System and method for electroporation using arbitrary electrode addressing

Abstract

Systems and methods for electroporation with arbitrary electrode addressing. A pulse generation circuit for an electroporation system is provided, the pulse generation circuit including a first voltage source, a second voltage source, and a plurality of electrode addressing circuits, each electrode addressing circuit configured to be coupled to an associated electrode and including a first switch coupleable between the electrode and the first voltage source, a second switch coupleable between the electrode and the second voltage source, and a third switch coupleable between the electrode and a return voltage.

Description

Technical Field

[0001] This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 332,398, filed on April 19, 2022, the entire contents and disclosures of which are incorporated herein by reference. Disclosure Field

[0002] The present disclosure relates generally to tissue ablation systems. In particular, the present disclosure relates to the application of an electroporation system including a pulse generation circuit for arbitrarily addressing individual electrodes.

Background Art

[0003] It is generally known that ablation therapy can be used to treat various conditions that afflict the anatomical structures of the human body. For example, ablation therapy can be used in the treatment of atrial arrhythmias. When tissue is ablated or at least exposed to ablation energy generated by an ablation generator and delivered by an ablation catheter, damage is formed in the tissue. Electrodes mounted on or within an ablation catheter are used to cause tissue destruction of heart tissue in order to improve conditions such as atrial arrhythmias (including, but not limited to, ectopic atrial tachycardia, atrial fibrillation, atrial flutter, etc.).

[0004] Arrhythmias (i.e., irregular heart rhythms) create various dangerous conditions, including loss of synchronized atrioventricular contractions and blood flow stagnation, and can lead to various diseases and even death. The main cause of atrial arrhythmias is thought to be errant electrical signals within the left or right atrium of the heart. An ablation catheter delivers ablation energy (such as high-frequency energy, cryoablation, lasers, chemicals, high-intensity focused ultrasound, etc.) to heart tissue, forming damage in the heart tissue. This damage disrupts unwanted electrical pathways, thereby limiting or preventing errant electrical signals that lead to arrhythmias.

[0005] Electroporation is a non-thermal ablation technique that involves applying a strong electric field to induce pore formation in the cell membrane. The electric field can be induced by applying pulses with relatively short durations, for example, from nanoseconds to milliseconds. Such pulses may be repeated to form a pulse train. When such an electric field is applied to tissue in vivo, cells within the tissue receive a transmembrane potential, causing pores in the cell wall to open. Electroporation can be reversible (i.e., the temporarily opened pores close again) or irreversible (i.e., the pores remain open). For example, in the field of gene therapy, reversible electroporation (i.e., temporarily opening pores) is used to introduce high molecular weight therapeutic vectors into cells. In other therapeutic applications, cell destruction can be induced, for example, by inducing irreversible electroporation using only a properly configured pulse train.

[0006] For example, pulsed-field ablation (PFA) can be used to perform instantaneous pulmonary vein isolation (PVI). PFA generally involves supplying a high-voltage pulse from electrodes placed on a catheter. For example, the voltage pulse can range from less than approximately 500 volts to approximately 2400 volts or more. These electric fields can be applied between a pair of electrodes (bipolar therapy) or between one or more electrodes and a return patch (monopolar therapy).

[0007] To generate a variety of waveforms, pulse generators selectively connect different electrodes to different voltage levels. In at least some known systems, a first subset of electrodes can be selectively connected to a first voltage level (e.g., positive voltage), and a second subset of electrodes can be selectively connected to a second voltage level (e.g., negative voltage). It should be noted that this architecture limits the possible energized configurations. For example, in such a configuration, the first subset of electrodes is generally not connectable to the second voltage level, and the second subset of electrodes is generally not connectable to the first voltage level. Therefore, it is desirable to have a pulse generation circuit that allows arbitrary electrode addressing. [Overview of the Initiative] [Problems that the invention aims to solve]

[0008] In one embodiment, a pulse generation circuit is provided configured to be coupled to a plurality of electrodes in an electroporation system. The circuit includes a first voltage source, a second voltage source, and a plurality of electrode addressing circuits, each electrode addressing circuit configured to be coupled to the associated electrode and includes a first switch that can be coupled between the electrode and the first voltage source, a second switch that can be coupled between the electrode and the second voltage source, and a third switch that can be coupled between the electrode and a return voltage.

[0009] In another embodiment, an electroporation system is provided. The electroporation system includes a catheter having a plurality of electrodes and a pulse generation circuit coupled to the plurality of electrodes, the pulse generation circuit including a first voltage source, a second voltage source and a plurality of electrode addressing circuits, each electrode addressing circuit being coupled to the associated electrode and also including a first switch coupled between the electrode and the first voltage source, a second switch coupled between the electrode and the second voltage source and a third switch coupled between the electrode and the return voltage.

[0010] In yet another embodiment, a method for controlling an electroporation system is provided. This method includes providing a catheter including a plurality of electrodes and coupling the plurality of electrodes to a pulse generation circuit, the pulse generation circuit comprising a first voltage source, a second voltage source and a plurality of electrode addressing circuits, each electrode addressing circuit being coupled to the associated electrode and also comprising a first switch coupled between the electrode and the first voltage source, a second switch coupled between the electrode and the second voltage source and a third switch coupled between the electrode and the return voltage.

