Irreversible electroporation and thermal ablation using a focal catheter

Abstract

To provide a catheter for combining irreversible electroporation and radiofrequency ablation treatments, and methods of constructing and using the same.SOLUTION: Embodiments presented herein generally include a catheter and a system configured to deliver electrical pulses for ablation by IRE, and methods for constructing and using the same. The catheter and system can further be configured to delivery RF electrical current for thermal ablation interleaved with ablation by IRE, simultaneously with ablation by IRE, and / or separately from ablation by IRE. The catheter can have a linear distal portion with a tip electrode, a middle ring electrode, and a proximal ring electrode. The electrodes are configured in several combinations to provide unipolar ablation, bipolar ablation, and / or a combination thereof.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a catheter for ablation using irreversible electroporation, particularly for combining irreversible electroporation and radiofrequency ablation therapy, and to a method for constructing and using the same. [Background technology]

[0002] Cardiac arrhythmias, such as atrial fibrillation (AF), occur when areas of cardiac tissue abnormally transmit electrical signals to adjacent tissues. This disrupts the normal cardiac cycle, resulting in an asynchronous rhythm. Treatment for arrhythmias may involve surgically destroying the source of the signals causing the arrhythmia and disrupting the conduction pathways of such signals. By selectively ablating cardiac tissue using energy applied through a catheter, it is sometimes possible to stop or alter the transmission of unwanted electrical signals from one part of the heart to another. The ablation process destroys unwanted electrical pathways by forming non-conductive damaged areas.

[0003] Radio frequency (RF) current-based thermal ablation is currently the most common ablation technique. Typically, in ablation procedures using thermal techniques, electrode potential and temperature are measured before, during, and after the actual ablation. When using thermal ablation techniques, care must be taken to avoid thermal damage to non-target tissues and organs that may be heated or cooled during treatment of the target area. Several catheters and probes are designed to provide RF ablation. An example of a probe suitable for intracardiac RF ablation is described in U.S. Patent No. 10,660,574, incorporated herein by reference, and attached to the priority application, U.S. Patent Application No. 63 / 220,252.

[0004] Throughout this disclosure, ablation by pulsed electric field (PEF) ablation and irreversible electroporation (IRE), interchangeably referred to as pulsed field ablation (PFA), is a more recently developed technique in which an electric potential (voltage) is applied to the entire target tissue, destroying the cellular structure of the myocardium and inducing cell death. The heat generated during IRE ablation is substantially lower than that of equivalent RF ablation treatment, as IRE ablation is heat-independent in inducing cell death. Several exemplary probes, catheters, and systems developed to provide IRE ablation are described in U.S. Patents No. 9,078,665, No. 9,314,620, and No. 9,931,161, and U.S. Patent Application Publication 2014 / 0296844, each incorporated herein by reference and attached to the priority application, U.S. Patent Application No. 63 / 220,252. Several additional exemplary probes, catheters, and systems developed to provide IRE ablation are described in U.S. Patents No. 10,188,449 and No. 10,258,406, which are incorporated herein by reference. [Overview of the project] [Means for solving the problem]

[0005] Examples presented herein generally include catheters and systems configured to deliver electrical pulses for IRE ablation, and methods for constructing and using them. The catheters and systems may be further configured to deliver an RF current for thermal ablation interleaved with the IRE ablation, simultaneously with and / or separately from the IRE ablation. The catheter may have a linear distal portion having a tip electrode, an intermediate ring electrode, and a proximal ring electrode. The electrodes may be configured in several combinations to provide unipolar ablation, bipolar ablation, and / or combinations thereof.

[0006] An exemplary catheter may include an elongated member extending along its longitudinal axis, a tip electrode at the distal end of the elongated member, a proximal ring electrode on the elongated member, and an intermediate ring electrode between the tip electrode and the proximal ring electrode. The tip electrode may be positioned on the distal end of the elongated member. The tip electrode may be configured to provide a radio frequency (RF) ablation electrical signal. The proximal ring electrode may be positioned on the elongated member about its longitudinal axis, proximal to the tip electrode. The catheter may be configured to withstand a biphasic pulse burst having an amplitude of approximately 1800 V between the tip electrode and the proximal ring electrode. The intermediate ring electrode may be positioned on the elongated member, proximal to the tip electrode and distal to the proximal ring electrode. The catheter may be configured to withstand a biphasic pulse burst having an amplitude of approximately 900 V between the intermediate ring electrode and the proximal ring electrode. The catheter may be configured to withstand a biphasic pulse burst having an amplitude of approximately 900 V between the intermediate ring electrode and the tip electrode.

[0007] The tip electrode may include an irrigation port. The tip electrode may include a thermocouple therein. The tip electrode may include two electrode halves electrically insulated from each other, each half positioned on the respective portion of the distal end of the catheter, and at least one of the halves configured to provide an RF ablation electrical signal. The tip electrode may have a height of approximately 3.5 millimeters measured along its longitudinal axis.

[0008] The proximal ring electrode and the intermediate ring electrode may each have a height of approximately 3 millimeters along their longitudinal axis. The intermediate ring electrode may be positioned at an edge-to-edge distance of approximately 4 millimeters from the tip electrode and approximately 4 millimeters from the proximal ring electrode.

[0009] The catheter may further include a contact force sensor positioned proximal to the tip electrode. The contact force sensor may be configured to sense the force applied to the tip electrode as well as the direction of the force relative to the longitudinal axis.

[0010] An exemplary ablation system console may include one or more output ports configured to provide ablation energy to catheter electrodes, a processor, and memory for communicating with the processor. The memory may include a non-temporary computer-readable medium containing instructions on a non-temporary computer-readable medium that can be executed by the processor to cause the ablation system console to perform various functions. The output ports may be configured to provide ablation energy to a first catheter electrode, a second catheter electrode, and a third catheter electrode, which are linearly aligned on the longitudinal axis of the distal portion of the catheter. Instructions on the memory are executed by the processor to cause the console to provide an RF ablation signal to the first catheter electrode via the output ports and to provide an IRE ablation signal to at least one of the second and third catheter electrodes via the output ports.

[0011] An exemplary ablation system console may be configured such that a first catheter electrode, a second catheter electrode, and a third catheter electrode each include a tip electrode positioned above the distal end of the catheter and two ring electrodes surrounding the body of the catheter proximal to the tip electrode. The tip electrode can function as either the first or second electrode. One of the ring electrodes can function as the third electrode. The other ring electrode can function as either the first or second electrode, such that when the tip electrode functions as the first electrode, the ring electrode functions as the second electrode, and when the tip electrode functions as the second electrode, the ring electrode functions as the first electrode. The tip electrode and the other ring electrode can alternately function as the first and second electrodes, respectively.

[0012] The ablation system console may further include a body patch port. Instructions in memory are executed by the processor to cause the console to provide an IRE ablation signal as a burst of biphasic pulses between the body patch via the body patch port and at least one of the catheter electrodes via the output port. Alternatively, if a body patch port is not required, instructions in memory are executed by the processor to cause the console to provide an IRE ablation signal as a burst of biphasic pulses between two of the catheter electrodes via the output port. Another alternative is that if the console includes a body patch port, instructions in memory are executed by the processor to cause the console to provide an IRE ablation signal between the body patch and at least one of the catheter electrodes, and also between two of the catheter electrodes.

[0013] Instructions in memory are executed by the processor, which can then provide the console with a burst of biphasic pulses between two of the catheter electrodes via the output port, and simultaneously provide RF ablation signals to the remaining catheter electrodes (the first, second, and third electrodes) via the output port.

[0014] Instructions in memory are executed by the processor to cause the console to provide an RF ablation signal to the tip electrode via the output port and an IRE ablation signal to at least one of the ring electrodes via the output port. Additionally, or alternatively, instructions in memory are executed by the processor to cause the console to provide a burst of biphasic pulses to at least the tip electrode via the output port and an RF ablation signal to both of one of the ring electrodes via the output port.

