Circumferential ablation device and method

Abstract

Methods and apparatus for providing pulsed electrical therapy (including high voltage, sub-microsecond pulsed electrical energy) to a body vessel are disclosed.SOLUTION: The device may include deployable electrodes that conform to a transition surface that includes the antrum of the pulmonary vein.SELECTED DRAWING: Figure 4C

Description

Technical Field

[0001] (Claim of Priority) This patent application claims the priority of U.S. Provisional Patent Application No. 63 / 180,022, entitled "CIRCUMFERENTIAL ABLATION CATHETER DEVICES AND METHODS," filed on April 26, 2021, and U.S. Provisional Patent Application No. 63 / 253,119, entitled "CIRCUMFERENTIAL ABLATION CATHETER DEVICES AND METHODS," filed on October 6, 2021, each of which is hereby incorporated by reference in its entirety.

[0002] (Incorporation by Reference) All publications and patent applications cited herein are hereby incorporated by reference in their entirety to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference.

Background Art

[0003] For the electronic manipulation of biological cells, short, high-intensity electrical pulses are described. For example, electrical pulses can be used in the treatment of human cells and tissues. The voltage induced in the cell membrane may depend on the pulse length and pulse amplitude. Pulses longer than approximately 1 microsecond can charge the outer cell membrane, which can result in permanent pore opening. Permanent opening may lead to instantaneous or near-instantaneous cell death. Pulses shorter than approximately 1 microsecond can affect the intracellular interior without adversely or permanently affecting the outer cell membrane, allowing for delayed cell death using an intact cell membrane. For example, such short pulses with electric field strengths varying in the range of 10 kV / cm to 100 kV / cm can induce apoptosis (i.e., programmed cell death) in some or all cells exposed to the described electric field strengths and pulse durations. These higher electric field strengths and shorter electrical pulses may be useful when manipulating intracellular structures such as the nucleus, endoplasmic reticulum, and mitochondria. For example, such sub-microsecond (e.g., nanosecond) high-voltage pulse generators have been proposed for biological and medical applications.

[0004] In some cases, two or more electrodes are used to deliver electrical pulses, including high-field-intensity electrical pulses, to a selected treatment area. The two electrodes can be configured for bipolar operation. The electrodes are placed in contact with the tissue within the area to be treated. In some cases, the treatment area may have a changing or irregular shape. For example, the treatment area may transition from a first diameter to a second diameter. Changing diameters and / or irregular shapes can make it difficult for the electrodes to maintain constant and uniform contraction.

[0005] Therefore, it may be beneficial to provide electrodes that can adapt to treatment areas of varying and / or irregular shapes. [Overview of the Initiative]

[0006] This specification describes medical devices (e.g., devices, systems, etc.) and methods that may be used to perform medical procedures for the treatment of 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 of vascular tissue, including blood vessels and other lumens.

[0007] For example, described herein are apparatus and methods for treating the walls of anatomical structures such as body passages, cavities, or blood vessels (e.g., veins, arteries, blood vessels, heart, trachea, pharynx, larynx, bronchi, ureters, urethra, Fallopian tube, cervix, uterus, intestines (large and / or small), 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 and microsecond pulsed electric fields. For convenience of explanation, all such anatomical structures, cavities, tubes, lumens, passages, or blood vessels are referred to herein as body vessels. In some examples, body vessels may include pulmonary veins, sinuses, and other suitable lumens. In particular, the methods and apparatus described herein may be configured to selectively treat body vessels with changing, transitional, and / or irregular surfaces. Electrodes that can be fitted into a body vascular system may include a first electrode and a second electrode, which are deployed from a catheter and configured to provide a submicrosecond (e.g., nanosecond) pulsed electric field in a localized manner to fit, for example, a portion of the wall of a body vascular system, thereby limiting or preventing damage to deeper non-target areas.

[0008] The methods and apparatus described herein are not limited to vascular treatments such as angioplasty procedures, but can be used to treat other body lumens where luminal narrowing may be a problem. For example, the lungs (airways), stomach cavity, tubes, etc., may be treated as described herein. In some examples, the instruments and methods described herein are configured for insertion and treatment by applying a submicrosecond (e.g., nanosecond) pulsed electric field into lumens or other otolaryngological structures such as the ear, nose, or throat, including anatomical structures such as the nasal turbinates, tonsils, tongue, soft palate, parotid gland, and structures connecting the pharynx to the stomach, for example. These instruments and devices may be configured for insertion into these structures, for example, as elongated applicator tools, which include catheters, tubes, etc., that are sized and shaped to fit into the ear, nose, or throat and / or to treat associated anatomical structures (e.g., nasal turbinates, tonsils, tongue, soft palate, parotid gland, etc.). For example, described herein are methods and apparatus configured for the delivery of submicrosecond (e.g., nanosecond) pulsed electric fields to portions of the gastrointestinal tract, including but not limited to the esophagus, such as the stomach, small intestine, large intestine, duodenum, and colon. Also described herein are methods and apparatus configured for the delivery of submicrosecond (e.g., nanosecond) pulsed electric fields to portions of the airway, including the trachea, pharynx, larynx, bronchi, and bronchioles. The methods and apparatus described herein are also particularly useful in cardiac applications, including but not limited to the treatment of atrial fibrillation.

[0009] The devices described herein may include elongated applicator tools (e.g., catheters) that can be inserted into body vessels or lumens, 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 applicator tools may include an elongated flexible body extending from proximal to distal. One or more electrodes configured for the delivery of electrical pulses (e.g., nanosecond pulses) to target tissue may be present in the end regions of the flexible body.

[0010] An applicator ("applicator tool") may be configured to be detachably coupled to, for example, a pulse generator configured to generate sub-microsecond (e.g., nanosecond) pulse energy, such coupling can be done via a handle located proximal to a distal end region containing an electrode. The electrode may be deployable and may be on an expandable member that expands to contact the vessel wall. This deployment can be controlled by the handle. Alternatively, in some cases, the applicator tool (also referred to herein as an apparatus or device) may be configured to be directly coupled to a pulse generator without requiring a handle. For example, the apparatus described herein comprises medical devices and instruments for use in a procedure to insert an applicator tool into a lumen. These apparatus can be introduced into a blood vessel, for example, through an external delivery catheter or guide sheath.

[0011] Any of the devices described herein may be configured to function within a region of a body having a varying diameter (e.g., from wide to narrow, or from narrow to wide) that includes a tapered or funnel-shaped region. For example, some of the devices described herein may include at least two ring-shaped (elliptical, circular, etc.) electrodes having different diameters. In some examples, these ring electrodes may be adjustable in diameter and / or lateral position relative to each other.

[0012] In some examples, the applicator may include one or more contact projections (e.g., ribs, wires, springs, contact plates, contact struts, balloons, etc.) that can be operated to extend from the proximal end of the applicator, for example, by the movement of the proximal handle to which the applicator tool is attached. The contact projections typically contact the wall of the lumen into which the applicator tool is inserted, improving access to and contact between the electrode and the tissue. For example, the contact projections may be inflatable elements (e.g., balloons) or mechanical elements (e.g., a pair of plates or arms). In some examples, multiple contact projections may be positioned along the length of the applicator and may be moved closer or further away along the length of the distal end region of the applicator. In some examples, the contact projections are located on the sides of the electrode. In some examples, the contact projections include the electrode. The contact projections may be retractable / removable within the applicator tool or simply relative to the applicator tool.

[0013] In one example, the applicator may include an elongated body, such as an elongated catheter body; a first electrode having a first diameter, formed from one or more loops and flexibly coupled to the elongated catheter body; and a second electrode having a second diameter, formed from one or more different flexible loops and flexibly coupled to the elongated catheter body. The first and second electrodes may come into contact with bodily blood vessels, particularly bodily blood vessels with irregular, changing, or transitioning surfaces.

[0014] In some examples, the first and second electrodes may be divided into lobes, each lobe being connected to an elongated body (e.g., an elongated catheter body) using arms. In some examples, the first and second electrodes may include two or more lobes.

[0015] 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 catheter body). In further examples, the first and second electrodes may be movable within the elongated catheter body and may be configured to extend outward from the elongated catheter body and fold when retracted into the elongated catheter body. In some other examples, one of the first and second diameters is smaller than the other. In yet another example, the first electrode is positioned distal to the end of the elongated catheter body (e.g., the distal end of the elongated catheter body), and the second electrode is positioned between the first electrode and the distal end of the elongated catheter body.

[0016] In some examples, the first and second electrodes are configured to flexibly contact sinuses associated with pulmonary veins. In some other examples, the first and second conductors are configured to deliver pulsed electrotherapy, with pulsed energy transmitted between the first and second conductors. In yet another example, the first and second conductors are configured to deliver pulsed electrotherapy, with energy transmitted between the first and third conductors, or between the second and third conductors.

[0017] In some examples, the first and second conductors are configured to vary the distance between them.

