Circumferential ablation device and method

Abstract

Methods and apparatus for providing pulsed electrical treatment (including high voltage, sub-microsecond pulsed electrical energy) to a body vessel are disclosed. The apparatus can include a deployable electrode that conforms to a transitional surface of a sinus including a pulmonary vein.

Description

[0001] Claim priority

[0002] This patent application claims priority to U.S. Provisional Patent Application No. 63 / 180,022, entitled “CIRCUMFERENTIAL ABLATION CATHETER DEVICES AND METHODS,” filed April 26, 2021, and U.S. Provisional Patent Application No. 63 / 253,119, entitled “CIRCUMFERENTIAL ABLATION CATHETER DEVICES AND METHODS,” filed October 6, 2021, the entire contents of each of which are incorporated herein by reference.

[0003] By incorporating via reference

[0004] All publications and patent applications mentioned in this specification are incorporated herein by reference in their entirety, to the extent that each individual publication or patent application is explicitly and individually indicated to be incorporated by reference. Background Technology

[0005] Short, high-field-strength electrical pulses for the electrical manipulation of biological cells have been described. For example, electrical pulses can be used to treat human cells and tissues. The voltage induced across the cell membrane can depend on the pulse length and pulse amplitude. Pulses longer than about 1 microsecond may charge the outer cell membrane and create permanent pore openings. Permanent openings can lead to transient or near-transient cell death. Pulses shorter than about 1 microsecond may affect the cell interior without adversely or permanently affecting the outer cell membrane, resulting in delayed cell death with intact cell membranes. Such shorter pulses, with field strengths varying in the range of, for example, 10 kV / cm to 100 kV / cm, may trigger apoptosis (i.e., programmed cell death) in some or all of the cases where cells are exposed to the described field strength and pulse duration. These higher electric field strengths and shorter electrical pulses can be used to manipulate intracellular structures such as the nucleus, endoplasmic reticulum, and mitochondria. For example, such submicrosecond (e.g., nanosecond) high-voltage pulse generators have been proposed for biological and medical applications.

[0006] In some cases, two or more electrodes are used to deliver electrical pulses, including high-field-intensity electrical pulses, to a selected treatment area. These electrodes may be configured for bipolar operation. The electrodes are positioned to contact the tissue in the area to be treated. In some cases, the treatment area may have a varied or irregular shape. For example, the treatment area may transition from a first diameter to a second diameter. Varying diameters and / or irregular shapes may make it difficult for the electrodes to maintain constant and uniform contraction.

[0007] Therefore, it may be beneficial to provide electrodes that can adapt to treatment areas of varying and / or irregular shapes. Summary of the Invention

[0008] This document describes medical devices (e.g., apparatus, systems, etc.) and methods that can be used to perform medical procedures to treat patients. Specifically, the devices and methods described herein can be used to deliver short, high-field electrical pulses to perform ablation, for example, circumferential ablation on body vessels, including blood vessels and other lumens.

[0009] For example, this document describes devices and methods for treating the walls of anatomical structures, such as body channels, cavities, or vessels (e.g., veins, arteries, blood vessels, heart, trachea, pharynx, larynx, bronchi, ureters, urethra, fallopian tubes, cervix, uterus, intestines (large and / or small intestine), gallbladder, pancreas, rectum, liver, esophagus, stomach, nasal cavity, seminal vesicles, vas deferens, etc.), using pulsed electric fields including (but not limited to) nanosecond pulsed electric fields, microsecond pulsed electric fields, etc. For ease of description, all such anatomical structures, cavities, tubes, lumen, channels, or vessels will be referred to herein as body vessels. In some examples, body vessels may include pulmonary veins, sinuses, and other suitable cavities. Specifically, the methods and devices described herein can be configured to selectively treat body vessels with varied, transitional, and / or irregular surfaces. An electrode adaptable to a body vascular system may include a first electrode and a second electrode configured to be deployed from a catheter and adapted to, for example, a portion of the wall of a body vascular system, and to provide a submicrosecond (e.g., nanosecond) pulsed electric field in a localized manner to limit or prevent damage to deeper, non-target areas.

[0010] The methods and devices described herein are not limited to vascular treatments, such as angioplasty, but can be used to treat other bodily cavities where narrowing of the lumen may be a problem. For example, treatment can be performed on the lungs (airways), stomach ventricles, catheters, etc., as described herein. In some examples, the instruments and methods described herein are configured for otolaryngological purposes, such as for insertion and treatment by applying submicrosecond (e.g., nanosecond) pulsed electric fields within cavities or other otolaryngological structures, including anatomical structures such as the turbinate bones, tonsils, tongue, soft palate, parotid glands, and those structures connecting the larynx (pharynx) to the stomach. These instruments and devices can be configured for insertion into these structures; for example, they can be configured as elongated application tools, including catheters, tubes, etc., sized and shaped to fit within the ear, nose, throat, and / or treat associated anatomical structures (e.g., turbinate bones, tonsils, tongue, soft palate, parotid glands, etc.). For example, this document describes methods and apparatuses configured to deliver submicrosecond (e.g., nanosecond) pulsed electric fields to a portion of the gastrointestinal tract (e.g., stomach, small intestine, large intestine, duodenum, colon, etc., including but not limited to the esophagus). This document also describes methods and apparatuses configured to deliver submicrosecond (e.g., nanosecond) pulsed electric fields to a portion of the respiratory tract (including the trachea, pharynx, larynx, bronchi, and bronchioles). Among other things, the methods and apparatuses described herein are particularly useful in cardiac applications, including but not limited to the treatment of atrial fibrillation.

[0011] The devices described herein may include elongated application tools (e.g., catheters) that can be inserted into bodily vessels or cavities, including but not limited to blood vessels (arteries, veins, etc.), esophagus, ear, nose, throat, trachea, pharynx, larynx, small intestine, large intestine, duodenum, colon, etc. These application tools may include an elongated flexible body extending in a proximal-to-distal direction. One or more electrodes configured to deliver electrical pulses (e.g., nanosecond pulses) to target tissue may be present at the end region of the flexible body.

[0012] An applicator (“application tool”) may be configured to be removably coupled to a pulse generator configured to generate, for example, submicrosecond (e.g., nanosecond) pulse energy, such coupling being made via a handle near a distal end region including an electrode. The electrode may be deployable and may be located on an expansion member that expands to contact the vessel wall. The handle controls deployment. Alternatively, in some cases, the application tool (also referred to herein as a device or apparatus) may be configured to be directly coupled to the pulse generator without a handle. According to one example, the devices described herein include medical devices and instruments for procedures of inserting the application tool into an intraluminal lumen. These devices may be introduced into the blood vessel, for example, via an external delivery catheter or guiding sheath.

[0013] Any of the devices described herein can be configured to function within a body region having a varying diameter (e.g., from wider to narrower, or from narrower to wider), including regions having a conical or funnel shape. For example, some devices described herein may include at least two annular (elliptical, circular, etc.) electrodes with different diameters. In some examples, the diameters and / or lateral positions of these annular electrodes relative to each other may be adjustable.

[0014] In some examples, the applicator may include one or more contact protrusions (e.g., ribs, wires, springs, contact plates, contact posts, balloons, etc.) that can be manipulated by operating, for example, a proximal handle coupled to the applicator tool, to extend from the proximal end of the applicator. The contact protrusions typically contact the wall of the lumen into which the applicator tool is inserted to enhance tissue access and contact between the electrode and the tissue. For example, the contact protrusions may be expandable elements (e.g., balloons) or mechanical elements (e.g., a pair of plates or arms). In some examples, multiple contact protrusions may be positioned along the length of the applicator and may move closer to or further away along the length of the distal end region of the applicator. In some examples, the electrodes are sandwiched between the contact protrusions; in some examples, the contact protrusions comprise electrodes. The contact protrusions may be retractable into / removable from the applicator tool, or simply retractable / removable relative to the applicator tool.

[0015] In one example, the applicator may include: an elongated body, such as an elongated catheter body; a first electrode formed of one or more rings having a first diameter and flexibly coupled to the elongated catheter body; and a second electrode formed of one or more rings having a second diameter and flexibly coupled to the elongated catheter body. The first and second electrodes may contact body vessels, particularly those with irregular, varied, or transitional surfaces.

[0016] In some examples, the first and second electrodes may be divided into lobes, each lobe being coupled to an elongated body (e.g., an elongated catheter body) via an arm. In some examples, the first and second electrodes may include two or more lobes.

[0017] In some examples, the first and second electrodes are coupled to the distal end region of an elongated body (which may be referred to as an elongated conduit body). In other examples, the first and second electrodes may be movable within the elongated conduit body and may be configured to extend out of the elongated conduit body and collapse when retracted into the elongated conduit body. In some other examples, one of the first and second diameters is smaller than the other. In still other examples, the first electrode is positioned distally relative to the end of the elongated conduit body (e.g., the distal end of the elongated conduit body), and the second electrode is disposed between the first electrode and the distal end of the elongated conduit body.

[0018] In some examples, the first and second electrodes are configured to flexibly contact the sinuses associated with the pulmonary veins. In some other examples, the first and second conductors are configured to deliver pulsed electrical therapy, wherein pulsed energy is transferred between the first and second conductors. In yet another example, the first and second conductors are configured to deliver pulsed electrical therapy, wherein energy is transferred between the first and third conductors or between the second and third conductors.

[0019] In some examples, the first and second conductors are configured to change the distance between them.

[0020] In another example, a device for delivering nanosecond pulsed electric fields may include: an elongated conduit body; a shape support member coupled to the elongated conduit body and configured to form a shape; a conductive braid configured to circumferentially surround the shape support member and form a first electrode; and one or more conductive strips configured to circumferentially surround a portion of the conductive braid and the shape support member and form a second electrode. The device may also include a tubular insulating member disposed between the shape support member and the conductive braid.

[0021] In some examples, the device may also include one or more tape insulators disposed between the conductive braid and the one or more conductive strips, the tape insulators being configured to electrically insulate the one or more conductive strips from the conductive braid. Furthermore, the position of the conductive strips may be configured to at least partially determine the density of the electric field.

[0022] In some other examples, the shape support member may be a nickel-titanium alloy. Furthermore, the shape support member may be conformable to the shape of the sinuses of the pulmonary veins. In some examples, the conductive braid and the one or more conductive strips may be configured to deliver bipolar nanosecond pulsed electrical therapy. In another example, the conductive braid and the one or more conductive strips may be configured to deliver monopolar nanosecond pulsed electrical therapy.

[0023] A method for delivering submicrosecond pulsed electric fields to a body's blood vessels may include: positioning an applicator comprising two or more electrodes within an identified treatment area; placing the two or more electrodes in contact with tissue within the identified treatment area; and applying pulsed electrical therapy via the two or more electrodes. In some examples, placing the two or more electrodes in contact with tissue may include deploying the two or more electrodes from an elongated catheter body. In some other examples, the two or more electrodes may include a first tangible electrode and a second tangible electrode. The first tangible electrode may have a first diameter and the second tangible electrode may have a second diameter, wherein the first diameter differs from the second diameter.

[0024] In some examples, the first tangible electrode may be disposed on a different plane than the second tangible electrode. In other examples, the first tangible electrode may be coplanar with the second tangible electrode.

[0025] In some examples, pulsed electrotherapy may include an electric field between two or more electrodes. In another example, pulsed electrotherapy may include an electric field between at least one of the two or more electrodes and a third electrode.

[0026] The devices described herein are typically configured to safely and reliably deliver pulses in the microsecond, nanosecond, and picosecond ranges, and may include electric fields with pulse widths ranging from 0.1 nanoseconds (ns) to less than 1000 nanoseconds or shorter (such as 1 picosecond), which may be referred to as submicrosecond pulsed electric fields. The pulse energy may have high peak voltages, such as 1 kV / cm to 5 kV / cm, 10 kV / cm, 20 kV / cm, 100 kV / cm, or higher. In some applications, the pulse energy may be less than 1 kV / cm. Treatment of biological cells can utilize multiple periodic pulses with frequencies ranging from 0.1 Hz to 100,000 Hz, and can trigger apoptosis, for example, in inwardly growing tissues causing restenosis. Selective treatment of the vessel wall with high-voltage, submicrosecond pulse energy can induce apoptosis within the restenosis-causing cells, while, due to its non-thermal nature, it substantially does not affect normal cells in the surrounding tissue. Subjects may be patients (human or non-human, including animals). Users may operate the devices described herein on subjects. Users can be physicians (doctors, surgeons, etc.), medical technicians, nurses, or other care providers.

[0027] Therefore, applying high-voltage, fast (e.g., microsecond or submicrosecond) electrical pulses may include applying a series of electrical pulses with pulse widths, for example, between 0.1 nanoseconds (ns) and 1000 nanoseconds. Applying high-voltage, fast electrical pulses may include applying a series of submicrosecond electrical pulses with peak voltages, for example, between 1 kilovolt per centimeter (kV / cm) and 500 kV / cm. Applying high-voltage, fast electrical pulses may include applying a series of submicrosecond electrical pulses with frequencies, for example, between 0.1 Hz and 100,000 Hz.

[0028] Any of these devices can be used in conjunction with a pulse generator. For example, this document describes a system for treating tissue that may include: an elongated applicator (e.g., an application tool) as described herein; a connector, such as a high-voltage connector adapted to couple the elongated application tool to a pulse generator; and a pulse generator configured to generate multiple electrical pulses having an amplitude of at least 0.1 kV and a duration of less than 1000 nanoseconds, the pulse generator including a port configured to connect to the high-voltage connector. In some examples, the application tool includes an elongated body having a distal end region from which one or more electrodes are configured to extend. In some examples, the distal end may be steerable (e.g., capable of joint movement).

[0029] As mentioned, any of these devices can be configured such that the proximal end of the application tool is adapted to be coupled to a robotic arm or movable arm, for example, for computer-controlled activation of the set of electrodes. Alternatively or additionally, the proximal end of the application tool may be adapted to be coupled to a handle of a pulse generator, which may then be adapted to be connected to a robotic arm.

[0030] In some examples, as described above, the device can be configured to adjust the distance between the electrodes to apply treatment at the distal end region of the applicator. In some examples, the applicator includes at least two circumferentially arranged electrodes, each circumferentially arranged around a support. The longitudinal position of one or both of the circumferentially arranged electrodes can be adjustable, such that the distance between the circumferentially arranged electrodes can be increased or decreased. In some cases, the applicator can be adjustable to adjust the spacing between the circumferentially arranged electrodes to, for example, between 5 mm and 40 mm (e.g., between 10 mm and 20 mm, etc.). The circumferentially arranged electrodes can be electrode rings (extending completely or partially circumferentially around the applicator), or they can be multiple individual electrodes circumferentially arranged around the applicator. Adjusting the spacing between the electrodes allows the user to adjust and / or correct the placement and allows the electrodes to fit within the inner wall or sinus, especially when the diameter / size of the blood vessel varies (including rapid changes) depending on the longitudinal position. One electrode ring can fit into one circumference, while another electrode ring can fit into a larger or smaller circumference, and in some examples, the spacing between the two electrodes can be adjusted.

[0031] In use, any of the devices described herein can be used to apply energy, particularly submicrosecond (e.g., nanosecond) pulsed fields. Submicrosecond pulsed electromagnetic fields can induce apoptosis in cellular structures.

[0032] For example, this document describes devices (e.g., apparatuses, systems, etc. including electrode applicators) for delivering pulsed electric fields within a body cavity. These devices may include: an elongated body (having an elongated flexible body); a first electrode including one or more first rings having a first active region formed on the first or more rings, wherein the first active region is arranged externally to the body cavity, and wherein the first or more rings are flexibly coupled to a distal end region of the elongated body; and a second electrode including one or more second rings having a second active region formed by the second or more rings, wherein the second active region is arranged externally to the body cavity, wherein the second or more rings are flexibly coupled to a distal end region of the elongated body, and wherein the first electrode is laterally offset from the second electrode along the distal end region of the elongated body.

[0033] In any of the devices described herein, each electrode of the device may include an elongated active region from which electrical energy is applied. For example, the active region may be a conductive (uninsulated) region of a conductive material (e.g., a conductive wire, etc.) configured to emit electrical energy. Generally, the devices described herein may include a first electrode having a first conductive region extending across multiple lengths of different loops forming the first electrode (or, in some examples, a second electrode). All loops of the first electrode (and thus all sub-regions of the loops forming the active region) may be electrically coupled together to form a single anode or a single cathode; and all loops forming the second electrode (and thus all sub-regions of the loops) may be electrically coupled together as a single anode or a single cathode.

[0034] In some examples, the first electrode comprises a single ring; in other examples, the first electrode comprises multiple rings forming the first electrode, and these rings are electrically connected. Similarly, the second electrode may be a single ring or multiple different rings.

[0035] In any of these devices, the first and / or second electrodes may be transverse to the distal end region of the elongated body, and / or the second electrode may be transverse to the distal end region of the elongated body. In any of these devices, the first and / or second electrodes may include a first plurality of rings arranged as flaps around the distal end region of the elongated body. The outer portion of each flap may form an active region for a single electrode. This configuration allows for more robust treatment around the entire periphery of the blood vessel without requiring multiple repositioning steps of the electrode pair to cover the same larger area around the circumference of the blood vessel.

[0036] Generally, the diameter of the first active region of the first electrode can be smaller than the diameter of the second active region (e.g., the diameter of the ring forming the first electrode and the diameter of the second active region of the second electrode can be different). In some examples, the diameters of the rings forming the first and second electrodes can be approximately the same.

[0037] Any of these devices may include an expandable frame. The expandable frame may be a balloon, a strut assembly, a mesh (e.g., an expandable wire mesh), etc. Generally, the first and second electrodes may be coupled to the outer periphery of the expandable member such that they are externally, at least partially, surrounding the periphery of the blood vessel. The expandable frame may support the first and second active electrodes. Therefore, the first and second electrodes may be arranged on the expandable frame. For example, the first and second electrodes may be arranged on an expandable balloon.

[0038] In any of these examples, the first electrode and the second electrode may each be formed from a wire, for example, a wire having a diameter of less than about 0.2 mm (less than about 0.19 mm, less than about 0.18 mm, less than about 0.17 mm, less than about 0.16 mm, less than about 0.15 mm, etc.).

[0039] Generally, the first and second electrodes are configured to flexibly conform to the body cavity, such that the active region extends circumferentially around the periphery of the cavity. As used herein, “arranged or configured to circumferentially surround the body cavity” can mean extending at least partially around the circumference of the body cavity (e.g., traveling in an arc less than 360 degrees, such as about 270 degrees or greater, such as 300 degrees or greater, 320 degrees or greater, 330 degrees or greater, 340 degrees or greater, 340 degrees or greater, about 360 degrees). Therefore, the first active region arranged to circumferentially surround the body cavity may include an active region extending completely or almost completely around the circumference of the cavity (circumferentially extending about 270 degrees or greater, about 300 degrees or greater, about 320 degrees or greater, about 330 degrees or greater, about 340 degrees or greater, about 340 degrees or greater, about 360 degrees, etc.). In some examples, the first active region is configured to circumferentially surround the body cavity in a nearly complete circle.

[0040] Any of these devices may include an external catheter or guiding sheath (e.g., a delivery catheter), wherein an elongated body forming or retaining the first electrode and the second electrode is slidably disposed within the external catheter. The first electrode and the second electrode are configured to collapse when retracted or introduced into the external catheter and / or to expand radially outward when extending outward from the distal end of the delivery (external) catheter.

[0041] The first electrode may be positioned distally relative to the end region of the elongated body, and the second electrode may be positioned proximal to the first electrode. In some examples, the longitudinal positions of the first and second electrodes may be fixed. In some examples, the longitudinal positions of the electrodes may be adjustable (e.g., variable). For example, the first electrode may be configured to slide axially proximal or distally relative to the second electrode.

