System and method for monitoring pulsed field ablation generator output

Abstract

A pulse generating circuit is described that is configured to be coupled to a plurality of electrodes of an electroporation system. The pulse generating circuit includes at least one voltage source, a plurality of output lines, a switching circuit coupled between the at least one voltage source and the plurality of output lines, each of the plurality of output lines configured to deliver at least one voltage pulse to a corresponding electrode of the plurality of electrodes, and a current sensing circuit coupled between the at least one voltage source and the plurality of output lines, the current sensing circuit is configured to sense a current flowing through at least one of the plurality of output lines.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to provisional application serial number 63 / 416680 filed on October 17, 2022, which is incorporated herein by reference in its entirety. Technical Field

[0003] The present disclosure relates generally to tissue ablation systems. In particular, the present disclosure relates to electroporation systems including circuitry for monitoring the output of a pulse generator. Background Art

[0004] It is well known that ablation therapy can be used to treat a variety of diseases that affect the human anatomy. For example, ablation therapy can be used to treat atrial arrhythmias. Lesions are formed in tissue when the tissue is ablated or at least subjected to ablative energy generated by an ablation generator and delivered by an ablation catheter. Electrodes mounted on or within the ablation catheter are used to cause tissue destruction in cardiac tissue to correct diseases such as atrial arrhythmias (including but not limited to ectopic atrial tachycardia, atrial fibrillation, and atrial flutter).

[0005] Arrhythmias (i.e., irregular heartbeats) can cause a variety of dangerous conditions, including unsynchronized contraction of the atria and ventricles and stagnant blood flow, which can lead to a variety of illnesses and even death. The primary cause of atrial arrhythmias is believed to be stray electrical signals within the left or right atrium of the heart. Ablation catheters deliver ablative energy (e.g., radiofrequency energy, cryoablation, lasers, chemicals, high-intensity focused ultrasound, etc.) to cardiac tissue to create lesions in the cardiac tissue. The lesions disrupt the undesirable electrical pathways, thereby limiting or preventing the stray electrical signals that cause arrhythmias.

[0006] Electroporation is a non-thermal ablation technique that involves applying a strong electric field to induce pore formation on the cell membrane. The electric field can be induced by applying a pulse of relatively short duration, which can last, for example, from one nanosecond to several milliseconds. Such pulses can be repeated to form a pulse train. When such an electric field is applied to a tissue in an in vivo environment, cells in the tissue are affected by the transmembrane potential, thereby opening pores in the cell wall. Electroporation can be reversible (i.e., the temporarily opened pore will reseal) or irreversible (i.e., the pore will remain open). For example, in the field of gene therapy, reversible electroporation (i.e., temporarily opened pores) is used to transfect high molecular weight therapeutic vectors into cells. In other therapeutic applications, appropriately configured pulse trains can be used alone to cause cell destruction, for example by causing irreversible electroporation.

[0007] For example, pulsed field ablation (PFA) can be used to perform transient pulmonary vein isolation (PVI). PFA generally involves delivering high voltage pulses from electrodes disposed on a catheter. For example, the voltage pulses can range from less than about 500 volts to about 2400 volts or more. These fields can be applied between pairs of electrodes (bipolar therapy) or between one or more electrodes and a return patch (monopolar therapy).

[0008] In at least some known systems, the output current from the pulse generator to one or more electrodes is not monitored. Instead, the upstream capacitor voltage may be measured, but no downstream current monitoring is performed after those capacitors are discharged through a switching circuit coupled between the capacitors and the electrodes. As a result, faults downstream of the capacitors may be difficult or impossible to detect and remedy. Therefore, it is desirable to have a pulse generating circuit that is capable of monitoring the output current from the pulse generator. Summary of the invention

[0009] In one aspect, a pulse generating circuit configured to be coupled to a plurality of electrodes of an electroporation system is provided. The pulse generating circuit includes at least one voltage source, a plurality of output lines, a switching circuit coupled between the at least one voltage source and the plurality of output lines, each of the plurality of output lines configured to transmit at least one voltage pulse to a corresponding electrode of the plurality of electrodes, and a current sensing circuit configured to sense a current flowing through at least one of the plurality of output lines.

[0010] In another aspect, an electroporation system is provided. The electroporation system includes a catheter, the catheter includes a plurality of electrodes, and a pulse generating circuit coupled to the plurality of electrodes. The pulse generating circuit includes: at least one voltage source, a plurality of output lines, a switching circuit coupled between the at least one voltage source and the plurality of output lines, each of the plurality of output lines configured to transmit at least one voltage pulse to a corresponding electrode of the plurality of electrodes, and a current sensing circuit configured to sense a current flowing through at least one of the plurality of output lines.

[0011] In another aspect, a method of operating an electroporation system is provided. The method includes: providing a catheter including a plurality of electrodes; coupling the plurality of electrodes to a pulse generation circuit, the pulse generation circuit including at least one voltage source, a plurality of output lines, and a switching circuit coupled between the at least one voltage source and the plurality of output lines; using each of the plurality of output lines to transmit at least one voltage pulse to a corresponding electrode of the plurality of electrodes; and using a current sensing circuit to sense a current flowing through at least one of the plurality of output lines.

[0012] The foregoing and other aspects, features, details, utilities and advantages of the present disclosure will become apparent from reading the following description and claims and from reviewing the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 is a schematic diagram and block diagram of an electroporation therapy system.

[0014] Figure 2A and 2B It is available with Figure 1 A view of one embodiment of a catheter assembly for use with the system shown in FIG.

[0015] Figures 3A-3C It is available with Figure 1 A view of an alternative embodiment of a catheter assembly for use with the illustrated system.

[0016] Figure 4 It is available with Figure 1 A view of an alternative embodiment of a catheter assembly for use with the illustrated system.

[0017] Figure 5 is a circuit diagram of one embodiment of a pulse generating circuit that may be included in a pulse generator.