[0018] In another example, a device for delivering nanosecond pulsed electric fields may include an elongated catheter body, a shape support member coupled to the elongated catheter body and configured to form a shape, a conductive blade circumferentially surrounding the shape support member and configured to form a first electrode, and one or more conductive bands circumferentially surrounding the conductive blade and a portion of the shape support member and configured to form a second electrode. The device may further include a tubular insulating member disposed between the shape support and the conductive blade.

[0019] In some examples, the apparatus may further comprise one or more band insulators disposed between a conductive blade and one or more conductive bands, configured to electrically isolate one or more conductive bands from the conductive blade. Furthermore, the position of the conductive bands may be configured to at least partially determine the electric field density.

[0020] In some other examples, the shape support member may be made of a nickel-titanium alloy. Furthermore, the shape support member can conform to the shape of the pulmonary vein sinuses. In some examples, the conductive blade and one or more conductive bands may be configured to deliver bipolar nanosecond pulsed electrotherapy. In other examples, the conductive blade and one or more conductive bands may be configured to deliver unipolar nanosecond pulsed electrotherapy.

[0021] A method for delivering a submicrosecond pulsed electric field to a body vascular system may include positioning an applicator containing two or more electrodes within a specified treatment area, placing the two or more electrodes in contact with tissue within the specified treatment area, and applying pulsed electrotherapy through 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 molded electrode and a second molded electrode. The first molded electrode may have a first diameter, and the second molded electrode may have a second diameter, the first diameter being different from the second diameter.

[0022] In some examples, the first molding electrode may be positioned on a different plane from the second molding electrode. In some other examples, the first molding electrode may be coplanar with the second molding electrode.

[0023] In some cases, pulsed electrotherapy may include an electric field between two or more electrodes. In other cases, pulsed electrotherapy may include an electric field between at least one of the two or more electrodes and a third electrode.

[0024] The devices described herein may generally be configured to safely and reliably deliver pulses such as microseconds, nanoseconds, and picoseconds, and may include electric fields with pulse widths of 0.1 nanoseconds (ns) to less than 1,000 nanoseconds, or shorter pulse widths such as 1 picosecond, which may be referred to as submicrosecond pulsed electric fields. These pulse energies may have high peak voltages such as 1 to 5 kilovolts / centimeter (kV / cm), 10 kV / cm, 20 kV / cm, or 100 kV / cm or more. In some applications, the pulse energy may be less than 1 kV / cm. Therapy of living cells can utilize numerous periodic pulses at frequencies ranging from 0.1 Hz to 100,000 Hz, for example, to induce apoptosis in endothelial growth tissue causing restenosis. Selective treatment of vascular walls using high-voltage, submicrosecond pulsed energy, due to its non-thermal nature, can induce apoptosis in restenotic cells without substantially affecting normal cells in the surrounding tissue. The subject may be a patient (human or non-human, including animals). The user may operate the device described herein on the subject. The user may be a physician (doctor, surgeon, etc.), medical technician, nurse, or other healthcare provider.

[0025] Therefore, the application of high-voltage, high-speed (e.g., microsecond or submicrosecond) electrical pulses may include, for example, the application of a series of electrical pulses having pulse widths of 0.1 nanoseconds (ns) to 1,000 nanoseconds. The application of high-voltage, high-speed electrical pulses may include, for example, the application of a series of submicrosecond electrical pulses having peak voltages of 1 kilovolt / centimeter (kV / cm) to 500 kV / cm. The application of high-voltage, high-speed electrical pulses may include, for example, the application of a series of submicrosecond electrical pulses at frequencies of 0.1 / second (Hz) to 100,000 Hz.

[0026] Any of these devices can be used with a pulse generator. For example, an elongated applicator (e.g., an applicator tool) as described herein, a connector, e.g., a high-voltage connector adapted to couple the elongated applicator tool to a pulse generator, and a pulse generator configured to generate a plurality of electrical pulses having an amplitude of at least 0.1 kV and a duration of less than 1000 nanoseconds, the pulse generator comprising a port configured to be connected to the high-voltage connector, can be included in a system for treating tissue described herein. In some examples, the applicator tool includes an elongated body having a distal end region configured such that one or more electrodes extend therefrom. The distal end can, in some examples, be steerable (e.g., capable of articulating).

[0027] As described above, any of these devices can be configured such that the proximal end of the applicator tool is adapted to be coupled to a robot or a movable arm, for example, for computer-controlled operation of a set of electrodes. Alternatively, or additionally, the proximal end of the applicator tool can be adapted to be coupled to the handle of the pulse generator, which in turn can be adapted for connection to a robotic arm.

[0028] In some examples, as described above, the device can be configured to adjust the distance between electrodes for applying treatment in the distal end region of the applicator. In some examples, the applicator includes at least two circumferentially arranged electrodes, each electrode being circumferentially arranged around the 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 separation between the circumferentially arranged electrodes to be, for example, between 5 mm and 40 mm (such as between 10 mm and 20 mm). The circumferentially arranged electrodes can be an electrode ring (extending completely or partially circumferentially around), or a plurality of separate electrodes circumferentially arranged around the applicator. By adjusting the spacing between the electrodes, the user can adjust and / or correct the placement and fit within the inner wall or cavity, especially when the diameter / size of the blood vessel changes (including rapidly changing) according to the longitudinal position. One electrode ring can fit one circumference, and the other electrode ring can fit a larger or smaller circumference, and the spacing between them can be adjusted in some examples.

[0029] In use, any of the devices described herein can be used to apply energy, particularly including sub-microsecond (e.g., nanosecond) pulse fields. Sub-microsecond pulsed electromagnetic fields can induce apoptosis in cell structures.

[0030] For example, described herein are devices (e.g., devices, systems, etc., including an electrode applicator) for delivering a pulsed electric field into a body lumen. These devices may include: an elongated body (having an elongated flexible body); a first electrode comprising one or more first loops and having a first active region formed on the one or more first loops, the first active region being positioned to surround a body lumen, and further comprising the one or more first loops being flexibly coupled to the distal end region of the elongated body; and a second electrode comprising one or more second loops and having a second active region formed from the one or more second loops, the second active region being positioned to surround a body lumen, the one or more second loops being flexibly coupled to the distal end region of the elongated body, and further comprising the first electrode being laterally offset from the second electrode along the distal end region of the elongated body.

[0031] 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 (non-insulating) region of a conductive material (e.g., a conductive wire) configured to release electrical energy. Generally, the devices described herein may include a first electrode with a first conductive region extending over multiple lengths of different loops forming a first electrode (or, in some examples, a second). All of the loops of the first electrode (and thus all of the 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 of the loops forming the second electrode (and thus all of the sub-regions of the loops) may be electrically coupled together as a single anode or a single cathode.

[0032] In some examples, the first electrode consists of a single loop. In other examples, the first electrode consists of multiple loops forming the first electrode, and these loops are electrically connected. Similarly, the second electrode may be a single loop or multiple distinct loops.

[0033] In any of these devices, the first electrode and / or the second electrode may traverse the distal end region of the elongated body, and / or the second electrode may traverse the distal end region of the elongated body. In any of these devices, the first electrode and / or the second electrode may include a plurality of first loops arranged as petals around the distal end region of the elongated body. The outer portion of each petal can form an active area for a single electrode. This configuration may enable more robust treatment around the entire circumference of a blood vessel without requiring multiple repositioning steps of the electrode pair to cover the same larger area around the circumference of the blood vessel.

[0034] Generally, the first active region of the first electrode may have a smaller diameter than the second active region (for example, the diameter of the loop forming the first electrode may be different from the diameter of the loop forming the second active region of the second electrode). In some examples, the diameters of the loops forming the first and second electrodes may be approximately the same.

[0035] 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 circumference of the expandable member, thereby being able to at least partially surround the blood vessel. The expandable frame can support the first and second active electrodes. Therefore, the first and second electrodes may be positioned on the expandable frame. For example, the first and second electrodes may be positioned on an expandable balloon.

[0036] In any of these examples, the first electrode and the second electrode may each be formed from a wire having a diameter of less than approximately 0.2 mm (e.g., less than approximately 0.19 mm, less than approximately 0.18 mm, less than approximately 0.17 mm, less than approximately 0.16 mm, less than approximately 0.15 mm, etc.).

[0037] Generally, the first and second electrodes are configured to flexibly conform to a body lumen such that the active region can extend circumferentially around the periphery of the lumen. As used herein, “arranged or configured to surround a body lumen” may mean at least partially extending around the circumference of the body lumen (e.g., less than 360 degrees, e.g., about 270 degrees or more, e.g., 300 degrees or more, 320 degrees or more, 330 degrees or more, 340 degrees or more, 340 degrees or more, about 360 degrees). Thus, the first active region arranged to surround a body lumen may include an active region that extends completely or almost completely around the circumference of the lumen (e.g., about 270 degrees or more, about 300 degrees or more, about 320 degrees or more, about 330 degrees or more, about 340 degrees or more, about 340 degrees or more, about 360 degrees, etc.). In some cases, the first active region is configured to enclose the body lumen in an almost perfect circle.