[0015] Instructions in memory are executed by the processor, which can cause the console to receive a first IRE ablation signal via the output port as a first burst of biphasic pulses between two of the catheter electrodes that function as a first pair of electrodes, and a second IRE ablation signal via the output port as a second burst of biphasic pulses between two catheter electrodes that function as a second pair of electrodes, having one electrode common to the first pair of electrodes and one electrode not common to the first pair of electrodes.

[0016] The instructions in memory are executed by the processor, which can then provide the console with a first burst of biphase pulses with an amplitude of approximately 900V and a second burst of biphase pulses with an amplitude of approximately 1800V.

[0017] Instructions in memory are executed by the processor, which can then send a first RF ablation signal to the second catheter electrode via an output port, and a second RF ablation signal to the first catheter electrode via an output port, to the console.

[0018] Instructions in memory are executed by the processor, which can simultaneously provide the console with a first IRE ablation signal and a first RF ablation signal via the output port, and simultaneously provide a second IRE ablation signal and a second RF ablation signal via the output port.

[0019] Instructions in memory can be executed by the processor to cause the console to provide IRE ablation energy to at least one of the ring electrodes and RF ablation energy to the tip electrode via an output port. Instructions in memory can be executed by the processor to cause the console to provide an RF ablation signal to the first half of the tip electrode, which is electrically isolated from the second half of the tip electrode. The first and second halves can each be positioned on the respective portions of the distal end of the catheter.

[0020] Instructions in memory are executed by the processor, which causes the console to determine the force vector applied to the distal portion of the catheter based on sensor signals received from the catheter by the console.

[0021] The ablation system console may further include an irrigation module configured to provide irrigation fluid to a first catheter electrode.

[0022] Instructions in memory are executed by the processor, which can cause the console to determine the temperature of a catheter electrode configured to provide RF ablation (e.g., a first electrode) based at least in part on thermal sensor signals received from the catheter.

[0023] A first exemplary method may include one or more of the following steps, performed in various orders, along with interchangeable steps as understood by those skilled in the art in accordance with the teachings herein. The first method may include: providing RF electrical energy from a tip electrode positioned above the distal end of a catheter into tissue adjacent to the tip electrode, thereby increasing the temperature of the tissue; and providing a voltage pulse between a proximal ring electrode and an intermediate ring electrode, thereby causing irreversible electroporation in the tissue. While providing the RF electrical energy and providing the voltage pulse, the proximal ring electrode, the intermediate ring electrode, and the tip electrode can be linearly aligned so that the intermediate ring electrode and the proximal ring electrode each surround the catheter, and the intermediate ring electrode is positioned between the proximal ring electrode and the tip electrode.

[0024] The second exemplary method can include one or more of the following steps, performed in various orders, along with compatible steps as understood by one of ordinary skill in the relevant art in accordance with the teachings herein. The second method can include providing RF electrical energy from an intermediate ring electrode surrounding a catheter into the tissue adjacent to the intermediate ring electrode and providing a voltage pulse between a proximal ring electrode and a tip electrode. Thereby, the RF electrical energy from the intermediate ring electrode can raise the temperature of the tissue. Thereby, the voltage pulse between the proximal ring electrode and the tip electrode can cause irreversible electroporation within the tissue, while providing the RF electrical energy and while providing the voltage pulse, the proximal ring electrode, the intermediate ring electrode, and the tip electrode can be linearly aligned such that the proximal ring electrode surrounds the catheter, the tip electrode is disposed on the distal end of the catheter, and the intermediate ring electrode is disposed between the proximal ring electrode and the tip electrode.

[0025] Either or both of the first exemplary method and the second exemplary method can include providing RF energy from the tip electrode into the tissue adjacent to the tip electrode and providing a voltage pulse between the proximal ring electrode and the intermediate ring electrode. Thereby, the RF energy from the tip electrode can raise the temperature of the tissue. Thereby, the voltage pulse between the proximal ring electrode and the intermediate ring electrode can cause irreversible electroporation within the tissue.

[0026] Either or both of the first exemplary method and the second exemplary method can include providing RF electrical energy to increase the temperature of the tissue to about 50°C.

[0027] Either or both of the first exemplary method and the second exemplary method can include providing a voltage pulse having an amplitude of about 900V between the proximal ring electrode and the intermediate ring electrode.

[0028] Either or both of the first and second exemplary methods may include providing a voltage pulse having an amplitude of about 1800 V between the proximal ring electrode and the tip electrode.

[0029] Either or both of the first and second exemplary methods may include providing RF electrical energy to a first half of a tip electrode. The first half may be electrically insulated from a second half of the tip electrode. The first and second halves may be positioned on the respective distal end portions of a catheter.

[0030] Either or both of the first and second exemplary methods may include determining a force vector applied to the distal end of the catheter, at least in part, based on sensor signals from the catheter.

[0031] Either or both of the first and second exemplary methods may include irrigation through a tip electrode.

[0032] Either or both of the first and second exemplary methods may include determining the temperature of the tip electrode based at least in part on a thermal sensor signal from the catheter. [Brief explanation of the drawing]

[0033] The above and further aspects of the present invention are further discussed below with reference to the accompanying drawings, where similar figures in various drawings indicate similar structural elements and features. The drawings are not necessarily to scale and are primarily intended to illustrate the principles of the present invention. The figures depict one or more implementations of the devices, systems, and methods of the present invention, not as limitations but merely as examples. [Figure 1] This is a diagram of the distal portion of an exemplary catheter according to an embodiment of the present invention. [Figure 2] This is a diagram illustrating an exemplary ablation system used to treat a patient according to an aspect of the present invention. [Figure 3A] This is a diagram of interleaved RF and IRE signals according to an aspect of the present invention. [Figure 3B] This is a diagram of interleaved RF and IRE signals according to an aspect of the present invention. [Figure 4] This is a diagram of additional interleaved RF and IRE signals according to an aspect of the present invention. [Figure 5A] This is a diagram illustrating an exemplary IRE signal according to an aspect of the present invention. [Figure 5B] This is a diagram illustrating an exemplary IRE signal according to an aspect of the present invention. [Figure 6] This is a diagram illustrating an exemplary method of treatment according to an aspect of the present invention. [Modes for carrying out the invention]

[0034] Documents incorporated herein by reference should be considered an integral part of this application, and unless any term is defined in such a way as to contradict the definitions expressly or implicitly provided herein, only the definitions herein should be considered.

[0035] While exemplary embodiments of the disclosed technology are described in detail herein, it should be understood that other embodiments are contemplated. Therefore, the scope of the disclosed technology is not intended to be limited to the structural and arrangement details of the components described or shown in the drawings below. Other embodiments of the disclosed technology are possible and can be implemented or performed in various ways. Features of the embodiments disclosed herein, including those disclosed in the attached priority application U.S. 63 / 220,252, can be combined in accordance with the teachings herein so as can be understood by those skilled in the art.

[0036] It should also be noted that in this specification and the appended claims, the singular “a,” “an,” and “the” also include plural subjects unless the context expressly indicates otherwise. “Comprising,” “containing,” or “including” means that at least the mentioned system, apparatus, device, component, compound, element, particle, method, or step of use is present in the system, apparatus, method, or use, but does not exclude the presence of other stems, apparatus, devices, components, compounds, materials, particles, methods, or steps of use, even if these other stems, apparatus, devices, components, compounds, materials, particles, methods, or steps of use have the same function as those mentioned.

[0037] Where used herein, the terms “about” or “approximately” for any number or range indicate a suitable dimensional tolerance that enables some or all of the components to function for the intended purposes described herein. More specifically, “about” or “approximately” may mean a range of values ​​within ±20% of the listed values; for example, “about 90%” may mean a range of values ​​between 71% and 99%.

[0038] The vascular systems of “patient,” “host,” “user,” and “subject” as used herein may be human or any animal vascular system. It should be understood that animals can be any applicable type, including but not limited to mammals, veterinary animals, domestic animals, or pets. For example, an animal may be an experimental animal specifically selected to have certain characteristics similar to humans (e.g., rats, dogs, pigs, monkeys, etc.). It should be understood that subjects may be, for example, any applicable human patient.