[0042] In some examples, the first electrode may include an anode and the second electrode may include a cathode. The device may be configured to deliver pulsed energy between the first electrode (anode) and the second electrode (cathode).

[0043] In any of the examples described herein, the length of each of the first and second active regions may be greater than 5 cm. Each of the first and second active regions may have a diameter less than 0.2 mm.

[0044] This document also describes a device for delivering a pulsed electric field, the device comprising: an elongated conduit body; a first electrode including a first lead loop flexibly extending from the elongated conduit body, wherein the first lead loop flexibly extends from the elongated conduit body, and further wherein the first electrode has a first active region including at least a portion of the first lead loop and extending for a length greater than 5 cm; and a second electrode including a second lead loop flexibly extending from the elongated conduit body, wherein the second electrode has a second active region including at least a portion of the second lead loop and extending for a length greater than 5 cm.

[0045] The first and second active regions may be spaced a fixed distance apart from each other along the long axis of the elongated catheter body. The first and second electrodes may be configured to flexibly conform to the body's blood vessels. The first loop may be smaller than the second loop. Alternatively, in some examples, the first and second loops are the same size.

[0046] The first electrode may be positioned distally relative to the distal end of the elongated catheter body, and the second electrode may be positioned between the first electrode and the distal end of the elongated catheter body.

[0047] Generally, the device described herein is configured to advantageously apply energy between a first electrode and a second electrode in a circumferential region surrounding a blood vessel within the body, without requiring multiple repositioning steps to treat the entire (or most) circumference. This solves a problem with many other electrodelivery systems that respond to multiple discrete active regions that may leave gaps. The device described herein is particularly suitable for applying nanosecond pulses, but is not limited to this use. Nanosecond pulse energy can work by entering cells in a non-thermal manner and altering the function of internal organelles, including mitochondria and endoplasmic reticulum. For example, a nanosecond pulse electric field induces intracellular disruption, which leads to regulated cell death. In examples where the applied energy is a nanosecond (or faster) pulse electric field, the active region of each electrode can be long and thin, for example formed by wires, and the applied field can result in the application of very little thermal energy, thus preventing damage to non-cellular tissues.

[0048] For example, this article also describes a method for delivering a pulsed electric field to the wall of a body vessel in a subject, the method comprising: positioning a first electrode including one or more first lead loops and a second electrode including one or more second lead loops within the body vessel, such that a first active region of the first or more lead loops is electrically connected to a first circumference of the wall, and a second active region of the second or more lead loops is electrically connected to a second circumference of the wall, the second circumference of the wall being longitudinally separated from the first circumference of the wall; and applying pulsed electrical therapy between the first active region and the second active region.

[0049] Positioning the first and second electrodes may include deploying them from a delivery catheter by moving the delivery catheter relative to an elongated body coupled to the first and second electrodes, such that at least one of the first and second electrodes expands from a delivery configuration to a deployment configuration. In some examples, deploying the first electrode includes contacting its walls with a plurality of electrically continuous conductor segments of a first or more conductor loops. In some examples, deploying the second electrode includes contacting its walls with a plurality of electrically continuous conductor segments of a second or more conductor loops. Deploying the first electrode may include expanding the first electrode to have a larger diameter than the second electrode. In some examples, deployment includes deployment within a sinus of a pulmonary vein. For example, deployment may include deploying the first electrode such that the first electrode is coplanar with the second electrode.

[0050] As mentioned, applying pulsed electrical therapy may include applying an electric field between a first active region and a second active region. Specifically, applying pulsed electrical therapy may include applying a pulse with a duration of nanoseconds (less than 1000 ns).

[0051] This document also describes a device comprising: an elongated body extending proximally to distally, wherein the elongated body is configured to be inserted into a body vascular system; an applicator region located at a distal end region of the elongated body, the applicator region including a plurality of expandable ribs configured to expand outward from a collapsed configuration within the body vascular system; wherein each rib includes an uninsulated active region; and further wherein a first subset of the plurality of expandable ribs is configured to have a first polarity, and a second subset of the plurality of expandable ribs is configured to have a second polarity.

[0052] For example, the uninsulated active region on each of the plurality of ribs may be configured to be substantially straight and parallel to the long axis of a portion of the applicator region. In some embodiments, the uninsulated active flat region of each rib is also configured to maintain the same length during rib expansion, regardless of how much each rib is expanded. Each of the plurality of ribs may include a hinged region on each side of the uninsulated active region. The hinged region may be covered by a flexible insulator.

[0053] In some examples, the elongated body may include a first elongated member coupled to the proximal end of each rib and a second elongated member coupled to the distal end of each rib, wherein the first and second elongated members are configured to slide axially relative to each other so that the applicator region changes between a collapsed configuration and an expanded configuration in which the plurality of expandable ribs expand outward.

[0054] In any of these devices, each of the expandable ribs can be biased to expand outward. In any of these devices, the elongated body can be a flexible elongated body; the plurality of expandable ribs can be substantially flat.

[0055] Any of these devices may include an expandable member located within the applicator region and configured to expand outward to drive the expansion of the plurality of ribs.

[0056] In some examples, the applicator region is configured to expand outward relative to the long axis of the applicator region into a shape with a larger cross-sectional area, i.e., the distal side is larger than the proximal side, or in some examples, the proximal side is larger than the distal side. For example, the applicator region may include a teardrop shape.

[0057] The uninsulated active region of each rib is located within the distal portion of the applicator region, such that the uninsulated active region faces the distal side in the expanded configuration.

[0058] Any of the devices disclosed herein may include a centering guide that extends distally from the applicator region. In some examples, the centering guide may be configured and used as one of the electrodes.

[0059] In some examples described herein, the device may include: an elongated body extending proximally to distally, wherein the elongated body is configured for insertion into a body vascular system; an applicator region located at the distal end region of the elongated body, the applicator region including: a first wire and a second wire, the first wire extending distally from the elongated body having a first active region adjacent to a first insulating region of the first wire, and the second wire extending distally from the elongated body having a second active region adjacent to a second insulating region of the second wire; wherein the first active region and the second active region are separated by a minimum distance d, the minimum distance d being substantially constant along the length of the first active region; and further wherein the first active region is configured to have a first polarity, and the second active region is configured to have a second polarity. The first wire may include a first loop, and the second wire may include a second loop concentrically positioned relative to the first loop or positioned within the first loop. In any of these devices, the first and second wires may extend from the elongated body in a plane. In some examples, the insulating region and / or elongated body may include bends such that the first and second conductors extend at an angle relative to the long axis of the elongated body.

[0060] This document also describes devices (e.g., apparatuses, systems, etc.) for delivering pulsed energy in a point-by-point or single-treatment manner. Point-by-point treatment typically involves applying energy to a region between two smaller electrically active regions, while single-treatment typically utilizes multiple electrically coupled active regions to treat a larger region. For example, the device may include: an elongated body; a plurality of rings or ribs extending radially outward from the elongated body at a first circumferential position, wherein each ring or rib includes a radially outward-facing, uninsulated electrically active region such that the uninsulated electrically active region surrounds the first circumferential position of the elongated body; and an electrical connector configured to switch between a first configuration and a second configuration, in which the plurality of electrically active regions of the uninsulated electrically active region are electrically coupled together to apply energy of a first polarity, and in the second configuration, the uninsulated electrically active regions are individually activated.

[0061] In some examples, the electrical connector may electrically couple all uninsulated, electrically active regions of the rings or ribs in the plurality of rings or ribs in a first configuration. The electrical connector may be configured such that, in the first configuration, the connector electrically couples a first subset of the uninsulated, electrically active regions of the rings or ribs in the plurality of rings or ribs to apply energy of a first polarity, and a second plurality of rings or ribs alternating with the first plurality of rings or ribs to apply energy of a second polarity.

[0062] In some examples, a device for delivering pulsed energy in a point-by-point or single-shot manner may include: an elongated body; a plurality of rings or ribs extending radially outward from the elongated body at a first circumferential position, wherein each ring or rib includes a radially outward-facing, uninsulated, electrically active region such that the uninsulated electrically active region surrounds the first circumferential position of the elongated body; a second electrically active region circumferentially offset from the first circumferential position; and an electrical connector configured to switch between a first configuration and a second configuration, in which all uninsulated electrically active regions are electrically coupled together, and in a second configuration, the uninsulated electrically active regions are individually activated. The second electrically active region may include a second plurality of rings or ribs extending radially outward from the elongated body at a second circumferential position, wherein each of the second plurality of rings or ribs includes a radially outward-facing, uninsulated electrically active region such that the uninsulated electrically active region surrounds the second circumferential position of the elongated body. The same electrical connector or individual electrical connectors can be configured to switch between a first configuration and a second configuration, in which all uninsulated active regions of the second plurality of rings or ribs are electrically coupled together, and in the second configuration, the uninsulated active regions of the second plurality of rings or ribs are individually activated. In some examples, the second active region is a distally facing electrode extending from the distal end of the elongated body.

[0063] For example, this document describes a device for delivering a pulsed electric field to the wall of an anatomical structure, the device comprising: an elongated body; a first electrode including one or more first rings having a first active region formed on the one or more first rings, wherein the first active region is configured to externally connect to a first region of the wall of the anatomical structure, and wherein the one or more first rings are flexibly coupled to a distal end region of the elongated body; and a second electrode including one or more second rings having a second active region formed by the one or more second rings, wherein the second active region is configured to externally connect to a second region of the wall of the anatomical structure, wherein the one or more second rings are flexibly coupled to a distal end region of the elongated body, and wherein the first electrode is radially offset, laterally offset, or both radially and laterally offset from the second electrode.

[0064] Any of the devices described herein may be configured such that at least one of the first and second active regions is configured to circumferentially enclose the wall of the anatomical structure in a partial, nearly complete, or complete circle.

[0065] Any of these devices may include multiple mapping and / or sensing electrodes located on a portion of a first electrode and / or a second electrode. For example, the sensing and / or mapping electrodes may be radially inside a first active region and / or a second active region. The sensing and / or mapping electrodes may have a total surface area smaller than the surface area of ​​the electrically active region in the first electrically active region and / or the second electrically active region (e.g., 80% or less, 70% or less, 60% or less, 50% or less, 40% or less, 30% or less, 20% or less, 10% or less, 5% or less, etc.). The sensing and / or mapping electrodes may be electrically isolated from the electrically active regions and may each be connected via one or more lines (e.g., wires, traces, etc.) or may be connected to a mapping system and / or subsystem.

[0066] This document also describes a device for delivering a pulsed electric field, the device comprising: an elongated body; a first electrode including a first conductive loop flexibly extending from the elongated body, the first electrode having a first active region extending along the length of the first conductive loop; and a second electrode including a second conductive loop flexibly extending from the elongated body, the second electrode having a second active region extending along the length of the second conductive loop, wherein the first electrode is radially offset, laterally offset, or both radially and laterally offset from the second electrode. As mentioned above, any of these devices may include a plurality of mapping and / or electrodes outside the first active region on the first electrode and / or outside the second active region on the second electrode.

[0067] This document also describes a method for delivering pulsed electric fields to the walls of an anatomical structure within a subject using an applicator, the method comprising: positioning a first electrode of the applicator, including one or more first rings, and a second electrode of the applicator, including one or more second rings, within the subject, such that a first active region of the first or more rings forms a first contact ring electrically connected to a first region of the wall of the anatomical structure, and such that a second active region of the second or more rings forms a second contact ring electrically connected to a second region of the wall of the anatomical structure, the second contact ring being radially and / or longitudinally separated from the first region of the wall of the anatomical structure; and applying pulsed electrical therapy between the first active region and the second active region. Any of these methods may include: using one or more mapping sensors on the applicator to map the position of the applicator relative to the wall of the anatomical structure. Any of these methods may include: using one or more sensors on the applicator to sense one or more electrical properties of the wall of the anatomical structure before and / or during and / or after the application of pulsed electrical therapy.

[0068] Any of these methods can be methods for treating cardiac tissue, including ablation of cardiac tissue. For example, this document describes a method for delivering a pulsed electric field to the wall of a heart in a subject using an applicator, the method comprising: positioning a first electrode of the applicator, including one or more first rings, and a second electrode of the applicator, including one or more second rings, in the subject's body such that a first active region of the first or more rings forms a first contact ring electrically communicating with a first region of the heart wall (e.g., pulmonary sinus, pulmonary venous orifice, and / or other cardiac wall muscle / tissue), and such that a second active region of the second or more rings forms a second contact ring electrically communicating with a second region of the heart wall, the second contact ring being radially and / or longitudinally separated from the first region of the heart wall; and applying pulsed electrical therapy between the first and second active regions. Any of these methods may include: using one or more mapping sensors on the applicator to map the position of the applicator relative to the heart wall. In some examples, the method may include: using one or more sensors on the applicator to sense one or more electrical properties of the heart wall before and / or during and / or after applying pulsed electrical therapy. In any of these methods, the method may include mapping tissue (e.g., heart) using, for example, 3D electroanatomical mapping; in some examples, the method may include mapping or otherwise locating the applicator on a mapping map of the tissue.

[0069] This document also describes devices comprising: an elongated body extending from a proximal to a distal side; an applicator region located at a distal end region of the elongated body, the applicator region comprising: a first conductor and a second conductor, the first conductor extending distally from the elongated body, the first conductor having a first active region adjacent to a first insulating region of the first conductor, the second conductor extending distally from the elongated body, the second conductor having a second active region adjacent to a second insulating region of the second conductor; wherein the first active region and the second active region are separated by a minimum distance d, the minimum distance d being substantially constant along the length of the first active region, and further wherein the first active region is configured to have a first polarity and the second active region is configured to have a second polarity.

[0070] An apparatus may include: an elongated body extending from a proximal to a distal side; and an applicator region located at a distal end region of the elongated body, the applicator region including: an expandable member configured to expand radially relative to the elongated body; a first conductor located on the expandable member, the first conductor having a first active region adjacent to a first insulating region of the first conductor; and a second conductor located on the expandable member, the second conductor having a second active region adjacent to a second insulating region of the second conductor, wherein the first active region and the second active region are separated by a minimum distance d, the minimum distance d being substantially constant along the length of the first active region, wherein the first conductor and the second conductor have a thickness of 0.38 mm or less, and further wherein the first active region is configured to have a first polarity and the second active region is configured to have a second polarity.

[0071] All the methods and apparatuses described herein are envisioned in any combination (including combinations of the various features disclosed with reference to various examples) and can be used to achieve the benefits described herein. Attached Figure Description

[0072] A better understanding of the features and advantages of these methods and apparatus will be gained by referring to the following detailed description of exemplary embodiments and the accompanying drawings, which are as follows:

[0073] Figure 1 An example of a system for delivering high-voltage, fast-pulse electrical energy is shown.

[0074] Figure 2 An example of an applicator configured to deliver electrical therapy (such as nanosecond pulse energy therapy) within the body's blood vessels is shown.

[0075] Figure 3A An example of an applicator configured to deliver energy therapy circumferentially or point-by-point within the body's blood vessels is shown.

[0076] Figure 3B An example of an applicator configured to deliver energy therapy within the body's blood vessels and configured for "forward-facing" and "side-facing" energy application is shown.

[0077] Figure 4A and Figure 4B Another example of an applicator configured to deliver nanosecond pulse energy therapy within the body's blood vessels is shown.

[0078] Figure 4C This is another example of a device used to deliver energy (e.g., nanosecond pulses of electrical energy) within the body's blood vessels as a single emission or point-by-point delivery.

[0079] Figure 4D This is another example of a device used to deliver energy (e.g., nanosecond pulses of electrical energy) within the body's blood vessels as a single emission or point-by-point delivery.

[0080] Figure 4E This is another example of a device used to deliver energy (e.g., nanosecond pulses of electrical energy) within the body's blood vessels.

[0081] Figure 5 A diagram of the applicator shown in Figure 4, which is positioned within the pulmonary vein, is illustrated.

[0082] Figure 6A Another applicator configured to deliver nanosecond pulse energy therapy within the body's blood vessels is shown.

[0083] Figure 6B It shows the use of and Figure 6A An example of the effect of treatment performed by an applicator similar to that of an applicator.

[0084] Figure 7 It shows the relationship with Figure 4A The applicator shown is similar to another applicator configured to deliver nanosecond pulse energy therapy within the body's blood vessels.

[0085] Figure 8A and Figure 8B Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0086] Figure 8C Another example of an applicator is shown, in which the spacing between the electrodes is adjustable.

[0087] Figure 9 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0088] Figure 10Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0089] Figure 11 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0090] Figure 12 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0091] Figure 13 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0092] Figure 14 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0093] Figure 15 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0094] Figure 16 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0095] Figure 17A Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0096] Figure 17B It shows Figure 17A Further details regarding the applicator.

[0097] Figure 18 Showing the manufacturing process Figure 17A An example of a fixing device for an applicator.

[0098] Figure 19 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0099] Figure 20 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0100] Figure 21 Another applicator configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown.

[0101] Figures 22A to 22C An example of a device for delivering pulsed electrical energy within a cavity is shown.

[0102] Figures 23A to 23F An example of a device for delivering pulsed electrical energy within a cavity is shown.

[0103] Figures 24A to 24E It shows the use of devices such as Figures 22A to 22C The device shown is used for the treatment of model tissue.

[0104] Figure 25 An example of a device for delivering pulsed electrical energy within a cavity is shown.

[0105] Figure 26 A device for delivering pulsed electrical energy within an internal cavity is shown.

[0106] Figure 27 This demonstrates the application of energy around the pulmonary veins. Figure 26 The equipment.

[0107] Figure 28A An example of a device for delivering pulsed electrical energy within a cavity is shown. Figure 28B and Figure 28C It shows that in a narrow ( Figure 28B )inner cavity and larger ( Figure 28C ) Diameter of the inner cavity Figure 28A The equipment.

[0108] Figure 29A An example of a curved rib in the applicator region is shown.

[0109] Figure 29B An example of a hinged rib in the applicator region, as described herein, is shown.

[0110] Figure 30A A device for delivering pulsed electrical energy within the body's blood vessels (lumens) is shown. Figure 30B It shows Figure 30A An enlarged view of the hinge area of ​​the device.

[0111] Figure 31 A device for delivering pulsed electrical energy within an intraluminal cavity is shown, the device comprising a balloon to expand the applicator region.

[0112] Figure 32 A device for delivering pulsed electrical energy within an internal cavity is shown.

[0113] Figure 33 It shows Figure 32 Another view of the device.

[0114] Figures 34A to 34C An example of a paddle-shaped device for delivering pulsed electrical energy within a cavity is shown.

[0115] Figure 35 An example of a device for delivering pulsed electrical energy within a cavity is shown.

[0116] Figures 36A to 36DAnother example of a device for delivering pulsed electrical energy within a cavity is shown.

[0117] Figure 37 The difficulty of using a positioning device to treat pulmonary veins is illustrated.

[0118] Figures 38A to 38B A device for delivering pulsed electrical energy within a cavity, including a centering guide, is shown.

[0119] Figure 39 This is an example of a device that includes a centering guide for delivering pulsed electrical energy within a cavity.

[0120] Figures 40A to 40D A method is shown using a device for delivering pulsed electrical energy within a cavity using a centering guide.

[0121] Figures 41A to 41D A method is shown using a device for delivering pulsed electrical energy within a cavity using a centering guide.

[0122] Figure 42 This is a flowchart illustrating an example of a method for delivering pulsed electrical therapy to a selected treatment area of ​​a patient.