[0018] Figure 6 It is available with Figure 5 A circuit diagram of one embodiment of a current sensing circuit for use with a pulse generating circuit is shown. DETAILED DESCRIPTION

[0019] The present disclosure provides systems and methods for a pulse generation circuit. The pulse generation circuit is configured to be coupled to a plurality of electrodes of an electroporation system. The pulse generation circuit includes at least one voltage source, a plurality of output lines, a switching circuit coupled between the at least one voltage source and the plurality of output lines, each of the plurality of output lines configured to transmit at least one voltage pulse to a corresponding electrode of the plurality of electrodes, and a current sensing circuit configured to sense a current flowing through at least one of the plurality of output lines.

[0020] Figure 1 is a schematic diagram and block diagram of a system 10 for electroporation therapy. Typically, the system 10 includes a catheter electrode assembly 12, which is disposed at the distal end 48 of a catheter 14. As used herein, "proximal" refers to the direction toward the end of the catheter near the clinician, while "distal" refers to the direction away from the clinician and (usually) within the patient's body. The electrode assembly includes one or more separate, electrically isolated electrode elements. Each electrode element (also referred to herein as a catheter electrode) is individually wired so that it can be selectively paired or combined with any other electrode element to be used as a bipolar or multipolar electrode.

[0021] The system 10 can be used for irreversible electroporation (IRE) to destroy tissue. Specifically, the system 10 can be used for electroporation induction therapy, which includes delivering an electric current in a manner that directly causes an irreversible loss of the integrity of the plasma membrane (cell wall), thereby causing its rupture and cell destruction. This cell destruction mechanism can be viewed as an "outside-in" process, meaning that the destruction of the plasma membrane on the outside of the cell can have adverse effects on the inside of the cell. Typically, for classical plasma membrane electroporation, the current is delivered as a pulsed electric field between closely spaced electrodes in the form of short pulses (e.g., having a duration of 10 nanoseconds (ns) to 100 milliseconds (ms)), capable of delivering an electric field strength of approximately 0.1 to 3.0 kilovolts per centimeter (kV / cm). In some alternative embodiments, the electric field strength may be higher (e.g., greater than or equal to 3.0 kV / cm). The system 10 can be used for high output (e.g., high voltage and / or high current) electroporation procedures. In addition, the system 10 can be used with devices such as Figure 2A and 2B The annular conduit shown and / or Figures 3A-3C In some embodiments, system 10 is used for reversible electroporation instead of or in addition to irreversible electroporation.

[0022] In one embodiment, stimulation is delivered selectively (eg, between pairs of electrodes) on catheter 14. Additionally, electrodes on catheter 14 can be switched between being connected to a 3D mapping system and being connected to an electroporation generator.

[0023] Irreversible electroporation via a multi-electrode catheter allows pulmonary vein isolation with only a single shock per vein, which results in shorter procedure times compared with sequential positioning of the radiofrequency (RF) ablation tip around the veins.

[0024] It should be understood that although the power-on strategy is described as involving direct current (DC) pulses, embodiments may use variations and remain within the spirit and scope of the present disclosure. For example, exponential decay pulses, exponential increase pulses, and combinations thereof may be used. In addition, in some embodiments, alternating current (AC) pulses may also be used.

[0025] Furthermore, it should be understood that the mechanism of cell destruction in electroporation is not primarily due to heating effects, but rather to rupture of the cell membrane through the application of a high voltage electric field. Therefore, electroporation can avoid some of the heating effects that may occur when using radio frequency (RF) energy. Therefore, this "cold therapy" has desirable properties.

[0026] Given this background, let us now refer 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 into a portion of a medical device (such as a catheter 14) for performing electroporation treatment on tissue 16 in a patient's body 17. In the illustrative embodiment, the tissue 16 includes a heart or cardiac tissue. However, it should be understood that the embodiments can be used to perform electroporation treatment on various other body tissues (e.g., kidney tissue, tumors, etc.).

[0027] Figure 1 Also shown are a plurality of return electrodes, labeled 18, 20, and 21, which are schematic diagrams of body connections that can be used by various subsystems included in the overall system 10, such as an electroporation generator 26, an electrophysiology (EP) monitor (e.g., an ECG monitor 28), and a positioning and navigation system 30 for visualization, mapping, and navigation of internal body structures. In an exemplary embodiment, to perform electroporation, an electric field is applied between a pair of electrodes on the electrode assembly 12 (in a bipolar approach), as further described below. Alternatively, an electric field may be applied between an external return electrode (e.g., return electrode 18) and one or more electrodes on the electrode assembly 12 (in a monopolar approach).

[0028] 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 schematic only (for clarity), and the subsystem to which these patch electrodes are connected can and typically will include more than one patch (body surface) electrode, and may include separate patch electrodes (as described herein). In other embodiments, the return electrodes 18, 20, and 21 can be any other type of electrode suitable for use as a return electrode, including, for example, one or more catheter electrodes. The return electrode as a catheter electrode can be part of the electrode assembly 12 or part of a separate catheter or device (not shown). The system 10 can also include a main computer system 32 (including an electronic control unit 50 and a data storage memory 52), which in some embodiments can be integrated with the positioning and navigation system 30. The system 32 can also include conventional interface components, such as various user input / output mechanisms 34A and a display 34B, as well as other components.

[0029] The electroporation generator 26 is configured to energize the electrode elements according to an electroporation energization strategy, which can be predetermined or user-selectable. For electroporation treatment, the generator 26 can be configured to generate an electric current that is transmitted as a pulsed electric field via the electrode assembly 12 in the form of a short-duration DC pulse (e.g., a duration of one nanosecond to several milliseconds, or any duration suitable for electroporation), the pulsed electric field being located between closely spaced electrodes and capable of transmitting an electric field strength of about 0.1 to 3.0 kV / cm (i.e., at the tissue site). In some alternative embodiments, the electric field strength may be higher (e.g., greater than or equal to 2.0 kV / cm). The amplitude required for irreversible electroporation is inversely proportional to the pulse width. That is, as the pulse width decreases, the amplitude can generally be increased to achieve time-effectiveness.