[0039] As used herein, “operator” may include a physician, surgeon, or any other individual or delivery device involved in the delivery of a multi-electrode balloon catheter to a subject for the treatment of drug-resistant atrial fibrillation.

[0040] As discussed herein, the terms “to ablate” or “ablation” refer to the devices and corresponding systems of this disclosure and refer to components and structural features configured to reduce or prevent the generation of irregular cardiac signals. Non-thermal ablation includes, throughout this disclosure, the use of pulsed electric field (PEF) and irreversible electroporation (IRE), interchangeably referred to as pulsed field ablation (PFA), to induce cell death. Thermal ablation includes the use of extreme temperatures to induce cell death and includes RF ablation. As relating to the devices and corresponding systems of this disclosure, “to ablate” or “ablation” is used throughout this disclosure to refer to ablation of cardiac tissue in specific conditions, including but not limited to arrhythmias, atrial flutter ablation, pulmonary vein isolation, supraventricular tachycardia ablation, and ventricular tachycardia ablation. The terms “to ablate” or “ablation” generally refer to known methods, devices, and systems and include various forms of body tissue ablation as understood by those skilled in the art.

[0041] As discussed herein, when the terms “bipolar” and “monopole” are used to refer to ablation schemes, they describe different ablation schemes with respect to current paths and electric field distributions. “Bipolar” refers to an ablation scheme that utilizes current paths between two electrodes, both located at the treatment site. The current density and electric flux density are typically approximately equal in each of the two electrodes. “Monopole” refers to an ablation scheme that utilizes current paths between two electrodes, where one electrode with high current density and high electric flux density is located at the treatment site, and a second electrode with relatively low current density and lower electric flux density is located at a distance from the treatment site.

[0042] As discussed herein, the terms “two-phase pulse” and “single-phase pulse” refer to the respective electrical signals. A “two-phase pulse” refers to an electrical signal having a positive voltage phase pulse (referred to herein as the “positive phase”) and a negative voltage phase pulse (referred to herein as the “negative phase”). A “single-phase pulse” refers to an electrical signal having only a positive phase or only a negative phase. Preferably, a system providing a two-phase pulse is configured to prevent the application of direct current voltage (DC) to the patient. For example, the average voltage of a two-phase pulse may be zero volts relative to ground or other common reference voltage. Additionally or alternatively, the system may include capacitors or other protective components. Where the voltage amplitudes of two-phase pulses and / or single-phase pulses are described herein, it is understood that the expressed voltage amplitude is the absolute value of the approximate peak amplitude of each of the positive voltage phase and / or negative voltage phase. Each phase of a two-phase pulse and a single-phase pulse preferably has a “square” with an essentially constant voltage amplitude for most of the phase duration. The phases of a biphasic pulse are temporally separated by an interphase delay. The duration of the interphase delay is preferably less than or approximately equal to the duration of the phases of the biphasic pulse. More preferably, the duration of the interphase delay is about 25% of the duration of the phases of the biphasic pulse.

[0043] As discussed herein, the terms “pulse train” and “train” are equivalent to an array of biphasic or monophasic pulses that are temporally distributed such that the pulses are separated by a short delay. The pulses in a pulse train are delivered at a pulse frequency that is the inverse of the duration of the pulses in the pulse train. In the case of a biphasic pulse train, the delay is preferably approximately equal to the interphase delay between phases in a single biphasic pulse of the pulse train.

[0044] As discussed herein, the terms “pulse burst” and “burst” are equivalent to an array of pulse trains distributed in time such that the pulse trains are separated by regular time intervals. Preferably, the pulse trains within a burst are distributed in time such that the end of the final phase of the leading train is separated in time from the beginning of the trailing train by an inter-pulse delay that is significantly longer in duration than the inter-pulse delay within the pulse train.

[0045] As discussed herein, the term “lesion” is intended to encompass tissue damage caused by ablation electrodes sufficient to substantially reduce or eliminate irregular cardiac signals propagating through damaged tissue. It should be noted that tissue damage under the term “lesion” is intended to encompass any tissue damage, including thermal and non-thermal damage, some of which may be invisible, but which can be detected up to visible tissue damage by a suitable modality.

[0046] As discussed herein, the term “processor” may include one or more processing units (for example, in a multicore configuration). Furthermore, the processors described herein may be implemented using one or more heterogeneous processor systems in which the main processor resides together with secondary processors on a single chip. In another exemplary embodiment, the processor may be a symmetric multiprocessor system comprising multiple processors of the same type. Furthermore, the processor may be implemented using one or more systems and any suitable programmable circuitry, including microcontrollers, microprocessors, reduced instruction set circuits (RISC), application-specific integrated circuits (ASICs), programmable logic circuits, field programmable gate arrays (FPGAs), and any other circuits capable of performing the functions described herein. In addition, the processor may perform partial processing and receive partial processing by the processor and / or a computing device communicatively coupled to the processor.

[0047] As used herein, the term “non-transient computer-readable medium” includes, but is not limited to, random-access memory (RAM), read-only memory (ROM), electronically erasable programmable ROM (EEPROM), flash memory or other memory technologies, compact disk ROM (CD-ROM), digital multipurpose disk (DVD) or other optical storage devices, magnetic cassettes, magnetic tapes, magnetic disk storage devices or other magnetic storage devices, or any other tangible physical medium that can be used to store computer-readable information.

[0048] This disclosure relates to a system, method, or use and apparatus for ablating cardiac tissue to treat cardiac arrhythmias. Ablation energy can be delivered to cardiac tissue by a distal portion of a catheter capable of delivering the ablation energy along the tissue to be excised. Exemplary catheters presented herein are configured to provide electrical energy for ablation using an IRE and to have morphological factors generally similar to catheters currently used for performing RF ablation. The catheter may be further configured to deliver an RF current for thermal ablation, interleaved with or concurrently with the ablation by the IRE.

[0049] RF catheter ablation is currently the dominant modality for ablation therapy of arrhythmias. When tissue is ablated using RF energy, most of the tissue heating that leads to lesion formation occurs as a result of heat conduction from a direct resistive heat source (i.e., the electrodes delivering the RF energy). The transfer of heat through the tissue follows basic thermodynamic principles, and the boundaries of the lesion are generally determined by a 50°C isotherm.

[0050] RF energy ablation is generally considered to have a high success rate and a low complication rate. However, the RF approach carries a risk of thermal cell damage to the patient, which can lead to tissue carbonization, burning, steam popping, phrenic nerve palsy, pulmonary vein stenosis, and esophageal fistula. Cryoablation is an alternative approach to RF ablation that can reduce some of the thermal risks associated with RF ablation. However, maneuvering the cryoablation device and selectively applying cryoablation is generally more difficult compared to RF ablation. Therefore, cryoablation is not feasible in certain anatomical geometries that can only be achieved by electrical ablation devices.

[0051] Electroporation can be induced by applying a pulsed electric field to biological cells to cause the reversible (temporary) or irreversible (permanent) generation of pores within the cell membrane. Cells have transmembrane electrostatic potentials that increase above the resting potential when a pulsed electric field is applied. If the transmembrane electrostatic potential remains below the threshold potential, electroporation is reversible, meaning that the pores can close when the applied electric field is removed, and the cell can self-repair and survive. If the transmembrane electrostatic potential increases above the threshold potential, electroporation is irreversible, and the cell becomes permanently permeable. As a result, the cell dies due to the loss of homeostasis, typically by apoptosis. Generally, different types of cells have different threshold potentials. For example, cardiac cells have a threshold potential of about 500 V / cm, while bone has a threshold potential of about 3000 V / cm. These differences in threshold potentials allow IRE to selectively target cells based on their threshold potential.