[0123] Figures 43A to 43B An example of an applicator including a therapeutic electrode and a sensing / mapping sensor is shown. Figure 43A A view of the distal end is shown, and Figure 43B A side perspective view is shown.

[0124] Figure 43C The illustration shows, for example, Figures 43A to 43B An example of an applicator system is shown.

[0125] Figures 44A to 44D An example of a device including small-diameter wire electrodes as described herein is shown. Detailed Implementation

[0126] This document describes systems and methods for treating the body (including internal cavities such as body vessels) using pulsed electric fields with electrodes suitable for insertion into body vessels (such as, for example, arteries, veins, sinuses, and any other vessels within the body as described above). Generally, the devices and methods described herein can be positioned inside any body cavity (including, but not limited to, internal cavities of the body, such as tubular body cavities or vessels), against any wall of an organ, and / or in transitional regions (e.g., sinuses, ostia, etc.).

[0127] In some cases, bodily vessels may have irregular or varied shapes. For example, the sinuses of pulmonary veins can transition from a relatively large area or diameter to a relatively small area or diameter. These bodily vessel surfaces may make it difficult for electrodes to establish effective contact for therapeutic purposes. This article describes various electrodes that can be readily adapted and conformed to irregular and / or varied shapes and provide positive contact with bodily vessels.

[0128] Pulsed electrotherapy can be microsecond pulse therapy or submicrosecond pulse therapy, including nanosecond pulses. For example, nanosecond pulsed electric field therapy can refer to the application of a relatively high voltage (in some cases, 5 kV or greater) for a relatively short duration (in some cases, between about 1 nanosecond and 999 ns). These high voltages and short durations generate a pulsed electric field in the region where the voltage is applied. In some cases, nanosecond pulses can induce apoptosis within cellular structures, which can reduce cellular inflammatory responses.

[0129] Any of the methods described herein can be an ablation method. For example, the methods described herein can be specifically used to treat cardiac regions, blood vessels, etc., such as, but not limited to, sinuses. In some examples, these methods and devices can be used to treat atrial fibrillation and other cardiac conditions, including for ablation of cardiac tissue. As will be described in more detail below, any of these methods and devices can be used to treat body regions with a conical or narrowed profile, such as the sinuses of the pulmonary veins. Thus, in some examples, the devices and methods described herein are suitable for use in cases where the shape of the body lumen in which these devices and methods are used has a diameter that changes abruptly.

[0130] Alternatively or additionally, these devices and methods can be used to treat the walls of blood vessels or other lumens that are not necessarily constricted or only slightly constricted. In some examples, these methods and devices can be used to treat the walls of vascular or respiratory lumens. For example, these methods and devices can be used to treat arterial stenosis, including in conjunction with stenting or angioplasty procedures. Therefore, in some cases, these methods can be performed within the first 2 to 4 days after angioplasty and / or stenting. Untreated smooth muscle cells (SMCs) at the luminal surface in non-endothelialized areas can continue to proliferate at a low rate. The methods and devices described herein can prevent or reduce this.

[0131] Figure 1An example of a system 100 for delivering rapid pulsed electrical energy is shown (also referred to herein by way of example as a submicrosecond generation system). This system may include an elongated application tool 102, a pulse generator 107, a foot switch 103, and a user interface 104. The foot switch 103 is connected via a cable and connector 106 to a housing 105 (which may enclose electronic components). The elongated application tool 102 may include electrodes and is connected via a cable 137 and a high-voltage connector 112 to the housing 105 and the electronic components therein. The system 100 may also include a handle 110 and a storage drawer 108. The system 100 may also include a retainer (e.g., a sheath, carrier, etc.) (not shown) configured to hold the elongated application tool 102. In some examples, the system may be configured for monopolar therapy and may optionally include a dispersive electrode 133 (e.g., a return electrode pad).

[0132] The application tool can be any of the devices used to deliver pulsed electric fields within the body's blood vessels, as described in detail herein. These devices typically include an elongated, flexible body (collectively referred to herein as an elongated body, catheter, or elongated catheter body) with one or more electrodes at its distal end, including electrodes forming one or more loops that can apply a pulsed electric field to the body. In some cases, the elongated application tool 102 includes one or more imaging sensors, such as one or more cameras and / or optical fibers, at or near its distal end. The camera (not shown for simplicity) may be forward-facing and / or side-facing. The system 100 may be configured to display images (in real-time and / or recorded) captured by the elongated application tool 102 to identify target treatment areas and / or zones.

[0133] Human operators can select the number of pulses, amplitude, pulse duration, and frequency information, for example, by inputting such parameters into a numeric keypad or touchscreen of user interface 104. In some examples, the pulse width can be varied. A microcontroller can send signals to pulse control elements within system 100. In some examples, fiber optic cables are used, which allow control signals to be transmitted while also electrically isolating the contents of the metal enclosure (e.g., housing 105) from the submicrosecond pulse generation system 100 (e.g., high-voltage circuitry). For further electrical insulation, system 100 can be powered by a battery instead of a wall-mounted power outlet.

[0134] The slender application tool 102 may be handheld (e.g., held by a user) or a movable arm that can be attached to a robotic system, and its operation may be at least partially or fully automated, including computer-controlled operation.

[0135] Figure 2An example of an applicator 200 configured to deliver therapy (such as nanosecond pulsed energy therapy) within a body vascular system is shown. The body vascular system can be any feasible vascular system, including but not limited to sinuses of pulmonary veins or the pulmonary veins themselves. In this example, the applicator 200 may include a proximal ring 210, a distal ring 220, and an elongated catheter body 230. Although the applicator 200 is shown as having two rings 210 and 220, in other examples, the applicator 200 may include any feasible number of rings. The term "distal" generally refers to the portion closest to the distal end of the applicator (and closest to the treated tissue / surface), and the term "proximal" generally refers to the portion relatively distant from the distal end of the applicator and the treated tissue / surface. However, those skilled in the art will recognize that other terms may be used to identify and distinguish features of the applicator 200, including the proximal ring 210 and the distal ring 220. For example, the proximal ring 210 and the distal ring 220 may be referred to as a first ring and a second ring.

[0136] The proximal ring 210 and distal ring 220 can be formed of any conformal material. In at least one example, the proximal ring 210 and distal ring 220 can be formed of nitinol (e.g., nickel-titanium), however any other feasible material, such as stainless steel, can be used. As shown in the exemplary applicator 200, the proximal ring 210 may have a larger diameter than the distal ring 220. In other examples, the proximal ring 210 may have a smaller diameter than the distal ring 220.

[0137] The proximal ring 210 and distal ring 220 can be used as circular electrodes to deliver, for example, nanosecond pulse energy to a selected treatment area. In this example, the entire outer periphery of each of the rings 220, 210 can be an active region (e.g., electrically continuous), such that the outer periphery of the ring, rather than the inner arms 211, 221 (which may be insulated), forms the active region for applying electrical energy. In some examples, the proximal ring 210 and distal ring 220 can be retracted into the catheter body 230. The applicator 200 can then be positioned in the treatment area. After confirming the placement of the applicator 200, the proximal ring 210 and distal ring 220 can then be deployed from the catheter 230.

[0138] In some examples, the annular electrodes 210 and 220 are not deployed from within the catheter body 230, but may be housed together with the catheter body 230 within the delivery catheter; once at or near the target treatment site within the body, the distal end of the device (e.g., the annular electrode in this example) can be deployed outside the delivery catheter. For example, the entire device (including the catheter body and electrodes) may be inserted into the proximal end of the delivery catheter (also referred to herein as a guide sheath). The guide sheath may already be in the patient's body such that the distal end of the sheath is positioned near the target area (e.g., in or near the left atrium in some examples). The elongated catheter body and electrodes (e.g., the annular electrodes) may be inserted into the proximal valve of the guide sheath using a guide (e.g., a plastic tube), and the device may slide distally within the sheath. In some examples, the delivery catheter, retaining the distal end (e.g., the annular electrode), may be advanced into the target tissue and then held in place while the distal end is driven out of the delivery catheter.

[0139] The proximal ring 210 may include two flaps. That is, the proximal ring 210 may be divided into two semicircular portions that engage with the arm 211. In some examples, the arm 211 may be insulated. Similarly, the distal ring 220 may include two flaps that engage with the arm 221. In other examples, the proximal ring 210 and the distal ring 220 may include any number of flaps and arms. In some cases, increasing the number of flaps may increase the flexibility of the proximal ring 210 and the distal ring 220, making them more easily conformable to different shapes of body vessels, thereby allowing the electrodes of the rings to be well juxtaposed with the target tissue. In some examples, the arms 211 and 221 may be formed of nitinol or any other feasible material. The arms 211 and 221 may be flexibly coupled to the proximal ring 210 and the distal ring 220 to the elongated catheter body 230. Note that in any of the devices described herein, the entire device may be referred to as a “catheter,” and the elongated, generally flexible body portion extending from the distal end may be referred to as the catheter body (e.g., catheter body 230). Electrodes extending from the distal end of the elongated catheter body may be movable relative to the distal end of the elongated catheter body, or they may be fixed relative to the distal end.

[0140] Figure 2 A distance 240 separating the proximal ring 210 and the distal ring 220 is shown. For example, distance 240 may describe the distance between a plane that typically includes the proximal ring 210 and a plane that typically includes the distal ring 220. When deploying the proximal ring 210 and the distal ring 220, distance 240 may be predetermined or may be variable and determined by the user. In some examples, the voltage potential between the proximal ring 210 and the distal ring 220, as well as distance 240, may determine the electric field density that can be delivered by the applicator 200. For example, a relatively smaller distance 240 may provide a higher electric field density compared to a relatively larger distance 240.

[0141] In some examples, the applicator 200 may consist of an elongated catheter body 230 and a proximal handle (such as, Figure 1 The handle portion of the elongated application tool 102 shown is guided to the identified treatment area. In some examples, the applicator 200 may also be guided by a guide wire (not shown for simplicity) and / or by using a fluoroscope. The device described herein (e.g., applicator 200) may include a central lumen (e.g., extending through the elongated catheter body) that allows operation of the device via the guide wire. Alternatively, a quick-change lumen may be present on one side of the distal end of the applicator.

[0142] The distal end of the device can be positioned within the approximate area of ​​the tissue to be treated (target tissue area), and the annular electrodes (e.g., proximal ring 210 and distal ring 220) can expand outwards, such as... Figure 3A As shown. Proximal ring 210 and distal ring 220 are flexibly coupled to and protrude from elongated catheter body 230 and are juxtaposed with body vessels. The precise positioning of the applicator 200, including the annular electrodes, can be verified, and / or the device can be repositioned before energy is applied.

[0143] Nanosecond pulsed energy therapy can then be initiated onto the body's blood vessels. In some examples, system 100 and applicator 200 can be configured for bipolar operation, for example, between proximal ring 210 and distal ring 220. In some examples, proximal ring 210 can be referred to as the cathode and distal ring 220 as the anode (or vice versa). In other examples, proximal ring 210 can be associated with a signal having a negative signal, and distal ring 220 can be associated with a signal having a positive signal. Proximal ring 210 and distal ring 220 can be used as electrodes to deliver nanosecond pulsed energy. Electrodes carrying signals of opposite polarity allow an electric field associated with the pulsed therapy to be generated between the electrodes. In some examples, system 100 (including applicator 200) can be configured for unipolar operation. For example, the proximal ring 210 and the distal ring 220 may be electrically coupled to each other, and signals may be applied between the proximal and distal rings and a return electrode (e.g., another conductor, such as a portion of the elongated catheter body 230, or a conductive pad or electrode) that can be in contact with the patient.

[0144] After delivering nanosecond pulse energy therapy, the applicator 200 can be moved to another area of ​​the body's blood vessels or removed from the patient.

[0145] Any of the devices described herein can also be resilient and configured for use in expandable and contractile body regions, such as during diastole / systole, respiration, etc. For example, as just described, electrodes can be formed into loops (or partial loops) that can be flexibly coupled to the distal end region of the catheter body. Flexible coupling can be achieved via wires or other components that allow the loops to bend with tissue movement while remaining in place within the tissue.

[0146] Figure 3A Another example of an applicator 300 configured to deliver therapy (such as nanosecond pulsed energy therapy) within the body's blood vessels is shown. Similar to... Figure 2 The applicator 200, applicator 300 may include a proximal ring 210, a distal ring 220, arms 211 and 221, and an elongated catheter body 230. The applicator 300 may also include a point-by-point ablation tip 310. The point-by-point ablation tip 310 may be disposed distally on the elongated catheter body 230 relative to the distal ring 220. In some examples, the point-by-point ablation tip 310 may provide targeted therapy independently of and separately from the proximal and distal rings 210 and 220. Thus, the point-by-point ablation tip 310 may include one or more electrodes to deliver nanosecond pulse energy (not shown for simplicity). Alternatively, in some examples, point-by-point ablation may be achieved using a subset of ring or flap electrodes extending outward from the elongated body (elongated catheter body) 230. This will be referenced below. Figure 7 and Figures 32 to 33 To describe in more detail.

[0147] Figure 3B Another example of a device is that is configured to apply circumferential treatment over a large area or point-by-point treatment over a smaller area using the “forward-facing” or “side-facing” methods described below. Figure 3B The device shown is configured as a 3-polarity ablation device, wherein an electric field can be applied between a distal ring 314, which is maintained in a first polarity (polarity 1), and a central electrode 310, which is maintained in a second polarity (polarity 2). The distal end or "front" of the device can "face" the tissue. Alternatively, energy can be applied between the distal ring 314 (e.g., in polarity 1) and a proximal ring 312, which can be set to polarity 2. The sides of the device can face the tissue. Thus, the device (applier 300') can be used to apply small (point) energy to a larger area or a single (e.g., circumferential) energy application.

[0148] Figure 3B The device shown can also apply treatment to a smaller area using only a portion of the distal or proximal ring (or both). For example, in Figure 3BIn this configuration, the distal ring 314 is formed by three sub-regions 314', 314" and 314"', which are electrically coupled together to form a single electrode. Similarly, the proximal ring 312 is also formed by three sub-regions 312', 312" and 312"' coupled together to form a single electrode. The device can also be configured to apply energy only between one or two sub-regions of the distal ring (or between a sub-region and a single central electrode, or between a sub-region and the entire proximal ring) to apply energy over a smaller area. Thus, in some configurations, each sub-region within the sub-rings can be powered individually. In some examples, adjacent sub-regions of the same ring can be used with different polarities to apply energy between them.

[0149] Figure 3A and Figure 3B The applicators 300, 300' are shown in deployment mode, for example, relative to a body vascular 320. An example of the body vascular 320 may be a pulmonary vein, which may include a sinus 325. The size of the sinus 325 may transition from a first diameter to a second diameter. Thus, the different diameters of the proximal ring 210 and the distal ring 220 advantageously allow the applicator 300 to adapt to different shapes of the sinus 325. In some examples, the diameters of the proximal and distal rings are different (e.g., the proximal ring is larger than the distal ring). In some examples, one (or both) of the proximal and distal rings is configured such that the diameter is adjustable, which allows the device to recognize different shapes and diameters.

[0150] In any of the devices described herein, the first ring and the second ring may be referred to as electrode rings, or simply as “electrodes.” In some examples, the first electrode (e.g., proximal electrode ring 210) is configured to have one or more rings ( Figure 2 Two rings are shown in the image, while the following description... Figure 4A Five rings are shown, and an electrically active region (“active region”) is formed on one or more rings. The active region is a conductive area configured to contact target tissue and apply a pulsed electric field therebetween. Compared to other areas of the rings, the active region may be exposed (e.g., may include a conductive surface) and uninsulated. All these conductive regions are electrically connected, for example, to form a single electrode. Therefore, the active region is typically long and narrow, for example, formed by a conductor, part of the one or more rings.

[0151] In the exemplary applicator 300, arms 211 and 221 are shown offset relative to each other by approximately ninety degrees. In other examples, arms 211 and 221 may be offset by any feasible amount. Applicator 300 can be used for a variety of cardiac applications, such as the treatment of atrial fibrillation, the treatment of ventricular tachycardia, and other cardiac-related ablation. However, the applicator is not limited to cardiac applications and can be used to apply electrical energy to other parts of the body.

[0152] Figure 4A Another example of an applicator 400 configured to deliver nanosecond pulsed energy therapy within the body's blood vessels is shown. The applicator 400 may include a proximal ring 410 and a distal ring 420. The proximal ring 410 and distal ring 420 may each include five flaps. Additionally, the applicator 400 may include five arms 430 to flexibly couple the proximal ring 410 and distal ring 420 to an elongated catheter body (not shown). As described above, the proximal ring 410 and distal ring 420 with relatively more flaps may be more flexible than proximal and distal rings with fewer flaps. Figure 4B A side view of the applicator 400 is shown. The proximal ring 410 and distal ring 420, as well as the arm 430, are shown coupled to the elongated catheter body 440.

[0153] Figures 4C to 4E Examples of applicators that can be used to deliver nanosecond pulsed electrical energy therapy within the body's blood vessels are shown. These examples are related to... Figure 2 , Figures 3A to 3B and Figures 4A to 4B The examples shown are similar; they may include multiple electrode rings that can be selectively activated to apply bipolar energy for treating tissue. These devices may also be referred to as conformal ring devices, which can be used to apply energy to tissue within the body. In a non-limiting example, Figures 4C to 4E The device shown can be used to apply bipolar electrical energy to myocardial tissue (such as for treating pulmonary veins), including but not limited to sinuses, ostia, and medial / lateral walls.

[0154] As mentioned above, regarding Figures 4A to 4B In some examples, the device described herein includes two electrode rings, an inner ring and an outer ring, which can be used to treat tissues, including (but not limited to) myocardial tissue in the sinuses and / or sinus ostia. In some examples, additional rings may be used. For example, Figure 4C The device shown includes three rings. Figure 4D An example with four rings is shown. Figure 4E An example of two rings with a central electrode is shown. These configurations can also be adapted to the patient's anatomy and can help achieve both single-treatment (e.g., treatment of an entire area, such as the circumference of a blood vessel, in a single treatment, including ablation) and point-by-point treatment (e.g., treatment of small portions of the body's blood vessels one at a time, including ablation).

[0155] Figure 4CAn example configuration of an applicator 460 device with three electrode rings (including an outer ring 461 with a diameter of approximately 30 mm) is shown. The outer electrode may be formed of multiple sub-regions (e.g., lobes or rings) that may be electrically coupled together to apply a first polarity; in some examples, the individual sub-regions may be activated independently. Figure 4C It also includes a second ring 463, which is smaller than the first ring and arranged concentrically. Figure 4C In this design, the second ring has a diameter of approximately 23 mm and may also be formed of multiple sub-regions that are electrically coupled to provide a second polarity. In some examples, these multiple sub-regions may also be activated individually. The same device may also include a third ring 465, which is arranged concentrically relative to the second ring and may similarly be formed of multiple sub-regions that are electrically coupled to provide a first polarity. Figure 4C In the first configuration, the third ring has a diameter of approximately 16 mm. The outer and middle rings can be used to treat larger sinuses and / or ostia, while the second configuration allows the second and third rings to be used for treatment in smaller sinuses and / or ostia. The varying diameters and / or numbers of the rings allow the system to select which pair of rings (in which polarity) to specify, providing greater adjustment and fit when treating tissue areas of different sizes, such as (but not limited to) sinuses and / or ostia.

[0156] For example, in Figure 4D In this device, four concentrically arranged rings are included. An outer electrode (ring 481) may be formed from multiple sub-regions electrically coupled together to apply a first polarity; in some examples, each sub-region may be activated independently. A second ring 483 is concentrically arranged relative to the first ring and may also be formed from multiple sub-regions electrically coupled together to provide a second polarity or may be activated independently (powered). A smaller circumference third ring 485 is concentrically arranged relative to the second ring and may similarly be formed from multiple sub-regions electrically coupled together to provide the first polarity. Finally, an even smaller circumference fourth electrode (ring 487) is concentrically arranged relative to the third ring.