[0030] The electroporation generator 26, sometimes also referred to as a DC energy source, is a biphasic electroporation generator 26 configured to generate a series of DC energy pulses, each of which generates current in two directions (i.e., positive pulses and negative pulses). In other embodiments, the electroporation generator is a single-phase or multi-phase electroporation generator. In some embodiments, the electroporation generator 26 is configured to output DC pulse energy at an optional energy level, such as fifty joules, one hundred joules, two hundred joules, etc. Other embodiments may have more or less energy settings, and the values ​​of the available settings may be the same or different. In order to successfully electroporate, some embodiments utilize a two hundred joule output level. For example, the electroporation generator 26 can output DC pulses with a peak amplitude from about 300 volts (V) to about 3,200V. Other embodiments may output any other suitable positive or negative voltage.

[0031] In some embodiments, variable impedance 27 allows the impedance of system 10 to be changed to limit arcing. In addition, variable impedance 27 can be used to change one or more characteristics of the output of electroporation generator 26, such as amplitude, duration, pulse shape, etc. Although shown as a separate component, variable impedance 27 can be incorporated into catheter 14 or generator 26.

[0032] Continue to refer Figure 1 As described above, catheter 14 may include electroporation functionality and, in some embodiments, additional ablation functionality (e.g., RF ablation). However, it should be understood that in those embodiments, the type of ablation energy provided may be different (e.g., cryoablation, ultrasound, etc.).

[0033] In the illustrative embodiment, the 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. The catheter 14 may also include other conventional components not shown herein, such as a temperature sensor, additional electrodes, and corresponding conductors or wires. The connector 40 provides a mechanical and electrical connection for a cable 56 extending from the generator 26. The connector 40 may include conventional components known in the art and, as shown, is disposed at the proximal end of the catheter 14.

[0034] The handle 42 provides a position for the clinician to hold the catheter 14, and may also provide a device for manipulating or guiding the shaft 44 in the body 17. For example, the handle 42 may include a device for changing the length of the wire extending through the catheter 14 to the distal end 48 of the shaft 44 or a device for manipulating the shaft 44. In addition, in some embodiments, the handle 42 may be configured to change the shape, size and / or direction of a portion of the catheter, and it should be understood that the configuration of the handle 42 may vary. In an alternative embodiment, the catheter 14 may be driven or controlled by a robot. Therefore, instead of the clinician manipulating the handle to advance / retract and / or manipulate or guide the catheter 14 (particularly its shaft 44), the robot is used to manipulate the catheter 14. The shaft 44 is an elongated tubular flexible member configured to move in the body 17. The shaft 44 is configured to support the electrode assembly 12 and contain associated conductors, and may be used for additional electronic devices for signal processing or conditioning. The shaft 44 may also allow for the transportation, delivery and / or removal of fluids (including flushing fluids and body fluids), drugs, biological agents and / or surgical tools or instruments. The shaft 44 can be made of conventional materials, such as polyurethane, and define one or more lumens configured to accommodate and / or transport electrical conductors, fluids, or surgical tools, as described herein. The shaft 44 can be introduced into a blood vessel or other structure within the body 17 via a conventional introducer. The shaft 44 can then be advanced / retracted and / or manipulated or guided through the body 17 to a desired location, such as the location of the tissue 16, including by using a guide wire or other means known in the art.

[0035] The positioning and navigation system 30 can be used to visualize, map, and navigate internal body structures. The positioning and navigation system 30 can include conventional equipment known in the art. For example, the positioning and navigation system 30 can be substantially similar to the EnSite Precision™ system, which is commercially available from Abbott Laboratories and as generally shown in the commonly assigned U.S. Patent 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 positioning and navigation system 30 can be substantially similar to the EnSite X™ mapping system, as generally shown in U.S. Patent Application Publication 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 positioning and navigation system 30 is merely an example and is not limiting in nature. Other technologies for positioning / navigating a catheter in space (and for visualization) are known, including, for example, the CARTO navigation and positioning system from Biosense Webster, the Rhythmia® system from Boston Scientific Scimed, the KODEX® system from Koninklijke Philips NV, the AURORA® system from Northern Digital Inc., or commonly available fluoroscopy systems.

[0036] In this regard, some positioning, navigation and / or visualization systems may include a sensor for generating a signal indicative of catheter position information, and may include, for example, one or more electrodes of an impedance-based positioning system, or, for example, one or more coils (i.e., windings) of a magnetic field-based positioning system, configured to detect one or more characteristics of a magnetic field. As another example, the system 10 may utilize a combination of electric field-based and magnetic field-based systems, as generally illustrated by reference to U.S. Patent No. 7,536,218, entitled “Hybrid Magnetic-Based and Impedance Based Position Sensing,” the disclosure of which is incorporated herein by reference in its entirety.

[0037] Pulsed field ablation (PFA) is a method of achieving irreversible electroporation that can be implemented using the systems and methods described herein. In some cases, PFA can be used at specific cardiac tissue sites (such as the pulmonary veins) to perform pulmonary vein isolation (PVI). In an example embodiment, an electric field is applied between adjacent electrodes (in a bipolar approach). Alternatively, an electric field can be applied between one or more electrodes and a return patch (in a monopolar approach). Each of these methods has advantages and disadvantages.

[0038] With respect to lesion size and proximity, a monopolar approach has a wider reach and may create deeper lesions with the same applied voltage. In addition, a monopolar approach may be able to create lesions from a distance (e.g., usually close to, but not necessarily in contact with, tissue). A bipolar approach can create smaller lesions and requires closer proximity or contact with tissue to create transmural lesions. However, a monopolar approach may create a larger lesion than necessary, and lesions created using a bipolar approach may be more localized.

[0039] Due to the wide range of action, the monopolar approach may result in unwanted skeletal muscle and / or nerve activation. In contrast, the bipolar approach has a limited range of action, proportional to the electrode spacing on the lead, and is less likely to depolarize cardiomyocytes or nerve fibers.

