Systems and methods for monitoring pulsed field ablation generator output - Patents.com

Abstract

A pulse generation circuit configured to be connected to a plurality of electrodes of an electroporation system is described, the pulse generation circuit including at least one voltage source, a plurality of output lines, a switching circuit connected between the at least one voltage source and the plurality of output lines, each of the plurality of output lines configured to send at least one voltage pulse to a corresponding electrode of the plurality of electrodes, and a current sensing circuit configured to sense a current through at least one of the plurality of output lines.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to Provisional Application No. 63 / 416,680, filed October 17, 2022, which is incorporated herein by reference in its entirety.

[0002] The present disclosure relates generally to tissue ablation systems, and more particularly to electroporation systems that include circuitry for monitoring output from a pulse generator. [Background technology]

[0003] It is generally known that ablation therapy can be used to treat various diseases that harm human anatomical structures. For example, ablation therapy is used to treat atrial arrhythmia. When tissue is ablated, or at least exposed to ablation energy generated by an ablation generator and delivered by an ablation catheter, lesions are formed in the tissue. To correct diseases such as atrial arrhythmias (including, but not limited to, ectopic atrial tachycardia, atrial fibrillation, atrial flutter, etc.), tissue destruction is caused in cardiac tissue using electrodes attached on or within the ablation catheter.

[0004] Cardiac arrhythmias (i.e., irregular heart rhythms) can cause a variety of dangerous conditions, including loss of atrioventricular contractile synchronization and blood flow stagnation, leading to various illnesses and even death. The primary cause of atrial arrhythmias is thought to be stray electrical signals within the left or right atrium of the heart. Ablation catheters deliver ablation energy (e.g., radiofrequency energy, cryoablation, laser, chemical, high-intensity focused ultrasound, etc.) to cardiac tissue, creating lesions in the tissue. This lesion disrupts unwanted electrical pathways, thereby limiting or preventing the stray electrical signals that lead to arrhythmias.

[0005] Electroporation is a non-thermal ablation technique that involves applying a strong electric field that creates pores in cell membranes. For example, an electric field can be induced by applying relatively short pulses, ranging from nanoseconds to milliseconds in duration. Such pulses can be repeated to form a pulse train. When such an electric field is applied to tissue in vivo, cells within the tissue experience a membrane potential, causing pores to open in the cell wall. Electroporation can be reversible (i.e., the temporarily opened pores reclose) or irreversible (i.e., the pores remain open). For example, in the field of gene therapy, reversible electroporation (i.e., temporary pore opening) is used to introduce high-molecular-weight therapeutic vectors into cells. In other therapeutic applications, only appropriately configured pulse trains can be used to cause irreversible electroporation, for example, resulting in cell destruction.

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

[0007] In at least some known systems, the output current from the pulse generator to one or more electrodes is not monitored. Instead, upstream capacitor voltages may be measured, but downstream current is not monitored after the capacitors are discharged via switching circuits connected between the capacitors and the electrodes. Therefore, it may be difficult or impossible to detect and repair faults downstream of the capacitors. Therefore, a pulse generation circuit that allows for monitoring of the output current from the pulse generator is desired. Summary of the Invention [Means for solving the problem]

[0008] In one aspect, a pulse generation circuit configured to be connected to a plurality of electrodes of an electroporation system is provided, the pulse generation circuit comprising: at least one voltage source, a plurality of output lines, a switching circuit connected between the at least one voltage source and the plurality of output lines, each of the plurality of output lines configured to send at least one voltage pulse to a corresponding electrode of the plurality of electrodes, and a current sensing circuit configured to sense a current through at least one of the plurality of output lines.

[0009] In another aspect, an electroporation system is provided, comprising: a catheter including a plurality of electrodes; and a pulse generation circuit connected to the plurality of electrodes. The pulse generation circuit comprises at least one voltage source, a plurality of output lines, a switching circuit connected between the at least one voltage source and the plurality of output lines, each of the plurality of output lines configured to send 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 yet another aspect, a method of operating an electroporation system is provided, the method including: providing a catheter including a plurality of electrodes; connecting 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 connected between the at least one voltage source and the plurality of output lines; sending at least one voltage pulse to a corresponding electrode of the plurality of electrodes using each of the plurality of output lines; and sensing a current through at least one of the plurality of output lines using a current sensing circuit.

[0011] The foregoing and other aspects, features, details, utilities, and advantages of the present disclosure will become apparent from a reading of the following description and claims, and a review of the accompanying drawings. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 is a schematic block diagram of an electroporation treatment system.

[0013] [Figure 2A] FIG. 2 is a diagram of one embodiment of a catheter assembly that can be used with the system shown in FIG. 1. [Figure 2B] FIG. 2 is a diagram of one embodiment of a catheter assembly that can be used with the system shown in FIG. 1.

[0014] [Figure 3A] 2 is a diagram of another embodiment of a catheter assembly that can be used with the system shown in FIG. 1. [Figure 3B] 2 is a diagram of another embodiment of a catheter assembly that can be used with the system shown in FIG. 1. [Figure 3C] 2 is a diagram of another embodiment of a catheter assembly that can be used with the system shown in FIG. 1.

[0015] [Figure 4] 2 is a diagram of another embodiment of a catheter assembly that can be used with the system shown in FIG. 1.

[0016] [Figure 5] FIG. 2 is a circuit diagram of one embodiment of a pulse generation circuit that may be included in the pulse generator.