[0038] Any of these devices may include an external catheter or a guide sheath (e.g., a delivery catheter), and an elongated body forming or holding the first and second electrodes may be slidably disposed within the external catheter. The first and second electrodes are configured to fold when retracted into or introduced into the external catheter and / or to expand radially outward when extending from the distal end of the delivery (external) catheter.

[0039] The first electrode may be positioned distal 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 distal to the second electrode.

[0040] In some examples, the first electrode may have an anode, and the second electrode may have a cathode. The device may be configured to deliver pulsed energy between the first electrode (anode) and the second electrode (cathode).

[0041] In any of the examples described herein, the first active region and the second active region may each be longer than 5 cm in length. The first active region and the second active region may each have a diameter of less than 0.2 mm.

[0042] Also described herein is a device for delivering a pulsed electric field, the device comprising: an elongated catheter body; a first electrode having a first wire loop, the first wire loop flexibly extending from the elongated catheter body, and further having a first active region including at least a portion of the first wire loop and extending to a length of more than 5 cm; and a second electrode having a second wire loop, the second wire loop flexibly extending from the elongated catheter body, and further having a second active region including at least a portion of the second wire loop and extending to a length of more than 5 cm.

[0043] The first and second active regions may be separated by a fixed distance in the direction of 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 loop is the same size as the second loop.

[0044] The first electrode may be positioned distal 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.

[0045] In general, the devices described herein are configured to favorably apply energy between a first electrode and a second electrode around a circumferential region of a blood vessel in the body without requiring multiple repositioning steps to treat the entire circumference (or a large portion thereof). This solves the problems of many other electrical delivery systems that respond to multiple distinct active regions that may leave gaps. The devices described herein are particularly well suited to, but are not limited to, the application of nanosecond pulses. Nanosecond pulsed energy can act by entering cells non-thermally and altering the function of internal organelles, including mitochondria and endoplasmic reticulum. For example, a nanosecond pulsed electric field can cause intracellular disruption, leading to controlled cell death. In examples where the applied energy is a nanosecond (or faster) pulsed electric field, the active region of each electrode may be long and thin, such as formed by a wire, so that the applied electric field applies very little thermal energy, thus preventing damage to non-cellular tissue.

[0046] For example, also described herein is a method for delivering a pulsed electric field to the wall of a body vascular vessel in a subject, the method comprising positioning a first electrode comprising one or more first wire loops and a second electrode comprising one or more second wire loops within the body vascular vessel such that a first active region of the first one or more wire loops is electrically in communication with a first circumference of the wall and a second active region of the second one or more wire loops is electrically in communication with a second circumference of the wall longitudinally separated from the first circumference of the wall, and applying pulsed electrotherapy between the first active region and the second active region.

[0047] Positioning the first and second electrodes may include deploying the first and second electrodes from the delivery catheter by moving the delivery catheter relative to an elongated body to which the first and second electrodes are coupled, and extending at least one of the first and second electrodes from a delivery configuration to a deployment configuration. In some examples, deploying the first electrode includes bringing its wall into contact with multiple electrically continuous wire lengths of one or more first wire loops. In some examples, deploying the second electrode includes bringing its wall into contact with multiple electrically continuous wire lengths of one or more second wire loops. Deploying the first electrode may include extending the first electrode to have a larger diameter than the second electrode. In some examples, deployment includes deploying into a pulmonary vein sinus. For example, deployment may include deploying the first electrode so that it is coplanar with the second electrode.

[0048] As described above, applying pulsed electrotherapy may involve applying an electric field between a first active region and a second active region. In particular, applying pulsed electrotherapy may involve applying pulses having a duration of nanoseconds (a duration of less than 1000 ns).

[0049] Also described herein is an elongated body extending from proximal to distal, the elongated body comprising: an elongated body configured to be inserted into a body vascular duct; and an applicator region located in the distal end region of the elongated body, comprising a plurality of expandable ribs configured to expand outward within the body vascular duct from a folded configuration, each rib comprising a non-insulating active region, and further comprising a first subset of the plurality of expandable ribs configured to have a first polarity, and a second subset of the plurality of expandable ribs configured to have a second polarity.

[0050] For example, the non-insulating active region of each of the multiple ribs may be configured to be substantially linear and parallel to the long axis of a portion of the applicator region. In some configurations, the non-insulating active flat region of each rib may also be configured to remain the same length during rib expansion, regardless of how much each rib is extended. Each of the multiple ribs may have an f-hinge region on each side of the non-insulating active region. The hinge region may be covered with a flexible insulator.

[0051] In some examples, the elongated body may comprise 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 to deform the applicator area between a folded configuration and an expanded configuration in which the multiple expandable ribs are expanded outward.

[0052] 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. Multiple expandable ribs may be substantially flat.

[0053] Any of these devices may include an inflatable member within the applicator region, configured to expand outward to drive the expansion of multiple ribs.

[0054] In some examples, the applicator region is configured to extend outward with respect to the long axis of the applicator region into a shape with a larger cross-sectional area, for example, larger distally than proximal, or in some examples, larger proximal than distal. For example, the applicator region may include a teardrop shape.

[0055] The non-insulating active region of each rib may be located within the distal portion of the applicator region such that the non-insulating active region faces distally in the extended configuration.

[0056] Any of these devices of this disclosure may include a centering guide extending distally from the applicator region. In some examples, the centering guide may be configured and used as one of the electrodes.

[0057] In some examples described herein, the device may comprise an elongated body extending proximal to distal, the elongated body being configured to be inserted into a body vascular duct; a first wire extending distally from the elongated body, the first wire having a first active region adjacent to a first insulating region of the first wire; and a second wire extending distally from the elongated body, the second wire having a second active region adjacent to a second insulating region of the second wire, wherein the first active region is separated from the second active region by a minimum distance d substantially constant along the length of the first active region, and further configured the first active region to have a first polarity, and the second active region to have a second polarity. The first wire may have a first loop, and the second wire may have a second loop positioned concentrically with respect to the first loop or within the first loop. In any of these devices, the first and second wires may extend from an elongated body in a plane. In some examples, the insulating region and / or the elongated body may have bends such that the first and second wires extend at an angle with respect to the long axis of the elongated body.

[0058] Also described herein are apparatuses (e.g., devices, systems, etc.) for delivering pulsed energy as point-by-point therapy or as single-shot therapy. Point-by-point therapy generally involves applying an area between two smaller electrically active regions, while single-shot therapy generally involves treating a larger area having multiple electrically coupled active regions. For example, the apparatus may include an elongated body and a plurality of loops or ribs extending radially outward from the elongated body at a first circumferential position, each loop or rib having a non-insulated electrically active region facing radially outward such that the non-insulated electrically active region surrounds the first circumferential position of the elongated body, and an electrical connector configured to switch between a first configuration in which the plurality of non-insulated electrically active regions are electrically coupled together to apply energy with a first polarity and a second configuration in which the non-insulated electrically active regions are activated separately.

[0059] In some examples, the electrical connector can electrically couple all of the non-isolated electrically active regions of multiple loops or ribs in a first configuration. In the first configuration, the electrical connector may be configured to electrically couple a first subset of the non-isolated electrically active regions, the loops or ribs of multiple loops or ribs, applying energy with a first polarity, and to apply energy with a second polarity to a second set of loops or ribs alternating with the first set of loops or ribs.

[0060] In some examples, a device for delivering pulse energy either point-by-point or as a single shot may include an elongated body, a plurality of loops or ribs extending radially outward from the elongated body at a first circumferential position, each loop or rib having a non-insulated electrically active region facing radially outward such that the non-insulated 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 in which all of the non-insulated electrically active regions are electrically coupled together and a second configuration in which the non-insulated electrically active regions are activated separately. The second electrically active region may include a second plurality of loops or ribs extending radially outward from the elongated body at a second circumferential position, each loop or rib of the second plurality of loops or ribs having a non-insulated electrically active region facing radially outward such that the non-insulated electrically active region surrounds the second circumferential position of the elongated body. The same or separate electrical connectors may be configured to switch between a first configuration in which all of the non-insulated electrically active regions of the second set of loops or ribs are electrically coupled together, and a second configuration in which the non-insulated electrically active regions of the second set of loops or ribs are activated separately. In some examples, the second electrically active region is a distal counter electrode extending from the distal end of an elongated body.

[0061] For example, the Specified herein 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 comprising one or more first loops and having a first active region formed on the one or more first loops, the first active region being configured to surround a first region of the wall of an anatomical structure, and the one or more first loops being flexibly coupled to the distal end region of the elongated body; and a second electrode comprising one or more second loops and having a second active region formed from the one or more second loops, the second active region being configured to surround a second region of the wall of an anatomical structure, the one or more second loops being flexibly coupled to the distal end region of the elongated body, and the first electrode being radially offset from the second electrode, or laterally offset, or both radially and laterally.

[0062] Any of the devices described herein may be configured such that at least one of the first and second active regions encloses the wall of an anatomical structure in a partial, nearly complete, or complete circle.

