is a triphasic pulse that may alternate between positive, negative, and positive polarities, and the second pulse 311t2 is a triphasic pulse that alternates between negative, positive, and negative polarities. In embodiments, the first pulse 311t1 and the second pulse 311t2 may be reversed without departing from the scope of this disclosure. As those skilled in the art will understand, these concepts can be extended to any number of pulses. Furthermore, even for short pulse distances, an increase in the number of openings in the cell membrane can be achieved proportionally to the high voltage amplitude. Each of these concepts can be achieved simultaneously by balancing charge and energy within the pulse sequence. The illustrated triphase pulse has symmetrical voltage amplitudes (V) and varying pulse lengths, such that d1 is approximately half the length of d2, and is therefore charge and energy balanced. However, depending on the intended application, these variables may be scaled to produce higher voltage amplitudes and shorter pulse lengths, and vice versa.

[0096] In embodiments, the three-phase pulse sequences 305e, 305f can be delivered in various forms while maintaining charge and energy balance. For example, boundary conditions can be established for each pulse and can include parameters of voltage amplitude and / or pulse length. When the pulse sequences 305e, 305f delivered to multiple anode-cathode pairs comprise one or more three-phase pulses, each three-phase pulse may have a first voltage amplitude and a second voltage amplitude, the first voltage amplitude being greater than or equal to the second voltage amplitude. Furthermore, each three-phase pulse may have a first voltage pulse length and a second voltage pulse length, the first voltage pulse length being less than or equal to the second voltage pulse length. The illustrated three-phase pulses have asymmetrical voltage amplitudes (v) and varying pulse lengths, such that d1 is less than d2, and are therefore charge and energy balanced while having higher voltage amplitudes (such as...) than symmetrical three-phase pulses. Figure 3E (Those shown in the diagram). Regardless of the form, pulse sequences such as those described above can be repeated during electroporation to systematically open more pores in the cell membrane.

[0097] In various embodiments, it may be advantageous to generate a sequence of charge-imbalanced electrical pulses and selectively deliver them to the target tissue to promote electrolysis within the target tissue. Generally, relatively short, high-voltage electrical pulses can effectively induce reversible or irreversible electroporation in cardiomyocytes. Conversely, relatively long, low-voltage electrical pulses can promote the formation of electrolytic byproducts in the cardiomyocyte tissue near the electrode. These electrolytic byproducts may tend to diffuse outward along the electric field gradient and enter the pores created in the cells via electroporation, thereby causing or at least promoting cell death due to intracellular electrolytic imbalance. This technique can lead to cell death in both irreversible and reversibly electroporated cells. Therefore, this disclosure contemplates interleaving electrical pulses configured to induce irreversible electroporation with pulses configured to promote the aforementioned electrolysis to increase the likelihood of successful ablation of the target tissue.

[0098] Figure 3GThis diagram schematically illustrates an exemplary pulse sequence series 301g, consisting of interleaved axially oriented electrical pulses 311g, 313g and circumferentially oriented electrical pulses 312g, 314g, wherein electrical pulses 312g, 314g are inserted between adjacent electrical pulses 311g, 313g. As shown, electrical pulses 311g, 313g are characterized by pulse length d1 and voltage V1, while electrical pulses 312g, 314g are characterized by pulse length d2 and voltage V2. In this embodiment, the pulse length d1 and voltage V1 are relatively short and high, respectively, and are designed to ablate target tissue via irreversible electroporation. Additionally, the pulse length d2 is substantially shorter than the pulse length d1, and the voltage V2 is substantially lower than the voltage V1. The resulting interleaved electric fields generated at the corresponding electrode pairs delivered by the electrical pulses 311g, 312g, 313g, and 314g can have the aforementioned dual effect of ablating cells via irreversible electroporation and via cell death due to electrolytic imbalance.