[0011] The above and other aspects, features, details, usefulness and advantages of this disclosure will become apparent from reading the following description and claims, as well as from examining the accompanying drawings. [Brief explanation of the drawing]

[0012] [Figure 1] Schematic and block diagrams of a system for electroporation therapy. [Figure 2] A diagram of one embodiment of a catheter assembly that may be used in conjunction with the system shown in Figure 1. [Figure 3] A diagram of an alternative embodiment of a catheter assembly that may be used with the system shown in Figure 1. [Figure 4] A diagram of an alternative embodiment of a catheter assembly that may be used with the system shown in Figure 1. [Figure 5] A circuit diagram of one embodiment of a pulse generation circuit that may be included in a pulse generator. [Modes for carrying out the invention]

[0013] This disclosure provides a system and method for a pulse generation circuit for an electroporation system. The pulse generation circuit includes a first voltage source, a second voltage source, and a plurality of electrode addressing circuits. Each electrode addressing circuit is configured to be coupled to the associated electrode and includes a first switch that can be coupled between the electrode and the first voltage source, a second switch that can be coupled between the electrode and the second voltage source, and a third switch that can be coupled between the electrode and the return voltage.

[0014] Figure 1 shows a schematic and block diagram of system 10 for electroporation therapy. Generally, system 10 includes a catheter electrode assembly 12 positioned at the distal end 48 of a catheter 14. As used herein, “proximal” refers to the direction toward the end of the catheter closer to the clinician, and “distal” refers to the direction toward the direction toward the clinician and (generally) within the patient’s body. The electrode assembly includes one or more electrically insulated individual electrode elements. Each electrode element, also referred to herein as a catheter electrode, is individually wired to be selectively paired with or combined with other electrode elements to function as a bipolar or multipolar electrode.

[0015] System 10 may be used for irreversible electroporation (IRE) to destroy tissue. In particular, System 10 may be used for electroporation-inducible therapies that involve supplying current in a manner that directly causes irreversible loss of integrity of the cell membrane (cell wall), leading to its destruction and cell destruction. This cell destruction mechanism can be considered an "outside-in" process, meaning that destruction of the cell's outer wall has harmful effects on the inside of the cell. Typically, in classical cell membrane electroporation, the current is delivered as a pulsed electric field in the form of short-duration pulses (e.g., having a duration of 500 nanoseconds (ns) to 20 microseconds (μs)) between closely spaced electrodes capable of delivering an electric field strength of about 0.1 to 1.0 kilovolts / centimeter (kV / cm). In some alternative embodiments, the electric field strength may be higher (e.g., 2.0 kV / cm or higher). System 10 may be used for high-power (e.g., high voltage and / or high current) electroporation treatments. Furthermore, system 10 may be used with a loop catheter as shown in Figures 2A and 2B, and / or with a basket catheter as shown in Figures 3A to 3C.

[0016] In one embodiment, stimulation is supplied selectively (for example, between a pair of electrodes) on the catheter 14. Furthermore, the electrodes on the catheter 14 may be switchable between connection to a 3D mapping system and connection to an electroporation generator.

[0017] Irreversible electroporation using multi-electrode catheters may allow for pulmonary vein isolation with just one shock per vein, potentially significantly reducing procedure time compared to sequentially placing radiofrequency (RF) ablation tips around the vein.

[0018] While the energizing strategy is described as including DC pulses, it should be understood that embodiments may use variations and remain within the spirit and scope of this disclosure. For example, exponentially decaying pulses, exponentially increasing pulses, and combinations thereof may be used. Furthermore, in some embodiments, AC pulses may also be used.

[0019] Furthermore, it should be understood that the mechanism of cell destruction in electroporation is not primarily due to the heating effect, but rather to the destruction of the cell membrane by the application of a high-voltage electric field. Therefore, electroporation may be able to avoid to some extent the thermal effects that can occur when using radio frequency (RF) energy. This "cryotherapy" has desirable characteristics.

[0020] With this background, referring again to Figure 1, the system 10 includes a catheter electrode assembly 12 which includes at least one catheter electrode. The electrode assembly 12 is incorporated as part of a medical device such as a catheter 14 for electroporation therapy of tissue 16 within the patient's body 17. In exemplary embodiments, the tissue 16 includes the heart or cardiac tissue. However, it should be understood that embodiments may be used to perform electroporation therapy with respect to various other body tissues (e.g., kidney tissue, tumors, etc.).

[0021] Figure 1 further illustrates several return electrodes designated 18, 20, and 21, which may be used by various subsystems included in the overall system 10, such as an electroporation generator 26, an electrophysiological (EP) monitor such as an ECG monitor 28, and a localization and navigation system 30 for visualization, mapping, and navigation of internal structures. In the illustrated embodiment, the return electrodes 18, 20, and 21 are patch electrodes. It should be understood that the illustration of a single patch electrode is illustrative (for clarity), and such subsystems to which these patch electrodes are connected may include multiple patch (body surface) electrodes, typically including multiple patch (body surface) electrodes, and may include split patch electrodes (as described herein). In other embodiments, the return electrodes 18, 20, and 21 may be other types of electrodes suitable for use as return electrodes, for example, including one or more catheter electrodes. The return electrodes that are catheter electrodes may be part of the electrode assembly 12 or part of a separate catheter or device (not shown). System 10 may further include a main computer system 32 (including an electronic control unit 50 and a data storage memory 52), which may be integrated with a localization and navigation system 30 in certain embodiments. System 32 may further include, among other components, conventional interface components such as various user input / output mechanisms 34A and a display 34B.