[0040] To monitor the operation of the system 10, one or more impedances may be measured between the catheter electrode 144 and / or the return electrodes 18, 20, and 21. For example, for the system 10, the impedance may be measured as described in U.S. Patent Application Publication No. 2019 / 0117113, filed on October 23, 2018, U.S. Patent Application Publication No. 2019 / 0183378, filed on December 19, 2018, and International Patent Application Publication No. WO2021 / 236341, filed on May 6, 2021, all of which are incorporated herein by reference in their entirety.

[0041] Figure 2A and 2B 1 is a view of one embodiment of a catheter assembly 146 that can be used with the catheter 14 in the system 10. The catheter assembly 146 can be referred to as a ring catheter. Those skilled in the art will appreciate that in other embodiments, any suitable catheter can be used. Specifically, Figure 2A is a side view of a catheter assembly 146 having a variable diameter ring 150 at the distal end 142 thereof. Figure 2B 1 is an end view of the variable diameter ring 150 of the catheter assembly 146. Those skilled in the art will appreciate that the methods and systems described herein may be implemented using any suitable catheter (e.g., a fixed ring catheter, a linear catheter, a basket catheter, etc.). Figure 2A and 2B As shown, the variable diameter ring 150 is coupled to the distal portion 151 of the shaft 44 .

[0042] The variable diameter ring 150 can be selectively adjusted to an expanded (also referred to as "opened") diameter 160 (eg, Figure 2A 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 can vary between any suitable open and closed diameters 160.

[0043] In the illustrated embodiment, the variable diameter ring 150 includes fourteen catheter electrodes 144 that are substantially evenly spaced around the circumference of the variable diameter ring 150 in the expanded configuration. In the collapsed configuration, one or more electrodes 144 may overlap. In other embodiments, other arrangements of catheter electrodes 144 may be implemented. For example, in one embodiment, the variable diameter ring 150 includes twelve catheter electrodes 144.

[0044] The catheter electrodes 144 are platinum ring electrodes configured to conduct and / or discharge current in the range of one kilovolts and / or ten amperes. In other embodiments, the variable diameter ring 150 may include any suitable number of catheter electrodes 144 made of any suitable material. The catheter electrodes 144 may include any catheter electrode suitable for conducting high voltages and / or high currents (e.g., in the range of one kilovolts and / or ten amperes). Each catheter electrode 144 is separated from each other by an insulating gap 152. In the exemplary embodiment, each catheter electrode 144 has the same length 164 (e.g., Figure 2B164 ), and each insulating gap 152 has the same length 166 as each other gap 152. In the example embodiment, the length 164 and the length 166 are both about 2.5 millimeters. In other embodiments, the length 164 and the length 166 may be different from each other. In addition, in some embodiments, the catheter electrodes 144 may not all have the same length 164 and / or the insulating gaps 152 may not all have the same length 166. In some embodiments, the catheter electrodes 144 are not evenly distributed around the circumference of the variable diameter ring 150.

[0045] The diameter 160 and catheter electrode 144 spacing can be designed to provide a targeted range of energy densities to the tissue, as well as to provide adequate electroporation coverage for different human anatomical geometries. Generally, a sufficient number of electrodes 144 of appropriate length 164 are required to provide substantially uniform and continuous coverage around the circumference of the variable diameter ring 150, while still allowing sufficient flexibility to allow the variable diameter ring 150 to expand and contract to change the diameter 160 to the desired extremes.

[0046] As described above, the length 164 of the catheter electrode 144 can vary. Increasing the length 164 of the catheter electrode 144 can increase the coverage of the electrode 144 around the circumference of the variable diameter ring 150 while also reducing the current density on the electrode 144 (by increasing the surface area), which can help prevent arcing during the electroporation operation. However, increasing the length 164 too much may prevent the variable diameter ring 150 from forming a smooth circular shape and may limit the closed diameter 160 of the variable diameter ring 150. In addition, too large a length 164 may increase the surface area of ​​the catheter electrode 144 to the point where the current density applied to the catheter electrode 144 by the power supply is less than the minimum current density required for successful treatment. Conversely, reducing the length 164 reduces the surface area, thereby increasing the current density on the catheter electrode 144 (assuming no other system changes). As described above, greater current density may result in an increased risk of arcing during electroporation and may result in the need to add greater additional system resistance to prevent arcing. In addition, in order to obtain the desired uniform coverage around the circumference of the variable diameter ring 150, more catheter electrodes 144 may be required if the length 164 is reduced. Increasing the number of catheter electrodes 144 on the variable diameter ring 150 may prevent the variable diameter ring 150 from being able to collapse to the desired minimum diameter 160 .

[0047] Figure 3Ais a perspective view of an alternative catheter assembly 200 that can be used with catheter 14. The catheter assembly 200 can be referred to as a basket catheter. The catheter assembly 200 includes a shaft 202 and a plurality of splines 204 surrounding a 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 can be selectively inflated to fill the spaces between the splines 204. Notably, the balloon 208 acts as an insulator and generally reduces energy loss, which can result in increased lesion size.

[0048] Each spline 204 includes a proximal end 210 coupled to the shaft 202 and a distal end 212 coupled to the shaft 202. From the proximal end 210 to the distal end 212, the spline 204 has an arc shape extending radially outward.

[0049] In this embodiment, each spline 204 includes one or more individual electrodes 220. For example, each spline 204 can include an elastic material (e.g., Nitinol) covered in a polymer tube 222, with the individual electrodes 220 attached to the outside of the polymer tube 222. In the illustrated embodiment, each spline 204 includes two electrodes 220. In addition, as shown in FIG. 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 will contact the pulmonary vein.

[0050] Alternatively, each spline 204 can include any suitable number and arrangement of electrodes 220. For example, in some embodiments, each spline 204 includes four electrodes 220.

[0051] In this embodiment, alternating splines 204 alternate polarity. That is, the electrodes 220 on a particular spline 204 have the same polarity, but the electrodes 220 on a particular spline 204 have a different polarity than the electrodes 220 on an adjacent spline 204. Alternatively, any suitable polarization scheme may be used. During delivery, the splines 204 may be folded toward the axis 202. Subsequently, to perform ablation, the splines 204 are unfolded to extend radially outward.