[0052] IRE-assisted ablation is a non-thermal cell death technique that can be used for ablation of atrial arrhythmias, reducing or eliminating the thermal risks associated with RF ablation. To ablate using IRE / PEF, a biphasic or monophasic voltage pulse is applied to destroy the cellular structure of the myocardium. The pulse is non-sinusoidal and can be tailored to target cells based on the electrophysiology of the cells. In contrast, to ablate using RF, a sinusoidal voltage waveform is applied to generate heat in the treatment area, indiscriminately heating all cells within the treatment area. IRE has the ability to save adjacent heat-sensitive structures or tissues, which would benefit from reducing potential complications known with ablation or isolation modalities. Therefore, exemplary systems and catheters configured for both IRE and RF ablation can provide a multifunctional tool for ablation therapy.

[0053] The exemplary systems and catheters may also be configured to induce reversible electroporation as part of a diagnostic procedure. Reversible electroporation temporarily blocks the electrical activation signals through targeted myocardial tissue, allowing observation of changes in electrical activity within the heart, which can be used to predict the outcome of ablation in the targeted tissue. The temporarily interrupted electrical activation signals induced through reversible electroporation can be reactivated as cellular self-repair.

[0054] The pulsed electric field, and its effectiveness in inducing reversible and / or irreversible electroporation, may be influenced by the system of electrical signals and the physical parameters of the pulse parameters. Physical parameters may include electrode contact area, electrode spacing, electrode geometry, etc. Pulse parameters of the electrical signal may include voltage amplitude, pulse duration, pulse-to-phase delay (biphasic pulse), inter-pulse delay, total application time, and delivery energy, etc. In some embodiments, the parameters of the electrical signal can be tuned to induce both reversible and irreversible electroporation given the same physical parameters.

[0055] Figure 1 shows a distal portion of an exemplary catheter 100 configured to provide electrical energy for ablation using both RF and IRE. Catheter 100 may be further configured to induce reversible electroporation. Catheter 100 includes a tip electrode 102, an intermediate ring electrode 104, and a proximal ring electrode 106. Electrodes 102, 104, and 106 may be configured to ablate using RF and IRE in an interleaved pattern and / or to ablate using RF and IRE simultaneously. Electrodes 102, 104, and 106 are aligned linearly with the longitudinal axis LL of catheter 100.

[0056] In some embodiments, any of electrodes 102, 104, and 106 can be configured to perform ablation using both RF and IRE, meaning that the electrodes are spaced apart, sized, and otherwise constructed to deliver current and voltage to perform both RF and IRE ablation. In such embodiments, the application of electrical signals to electrodes 102, 104, and 106 for performing RF or IRE ablation can be selected for a particular treatment. Alternatively, any of electrodes 102, 104, and 106 can be configured to perform ablation using either RF or IRE, but not both. The catheter may include an additional ring electrode (not shown) configured for RF ablation and / or IRE ablation. Electrodes configured to perform RF ablation may be configured to provide a sufficient contact area with the tissue to facilitate heat transfer to the tissue. Catheter 100 can be configured for IRE ablation by being configured to withstand biphasic pulse bursts having an amplitude of about 200V to about 2,000V. Preferably, the catheter 100 may be configured such that the pulse between the alternate electrodes has an amplitude about twice that of the pulse between adjacent electrodes. In one embodiment, the catheter 100 can be configured for IRE ablation by being configured to withstand biphasic pulse bursts having amplitudes of about 900 V between adjacent electrodes and 1800 V between alternating electrodes. The maximum voltage amplitude that the catheter 100 is configured to withstand may depend on the electrode length, electrode diameter, electrode spacing, return electrode size, internal dimensions of the conductors within the catheter, insulation between the conductors within the catheter, etc., as will be understood by those skilled in the art.

[0057] The tip electrode 102 is shaped as a dome located at the distal end 114 of the catheter 100. The tip electrode 102 includes an irrigation port 112 configured to provide irrigation fluid to regulate tissue temperature during ablation. Since IRE ablation does not rely on thermal damage to cause irrigation of the lesion, regulating tissue temperature may not be necessary in some treatments. Therefore, the irrigation port 112 and associated structures (e.g., irrigation tube 120) may be omitted for exemplary catheters configured for such treatments.

[0058] The tip electrode 102 preferably has a height H1 measured along the longitudinal axis LL of the catheter 100, which is about 3.5 millimeters (mm).

[0059] The tip electrode may include two electrode halves (not shown) electrically insulated from each other. Each half may be positioned on the respective portion of the distal end of the catheter. At least one of the halves may be configured to provide an RF ablation electrical signal.

[0060] The tip electrode 102 may further include a thermocouple and other sensors, and may otherwise be configured similarly to the corresponding structure in U.S. Patent No. 10,660,574, which is incorporated herein by reference and attached to the appendix of priority application U.S. 63 / 220,252, or otherwise similarly to those known to those skilled in the art.

[0061] The catheter 100 may further include a contact force sensor 108 surrounded by a flexible sheath 118 configured similarly to the corresponding structures in U.S. Patent No. 10,660,574, its variations, and their substitutes as understood by those skilled in the art. The sheath 118 is shown transparent for illustrative purposes only. The contact force sensor 108 may be configured to respond to a sensor force applied to the tip electrode 102.

[0062] The ring electrodes 104 and 106 are positioned proximal to the tip electrode 102 around the tubular body of the catheter 100. Each ring electrode 104 and 106 has a height H2 and H3, respectively, preferably measured along the longitudinal axis LL of about 3 mm. The intermediate electrode 104 is preferably spaced about 4 mm from the tip electrode 102 by a length L1 measured from the edge. The proximal electrode 106 is preferably spaced about 4 mm from the intermediate electrode 104 by a length L2 measured from the edge. Although not shown, either or both of the ring electrodes 104 and 106 may optionally include an irrigation port and be configured to provide irrigation for regulating tissue temperature during treatment.

[0063] The catheter 100 may include electrodes 102, 104, and 106, a contact force sensor 108, and wires and cables 116 configured to carry electrical signals to other electronic components. The catheter 100 may include a support tube 122 between the intermediate ring electrode 104 and the proximal ring electrode 106, which are illustrated transparently for illustrative purposes.

[0064] The catheter 100 has an elongated shaft 110 that can be manipulated to position its distal portion at the treatment site, for example, within or adjacent to the heart in a living patient 24. Preferably, but not limited to, the catheter 100 may have an outer diameter (OD) of approximately 7.6 French (Fr), a sheath fit of approximately 8.5 Fr or more, an electrode constructed of platinum-iridium, and a shaft size with bidirectional deflection. However, the catheter 100 is not so limited and may vary to meet the needs of a particular use. The catheter 100 may be sized and otherwise configured to be introduced through the femoral artery, the wrist artery (radial access), directly through the carotid artery, or via other approaches known to those skilled in the art.

[0065] Figure 2 shows an exemplary system 20 configured to utilize a catheter 100 in an exemplary ablation procedure. A handle 70 is used by a physician 22 to move the distal portion of the catheter 100 to the treatment site. Some or all of the electrodes 102, 104, and 106 may be positioned against the tissue 58 at the treatment site. The contact force can be measured using a force sensor.

[0066] IRE is primarily a non-thermal process, raising tissue temperature by a few milliseconds, at most a few degrees. Therefore, IRE differs from RF (radio frequency) ablation, which raises tissue temperature by 20-70°C and destroys cells through heating. To avoid muscle contraction caused by DC voltage, IRE can utilize biphasic pulses, i.e., a combination of positive and negative pulses. IRE pulses, used alone or in combination with RF ablation, are described in U.S. Patent Publication Nos. 2021 / 0169550, 2021 / 0169567, and 2021 / 0169568, U.S. Patent Application No. 62 / 949,999 (Patent Attorney No. BIO6206USPSP1), U.S. Patent Application Publication Nos. 2021 / 0161592, 16 / 731,238 (Patent Attorney No. BIO6208USNP1), and U.S. Patent Application No. 16 / 710,062 (Patent Attorney No. BIO6209USNP1), and U.S. Patent Application Publication No. 2021 / 0186604, incorporated herein by reference and attached to the priority application U.S. Patent No. 63 / 220,252. U.S. Patent Application No. 16 / 989,445 claims priority over U.S. Patent No. 62 / 949,999 and is incorporated herein by reference in U.S. Patent Publication No. 2021 / 0191642. U.S. Patent Application No. 16 / 731,238 is incorporated herein by reference in U.S. Patent Publication No. 2021 / 0196372. Application No. 16 / 710,062 is incorporated herein by reference in U.S. Patent Publication No. 2021 / 0177503.