[0022] The electroporation generator 26 is configured to energize the electrode elements according to an electroporation energization strategy that may be predetermined or selectable by the user. For electroporation therapy, the generator 26 can deliver an electric field strength of about 0.1 to 1.0 kV / cm (i.e., at the tissue site) in the form of a pulsed electric field between closely spaced electrodes in the form of short-duration DC pulses (e.g., having a duration from nanoseconds to several milliseconds, or any duration suitable for electroporation) via the electrode assembly 12. In some alternative embodiments, the electric field strength may be higher (e.g., 2.0 kV / cm or more). The amplitude and pulse width required for irreversible electroporation are in an inverse relationship. That is, as the pulse width decreases, the amplitude generally may increase to achieve chronaxy.

[0023] The electroporation generator 26, which may also be referred to herein as a DC energy source, is a biphasic electroporation generator 26 configured to generate a series of DC energy pulses that generate current in both directions (i.e., positive and negative pulses). In other embodiments, the electroporation generator is a monophasic electroporation generator or a polyphasic electroporation generator. In some embodiments, the electroporation generator 26 is configured to output energy in DC pulses at selectable energy levels such as 50 joules, 100 joules, 200 joules, etc. Other embodiments may have more or fewer energy settings, and the values of the available settings may be the same or different. To successfully perform electroporation, some embodiments utilize a 200-joule output level. For example, the electroporation generator 26 may output a DC pulse having a peak magnitude from about 300 volts (V) to about 3,200 V at a 200-joule output level. In other embodiments, any other suitable positive or negative voltage may be output.

[0024] In some embodiments, variable impedance 27 enables changing the impedance of system 10 to limit arc discharge. Further, variable impedance 27 may be used to modify one or more characteristics such as the amplitude, duration, pulse shape, etc. of the output of electroporation generator 26. Although shown as a separate component, variable impedance 27 may be incorporated into catheter 14 or generator 26.

[0025] Continuing to refer to FIG. 1, as described above, catheter 14 may include functionality for electroporation and, in certain embodiments, may also include an additional ablation function (e.g., RF ablation). However, it should be understood that in those embodiments, variations are possible with respect to the type of ablation energy provided (e.g., cryoablation, ultrasound, etc.).

[0026] In the illustrated embodiment, catheter 14 includes a cable connector or interface 40, a handle 42, and a shaft 44 having a proximal end 46 and a distal end 48. Catheter 14 may also include other conventional components not shown herein, such as temperature sensors, additional electrodes, and corresponding wires or leads. Connector 40 provides a mechanical and electrical connection to cable 56 extending from generator 26. Connector 40 may include conventional components known in the art and is disposed at the proximal end of catheter 14 as shown.

[0027] The handle 42 may provide a place for the clinician to grasp the catheter 14 and may further provide means for maneuvering or guiding the shaft 44 within the body 17. For example, the handle 42 may include means for changing the length of a guidewire extending through the catheter 14 to the distal end 48 of the shaft 44, or means for maneuvering the shaft 44. Furthermore, in some embodiments, the handle 42 may be configured to change the shape, size, and / or orientation of a portion of the catheter, and it will be understood that the structure of the handle 42 may vary. In another embodiment, the catheter 14 may be robotically driven or controlled. Thus, the catheter 14 is operated using a robot rather than the clinician operating a handle to move the catheter 14 (and in particular its shaft 44) forward / backward and / or steer or guide it. The shaft 44 is an elongated tubular flexible member configured to move within the body 17. The shaft 44 supports the electrode assembly 12 and is configured to include associated conductors and, optionally, additional electronics used for signal processing or adjustment. The shaft 44 may also allow for the transport, delivery, and / or removal of fluids (including irrigation fluids and body fluids), pharmaceuticals, and / or surgical instruments or devices. The shaft 44 may be made of a conventional material such as polyurethane and define one or more lumens configured to accommodate and / or transport electrical conductors, fluids, or surgical instruments, as described herein. The shaft 44 may be introduced into a blood vessel or other structure within the body 17 via a conventional introducer. The shaft 44 may then advance / retract and / or be guided or led through the body 17 to a desired location, such as a site of tissue 16, including the use of a guidewire or other means known in the art.

[0028] A localization and navigation system 30 may be provided for the visualization, mapping, and navigation of internal structures. The localization and navigation system 30 may include conventional devices commonly known in the art. For example, the localization and navigation system 30 may be substantially similar to the EnSite Precision® system, which is commercially available and publicly transferred from Abbott Laboratories, Inc., and is described in its entirety in U.S. Patent Application No. 7,263,397, entitled “Method and Apparatus for Catheter Navigation and Location and Mapping in the Heart,” the entire disclosure of which is incorporated herein by reference. In another example, the localization and navigation system 30 may be substantially similar to the EnSite X® mapping system, which is described in its entirety in U.S. Patent Application No. 2020 / 0138334, entitled “Method for Medical Device Localization Based on Magnetic and Impedance Sensors,” the entire disclosure of which is incorporated herein by reference. However, it should be understood that the localization and navigation system 30 is illustrative and not inherently limiting. Other techniques are known for positioning / navigating (and visualizing) catheters in space, including, for example, Biosense-Webster's CARTO navigation and positioning system, Boston Scientific Symed's Rhythmia® system, Koninklijke-Philips' KODEX® system, Northern Digital's AURORA® system, commonly available fluoroscopy systems, or magnetic positioning systems such as Mediguide's gMPS system.