[0017] [Figure 6] FIG. 6 is a circuit diagram of one embodiment of a current sensing circuit that can be used with the pulse generation circuit shown in FIG. 5. DETAILED DESCRIPTION OF THE INVENTION

[0018] The present disclosure provides a system and method for a pulse generation circuit configured to be connected to multiple electrodes of an electroporation system, the pulse generation circuit including at least one voltage source, multiple output lines, a switching circuit connected between the at least one voltage source and the multiple output lines, each of the multiple output lines configured to send at least one voltage pulse to a corresponding electrode of the multiple electrodes, and a current sensing circuit configured to sense a current flowing through at least one of the multiple output lines.

[0019] FIG. 1 is a schematic block diagram of a system 10 for electroporation therapy. Generally, the system 10 includes a catheter electrode assembly 12 disposed at the distal end 48 of a catheter 14. As used herein, "proximal" refers to the direction toward the end of the catheter closest to the clinician, and "distal" refers to the direction away from the clinician, typically within the patient's body. The electrode assembly includes one or more individual electrode elements that are electrically isolated from one another. Each of the electrode elements, also referred to herein as catheter electrodes, is separately wired and can be selectively paired or combined with any other electrode element to function as a bipolar or multipolar electrode.

[0020] System 10 may be used for irreversible electroporation (IRE) to destroy tissue. In particular, system 10 may be used for electroporation-induced treatments, which involve delivering an electric current to directly and irreversibly lose the integrity of cell membranes (cell walls), resulting in their collapse and destruction. This mechanism of cell destruction can be considered an "outside-in" process, meaning that the disruption of the cell's outer membrane has a detrimental effect on the cell's interior. Typically, in conventional plasma membrane electroporation, the electric current is delivered as a pulsed electric field in the form of short pulses (e.g., 10 nanoseconds (ns) to 100 milliseconds (ms) in duration) between closely spaced electrodes, capable of delivering an electric field strength of approximately 0.1 to 3.0 kilovolts per centimeter (kV / cm). In some other embodiments, the electric field strength may be higher (e.g., 3.0 kV / cm or greater). System 10 may be used for high-power (e.g., high voltage and / or high current) electroporation procedures. Additionally, system 10 may be used with loop catheters such as those shown in Figures 2A and 2B and / or basket catheters such as those shown in Figures 3A-3C. In some embodiments, system 10 is used for reversible electroporation instead of or in addition to irreversible electroporation.

[0021] In one embodiment, stimulation is selectively delivered (e.g., between pairs of electrodes) on catheter 14. Additionally, electrodes on catheter 14 may be switchable between being connected to a 3D mapping system and an electroporation generator.

[0022] Irreversible electroporation using a multielectrode catheter may enable pulmonary vein isolation with as few as one shock per vein, which can significantly reduce procedure time compared to sequential placement of radiofrequency (RF) ablation tips around the veins.

[0023] Although the energization strategy is described as involving DC pulses, it should be understood that variations may be used in embodiments and remain within the spirit and scope of the present disclosure. For example, exponentially decaying pulses, exponentially increasing pulses, and combinations may be used. Additionally, in some embodiments, AC pulses may be used.

[0024] Furthermore, it should be appreciated that the mechanism of cell destruction in electroporation is not primarily due to the effects of heat, but rather to the disruption of cell membranes by the application of a high-voltage electric field. Thus, electroporation avoids the thermal effects that can occur when using radiofrequency (RF) energy. This "cold therapy" offers desirable characteristics.

[0025] With this background in mind, and referring again to FIGURE 1, system 10 includes a catheter electrode assembly 12 including at least one catheter electrode. Electrode assembly 12 is incorporated as part of a medical device, such as a catheter 14, for electroporation treatment of tissue 16 within a patient's body 17. In the exemplary embodiment, tissue 16 includes cardiac or myocardial tissue. However, it should be understood that embodiments may be used to perform electroporation treatment on a variety of other bodily tissues (e.g., renal tissue, tumors, etc.).

[0026] 1 further illustrates multiple return electrodes, designated 18, 20, and 21, which illustrate body connections that may be used by various subsystems included in overall system 10, such as electroporation generator 26, electrophysiology (EP) monitors such as ECG monitor 28, and localization 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 electrode assembly 12 (a bipolar approach), as described further below. Alternatively, an electric field may be applied between an external return electrode (e.g., return electrode 18) and one or more electrodes on electrode assembly 12 (a monopolar approach).

[0027] In the illustrated embodiment, the return electrodes 18, 20, 21 are patch electrodes. Only one patch electrode is shown for illustrative purposes (for clarity), and it should be understood that the subsystem to which these patch electrodes are connected may (and typically does) include multiple patch (body surface) electrodes, including split-patch electrodes (as described herein). In other embodiments, the return electrodes 18, 20, 21 may be other types of electrodes suitable for use as return electrodes, including, for example, one or more catheter electrodes. A catheter return electrode may be part of the electrode assembly 12 or may be part of another catheter or device (not shown). The system 10 may further include a main computer system 32 (including an electronic control unit 50 and a data storage memory 52), which in certain embodiments may be integrated with the localization navigation system 30. The system 32 may further include conventional interface components, such as various user input / output mechanisms 34A and a display 34B.

[0028] The electroporation generator 26 is configured to energize the electrode elements according to a predetermined or user-selectable electroporation energization strategy. For electroporation treatments, the generator 26 may be configured to generate current delivered through the electrode assembly 12 as a pulsed electric field in the form of short DC pulses (e.g., nanosecond to millisecond durations, or any duration suitable for electroporation) between closely spaced electrodes capable of delivering an electric field strength (i.e., electric field strength at the tissue site) of approximately 0.1 to 3.0 kV / cm. In some alternative embodiments, the electric field strength may be even higher (e.g., 2.0 kV / cm or greater). The amplitude and pulse width required for irreversible electroporation are inversely proportional; that is, the smaller the pulse width, the greater the amplitude required to achieve chronaxie.