[0067] The pulses for IRE ablation can be applied in bipolar mode between the two electrodes 102, 104, and 106 of catheter 100, or in unipolar mode between catheter electrodes 102, 104, and 106 and the body patch 65. The applied voltage during IRE ablation can reach up to 2000V, which is much higher than the typical voltage of 10-200V in thermal RF ablation. The signal applied during RF ablation can be applied between electrodes 102, 104, and 106 and one or more of the same or different body patches 65.

[0068] The illustrated ablation system 20 includes a processor 32, an IRE module 34, an RF module 35, an electrocardiogram (ECG) module 46, a tracking module 60, and a temperature module 54. Modules 34, 35, 46, 60, and 54 may collectively or individually include non-temporary memories having instructions that can be executed by the processor, which perform a variety of functions, including those described herein and those understood by those skilled in the art in accordance with the teachings herein.

[0069] The IRE module includes an IRE generator 36 and an IRE controller 38. The RF module 35 includes an RF generator 37 and an RF controller 39. The RF controller 39 and the IRE controller 38 are integrated or configured to function in conjunction with each other to generate, for example, interleaved waveforms similar to those disclosed in U.S. Patent Application Publication 2021 / 0169550 (disclosed in U.S. Patent Application Publication 2021 / 0161592), or other waveform patterns disclosed herein, including those disclosed in the appendix to the attached priority application U.S. Patent Application 63 / 220,252. The ablation system 20 can be configured to provide simultaneous and / or sequential RF and IRE signals to electrodes 102, 104, and 106.

[0070] The RF module 35 and IRE module 34 are shown as separate modules for illustrative purposes, and it should be understood that the modules may share common hardware and software components. The processor 32, IRE controller 38, and RE controller 39 may each include a programmable processor, which is programmed with software and / or firmware to perform the functions described herein. Alternatively, or additionally, the IRE controller 38, RF controller 39, and / or processor 32 may each include hard wired and / or programmable hardware logic circuits that perform at least some of these functions. Although the processor 32 is illustrated as a separate functional block from the IRE controller 38 and RF controller 39, in practice some of these functions may be combined within a single processing and control unit having a suitable interface for receiving and outputting the signals shown in the figures and described in the text. For example, the IRE controller 38 may reside in the IRE module 34, since high-speed control signals are transmitted from the IRE controller to the IRE generator 36. However, if a sufficiently high-speed signal can be transmitted from the processor 32 to the IRE generator 36, the IRE controller 38 can reside within the processor.

[0071] The processor 32 and the IRE module 34 can reside within the console 40. The console 40 includes input devices 42 such as a keyboard and a mouse. The display screen 44 is located adjacent to (or integrated with) the console 40. The display screen 44 may optionally include a touchscreen, thereby providing another input device.

[0072] The electrocardiogram (ECG) module 46, the temperature module 54, and / or the tracking module 60 can reside within the console 40 and can be connected to suitable interfaces and devices within the system 20. As shown, the electrocardiogram (ECG) module 46 is coupled via cable 48 to an ECG electrode 50 attached to the subject 24. The ECG module 46 is configured to measure the electrical activity of the subject 24's heart 52. The temperature module 54 is coupled to any temperature sensor, such as a thermocouple in the distal tip electrode 102 of the catheter 100. The tracking module 60 is coupled to one or more electromagnetic position sensors (not shown) in the distal portion of the catheter 100. In the presence of an external magnetic field generated by one or more magnetic field generators 62, the electromagnetic position sensors output signals that change with the position of the sensors. Based on these signals, the tracking module 60 can determine the position of electrodes 102, 104, and 106 within the heart 52. Modules 46, 54, and 60 typically include both analog and digital components and are configured to receive analog signals and transmit digital signals. Each module may further include hardwired and / or programmable hardware logic circuits that perform at least some of the module's functions.

[0073] The catheter 100 is connected to the console 40 via an electrical interface 64, such as a port or socket. Thus, IRE signals and RF signals are delivered to the distal portion of the catheter 100 via the console interface 64. Similarly, signals for tracking the positions of electrodes 102, 104, and 106, and / or signals for tracking the temperature of tissue 58, are received by the processor 32 via the interface 64 and may be applied by the IRE controller 38 when controlling pulses generated by the IRE generator 36 and / or by the RF controller 39 when controlling RF signals generated by the RF generator 37.

[0074] One or more external electrodes 65 or “return patches” may be attached externally to the subject 24, typically via a body patch port 69 to the skin of the subject's torso and onto the console 40. The return patches 65 can provide a return pathway for the unipolar ablation signals applied in one or more of the ablation electrodes 102, 104, and 106 of the catheter 100. RF ablation and IRE ablation may each be applied in a unipolar ablation scheme. Furthermore, RF ablation and IRE ablation may each be applied in a bipolar ablation scheme. Currently, it is more common for RF ablation to be performed in a unipolar ablation scheme and IRE to be performed in a bipolar ablation scheme. The exemplary catheter 100 and exemplary system 20 may be adapted to perform unipolar RF ablation, unipolar IRE ablation, bipolar RF ablation, unipolar IRE ablation, or any combination thereof.

[0075] During unipolar RF ablation, RF energy is delivered between at least one of the electrodes 102, 104, and 106 of the catheter 100 and the return patch 65. When multiple catheter electrodes 102, 104, and 106 are activated for unipolar RF ablation, the electrodes can be electrically synchronized or electrically coupled together to block the flow of current between the activated electrodes. The alternating electrical current flowing through the tissue encounters resistance, and the energy is converted into heat. This energy, resistive heat, destroys the tissue near the activated catheter electrodes 102, 104, and 106. The heat is then transferred to the surrounding tissue by conduction and radiation, resulting in lesion formation. Scar formation is related to the electrode size, the power of the energy, the contact force between the electrode and the tissue, and the cooling effect of the surrounding fluid, even when only a small amount of energy is delivered to the tissue. Cooling the electrodes reduces the risk of overheating the tissue, thereby enabling the formation of deeper lesions. A decrease in the distance between electrodes 102, 104, and 106 and the return patch 65 can result in a greater current density accompanied by higher resistance heating, which leads to deeper lesion formation. Bipolar RF ablation is when the RF current flows between two of the catheter electrodes 102, 104, and 106. Lesions produced by bipolar RF ablation are generally narrower, deeper, and denser than those produced by unipolar RF ablation, resulting in transwalled scarring within the tissue of approximately 25 mm.

[0076] During bipolar IRE ablation, a biphasic pulse is applied between catheter electrodes 102, 104, and 106 (typically in pairs) to generate an electric field between the electrodes. Cells at and between the electrodes experience the maximum electric field and undergo electroporation. During unipolar IRE ablation, a biphasic pulse is applied between one or more catheter electrodes 102, 104, and 106 and a return patch 65 to generate an electric field between the distal portion of catheter 100 and the return patch. When multiple catheter electrodes 102, 104, and 106 are activated for unipolar IRE ablation, the electrodes can be electrically synchronized or electrically coupled together to block the flow of current between the activated electrodes. The electric flux density is maximum at the activated electrodes, and therefore, cells of higher density experience electroporation at the electrodes. Unipolar IRE ablation may be useful in certain treatments of advances in the art, for example, when ablating thicker cardiac tissue in the ventricles.