[0063] Any of these devices may include a plurality of mapping and / or sensing electrodes on a portion of the first and / or second electrode. For example, the sensing and / or mapping electrodes may be radially inward of the first and / or second active region. The sensing and / or mapping electrodes may have a total surface area smaller than the surface area of ​​either the first and / or 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 insulated from the electrically active region and each may be connected to or connectable to the mapping system and / or subsystem via one or more lines (e.g., wires, traces, etc.).

[0064] Also described herein are apparatus for delivering a pulsed electric field, comprising: an elongated body; a first electrode having a first wire loop, the first wire loop flexibly extending from the elongated body, and the first electrode having a first active region extending along the length of the first wire loop; and a second electrode having a second wire loop, the second wire loop flexibly extending from the elongated body, and the second electrode having a second active region extending along the length of the second wire loop, and the first electrode being offset radially from the second electrode, or offset laterally, or both radially and laterally. As described above, any of these apparatuses may include a plurality of mappings and / or electrodes on the first electrode outside the first active region and / or on the second electrode outside the second active region.

[0065] Also described herein are methods for delivering a pulsed electric field to the wall of an anatomical structure within a target body using an applicator, the method comprising positioning a first electrode of an applicator having one or more first loops and a second electrode of an applicator having one or more second loops within the target body such that a first active region of the first one or more loops forms a first contact loop electrically communicating with a first region of the wall of the anatomical structure, and a second active region of the second one or more loops forms a second contact loop electrically communicating with a second region of the wall of the anatomical structure, the second contact loop being radially and / or longitudinally separated from the first region of the wall of the anatomical structure, and applying pulsed electrotherapy between the first active region and the second active region. Any of these methods may include mapping the location of the applicator relative to the wall of the anatomical structure using one or more mapping sensors on the applicator. Any of these methods may involve using one or more sensors on an applicator to sense one or more electrical properties of the wall of an anatomical structure before applying pulsed electrotherapy, and / or during the application of pulses of pulsed electrotherapy, and / or after applying pulsed electrotherapy.

[0066] Any of these methods may be methods for treating cardiac tissue, including ablation of cardiac tissue. For example, described herein is a method for delivering a pulsed electric field to the wall of a heart in the body of a subject using an applicator, the method comprising positioning a first electrode of an applicator having one or more first loops and a second electrode of an applicator having one or more second loops in the body of a subject such that the first active region of the first one or more loops forms a first contact loop that is electrically in communication with a first region of the heart wall (e.g., pulmonary sinuses, pulmonary vein foramina, and / or other cardiac wall muscle / tissue), and the second active region of the second one or more loops forms a second contact loop that is electrically in communication with a second region of the heart wall, the second contact loop being separated radially and / or longitudinally from the first region of the heart wall, and applying pulsed electrotherapy between the first active region and the second active region. Any of these methods may include mapping the applicator's location relative to the heart wall using one or more mapping sensors on the applicator. In some examples, the method may include sensing one or more electrical properties of the heart wall using one or more sensors on the applicator before applying pulsed electrotherapy and / or during the application of pulses of pulsed electrotherapy and / or after applying pulsed electrotherapy. Any of these methods may include mapping tissue (e.g., the heart) using, for example, 3D electroanatomical mapping. In some examples, the method may include mapping or otherwise locating the applicator on the tissue map.

[0067] Also described herein is an apparatus comprising an elongated body extending from proximal to distal, and an applicator region at the distal end region of the elongated body, wherein the applicator region comprises a first wire extending distally from the elongated body, the first wire having a first active region adjacent to a first insulating region of the first wire, and a second wire extending distally from the elongated body, the second wire having a second active region adjacent to a second insulating region of the second wire, wherein the first active region is separated from the second active region by a minimum distance d that is substantially constant along the length of the first active region, and further, the first active region is configured to have a first polarity, and the second active region is configured to have a second polarity.

[0068] The apparatus may comprise an elongated body extending from proximal to distal, and an applicator region located at the distal end of the elongated body, wherein the applicator region comprises an expandable member configured to expand radially relative to the elongated body, a first wire on the expandable member having a first active region adjacent to a first insulating region of the first wire, and a second wire on the expandable member having a second active region adjacent to a second insulating region of the second wire, the first active region being separated from the second active region by a minimum distance d substantially constant along the length of the first active region, the first and second wires having a thickness of 0.38 mm or less, and further comprising a second wire having a first polarity in the first active region and a second active region having a second polarity.

[0069] All methods and apparatus described herein, including various combinations of features disclosed with reference to various examples, may be used in any combination to achieve the interests contemplated and described herein. [Brief explanation of the drawing]

[0070] A better understanding of the features and advantages of the methods and apparatus described herein will be obtained by referring to the following detailed description, which includes exemplary embodiments, and the accompanying drawings. [Figure 1] Figure 1 illustrates an example of a system for delivering high-voltage, high-speed pulses of electrical energy. [Figure 2] Figure 2 illustrates an example of an applicator configured to deliver electrotherapy, such as nanosecond pulsed energy therapy, into the body's blood vessels. [Figure 3A] Figure 3A shows an example of an applicator configured to deliver energy therapy into the body's blood vessels either circumferentially or point-by-point. [Figure 3B] Figure 3B shows an example of an applicator configured to deliver energy therapy into the body's blood vessels and configured for "front-facing" and "side-facing" energy application. [Figure 4A] Figure 4A shows another example of an applicator configured to deliver nanosecond pulsed energy therapy into the body's blood vessels. [Figure 4B] Figure 4B shows another example of an applicator configured to deliver nanosecond pulsed energy therapy into the body's blood vessels. [Figure 4C] Figure 4C shows another example of a device for delivering energy (e.g., nanosecond pulsed electrical energy) into the body's blood vessels, either as a single shot or point-by-point. [Figure 4D] Figure 4D shows another example of a device for delivering energy (e.g., nanosecond pulsed electrical energy) into the body's blood vessels, either as a single shot or point-by-point. [Figure 4E] Figure 4E shows another example of a device for delivering energy (e.g., nanosecond pulsed electrical energy) into the body's blood vessels. [Figure 5] Figure 5 shows the applicator from Figure 4 positioned within the pulmonary vein. [Figure 6A] Figure 6A shows another applicator configured to deliver nanosecond pulsed energy therapy into the body's blood vessels. [Figure 6B] Figure 6B shows an example of the effect of treatment using an applicator similar to the one in Figure 6A. [Figure 7] Figure 7 shows another applicator similar to the one shown in Figure 4A, configured to deliver nanosecond pulsed energy therapy into the body's blood vessels. [Figure 8A] Figure 8A shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 8B] Figure 8B shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 8C] Figure 8C shows another example of an applicator in which the spacing between electrodes is adjustable. [Figure 9] Figure 9 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 10] Figure 10 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 11] Figure 11 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 12] Figure 12 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 13] Figure 13 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 14] Figure 14 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 15] Figure 15 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 16] Figure 16 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 17A]Figure 17A shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 17B] Figure 17B shows further details of the applicator in Figure 17A. [Figure 18] Figure 18 shows an example of a fixture for manufacturing the applicator shown in Figure 17A. [Figure 19] Figure 19 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 20] Figure 20 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 21] Figure 21 shows another applicator configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. [Figure 22A] Figure 22A illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 22B] Figure 22B illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 22C] Figure 22C illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 23A] Figure 23A illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 23B] Figure 23B illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 23C] Figure 23C illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 23D] Figure 23D illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 23E] Figure 23E illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 23F] Figure 23F illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 24A]Figure 24A illustrates the treatment of model tissue using devices such as those shown in Figures 22A to 22C. [Figure 24B] Figure 24B illustrates the treatment of model tissue using devices such as those shown in Figures 22A to 22C. [Figure 24C] Figure 24C illustrates the treatment of model tissue using devices such as those shown in Figures 22A to 22C. [Figure 24D] Figure 24D illustrates the treatment of model tissue using devices such as those shown in Figures 22A to 22C. [Figure 24E] Figure 24E illustrates the treatment of model tissue using devices such as those shown in Figures 22A to 22C. [Figure 25] Figure 25 shows an example of a device for delivering pulsed electrical energy into a lumen. [Figure 26] Figure 26 shows a device for delivering pulsed electrical energy into a lumen. [Figure 27] Figure 27 illustrates the apparatus shown in Figure 26, which applies energy around the pulmonary veins. [Figure 28A] Figure 28A illustrates an example of a device for delivering pulsed electrical energy into a lumen. [Figure 28B] Figure 28B shows the apparatus of Figure 28A in a lumen with a narrow (Figure 28B) diameter and a larger (Figure 28C) diameter. [Figure 28C] Figure 28C shows the apparatus of Figure 28A in a lumen with a narrow (Figure 28B) diameter and a larger (Figure 28C) diameter. [Figure 29A] Figure 29A shows an example of a rib in the applicator region that bends in a curve. [Figure 29B] Figure 29B shows an example of ribs in the applicator region that are hinged together as described herein. [Figure 30A] Figure 30A shows a device for delivering pulsed electrical energy into the body's blood vessels (lumens). [Figure 30B] Figure 30B shows a magnified view of the hinge area of ​​the device shown in Figure 30A. [Figure 31]Figure 31 shows a device for delivering pulsed electrical energy into a lumen, including a balloon for expanding the applicator area. [Figure 32] Figure 32 shows a device for delivering pulsed electrical energy into a lumen. [Figure 33] Figure 33 shows another diagram of the apparatus shown in Figure 32. [Figure 34A] Figure 34A shows an example of a paddle-shaped device for delivering pulsed electrical energy into a lumen. [Figure 34B] Figure 34B shows an example of a paddle-shaped device for delivering pulsed electrical energy into a lumen. [Figure 34C] Figure 34C shows an example of a paddle-shaped device for delivering pulsed electrical energy into a lumen. [Figure 35] Figure 35 shows an example of a device for delivering pulsed electrical energy into a lumen. [Figure 36A] Figure 36A illustrates a further example of a device for delivering pulsed electrical energy into a lumen. [Figure 36B] Figure 36B illustrates a further example of a device for delivering pulsed electrical energy into a lumen. [Figure 36C] Figure 36C illustrates a further example of a device for delivering pulsed electrical energy into a lumen. [Figure 36D] Figure 36D illustrates a further example of a device for delivering pulsed electrical energy into a lumen. [Figure 37] Figure 37 illustrates the difficulties in positioning the device for treating the pulmonary veins. [Figure 38A] Figure 38A shows a device for delivering pulsed electrical energy into a lumen, including a centering guide. [Figure 38B] Figure 38B shows a device for delivering pulsed electrical energy into a lumen, including a centering guide. [Figure 39] Figure 39 shows an example of a device for delivering pulsed electrical energy into a lumen, including a centering guide. [Figure 40A] Figure 40A illustrates how to use a device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 40B] Figure 40B illustrates how a device can be used to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 40C] Figure 40C illustrates how a device can be used to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 40D] Figure 40D illustrates how to use a device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 41A] Figure 41A illustrates how to use a device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 41B] Figure 41B illustrates how a device can be used to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 41C] Figure 41C illustrates how a device can be used to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 41D] Figure 41D illustrates how to use a device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 42] Figure 42 is a flowchart illustrating one example of a method for delivering pulsed electrotherapy to a selected treatment area of ​​a patient. [Figure 43A] Figure 43A illustrates an example of an applicator including a treatment electrode and a sensing / mapping sensor. Figure 43A shows a distal end view, and Figure 43B shows a lateral perspective view. [Figure 43B] Figure 43B illustrates an example of an applicator including a treatment electrode and a sensing / mapping sensor. Figure 43A shows the distal end view, and Figure 43B shows a lateral perspective view. [Figure 43C] Figure 43C schematically illustrates an example of a system including an applicator as shown in Figures 43A to 43B. [Figure 44A] Figure 44A shows an example of a device including a small-diameter wire electrode as described herein. [Figure 44B] Figure 44B shows an example of a device including a small-diameter wire electrode as described herein. [Figure 44C] Figure 44C shows an example of a device including a small-diameter wire electrode as described herein. [Figure 44D] Figure 44D shows an example of a device including a small-diameter wire electrode as described herein. [Modes for carrying out the invention]