[0099] Figure 3H and Figure 3I Additional exemplary forms of electrical pulses that may be employed in various embodiments are schematically illustrated to facilitate ablation via irreversible electroporation and by creating cell death due to electrolytic imbalance in the target cells. Figure 3H The illustration depicts a series 301h of pulse sequences consisting of multiple three-phase charge-imbalanced electrical pulses 311h1, 311h2, each having a first and a third phase characterized by the same polarity as phase length d1 and voltage V1, and a second phase characterized by phase length d2 and voltage V2. Pulse 311h2 differs from pulse 311h1 in that the polarity of each phase is opposite to that of the corresponding phase in pulse 311h1, although in other embodiments each corresponding phase may have the same polarity. As shown, in embodiments, phase lengths d1, d2 and voltages V1, V2 can be selected to result in an overall charge imbalance in pulses 311h1 or 311h2, wherein phase length d1 and voltage V1 are selected to induce electroporation, and phase length d2 and voltage V2 are selected to promote electrolysis and the formation of electrolytic imbalances leading to cell death.

[0100] By adopting Figure 3I The schematically illustrated four-phase electrical pulse 311i can achieve a similar effect. As shown, the electrical pulse 311i includes a first phase and a fourth phase with opposite polarities, characterized by a phase length d1 and a voltage V1, and a second phase and a third phase with opposite polarities, each having the same phase length d2 and voltage V2. As shown, the phase length d1 is substantially shorter than the phase length d2, and the voltage V1 is substantially greater than the voltage V2, resulting in the aforementioned charge imbalance and the corresponding dual effect of cell death caused by electroporation and electrolytic imbalance.

[0101] An electroporation generator can be configured to execute a feedback loop to cycle the electroporation ablation system through multiple pulse sequences 305. In embodiments, the feedback loop can be automatic and / or can follow a programmed pattern. In either case, the change in electric field orientation can be continuous or intermittent. The feedback loop can be executed based on a target metric, such as a decrease in electrogram amplitude, a change in impedance, or another similar metric. For example, when a target metric is reached, the electroporation generator can apply a generated pulse sequence across different electrodes previously used. As an example, the feedback loop can generate an axially oriented electric field followed by a transversely oriented electric field. It should be understood that the feedback loop can also employ a mixture of multidirectional and unidirectional electric fields in any order, and therefore this concept is not beyond the scope of this disclosure. The methods of this disclosure can utilize these concepts as well as those described with respect to other embodiments disclosed herein.

[0102] Figure 4 This is a diagram illustrating the steps of a method 400 for generating and delivering signals to electrodes in an electroporation ablation system. This method 400 and other related methods for generating and delivering signals to electrodes in an electroporation ablation system are disclosed herein. Step 402 of method 400 may include selecting an electroporation ablation system, which may be similar to those disclosed elsewhere herein. Method 400 may include generating a set of generated pulse sequences, including at least two of a first pulse sequence, a second pulse sequence, and a third pulse sequence, via an electroporation generator. Method 400 may include delivering the generated pulse sequence set to an ablation catheter. Examples include generating a first generated pulse sequence set at step 404 and delivering the first generated pulse sequence set to the ablation catheter at step 406. At step 408, a second generated pulse sequence set may be generated and delivered to the ablation catheter at step 410. At step 412, method 400 may include determining whether a feedback loop should be used as described below.

[0103] The generated pulse sequence set may include generating multiple pulse sequence sets. At step 404, a first generated pulse sequence set may be generated, and at step 408, a second generated pulse sequence set, different from the first generated pulse sequence set, may be generated. For example, the first generated pulse set may resemble those disclosed elsewhere herein, such as those with an axial orientation. And the second generated pulse set may resemble those disclosed elsewhere herein, such as those with a circumferential orientation. In embodiments, generating the generated pulse sequence set may include alternately generating at least two of the first, second, and third pulse sequences within a time period to generate a dynamic rotating electric field including a changing pattern within the time period.

[0104] The rotating electric field can be implemented via a feedback loop, such as those disclosed elsewhere herein. For example, at step 412, it can be determined whether a feedback loop is used. If so, method 400 can loop back to previous steps, such as step 404, to generate a first generated pulse sensing set. And if no feedback loop is used at step 412, method 400 can terminate.