[0052] The splines 204 can all have the same length, or at least some of the splines 204 can have different lengths. Additionally, the insulating material on each spline 204 can have the same length, or at least some of the splines 204 can have insulating material of different lengths. Additionally, in some embodiments, the catheter assembly 200 includes a distal electrode (not shown) located at the distal end of the splines 204. The distal electrode can be used to perform point ablation (e.g., by creating a bipolar between the distal electrode and one of the splines 204), and / or can be used for visualization / mapping purposes (e.g., using the distal electrode in conjunction with an electrode on the shaft 202).

[0053] Figure 3B is a perspective view of an alternative catheter assembly 250 that may be used with catheter 14, Figure 3C 2 is a side view of the catheter assembly 250. Figure 3A As shown in FIG. 2 , catheter assembly 250 may be referred to as a basket assembly.

[0054] The catheter assembly 250 includes a shaft 252 and a plurality of splines 254 surrounding a 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 can be selectively inflated to occupy the spaces between the splines 254. Notably, the balloon 258 acts as an insulator and generally reduces energy, which can result in an increase in lesion size.

[0055] Each spline 254 includes a proximal end 260 coupled to the shaft 252 and a distal end 262 coupled to the shaft 252. From the proximal end 260, the splines 1004 extend radially outward to an inflection point 264 and then extend radially inward to the distal end 262. Figure 3C Catheter assembly 250 is shown positioned within pulmonary vein 266.

[0056] The body of each spline 254 is made of an elastic material (e.g., Nitinol) and acts as a relatively large electrode. In this embodiment, the alternating splines 254 alternate polarity. That is, each positive spline 254 is located between two negative splines 254, and vice versa. Alternatively, any suitable polarization scheme may be used.

[0057] To control the ablation area of ​​each spline 254, a portion of each spline 254 can be covered with an insulating material 270 (e.g., heat shrink tubing or polymer tubing or spray or dip coating with polyimide or PEBAX), and the exposed portion of the spline 254 used as an electrode. Figure 3B and 3C In the illustrated embodiment, the inflection point 264 and the portion of the spline 254 between the inflection point 264 and the distal end 262 are generally exposed, while the portion of the spline 254 between the inflection point 264 and the proximal end 260 is generally insulated. This results in the portion of the spline 254 that contacts the pulmonary vein 266 being exposed (see Figure 3C ). Alternatively, any suitable insulation arrangement may be used.

[0058] During delivery, the splines 254 and balloon 258 can be collapsed. To perform ablation, the splines 254 are unfolded, the inflection points 264 extend radially outward, and the balloon 258 is selectively inflated to occupy the space between the splines 254.

[0059] The combination of the balloon 258 and the splines 254 facilitates straightforward delivery and deployment of the catheter assembly 250. In addition, the balloon 258 drives more energy into the ablated tissue and stabilizes the splines 254 to prevent lateral movement. In addition, using the splines 254 as electrodes rather than separate smaller electrodes can help reduce costs and improve the reliability of the catheter assembly 250.

[0060] The splines 254 can all have the same length, or at least some of the splines 254 can have different lengths. In addition, the insulating material 270 on each spline 254 can have the same length, or at least some of the splines 254 can have different lengths of insulating material 270. In addition, in some embodiments, the catheter assembly 250 includes a distal electrode (not shown) located at the distal end of the splines 254. The distal electrode can be used to perform point ablation (e.g., by creating a bipolar between the distal electrode and one of the splines 254), and / or can be used for visualization / mapping purposes (e.g., using the distal electrode in conjunction with an electrode on the shaft 252).

[0061] Figure 4 FIG. 2 is a side view of an alternative catheter assembly 280 that may be used with catheter 14. Catheter assembly 280 may be referred to as a mesh assembly. Figure 4 As shown, the catheter assembly 280 is coupled to a distal end portion 282 of a shaft, such as the shaft 44 (eg, Figure 1 as shown).

[0062] The catheter assembly 280 includes a plurality of splines 284 extending from a proximal end 286 to a distal end 288. Each spline 284 includes a plurality of electrodes 290. Figure 4 In the illustrated embodiment, the catheter assembly 280 includes four splines 284, and each spline 284 includes four electrodes 290, so that the electrodes 290 form a grid configuration. Therefore, the catheter assembly 280 provides a four-by-four grid of electrodes 290. In one embodiment, the spacing between each pair of adjacent electrodes 290 is about 4 millimeters (mm), so that the size of the electrode 290 grid is about 12mm×12mm. Alternatively, the catheter assembly 280 can 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 about 2 millimeters (mm). In addition, in some embodiments, the catheter assembly 280 can include, for example, 56 electrodes arranged in a 7×8 grid.

[0063] Using catheter assembly 280, lesions may be created at a single electrode 290 using a monopolar approach (e.g., by applying a voltage between a single electrode 290 and a return patch), or between pairs of electrodes 290 using a bipolar approach. Lesions may be created within the anatomy by selectively energizing the electrodes in a particular configuration and / or pattern (e.g., including independently energizing a single electrode 290, or energizing multiple electrodes 290 simultaneously).

[0064] Those skilled in the art will appreciate that the catheter assembly 146 (eg Figure 2A and 2B As shown), catheter assembly 200 (as Figure 3A As shown), catheter assembly 250 (as Figure 3B and 3C ) and catheter assembly 280 (as shown Figure 4 ) are merely examples. It is noteworthy that the systems and methods described herein can be implemented using any suitable catheter assembly.

[0065] For electroporation therapy, a pulse generator (e.g., electroporation generator 26 (e.g., Figure 1 A waveform is generated by a catheter electrode pair (i.e., a bipolar approach) and applied between a catheter electrode pair (i.e., a bipolar approach) or between a single catheter electrode and a return patch (i.e., a monopolar approach). The waveform may be monophasic, biphasic (i.e., having positive and negative pulses), or polyphasic. Furthermore, the waveform may include one or more pulse trains (each pulse train including multiple pulses). Furthermore, the waveform is defined by multiple parameters (e.g., pulse width, pulse amplitude, frequency, etc.).