[0029] The electroporation generator 26, sometimes referred to herein as a DC energy source, is a biphasic electroporation generator 26 configured to produce a series of DC energy pulses, all of which produce current in two directions (i.e., positive and negative pulses). In other embodiments, the electroporation generator is a monophasic or multiphasic 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, or 200 joules. In other embodiments, more or less energy settings may be used, and the available settings may have the same or different values. For successful electroporation, a power level of 200 joules is used in some embodiments. For example, the electroporation generator 26 may output DC pulses having a maximum amplitude of about 300 volts (V) to about 3,200 V. In other embodiments, any other suitable positive or negative voltage may be output.

[0030] In some embodiments, the impedance of the system 10 can be varied by the variable impedance 27 to limit arcing. Additionally, the variable impedance 27 may be used to change one or more characteristics of the output of the electroporation generator 26, such as the amplitude, duration, pulse shape, etc. Although the variable impedance 27 is shown as a separate component, it may also be incorporated into the catheter 14 or the generator 26.

[0031] 1, as noted above, catheter 14 may include electroporation capabilities and, in certain embodiments, may also include ablation capabilities (e.g., RF ablation). However, it should be understood that variations are possible in those embodiments regarding the type of ablation energy provided (e.g., cryoablation, ultrasound, etc.).

[0032] In the illustrated 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 described herein, such as a temperature sensor, additional electrodes, and corresponding electrical conductors or leads. The connector 40 provides a mechanical and electrical connection to a cable 56 extending from the generator 26. The connector 40 may include conventional components known in the art and is located at the proximal end of the catheter 14, as shown.

[0033] The handle 42 provides a location for the clinician to grasp the catheter 14 and may further provide means for steering or guiding the shaft 44 within the body 17. For example, the handle 42 may include means for varying the length of a guidewire extending through the catheter 14 to the distal end 48 of the shaft 44, as well as means for steering the shaft 44. Additionally, 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 configuration of the handle 42 may vary. In another embodiment, the catheter 14 may be robotically driven or controlled. Thus, rather than a clinician manipulating the handle to advance / retract and / or steer or guide the catheter 14 (and particularly the shaft 44), the catheter 14 is steered using a robot. The shaft 44 is an elongated, tubular, flexible member configured to move within the body 17. The shaft 44 is configured to support the electrode assembly 12 and contain associated conductors and, in some cases, additional electronics used for signal processing or conditioning. Shaft 44 may further allow for the movement, delivery, and / or removal of fluids (including irrigation fluids and bodily fluids), drugs, biologics, and / or surgical tools and instruments. Shaft 44 may be made of conventional materials, such as polyurethane, and may define one or more lumens configured to accommodate and / or move electrical conductors, fluids, or surgical tools, as described herein. Shaft 44 may be introduced into a blood vessel or other structure within body 17 via a conventional introducer. Shaft 44 may then be advanced / retracted and / or manipulated or guided within body 17 to a desired location, such as a site at tissue 16, using a guidewire or other means known in the art.

[0034] A localization navigation system 30 may be provided for visualizing, mapping, and navigating internal body structures. The localization navigation system 30 may include conventional devices commonly known in the art. For example, the localization navigation system 30 may be very similar to the EnSite Precision® system commercially available from Abbott Laboratories and outlined in commonly assigned U.S. Patent No. 7,263,397, entitled "Method and Apparatus for Catheter Navigation and Location and Mapping in the Heart," the disclosure of which is incorporated herein by reference in its entirety. In another example, the localization navigation system 30 may be very similar to the EnSite X® mapping system outlined in U.S. Patent Application Publication No. 2020 / 0138334, entitled "Method for Medical Device Localization Based on Magnetic and Impedance Sensors," the disclosure of which is incorporated herein by reference in its entirety. However, it should be understood that the localization navigation system 30 is exemplary only and not limiting in nature. Other techniques for localizing / navigating a catheter in space (for visualization) are known, such as the CARTO navigation and localization system from Biosense Webster, the Rhythmia® system from Boston Scientific Scimed, the KODEX® system from Koninklijke Philips, the AURORA® system from Northern Digital, or commonly available fluoroscopy systems.

[0035] In this regard, some localization, navigation, and / or visualization systems may include sensors for generating signals indicative of catheter position information, which may include one or more electrodes, for example, in the case of an impedance-based localization 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 localization system. In yet another example, system 10 may use a combined electric-field-based and magnetic field-based system as outlined in 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.

[0036] Pulsed 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 to perform pulmonary vein isolation (PVI) at specific cardiac tissue sites, such as pulmonary veins. In an exemplary embodiment, the electric field is applied between adjacent electrodes (bipolar approach). Alternatively, the electric field may be applied between one or more electrodes and a return patch (monopolar approach). Each of these approaches has advantages and disadvantages.

[0037] In terms of lesion size and proximity, the monopolar approach has a wider effective range and can create deeper lesions for the same applied voltage. Furthermore, the monopolar approach allows lesions to be created from a distance (e.g., roughly adjacent to the tissue, but not necessarily in contact with the tissue). The bipolar approach creates smaller lesions and therefore requires closer proximity or contact with the tissue to create transmural lesions. However, the monopolar approach may create larger lesions than necessary, while the lesions created with the bipolar approach may be more localized.

[0038] The unipolar approach has a wide area of ​​effect, which may unnecessarily activate skeletal muscle and / or nerves. In contrast, the bipolar approach has a limited area of ​​effect proportional to the electrode spacing on the lead, making it less likely to depolarize cardiac muscle cells or nerve fibers.