[0157] like Figure 4E As shown, any of these devices can provide a small (e.g., point) central electrode. Figure 4E and Figure 4A and Figure 4B The similarity lies in having two concentrically arranged electrode rings. The first ring electrode 491 can be formed from multiple sub-region electrodes, each formed from a wire with an exposed electrically active region. As in any of these examples, in some configurations, each sub-region can be individually controlled and / or they can all be electrically coupled together to form a single electrode. The second ring electrode 493 is concentrically arranged relative to the first ring electrode and can be formed from multiple sub-regions, just like the first ring electrode. Finally, Figure 4E The example shown may also include a single central electrode 495, which may be configured to apply a polarity opposite to that applied to a larger outer ring (or a sub-region of the outer ring) or an inner ring (or a sub-region of the inner ring).

[0158] Any of these devices can be used as the distal portion of a slender body (such as a catheter) and can be used to treat, for example, atrial fibrillation. Treatment of atrial fibrillation can include a variety of target sites, including but not limited to: pulmonary vein (PV) sinuses, PV ostia, and cardiac wall muscle / tissue. As described herein, these devices can be used to treat large areas (e.g., with a single application of submicrosecond pulsed energy), for example, to treat pulmonary vein sinuses / ostia of different sizes, and / or have the ability to provide point-by-point tissue treatment (e.g., ablation) throughout the cardiac anatomy. These devices can also be used to apply submicrosecond treatments in other parts of the body. For example, a larger diameter outer ring can be used for single-application treatment of sinuses and ostia, while a smaller inner ring can be used for point-by-point ablation of target tissues. Due to the conformability and adjustability of these configurations, treatment can be achieved more efficiently, while also being able to be adjusted / adapted to anatomical structures of different sizes.

[0159] Figure 5 The illustration 500 shows the applicator 400 of Figure 4 disposed within the sinus 510 of the pulmonary vein. The proximal ring 410 and the distal ring 420 are conformable to the surface of the pulmonary vein.

[0160] Figure 6A Another applicator 600 configured to deliver therapy (such as nanosecond pulsed energy therapy) within the body's blood vessels is shown. Applicator 600 may include a first ring 610, a second ring 620, an elongated catheter body 630, and an arm 640. The arm 640 electrically and flexibly couples the first ring 610 and the second ring 620 to system 100 (not shown) via the elongated catheter body 630. The first ring 610, the second ring 620, and the arm 640 may be formed of nitinol or any other feasible material. Additionally, the first ring 610 may have a first diameter, and the second ring 620 may have a second diameter different from the first diameter. The different diameters may at least partially determine the density of the electric field associated with nanosecond pulsed energy therapy. Although two flaps are shown, the first ring 610 and the second ring 620 may include any feasible number of flaps. The first ring 610 and the second ring 620 may collapse and retract into a delivery catheter (not shown), or in some embodiments, into an elongated catheter body 630 to allow placement of the applicator 600 relative to the treatment area.

[0161] Compared to applicators 200, 300, and 400, the first ring 610 and the second ring 620 of applicator 600 are substantially coplanar. This coplanar arrangement allows the electrodes (e.g., the first ring 610 and the second ring 620) to provide better contact with planar tissue and / or tissues shaped like sinuses of the pulmonary veins. In some examples, the electrodes may even have a "funnel" configuration facing in the opposite direction to the sinuses of the pulmonary veins.

[0162] The applicator 600 can be configured for bipolar operation. Pulse energy can be transferred between a first ring 610 and a second ring 620. Thus, the first ring 610 can be associated with a signal having a first polarity (e.g., a positive signal), and the second ring 620 can be associated with a signal having a second polarity (e.g., a negative signal). In other examples, the first ring 610 can be associated with a signal having a negative signal, and the second ring 620 can be associated with a signal having a positive signal. In yet another example, the applicator 600 can be configured for unipolar operation. For example, the first ring 610 and the second ring 620 can be electrically coupled together and can be used with a return electrode (e.g., on an elongated conduit body 630 or a conductive pad).

[0163] Figure 6B The diagram shows the use of... Figure 6A The example shown is an applicator similar to the one used to treat model tissue 651. Figure 6B In China, use and Figure 6A A similar applicator is used to apply nanosecond pulsed treatment to model tissue (potatoes immersed in saline solution), where treatment of two regions 653, 653' is shown (e.g., the device is applied twice). Specifically, the applicator has been used to apply pulsed electrical treatment to two target regions. Two annular regions are formed by applying a first annular electrode and a second annular electrode. In this example, a darker area of ​​the test tissue shows the effect of the nanosecond pulsed electric field on the target tissue model. For each of the two applied treatments (shown as overlapping in this example), approximately 320 degrees were treated; 357 shows a small gap where the active area of ​​the electrode is not covered.

[0164] Figure 7Another applicator 700 configured to deliver nanosecond pulsed energy therapy within the body's blood vessels is shown. The applicator 700 may include a first ring 710, a second ring 720, an elongated catheter body 730, and an arm 740. The arm 740 electrically and flexibly couples the first ring 710 and the second ring 720 to system 100 (not shown) via the elongated catheter body 730. The first ring 710, the second ring 720, and the arm 740 may be formed of nitinol or any other feasible material. Additionally, the first ring 710 may have a first diameter, and the second ring 720 may have a second diameter different from the first diameter. The different diameters may at least partially determine the density of the electric field associated with the nanosecond pulsed energy therapy.

[0165] Figure 7 The rings within can be formed from multiple sub-parts (“lobes”) as shown. For example, in Figure 7 In this system, each ring comprises five sub-sections. These sub-sections can be configured to act as a single ring, for example, by applying energy together to all sub-sections, or one or more sub-sections (lobes) can be activated individually. For example, in... Figure 7 In this configuration, the outer lower sub-part 733 and the inner lower sub-part 734 can be activated without activating adjacent sub-parts. The use of these ring sub-parts allows the device to be used for point-by-point treatment, thereby providing a smaller treatment area, as described herein.

[0166] Similar to Figure 6A The applicator 600, with its first ring 710 and second ring 720, is substantially coplanar. Therefore, the function and use of the applicator 700 can be similar to that of the applicator 600. The applicator 700 is shown as having five lobes, but in other examples, other numbers of lobes are possible. As mentioned above, an applicator with relatively more lobes is more flexible than an applicator with relatively fewer lobes, and therefore can be more easily adapted to some bodily vessels.

[0167] The applicator 700 can be configured for bipolar operation. Pulsed energy can be applied between the first ring 710 and the second ring 720. In some examples, the first ring 710 can be configured as the anode and the second ring 720 as the cathode (or vice versa). In another example, the applicator 700 can be configured for unipolar operation. For example, the first ring 710 and the second ring 720 can be coupled together, and a return electrode (on another portion of the elongated catheter body 730 or on a conductive pad or electrode) can contact the patient.

[0168] Figure 8A and Figure 8BAnother applicator 800 configured to deliver energy (such as nanosecond pulsed energy therapy) into the body's blood vessels is shown. Applicator 800 may include a proximal ring 810, a proximal arm 811, a distal ring 820, a distal arm 821, and an elongated catheter body 830. The proximal arm 811 and distal arm 821 may be electrically and flexibly coupled to system 100 (not shown) via the elongated catheter body 830. The proximal ring 810 and distal ring 820, as well as the proximal arm 811 and distal arm 821, may be formed of nitinol or any other feasible material. Additionally, the proximal ring 810 may have a first diameter, and the distal ring 820 may have a second diameter different from the first diameter. The different diameters may at least partially determine the density of the electric field associated with nanosecond pulsed energy therapy. The proximal ring 810 and distal ring 820 can collapse and retract into the elongated catheter body 830 to allow placement of the applicator 800 relative to the treatment area.

[0169] The proximal ring 810 and the distal ring 820 are separable by a distance 840. In some examples, the proximal ring 810 and the distal ring 820 are retractable relative to the elongated conduit body 830 and / or relative to each other. Thus, the distance 840 can be changed by retracting or extending one or both of the proximal ring 810 and the distal ring 820. In some examples, the elongated application tool 102 can control the distance 840 by retracting (positioning) the proximal ring 810 and / or the distal ring 820 by moving control lines, push rods, prestressing tendons, cables, etc.

[0170] The applicator 800 can be configured for bipolar operation. Pulsed energy can be transferred between the proximal ring 810 and the distal ring 820. Therefore, the proximal ring 810 can be the anode and the distal ring can be the cathode, or vice versa. In other examples, the applicator 800 can be configured for unipolar operation.

[0171] In some examples, the proximal ring 810 and the distal ring 820 may not form a continuous circle. The region 850 of the distal ring 820 is... Figure 8B The image is magnified to show details. The distal arm 821 can be bent to form the distal ring 820. For example, the distal ring 820 is bent to the right, as shown in region 850. However, the tip of the distal ring 820 is not connected to or attached to the distal arm 821. Leaving the end of the distal ring 820 unconnected provides increased flexibility to the distal ring 820. Although not shown, the proximal ring 810 and proximal arm 811 can have similar features.

[0172] Figure 8C It shows the relationship with Figure 8A Another example and view of an applicator similar to applicator 800. In this view, the distance 840 between the proximal ring 810 and the distal ring 820 is shown relative to... Figure 8AThe distance 840 between the applicator 800 is increased. For example, the proximal ring 810 and / or the distal ring 820 can be moved to increase the distance 840 between the respective rings. As described above, changing the distance 840 can affect the density of the electric field associated with nanosecond pulse energy therapy.

[0173] Figure 9 Another applicator 900 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels is shown. The applicator 900 may include a proximal ring 910, a proximal arm 911, a distal ring 920, a distal arm 921, and an elongated catheter body 930. The proximal ring 910 and distal ring 920, as well as the proximal arm 911 and distal arm 921, may be formed of nitinol or any other feasible material. Additionally, the proximal ring 910 may have a first diameter, and the distal ring 920 may have a second diameter different from the first diameter. The different diameters may at least partially determine the density of the electric field associated with the nanosecond pulsed energy therapy. Although six flaps are shown, the proximal ring 910 and distal ring 920 may include any feasible number of flaps.

[0174] The applicator 900 can be configured for bipolar operation. Pulsed energy can be transferred between the proximal ring 910 and the distal ring 920. The proximal ring 910 can be a cathode, and the distal ring 920 can be an anode (or vice versa). In another example, the applicator 900 can be configured for unipolar operation.

[0175] Figure 10 Another applicator 1000 configured to deliver submicrosecond pulsed energy therapy into the body's blood vessels is shown. The applicator 1000 may include a proximal ring 1010, a distal ring 1020, an expandable sphere 1025, and an elongated catheter body 1030. The proximal ring 1010 and distal ring 1020 may be coupled to system 100 (also not shown) via conductors (not shown) and the elongated catheter body 1030. The proximal ring 1010 and distal ring 1020, as well as the expandable sphere 1025, may be formed of nitinol or any other feasible material. In some examples, the proximal ring 1010 and distal ring 1020 may be electrically insulated from the expandable sphere 1025.

[0176] The proximal ring 1010 and the distal ring 1020 may be disposed on and / or coupled to the expandable sphere 1025. Thus, the expandable sphere 1025, as well as the proximal ring 1010 and the distal ring 1020, can collapse and retract into the delivery catheter or sheath to allow the applicator 1000 to be positioned relative to the treatment area.

[0177] Additionally, the proximal ring 1010 may have a first diameter, and the distal ring 1020 may have a second diameter different from the first diameter. The different diameters may at least partially determine the density of the electric field associated with nanosecond pulsed energy therapy. Although six lobes are shown, the proximal ring 1010 and distal ring 1020 may include any feasible number of lobes.

[0178] The applicator 1000 can be configured for bipolar operation. The proximal ring 1010 can be the anode, and the distal ring 1020 can be the cathode (or vice versa). In another example, the applicator 1000 can be configured for unipolar operation.

[0179] Figure 11 Another applicator 1100 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels is shown. Applicator 1100 may include one or more strip electrodes 1110, conductive braid 1120, an elongated catheter body 1130, a shape support member 1140, a tubular insulating member 1150, and one or more strip insulators 1160. The one or more strip electrodes 1110 and conductive braid 1120 may be coupled to system 100 (also not shown) via conductors (not shown) and the elongated catheter body 1130. In some examples, the one or more strip electrodes 1110 may be coupled to each other.

[0180] The shape support member 1140, conductive braid 1120, and one or more strip electrodes 1110 may be formed of nitinol or any other feasible material. In some examples, the shape support member 1140 may be formed substantially circular. In some cases, the diameter of the shape support member 1140 may be selected to substantially match the shape of a body vascular bundle. A tubular insulating member 1150 may be disposed circumferentially around and adjacent to (e.g., in contact with) the shape support member 1140. The conductive braid 1120 may be disposed circumferentially around the tubular insulating member 1150 and may be used as a first electrode of the applicator 1100. The conductive braid 1120 may be formed of woven or braided conductive wire or any other feasible conductive material. One or more strip electrodes 1110 may be disposed above one or more strip insulators 1160, which in turn are disposed above the conductive braid 1120. One or more strip electrodes 1110 and one or more strip insulators 1160 may be distributed on the conductive braid 1120. Although Figure 11 Six strip electrodes 1110 are shown, but in other examples, the applicator 1100 may include any feasible number of strip electrodes.

[0181] The applicator 1100 can be configured for bipolar operation. Pulsed energy can be transmitted between one or more strip electrodes 1110 and conductive braid 1120. The distance between the strip electrodes can vary, thus making the braided electrode portions between them shorter or longer, and simultaneously (assuming the diameter of the components remains the same) changing the total number of bipolar pairs. In another example, the applicator 1100 can be configured for unipolar operation. The spacing between one or more strip electrodes 1110 and conductive braid 1120 can at least partially determine the density of the electric field associated with nanosecond pulsed energy therapy.

[0182] Figure 12 Another applicator 1200 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels is shown. The applicator 1200 may include one or more first electrodes 1210, one or more second electrodes 1220, an elongated catheter body 1230, and a helical member 1240. One or more first electrodes 1210 and one or more second electrodes 1220 may be electrically coupled to system 100 (not shown) via the elongated catheter body 1230. The helical member 1240, as well as the one or more first electrodes 1210 and one or more second electrodes 1210, may be formed of nitinol or any other feasible material. Additionally, the helical member 1240 may spiral outward from the elongated catheter body 1230 while extending distally away from the elongated catheter body 1230 (e.g., distally away from the elongated catheter body), thereby forming a conical shape. This conical shape allows one or more first electrodes 1210 and one or more second electrodes 1220 to uniformly contact some tissue surface.

[0183] One or more first electrodes 1210 and one or more second electrodes 1220 may be formed of any feasible conductive material. In some examples, one or more first electrodes 1210 and one or more second electrodes 1220 may be helically wound around a helical member 1240. In other examples, one or more first electrodes 1210 and one or more second electrodes 1220 may be separate strips electrically coupled together. Furthermore, an insulator (not shown) may be disposed between one or more first electrodes 1210 and one or more second electrodes 1220, particularly when the helical member 1240 is conductive. The first electrodes 1210 and second electrodes 1220, as well as the helical member 1240, may be retracted into a delivery catheter or sheath (not shown), or, in some specific embodiments, into an elongated catheter body 1230 to allow placement of the applicator 1200 relative to the treatment area.

[0184] The applicator 1200 can be configured for bipolar operation. Pulsed energy can be transferred between one or more first electrodes 1210 and one or more second electrodes 1220. Thus, one or more first electrodes 1210 can be configured as a single cathode, and one or more second electrodes 1220 can be configured as a single anode (or vice versa). In another example, the applicator 1200 can be configured for unipolar operation. For example, one or more first electrodes 1210 and one or more second electrodes 1220 can be electrically coupled together, and a return electrode (e.g., a conductive pad or electrode that can contact the patient) can be used.

[0185] Figure 13 Another applicator 1300 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels is shown. Applicator 1300 may include one or more first electrodes 1310, one or more second electrodes 1320, an elongated catheter body 1330, and a helical member 1340. One or more first electrodes 1310 and one or more second electrodes 1320 may be electrically coupled to system 100 (not shown) via the elongated catheter body 1330. The helical member 1340, as well as the one or more first electrodes 1310 and one or more second electrodes 1320, may be formed of nitinol or any other feasible material. Additionally, the helical member 1340 may spiral from the outer circumference toward the inner circumference while extending distally away from the elongated catheter body 1330 (e.g., distally away from the elongated catheter body), thereby forming an inverted conical shape (relative to applicator 1200). This inverted conical shape allows one or more first electrodes 1310 and one or more second electrodes 1320 to uniformly contact some tissue surface.

[0186] One or more first electrodes 1310 and one or more second electrodes 1320 may be formed of any feasible conductive material. In some examples, one or more first electrodes 1310 and one or more second electrodes 1320 may be helically wound around a helical member 1340. In other examples, one or more first electrodes 1310 and one or more second electrodes 1320 may be separate strips electrically coupled together. Furthermore, an insulator (not shown) may be disposed between one or more first electrodes 1310 and one or more second electrodes 1320 and the helical member 1340, particularly when the helical member 1340 is conductive. One or more first electrodes 1310 and one or more second electrodes 1320 and the helical member 1340 may collapse and retract into a delivery sheath (not shown), or, in some specific embodiments, into an elongated catheter body 1330, to allow placement of the applicator 1300 relative to the treatment area.

[0187] The applicator 1300 can be configured for bipolar operation. Pulsed energy can be transferred between one or more first electrodes 1310 and one or more second electrodes 1320. Thus, one or more first electrodes 1310 can be configured as anodes, and one or more second electrodes 1320 can be configured as cathodes (or vice versa). In another example, the applicator 1300 can be configured for unipolar operation.

[0188] Figure 14 Another applicator 1400 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels is shown. The applicator 1400 may include a plurality of first electrodes 1410, a plurality of second electrodes 1420, an elongated catheter body 1430, and a helical member 1440. The plurality of first electrodes 1410 and the plurality of second electrodes 1420 may be electrically coupled to system 100 (not shown) via the elongated catheter body 1430. The helical member 1440, as well as the plurality of first electrodes 1410 and the plurality of second electrodes 1420, may be formed of nitinol or any other feasible material. Additionally, the helical member 1440 may spiral outward from the elongated catheter body 1430 while extending distally away from the elongated catheter body 1430 (e.g., distally away from the elongated catheter body), thereby forming a conical shape. This conical shape allows the plurality of first electrodes 1410 and the plurality of second electrodes 1420 to uniformly contact some tissue surface.

[0189] Multiple first electrodes 1410 and multiple second electrodes 1420 may be arranged alternately on the helical member 1440. Changing the spacing between the multiple first electrodes 1410 and the multiple second electrodes 1420 can affect the density of the electric field associated with nanosecond pulse energy therapy. Furthermore, an insulator (not shown) may be disposed between the multiple first electrodes 1410 and the multiple second electrodes 1420 and the helical member 1440, particularly when the helical member 1440 is conductive.

[0190] The applicator 1400 can be configured for bipolar operation. Pulsed energy can be transferred between a plurality of first electrodes 1410 and a plurality of second electrodes 1420. Thus, the plurality of first electrodes 1410 can be configured as anodes, and the plurality of second electrodes 1420 can be configured as cathodes. In another example, the applicator 1400 can be configured for unipolar operation.