[0066] To generate different waveforms, the pulse generator selectively connects different electrodes to different voltage levels. In at least some known systems, a first subset of electrodes may be selectively connected to a first voltage level (e.g., a positive voltage) and a second subset of electrodes may be selectively connected to a second voltage level (e.g., a negative voltage).

[0067] In at least some known systems, the output current from the pulse generator to one or more electrodes is not monitored. Instead, the upstream capacitor voltage is measured, but no downstream current monitoring is performed after those capacitors are discharged through the switching circuit coupled between the capacitors and the electrodes. As a result, faults downstream of the capacitors may be difficult or impossible to detect and remedy.

[0068] The systems and methods described herein can detect the output current from the pulse generator using a current sensing circuit. The current sensing circuit can be implemented using a relatively small, inexpensive transformer. In addition, the current sensing circuit can detect faults and measure the current and other parameters at the output of the pulse generator.

[0069] Figure 5is a circuit diagram of one embodiment of a pulse generating circuit 400 that may be included in a pulse generator, such as an electroporation generator 26 (eg, Figure 1 The pulse generation circuit 400 may be coupled to a plurality of electrodes 408 (labeled 1, 2, 3 ... (N-1), N), such as a catheter electrode assembly 12 (eg Figure 1 electrodes on the surface of the substrate.

[0070] The pulse generating 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 can be, for example, high voltage direct current (DC) voltage sources. The first voltage source 402 and the second voltage source 404 can have any suitable voltage level. For example, in one embodiment, the first voltage source 402 can have a voltage level of 1400V, and the second voltage source 404 can have a voltage level of 1800V.

[0071] 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, one skilled in the art will appreciate 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 being associated with four electrodes 408, thereby forming a circuit for a total of sixteen electrodes 408.

[0072] like Figure 5 As shown, within the module 406, an electrode addressing circuit 410 is coupled to each electrode 408. The electrode addressing circuit 410 is an example of a switching circuit that can be used to selectively couple the electrode 408 to the first voltage source 402 and the second voltage source 404. The electrode addressing circuit 410 enables 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 the electrode 408 and the first voltage source 402, a second switch 414 coupled between the electrode 408 and the second voltage source 404, and a third switch 416 coupled between the electrode 408 and the return voltage 418. Using the switches 412, 414, and 416, the electrode 408 can be selectively connected to one of the first voltage source 402, the second voltage source 404, and the return voltage 418 as needed. The operation of the switches 412, 414, and 416 can be controlled using any suitable controller device (not shown).

[0073] Switches 412, 414, and 416 may be any suitable switching devices. 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 a silicon carbide depletion mode JFET combined with a silicon MOSFET).

[0074] Thus, each electrode 408 can be selectively connected to the first voltage source 402, the second voltage source 404, or the return voltage 418 without being affected by the other electrodes 408. This allows for great flexibility in selecting a treatment regimen, allowing various electrode combinations to generate pulses at different voltage levels and / or different pulse widths.

[0075] Furthermore, by controlling the time interval between each phase, charge can be delivered bidirectionally, while energy is delivered unidirectionally. This helps achieve desired electrophysical effects (e.g., selective irreversible electroporation of tissues) while minimizing undesirable effects (e.g., involuntary recruitment of skeletal muscle).

[0076] exist Figure 5 In the illustrated embodiment, the electrode addressing circuit 410 includes a plurality of current limiting resistors 430. For example, one current limiting resistor 430 may be coupled between the first switch 412 and the first voltage source 402, another current limiting resistor 430 may be coupled between the second switch 414 and the second voltage source 404, and another current limiting resistor 430 may be coupled between the third switch 416 and the electrode 408. The current limiting resistors 430 also serve to provide fault protection.

[0077] Additionally, in some embodiments, the pulse generation circuit 400 may include a plurality of isolation switches (not shown). Each isolation switch is coupled in series between the electrode addressing circuit 410 and the associated electrode 408, and is an electromechanical switch capable of completely disconnecting the electrode 408 from the first voltage source 402 and the second voltage source 404 (e.g., without allowing any leakage current to flow to the electrode 408). Thus, the isolation switch provides protection for the patient by preventing any current from reaching the electrode 408 when the isolation switch is open.

[0078] like Figure 5 As shown, output lines 450 extend between each electrode addressing circuit 410 and the associated electrode 408. In addition, current through each output line 450 is sensed using current sensing circuit 452. Resistors 460 downstream of electrodes 408 represent the resistance in the patient's tissue.

[0079] Figure 64 is a circuit diagram of one embodiment of a current sensing circuit 452 that can be used to sense current through an output line 450. In the illustrated embodiment, the current sensing circuit 452 includes a current transformer 502 coupled to the output line 450. The current sensing circuit 452 also includes a signal processing circuit 504 and a rectifier 506 coupled between the signal processing circuit 504 and the current transformer 502. The rectifier 506 includes a plurality of diodes 510, and a resistor 512 is coupled in parallel with the rectifier 506. Those skilled in the art will appreciate that the signal processing circuit 504 can be implemented using any suitable digital or analog circuit. In addition, those skilled in the art will appreciate that the current sensing circuit 452 can also be implemented using other circuit architectures and components instead.

[0080] In this embodiment, the current transformer 502 is a relatively small, relatively inexpensive transformer. For example, the current transformer 502 may be approximately 10 millimeters (mm)×17 mm×20 mm in size. When current flows through the output line 450, an isolated signal proportional to the current in the output line 450 is generated by the current transformer 502. Therefore, detecting the current flowing through the current transformer 502 (e.g., using the signal processing circuit 504) can confirm that the current is flowing through the output line 450 (i.e., flowing to the corresponding electrode 408) and calculate the magnitude of the current.