[0029] In this regard, some positioning, navigation, and / or visualization systems may include sensors for generating signals indicating the position of a catheter, for example, one or more electrodes in the case of an impedance-based positioning system, or one or more coils (i.e., wire windings) configured to detect one or more characteristics of a magnetic field, for example, in the case of a magnetic field-based positioning system. In yet another example, system 10 may utilize a combination of electric field-based and magnetic field-based systems, as shown in whole with reference to U.S. Patent No. 7,536,218. The disclosure of Patent No. 7,536,218, titled "Hybrid Magnetic-Based and Impedance Based Position Sensing," is incorporated herein by reference in its entirety.

[0030] Pulse-field ablation (PFA), a method for achieving irreversible electroporation, may be performed using the systems and methods described herein. In some cases, PFA may be used in specific cardiac tissue sites, such as pulmonary veins, to perform pulmonary vein isolation (PVI). In PFA, the electric field may be applied between adjacent electrodes (bipolar approach) or between one or more electrodes and a return patch (monopolar approach). Each of these approaches has its own advantages and disadvantages.

[0031] Regarding wound size and proximity, the monopolar approach has a wider effective range and may be able to create deeper wounds with the same applied voltage. Furthermore, the monopolar approach may be able to create wounds from a distance (e.g., from a distance that is generally close but not necessarily in contact with the tissue). The bipolar approach can create smaller wounds, and proximity to or contact with the tissue is necessary to create percutaneous wounds. However, the monopolar approach may result in wounds that are larger than necessary, while wounds created by the bipolar approach may be more localized.

[0032] Due to their broad area of ​​effect, monopolar approaches can potentially cause undesirable activation of skeletal muscle and / or nerves. In contrast, bipolar approaches have a limited area of ​​effect proportional to the electrode spacing on the leads and are less likely to depolarize cardiomyocytes or nerve fibers.

[0033] To monitor the operation of system 10, one or more impedances between the catheter electrode 144 and / or return electrodes 18, 20, 21 may be measured. For example, in the case of system 10, the impedance may be measured as described in U.S. Patent Application Publication No. 2019 / 0117113 filed on 23 October 2018, U.S. Patent Application Publication No. 2019 / 0183378 filed on 19 December 2018, and U.S. Patent Application No. 63 / 027,660 filed on 20 May 2020, all of which are incorporated herein by reference in their entirety.

[0034] Figures 2A and 2B illustrate one embodiment of a catheter assembly 146 that may be used with a catheter 14 in system 10. The catheter assembly 146 is sometimes referred to as a loop catheter. Those skilled in the art will understand that in other embodiments, any suitable catheter may be used. Specifically, Figure 2A is a side view of a catheter assembly 146 having a variable diameter loop 150 at its distal end 142. Figure 2B is an end view of the variable diameter loop 150 of the catheter assembly 146. Those skilled in the art will understand that the methods and systems described herein can be implemented using any suitable catheter (e.g., a fixed loop catheter, a linear catheter, a basket catheter, etc.). As shown in Figures 2A and 2B, the variable diameter loop 150 is coupled to the distal section 151 of a shaft 44.

[0035] The variable diameter loop 150 is selectively transitionable between an expanded (also called "open") diameter 160 (shown in Figure 2A) and a contracted (also called "closed") diameter 160 (not shown). In the exemplary embodiment, the expanded diameter 160 is 28 mm and the contracted diameter 160 is 15 mm. In other embodiments, the diameter 160 may be variable between any suitable open diameter 160 and closed diameter 160.

[0036] In the illustrated embodiment, the variable diameter loop 150 includes, in the expanded configuration, 14 catheter electrodes 144 arranged substantially equally spaced on the circumference of the variable diameter loop 150. In the contracted configuration, one or more of the electrodes 144 may overlap. In other embodiments, other arrangements of the catheter electrodes 144 may be implemented. For example, in one embodiment, the variable diameter loop 150 includes 12 catheter electrodes 144.

[0037] The catheter electrode 144 is a platinum ring electrode configured to conduct and / or discharge currents in the range of 1000 volts and / or 10 amperes. In other embodiments, the variable diameter loop 150 may include any suitable number of catheter electrodes 144 made of any suitable material. The catheter electrodes 144 may include any catheter electrodes suitable for conducting high voltages and / or high currents (e.g., in the range of 1000 volts and / or 10 amperes). Each catheter electrode 144 is separated from each other catheter electrode by an insulating gap 152. In the exemplary embodiment, each catheter electrode 144 has the same length 164 (shown in Figure 2B), and each insulating gap 152 has the same length 166 as each other gap 152. Lengths 164 and 166 are both about 2.5 mm in the exemplary embodiment. In other embodiments, lengths 164 and 166 may be different from each other. Furthermore, in some embodiments, the catheter electrodes 144 do not all have to be the same length 164, and / or the insulation spacings 152 do not all have to be the same length 166. In some embodiments, the catheter electrodes 144 are not evenly spaced on the circumference of the variable diameter loop 150.

[0038] The diameter 160 and the spacing of the catheter electrodes 144 may be developed to provide a target range of energy density for the tissue and to provide sufficient electroporation coverage for various human anatomical shapes. Generally, it is desirable to provide a sufficient number of electrodes 144 with appropriate lengths 164 to provide substantially uniform and continuous coverage around the circumference of the variable diameter loop 150, while still allowing sufficient flexibility to enable the variable diameter loop 150 to stretch and contract to change the diameter 160 to the desired extreme.