[0191] Figure 15Another applicator 1500 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels is shown. Applicator 1500 may include a first electrode 1510, a second electrode 1520, an elongated catheter body 1530, a third electrode 1540, a fourth electrode 1550, and a helical member 1560. The first electrode 1510, second electrode 1520, third electrode 1540, and fourth electrode 1550 may be electrically coupled to system 100 (not shown) via the elongated catheter body 1530. The helical member 1560, as well as the first electrode 1510, second electrode 1520, third electrode 1540, and fourth electrode 1550, may be formed of nitinol or any other feasible material. Additionally, the helical member 1560 may spiral outward from the elongated catheter body 1530 while extending distally away from the elongated catheter body 1530 (e.g., distally away from the elongated catheter body), thereby forming a conical shape. This conical shape allows the first and second electrodes to uniformly contact some tissue surface.

[0192] The first electrode 1510, second electrode 1520, third electrode 1540, and fourth electrode 1550 may be formed of any feasible conductive material. In some examples, the first electrode 1510, second electrode 1520, third electrode 1540, and fourth electrode 1550 may be helically wound around the helical member 1560. Furthermore, an insulator (not shown) may be disposed between the first electrode 1510, second electrode 1520, third electrode 1540, and fourth electrode 1550, particularly when the helical member 1560 is conductive. In some examples, the first electrode 1510 and third electrode 1540 may be electrically coupled together, and the second electrode 1520 and fourth electrode 1550 may be electrically coupled together.

[0193] The applicator 1500 can be configured for bipolar operation. Pulsed energy can be transferred between two sets of electrodes. For example, the first electrode 1510 and the third electrode 1540 can be configured as a single cathode, and the second electrode 1520 and the fourth electrode 1550 can be configured as a single anode (or vice versa). In another example, the applicator 1500 can be configured for unipolar operation.

[0194] Figure 16Another applicator 1600 configured to deliver nanosecond pulse energy therapy into the body's blood vessels is shown. The applicator 1600 may include a first electrode 1610, a second electrode 1620, an elongated conduit body 1630, a third electrode 1640, a fourth electrode 1650, a support member 1660, and a connecting member 1670. The first electrode 1610, second electrode 1620, third electrode 1640, and fourth electrode 1650 may be electrically coupled to system 100 (not shown) via the elongated conduit body 1630. The first electrode 1610, second electrode 1620, third electrode 1640, and fourth electrode 1650 may be disposed on the support member 1660, which may protrude from the elongated conduit body 1630. In some examples, an insulator (not shown) may be disposed between the first electrode 1610, second electrode 1620, third electrode 1640, and fourth electrode 1650, particularly when the support member 1660 is conductive. The connecting member 1670 may be coupled to the opposite end of the support member 1660. Although only four electrodes are shown, in other examples, the applicator 1600 may include any feasible number of electrodes.

[0195] The first electrode 1610, second electrode 1620, third electrode 1640, and fourth electrode 1650, support member 1660, and connecting member 1670 may be formed of nitinol or any other feasible material. The connecting member 1670 may be smaller and / or more flexible than the support member 1660, allowing the support member 1660, as well as the first electrode 1610, second electrode 1620, third electrode 1640, and fourth electrode 1650, to be more easily retracted into the elongated catheter body 1630, facilitating placement of the applicator 1600 relative to the treatment area.

[0196] The applicator 1600 can be configured for bipolar operation. Pulsed energy can be transferred between the two sets of electrodes. For example, pulsed energy can be transferred between the first electrode 1610 and the third electrode 1640 forming the combined anode and the second electrode 1620 and the fourth electrode 1650 forming the combined cathode, or vice versa. In another example, the applicator 1600 can be configured for unipolar operation.

[0197] Figure 17AAnother applicator 1700 configured to deliver treatment into the body's blood vessels is shown. Applicator 1700 may include a first insulating conductor 1710, a second insulating conductor 1720, and an elongated catheter body 1730. The first insulating conductor 1710, the second insulating conductor 1720, and the elongated catheter body 1730 may be formed of nitinol or any other feasible material. Furthermore, the first insulating conductor 1710 and the second insulating conductor 1720 may be woven into a basket. In some examples, the first insulating conductor 1710 and the second insulating conductor 1720 may be woven together in the distal portion of the basket (as shown, the distal portion is closer to the axis 1730 in the circumferential direction). A double-woven region of the basket is shown in enlarged area 1740. The basket formed by the first insulating conductor 1710 and the second insulating conductor may collapse and retract into a delivery catheter (not shown) to allow placement of applicator 1700 relative to the treatment area.

[0198] Figure 17B It shows Figure 17A Another view of the applicator 1700. The insulating regions of the first insulating conductor 1710 and the second insulating conductor 1720 can be selectively removed to expose the associated bare conductors. Thus, removing the insulation from the first insulating conductor 1710 forms the first electrode 1711, and removing the insulation from the second insulating conductor 1720 forms the second electrode 1721.

[0199] The applicator 1700 can be configured for bipolar operation. Pulsed energy can be transferred between two sets of electrodes. For example, pulsed energy can be transferred between a first electrode 1711 and a second electrode 1721. Thus, the first electrode 1711 can be configured as an anode and the second electrode 1721 can be configured as a cathode (or vice versa). In another example, the applicator 1700 can be configured for unipolar operation.

[0200] Figure 18 It shows the manufacturing process. Figure 17A An example of a fixing device 1800 for an applicator 1700. The fixing device 1800 may include a cylinder 1810, a first set of pins 1820, a second set of pins 1830, and a third set of pins 1840. For manufacturing the applicator 1700, a first insulating conductor 1710 is selectively wound between the first set of pins 1820 and the third set of pins 1840. Similarly, a second insulating conductor 1720 is selectively wound between the first set of pins 1820 and the second set of pins 1830. After the first insulating conductor 1710 and the second insulating conductor 1720 are wound around the cylinder 1810, insulation can be selectively removed from the first insulating conductor 1710 and the second insulating conductor 1720 to form a first electrode 1711 and a second electrode 1721.

[0201] Figure 19Another applicator 1900 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels is shown. The applicator 1900 may include a first electrode 1910, a second electrode 1920, a braided member 1925, and an elongated catheter body 1930. The first electrode 1910, the second electrode 1920, and the braided member 1925 may be formed of nitinol or any other feasible material. In some examples, the braided member 1925 may be a non-conductive material or be made of a non-conductive material. The braided member 1925 may expand (as shown) to deploy the first electrode 1910 and the second electrode 1920, such that the first electrode 1910 forms a distal circular electrode and the second electrode 1920 forms a proximal circular electrode. Although only two electrodes are shown, in other examples, the applicator 1900 may include any feasible number of electrodes. The braided member 1925 may collapse and retract into a delivery sheath to allow the applicator 1900 to be positioned relative to the treatment area.

[0202] The applicator 1900 can be configured for bipolar operation. Pulsed energy can be transferred between two sets of electrodes. For example, pulsed energy can be transferred between a first electrode 1910 and a second electrode 1920. Thus, the first electrode 1910 can be configured as a cathode and the second electrode 1920 as an anode (or vice versa). In another example, the applicator 1900 can be configured for unipolar operation.

[0203] Figure 20 It shows the relationship with Figure 19 Another applicator 2000, similar to and configured to deliver treatment into the body's blood vessels, is also present. Applicator 2000 may include a first electrode 2010, a second electrode 2020, a braided member 2025, and an elongated catheter body 2030. The first electrode 2010, second electrode 2020, and braided member 2025 may be formed of nitinol or any other feasible material. The braided member 2025 may expand (as shown) to deploy the first electrode 2010 and the second electrode 2020, such that the first electrode 2010 forms a proximal electrode and the second electrode 2020 forms a distal electrode. Although only two electrodes are shown, in other examples, applicator 2000 may include any feasible number of electrodes. The first electrode 2010, second electrode 2020, and braided member 2025 may collapse to allow placement of applicator 2000 relative to the treatment area.

[0204] The applicator 2000 can be configured for bipolar operation. Pulsed energy can be transferred between two sets of electrodes. For example, pulsed energy can be transferred between a first electrode 2010 and a second electrode 2020. Thus, the first electrode 2010 can be configured as an anode and the second electrode 2020 can be configured as a cathode (or vice versa). In another example, the applicator 2000 can be configured for unipolar operation.

[0205] Figure 21 Another applicator 2100 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels is shown. Applicator 2100 may include a first set of electrodes 2110, a second set of electrodes 2120, an elongated catheter body 2130, and an expandable member 2140. The first set of electrodes 2110 and the second set of electrodes 2120 may be formed of nitinol or any other feasible material. In some examples, the expandable member 2140 may be a balloon that can inflate to expand and deploy the first set of electrodes 2110 and the second set of electrodes 2120. In some cases, the expandable member 2140, as well as the first set of electrodes 2110 and the second set of electrodes 2120, may collapse to allow placement of applicator 2100 relative to the treatment area.

[0206] The applicator 2100 can be configured for bipolar operation. Pulse energy can be transferred between two sets of electrodes. For example, pulse energy can be transferred between the first electrode 2110 and the second electrode 2120. In another example, the applicator 2100 can be configured for unipolar operation.

[0207] This document also describes devices (e.g., applicators, application devices, etc.) configured to apply electrical energy, particularly submicrosecond (e.g., nanosecond) pulsed electrical energy, within tubular structures (such as cavities of the body, also known as bodily vessels). As mentioned above, tubular structures can generally be: cavities, such as blood vessels (veins, arteries, etc.); airways, such as nasal passages, oral cavity, sinuses, larynx, trachea, bronchi, etc.; organs, such as the heart (atria, ventricles, etc.), lungs, bladder, etc. Any of these devices can be configured for bipolar application of electrical energy to a tubular structure and may include an elongated body having a distal end region comprising a plurality of longitudinally extending ribs configured to expand outwards. In any of these examples, the elongated body may be a catheter. The elongated body may include one or more channels, including a guideline lumen. The ribs may be part of an expansion / contraction frame. A plurality of these ribs may be arranged radially around the circumference of the distal end region of the device. Each rib may correspond to an electrode. In some examples, the device may be configured as a bipolar device, wherein a first subset of the ribs has a first polarity and a second subset of the ribs has a second polarity. In some examples, ribs of opposite polarities may be alternating.

[0208] A rib may be attached at its proximal end to a first elongated member forming an elongated body. In some examples, the rib may be attached at its distal end to a second elongated member that is axially slidable within the first elongated member. The rib can be expanded (e.g., in a deployment device) by sliding the first elongated member relative to the second elongated member (or vice versa) to shorten the distance between the distal and proximal ends of the rib. Similarly, the rib can be retracted (e.g., in a retractable device) by sliding the first elongated member relative to the second elongated member (or vice versa). In some examples, the rib may be biased (or connected to a biasing device) to tend to expand the rib outward. Alternatively, in some examples, the rib may be biased (or connected to a biasing device) to tend to collapse the rib inward. For example, the ribs may be formed of a shape memory alloy (e.g., a nickel-titanium alloy, such as nitinol), which is shaped to be in an expanded configuration or alternatively in a collapsed configuration. In some examples, the ribs may be in communication with biasing devices such as leaf springs, balloons, etc.

[0209] The ribs may be uninsulated for a portion of their length, from which energy can be applied. For example, each rib may be uninsulated in the middle region of its extended length F; this middle region may be referred to as the active length or active region of each rib. In some examples, only the outward-facing sides of each rib are uninsulated. Any suitable electrical insulator can be used, including polymer insulators, especially biocompatible polymer insulators.

[0210] For example, Figure 22A An example of a device as described herein is shown, configured to deliver submicrosecond (e.g., nanosecond) pulse energy within a tubular structure. Figure 22A In this device 2200, the elongated body 2203 extends proximally to distally. The elongated body is configured to be inserted into a body cavity. In some examples, the elongated body may be flexible; in others, it may be rigid. The elongated body may be curved or steerable (e.g., using one or more prestressed tendons). The device also includes an applicator region 2201 located at the distal end region of the elongated body. Figure 22A and Figure 22B In the diagram, the applicator region is shown in a collapsed (unexpanded) configuration. The applicator region may include a plurality of expandable ribs 2221, each expandable rib configured to expand outward from the collapsed configuration within the cavity. For example, in Figure 22B In the image, the collapsed rib is shown as collapsed, such that the cross-sectional diameter of the applicator region has approximately the same diameter as the rest of the elongated body.

[0211] Figure 22CAn applicator region 2201 in an expanded configuration is shown, wherein the plurality of ribs extend radially outward in a curved manner. In this example, eight ribs 2221 are shown, but any suitable number can be used (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, etc.). Each rib includes an uninsulated active region 2225 in which conductive material is exposed. The ribs can be formed of any suitable material, including, for example, stainless steel, nickel-titanium (e.g., nitinol), etc. Figure 22C In this configuration, each rib 2221 includes a centrally located active region flanked by insulating regions 2223, 2223'. The active region may have any suitable length, such as between 1 mm and 3 cm (e.g., between 1 mm and 2 cm, between 1 mm and 1.5 cm, between 1 mm and 10 mm, between 1 mm and 8 mm, between 2 mm and 10 mm, between 2 mm and 8 mm, between 2 mm and 7 mm, etc.).

[0212] Generally, the plurality of ribs may comprise two subsets, each with a different polarity. In some examples, a first subset of the plurality of ribs in the active region is configured to have a first polarity, and a second subset of the ribs is configured to have a second polarity. Therefore, energy (e.g., pulsed submicrosecond energy) can be applied between the two subsets of the ribs. In this example, every other rib (or spline) arranged radially around the active region may have a different polarity, and ribs with the same polarity may be electrically coupled together. Thus, the polarities alternate around the active region.

[0213] exist Figures 22A to 22C In this configuration, a plurality of ribs forming an expandable active region are coupled to a pair of elongated members forming an elongated body extending proximally to distally, such that relative movement of the first and second elongated members causes the active region to expand or contract. For example, the proximal end of each of the plurality of ribs may be connected to a first (e.g., external in some examples) elongated member 2205, and the distal end of the plurality of ribs may be connected to a second (e.g., internal in some examples) elongated member 2207. The second elongated member is coaxially positioned relative to the first elongated member and is slidable proximally to distally within the first elongated member to expand or contract the active region.

[0214] The device also includes a pair of electrical connectors coupled to a pulse generator for applying electrical power to the device. For example, in Figure 22AIn the diagram, a first electrical connector 2215 is shown coupled to a first elongated member and may be coupled to a first subset of the ribs (having a first polarity). A second electrical connector 2217 is connected to a second elongated member and may be coupled to a second subset of the ribs (having a second polarity). Alternatively, in some examples, the same applicator can be used to apply a single polarity from all the ribs, and separate return pads (e.g., similar) can be used. Figure 1 The grounding pad of pad 133 shown in the figure (not shown).

[0215] Figures 22A to 22C The exemplary device shown includes eight (8) stainless steel ribs, each approximately 0.015" by 0.005" (e.g., 0.38mm × 0.13mm). Each rib is insulated with a polymer insulator (such as polyimide) to provide electrical insulation to prevent arcing and to expose only the necessary length of the rib (also referred to herein as a spline or strut) for energy delivery.

[0216] Figures 23A to 23F It shows the relationship with Figures 22A to 22C Another example of a device similar to the one shown. In this example, the distal active region of device 2301 is shown as being in the position of... Figure 22A The device also includes an elongated body 2303 comprising a first elongated member (outer elongated member 2305) and a second (e.g., inner) elongated member 2307. The first elongated member is coupled to a proximal end of the active region, and the second elongated member is coupled to a distal end of the active region. Therefore, pulling the second elongated member proximally and / or pushing the first elongated member distally can shorten the distance between the proximal and distal ends of the active region (e.g., a rib or spline) and cause the rib to expand outward.

[0217] Figure 23B An enlarged view of an active region 2301 including multiple ribs 2321 is shown, which are shown in a collapsed (unexpanded) configuration. Figure 23C and Figure 23D An enlarged end view of the rib forming the aforementioned active region is shown. Figure 23E and Figure 23F End views of each of the distal and proximal ends are shown separately. Figure 23E and Figure 23F An example of electrical connection between alternating ribs of the same polarity around a perimeter is shown. An end view showing the distal end of the active region is also included. Figure 23E In this process, every other rib or spline is electrically coupled to 2335, thus forming the first subset of the spline. Figure 23F An end view of the proximal end of the active region is shown, illustrating the electrical connection 2337 of the second subset of the spline. Figures 23A to 23F In the example, each spline 2321 includes a central active region 2325 flanked by a pair of insulating regions 2323, 2323'. Figures 23A to 23F In this configuration, power distribution can be set to use high-voltage lines and return voltage lines. Figure 23E The diagram shows the distal ends of four flat wires forming the spline of the first subset, which are bent and welded together for one polarity. The proximal ends of the four flat wires forming the second subset of the spline can be bent and welded together to form another polarity, as shown... Figure 23F As shown.

[0218] As mentioned, the internal second elongated member can move (e.g., pull / push) relative to the first elongated member to expand and contract the spline (and thus expand and contract the diameter of the active region). For example, the selected diameter can be set by the user (expanding within the lumen of the blood vessel), and the expanded state of the device can be locked in place, for example, using a lock or latching mechanism that secures the first elongated member relative to the second elongated member. Once in place, energy can be applied.

[0219] For example, Figures 24A to 24E An example of a device is shown, such as Figures 22A to 22C and Figures 23A to 23F The device shown applies pulsed submicrosecond energy to a sample of tissue during operation. In this example, the sample tissue is a potato, in which an internal cavity has been formed for insertion of the device. Figure 24A An end view of the lumen 2402 through the sample tissue is shown, into which the device 2401 has been inserted and expanded as described above. In this example, eight (8) ribs are expanded until they just contact the wall of the simulated lumen. The bipolar device is constructed as described above and inserted into the lumen and expanded. Figure 24B and Figure 24D It shows an inner cavity diameter of 20 mm, while Figure 24C and Figure 24E The inner cavity diameter is shown as 14 mm. (Example) Figures 24B to 24E As shown, all the parameters and apparatus used in the tests resulted in circumferential treatment 2404 around the periphery of the lumen. All these examples were tested using pulses in the nanosecond range (e.g., between 1 ns and 1000 ns) and voltages of approximately 2500 V.

[0220] exist Figures 22A to 22C and Figures 23A to 23FIn the example shown, the device includes an exposed (active) portion of the spline located in the middle of each rib (e.g., spline). Alternatively, in some examples, the location of the exposed active portion may be biased toward the distal or proximal end of the electrode assembly. If the ribs (splines) are made of a shape memory material such as nitinol, the ribs may be shaped into a preferred configuration.

[0221] For example, Figure 25 and Figure 26 Examples of devices 2500 and 2600 are shown, wherein the exposed active regions of the ribs forming the expandable / collapseable frame of the applicator region are biased toward the distal end. Figure 25 In this configuration, the applicator region has an approximately teardrop shape in its longitudinal cross-section. Therefore, the applicator region is configured to expand outwards into a shape with a larger cross-sectional area relative to the long axis of the applicator region (i.e., the distal side is larger than the proximal side). Each rib (spline) 2521 has a curved shape in the expanded configuration, wherein the slope of the distal-facing region is greater than (steeper than) the slope of the proximal portion. As described above, each rib also includes an exposed active region 2525 sandwiched on both sides by insulating regions 2623, 2623'. Figure 26 Similar to Figure 25 The example shown, however, has the entire distal end region of each rib 2621 exposed (uninsulated) 2625, and only the proximal end of the rib is insulated 2623.