[0039] To monitor the operation of system 10, one or more impedances between catheter electrode 144 and / or return electrodes 18, 20, 21 may be measured. For example, impedances may be measured with respect to system 10 as described in U.S. Patent Application Publication No. 2019 / 0117113, filed October 23, 2018, U.S. Patent Application Publication No. 2019 / 0183378, filed December 19, 2018, and International Patent Application Publication No. WO2021 / 236341, filed May 6, 2021, all of which are incorporated herein by reference in their entireties.

[0040] 2A and 2B are diagrams of one embodiment of a catheter assembly 146 that can be used with the catheter 14 in the system 10. The catheter assembly 146 is also referred to as a loop catheter. Those skilled in the art will appreciate that in other embodiments, any suitable catheter may be used. Specifically, FIG. 2A is a side view of the catheter assembly 146 having a variable diameter loop 150 at the distal end 142. FIG. 2B is an end view of the variable diameter loop 150 of the catheter assembly 146. Those skilled in the art will appreciate that the methods and systems described herein may be practiced with any suitable catheter (e.g., a fixed-loop catheter, a linear catheter, a basket catheter, etc.). As shown in FIGS. 2A and 2B, the variable diameter loop 150 is connected to the distal portion 151 of the shaft 44.

[0041] Variable diameter loop 150 is selectively transitionable between an expanded diameter 160 (shown in FIG. 2A ) (also referred to as an “open diameter”) and a retracted diameter 160 (not shown) (also referred to as a “closed diameter”). In an exemplary embodiment, expanded diameter 160 is 28 mm and retracted diameter 160 is 15 mm. In other embodiments, diameter 160 may vary between any suitable open and closed diameters 160.

[0042] In the illustrated embodiment, the variable diameter loop 150 includes fourteen catheter electrodes 144 that are approximately equally spaced around the circumference of the variable diameter loop 150 in the expanded configuration. In the retracted configuration, one or more of the electrodes 144 may overlap. In other embodiments, the catheter electrodes 144 may be arranged in other ways. For example, in one embodiment, the variable diameter loop 150 includes twelve catheter electrodes 144.

[0043] The catheter electrodes 144 are platinum ring electrodes configured to carry and / or discharge current in the range of 1000 volts and / or 10 amps. 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 carrying high voltages and / or high currents (e.g., in the range of 1000 volts and / or 10 amps). Each of the catheter electrodes 144 is separated from the other by an insulating gap 152. In an exemplary embodiment, each catheter electrode 144 has the same length 164 (shown in FIG. 2B ), and each insulating gap 152 has the same length 166 as the other gaps 152. In an exemplary embodiment, the lengths 164 and 166 are both approximately 2.5 mm. In other embodiments, the lengths 164 and 166 may be different from one another. Additionally, 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 spaced around the circumference of the variable diameter loop 150.

[0044] The diameter 160 and spacing between the catheter electrodes 144 may be set to provide a targeted range of energy densities across the tissue and to provide sufficient electroporation coverage for different human anatomy. Generally, a sufficient number of electrodes 144 with appropriate lengths 164 are desired to provide substantially uniform and continuous coverage around the circumference of the variable diameter loop 150, while still allowing the variable diameter loop 150 to have sufficient flexibility to expand and contract to change the diameter 160 to the desired extremes.

[0045] 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 area of ​​the circumference of the variable diameter loop 150 occupied by the electrode 144 and, by increasing the surface area of ​​the electrode 144, reduces the current density at the electrode 144, thereby preventing arcing during an electroporation procedure. However, increasing the length 164 too much may prevent the variable diameter loop 150 from forming a smooth circle, limiting the closed diameter 160 of the variable diameter loop 150. Furthermore, increasing the length 164 too much may increase the surface area of ​​the catheter electrode 144 to the point where the current density applied by the power supply to the catheter electrode 144 is less than the minimum current density required for successful treatment. Conversely, decreasing the length 164 reduces the surface area, thereby increasing the current density at the catheter electrode 144 (assuming no other system modifications). As discussed above, higher current densities may increase the risk of arcing during electroporation, potentially requiring the addition of more system resistance to prevent arcing. Additionally, a shorter length 164 may require more catheter electrodes 144 to achieve the desired uniform coverage around the circumference of the variable diameter loop 150. Increasing the number of catheter electrodes 144 on the variable diameter loop 150 may prevent the variable diameter loop 150 from contracting to the desired minimum diameter 160.

[0046] 3A is a perspective view of another catheter assembly 200 that can be used with the catheter 14. The catheter assembly 200 is also referred to as a basket catheter. The catheter assembly 200 includes a shaft 202 and a plurality of splines 204 that surround a distal portion 206 of the shaft 202. In this embodiment, the catheter assembly 200 further includes a balloon 208 that is surrounded by the splines 204. The balloon 208 may be selectively inflated to fill spaces between the splines 204. In particular, the balloon 208 acts as an insulator and generally reduces energy loss so that the size of the lesion may increase.

[0047] Each spline 204 includes a proximal end 210 connected to the shaft 202 and a distal end 212 connected to the shaft 202. The splines 204 have an arcuate shape that extends radially outward from the proximal end 210 to the distal end 212.

[0048] In this embodiment, each spline 204 includes one or more individual electrodes 220. For example, each spline 204 may include a resilient material (e.g., nitinol) covered with a polymer tube 222, with the individual electrodes 220 attached to the outer surface of the polymer tube 222. In the illustrated embodiment, each spline 204 includes two electrodes 220. Furthermore, as shown in FIG. 3A , the electrodes 220 are generally positioned closer to the distal end 212 than to the proximal end 210 to correspond to the portion of the spline 204 that contacts the pulmonary veins.