[0039] As described above, the length 164 of the catheter electrode 144 may be varied. Increasing the length 164 of the catheter electrode 144 increases the coverage of the electrode 144 around the circumference of the variable diameter loop 150, while decreasing the current density on the electrode 144 (by increasing the surface area), which can help prevent arc discharge during the electroporation procedure. However, increasing the length 164 too much may prevent the variable diameter loop 150 from forming a smooth circular shape and may limit the closed diameter 160 of the variable diameter loop 150. Furthermore, if the length 164 is made too large, the surface area of ​​the catheter electrode 144 may increase to the point where the current density applied to the catheter electrode 144 by the power supply falls below the minimum current density required for successful treatment. Conversely, shortening the length 164 decreases the surface area, thereby increasing the current density of the catheter electrode 144 (assuming no other system changes). As described above, a higher current density increases the risk of arc discharge during electroporation, which may necessitate the addition of greater system resistance to prevent arc discharge. Furthermore, reducing the length 164 to obtain the desired uniform coverage around the circumference of the variable diameter loop 150 may require more catheter electrodes 144. Increasing the number of catheter electrodes 144 on the variable diameter loop 150 may prevent the variable diameter loop 150 from being contracted to the desired minimum diameter 160.

[0040] Figure 3A is a perspective view of an alternative catheter assembly 200 that may be used with catheter 14. The catheter assembly 200 is sometimes referred to as a basket catheter. The catheter assembly 200 includes a shaft 202 and a plurality of splines 204 surrounding the distal portion 206 of the shaft 202. In this embodiment, the catheter assembly 200 also includes a balloon 208 surrounded by the splines 204. The balloon 208 may be selectively inflated to fill the space between the splines 204. In particular, the balloon 208 acts as an insulator, generally reducing energy loss, which may result in an increased wound size.

[0041] Each spline 204 includes a proximal end 210 connected to the shaft 202 and a distal end 212 connected to the shaft 202. From the proximal end 210 to the distal end 212, the spline 204 has an arc shape that extends radially outward.

[0042] In this embodiment, each spline 204 includes one or more individual electrodes 220. For example, each spline 204 may include an elastic material (e.g., nitinol) covered with a polymer tube 222, and the individual electrodes 220 may be mounted on the outside of the polymer tube 222. In the illustrated embodiment, each spline 204 includes two electrodes 220. Furthermore, as shown in Figure 2, the electrodes 220 are generally positioned closer to the distal end 212 than the proximal end 210 to correspond to the portion of the spline 204 that is intended to contact the pulmonary veins.

[0043] Alternatively, each spline 204 may include any appropriate number and arrangement of electrodes 220. For example, in some embodiments, each spline 204 includes four electrodes 220.

[0044] In this embodiment, the alternately arranged splines 204 alternate in polarity. That is, electrodes 220 on a particular spline 204 have the same polarity, but electrodes 220 on a particular spline 204 have a different polarity from electrodes 220 on adjacent splines 204. Alternatively, any suitable polarization scheme may be used. During delivery, the splines 204 may be folded toward the shaft 202. Then, to perform ablation, the splines 204 are unfolded to extend radially outward.

[0045] All splines 204 may have the same length, or at least some splines 204 may have different lengths. Furthermore, the insulating material on each spline 204 may have the same length, or at least some splines 204 may have insulating material of different lengths. In addition, in some embodiments, the catheter assembly 200 includes a distal electrode (not shown) positioned distal to the splines 204. The distal electrode may be used to perform point ablation (e.g., by forming a bipolar field between the distal electrode and one of the splines 204) and / or for visualization / mapping purposes (e.g., by using the distal electrode in combination with an electrode on the shaft 202).

[0046] Figure 3B is a perspective view of an alternative catheter assembly 250 that may be used with catheter 14, and Figure 3C is a schematic side view of catheter assembly 250. Like catheter assembly 200 (shown in Figure 3A), catheter assembly 250 is sometimes referred to as a basket assembly.

[0047] The catheter assembly 250 includes a shaft 252 and a plurality of splines 254 surrounding the distal portion 256 of the shaft 252. In this embodiment, the catheter assembly 250 includes a balloon 258 surrounded by the splines 254. The balloon 258 may be selectively inflated to occupy the space between the splines 254. It should be noted that the balloon 258 acts as an insulator and generally reduces energy, which may result in an increased wound size.

[0048] Each spline 254 includes a proximal end 260 connected to the shaft 252 and a distal end 262 connected to the shaft 252. From the proximal end 260, the spline 1004 extends radially outward to an inflection point 264, and then radially inward to the distal end 262. Figure 3C shows the catheter assembly 250 positioned within a pulmonary vein 266.

[0049] The body of each spline 254 is made of an elastic material (e.g., nitinol) and functions as a relatively large electrode. In this embodiment, the alternately arranged splines 254 alternate in polarity; that is, each positive spline 254 is positioned between two negative splines 254, and vice versa. Alternatively, any suitable polarization scheme may be used.

[0050] To control the ablation zone of each spline 254, portions of each spline 254 may be covered with insulating material 270 (e.g., heat-shrinkable or polymer tubing, or spray or dip-coat with polyimide or PEBAX), and the exposed portions of the spline 254 function as electrodes. In the embodiments shown in Figures 3B and 3C, the portions of the spline 254 between the inflection point 264 and the distal end 262 are generally exposed, while the portions of the spline 254 between the inflection point 264 and the proximal end 260 are generally insulated. As a result, portions of the spline 254 that come into contact with the pulmonary veins 266 are exposed (see Figure 3C). Alternatively, any suitable insulating configuration may be used.