[0105] In embodiments, the delivery of the generated pulse sequence set to the ablation catheter may employ an electrode pairing set or depend on the patient's characteristics. For example, at step 408, a first generated pulse sequence may be applied across a first set of axial, lateral, or circumferential septal electrodes to generate an electric field in the corresponding orientation. And at step 410, a second generated pulse sequence may be applied across any of the first set of axial, lateral, or circumferential septal electrodes not used in the first generated pulse sequence. In embodiments, the first and second generated pulse sequences may share at least one common electrode to which both sequences are applied. In embodiments, alternating waveforms may be delivered at different phases of the cardiac cycle (e.g., using local EGM sensing).

[0106] Various modifications and additions may be made to the exemplary embodiments discussed without departing from the scope of the invention. For example, while the embodiments described above relate to specific features, the scope of the invention also includes embodiments with different combinations of features and embodiments that do not include all the features described. Therefore, the scope of the invention is intended to cover all such alternatives, modifications, and variations and all equivalents falling within the scope of the claims.

Claims

1. An electroporation ablation system for treating target tissue, the electroporation ablation system comprising: Ablation catheters, including: The axis defining the longitudinal axis of the ablation catheter; and An electroporation electrode arrangement, located at the distal end of the axis and comprising a plurality of electrodes, the plurality of electrodes being arranged to define a plurality of anode-cathode pairs, each anode-cathode pair being configured to generate an electric field when a sequence of electrical pulses is delivered thereto, the plurality of anode-cathode pairs comprising: A first anode-cathode pair is arranged to generate a first electric field having a first orientation relative to the longitudinal axis when a first electrical pulse sequence is delivered thereto; and A second anode-cathode pair is arranged to generate a second electric field having a second orientation relative to the longitudinal axis when a second electrical pulse sequence is delivered thereto; and An electroporation generator operatively coupled to the electroporation electrode arrangement and configured to selectively generate the first electrical pulse sequence and deliver it to the first anode-cathode pair, and selectively generate the second electrical pulse sequence and deliver it to the second anode-cathode pair.

2. The electroporation ablation system according to claim 1, wherein, The first orientation is generally aligned with the longitudinal axis, and the second orientation is circumferentially surrounding the longitudinal axis.

3. The electroporation ablation system according to claim 1, wherein, The first orientation is generally aligned with the longitudinal axis, and the second orientation is transverse to the longitudinal axis.

4. The electroporation ablation system according to claim 1, wherein, The first orientation is transverse to the longitudinal axis, and the second orientation is generally circumferentially surrounding the longitudinal axis.

5. The electroporation ablation system according to any one of claims 1-4, wherein, Each of the first pulse sequence and the second pulse sequence includes multiple direct current (DC) pulses.

6. The electroporation ablation system according to claim 5, wherein the DC pulse is a single-phase pulse, a bi-phase pulse, or a three-phase pulse.

7. The electroporation ablation system according to claim 6, wherein, The electroporation generator is configured to generate DC pulses for each electrical pulse sequence separated by an inter-pulse delay, wherein at least some of the DC pulses of the second electrical pulse sequence are delivered during the corresponding inter-pulse delay of the first electrical pulse sequence.

8. The electroporation system according to claim 6, wherein, The electroporation generator is configured to generate a plurality of electrical pulse sequence sets with pauses therebetween, wherein each electrical pulse sequence set includes the first electrical pulse sequence and the second electrical pulse sequence.

9. The electroporation ablation system according to claim 6, wherein, The DC pulse is a biphasic pulse, and the electroporation ablation generator is configured to alternate between delivering the first electrical pulse sequence to the first anode-cathode pair and delivering the second electrical pulse sequence to the second anode-cathode pair.

10. The electroporation ablation system of claim 6, wherein each of the DC pulses is a three-phase pulse defined by a first phase having a first phase voltage and a first phase length, a second phase having a second phase voltage and a second phase length, and a third phase having a third phase voltage and a third phase length, wherein the first phase and the third phase have the same polarity, and the second phase has the opposite polarity.

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