[0049] Alternatively, each spline 204 may include any suitable number and arrangement of electrodes 220. For example, in some embodiments, each spline 204 includes four electrodes 220.

[0050] In this embodiment, the 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 adjacent splines 204. Alternatively, any suitable polarization scheme may be employed. The splines 204 may be collapsed toward the shaft 202 during delivery. Then, for ablation, the splines 204 are deployed to extend radially outward.

[0051] The splines 204 may all have the same length, or at least some of the splines 204 may have different lengths. Further, the insulating material on each spline 204 may have the same length, or at least some of the splines 204 may have different lengths. Furthermore, in some embodiments, the catheter assembly 200 includes a distal electrode (not shown) located distal to the splines 204. The distal electrode may be used to perform point ablation (e.g., by forming a bipole between the distal electrode and one of the splines 204) and / or for visualization / mapping (e.g., by using the distal electrode in combination with an electrode on the shaft 202).

[0052] Figure 3B is a perspective view and Figure 3C is a schematic side view of another catheter assembly 250 that can be used with catheter 14. Like catheter assembly 200 (shown in Figure 3A), catheter assembly 250 is also referred to as a basket assembly.

[0053] Catheter assembly 250 includes a shaft 252 and a plurality of splines 254 that surround a distal portion 256 of shaft 252. In this embodiment, catheter assembly 250 includes a balloon 258 that is surrounded by splines 254. Balloon 258 may be selectively inflated to occlude spaces between splines 254. Notably, balloon 258 acts as an insulator and generally reduces energy loss so that the size of the lesion may increase.

[0054] Each spline 254 includes a proximal end 260 connected to shaft 252 and a distal end 262 connected to shaft 252. Splines 254 extend radially outward from proximal end 260 to an inflection point 264, from which they extend radially inward to distal end 262. Figure 3C shows catheter assembly 250 positioned within a pulmonary vein 266.

[0055] The body of each spline 254 is made of a resilient material (e.g., nitinol) and functions 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 employed.

[0056] To control the ablation zone of each spline 254, a portion of each spline 254 may be covered with an insulating material 270 (e.g., heat shrink or polymer tubing, or a spray or dip coat of polyimide or PEBAX), with the exposed portion of the spline 254 functioning as an electrode. In the embodiment shown in Figures 3B and 3C, 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. Thus, the portion of the spline 254 that contacts the pulmonary vein 266 is exposed (see Figure 3C). Alternatively, any suitable insulating configuration may be used.

[0057] The splines 254 and balloon 258 may be folded during delivery. To perform ablation, the inflection points 264 extend radially outward, deploying the splines 254, and the balloon 258 is selectively inflated to fill the spaces between the splines 254.

[0058] The combination of balloon 258 and spline 254 facilitates linear delivery and deployment of catheter assembly 250. Additionally, balloon 258 delivers more energy to the tissue being ablated and stabilizes spline 254 from lateral movement. Additionally, using spline 254 as an electrode instead of individual small electrodes facilitates cost reduction and improved reliability of catheter assembly 250.

[0059] The splines 254 may all have the same length, or at least some of the splines 254 may have different lengths. Furthermore, the insulating material 270 on each spline 254 may have the same length, or at least some of the splines 254 may have different lengths of insulating material 270. Furthermore, in some embodiments, the catheter assembly 250 includes a distal electrode (not shown) disposed distal to the splines 254. The distal electrode may be used to perform point ablation (e.g., by forming a bipole between the distal electrode and one of the splines 254) and / or for visualization / mapping (e.g., by using the distal electrode in combination with an electrode on the shaft 252).

[0060] Figure 4 is a side view of another catheter assembly 280 that may be used with catheter 14. Catheter assembly 280 is also referred to as a grid assembly. As shown in Figure 4, catheter assembly 280 is connected to a distal portion 282 of a shaft, such as shaft 44 (shown in Figure 1).

[0061] 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. In the embodiment shown in FIG. 4, the catheter assembly 280 includes four splines 284, each including four electrodes 290, with the electrodes 290 forming a grid configuration. Thus, the catheter assembly 280 provides a 4×4 grid of electrodes 290. In one embodiment, the spacing between each pair of adjacent electrodes 290 is approximately 4 millimeters (mm), and the dimensions of the grid of electrodes 290 are approximately 12 mm×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). Additionally, in some embodiments, the catheter assembly 280 may include, for example, 56 electrodes arranged in a 7x8 grid.

[0062] The catheter assembly 280 may be used to create lesions at individual electrodes 290 using a monopolar approach (e.g., applying a voltage between an individual electrode 290 and a return patch) or a bipolar approach to create lesions between pairs of electrodes 290. Lesions may be created in the anatomical structure by selectively energizing the electrodes in specific configurations and / or patterns (e.g., including energizing individual electrodes 290 separately or energizing multiple electrodes 290 simultaneously).

[0063] Those skilled in the art will appreciate that catheter assembly 146 (shown in FIGS. 2A and 2B), catheter assembly 200 (shown in FIG. 3A), catheter assembly 250 (shown in FIGS. 3B and 3C), and catheter assembly 280 (shown in FIG. 4) are merely examples. In particular, the systems and methods described herein may be practiced with any suitable catheter assembly.

[0064] In electroporation therapy, a waveform is generated using a pulse generator (e.g., electroporation generator 26 (shown in FIG. 1)) and applied between a pair of catheter electrodes (i.e., a bipolar approach) or between an individual catheter electrode and a return patch (i.e., a monopolar approach). The waveform may be monophasic, biphasic (i.e., having both positive and negative pulses), or polyphasic. Furthermore, the waveform may include one or more bursts of pulses (each burst including multiple pulses). Furthermore, the waveform is defined by multiple parameters (e.g., pulse width, pulse amplitude, frequency, etc.).