[0051] During delivery, the spline 254 and balloon 258 may be folded. To perform ablation, the spline 254 is unfolded at an inflection point 264 extending radially outward, and the balloon 258 is selectively inflated to occupy the space between the splines 254.

[0052] The combination of balloon 258 and spline 254 facilitates the direct delivery and deployment of the catheter assembly 250. Furthermore, balloon 258 delivers more energy to the tissue being ablated and stabilizes spline 254, preventing lateral movement. Additionally, using spline 254 as the electrode instead of individual small electrodes promotes cost reduction and improved reliability of the catheter assembly 250.

[0053] All splines 254 may have the same length, or at least some splines 254 may have different lengths. Furthermore, the insulating material 270 on each spline 254 may have the same length, or at least some splines 254 may have insulating material 270 of different lengths. In addition, in some embodiments, the catheter assembly 250 includes a distal electrode (not shown) positioned distal to the splines 254. The distal electrode may be used to perform point ablation (e.g., by forming a bipolar field between the distal electrode and one of the splines 254) and / or for visualization / mapping purposes (e.g., by using the distal electrode in combination with an electrode on the shaft 252).

[0054] Figure 4 is a side view of an alternative catheter assembly 280 that may be used with catheter 14. Catheter assembly 280 is sometimes called a grid assembly. As shown in Figure 4, catheter assembly 280 is coupled to the distal section 282 of a shaft, such as shaft 44 (shown in Figure 1).

[0055] The catheter assembly 280 includes a plurality of splines 284 extending from the proximal end 286 to the distal end 288. Each spline 284 includes a plurality of electrodes 290. In the embodiment shown in Figure 4, the catheter assembly 280 includes four splines 284, each spline 284 including four electrodes 290, such that the electrodes 290 form a grid configuration. Thus, the catheter assembly 280 provides a 4x4 grid of electrodes 290. In one embodiment, the spacing between each pair of adjacent electrodes 290 is approximately 4 millimeters (mm), such that the dimensions of the grid of electrodes 290 are approximately 12 mm x 12 mm. Alternatively, the catheter assembly 280 may include any suitable number of splines 284, any suitable number of electrodes 290, and / or any suitable arrangement of electrodes 290. For example, in some embodiments, the spacing between each pair of adjacent electrodes is approximately 2 millimeters (mm). Furthermore, in some embodiments, the catheter assembly 280 may include 56 electrodes arranged in a 7x8 grid, for example.

[0056] Using the catheter assembly 280, wounds may be generated on individual electrodes 290 using a monopolar approach (e.g., by applying a voltage between individual electrodes 290 and a return electrode), or wounds may be generated between pairs of electrodes 290 using a bipolar approach. The wounds may be generated within anatomical structures by selectively energizing the electrodes in a particular configuration and / or pattern (e.g., energizing individual electrodes 290 independently of each other, or energizing multiple electrodes 290 simultaneously).

[0057] Those skilled in the art will understand that catheter assembly 146 (shown in Figures 2A and 2B), catheter assembly 200 (shown in Figure 3A), catheter assembly 250 (shown in Figures 3B and 3C), and catheter assembly 280 (shown in Figure 4) are merely illustrative examples. In particular, the systems and methods described herein may be carried out using any suitable catheter assembly.

[0058] In electroporation therapy, a pulse generator (e.g., electroporation generator 26 (shown in Figure 1)) is used to generate a waveform, which is then applied between pairs of catheter electrodes (i.e., bipolar approach) or between individual catheter electrodes and a return patch (i.e., monopolar approach). The waveform may be monophasic, biphasic (i.e., having both positive and negative pulses), or polyphasic. Furthermore, the waveform may include bursts of one or more pulses (each burst containing multiple pulses). In addition, the waveform is defined by several parameters (e.g., pulse width, pulse amplitude, frequency, etc.).

[0059] To generate a variety of waveforms, pulse generators selectively connect different electrodes to different voltage levels. In at least some known systems, a first subset of electrodes can be selectively connected to a first voltage level (e.g., positive voltage), and a second subset of electrodes can be selectively connected to a second voltage level (e.g., negative voltage). Notably, this architecture limits the possible energized configurations. In such configurations, for example, the first subset of electrodes is generally not connectable to the second voltage level, and the second subset of electrodes is generally not connectable to the first voltage level.

[0060] The systems and methods described herein provide electrode addressing circuits that enable arbitrary electrode addressing; that is, each electrode can be selectively connected to multiple different voltage levels. This increases the flexibility of the energized configuration.

[0061] Figure 5 is a circuit diagram of one embodiment of a pulse generation circuit 400, which may be included in a pulse generator such as an electroporation generator 26 (shown in Figure 1). The pulse generation circuit 400 can be coupled to a plurality of electrodes 408 (numbered 1, 2, 3, (N-1), N), such as electrodes on a catheter electrode assembly 12 (shown in Figure 1).

[0062] The pulse generation circuit 400 includes a first voltage source 402, a second voltage source 404, and a plurality of modules 406. The first voltage source 402 and the second voltage source 404 may be, for example, high-voltage direct current (DC) voltage sources.