[0081] In one example, the current sensing circuit 452 operates as follows. The rectifier 506 rectifies the signal passing through the current transformer 502. The rectified signal is then compared to a threshold (using the signal processing circuit 504). Based on the comparison, the signal processing circuit 504 determines whether a fault has occurred in the pulse generating circuit.

[0082] For example, if current should flow through output line 450 (i.e., during pulse delivery to electrode 408), but the rectified signal is below the threshold, signal processing circuit 504 determines that a fault has occurred (because during pulse delivery, the rectified signal should be equal to or above the threshold). As another example, if current should not flow through output line 450 (i.e., when pulses should not be delivered to electrode 408), but the rectified signal is equal to or above the threshold, signal processing circuit 504 determines that a fault has occurred (because the rectified signal should be below the threshold in the absence of an expected pulse delivery).

[0083] The signal through the current transformer 502 can also be used to determine parameters other than the current through the output line 450. For example, the signal can be integrated (or measured in the analog or digital domain) to determine an estimate of the total charge delivered to the electrode 408 over a period of time (e.g., over the pulse length), and the total estimated charge can be compared to the total expected charge. In another example, a detailed capture of each pulse delivered to the electrode 408 can be recorded for further analysis. In another example, the signal can be used to measure tissue impedance and the energy delivered for each pulse delivered to the electrode 408.

[0084] The current sensing circuit 452 is also capable of detecting faults in the pulse generating circuit 400. For example, if the pulse generating circuit 400 is controlled to transmit a pulse to the electrode 408, but no signal is detected by the current transformer 502, the signal processing circuit may determine that a fault has occurred and may take appropriate action (e.g., generating an alarm to notify a user, terminating the operation of the pulse generating circuit 400).

[0085] Furthermore, in some embodiments, the current sensing circuit 452 can be used to perform closed-loop control of the pulse generation circuit 400. For example, if the current sensing circuit 452 determines that the current through the output line 450 exceeds a predetermined threshold, the system can reduce the voltage and / or pulse length of subsequent pulses. Alternatively, if the current sensing circuit 452 determines that the current through the output line 450 is below a predetermined threshold, the system can increase the voltage and / or pulse length of subsequent pulses.

[0086] As another example of closed-loop control, using current sensing circuit 452, the actual current transmitted through output line 450 can be estimated. Therefore, the active load impedance can be estimated more accurately. Based on the estimated active load impedance, the timing and / or voltage of the pulses generated by pulse generation circuit 400 can be increased or decreased as appropriate.

[0087] In one embodiment, the current sensing circuit 452 can be used to measure at least one of the peak current and the total charge delivered by each positive pulse and each negative pulse. Based on this data, at least one of the timing and voltage of subsequent pulses can be adjusted. Typically, the timing of subsequent pulses can be adjusted relatively quickly. However, the voltage of subsequent pulses is typically adjusted at a slower rate.

[0088] Specifically, pulse timing can be varied on a pulse-by-pulse basis. For example, measured tissue impedance (e.g., determined using data collected by current sensing circuit 452) can be correlated to lesion depth or lesion formation progression. Sufficient changes in impedance can indicate that a lesion has reached a target size, and in response, the pulse width of subsequent pulses can be reduced, or subsequent pulses can be terminated entirely.

[0089] In contrast, for voltage modification, the voltage on the capacitor that is discharged to produce the pulse may only change relatively slowly. For example, if it is determined based on data collected by the current sensing circuit 452 that the voltage should increase, the voltage may only increase relatively slowly (the rate of change being determined by the available current divided by the capacitance).

[0090] For example, a 30 milliamp (mA) current source charges an 87 microfarad (µF) capacitor at a rate of 0.345 volts / millisecond (V / ms). Similarly, a 60mA current source charges an 87µF capacitor at a rate of 0.345V / ms. Therefore, for a 30mA current source, it takes about 816 milliseconds to increase the voltage by 200V, while for a 60mA current source, it takes about 408 milliseconds.

[0091] Other closed loop techniques may also be implemented. For example, in one embodiment, current sensing circuit 452 measures current to determine accumulated charge, and in response, adjusts pulse timing (eg, pulse by pulse) to maintain charge balance.

[0092] The current sensing circuit 452 may also be used to supplement or replace upstream current sensing functions (e.g., upstream of the switching circuit). For example, at least some known pulse switching circuits monitor internal currents (proportional to or identical to the current of interest) for only a portion of the operating cycle and / or only a portion of the complete path of the current of interest for simplicity reasons. This results in current sampling of the current of interest rather than continuous monitoring of the current of interest.

[0093] As an example, at least some known systems may monitor only the voltage drop or current across a resistor in a first switch, while the complete path to the catheter also includes a second (upstream or downstream) switch and resistor. This monitoring scheme may be sufficient for normal operation of the circuit. However, a fault in the circuit (e.g., a faulty device and / or connection) may cause a short circuit, effectively changing the topology of the circuit, making the voltage / current monitoring inaccurate.

[0094] For example, assume that the system includes current sampling of a first switch upstream, but does not include current sampling of a second switch downstream. If the second switch fails (e.g., due to a conduit failure), the current sampling will not detect the failure. Instead, the current sensing circuit 452 (as described herein) located downstream of the switch circuit will be able to detect the failure.

[0095] Those skilled in the art will appreciate that modifications may be made to the pulse generation circuit 400. For example, in some embodiments, one or more high voltage differential amplifiers (not shown) may be added to the pulse generation circuit 400 to measure the high voltage outputs of the first voltage source 402 and the second voltage source 404. This enables a parity check to be performed between the voltage outputs of the voltage sources 402 and 404 (measured using the high voltage differential amplifier) ​​and the current output through the output line 450 (measured using the current sensing circuit 452).

[0096] In another embodiment, the test output line (not shown) can extend between the switch circuit and the test load (rather than between the switch circuit and the catheter). Then, similar to the current sensing circuit 452, a current transformer can be used to monitor the current flowing to the test load. This will enable initially delivering pulses to the test load and monitoring the current to ensure that the pulse generation circuit 400 is operating properly, and then switching to delivering pulses to the catheter once the pulse generation circuit is verified to be operating properly.