[0077] The processor 32 is configured to receive setting parameters 66 from the physician 22 or another user or device. Using one or more suitable input devices 42, the physician 22 can input parameters for the ablation signals for RF ablation and / or IRE ablation. The physician 22 may select the ablation electrodes 102, 104, 106 to be activated (to receive the IRE pulse and / or RF signal) and the order in which they are activated. When setting up the ablation, the physician 22 may also select a mode of synchronization of the IRE pulse to the heart cycle 52.

[0078] In response to receiving the setting parameters 66, the processor 32 transmits these parameters to the IRE controller 38 and RF controller 39, which then instruct the IRE generator 36 and RF generator 37, respectively, to generate IRE and RF signals according to the settings requested by the physician 22. Additionally, the processor 32 can display the setting parameters 66 on the display screen 44.

[0079] The processor 32 may be configured to display on the display 44 relevant images 68 of the subject's anatomical structures, annotated to indicate, for example, the current position and orientation of electrodes 102, 104, and 106, based on signals received from the tracking module 60. Alternatively or additionally, based on signals received from the temperature module 54 and the ECG module 46, the processor 32 may display on the display screen 44 the temperature of the tissue 58 and the electrical activity of the heart 52.

[0080] To begin the procedure, physician 22 inserts the catheter 100 into the subject 24 and then navigates the catheter to the appropriate location inside or outside the heart 52 using the control handle 70. Subsequently, physician 22 brings some or all of the electrodes 102, 104, and 106 into contact with tissue 58 such as myocardial or epicardial tissue of the heart 52. Then, an ablation signal is applied to some or all of the electrodes 102, 104, and 106.

[0081] In some treatments, the treatment site can be ablated using IRE ablation via electrodes 102, 104, and 106. Once the bipolar IRE ablation is complete, RF ablation can be performed using the distal tip electrode 102 to touch up any areas of the treatment site that were not ablated by the IRE ablation (e.g., keel bone).

[0082] The processor 32 (which may be a single processor or multiple processors) can communicate with a non-temporary computer-readable medium 72 (hereinafter referred to as "memory" for brevity), which has instructions on the non-temporary computer-readable medium 72 that are executed by the processor 32 and cause the ablation system console 40 to perform various functions. The memory 72 may include one or more separate hardware components, which may be located within the console 40, fixed within the console 40, removable from the console 40, and / or remote from the console (for example, accessible by the console 40 and providing software as a service). Preferably, the memory 72 is fixed within the console 40, and the various modules 34, 35, 46, 54, 60 of the console 40 are represented as software modules of the memory 72. Alternatively, some or all of the modules 34, 35, 46, 54, 60 may include dedicated processors and / or memories electrically isolated from the other modules. As discussed herein, the terms “processor” and “memory” include a variety of physical manifestations as understood by those skilled in the art, and references to “processor” and “memory” in the singular are intended to include non-singular manifestations unless otherwise clearly stated.

[0083] During an exemplary treatment, instructions on memory 72 are executed by processor 32, causing console 40 to provide an RF ablation signal to one of the catheter electrodes 102, 104, and 106 via output port 64 (which may include multiple output ports), and to provide an IRE ablation signal to at least one of the other catheter electrodes 102, 104, and 106 via output port 64. The IRE ablation signal may include monophasic and / or biphasic pulses, and is preferably biphasic to avoid the application of DC voltage. The IRE ablation signal may be bipolar or unipolar, and is preferably bipolar to avoid skeletal and myofascial pain. The RF ablation signal may be unipolar or bipolar. Although unipolar RF ablation is currently more common than bipolar RF ablation, bipolar RF ablation may have several advantages, as discussed elsewhere in this specification.

[0084] As the exemplary treatment continues, the instructions on memory 72 are executed by the processor 32, causing the console 40 to provide an IRE ablation signal as a burst of biphasic pulses between the body patch 65 via the body patch port 67 and at least one of the catheter electrodes 102, 104, and 106 via the output port 64. Alternatively, if the body patch port 69 is not required, the instructions on memory 72 are executed by the processor 32, causing the console 40 to provide an IRE ablation signal as a burst of biphasic pulses between two of the catheter electrodes 102, 104, and 106 via the output port 64. Another alternative is that if the console 40 includes the body patch port 69, the instructions on memory 72 are executed by the processor 32, causing the console 40 to provide an IRE ablation signal between the body patch 65 and at least one of the catheter electrodes 102, 104, and 106, and also between two of the catheter electrodes 102, 104, and 106.

[0085] Instructions on memory 72 are executed by processor 32, which can cause console 40 to provide a burst of biphasic pulses between two of the catheter electrodes 102, 104, and 106 via output port 64, and simultaneously provide an RF ablation signal to the remaining catheter electrodes 102, 104, and 106 via output port 64. In this case, the biphasic pulse is bipolar between the two catheter electrodes 102, 104, and 106 to provide bipolar IRE ablation. The RF ablation signal can be provided to tip electrode 102, thereby providing unipolar RF ablation using return patch 65, while the burst of biphasic pulses is provided between ring electrodes 104 and 106, thereby providing bipolar IRE ablation. Alternatively, or subsequently, an RF ablation signal can be provided to one of the ring electrodes (e.g., the proximal ring electrode 106), thereby providing unipolar RF ablation, while a burst of biphasic pulses is provided between the remaining ring electrodes (e.g., the intermediate ring electrode 104) and the tip electrode 102, thereby providing bipolar IRE ablation.

[0086] Instructions on memory 72 are executed by the processor 32, causing the console 40 to provide a first IRE ablation signal via output port 64 as a first burst of biphasic pulses between two of the catheter electrodes that function as a first pair of electrodes, and a second IRE ablation signal via output port 64 as a second burst of biphasic pulses between two catheter electrodes that function as a second pair of electrodes, having one electrode common to the first pair of electrodes and one electrode not common to the first pair of electrodes. For example, the first pair of electrodes may include an intermediate ring electrode 104 and a proximal ring electrode 106, and the second pair of electrodes may include a tip electrode 102 and a proximal ring electrode 106. Instructions on memory 72 are executed by the processor, causing the console to provide a first burst of biphasic pulses with an amplitude of approximately 900V and a second burst of biphasic pulses with an amplitude of approximately 1800V. A third IRE ablation signal can be applied between the tip electrode 102 and the intermediate ring electrode 104. The amplitude of the third IRE ablation signal may be approximately 900V. The first, second, and third IRE ablation signals can be applied in any order to form a triplet pattern. Each of the first, second, and third IRE ablation signals may contain pulse trains that are synchronized with each other and repeat the triplet pattern over the duration of their respective pulse trains.

[0087] Instructions on memory 72 are executed by the processor and can cause the console to provide one or more RF ablation signals before and / or after the IRE ablation signal, interleaved with the IRE ablation signal, and / or simultaneously with the IRE ablation signal. For example, the console can provide the IRE ablation signal and the RF ablation signal simultaneously via output port 64, and then subsequently provide the subsequent IRE ablation signal and the subsequent RF ablation signal simultaneously via output port 64 such that the electrode providing RF ablation and the electrode providing IRE ablation change when the subsequent ablation signal is applied.

[0088] In embodiments where the tip electrode 102 has two electrically insulated halves, instructions on the memory 72 can be executed by the processor 32 to cause the console 40 to provide the RF ablation signal to the first half of the tip electrode 102 but not to the second half.

[0089] In embodiments in which the catheter 100 includes a force sensor 108, instructions on the memory 72 are executed by the processor 32, causing the console 40 to determine a force vector applied to the distal portion of the catheter 100 based on the sensor signal received by the console 40 from the catheter 100.

[0090] The ablation system console may further include an irrigation module (not shown) configured to provide irrigation fluid to a first catheter electrode. The console 40 and system 20 may be modified to include irrigation, as will be understood by those skilled in the art.

[0091] Instructions on memory 72 are executed by the processor, which causes the console 40 to determine the temperatures of catheter electrodes 102, 104, and 106, which are configured to provide RF ablation (e.g., tip electrode 102), at least in part based on thermal sensor signals received from catheter 100.