[0065] To generate various waveforms, the pulse generator selectively connects different electrodes to different voltage levels. In at least some known systems, a first subset of the electrodes is selectively connectable to a first voltage level (e.g., a positive voltage) and a second subset of the electrodes is selectively connectable to a second voltage level (e.g., a negative voltage).

[0066] In at least some known systems, the output current from the pulse generator to one or more electrodes is not monitored. Instead, upstream capacitor voltages are measured, but downstream current is not monitored after those capacitors are discharged via switching circuits connected between the capacitors and the electrodes. Therefore, it may be difficult or impossible to detect and correct faults downstream of the capacitors.

[0067] The systems and methods described herein enable detection of the output current from a pulse generator using a current sensing circuit, which may be implemented using a relatively small and inexpensive current transformer. Additionally, the current sensing circuit enables fault detection and measurement of the current and other parameters at the output of the pulse generator.

[0068] 5 is a circuit diagram of one embodiment of a pulse generation circuit 400 that may be included in a pulse generator such as electroporation generator 26 (shown in FIG. 1). Pulse generation circuit 400 is connectable to a plurality of electrodes 408 (designated 1, 2, 3, ... (N-1), N), such as electrodes on catheter electrode assembly 12 (shown in FIG. 1).

[0069] 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. The first voltage source 402 and the second voltage source 404 may have any suitable voltage levels. For example, in one embodiment, the first voltage source 402 may have a voltage level of 1400 V, and the second voltage source 404 may have a voltage level of 1800 V.

[0070] Each module 406 is associated with multiple 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 associated with four electrodes 408, resulting in a circuit for a total of 16 electrodes 408.

[0071] 5 , within the module 406, an electrode address circuit 410 is connected to each electrode 408. The electrode address circuit 410 is an example of a switching circuit that may be used to selectively connect the electrode 408 to the first voltage source 402 and the second voltage source 404. The electrode address circuit 410 allows each electrode 408 to be optionally addressed. Specifically, for a given electrode 408, the electrode address circuit 410 includes a first switch 412 connected between the electrode 408 and the first voltage source 402, a second switch 414 connected between the electrode 408 and the second voltage source 404, and a third switch 416 connected between the electrode 408 and a return voltage 418. Using the switches 412, 414, and 416, the 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. Any suitable controller (not shown) may be used to control the operation of switches 412, 414, 416.

[0072] 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 combining silicon MOSFETs and silicon carbide depletion-mode JFETs).

[0073] Thus, each electrode 408 may be selectively connected to the first voltage source 402, the second voltage source 404, or the return voltage 418, independent of the other electrodes 408. This allows for great flexibility in selecting treatment regimens, allowing for various combinations of electrodes pulsing at different voltage levels and / or different pulse widths.

[0074] Furthermore, by controlling the time interval between each phase, charge is delivered in both directions but energy is delivered in one direction, which facilitates achieving desired electrophysical effects (e.g., selective irreversible electroporation of tissue) while suppressing undesired effects (e.g., involuntary skeletal muscle movements).

[0075] 5, the electrode address circuit 410 includes multiple current-limiting resistors 430. For example, one current-limiting resistor 430 may be connected between the first switch 412 and the first voltage source 402, another current-limiting resistor 430 may be connected between the second switch 414 and the second voltage source 404, and yet another current-limiting resistor 430 may be connected between the third switch 416 and the electrode 408. The current-limiting resistors 430 also function to provide fault protection.

[0076] Additionally, in some embodiments, the pulse generation circuit 400 may include multiple isolation switches (not shown). Each isolation switch is connected in series between the electrode address circuit 410 and its associated electrode 408 and is an electromechanical switch that allows the electrode 408 to be completely disconnected from the first voltage source 402 and the second voltage source 404 (e.g., without allowing leakage current to the electrode 408). Thus, the isolation switches protect the patient by preventing current from reaching the electrode 408 when the isolation switch is open.

[0077] 5, an output line 450 extends between each electrode address circuit 410 and its associated electrode 408. Additionally, the current through each output line 450 is sensed using a current sensing circuit 452. A resistor 460 downstream of the electrode 408 represents the resistance of the patient tissue.

[0078] 6 is a circuit diagram of one embodiment of a current sense circuit 452 that may be used to sense current flowing through output line 450. In the illustrated embodiment, current sense circuit 452 includes a current transformer 502 connected to output line 450. Current sense circuit 452 further includes a signal processing circuit 504 and a rectifier 506 connected between signal processing circuit 504 and current transformer 502. Rectifier 506 includes a plurality of diodes 510, and resistor 512 is connected in parallel with rectifier 506. Those skilled in the art will appreciate that signal processing circuit 504 may be implemented using any suitable digital or analog circuitry. Furthermore, those skilled in the art will appreciate that current sense circuit 452 may alternatively be implemented using other circuit configurations and components.

[0079] In this embodiment, current transformer 502 is a relatively small and relatively inexpensive current transformer. For example, current transformer 502 may have dimensions of approximately 10 millimeters (mm) by 17 mm by 20 mm. When a current flows through output line 450, an isolated signal proportional to the current in output line 450 is generated through current transformer 502. Therefore, by detecting the current through current transformer 502 (e.g., using signal processing circuitry 504), it is possible to determine that a current is flowing through output line 450 (i.e., to the corresponding electrode 408) and calculate the magnitude of that current.

[0080] In one example, the current sense circuit 452 operates as follows: The rectifier 506 rectifies the signal from the current transformer 502. The rectified signal is then compared (using the signal processing circuit 504) to a threshold value. Based on this comparison, the signal processing circuit 504 determines whether a malfunction has occurred in the pulse generation circuit.