[0222] Figures 22A to 22C , Figures 23A to 23F , Figure 25 and Figure 26 The illustrated device can expand by coupling the applicator region proximally to a first elongated member, which is axially slidable relative to a second elongated member coupled to the distal end of the applicator region, as described above. Alternatively or additionally, any of these devices can expand by extending the catheter or cannula distally, causing the applicator region to expand (e.g., self-expand); the ribs of the applicator region can be biased to expand radially outward as they are driven distally out of the catheter / cannula. Similarly, the applicator region can collapse by being pulled proximally back into the catheter / cannula. Figure 25 and Figure 26 The example shown is configured in such a way that the elongated body does not necessarily extend into the expandable applicator region. In this example, the active region of each rib (spline) may be electrically coupled at its proximal end, including electrically coupling a first subset of the active region to a first polarity and electrically coupling a second subset of the active region to a second polarity; in some examples, ribs with the first polarity may alternate with ribs with the second polarity.

[0223] Any of the devices described herein can be configured to treat the sidewall of a lumen and / or to treat an anterior (distal) region of tissue. For example, the devices described herein can be configured to treat tissue surrounding the sinuses of the pulmonary veins (PV) in the left atrium (LA) of the heart, for example, to treat atrial fibrillation (AFIB) via PV isolation (PVI). Using devices (such as...) Figure 26 An example of this treatment performed using the device shown is in Figure 27 As shown in the image.

[0224] For example, to access the LA (laminar vein) of the heart, a needle can be used to perform a puncture of the femoral vein under fluoroscopy and / or ultrasound guidance. After puncture under fluoroscopy guidance, a guide liner (e.g., a 0.032-inch J-tip guide liner) can be advanced. The needle can be removed, and a sheath guide (e.g., an 8F-12F guide) can then be inserted into the vein and flushed. A transseptal sheath and dilator can be advanced along the guide liner to the superior vena cava (SVC). Once the sheath has reached 3 to 4 cm above the junction of the SVC and atrium, the liner can be removed. A transseptal puncture needle can be advanced under fluoroscopy guidance until it reaches the tip of the sheath. The needle can then be advanced with a patency needle inserted until it reaches a position 4 cm from the tip. The patency needle prevents the needle tip from scraping the inner lumen of the sheath. The patency needle can then be removed. Puncture can then be performed, and the sheath can be advanced into the LA. Devices including electrodes formed as part of the applicator area (e.g., including...) Figure 26 The catheter of device 2600 shown can be introduced into the LA through a sheath. The active area (e.g., an electrode) of the dilated or partially dilated rib can be pushed against the wall of the LA 2718 surrounding the pulmonary vein 2719, as... Figure 27 As shown. In any of the devices described herein, the distal end of the device may be deflectable or fully articulated. For example, the elongated body may include one or more prestressed tendons for articulating the distal end (application area). Thus, electrode positioning may be assisted by the deflectable or fully articulated distal end of the conduit, controlled via a steering mechanism in the handle and a drawwire (prestressed tendon) located within the shaft of the elongated body.

[0225] The catheter's position within the body can be verified using fluoroscopy and / or ultrasound (e.g., ICE), as well as impedance and / or magnetic localization via additional electrodes and / or magnetic sensors. Contact between the active area of ​​the device (e.g., electrodes) and the tissue wall (e.g., LA) can be verified, for example, by acquiring signals generated by cardiac tissue. Electrodes incorporated into the catheter design for impedance-based localization can also be used for this purpose. After confirming the desired location and contact of the electrodes, energy (e.g., submicrosecond pulses, microsecond pulses, RF, etc.) can be applied to achieve the desired therapeutic effect, in some examples including non-thermal ablation of all or selected portions of the target tissue. Active electrodes and / or electrodes for impedance-based localization and / or contact assessment prior to ablation can be used for post-ablation signal acquisition. In some examples, tissue-contact electrodes can be used for impedance-based localization and contact assessment. For example, the absence of electrical signals from cardiac tissue can indicate an effective acute effect from ablation. The device can be repositioned once or multiple times, and energy application can be repeated in other areas of the tissue (e.g., the LA area surrounding other pulmonary veins). For example, complete PVI can be achieved when treated in LA.

[0226] In some examples, the ribs may be configured such that the uninsulated region forms a substantially flat area, such as a region substantially parallel to the long axis of the distal end region (e.g., within approximately + / - 8 degrees, within approximately + / - 5 degrees, within approximately + / - 4 degrees, within approximately + / - 3 degrees, within approximately + / - 2 degrees, within approximately + / - 1 degree, etc. relative to that long axis), such as a region extending through multiple ribs. For example, each rib may include a hinged region adjacent to one or both ends of the uninsulated (active) region, which allows the rib to bend or fold so that the uninsulated region is substantially flat.

[0227] For example, Figures 28A to 28C An example is shown in which the ribs forming the expandable frame of the applicator region can be shaped with their long axes substantially parallel to the centerline of the applicator region, such that these ribs appear substantially “flat” and align with the walls of the cavity when expanded radially outward. Figure 28A In the middle, equipment 2800 and Figures 22A to 22C and Figures 23A to 23F The illustrated device is similar in that it includes a plurality of ribs (splines) 2821 arranged radially around a central centerline 2855. Each rib includes an active (electrode) region 2825 sandwiched on both sides by insulating regions 2823, 2823'. In this example, eight ribs are arranged radially around the centerline. The central centerline may be formed by an internal elongated member coupled to the distal end region of the ribs and slidable distally or proximally to expand / contract the applicator region.

[0228] exist Figure 28A In this configuration, each rib is shaped such that the active region 2825 extends substantially flat (without bending) to expose an active region (electrode) of approximately the same size, regardless of the amount of expansion of the applicator region (e.g., the frame). For example, in Figure 28B In the middle, the inner cavity is more than Figure 28C The cavity shown is narrower, and the applicator area is comparable to... Figure 28C The applicator region expands less to contact the wall of the cavity. As the applicator region expands outward, the active region of the rib remains substantially parallel to the central midline and also substantially parallel to the wall of the cavity 2866, as... Figure 28B and Figure 28C As shown. Furthermore, the lengths of the active regions in contact with the tissue are substantially similar.

[0229] Therefore, in some examples, the ribs can be shaped or formed to ensure that the contact length between the exposed active (electrode) portion of each rib and the tissue does not change significantly regardless of the ID of the lumen (including organs such as bronchi, esophagus, blood vessels, etc.). For example, device 2800 can be introduced into the interior of a lumen (organ) with an ID of approximately 20 mm (e.g., Figure 28C The same device can be used within a lumen with an ID of approximately 10 mm (e.g., Figure 28B ).exist Figure 28A In the device shown, the ribs can be formed of shape memory alloys (such as nitinol) and can have an active (exposed electrode) region with a length of, for example, about 10 mm. Generally, the length of the exposed portion can vary depending on the application.

[0230] In any of these devices, the ribs can be hinged to include more flexible regions, thereby allowing preferential bending on both sides of the active region, similar to... Figure 28A The configuration is shown. The hinge can be a movable hinge. In some examples, the hinge is formed by a narrowed or cut-out region on one or both sides of the rib. The hinge can act as a stress concentrater to allow contact bending along the exposed, uninsulated active area of ​​the rib.

[0231] Figure 29A An example of a rib member excluding one or more hinges is shown. In this example, rib member 2921 includes an uninsulated active region (electrode) 2925 flanked by a pair of insulating regions 2923, 2923'. The rib member extends in an arc shape. Figure 29BA similar rib is shown, including a hinge region 2970. In this example, the hinge region is formed by two cut-out regions 2971 that provide preferential bending at the hinge region. In some examples, the hinge region may be formed by thinning the rib at the hinge region, perforating at the hinge region, shaping the bend at the hinge region, and / or using one or more different materials at the hinge region (e.g., a region that bends more preferentially than the active region). A second hinge region may be included on the opposite side of the active region 2925 (not shown). In any of these examples, the hinge region may be within an insulating region 2923, within an uninsulated region 2925, or span both regions. Figure 29B In this design, the hinged area is within the insulating area 2923. The insulating material provides support for the hinged area, preventing the ribs from breaking at the hinged area.

[0232] Figure 30A and Figure 30B Another example of a device including an applicator region is shown, the applicator region comprising a plurality of ribs 3021, each rib being configured to have an active region 3025 (electrode) that is configured to remain substantially flat and parallel to the central longitudinal axis of the applicator region 3055 in any expanded configuration. Figure 30B It shows Figure 30A A magnified view of part B, showing the hinge region 3070 of one of the ribs. In this example, the hinge region is similar to... Figure 29B The hinged area is shown and is covered by an electrically insulating material in the insulating area 3023.

[0233] As mentioned above, any of these devices may also, or alternatively, include a balloon to aid in expanding the applicator region. For example, the balloon may be positioned within an expandable frame formed by the applicator region, such as... Figure 31 As shown. In this example, device 3100 includes a balloon 3185, which is shown to inflate within an applicator region formed by eight ribs and to drive (or assist in driving) the expansion of the applicator region. The balloon can be inflated by injecting fluid (such as saline) into the balloon via an elongated body 3103. Each rib includes an active region 3125, which in this example is shown as a centrally located active region (electrode) sandwiched on both sides by a pair of insulating regions 3123, 3123'. In some examples, the applicator region can be shaped to collapse such that the compression of the balloon allows the ribs to collapse back to an uninflated configuration. In some examples, the applicator region can also collapse by pulling it proximally back into a catheter or cannula. In addition to the balloon as described above, the applicator region may also include one or more elongated members to assist in expansion / collapse. Balloons (such as...) Figure 31The balloon shown can also be used as an insulator to prevent electric arcing between electrodes of different polarities. For example, the balloon can be formed of an electrically insulating material. Figure 31 The device shown also includes a damage-resistant distal tip 3186, which in some examples may additionally or alternatively serve as a centering guide.

[0234] Point-to-point treatment

[0235] The devices described herein can be used for point-to-point treatment as mentioned above. For example, any of these devices may include smaller electrodes (e.g., reference...). Figure 3A or Figure 3B (showing the center electrode) or a sub-section of the applicator area (as shown in the reference) Figure 3B and Figure 7 (as described). In some examples, such as Figures 22A to 22C The device shown can use single pairs of ribs of different polarities to apply treatment to smaller areas of tissue. Therefore, larger sub-sections or sub-regions of circumferential electrode sets can be used. For example, the device described herein can be used to perform cardiac ablation to address various problems such as atrial fibrillation, ventricular tachycardia, ventricular wall thickening, etc., and to perform ablation in other organs such as the esophagus (e.g., Barrett's esophagus), bronchi (e.g., chronic bronchitis, asthma, etc.). The same device can be configured, for example, to apply treatment to a larger area using the entire applicator region, and to apply treatment to smaller areas suitable for point-by-point treatment using sub-sections of the applicator region.

[0236] The device described herein can be configured to generate a treatment area of ​​approximately 5 mm to 15 mm (e.g., an ablation area in some examples). In some cases, a larger treatment area may be unnecessary or not recommended. For example, ablating too much of the proximal wall or top of the left atrium (LA) of the heart may lead to loss of myocardial function or disruption of the proper pathway for the propagation of electrical impulses to the heart. The device described herein can limit the ablation “footprint” to, for example, approximately 5 mm to 15 mm depending on the distance between the electrodes and can generate an electric field strong enough to achieve a transmural effect.

[0237] Figure 32 and Figure 33Another example of an applicator device is shown, wherein the applicator region includes a distal ring 3214 with three independently addressable electrodes 3212', 3212", 3212"' and a proximal ring 3212 with three independently addressable electrodes 3214', 3214", 3214"'. Treatment energy can be applied across the entire distal and proximal rings, for example, to circumferentially treat (e.g., ablate) the lumen, or energy can be applied only between a subset of the distal and proximal ring electrodes (e.g., only between 3214' and 3212'). Therefore, treatment can be applied only when the applicator region is lateral to the tissue.

[0238] Figures 34A to 34C , Figure 35 and Figures 36A to 36D An example of an applicator that can be configured as described herein is shown. Figures 34A to 34C An example of a flat "paddle-shaped" applicator including an outer electrode (wire electrode) and an inner electrode (wire electrode) is shown. For example, Figure 34A An example of a substantially flat paddle-shaped applicator is shown, comprising an outer (farther) active region electrode 3401 and an inner (proximal) active region electrode 3403. The outer and inner electrodes are arranged such that the minimum distance d between the outer and inner lead electrodes is substantially the same along their length. Each electrode is formed of a lead wire that is insulated 3405 on the proximal side but not insulated in the active region. Similarly, Figure 34B The wire paddle device also includes an outer (more distal) active region electrode 3401' and an inner (more proximal) active region electrode 3403'. The outer and inner electrodes are arranged such that the minimum distance d' between the outer and inner wire electrodes is substantially the same along their length. Figure 34C Another example of a wire paddle device is shown, which also includes an outer (more distal) active region electrode 3401" and an inner (more proximal) active region electrode 3403". The outer and inner electrodes are arranged such that the minimum distance d" between the outer and inner wire electrodes is substantially the same along their length. Figure 34C In the middle, the overall shape is semi-circular.

[0239] Figure 35 This is another example of a paddle-shaped applicator formed by two longitudinally arranged parallel wires. The elongated body and / or the insulating portion of the wire 3505 forming the electrode can be L-shaped, allowing the electrode to be placed flat against the target tissue without the elongated body contacting the tissue. Figure 35 In the process, the first conductor 3503 and the second conductor 3501 are separated by a fixed distance along the active (uninsulated) length of the electrode.

[0240] Figures 36A to 36D An example of an applicator with an electrode facing forward (far side) is shown. Figure 36AIt includes multiple (e.g., six in this example) ribs, each rib including a distally facing electrode 3603. Active regions (electrodes) in this example are formed by the uninsulated portion of each rib (spline), and each of these active regions can be electrically coupled together to form a unipolar electrode. A central electrode 3605 is positioned on the distal end face of the electrode. As described above... Figures 22A to 22C and Figures 23A to 23F In the device shown, Figure 36A The device shown can be expandable and collapsible, including by coupling the distal end of each rib to an axially slidable elongated member that can slide relative to the proximal end of the rib.

[0241] Figure 36B An example of a device configured as a distal applicator is shown, comprising a pair of wings 3613, 3615 that can be powered with different polarities to apply energy therebetween. Figure 36C The example of the applicator shown is similar to Figure 36B The applicator shown also includes a pair of wings 3613', 3615', which can be powered with different polarities to apply energy therebetween. The electrodes in this example maintain a constant distance between them along their length, which can be advantageous in applying energy of uniform density to tissue.

[0242] Figure 36D An example of a device is shown with radially separated active regions (electrodes) 3661, 3662, 3663, and 3664, which form a circle facing distally. The first active region 3661 and the third active region 3663, separated by the second active region 3662 and the fourth active region 3664, can be of a first polarity (and can be electrically coupled to each other), while the second active region 3662 and the fourth active region 3664 can be of a second polarity and can be electrically coupled to each other. In some examples, only two of the four electrodes may be used, where each electrode applies energy of opposite polarity, such as the first active region and the second active region.

[0243] Any of these devices can be used as a device or distal portion of an elongated body (e.g., a catheter) for intracavitary treatments such as (but not limited to) atrial fibrillation, ventricular tachycardia, or other cardiac-related ablation. For example, these devices can be used to apply nanosecond pulsed electric fields to virtually any part of the human body. For example, in some specific implementations, these devices can be used to apply other types of energy, such as RF or microsecond pulsed energy. These applicators can be part of a catheter used during minimally invasive surgery or as part of a device used during surgery (e.g., cardiac surgery). In some cases, the method of using the device can be performed as a concomitant procedure if necessary, and the device may not be catheter-based.

[0244] In any of these devices, the distance between the electrodes can be varied, which determines the intensity of the pulse field at each given voltage, and thus the size of the treatment area.

[0245] Centering feature

[0246] Any of the devices described herein may also include a centering guide (centering feature) to aid in positioning the device within tissue. Therefore, any of these devices may include a centering guide to aid in positioning the device such that the electrode (e.g., a single-position electrode) is oriented relative to the tissue. In some examples, the device may include a centering guide to position the electrode of the device relative to the sinus / ostium region of various blood vessels (such as the pulmonary veins of the heart), thereby achieving proper positioning and more effective ablation while achieving PVI (pulmonary vein isolation).

[0247] Figure 37 The difficulty of centering a device 3700 (such as the applicator device described herein) relative to the target tissue is illustrated; in this example, the target tissue is the left atrium (LA) 3706 of the pulmonary vein (PV) 3708. Locating the device relative to the LAPV can be particularly challenging without 3D visualization. Many facilities performing procedures for atrial fibrillation (AFIB) do not have 3D mapping capabilities and rely on fluorescence imaging to place their devices. Therefore, navigating the device toward the PV can be difficult. In some cases, such as... Figure 37 As shown, the device can be placed off-center from the sinus of the PV, thereby preventing circumferential ablation.

[0248] Therefore, any of the devices described herein may include one or more additional centering guides, which may be part of the device or as additional devices that can be used in conjunction with the device to enable centering relative to the lumen in which treatment is to be applied (such as, but not limited to, sinuses of the PV). Generally, the centering guide may be an expandable, damage-resistant protrusion that extends distally from the distal end of the device. Figure 38A An example of an applicator device 3800 including a centering guide 3840 as described herein is shown. In this example, the centering guide feature 3840 is integrated into the device and extends distally beyond the electrodes of the first (outer) ring 3814 and the second (inner) ring 3812.

[0249] Figure 38B Another example of a device is shown, including a centering guide 3842 extending from the distal end of the device 3800', away from a first ring 3814 and a second ring 3812 forming an active region (electrode) extending from the elongated body 3803. Figure 38A In this context, the centering guide is an expandable and collapsible balloon, while... Figure 38B In this device, the centering guide is formed from multiple inflatable and collapsible splines. The centering guide is typically initially positioned within a lumen and then expanded to guide positioning within the traumatic tissue. Any of these devices may also use a guide wire for positioning. For example, a balloon or spline may have an integrated guide wire or a lumen for the guide wire, which can be used to introduce the device. For instance, a balloon or spline (centering guide) may be integrated into the ablation device and introduced together with the guide wire. Figure 39 An example of a device 3900 is shown, comprising a pair of annular electrodes 3912, 3914, a centering guide 3942, and a guide wire 3945. The guide wire extends through an inner cavity in an elongated body 3903.

[0250] In some examples, the centering guide may also act as or may include an electrode for delivering pulsed energy to the tissue. For example, in Figure 39 In this context, basket 3942 (formed from a spline / rib) may include an electrode that can be used in a first polarity when one or both of the annular electrodes 3912, 3914 are used in a second polarity, to apply treatment to tissue, such as by applying a submicrosecond (e.g., nanosecond) pulse between the annular electrode and the basket.

[0251] For example, Figures 40A to 40D The use of a centering guide for an expandable balloon configured as part of a device is shown. Figure 40A In this process, device 4000, including a compressed balloon 4040, is introduced and positioned near LA 4006. (As...) Figure 40BAs shown, the centering guide (e.g., balloon) 4040 is partially compressed to have an OD of less than the ID of PV 4008. Figure 40C In this process, the centering guide (balloon) moves within the PV until the annular electrode contacts the sinus, as shown in the figure. Finally, as... Figure 40D As shown, this causes the balloon to inflate.

[0252] Figures 41A to 41D This illustrates when the centering guide is, for example, made of, such as Figure 38B A similar method of use when forming an expandable basket-like structure from the spline (rib) shown. Figure 41A In this process, device 4100, including the collapsed basket 4140, is introduced into the vicinity of LA4106 and positioned. For example... Figure 41B As shown, the centering guide (e.g., a basket) 4140 partially expands to have an OD with an ID smaller than PV 4108. Figure 41C In the process, the centering guide (basket-shaped object) moves within the PV until the annular electrode contacts the sinus, as shown in the figure. Finally, as... Figure 41D As shown, this causes the balloon to inflate.