[0071] Described herein are systems and methods for treating a body, including a body lumen such as a body vascular system, with a pulsed electric field, using electrodes adapted to be inserted into a body vascular system, such as an artery, vein, sinus, and any other blood vessel in the body as described above. Generally, the apparatus and methods described herein, but not limited to, can be positioned inside any body chamber, including a tubular body member or a body lumen such as a blood vessel, against any wall of an organ, and / or within a transition area (e.g., sinus, pore, etc.).

[0072] In some cases, body vessels may have irregular or variable shapes. For example, pulmonary venous sinuses may transition from relatively large area or diameter to relatively small area or diameter. On these body vessel surfaces, it may be difficult for electrodes to establish effective contact for providing treatment. Described herein are various electrodes that can readily adapt and conform to irregular and / or changing shapes and provide reliable contact with body vessels.

[0073] Pulsed electrotherapy can be microsecond pulse therapy or submicrosecond pulse therapy, including nanosecond pulses. For example, nanosecond pulsed electric field therapy may refer to the application of a relatively high voltage (sometimes 5kV or more) for a relatively short time (sometimes about 1 nanosecond to 999ns). These high voltages and short durations generate a pulsed electric field in the area to which the voltage is applied. In some cases, nanosecond pulses can induce apoptosis in cellular structures, which can reduce the inflammatory response of cells.

[0074] Any of the methods described herein may be ablation methods. For example, the methods described herein may be particularly useful for the treatment of cardiac regions, blood vessels, etc. (e.g., sinuses, but not limited to sinuses). In some cases, these methods and apparatus may be used for the treatment of atrial fibrillation and other cardiac conditions, including ablation of cardiac tissue. As will be described in more detail below, any of these methods and apparatus may be used to treat body regions, such as pulmonary sinuses, which have a tapered or narrow shape. Thus, in some cases, the apparatus and methods described herein are adapted for use when the shape of the body lumen in which they are used has a diameter that changes abruptly.

[0075] Alternatively, or additionally, these devices and methods may be used to treat the walls of blood vessels or other lumens that are not necessarily tapered, or are only slightly tapered. In some cases, these methods and devices can be used to treat the walls of blood vessels or respiratory lumens. For example, these methods and devices can be used to treat arterial stenosis, including in combination with stenting or angioplasty procedures. Therefore, in some cases, these methods can be performed within the first 2-4 days after angioplasty and / or stenting. Untreated smooth muscle cells (SMCs) on the lumen surface in areas where endothelium has been removed may continue to proliferate at a low rate. The methods and devices described herein can prevent or reduce this.

[0076] Figure 1 illustrates an example of a system 100 (also referred to herein as a sub-microsecond generation system for example) for delivering high-speed pulses of electrical energy. Such a system may include an elongated applicator tool 102, a pulse generator 107, a foot switch 103, and a user interface 104. The foot switch 103 is connected to a housing 105 (which may contain electronic components) via a cable and connector 106. The elongated applicator tool 102 may include electrodes and may be connected to the housing 105 and the electronic components therein via a cable 137 and a high-voltage connector 112. The system 100 may also include a handle 110 and a storage drawer 108. The system 100 may also include a holder (e.g., a holster, carrier, etc.) (not shown) which may be configured to hold the elongated applicator tool 102. In some examples, the system may be configured for unipolar treatment and may optionally include a dispersed electrode 133 (e.g., a return electrode pad).

[0077] The applicator tool may be one of the devices for delivering pulsed electric fields into the body's blood vessels, as described in detail herein. These devices may generally include an elongated flexible body (hereinafter generally referred to herein as an elongated body, catheter, or elongated catheter body), with one or more electrodes at its end, including electrodes that form one or more loops into which a pulsed electric field can be applied to the body. In some cases, the elongated applicator tool 102 includes one or more cameras and / or one or more imaging sensors, such as optical fibers, at or near the distal end of the elongated applicator tool 102. The cameras (not shown for simplicity) may be forward-facing and / or lateral-facing. The system 100 may be configured to display (in real time and / or recorded) images captured by the elongated applicator tool 102 in order to identify a target therapeutic area and / or region.

[0078] A human operator may select the number of pulses, amplitude, pulse duration, and frequency information by, for example, inputting such parameters into a numeric keypad or touchscreen on the user interface 104. In some examples, the pulse width can be varied. A microcontroller can transmit signals to pulse control elements within the system 100. In some examples, a fiber optic cable is used to enable control signal transmission while electrically isolating the contents of the submicrosecond pulse generation system 100, for example, a metal cabinet (e.g., housing 105) with high-voltage circuits from the outside. To further electrically isolate the system, the system 100 may be battery-powered instead of being powered from a wall outlet.

[0079] The elongated applicator tool 102 may be handheld (for example, by a user) or mounted on a movable arm of a robotic system, and its operation may be at least partially automated or fully automated, including computer-controlled operation.

[0080] Figure 2 illustrates an example of an applicator 200 configured to deliver a treatment, such as nanosecond pulsed energy therapy, into a body vascular system. The body vascular system may include, but is not limited to, any feasible vascular system, including the sinuses of the 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. While the applicator 200 is shown with two rings 210 and 220, in other examples, the applicator 200 may include any feasible number of rings. The term “distal” may generally refer to the portion of the applicator closest to the distal end (and closest to the treatment tissue / surface), and the term “proximal” may generally refer to the portion of the applicator relatively far from the distal end and the treatment 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 and distal rings 210 and 220. For example, the proximal ring 210 and the distal ring 220 may be referred to as the first ring and the second ring.

[0081] The proximal ring 210 and distal ring 220 may be formed from any suitable material. In at least one example, the proximal ring 210 and distal ring 220 may be formed from nitinol (e.g., nickel-titanium), but any other feasible material such as stainless steel may 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.