[0092] Figures 3A and 3B illustrate the interleaved RF and IRE signals 302. Figure 3B is a diagram of the signal 302 shown in Figure 3A on a shorter time scale, allowing for a more detailed visualization of the characteristics of the signal 302. The signal 302 can be generated as described in detail in U.S. Patent Application Publication No. 2021 / 0169550 and U.S. Patent Application Publication No. 2021 / 0161592.

[0093] As illustrated in Figure 3A, the interleaved signal 302 may include a sinusoidal RF signal 308 interleaved between pulse trains 330. Pulse train 330 is illustrated as containing two biphasic pulses. However, pulse train 330 may include additional biphasic pulses to achieve the desired therapeutic outcome. The interleaved signal 302 may be applied to perform unipolar and / or bipolar ablation. For example, the interleaved signal 302 may be applied between the tip electrode 102 and the reference patch 65 to provide unipolar IRE ablation and RF ablation (Figure 2). In another embodiment, the interleaved signal 302 may be applied between ring electrodes 104, 106 to provide bipolar IRE and RF ablation. In another embodiment, the interleaved signal 302 can be applied to the tip electrode, while the switch can toggle the return path of the interleaved signal 302 between the reference patch 65 and the ring electrodes 104, 106 to provide unipolar RF ablation and bipolar IRE ablation. Based on this logic, the interleaved signal 302 can be applied to numerous combinations of electrodes 102, 104, 106 to achieve various combinations of unipolar and bipolar ablation schemes, as will be understood by those skilled in the art.

[0094] As shown in Figure 3B, curve 306 shows the voltage V of the RF signal 308 as a function of time t between two bipolar pulses 310, 312 from the pulse train 330 illustrated in Figure 3A. The amplitude of the RF signal 308 is V RF It is written as and its frequency is f RF It is written as such, and the separation between pulses 310 and 312 and (therefore pulse train 330) is Δ RF It is written as follows. Preferably, frequency f RF The frequency range is approximately 350 kilohertz (kHz) to 500 kHz, but higher or lower frequencies may be used as alternatives.

[0095] FIG. 4 is a diagram of another exemplary interleaved RF and IRE signal 304 having a curve 314 with an RF signal 316 between the positive phase 318 and the negative phase 320 of the biphasic pulse. The interphase delay t between the positive phase 318 and the negative phase 320 間隔 can be extended to accommodate the RF signal between the phases 318, 320 as compared to the biphasic pulses 310, 312 shown in FIGS. 3A and 3B. Repeating the interleaved signal 304 shown in FIG. 4 can generate pulse trains and pulse bursts.

[0096] FIG. 5A is a diagram of a biphasic pulse 80. Curve 82 shows the voltage V of the biphasic IRE pulse 80 as a function of time t. Pulse 80 includes a positive phase 84 and a negative phase 86. The amplitude of the positive phase 84 is denoted as V+, and the time pulse width of the phase is denoted as t+. Similarly, the amplitude of the negative phase 86 is denoted as V−, and the time pulse width of the phase 86 is denoted as t−. The interphase delay is t 間隔 denoted as. The values of the parameters of pulse 80 can be found in the appendix of priority application US Patent No. 63 / 220,252, particularly in the references attached to US Patent Application Publication No. 2021 / 0161592 and US Patent No. 16 / 710,062 (Attorney Docket No. BIO6209USNP1).

[0097] FIG. 5B is a diagram of a curve 92 of a burst 90 of a biphasic pulse train 94. Burst 90 includes N T pulse trains 94, each train including N P biphasic pulses. The length of the pulse train 94 is denoted as t PP and the interval between consecutive trains is denoted as Δ T The values of the parameters of pulse 80 can be found in the appendix of priority application US Patent No. 63 / 220,252, particularly in the references attached to US Patent Application Publication No. 2021 / 0161592 and US Patent No. 16 / 710,062 (Attorney Docket No. BIO6209USNP1).

[0098] Any of the exemplary signals 302, 304, and 90 illustrated in Figures 3A to 5B can be applied in a triplet configuration where each signal 302, 304, and 90 is applied synchronously and bipolarly between three electrode pairs: from the tip electrode 102 to the intermediate ring electrode 104, from the intermediate ring electrode 104 to the proximal ring electrode 106, and from the tip electrode 102 to the proximal ring electrode 106. At least the voltage amplitude of the IRE pulse can be increased for the pair including the tip electrode 102 and the proximal ring electrode 106 compared to other pairs, taking into account the increasing distance between the electrodes of that pair.

[0099] Figure 6 is a flowchart of an exemplary method 200 for performing ablation. Method 200 can be performed using catheters 100 and / or systems 20, their variations, and alternatives thereof as will be understood by those skilled in the art, as illustrated in Figures 1 and 2, respectively.

[0100] In step 202, RF electrical energy is supplied to the adjacent tissue from the intermediate ring electrode surrounding the catheter, thereby increasing the temperature of the tissue. The intermediate ring electrode can be configured as the intermediate ring electrode 104 of the catheter 100 illustrated in Figure 1, a variation thereof, or any alternative thereof as understood by those skilled in the art.

[0101] In step 204, a voltage pulse is provided between the proximal ring electrode and the tip electrode, thereby inducing irreversible electroporation within the tissue. The proximal ring electrode, intermediate ring electrode, and tip electrode are linearly aligned while providing RF electrical energy and a voltage pulse. The proximal ring electrode may surround the catheter, the tip electrode may be positioned above the distal end of the catheter, and the intermediate ring electrode may be positioned between the proximal ring electrode and the tip electrode. The proximal ring electrode and tip electrode may be configured similarly to the corresponding structures 106, 102 of the catheter 100 illustrated in Figure 1, variations thereof, or alternatives thereof as understood by those skilled in the art.

[0102] In step 206, RF energy is supplied from the tip electrode to the tissue adjacent to the tip electrode, thereby increasing the temperature of the tissue.

[0103] In step 208, a voltage pulse is applied between the proximal ring electrode and the intermediate ring electrode, thereby inducing irreversible electroporation within the tissue.

[0104] Method 200 may further include providing a voltage pulse between the tip electrode and the intermediate ring electrode in a triplet pattern. This method may further include providing RF electrical energy from the proximal electrode. These steps can be performed simultaneously with each other in various orders and in various combinations thereof, as will be understood by those skilled in the art in accordance with the teachings herein. Method 200 may include additional steps to achieve functions as described elsewhere herein, such as measuring a force at the catheter tip and / or irrigating through one or more of the electrodes.

[0105] [Implementation Method] (1) A catheter, A long, slender member extending along its longitudinal axis, A tip electrode is positioned on the distal end of the elongated member and configured to provide a radio frequency (RF) ablation electrical signal. A proximal ring electrode is positioned on the elongated member with respect to the longitudinal axis and is positioned proximal to the tip electrode, wherein the catheter is configured to withstand a biphasic pulse burst having an amplitude of approximately 1800V between the tip electrode and the proximal ring electrode. A catheter comprising: an intermediate ring electrode disposed on the elongated member and positioned proximal to the tip electrode and distal to the proximal ring electrode, wherein the electrode is configured to withstand a biphasic pulse burst having an amplitude of approximately 900V between the intermediate ring electrode and the proximal ring electrode, and is configured to withstand a biphasic pulse burst having an amplitude of approximately 900V between the intermediate ring electrode and the tip electrode. (2) The tip electrode further comprises an irrigation port, The catheter according to Embodiment 1, wherein the tip electrode further comprises a thermocouple. (3) The catheter according to Embodiment 1, wherein the tip electrode further comprises two electrode halves electrically insulated from each other, each half positioned on the respective portion of the distal end of the catheter, and at least one of the halves is configured to provide an RF ablation electrical signal. (4) The tip electrode has a height of approximately 3.5 millimeters measured along the longitudinal axis, The catheter according to Embodiment 1, wherein the proximal ring electrode and the intermediate ring electrode each have a height of approximately 3 millimeters measured along the longitudinal axis. (5) The catheter according to Embodiment 1, wherein the intermediate ring electrode is positioned at an inter-edge distance of approximately 4 millimeters from the tip electrode and at an inter-edge distance of approximately 4 millimeters from the proximal ring electrode.