[0063] Each module 406 is associated with a plurality of electrodes 408. In the illustrated embodiment, each module 406 is associated with four electrodes 408. Alternatively, those skilled in the art will understand that each module 406 may be associated with any suitable number of electrodes 408. Furthermore, the pulse generation circuit 400 may include any suitable number of modules 406. For example, the pulse generation circuit 400 may include four modules 406, each module associated with four electrodes 408, resulting in a circuit for a total of 16 electrodes 408.

[0064] As shown in Figure 5, within module 406, an electrode addressing circuit 410 is coupled to each electrode 408. The electrode addressing circuit 410 allows each electrode 408 to be arbitrarily addressed. Specifically, for a given electrode 408, the electrode addressing circuit 410 includes a first switch 412 coupled between electrode 408 and a first voltage source 402, a second switch 414 coupled between electrode 408 and a second voltage source 404, and a third switch 416 coupled between electrode 408 and a return voltage 418. Using switches 412, 414, and 416, electrode 408 may be selectively connected to one of the first voltage source 402, the second voltage source 404, and the return voltage 418, as desired. The operation of switches 412, 414, and 416 may be controlled using any suitable control device (not shown).

[0065] Switches 412, 414, and 416 may be any suitable switching device. For example, switches 412, 414, and 416 may be insulated-gate bipolar transistors (IGBTs), silicon metal-oxide-semiconductor field-effect transistors (MOSFETs), silicon carbide MOSFETs, silicon carbide junction field-effect transistors (JFETs), or other combinations of enhancement-mode and / or depletion-mode devices (e.g., a cascode of silicon carbide depletion-mode JFETs combined with silicon MOSFETs).

[0066] Therefore, each electrode 408 may be selectively connected to the first voltage source 402, the second voltage source 404, or the return voltage 418, independently of the other electrodes 408. This allows for various combinations of electrodes that generate pulses at different voltage levels and / or different pulse widths, providing great flexibility in the selection of treatment schemes.

[0067] For example, the first voltage source 402 may output a positive voltage and the second voltage source 404 may output a negative voltage. In the first phase, the first electrode 408 may be connected to the first voltage source 402 and the second electrode 408 may be connected to the return voltage 418 (so that the voltage of the first electrode 408 is higher than that of the second electrode 408). In the second complementary phase, the first electrode 408 may be connected to the second voltage source 404 and the second electrode 408 may be connected to the return voltage 418 (so that the voltage of the first electrode 408 is lower than that of the second electrode 408).

[0068] Furthermore, by controlling the time intervals between each phase, energy can be delivered in one direction while charge can be delivered in both directions. This makes it easier to achieve desired electrophysical effects (e.g., selective and irreversible electroporation of tissue) while reducing undesirable effects (e.g., involuntary recruitment of skeletal muscle).

[0069] This architecture also significantly reduces the number of switches required compared to at least some known multiplexing approaches. Reducing the number of switches reduces parasitic capacitance, which could otherwise cause distortion and ringing in the output waveform.

[0070] In the embodiment shown in Figure 5, the electrode addressing circuit 410 includes a plurality of current-limiting resistors 430. For example, one current-limiting resistor 430 may be coupled between a first switch 412 and a first voltage source 402, another current-limiting resistor 430 may be coupled between a second switch 414 and a second voltage source 404, and yet another current-limiting resistor 430 may be coupled between a third switch 416 and an electrode 408. The current-limiting resistors 430 provide fault protection.

[0071] Furthermore, in the embodiment shown in Figure 5, the pulse generation circuit 400 includes a plurality of isolation switches 432. Each isolation switch 432 is coupled in series between the electrode addressing circuit 410 and the associated electrode 408. As described above, switches 412, 414, and 416 of the electrode addressing circuit 410 may be implemented using transistors. Therefore, even when switches 412, 414, and 416 are all open, some leakage current may flow from the first voltage source 402 and the second voltage source 404 to the electrode 408.

[0072] In contrast to switches 412, 414, and 416, in this embodiment, the isolation switch 432 is an electromechanical switch that is not implemented using a transistor. Therefore, when open, the isolation switch 432 completely disconnects the electrode 408 from the first and second voltage sources 402 and 404 (for example, without allowing leakage current to the electrode 408). Thus, when the isolation switch 432 is open, it prevents any current from reaching the electrode 408 and provides protection to the patient.

[0073] The systems and methods described herein relate to pulse generation circuits for electroporation systems. The pulse generation circuit includes a first voltage source, a second voltage source, and a plurality of electrode addressing circuits. Each electrode addressing circuit is configured to be coupled to the associated electrode and includes a first switch that can be coupled between the electrode and the first voltage source, a second switch that can be coupled between the electrode and the second voltage source, and a third switch that can be coupled between the electrode and the return voltage.

[0074] While certain embodiments of this disclosure have been described above with a degree of specificity, those skilled in the art can make numerous modifications to the disclosed embodiments without departing from the spirit or scope of this disclosure. References to all directions (e.g., top, bottom, upward, downward, left, right, leftward, rightward, top, bottom, upward, downward, downward, vertical, horizontal, clockwise, and counterclockwise) are used solely for identification purposes to aid the reader's understanding of this disclosure and do not, in particular, impose any limitations on the location, orientation, or use of this disclosure. References to connections (e.g., attached, joined, connected, etc.) should be interpreted broadly and may include intermediate members between the connection of elements and relative movement between elements. Thus, references to connections do not necessarily imply that two elements are directly connected and in a fixed relationship with one another. All matters included in the above description or shown in the accompanying drawings are intended to be interpreted only as illustrative and not limiting. Modifications to details or structures can be made without departing from the spirit of this disclosure as defined in the accompanying claims.