[0082] The proximal ring 210 and distal ring 220 may be used as circular electrodes, for example, to deliver nanosecond pulsed energy to a selected treatment area. In this example, the entire outer circumference of each ring 220, 210 may be an active region (e.g., electrically continuous), so that the outer circumference of the rings, rather than the (possibly insulated) inner arms 211, 221, 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 confirmation of the placement of the applicator 200, the proximal ring 210 and distal ring 220 can be deployed from the catheter 230.

[0083] In some cases, the ring 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, and the distal end of the device (e.g., the ring electrodes in this example) may be deployed from the delivery catheter once it reaches or near the target therapeutic site in the body. For example, the entire device (including the catheter body and electrodes) may be inserted into the proximal end of a delivery catheter (also referred herein as a guide sheath). The guide sheath may already be in the patient's body, and the distal end of the sheath is positioned near the target area (e.g., in some cases, in or near the left atrium). The elongated catheter body and electrodes (e.g., ring electrodes) may be inserted into the proximal valve of the guide sheath using an introducer (e.g., a plastic tube), and the device may slide distally within the sheath. In some cases, the delivery catheter holding the distal end (e.g., the ring electrodes) may advance to the target tissue and then be held in place while the distal end is driven from the delivery catheter.

[0084] The proximal ring 210 may include two lobes; that is, the proximal ring 210 may be divided into two semicircular portions that are joined to the arm 211. In some examples, the arm 211 may be insulated. Similarly, the distal ring 220 may include two lobes that are joined to the arm 221. In other examples, the proximal ring 210 and distal ring 220 may include any number of lobes and arms. In some cases, increasing the number of lobes can increase the flexibility of the proximal ring 210 and distal ring 220, allowing them to more easily conform to different shapes of body blood vessels and enabling 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 can flexibly connect the proximal ring 210 and distal ring 220 to the elongated catheter body 230. In any of the devices described herein, the entire device may be referred to as a “catheter,” and the elongated, typically flexible body portion extending from the distal end may be referred to as the catheter body (e.g., catheter body 230). The electrode extending from the distal end of the elongated catheter body may be movable relative to the distal end of the elongated catheter body, or it may be fixed relative to the distal end.

[0085] Figure 2 shows the distance 240 separating the proximal ring 210 and the distal ring 220. For example, the distance 240 may represent the distance between a plane that roughly contains the proximal ring 210 and a plane that roughly contains the distal ring 220. The distance 240 may be predetermined or variable and determined by the user when the proximal ring 210 and the distal ring 220 are deployed. In some examples, the potential and distance 240 between the proximal ring 210 and the distal ring 220 can determine the electric field density that can be delivered by the applicator 200. For example, a relatively small distance 240 can provide a higher electric field density compared to a relatively large distance 240.

[0086] In some cases, the applicator 200 may be guided to a specified treatment area by an elongated catheter body 230 and a proximal handle (such as the handle portion of the elongated applicator tool 102 shown in Figure 1). In some cases, the applicator 200 may also be guided by the use of a guidewire (not shown for simplification) and / or a fluoroscopy device. The device described herein (e.g., the applicator 200) may include a central lumen that can enable the device to operate on a guidewire (e.g., through the elongated catheter body). Alternatively, a rapid exchange lumen may be located on the side of the distal end of the applicator.

[0087] The distal end of the device can be positioned within an approximate region of the tissue to be treated (target tissue region), and the ring electrodes (e.g., proximal ring 210 and distal ring 220) can be extended as shown in Figure 3A. The proximal and distal rings 210 and 220 can be flexibly coupled to an elongated catheter body 230, from which they emerge and be positioned alongside the body's blood vessels. The precise position of the applicator 200, including the ring electrodes, can be verified, and / or the device can be repositioned before energy is applied.

[0088] Next, nanosecond pulsed energy therapy to the body's blood vessels can be initiated. In some examples, the system 100 and applicator 200 can be configured for bipolar operation between, for example, a proximal ring 210 and a distal ring 220. In some examples, the proximal ring 210 may be referred to as the cathode and the distal ring 220 as the anode (or vice versa). In other examples, the proximal ring 210 may be associated with a signal having a negative signal and the distal ring 220 may be associated with a signal having a positive signal. The proximal ring 210 and distal ring 220 can function as electrodes for delivering nanosecond pulsed energy. Electrodes carrying signals of opposite polarity may allow an electric field associated with pulsed therapy to be generated between the electrodes. In some examples, the system 100 (including the 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 the signal may be applied between the proximal ring 210 and the distal ring 220 and a return electrode that can come into contact with the patient (for example, another conductor such as a part of the elongated catheter body 230, or a conductive pad or electrode).

[0089] Following the delivery of nanosecond pulsed energy therapy, the applicator 200 may be moved to another area of ​​the body's blood vessels or removed from the patient.

[0090] Any of the devices described herein may also be elastically flexible and configured for use in areas of the body that expand and contract, for example, during diastole / systole, respiration, etc. For example, as described herein, the electrode may be formed as a ring (or partial ring) that can be flexibly coupled to the distal end region of the catheter body. The flexible coupling may be made via a wire or other member that allows the ring to bend in accordance with the movement of the tissue while remaining in place in the tissue.

[0091] Figure 3A shows another example of an applicator 300 configured to deliver therapies, such as nanosecond pulsed energy therapy, into the body's blood vessels. Similar to the applicator 200 in Figure 2, the 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 positioned distal to the distal ring 220 on the elongated catheter body 230. In some examples, the point-by-point ablation tip 310 can deliver targeted therapy independently of the proximal ring 210 and the distal ring 220. Thus, the point-by-point ablation tip 310 may include one or more electrodes for delivering nanosecond pulsed energy (not shown for simplicity). Alternatively, in some cases, point-by-point ablation may be achieved by using a subset of ring or petal electrodes extending outward from an elongated body (elongated catheter body) 230. This will be described in more detail below with reference to Figures 7 and 32-33.

[0092] Figure 3B shows another example of a device configured to apply either circumferential treatment over a large area or point-by-point treatment over a smaller area by using either a “front-facing” or “side-facing” approach, as described below. The device shown in Figure 3B is configured as a trielectrode ablator (device) in which an electric field can be applied either between a distal ring 314, which can be held in a first polarity (polarity 1), and a central electrode 310, which can be held in a second polarity (polarity 2). The distal end or “front” of the device can “facing” the tissue. Alternatively, energy can be applied between the distal ring 314 (e.g., polarity 1) and a proximal ring 312, which can be set to polarity 2. The side of the device may face the tissue. Thus, the device (applicator 300') can be used to apply smaller (point) applications of energy or single-shot (e.g., circumferential) applications of energy over a larger area.

[0093] The apparatus shown in Figure 3B can also use only a portion of either the distal or proximal (or both) ring to apply a smaller treatment area. For example, in Figure 3B, the distal ring 314 is formed from three sub-regions 314', 314'', and 314'''' which can be electrically coupled together to form a single electrode. Similarly, the proximal ring 312 is also formed from three sub-regions 312', 312'', and 312''' which are coupled together to form a single electrode. The apparatus can also be configured to apply energy between only one or two sub-regions of the distal ring (or a sub-region and a single central electrode, or a sub-region and the complete proximal ring) to apply energy over a smaller area. Thus, in some configurations, each sub-region can be energized individually. In some examples, adjacent sub-regions of the same ring can be used with different polarities to apply energy between them.

[0094] Applicators 300, 300' in Figures 3A and 3B are shown in deployed mode, for example, relative to a body vessel 320. An example of a body vessel 320 may be a pulmonary vein, which may include a sinus 325. The sinus 325 may have a size transition from a first diameter to a second diameter. Thus, the different diameters of the proximal ring 210 and the distal ring 220 may advantageously allow the applicator 300 to conform to the changing shape 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 may be configured to have an adjustable diameter, which may allow the device to detect different shapes and diameters.

[0095] In any of the apparatuses described herein, the first ring and the second ring may be referred to as electrode rings, or simply “electrodes.” In some examples, the first electrode (e.g., proximal electrode ring 210) is configured to have one or more loops (two loops are shown in Figure 2, while Figure 4A, described below, shows five loops) and includes electrically active regions (“active regions”) formed on one or more loops. The active regions are conductive regions configured to contact target tissue, with a pulsed electric field applied between them. The active regions may be exposed (e.g., may include conductive surfaces) and may not be insulated compared to other regions of the loops. All of these conductive regions are electrically connected to form, for example, a single electrode. Thus, the active regions are typically long and narrow, formed, for example, from wires of a portion of one or more loops.

[0096] In the exemplary applicator 300, arms 211 and 221 are shown offset from each other by approximately 90 degrees. In other examples, arms 211 and 221 can be offset by any feasible amount. Applicator 300 can be used for a variety of cardiac applications, such as the treatment of atrial fibrillation, ventricular tachycardia, and other cardiac ablations. However, the present invention is not limited to cardiac applications and can be used to apply electrical energy to other parts of the body.