[0253] Ablation methods for treating the heart

[0254] Generally, the methods and devices described herein can use pulsed electrical energy (e.g., microsecond, submicrosecond, nanosecond, etc.) to treat atrial fibrillation, ventricular tachycardia, and perform other cardiac-related ablation. The applicator described herein can be used to deliver pulsed electrical energy to the desired treatment area during minimally invasive procedures or during procedures such as cardiac surgery.

[0255] For example, these methods and devices can be used to perform cardiac ablation by delivering pulsed energy to the coronary arteries as well as peripheral arteries and veins. For instance, any of the applicators described herein can be used to deliver pulsed energy to the sinuses of the pulmonary veins. Specifically, the applicator can be adapted to a transitional region of the sinus that begins as a relatively larger area (relative to the distal region of the applicator) and transitions to a relatively smaller area. A first or distal electrode with a relatively smaller diameter can contact the smaller area, while a second or proximal electrode with a relatively larger diameter can contact the larger area.

[0256] In another example, the diameters of the first and second electrodes can be reversed, such that the diameter of the first electrode is relatively larger than the diameter of the second electrode. The use of such an applicator is well-suited for treating tissue areas that begin in a relatively small region and transition to a relatively large region.

[0257] An exemplary use of the applicator described herein is to deliver a single ablation for pulmonary vein isolation in the left atrium to treat atrial fibrillation. To access the left atrium, a needle may be used to perform a puncture of the femoral vein under fluoroscope and / or ultrasound guidance. Following fluoroscope-guided puncture, a 0.032-inch J-tip guide wire may be advanced. The needle can be removed, and a sheathed guide (typically 8F-12F) can be inserted into the vein and flushed. The guide wire is advanced through the septal sheath (which can carry any applicator described herein) to the superior vena cava (SVC). Alternatively, in cases where the initial puncture is performed in the femoral vein, the device of this disclosure may be advanced through the inferior vena cava (IVC).

[0258] Once the sheath is positioned three to four centimeters (cm) above the junction of the vena cava and atrium, remove the suture. Under fluorescein guidance, advance the transseptal puncture needle until it reaches the tip of the sheath. With the cardioverter-cushion inserted, advance the needle until it reaches a position 4 cm from the tip. The cardioverter-cushion prevents the needle tip from scraping the inner lumen of the sheath. The cardioverter-cushion can then be removed. Perform the puncture and advance the sheath into the left atrium. A catheter with electrodes can be introduced into the left atrium through the sheath.

[0259] The electrodes can be pushed against the wall of the left atrium, particularly the wall surrounding the pulmonary veins. Proper electrode positioning is aided by a deflectable or fully articulated distal end of the slender catheter body, controlled via a mechanism in the slender handle and a pull wire located within the axis of the slender catheter body. Proper catheter placement can be verified using fluoroscopy and / or ultrasound (TEE and / or ICE) as well as impedance and / or magnetic positioning via additional electrodes and / or magnetic sensors on the catheter. Proper contact between the applicator's electrodes and the left atrial wall can be verified via impedance readings achieved by transmitting, for example, a low-amplitude, non-therapeutic electrical "test" signal. After confirming proper placement and contact of the electrode bipolar pair, energy (nanosecond pulses, microsecond pulses, RF) can be applied to achieve the desired ablation effect. Complete pulmonary vein isolation can be achieved by subsequently repositioning the catheter and distal bipolar pair and repeating energy applications in additional left atrial regions surrounding other pulmonary veins.

[0260] Pulsed electrical therapy (e.g., nanosecond pulses) may include a pulse profile having a pulse rise and / or fall time, which may be less than 20 ns, about 20 ns, about 25 ns, about 30 ns, about 40 ns, about 50 ns, about 60 ns, about 75 ns, or greater than 75 ns. In some examples, the pulse voltage may be less than 1 kV, less than 5 kV, about 5 kV, between about 5 kV and about 10 kV, about 15 kV, about 20 kV, about 25 kV, about 30 kV, greater than 5 kV, greater than 10 kV, greater than 15 kV, greater than 20 kV, greater than 30 kV, etc. In some examples, the current may be less than 10A, about 10A, about 25A, about 40A, about 50A, about 60A, about 75A, about 100A, about 125A, about 150A, about 175A, about 200A, or greater than 200A. In some examples, the pulse duration may be less than 10 ns, about 10 ns, about 15 ns or less, about 20 ns or less, about 25 ns or less, about 30 ns or less, about 40 ns or less, about 50 ns or less, about 60 ns or less, about 75 ns or less, about 100 ns or less, about 125 ns or less, about 150 ns or less, about 175 ns or less, about 200 ns or less, about 300 ns or less, about 400 ns or less, about 500 ns or less, about 750 ns or less, about 1 ps or less, about 2 ps or less, about 3 ps or less, about 4 ps or less, about 5 ps or less, or greater than 5 ps. In addition to instruments (e.g., elongated application tools), the devices (e.g., systems) described herein may also include pulse generators, such as... Figure 1 The pulse generator shown schematically is configured to emit pulses, for example, in the submicrosecond range.

[0261] Generally, the systems disclosed herein may include additional components, such as a power supply, and / or a high-voltage connector for securely connecting an elongated application tool device to a high-voltage power supply. As described above, these systems and devices are configured to apply high-voltage, submicrosecond pulsed electrical energy.

[0262] Figure 42 This is a flowchart illustrating an example of a method 4200 for delivering pulsed electrical therapy to a selected treatment area of ​​a patient. Some examples may perform the operations described herein, as well as additional operations, fewer operations, operations in different sequences, parallel operations, and several different operations. Method 4200 can be used to treat atrial fibrillation, ventricular tachycardia, or to perform other cardiac ablation procedures. Method 4200 is not limited to cardiac applications but can also be used to treat various vascular systems throughout the body.

[0263] exist Figure 42In method 4200, the treatment area can be identified starting in box 4202. Box 4202 can be optional, such as... Figure 42 As shown by the dashed lines. For example, one or more diagnostic tests used on a patient can identify areas of veins, arteries, or other bodily vessels for receiving pulsed electrical therapy. In other examples, the treatment area can be any technically feasible lumen, channel, or structure. Diagnostic tests may include radiological tests, vascular tests, ultrasound tests, or any other feasible tests capable of identifying the treatment area.

[0264] In box 4204, the applicator is positioned within the identified treatment area. For example, Figure 1 System 100 can be used to apply an applicator (such as, but not limited to, Figures 2 to 41D The applicator is positioned within the identified treatment area. For example, the applicator can be positioned by expanding a spaced-apart first electrode (e.g., a first annular electrode having one or more rings) and a second electrode (e.g., a second annular electrode having one or more rings).

[0265] In box 4206, the electrodes of the applicator can be positioned to contact target tissue within the identified treatment area. The electrodes can be positioned such that an active region on a first electrode (which may extend circumferentially (completely or partially) into the target tissue) is spaced apart from an active region on a second electrode (which may also extend circumferentially (completely or partially) into the target tissue). The area between the active regions of the first and second electrodes can be treated. In some examples, the first active region of the first electrode and the second active region of the second electrode can be circumferentially positioned around a lumen (e.g., a vessel wall); in some examples, the first active region of the first electrode and the second active region of the second electrode can be circumferentially positioned around a portion of a body vessel, for example, in a non-limiting example, circumferentially positioned around the sinus of a pulmonary vein. In some cases, the electrodes can be positioned to contact the tissue via an attached elongated catheter body. In some other cases, the electrodes can protrude from the elongated catheter body and expand to allow the electrodes into the treatment area. After expansion, the applicator can be moved to position the electrodes in contact with the tissue.

[0266] When the electrodes are positioned to contact the tissue, in some examples, the spacing (e.g., longitudinal spacing) between the electrodes (e.g., electrode groups) on the applicator can be adjusted. For example, particularly with reference to... Figure 2 Figures 3 and 8 Figure 9 The applicator can adjust the spacing between the electrodes on the applicator to change the density of the pulsed electric field or adapt to changing tissue shape and topology.

[0267] In optional block 4207, contact with tissue can be confirmed by any suitable method (e.g., impedance testing, electrophoresis, imaging, etc.). In this optional step, a low-level or low-amplitude signal (e.g., voltage and / or current) can be supplied to the electrode. System 100 can determine and / or measure the impedance associated with the electrode based on the signals supplied to and returned from the electrode. When the impedance is within the expected value, contact with tissue can be confirmed.

[0268] In block 4208, pulsed electrotherapy is applied to the identified treatment area via an applicator. For example, system 100 can deliver energy via an applicator (e.g., between the active regions of the first electrode and the active regions of the second electrode). In some examples, the energy can be provided by a pulse generator configured to provide electrical pulses with an amplitude greater than 0.1 kV and a duration of less than 1000 nanoseconds.

[0269] Additional treatments can be performed, including repeated application of energy to the tissue via a first and second electrode; the effectiveness of each pulse of electrical therapy can be assessed. If the treatment is sufficient, no further treatment is required (e.g., as determined by imaging, impedance testing, electrophoresis, etc.). In some examples, it may be advantageous to apply energy in the circumferential pattern described herein (see, for example...). Figure 6B ( ), without having to move the device to obtain near-complete or complete circumferential treatment.

[0270] In box 4210, the electrode of the applicator is retrieved from the tissue. In some cases, the catheter may be moved relative to the surface of the already treated tissue to provide further treatment. The applicator may be moved to another treatment area or may be removed from the patient.

[0271] Used with cardiac mapping

[0272] As described above, any of these devices and methods can be used with a cardiac mapping system. For example, any of these devices and methods can be part of an ablation method for treating cardiac regions, including but not limited to pulmonary veins (or sinuses associated with pulmonary veins), and can include the placement of electrodes by coordinating the energy application (e.g., submicrosecond pulse energy application) of an applicator using mapping (such as 3D electroanatomical mapping / mapping of relevant tissues).

[0273] As mentioned, the device may include one or more sensors, including electrical sensors (e.g., sensing electrodes) and / or imaging sensors. The device may integrate data from these one or more sensors with one or more mappings of the tissue to be treated. These electroanatomical mappings may be generated by separate mapping systems, including commercially available mapping systems, or the device described herein may include a mapping system or subsystem integrated into the device. In some examples, the sensors are configured as electrodes that can be used as sensors for a mapping (e.g., 3D electroanatomical mapping) system or subsystem, and are used in conjunction with one or more patches that can be applied to the patient and connected to the mapping system / subsystem.

[0274] Any of the applicators described herein may include additional electrodes to allow visualization of the device in conjunction with the mapping system.

[0275] For example, Figures 43A to 43B It shows the relationship with Figure 4A rule Figure 4E and Figure 7 Examples of devices similar to the one shown include therapeutic electrodes 4311, 4321 and mapping electrodes 4350, 4350'; in Figure 43A In this application, ten individual mapping electrodes 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 are positioned distally on the lateral side of the applicator. These mapping electrodes may also be referred to as sensing electrodes. As described above, the applicator 4300 is configured to deliver nanosecond pulsed energy therapy. The applicator 4300 in this example includes an inner proximal ring 4320 and an outer distal ring 4310. Each of the inner and outer rings 4320 includes five flaps formed by a conductor of a certain length forming the treatment electrodes 4311 and 4321. Additionally, the applicator 4300 includes five arms 4330 that flexibly couple the inner and outer rings to an elongated catheter body 4340. As described above, the inner and outer rings may have more flaps (e.g., more treatment electrodes) and / or fewer flaps.

[0276] Sensing or mapping electrodes are typically smaller than treatment electrodes; in this example, these treatment electrodes are elongated wires of a certain length. For example, the length and / or width of the sensing or mapping electrode may be 5 mm or less (e.g., it may have maximum dimensions of 5 mm or less, 4.5 mm or less, 4 mm or less, 3.5 mm or less, 3 mm or less, 2.5 mm or less, 2 mm or less, 1.5 mm or less, 1 mm or less, etc.). The mapping electrode may be electrically isolated from the treatment electrode. Figure 43AIn the example shown, sensing or mapping electrodes 4350, 4350' are formed of strips or hoops of a conductive material (e.g., metal) that are coiled around or otherwise coupled to an insulating material on the arm 4330 of the device. Some examples of insulating materials or coatings include polyimide, PET, etc. Each sensing or mapping electrode may include a lead (e.g., a wire) extending from the sensing or mapping electrode through a conduit and to a coupling site (not shown) to couple to a sensing or readout subassembly and / or to a separate mapping system or subsystem. The sensing or mapping electrodes may be electrically separate and isolated from the treatment electrodes.

[0277] During operation, sensing and / or mapping electrodes (e.g., sensing / mapping electrodes) can be used to isolate the position of the applicator relative to tissue or relative to a mapping map of the tissue. For example, sensing / mapping electrodes 1, 3, 5, 7, and 9 can provide the contour of an outer ring, while sensing / mapping electrodes 2, 4, 6, 8, and 10 can provide the contour of an inner ring. Combinations of sensing / mapping electrodes (e.g., 1-2, 3-4, 5-6, 7-8, 9-10, or other combinations) can also or alternatively be used to improve signal acquisition and / or for more reliable tissue contact. In some examples, sensing / mapping electrodes can be used for position detection without requiring tissue contact.

[0278] Generally, sensing / mapping electrodes (in lieu of or as a supplement to treatment electrodes) can be used to monitor treatment progress. For example, sensing / mapping electrodes can be used to determine whether one or more electrical properties and / or electrical activity of the target tissue has changed. For instance, sensing / mapping electrodes can be used to determine or monitor electrical activity on or near the target tissue before and / or during the application of pulsed (e.g., nanosecond pulse) energy from the treatment electrode. Ableasing tissue using the methods described herein (e.g., by applying non-thermal therapeutic energy such as nanosecond pulses) is expected to reduce the electrical activity of the underlying target (e.g., the heart) tissue. Generally, the methods described herein can apply submicrosecond (e.g., nanosecond) pulses, for example, between 0.1 Hz and 100,000 Hz. Even at faster (e.g., kHz) frequencies, nanosecond pulses can provide a relatively long period during which no energy is applied to the tissue, during which the sensing / mapping electrodes can detect electrical activity on the tissue. In some examples, sensing / mapping electrodes can be used to determine the impedance and / or changes in impedance of the underlying tissue over time.

[0279] The device described herein may also include one or more magnetic sensors 4342 (e.g., magnetic coils, rods, etc.). In this example, the magnetic sensors are attached to the distal portion of the catheter body 4340 and centered relative to the treatment electrode. This increases the accuracy of the catheter's position.

[0280] Figure 43BA side view of the applicator 4300 is shown. The inner ring 4320, outer ring 4310, and arm 4330 are shown coupled to the elongated body 4340. In this example, one or more (e.g., two, eleven, or twelve) additional sensing / mapping electrodes may be positioned on the axis of the elongated body 4340 and may be used in conjunction with one or more of the other sensing / mapping electrodes mentioned above.

[0281] These devices can be configured for magnetic sensing or electrical characteristic (e.g., impedance-based) sensing, or both. For example, in addition to therapeutic electrodes, Figures 43A to 43B The illustrated device also includes both mapping electrodes 4350, 4350' and a magnetic sensor 4342. In some examples, the applicator may be coupled to a third-party mapping system (e.g., Carto) by providing input to the mapping system directly or indirectly from the sensing / mapping electrodes. TM System, Navx TM (Systems, etc.). The applicators described herein can be used in conjunction with standalone mapping catheters. For example, mapping catheters and systems can be used to map tissue, generating mapping maps or models of tissue (such as cardiac tissue), including, in particular, the target area to be treated, and any of the applicators described herein can be introduced and one or more sensors (including electrodes) can be used to position the applicator on the mapping map or model of the tissue. The device can display an image of the mapping map or model and simultaneously indicate the position of the applicator on the image of the mapping map or model to help guide the user (e.g., a physician, surgeon, etc.) to treat the target tissue. Alternatively, the applicators described herein can be used for both mapping and ablation. In some examples, the devices described herein may include a mapping system or subsystem integrated into the device.

[0282] For example, Figure 43C An example of a device comprising both mapping and treatment, as described herein, is schematically illustrated. In a first embodiment of this example, the device includes an applicator 4394 similar to those described above, which includes multiple treatment electrodes and multiple sensing / mapping electrodes. The applicator is coupled to a nanosecond pulsed energy therapy system 4392, which may also include, as described above (e.g., ...). Figure 1The system 4392 includes a pulse generator and controller (which includes one or more processors). System 4392 may be separate from mapping system 4393 and / or output 4395; the output may include one or more displays and may show a mapping map of the tissue, including the position of the applicator based on input from one or more sensing / mapping electrodes (or other mapping sensors) on the applicator. In some examples, as shown by dashed line 4390", the device may include nanosecond pulsed energy therapy system 4392 and output 4395, and may be used in conjunction with a separate mapping system / subsystem 4393. Alternatively, in some examples, the mapping system / subsystem may be included as part of the device, as shown by dashed box 4390'. In any of these devices, a separate mapping catheter 4396 may be coupled to mapping system / subsystem 4393, as shown.

[0283] Wire-based bipolar electrode for nanosecond pulse energy application

[0284] Any of the methods and apparatus described herein can be used for the application of bipolar submicrosecond (e.g., nanosecond) pulses using electrodes formed from fine (small profile) wires. These small profile wires may have a maximum diameter of 0.015" (e.g., 0.38 mm) or smaller (e.g., 0.35 mm, 0.30 mm, 0.25 mm, 0.20 mm, 0.15 mm, 0.13 mm, 0.12 mm, 0.10 mm, etc. or smaller). These wires may be formed from any conductive material. Smaller profile wires are particularly suitable for emitting the electromagnetic fields described herein. Generally, such small profile wires have been avoided for use with systems that generate heat energy because finer profile wires may limit the ablation area and may be more prone to breakage.

[0285] For example, most energy-based therapeutic devices, such as radio frequency (RF) devices, employ electrodes with a diameter of approximately 2 mm to 3 mm or larger. RF thermal ablation, for instance, relies on two types of heating: resistive heating and conductive heating. Tissue in direct contact with the electrode is heated via resistive heating, based on the voltage applied to the electrode and the electrode material, and the impedance between the electrode and the tissue. Tissue farther from the electrode can be heated either by conductive heating directly from the electrode or by transferring heat from the already “heated” portion of the tissue to a “cooler” region. Electrode size is particularly important in this context because larger electrodes cover a larger area of ​​tissue, thus increasing “direct” conductive heat transfer between the electrode and the tissue. Furthermore, if multiple electrodes are used (e.g., in a bipolar RF system), larger electrode sizes reduce the distance between them, thus reducing the volume of tissue that needs to be heated via “indirect” conductive heat transfer. Even for some applications involving pulsed signals (e.g., millisecond or microsecond pulses), larger electrodes are considered advantageous because the highest energy concentration is at the electrode, and the field generated by a typical 2 kV to 3 kV (e.g., approximately the voltage used by most microsecond pulse devices) is not high enough for treatment. Therefore, most microsecond-based devices typically require repositioning of electrodes to create continuous treatment zones.

[0286] In contrast to the much larger tubular electrodes used, for example, with RF ablation, the use of such small-profile leads as disclosed herein allows the devices described herein to have a relatively smaller cross-sectional profile. This allows any of these devices to retract into the lumen of, for example, the working channel of a bronchoscope / gastroscopy or a delivery sheath for cardiac applications, which simplifies and / or enables specific procedures.

[0287] Even when the electrodes are constructed from small-diameter (e.g., 0.005" to 0.015" or smaller) wires, the bipolar submicrosecond (e.g., nanosecond) pulse energy described herein can be applied at voltages sufficiently high to generate a therapeutic field (e.g., 12 kV to 15 kV or greater). Surprisingly, testing with such small-diameter wires has been found to be highly effective for tissue ablation, without the need for repositioning to ablate the tissue between them.