[0081] For example, if the rectified signal is below the threshold when current should be flowing through output line 450 (i.e., a pulse is being delivered to electrode 408), signal processing circuitry 504 determines that a malfunction has occurred (because the rectified signal should be above the threshold when a pulse is being delivered). As another example, if the rectified signal is above the threshold when current should not be flowing through output line 450 (i.e., a pulse should not be delivered to electrode 408), signal processing circuitry 504 determines that a malfunction has occurred (because the rectified signal should be below the threshold when a pulse is not being delivered intentionally).

[0082] The signal of the current transformer 502 may be used to determine parameters other than the current through the output line 450. For example, the signal may 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., pulse length), and the estimated total charge may be compared to an expected total charge. In another example, a detailed capture of each pulse delivered to the electrode 408 may be recorded for further analysis. In yet another example, the signal may be used to measure tissue impedance and energy for each pulse delivered to the electrode 408.

[0083] The current sensing circuit 452 also allows for detection of malfunctions in the pulse generation circuit 400. For example, if the pulse generation circuit 400 is being controlled to deliver a pulse to the electrode 408 but no signal is detected via the current transformer 502, the signal processing circuit may determine that a malfunction has occurred and take appropriate action (e.g., issuing an alarm to notify a user, terminating operation of the pulse generation circuit 400).

[0084] Additionally, in some embodiments, the current sense circuit 452 may be used to provide closed-loop control of the pulse generation circuit 400. For example, if the current sense circuit 452 determines that the current through the output line 450 exceeds a predetermined threshold, the system may decrease the voltage and / or pulse length of a subsequent pulse. Alternatively, if the current sense circuit 452 determines that the current through the output line 450 is below a predetermined threshold, the system may increase the voltage and / or pulse length of a subsequent pulse.

[0085] In another example of closed-loop control, the current sensing circuit 452 may be used to estimate the actual current being sent through the output line 450. As a result, the active load impedance may be more accurately estimated. Based on the estimated active load impedance, the timing and / or voltage of the pulses generated by the pulse generation circuit 400 may be increased or decreased accordingly.

[0086] In one embodiment, current sense circuit 452 may be used to measure at least one of the peak current and total charge delivered for each positive and negative pulse. Based on this data, at least one of the timing and voltage of subsequent pulses may be adjusted. Generally, the timing of subsequent pulses can be adjusted relatively quickly. However, adjusting the voltage of subsequent pulses generally takes more time.

[0087] Specifically, the timing of the pulses may be varied from pulse to pulse. For example, measured tissue impedance (e.g., determined using data collected by current sensing circuitry 452) may be correlated with lesion depth or progression of lesion formation. A sufficient change in impedance indicates that the lesion has reached a target size, and the pulse width of subsequent pulses may be decreased accordingly, or subsequent pulses may be terminated entirely.

[0088] In contrast, in the case of voltage changes, the voltage on a capacitor that is discharged to generate a pulse may be changed relatively slowly. For example, even if it is determined that the voltage should be increased based on data collected by the current sense circuit 452, the voltage may only be increased relatively slowly (at a rate determined by the available current divided by the capacitance).

[0089] For example, a 30 milliamp (mA) current source will charge an 87 microfarad (µF) capacitor at a rate of 0.345 volts per millisecond (V / ms). Similarly, a 60mA current source will charge an 87µF capacitor at a rate of 0.345V / ms. Therefore, to raise the voltage by 200V, a 30mA current source will take approximately 816ms, and a 60mA current source will take approximately 408ms.

[0090] Other closed-loop techniques may also be implemented. For example, in one embodiment, measurements from the current sense circuit 452 are used to determine the accumulated charge and the timing of the pulses (e.g., on a pulse-by-pulse basis) is adjusted accordingly to maintain charge balance.

[0091] The current sensing circuit 452 may be used to supplement or replace an upstream current sensing function (e.g., upstream of the switching circuit). For example, at least some known pulse switching circuits, for simplicity reasons, monitor an internal current (proportional to or the same as the current of interest) for only a portion of the operating cycle and / or only a portion of the total path of the current of interest. This results in current sampling of the current of interest rather than continuous monitoring of the current of interest.

[0092] In one example, at least some known systems may monitor only the voltage drop across or current through the resistance of a first switch, even though the entire path to the catheter also includes a second (upstream or downstream) switch and resistor. This monitoring scheme may be sufficient when the circuit is operating properly. However, a fault in the circuit (e.g., a faulty device and / or connection) may create a short circuit that effectively changes the topology of the circuit, causing inaccurate voltage / current monitoring.

[0093] For example, a system may have current sampling for a first upstream switch but not for a second downstream switch. If the second switch fails (e.g., due to a catheter malfunction), current sampling will not detect the failure. In contrast, the current sensing circuit 452 described herein, located downstream from the switching circuit, can detect the failure.

[0094] Those skilled in the art will appreciate that modifications may be made to pulse generation circuit 400. For example, in some embodiments, one or more high voltage differential amplifiers (not shown) may be added to pulse generation circuit 400 to measure the high voltage outputs of first voltage source 402 and second voltage source 404. This allows a parity check to be performed between the voltage outputs from voltage sources 402 and 404 (measured using the high voltage differential amplifiers) and the currents (measured using current sense circuit 452) output through output line 450.

[0095] In another embodiment, a test output line (not shown) may extend between the switching circuit and the test load (rather than between the switching circuit and the catheter), and a current transformer may be used to monitor the current flowing into the test load, similar to current sense circuit 452. This allows pulses to be sent to the test load first, monitoring the current to verify that the pulse generation circuit 400 is operating properly, and then switching to sending pulses to the catheter after verifying that the pulse generation circuit is operating properly.