[0097] The systems and methods described herein are directed to a pulse generating circuit. The pulse generating circuit is configured to be coupled to a plurality of electrodes of an electroporation system. The pulse generating circuit includes at least one voltage source, a plurality of output lines, a switching circuit coupled between the at least one voltage source and the plurality of output lines, each of the plurality of output lines being configured to transmit at least one voltage pulse to a corresponding electrode of the plurality of electrodes, and a current sensing circuit configured to sense a current flowing through at least one of the plurality of output lines.

[0098] Although certain embodiments of the present disclosure have been described above in some detail, those skilled in the art may make many modifications to the disclosed embodiments without departing from the spirit or scope of the present disclosure. All directional references (e.g., up, down, upward, downward, left, right, leftward, rightward, top, bottom, above, below, vertical, horizontal, clockwise and counterclockwise) are used only for identification purposes to help readers understand the present disclosure and will not cause limitations, particularly for the position, direction or use of the present disclosure. Connection references (e.g., attachment, coupling, connection, etc.) should be interpreted broadly and may include intermediate members between element connections and relative movement between elements. Therefore, a connection reference does not necessarily mean that two elements are directly connected and fixed to each other. It is intended that all contents contained in the above description or shown in the accompanying drawings should be interpreted only as illustrative and not restrictive. Changes may be made to details or structures without departing from the spirit of the present disclosure as defined by the appended claims.

[0099] When introducing elements of the present disclosure or the preferred embodiments thereof, the articles "a," "an," "the," and "said" are intended to mean that there are one or more of the elements. The terms "comprising," "including," and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.

[0100] As various changes could be made in the above construction without departing from the scope of the disclosure, it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

Claims

1. A pulse generating circuit configured to be coupled to a plurality of electrodes of an electroporation system, the pulse generating circuit comprising: at least one voltage source; Multiple output lines; a switching circuit coupled between the at least one voltage source and the plurality of output lines, each of the plurality of output lines being configured to transmit at least one voltage pulse to a corresponding electrode of the plurality of electrodes; as well as A current sensing circuit is configured to sense a current flowing through at least one of the plurality of output lines.

2. The pulse generating circuit according to claim 1, wherein the current sensing circuit comprises: a current transformer coupled to the at least one output line; as well as A signal processing circuit is coupled to the current transformer. 3 . The pulse generating circuit according to claim 2 , wherein the current sensing circuit further comprises a rectifier coupled between the current transformer and the signal processing circuit.

4. The pulse generating circuit according to claim 3, wherein the transformer is configured to generate a signal in response to the current flowing through the at least one output line, wherein the rectifier is configured to rectify the generated signal, and wherein the signal processing circuit is configured to compare the rectified signal with a threshold value. 5 . The pulse generation circuit of claim 1 , wherein the current sensing circuit is configured to adjust a parameter of a subsequent voltage pulse based on the sensed current. 6 . The pulse generation circuit of claim 1 , wherein the current sensing circuit is configured to estimate a total charge delivered to at least one electrode of the plurality of electrodes based on a sensed current. 7 . The pulse generating circuit of claim 1 , wherein the current sensing circuit is configured to detect a fault in the pulse generating circuit based on a sensed current.

8. An electroporation system comprising: a catheter comprising a plurality of electrodes; as well as A pulse generating circuit is coupled to the plurality of electrodes, the pulse generating circuit comprising: at least one voltage source; Multiple output lines; a switching circuit coupled between the at least one voltage source and the plurality of output lines, each of the plurality of output lines being configured to transmit at least one voltage pulse to a corresponding electrode of the plurality of electrodes; and A current sensing circuit is configured to sense a current flowing through at least one of the plurality of output lines.

9. The electroporation system of claim 8, wherein the current sensing circuit comprises: a current transformer coupled to the at least one output line; as well as A signal processing circuit is coupled to the current transformer.

10. The electroporation system of claim 9, wherein the current sensing circuit further comprises a rectifier coupled between the current transformer and the signal processing circuit.

11. The electroporation system of claim 10, wherein the transformer is configured to generate a signal in response to current flowing through the at least one output line, wherein the rectifier is configured to rectify the generated signal, and wherein the signal processing circuit is configured to compare the rectified signal with a threshold value.

12. The electroporation system of claim 8, wherein the current sensing circuit is configured to adjust a parameter of a subsequent voltage pulse based on the sensed current.

13. The electroporation system of claim 8, wherein the current sensing circuit is configured to estimate a total charge delivered to at least one electrode of the plurality of electrodes based on the sensed current.

14. The electroporation system of claim 8, wherein the current sensing circuit is configured to detect a fault in the pulse generation circuit based on the sensed current.

15. A method of operating an electroporation system, the method comprising: providing a catheter including a plurality of electrodes; coupling the plurality of electrodes to a pulse generating circuit, the pulse generating circuit comprising at least one voltage source, a plurality of output lines, and a switching circuit coupled between the at least one voltage source and the plurality of output lines; delivering at least one voltage pulse to a corresponding electrode of the plurality of electrodes using each of the plurality of output lines; as well as A current flowing through at least one of the plurality of output lines is sensed using a current sensing circuit.

16. The method of claim 15, wherein the current sensing circuit comprises a current transformer coupled to the at least one output line, a signal processing circuit coupled to the current transformer, and a rectifier coupled between the current transformer and the signal processing circuit.

17. The method according to claim 16, further comprising: using the transformer to generate a signal in response to current flowing through the at least one output line; rectifying the generated signal using the rectifier; as well as The rectified signal is compared to a threshold value using the signal processing circuit.

18. The method of claim 15, further comprising adjusting parameters of subsequent voltage pulses based on the sensed current.

19. The method of claim 15, further comprising estimating a total charge delivered to at least one electrode of the plurality of electrodes based on the sensed current.

20. The method of claim 15, further comprising detecting a fault in the pulse generating circuit based on a sensed current.

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