[0097] Figure 4A shows another example of an applicator 400 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels. The applicator 400 may include a proximal ring 410 and a distal ring 420. The proximal and distal rings 410 and 420 may each include five lobes. In addition, the applicator 400 may include five arms 430 to flexibly connect the proximal and distal rings 410 and 420 to an elongated catheter body (not shown). As mentioned above, the proximal ring 410 and distal ring 420, having relatively more lobes, may be more flexible than the proximal and distal rings, having fewer lobes. Figure 4B shows a side view of the applicator 400. The proximal and distal rings 410 and 420 and the arms 430 are shown connected to an elongated catheter body 440.

[0098] Figures 4C–4E illustrate examples of applicators that may be used to deliver nanosecond pulsed electrical energy therapy into the body's blood vessels. These examples are similar to those shown in Figures 2, 3A–3B, and 4A–4B in that they may include multiple rings of electrodes that can be selectively actuated to apply bipolar energy for treating tissue. These devices may also be referred to as adaptable ring devices that can be used to apply energy to tissues within the body. In one non-limiting example, the devices shown in Figures 4C–4E may be used for bipolar application of electrical energy to myocardial tissue, including sinuses, pores, and medial / lateral walls (such as for treating pulmonary veins), but are not limiting.

[0099] As described above with respect to Figures 4A to 4B, in some examples, the apparatus described herein includes two electrode rings, namely an inner ring and an outer ring, which can be used to treat tissue including (but not limited to) myocardial tissue in sinuses and / or sinus orifices. In some examples, additional rings can be used. For example, Figure 4C shows an apparatus including three rings, and Figure 4D shows an example with four rings. Figure 4E illustrates an example with two rings accompanied by a central electrode. These configurations can also enable adaptability to the patient's biostructure and can help achieve both single-shot treatment (e.g., treatment of an entire area such as around a blood vessel in a single treatment, including ablation) and point-by-point treatment (e.g., treatment of small portions of body blood vessels one by one, including ablation).

[0100] Figure 4C shows an example configuration of an applicator 460 apparatus having three rings of electrodes, including an outer ring 461 having a diameter of approximately 30 mm. The outer electrode may be formed from multiple sub-regions (e.g., petals or loops) that can be electrically coupled together to apply a first polarity. In some examples, the individual sub-regions may be activated independently. Figure 4C also includes a second ring 463, which is smaller than the first ring and arranged concentrically with respect to the first ring. In Figure 4C, the second ring may have a diameter of approximately 23 mm and be formed from multiple sub-regions that can be electrically coupled to provide a second polarity. The multiple sub-regions may also be activated separately in some examples. The same apparatus may also include a third ring 465, which may be similarly formed from multiple sub-regions arranged concentrically with respect to the second ring and that can be electrically coupled to provide a first polarity. In Figure 4C, the third ring has a diameter of approximately 16 mm. The outer and intermediate rings can be used to treat larger cavities and / or holes, while the second configuration allows the use of the second and third rings to apply treatment to smaller cavities and / or holes. Varying the ring diameter and / or number of rings may allow the system to select which pair of rings to specify (in which polarity) to provide better adjustment and mating when treating tissue areas of different sizes, such as cavities and / or holes (but not limited to).

[0101] For example, in Figure 4D, the device includes four concentrically arranged rings. The outer electrode (ring 481) can be formed from multiple sub-regions that can be electrically coupled together to apply a first polarity. In some examples, the individual sub-regions can be activated independently. The second ring 483 can be formed from multiple sub-regions that are concentrically arranged with respect to the first ring and can be electrically coupled to provide a second polarity, or can be independently activated (energized). A third ring 485 with a smaller circumference can be formed from multiple sub-regions that are concentrically arranged with respect to the second ring and can similarly be electrically coupled to provide a first polarity. Finally, a fourth electrode (ring 487) with an even smaller circumference is concentrically arranged with respect to the third ring.

[0102] Any of these devices can provide a small central (e.g., point) electrode, as shown in Figure 4E. Figure 4E is similar to Figures 4A and 4B in that it has two electrode rings arranged concentrically. The first ring electrode 491 may be formed from a plurality of sub-region electrodes, each formed from a wire having an exposed electrically active region. As in any of these examples, in some configurations, each sub-region may be controlled individually and / or they may all be electrically coupled together to form a single electrode. The second ring electrode 493 is arranged concentrically with respect to the first ring electrode and, like the first ring electrode, may be formed from a plurality of sub-regions. Finally, the example shown in Figure 4E may also include a single central electrode 495, which can be configured to apply a polarity opposite to the polarity applied to either the larger outer ring (or sub-regions of the outer ring) or the inner ring (or sub-regions of the inner ring).

[0103] Any of these devices can be used as the distal portion of an elongated body (such as a catheter) and may be used, for example, in the treatment of atrial fibrillation. The treatment of atrial fibrillation may include, but is not limited to, various target sites including pulmonary vein (PV) sinuses, PV foramina, and cardiac wall muscle / tissue. As described herein, these devices may be useful for treating large areas (e.g., single-shot application of sub-microsecond pulse energy), for treating pulmonary vein sinuses / foramina of varying sizes, and / or for providing point-by-point tissue treatment (e.g., ablation) throughout the entire biostructure of the heart. These devices may also be used to apply sub-microsecond treatment to other parts of the human body. For example, a larger diameter outer ring may be used for single-shot treatment of sinuses and foramina, while a smaller inner ring may be used for point-by-point ablation of target tissue. Due to the adaptability and adjustability of these configurations, treatment can be achieved more efficiently and can be adjusted / adapted to biostructures of variable size.

[0104] Figure 5 shows the applicator 400 of Figure 4 positioned within the pulmonary vein sinus 510. The proximal ring 410 and distal ring 420 can be fitted to the surface of the pulmonary vein.

[0105] Figure 6A shows another applicator 600 configured to deliver a treatment, such as nanosecond pulsed energy therapy, into the body's blood vessels. Applicator 600 may include a first ring 610, a second ring 620, an elongated catheter body 630, and an arm 640. The arm 640 can electrically and flexibly couple the first ring 610 and the second ring 620 to a system 100 (not shown) through the elongated catheter body 630. The first ring 610 and the second ring 620, as well as the arm 640, may be formed from nitinol or any other feasible material. In addition, 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 can at least partially determine the density of the electric field associated with nanosecond pulsed energy therapy. Although shown having two lobes, the first ring 610 and the second ring 620 may contain any number of lobes as feasible. The first ring 610 and the second ring 620 may be folded and retracted into a delivery catheter (not shown), or in some implementations into an elongated catheter body 630, allowing for placement of the applicator 600 relative to the treatment area.

[0106] In contrast to applicators 200, 300, and 400, the first ring 610 and the second ring 620 of applicator 600 may be substantially coplanar. This coplanar arrangement may allow the electrodes (e.g., the first ring 610 and the second ring 620) to provide better contact with planar tissue and / or tissue formed as well as the pulmonary vein sinuses. In some examples, the electrodes may have a configuration with a “funnel” facing away from the pulmonary vein sinuses.

[0107] The applicator 600 can be configured for bipolar operation. Pulse energy can be transmitted between the first ring 610 and the 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 another example, 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, both the first ring 610 and the second ring 620 may be electrically coupled together, and a return electrode (e.g., on an elongated catheter body 630 or a conductive pad) may be used.

[0108] Figure 6B shows an example of using an applicator similar to that shown in Figure 6A to treat a model tissue 651. In Figure 6B, nanosecond pulse therapy is applied to the model tissue (potato immersed in saline) using an applicator similar to that in Figure 6A, showing treatment of two regions 653, 653' (e.g., two applications of the device). In particular, the applicator is used to apply pulsed electrotherapy to two target regions. The two annular regions are formed by the application of the first and second loop electrodes. In this example, the darker regions of the test tissue indicate the effect of the nanosecond pulsed electric field on the target tissue model. For each of the two applied treatments (shown overlapping in this example), a treatment of approximately 320 degrees is performed, and a small gap not covered by the active region of the electrode is shown in 357.

[0109] Figure 7 shows another applicator 700 configured to deliver nanosecond pulsed energy therapy into the body's blood vessels. Applicator 700 may include a first ring 710, a second ring 720, an elongated catheter body 730, and an arm 740. The arm 740 can electrically and flexibly couple the first ring 710 and the second 720 to a system 100 (not shown) through the elongated catheter body 730. The first ring 710 and the second 720, as well as the arm 740, may be formed from nitinol or any other feasible material. In addition, 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 can at least partially determine the density of the electric field associated with the nanosecond pulsed energy therapy.

[0110] The ring in Figure 7 may be formed from multiple subsections ("petals") as shown. For example, in Figure 7, each ring includes five subsections. These subsections may be configured to act as a single ring by, for example, applying energy to all of the subsections together, or one or more subsections (petals) may be activated separately. For example, in Figure 7, the outer lower subsection 733 and the inner lower subsection 734 may be activated without activating adjacent subsections. The use of these subsections of the ring may allow the device to be used for point-by-point treatment and provide a smaller treatment area, as described herein.

[0111] Similar to applicator 600 in Figure 6A, the first ring 710 and the second ring 720 may be substantially coplanar. Therefore, the function and use of applicator 700 may be similar to those of applicator 600. Applicator 700 is shown having five lobes, but other examples may have other numbers of lobes. As mentioned above, applicators with a relatively large number of lobes are more flexible than applicators with a relatively small number of lobes and can therefore be more easily adapted to some body vessels.