[0288] For example, Figures 44A to 44D Examples of different configurations of wire-based designs for devices used to deliver pulsed electrical energy are shown. The small diameter of the wire electrodes in all these designs enhances the collapsibility of these configurations and makes them compatible with the small lumens of the delivery devices. For example, such devices can be more easily fitted into the 2.8 mm or 3.7 mm working channels of bronchoscopy and gastroscopy, where the inner diameter (ID) of cardiovascular guide sheaths, etc., is 8.5 Fr, 9 Fr, and 12 Fr. The catheter carrying such electrodes can be deflectable and / or steerable, for example, as described below. Figure 44D It can be delivered through the working channel of a bronchoscope and / or a gastroscope, and can come into contact with the target tissue by deflecting the distal end of the bronchoscope or gastroscope.

[0289] Figures 44A to 44D The examples shown can be used as distal portions of catheters for treating tubular regions of human or animal anatomy. Such tubular regions may include, but are not limited to, the esophagus, bronchi, pulmonary veins, other parts of the venous and arterial systems, etc. These devices can be used to apply submicrosecond pulsed fields to other parts of the human body. For example, these devices can be used as part of catheters used during minimally invasive surgery, or as part of devices used during surgery.

[0290] For example, Figure 44A A first example of a device as described herein is shown, which includes multiple small-diameter wires (e.g., wires with a diameter of 0.015" or less). Figure 44A In this device, leads are arranged on an expandable member, such as a balloon 4485. Three pairs of laterally spaced first polarity leads 4463 and second polarity leads 4465 are shown. The balloon is positioned at the end of an elongated body (such as a catheter elongated body 4460). The device may include a distal tip region 4469 extending distally from the balloon. The balloon can be compressed to collapse the radial profile of the device (not shown) and can be inflated to expand the radial profile; in Figure 44A In the diagram, the device is shown as an expanding apparatus. Laterally spaced wires (electrodes or wire electrodes) may be spaced between, for example, 1 mm or less (e.g., 0.5 mm, etc.) and 10 mm apart.

[0291] Figure 44B Another example of an expandable device is shown, comprising a single pair of small-diameter wires (e.g., wires with a diameter of 0.015" or less). In this example, it is similar to... Figure 44A Lead electrodes 4463' and 4465' are positioned on an expandable member (e.g., balloon 4485) coupled to, for example, catheter 4460', and the device includes a distal region 4469' extending beyond the expandable member and electrodes. Figure 44B In this configuration, the pair of conductive electrodes includes a first polarized conductor 4463' that is laterally spaced from the second polarized conductor 4465'. (As in...) Figure 44A In this configuration, the electrodes extend radially, partially (or, in some examples, entirely), around the periphery of the expandable member, such as extending around the periphery at approximately 45 to 235 degrees (e.g., between 90 and 135 degrees). Although Figure 44A and Figure 44B A wire electrode extending transversely to the long axis of the expandable member is shown; however, in some examples, the electrode may extend longitudinally along the length of the expandable member and may be located at separate radial positions, such as... Figure 44C As shown.

[0292] exist Figure 44C The device includes expandable components 4485 (e.g., balloons, baskets, etc.). Figure 44C The device (shown as a balloon) allows multiple lead electrodes of different polarities to be arranged on the expandable member, extending longitudinally along the length of the expandable member from different radial positions. For example, the active region of the first polarity lead electrode 4463" extends part or all of the length of the balloon 4485 and is radially separated from the active region of the second lead electrode 4465" by an angle between approximately 40 and 60 degrees (in this example, a distance between 2 and 5 mm). The device includes an elongated catheter body 4460" and a distal end region 4469". The active region of each electrode is typically the exposed area of ​​the lead electrode; unexposed (e.g., insulated) regions 4467 may be positioned more closely together, such as... Figure 44C As shown. (As in...) Figures 44A to 44B In the example shown, Figure 44C The expandable member can switch between a collapsed configuration (not shown) and an expanded configuration (shown). Therefore, the spacing between the wire electrodes can be controlled by controlling the expansion of the expandable member.

[0293] Alternatively, in some examples, the device may not include expandable components, such as... Figure 44D As shown. In this example, the device includes an elongated body 4460"' from which a pair of wire electrodes 4463"', 4465"' extend. The wire electrodes may be supported by an insulating region 4467', as shown, and may be spaced apart radially (and / or in some cases, longitudinally) by a distance. The wires may collapse from a collapsed configuration (not shown) to an expanded configuration (shown), or vice versa.

[0294] Method of using the device disclosed herein

[0295] The devices described herein may include, or be included as part of a catheter used during minimally invasive surgery, or as part of a device used during surgery. As mentioned above, the devices described herein include (but are not limited to) [specific examples]. Figures 22A to 22C , Figures 23A to 23F , Figure 25 and Figure 26 The devices shown can be used to treat cavities within the body by applying pulses of submicrosecond (e.g., nanosecond) energy. For example, these devices can be used to treat arterial stenosis or restenosis. In some examples, these devices can be used to treat Barrett's esophagus.

[0296] Generally, the methods and devices described herein can be used to apply sub-submicrosecond (e.g., nanosecond) pulse energy. However, any of the devices described herein can also be configured to apply other types of energy, such as RF or micropulse-based electric field energy.

[0297] In some examples, the devices described herein can be inserted and / or used with catheters or other delivery devices. For example, any of these devices can be inserted through the working channel of an endoscope (such as a bronchoscope or gastroscope). In some examples, the device may include a catheter, for example having an expandable active region including electrodes, which can be used with an expandable frame (e.g., struts, ribs, etc.) and / or a balloon that can be used in the bronchial system or esophagus and can be introduced through the working channel of a bronchoscope or gastroscope. The endoscope (e.g., a bronchoscope or gastroscope) can be positioned adjacent to a treatment site that can be visualized (imaged) via a scopy or camera such as a bronchoscope (a camera built into the scopy). The device is then introduced through the working channel of the scopy. Subsequently, the device (e.g., the frame and / or balloon) can be expanded so that it expands and the electrodes on the surface of the frame / balloon are positioned to contact the tissue at the treatment site. Energy can then be delivered to the electrodes. The device can then be collapsed (e.g., by compressing the balloon, shrinking the frame, etc.) and repositioned by moving the device or endoscope and apparatus together to the next treatment site, where active area expansion and energy application can be repeated.

[0298] For example, the devices disclosed herein can be used to treat intraluminal cancers, for instance, by inserting the devices of this disclosure through a blood vessel (using a catheter, or, where applicable, a laparoscopic device), expanding the device at the treatment site (e.g., at or near the cancer within the lumen), and applying energy, particularly nanosecond pulsed electrical energy, to treat the tissue. In some examples, these devices described herein can be used to treat the prostate, such as for treating prostate cancer and / or benign prostatic hyperplasia. For example, this document describes a method of treating the prostate by inserting the devices described herein through the urethra (e.g., using various catheter-based designs described herein). In some examples, the device may be inserted transurethrally, while in some examples, the device may be inserted percutaneously. Transurethral delivery may include inserting an endourological catheter through the penis, through the urethra, and into the prostate, where energy delivery may be applied.

[0299] Other examples of treatable tissues may include the lungs (e.g., treating lung cancer), the pancreas (e.g., pancreatic cancer), and so on. This article describes other exemplary tissues (body vessels) and treatment methods.

[0300] For ease of description, the foregoing methods and apparatus describe an example of arterial treatment using pulsed electrical therapy. However, other treatments are envisioned.

[0301] As mentioned above, any of the devices described herein can be implemented in robotic systems that can be used to position and / or control electrodes during treatment. For example, a robotic system may include a movable (robotic) arm to which an elongated application tool is coupled. Various motors and other motion devices can be incorporated to enable precise movement of the operating tip of the elongated application tool in multiple directions. The robotic system and / or the elongated application tool may further include at least one image acquisition device (and preferably two or more for stereoscopic vision), which may be mounted in a fixed position or may be coupled (directly or indirectly) to the robotic arm or other controllable motion devices. In some examples, the image acquisition device may be integrated into the elongated application tool.

[0302] Examples of methods of this disclosure may be implemented using computer software, firmware, or hardware. Various programming languages ​​and operating systems may be used to implement this disclosure. A program running the method and system may contain individual program code comprising a set of instructions for performing the desired operation, or may contain multiple modules performing such sub-operations, or may be part of a single module of a larger program providing the operation. Modular construction facilitates the addition, deletion, updating, and / or modification of modules and / or features within modules.

[0303] In some examples, the user can select a specific method or example of this application, and the processor will run a program or algorithm associated with the selected method. In some examples, various types of positioning sensors can be used. For example, in some examples, a non-optical encoder can be used, where the voltage level or polarity can be adjusted based on encoder signal feedback to achieve a desired angle, speed, or force.

[0304] Some examples may relate to machine-readable media (e.g., computer-readable media) or computer program products that include program instructions and / or data (including data structures) for performing various computer-implemented operations. Machine-readable media can be used to store software and data that cause a system to perform the methods of this disclosure. The aforementioned machine-readable media can include any suitable medium capable of storing and transmitting information in a form accessible to a processing apparatus such as a computer. Some examples of machine-readable media include, but are not limited to, disk storage, such as hard disks, floppy disks, and magnetic tapes. It can also include flash memory devices, optical storage, random access memory, etc. Data and program instructions may also be embodied on a carrier wave or other transmission medium. Examples of program instructions include both machine code generated by a compiler and files containing higher-level code that can be executed using an interpreter.

[0305] Any method described herein (including a user interface) can be implemented as software, hardware, or firmware, and can be described as a non-transitory computer-readable storage medium storing a set of instructions executable by a processor (e.g., a computer, tablet, smartphone, etc.), which, when executed by the processor, causes the processor to perform or control the execution of any step in the steps, including, but not limited to: displaying, communicating with a user, analyzing, modifying parameters (including timing, frequency, intensity, etc.), determining, issuing alarms, etc. In some exemplary examples, hardware may be used in conjunction with software instructions to implement this disclosure.

[0306] When a feature or element is referred to herein as being “on” another feature or element, it may be directly on the other feature or element, or there may be intermediate features and / or elements present. Conversely, when a feature or element is referred to as being “directly on” another feature or element, there are no intermediate features or elements present. It should also be understood that when a feature or element is referred to as being “connected,” “attached,” or “coupled” to another feature or element, it may be directly connected, attached, or coupled to the other feature or element, or there may be intermediate features or elements present. Conversely, when a feature or element is referred to as being “directly connected,” “directly attached,” or “directly coupled” to another feature or element, there are no intermediate features or elements present. Although one example has been described or illustrated, features and elements so described or illustrated can be applied to other examples. Those skilled in the art will also understand that a structure or feature referred to as being “adjacent” to another feature may have portions that overlap with or are located below the adjacent feature.

[0307] The terminology used herein is for the purpose of describing particular examples only and is not intended to limit the invention disclosed herein. For example, unless the context clearly indicates otherwise, the singular forms “a” and “the” are intended to include the plural forms as used herein. It should also be understood that when the terms “comprising” and / or “including” are used in this specification, they specify the presence of this feature, step, operation, element, and / or component, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or combinations thereof. As used herein, the terms “and / or” include any and all combinations of one or more of the associated enumerations and may be abbreviated to “ / ”.

[0308] For ease of description, spatial relative terms such as “below,” “under,” “lower,” “above,” “upper,” etc., are used herein to describe the relationship of one element or feature to one or more other elements or features, as illustrated in the figures. It will be understood that, in addition to the orientations depicted in the figures, spatial relative terms are also intended to cover different orientations of the device during use or operation. For example, if the device in the figures is inverted, an element described as “below” or “under” other elements or features would be oriented as being “above” other elements or features. Thus, the exemplary term “below” can encompass both “above” and “below” orientations. The device may be oriented in other ways (rotated 90 degrees or in other orientations), and the spatial relative descriptive terms used herein will be interpreted accordingly. Similarly, unless otherwise specifically indicated, the terms “up,” “down,” “vertical,” “horizontal,” etc., are used herein solely for illustrative purposes.

[0309] Although the terms “first” and “second” may be used herein to describe various features / elements (including steps), these features / elements should not be limited by these terms unless the context otherwise indicates. These terms can be used to distinguish one feature / element from another. Therefore, without departing from the teachings of the invention, the first feature / element discussed below may be referred to as the second feature / element, and similarly, the second feature / element discussed below may be referred to as the first feature / element.

[0310] Throughout this specification and the following claims, unless the context otherwise requires, the word "comprising" and variations thereof mean a variety of components that may be used in common in a method and article of manufacture (e.g., compositions and apparatuses comprising means and methods). For example, the term "comprising" shall be understood to imply the inclusion of any stated element or step, but does not exclude any other element or step.

[0311] In general, any device or method described herein should be understood as inclusive, but all or a subset of components and / or steps may alternatively be exclusive where they can be expressed as “consisting of various components, steps, sub-components or sub-steps” or alternatively “consisting substantially of various components, steps, sub-components or sub-steps”.

[0312] As used herein in the specification and claims, including as used in the examples, and unless otherwise expressly stated, all figures, even if the term is not explicitly stated, may be interpreted as beginning with the words “about” or “approximately.” When describing magnitude and / or location, the phrase “about” or “approximately” may be used to indicate that the described value and / or location is within a reasonably expected range of the value and / or location. For example, a value may have + / - 0.1% of a specified value (or range), + / - 1% of a specified value (or range), + / - 2% of a specified value (or range), + / - 5% of a specified value (or range), + / - 10% of a specified value (or range), etc. Unless the context otherwise requires, any value given herein should also be understood to include approximately or approximate values. For example, if the value “10” is disclosed, “about 10” is also disclosed. All numerical ranges described herein are intended to encompass all subranges included therein. It should also be understood that, as those skilled in the art will appropriately understand, when a disclosed value is “less than or equal to” the stated value, it also discloses “greater than or equal to” the stated value and possible ranges between values. For example, if the value “X” is disclosed, it also discloses “less than or equal to X” and “greater than or equal to X” (e.g., where X is a numerical value). It should also be understood that throughout the application, data is provided in a variety of different formats, and this data represents a range of any combination of endpoints and start points and data points. For example, if a specific data point “10” and a specific data point “15” are disclosed, it should be understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15, as well as values ​​between 10 and 15, are disclosed. It should also be understood that each unit between two specific units is also disclosed. For example, if 10 and 15 are disclosed, 11, 12, 13, and 14 are also disclosed.

[0313] Although various illustrative examples have been described above, any of a variety of modifications may be made to the various examples without departing from the scope of the invention as defined in the claims. For example, in alternative examples, the order in which the various method steps are performed may often be changed, while in other alternative examples, one or more method steps may be skipped entirely. Optional features of the various apparatus and system examples may be included in some examples and not in others. Therefore, the foregoing description is provided primarily for illustrative purposes and should not be construed as limiting the scope of the invention as set forth in the claims.

[0314] The examples and illustrations contained herein show specific embodiments in which the subject matter can be practiced by way of illustration and not limitation. As mentioned, other examples and variations can be utilized and other embodiments derived therefrom, allowing for structural and logical substitutions and changes without departing from the scope of this disclosure. These examples of the subject matter of the invention may be referred to individually or collectively herein as the term "invention," which is merely for convenience, and if more than one invention or inventive concept is actually disclosed, this does not imply a voluntary limitation of the scope of this application to any single invention or inventive concept. Thus, although specific examples have been illustrated and described herein, any arrangement suitable for achieving the same purpose may replace the specific examples shown. This disclosure is intended to cover any and all adaptations or variations of the various examples. By reviewing the foregoing description, combinations of features of the above examples or the examples provided, as well as other examples not specifically described herein, will be apparent to those skilled in the art.

Claims

1. A device for delivering a pulsed electric field, the device comprising: Slender body; Multiple arms, the multiple arms including a first arm and a second arm configured to extend from the elongated body; A first electrode, the first electrode including a wire of a first length extending between and connected to the plurality of arms to form a first therapeutic electrode; The second electrode includes a wire of a second length that extends between and connects to the plurality of arms to form a second therapeutic electrode. as well as One or more mapping and / or sensing electrodes, said one or more mapping and / or sensing electrodes being located on one or more of the plurality of arms. The first electrode is offset from the second electrode along the length of each of the plurality of arms.

2. The device of claim 1, wherein the first electrode comprises a first or more individually controlled rings.

3. The device of claim 1, wherein the second electrode is configured to have a different polarity from the first electrode, and the second electrode is arranged concentrically relative to the first electrode.

4. The device according to any one of claims 1 to 3, wherein the first electrode and the second electrode are configured to flexibly conform to the wall of the anatomical structure.

5. The device according to any one of claims 1 to 3, wherein the first electrode comprises one or more active regions, the one or more active regions being configured to externally circumferentially connect to the walls of the anatomical structure in a partially circular or fully circular manner.

6. The device according to any one of claims 1 to 3, wherein the first electrode and the second electrode are configured to collapse when retracted into the external delivery conduit, and the elongated body is axially movable in the external delivery conduit.

7. The device according to any one of claims 1 to 3, wherein the first electrode and the second electrode have different circumferences.

8. The device according to any one of claims 1 to 3, further comprising one or more additional electrodes, said one or more additional electrodes being arranged concentrically relative to the first electrode and the second electrode and having a different length than the first electrode and the second electrode.

9. The device of claim 8, wherein any two electrodes from the first electrode, the second electrode, and the one or more additional electrodes are configured to be selected for simultaneous activation to treat tissue regions of different sizes.

10. The device according to any one of claims 1 to 3, wherein the device further comprises a magnetic sensor.

11. The device according to any one of claims 1 to 3, wherein the second electrode comprises a second one or more rings arranged around a distal end region of the elongated body, each of the second one or more rings having an active region extending along at least a portion of the length of each of the second two or more rings.

12. The device of claim 11, wherein each active region of the first one or more rings is spaced a fixed distance from each corresponding active region of the second one or more rings in the direction of the long axis of the elongated body.

13. The device according to any one of claims 1 to 3, wherein the first electrode and the second electrode are arranged on an expandable frame or an expandable balloon.

14. The device according to any one of claims 1 to 3, wherein the first electrode and the second electrode are each formed of a wire having a diameter of less than 0.2 mm.

15. The device according to any one of claims 1 to 3, wherein the first electrode is positioned distally relative to the distal end region of the elongated body, and the second electrode is positioned proximal to the first electrode.

16. The device according to any one of claims 1 to 3, wherein the first electrode is configured to slide axially proximally or distally relative to the second electrode.

17. The device according to any one of claims 1 to 3, the device further comprising a plurality of mapping and / or sensing electrodes located on the axis of the elongated body and / or at the distal end of the device.

18. The device according to any one of claims 1 to 3, wherein the first electrode and / or the second electrode comprises at least three rings.

19. The device according to any one of claims 1 to 3, wherein the first electrode and the second electrode are coplanar.

20. The device according to any one of claims 1 to 3, wherein the device is configured for bipolar or unipolar applications.

21. The device according to any one of claims 1 to 3, further comprising a central electrode.

22. The device according to any one of claims 1 to 3, further comprising a centering guide extending distally from a distal end of the device.

23. The device of claim 22, wherein the centering guide serves as or includes an additional therapeutic electrode.

24. The device according to any one of claims 1 to 3, wherein the device is configured for treating atrial fibrillation, ventricular tachycardia and other heart-related conditions.

25. The device according to any one of claims 1 to 3, wherein the device is configured to apply electrical pulses to a portion of the gastrointestinal tract, the respiratory tract, or a portion of other organs or biological tissues.

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