[0106] (6) The catheter according to Embodiment 1, further comprising a contact force sensor positioned proximal to the tip electrode and configured to sense the force applied to the tip electrode and the direction of the force with respect to the longitudinal axis. (7) Ablation system console, One or more output ports are configured to supply ablation energy to the first catheter electrode, the second catheter electrode, and the third catheter electrode while the first catheter electrode, the second catheter electrode, and the third catheter electrode are aligned linearly along the longitudinal axis of the distal portion of the catheter. Processor and A non-temporary computer-readable medium that communicates with the processor, and when executed by the processor, displays on the console: The output port provides the first catheter electrode with an RF ablation signal, and Ablation system console comprising: a non-temporary computer-readable medium containing instructions on the non-temporary computer-readable medium that cause at least one of the second catheter electrode and the third catheter electrode to provide an IRE ablation signal via the output port. (8) Further equipped with body patch ports, When the non-temporary computer-readable medium is executed by the processor, the console displays: The ablation system console according to Embodiment 7, further comprising instructions on the non-temporary computer-readable medium for providing the IRE ablation signal as a burst of biphasic pulses between a body patch via the body patch port and at least one of the second catheter electrode and the third catheter electrode via the output port. (9) When the non-temporary computer-readable medium is executed by the processor, the console displays: The ablation system console according to Embodiment 7, further comprising on the non-temporary computer-readable medium instructions to provide the IRE ablation signal via the output port as a burst of biphasic pulses between the second catheter electrode and the third catheter electrode. (10) When the non-temporary computer-readable medium is executed by the processor, the console displays: The ablation system console according to Embodiment 9, further comprising on the non-temporary computer-readable medium instructions to provide a burst of the biphasic pulse between the second catheter electrode and the third catheter electrode via the output port, and simultaneously provide the RF ablation signal to the first catheter electrode via the output port.

[0107] (11) When the non-temporary computer-readable medium is executed by the processor, the console displays: The ablation system console according to Embodiment 9, further comprising instructions on the non-temporary computer-readable medium for providing the biphasic pulse burst and the RF ablation signal via the output port, such that the first catheter electrode is configured as a tip electrode positioned on the tip of the catheter, and the second catheter electrode and the third catheter electrode are each configured as ring electrodes surrounding the body of the catheter in a proximal direction relative to the tip electrode. (12) When the non-temporary computer-readable medium is executed by the processor, the console displays: The ablation system console according to Embodiment 9, further comprising on the non-temporary computer-readable medium instructions for providing the biphasic pulse burst and the RF ablation signal via the output port, such that the second catheter electrode is configured as a tip electrode positioned above the tip of the catheter, and the first catheter electrode and the third catheter electrode are each configured as ring electrodes surrounding the body of the catheter in a proximal direction relative to the tip electrode. (13) When the non-temporary computer-readable medium is executed by the processor, the console displays: A first IRE ablation signal is provided between the second catheter electrode and the third catheter electrode via the output port as a first burst of biphasic pulses, and The ablation system console according to Embodiment 7, further comprising on the non-temporary computer-readable medium an instruction causing the output port to provide a second IRE ablation signal as a second burst of biphasic pulses between the first catheter electrode and the third catheter electrode. (14) When the non-temporary computer-readable medium is executed by the processor, the console displays: To provide the first burst of a biphase pulse with an amplitude of approximately 900V, and The ablation system console according to embodiment 13 further includes instructions on the non-temporary computer-readable medium for providing the second burst of biphasic pulses with an amplitude of approximately 1800V. (15) When the non-temporary computer-readable medium is executed by the processor, the console displays: The output port is used to provide the second catheter electrode with the first RF ablation signal. The output port is used to provide the first catheter electrode with a second RF ablation signal. The output port is used to simultaneously provide the first IRE ablation signal and the first RF ablation signal, and The ablation system console according to embodiment 13, further including on the non-temporary computer-readable medium an instruction to simultaneously provide the second IRE ablation signal and the second RF ablation signal via the output port.

[0108] (16) When the non-temporary computer-readable medium is executed by the processor, the console displays: The ablation system console according to Embodiment 13, further comprising instructions on the non-temporary computer-readable medium for providing the ablation energy via the output port, such that the first catheter electrode is configured as a tip electrode positioned on the tip of the catheter, and the second catheter electrode and the third catheter electrode are each configured as ring electrodes surrounding the body of the catheter in a proximal direction relative to the tip electrode. (17) When the non-temporary computer-readable medium is executed by the processor, the console displays: The ablation system console according to Embodiment 7, further comprising on the non-temporary computer-readable medium an instruction causing the first half of the first catheter electrode to provide the RF ablation signal, wherein the first half is electrically isolated from the second half of the first catheter electrode, and the first and second halves are positioned on the respective portions of the distal end of the catheter. (18) When the non-temporary computer-readable medium is executed by the processor, the console displays: The ablation system console according to Embodiment 7 further includes on the non-temporary computer-readable medium a command to determine a force vector applied to the distal portion of the catheter based on sensor signals received by the console from the catheter. (19) The ablation system console according to Embodiment 7, further comprising an irrigation module configured to provide irrigation fluid to the first catheter electrode. (20) When the non-temporary computer-readable medium is executed by the processor, the console displays: The ablation system console according to Embodiment 7 further includes on the non-temporary computer-readable medium a command to determine the temperature of the first catheter electrode based at least in part on a thermal sensor signal received from the catheter.

Claims

1. It is a catheter, A long, slender member extending along its longitudinal axis, A tip electrode is positioned on the distal end of the elongated member and configured to provide a radio frequency (RF) ablation electrical signal. A proximal ring electrode is positioned on the elongated member with respect to the longitudinal axis and in a proximal direction relative to the tip electrode, wherein the catheter is configured to deliver a biphasic pulse burst having an amplitude of approximately 1800 V between the tip electrode and the proximal ring electrode in a bipolar configuration. An intermediate ring electrode is disposed on the elongated member and positioned proximal to the tip electrode and distal to the proximal ring electrode, wherein the catheter is configured to deliver a biphasic pulse burst having an amplitude of approximately 900 V between the intermediate ring electrode and the proximal ring electrode in a bipolar configuration, and is configured to deliver a biphasic pulse burst having an amplitude of approximately 900 V between the intermediate ring electrode and the tip electrode in a bipolar configuration, The system comprises an IRE module including an IRE generator and an IRE controller, a processor, and a console having memory. A catheter in which the processor of the console is configured to execute an instruction stored in the memory of the console, which controls the IRE generator and the IRE controller to deliver a biphasic pulse burst having an amplitude of approximately 1800 V between the tip electrode and the proximal ring electrode and a biphasic pulse burst having an amplitude of approximately 900 V between the intermediate ring electrode and the tip electrode.

2. The aforementioned tip electrode further comprises an injection port, The catheter according to claim 1, wherein the tip electrode further comprises a thermocouple therein.

3. The catheter according to claim 1, wherein the tip electrode further comprises two electrode halves electrically insulated from each other, each electrode half positioned on the respective portion of the distal end of the catheter, and at least one of the two electrode halves is configured to provide an RF ablation electrical signal.

4. The tip electrode has a height of approximately 3.5 millimeters measured along the longitudinal axis, The catheter according to claim 1, wherein the proximal ring electrode and the intermediate ring electrode each have a height measured along the longitudinal axis of approximately 3 millimeters.

5. The catheter according to claim 1, wherein the intermediate ring electrode is positioned at an inter-edge distance of approximately 4 millimeters from the tip electrode and at an inter-edge distance of approximately 4 millimeters from the proximal ring electrode.

6. The catheter according to claim 1, further comprising a contact force sensor positioned proximal to the tip electrode and configured to sense the force applied to the tip electrode and the direction of the force with respect to the longitudinal axis.

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