[0075] When describing elements or preferred embodiments of the present disclosure, the articles “a,” “an,” “the,” and “said” are intended to indicate the presence of one or more of the elements. The terms “comprising,” “including,” and “having” are intended to be comprehensive and mean that additional elements other than those listed may exist.

[0076] Various modifications can be made to the above configuration without departing from the scope of this disclosure, so all matters included in the above description or shown in the accompanying drawings are intended to be interpretable, not limited to, meaning.

Claims

1. A pulse generation circuit configured to be coupled to multiple electrodes of an electroporation system, First voltage source and The second voltage source and It comprises multiple electrode addressing circuits, Each electrode addressing circuit is: It is configured to be coupled to the relevant electrodes, A first switch that can be coupled between the electrode and the first voltage source, A second switch that can be coupled between the electrode and the second voltage source, A third switch that can be coupled between the electrode and the return electrode is provided, Each of the electrode addressing circuits is controlled by a control device, which selectively closes one of the first switch, the second switch, and the third switch to selectively connect the corresponding one of the first voltage source, the second voltage source, and the return electrode to the electrode. Pulse generation circuit.

2. The pulse generation circuit according to claim 1, wherein the first voltage source is a positive voltage source and the second voltage source is a negative voltage source.

3. The pulse generation circuit includes a first module and a second module, The first module is, The first electrode addressing circuit, The first electrode is coupled to the first electrode addressing circuit, The second module described above is The second electrode addressing circuit, The second electrode is coupled to the second electrode addressing circuit, The pulse generation circuit according to claim 1.

4. The pulse generation circuit according to claim 1, further comprising a current-limiting resistor coupled between the first switch and the first voltage source.

5. The pulse generation circuit according to claim 1, further comprising a current-limiting resistor coupled between the second switch and the second voltage source.

6. The pulse generation circuit according to claim 1, wherein at least one of the first switch, the second switch, and the third switch comprises an insulated gate bipolar transistor.

7. The pulse generation circuit according to claim 1, wherein at least one of the first switch, the second switch, and the third switch comprises a metal-oxide-semiconductor field-effect transistor.

8. The pulse generation circuit according to claim 1, further comprising a plurality of isolation switches, each isolation switch being coupled between one of the plurality of electrode addressing circuits and the associated electrode.

9. It is an electroporation system, A catheter equipped with multiple electrodes, The system comprises a pulse generation circuit coupled to the plurality of electrodes, The pulse generation circuit is First voltage source and The second voltage source and It comprises multiple electrode addressing circuits, Each electrode addressing circuit is: It is coupled to the relevant electrodes, A first switch coupled between the electrode and the first voltage source, A second switch coupled between the electrode and the second voltage source, A third switch coupled between the electrode and the return electrode, Each of the electrode addressing circuits is controlled by a control device, which selectively closes one of the first switch, the second switch, and the third switch to selectively connect the corresponding one of the first voltage source, the second voltage source, and the return electrode to the electrode. Electroporation system.

10. The electroporation system according to claim 9, wherein the first voltage source is a positive voltage source and the second voltage source is a negative voltage source.

11. The pulse generation circuit includes a first module and a second module, The first module is, The first electrode addressing circuit, The first electrode is coupled to the first electrode addressing circuit, The second module described above is The second electrode addressing circuit, The second electrode is coupled to the second electrode addressing circuit, The electroporation system according to claim 9.

12. The electroporation system according to claim 9, wherein the pulse generation circuit further comprises a current-limiting resistor coupled between the first switch and the first voltage source.

13. The electroporation system according to claim 9, wherein the pulse generation circuit further comprises a current-limiting resistor coupled between the second switch and the second voltage source.

14. The electroporation system according to claim 9, wherein at least one of the first switch, the second switch, and the third switch comprises an insulated gate bipolar transistor.

15. The electroporation system according to claim 9, wherein at least one of the first switch, the second switch, and the third switch comprises a metal-oxide-semiconductor field-effect transistor.

16. The electroporation system according to claim 9, wherein at least one of the first switch, the second switch, and the third switch comprises a junction field-effect transistor.

17. It is an electroporation system, A catheter containing multiple electrodes, The system comprises a pulse generation circuit that can be coupled to the plurality of electrodes, The pulse generation circuit is First voltage source and The second voltage source and It comprises multiple electrode addressing circuits, Each electrode addressing circuit is: It is coupled to the relevant electrodes, A first switch coupled between the electrode and the first voltage source, A second switch coupled between the electrode and the second voltage source, A third switch coupled between the electrode and the return electrode, The system comprises means for selectively closing one of the first switch, the second switch, and the third switch to selectively couple the corresponding one of the first voltage source, the second voltage source, and the return electrode to the electrode, Electroporation system.

18. The electroporation system according to claim 17, wherein the first voltage source is a positive voltage source and the second voltage source is a negative voltage source.

19. The pulse generation circuit includes a plurality of modules, The electroporation system according to claim 17, wherein each module of the plurality of modules includes at least two electrode addressing circuits from the plurality of electrode addressing circuits and at least two electrodes corresponding to the at least two electrode addressing circuits.

20. The electroporation system according to claim 17, wherein the pulse generation circuit further includes a current-limiting resistor coupled between the first switch and the first voltage source.

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