[0096] The systems and methods described herein relate to a pulse generation circuit configured to be connected to multiple electrodes of an electroporation system, the pulse generation circuit including at least one voltage source, multiple output lines, a switching circuit connected between the at least one voltage source and the multiple output lines, each of the multiple output lines configured to send at least one voltage pulse to a corresponding electrode of the multiple electrodes, and a current sensing circuit configured to sense a current flowing through at least one of the multiple output lines.

[0097] While specific embodiments of the present disclosure have been described in some detail above, those skilled in the art will be able to make numerous modifications to the disclosed embodiments without departing from the spirit or scope of the present disclosure. All directional references (e.g., up, down, top, bottom, left, right, left, right, upper, lower, up, down, vertical, horizontal, clockwise, and counterclockwise) are used for identification purposes only to aid the reader in understanding the present disclosure and are not intended to impose any limitations on the location, orientation, or use of the present disclosure. References to connections (e.g., attached, connected, coupled, etc.) should be interpreted broadly and may include intermediate members between connections between elements and relative movement between elements. As such, references to connections do not necessarily infer that two elements are directly connected and in a fixed relationship to each other. All matter contained in the above description or shown in the accompanying drawings should be interpreted as illustrative only and not limiting. Changes in detail or structure may be made without departing from the spirit of the present disclosure, as defined by the appended claims.

[0098] When introducing elements of the disclosure or preferred embodiments thereof, the articles "a," "an," "the," and "said" mean that there are one or more of the element. The words "comprise," "include," and "have" are intended to be inclusive and mean that there may be other elements other than the listed elements.

[0099] Since various changes may be made in the above configurations without departing from the scope of the present disclosure, all matter contained in the above description or shown in the accompanying drawings should be interpreted as illustrative and not in a limiting sense.

Claims

1. 1. A pulse generation circuit configured to be connected to a plurality of electrodes of an electroporation system, the pulse generation circuit comprising: at least one voltage source; a plurality of output lines; a switching circuit connected between the at least one voltage source and the plurality of output lines, each of the plurality of output lines configured to send at least one voltage pulse to a corresponding one of the plurality of electrodes; a current sensing circuit configured to sense a current through at least one of the plurality of output lines; Pulse generating circuit.

2. The current sensing circuit a current transformer connected to the at least one output line; a signal processing circuit connected to the current transformer; 2. The pulse generating circuit according to claim 1.

3. the current sensing circuit further comprises a rectifier connected between the current transformer and the signal processing circuit.

3. The pulse generating circuit according to claim 2.

4. the current transformer is configured to generate a signal in response to a current through the at least one output line; the rectifier is configured to rectify the generated signal; the signal processing circuitry is configured to compare the rectified signal with a threshold value; 4. The pulse generating circuit according to claim 3.

5. the current sensing circuitry is configured to adjust parameters of a subsequent voltage pulse based on the sensed current.

2. The pulse generating circuit according to claim 1.

6. the current sensing circuitry is configured to estimate a total charge delivered to at least one of the plurality of electrodes based on the sensed current; 2. The pulse generating circuit according to claim 1.

7. the current sensing circuit is configured to detect a malfunction of the pulse generating circuit based on the sensed current.

2. The pulse generating circuit according to claim 1.

8. 1. An electroporation system comprising: a catheter having a plurality of electrodes; a pulse generating circuit connected to the plurality of electrodes; The pulse generating circuit at least one voltage source; a plurality of output lines; a switching circuit connected between the at least one voltage source and the plurality of output lines, each of the plurality of output lines configured to send at least one voltage pulse to a corresponding one of the plurality of electrodes; and a current sensing circuit configured to sense a current through at least one of the plurality of output lines. Electroporation system.

9. the current sensing circuit a current transformer connected to the at least one output line; a signal processing circuit connected to the current transformer; 9. The electroporation system of claim 8.

10. the current sensing circuit further comprises a rectifier connected between the current transformer and the signal processing circuit.

10. The electroporation system of claim 9.

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

12. the current sensing circuitry is configured to adjust parameters of a subsequent voltage pulse based on the sensed current.

9. The electroporation system of claim 8.

13. the current sensing circuitry is configured to estimate a total charge delivered to at least one of the plurality of electrodes based on the sensed current; 9. The electroporation system of claim 8.

14. the current sensing circuit is configured to detect a malfunction of the pulse generating circuit based on the sensed current.

9. The electroporation system of claim 8.

15. 1. A method of operating an electroporation system, the method comprising: providing a catheter including a plurality of electrodes; connecting 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 connected between the at least one voltage source and the plurality of output lines; sending at least one voltage pulse to a corresponding electrode of the plurality of electrodes using each of the plurality of output lines; and sensing a current through at least one of the plurality of output lines using a current sensing circuit. method.

16. the current sensing circuit includes a current transformer connected to the at least one output line, a signal processing circuit connected to the current transformer, and a rectifier connected between the current transformer and the signal processing circuit.

16. The method of claim 15.

17. generating a signal in response to a current flowing through the at least one output line using the current transformer; rectifying the generated signal with the rectifier; and comparing the rectified signal with a threshold using the signal processing circuitry.

17. The method of claim 16.

18. adjusting parameters of a subsequent voltage pulse based on the sensed current.

16. The method of claim 15.

19. and estimating a total charge delivered to at least one of the plurality of electrodes based on the sensed current.

16. The method of claim 15.

20. detecting a malfunction of the pulse generation circuit based on the sensed current.

16. The method of claim 15.

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