[0112] The applicator 700 can be configured for bipolar operation. Pulse energy can be applied between the first ring 710 and the second ring 720. In some examples, the first ring 710 may be configured as the anode and the second ring 720 as the cathode (or vice versa). In other examples, the applicator 700 can be configured for unipolar operation. For example, both the first ring 710 and the second ring 720 may be coupled together, and a return electrode (on another part of the elongated catheter body 730 or on a conductive pad or electrode) may be in contact with the patient.

[0113] Figures 8A and 8B show another applicator 800 configured to deliver energy, such as nanosecond pulsed energy therapy, to the body's blood vessels. 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 the distal arm 821 can electrically and flexibly connect the proximal ring 810 and the distal ring 820 to a system 100 (not shown) through the elongated catheter body 830. The proximal and distal rings 810 and 820 and the proximal and distal arms 811 and 821 may be formed from nitinol or any other feasible material. In addition, 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 can at least partially determine the density of the electric field associated with nanosecond pulsed energy therapy. The proximal and distal rings 810 and 820 can be folded and retracted into the elongated catheter body 830, allowing for placement of the applicator 800 relative to the treatment area.

[0114] The proximal and distal rings 810 and 820 can be separated by a distance of 840. In some examples, the proximal and distal rings 810 and 820 may expand and contract relative to and / or relative to the elongated catheter body 830. Thus, the distance 840 can be changed by expanding or contracting either or both of the proximal ring 810 and the distal ring 820. In some examples, the distance 840 can be controlled by moving a control wire, push rod, tendon, cable, etc., to expand and contract (position) the proximal ring 810 and / or the distal ring 820.

[0115] Applicator 800 can be configured for bipolar operation. Pulse energy can be transmitted between the proximal ring 810 and the distal ring 820. Thus, the proximal ring 810 may be the anode and the distal ring may be the cathode, or vice versa. In other examples, applicator 800 can be configured for unipolar operation.

[0116] In some examples, the proximal ring 810 and the distal ring 820 do not have to form a continuous circle. The region 850 of the distal ring 820 is enlarged in Figure 8B for detail. The distal arm 821 may 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 tip of the distal ring 820 unconnected can increase the flexibility of the distal ring 820. Although not shown, the features of the proximal ring 810 and the proximal arm 811 may be similar.

[0117] Figure 8C shows another example and diagram of applicator 800 similar to the applicator in Figure 8A. In this diagram, the distance 840 between the proximal ring 810 and the distal ring 820 is shown to increase relative to the distance 840 of applicator 800 in Figure 8A. For example, the proximal ring 810 and / or distal ring 820 may be moved to increase the distance 840 between each ring. As described above, changing the distance 840 can affect the density of the electric field associated with nanosecond pulsed energy therapy.

[0118] Figure 9 shows another applicator 900 configured to deliver nanosecond pulsed energy therapy to a body vascular system. 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 and distal rings 910 and 920, as well as the proximal and distal arms 911 and 921, may be formed from nitinol or any other feasible material. In addition, 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 can at least partially determine the density of the electric field associated with the nanosecond pulsed energy therapy. Although shown having six lobes, the proximal ring 910 and the distal ring 920 may contain any feasible number of lobes.

[0119] The applicator 900 can be configured for bipolar operation. Pulse energy can be transmitted between the proximal ring 910 and the distal ring 920. The proximal ring 910 may be the cathode and the distal ring 920 may be the anode (or vice versa). In another example, the applicator 900 can be configured for unipolar operation.

[0120] Figure 10 shows another applicator 1000 configured to deliver submicrosecond pulsed energy therapy to a body vascular system. Applicator 1000 may include a proximal ring 1010, a distal ring 1020, an expandable sphere 1025, and an elongated catheter body 1030. The proximal and distal rings 1010 and 1020 may be coupled to a system 100 (not shown) through a conductor (not shown) and an elongated catheter body 1030. The proximal and distal rings 1010 and 1020 and the expandable sphere 1025 may be formed from nitinol or any other feasible material. In some examples, the proximal and distal rings 1010 and 1020 may be electrically isolated from the expandable sphere 1025.

[0121] The proximal and distal rings 1010 and 1020 are disposed on and / or coupled to the expandable sphere 1025. Thus, the expandable sphere 1025 and the proximal and distal rings 1010 and 1020 can be folded and retracted into a delivery catheter or sheath, enabling the positioning of the applicator 1000 relative to the treatment area.

[0122] In addition, 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 can at least partially determine the density of the electric field associated with nanosecond pulsed energy therapy. Although shown having six lobes, the proximal ring 1010 and the distal ring 1020 may contain any feasible number of lobes.

[0123] The applicator 1000 can be configured for bipolar operation. The proximal ring 1010 may be the anode, and the distal ring 1020 may be the cathode (or vice versa). In another example, the applicator 1000 can be configured for unipolar operation.

[0124] Figure 11 shows another applicator 1100 configured to deliver nanosecond pulsed energy therapy to a body vascular system. Applicator 1100 may include one or more band electrodes 1110, a conductive blade 1120, an elongated catheter body 1130, a shape support member 1140, a tubular insulating member 1150, and one or more band insulators 1160. One or more band electrodes 1110 and the conductive blade 1120 may be coupled to a system 100 (not shown) through a conductor (also not shown) and an elongated catheter body 1130. In some examples, one or more band electrodes 1110 may be coupled to one another.

[0125] The shape support member 1140, the conductive blade 1120, and one or more band electrodes 1110 may be formed from nitinol or any other feasible material. In some examples, the shape support member 1140 may be formed substantially circularly. In some cases, the diameter of the shape support member 1140 may be selected to substantially conform to the shape of a body blood vessel. The tubular insulating member 1150 may be disposed circumferentially around the shape support member 1140 and adjacent to it (e.g., in contact with it). The conductive blade 1120 may be disposed circumferentially around the tubular insulating member 1150 and may function as the first electrode of the applicator 1100. The conductive blade 1120 may be formed from woven or braided conductive wire or any other feasible conductive material. One or more band electrodes 1110 may be disposed on one or more band insulators 1160 and then on the conductive blade 1120. One or more band electrodes 1110 and one or more band insulators 1160 can be dispersed on the conductive blade 1120. Figure 11 shows six band electrodes 1110, but in other examples, the applicator 1100 may contain any feasible number of band electrodes.

[0126] The applicator 1100 can be configured for bipolar operation. Pulse energy can be transmitted between one or more band electrodes 1110 and conductive blades 1120. The distance between the band electrodes can be varied, resulting in shorter or longer braided electrode sections between them, and simultaneously changing the total number of bipolar pairs (assuming the assembly diameter remains the same). In another example, the applicator 1100 can be configured for unipolar operation. The spacing between one or more band electrodes 1110 and conductive blades 1120 can at least partially determine the density of the electric field associated with nanosecond pulse energy therapy.

[0127] Figure 12 shows another applicator 1200 configured to deliver nanosecond pulsed energy therapy to a body vascular system. 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 a system 100 (not shown) through the elongated catheter body 1230. The helical member 1240 and one or more first electrodes 1210 and second electrodes 1210 may be formed from nitinol or any other feasible material. In addition, the helical member 1240 may spiral outward from the elongated catheter body 1230 while simultaneously extending away from the elongated catheter body 1230 (e.g., distally therefrom), thereby forming a conical shape. This conical shape may allow one or more first electrodes 1210 and second electrodes 1220 to make uniform contact with a portion of the tissue surface.

[0128] One or more first electrodes 1210 and second electrodes 1220 can be formed from any feasible conductive material. In some examples, one or more first electrodes 1210 and second electrodes 1220 can be spirally wound around a helical member 1240. In other examples, one or more first electrodes 1210 and second electrodes 1220 may be individual bands electrically coupled together. Furthermore, especially if the helical member 1240 is conductive, an insulator (not shown) may be disposed between one or more first electrodes 1210 and second electrodes 1220. The first electrodes 1210 and second electrodes 1220 and the helical member 1240 can be drawn into a delivery catheter or sheath (not shown), or in some implementations, into an elongated catheter body 1230, allowing for placement of the applicator 1200 over the treatment area.

[0129] The applicator 1200 can be configured for bipolar operation. Pulse energy can be transmitted between one or more first electrodes 1210 and one or more second electrodes 1220. Thus, one or more first electrodes 1210 may be configured as a single cathode, and one or more second electrodes 1220 may be configured as a single anode (and vice versa). In another example, the applicator 1200 can be configured for unipolar operation. For example, one or more first electrodes 1210 and second electrodes 1220 may both be electrically coupled together, and a return electrode (e.g., a conductive pad or electrode that can come into contact with the patient) may be used.

[0130] Figure 13 shows another applicator 1300 configured to deliver nanosecond pulsed energy therapy to a body vascular system. 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 a system 100 (not shown) through the elongated catheter body 1330. The helical member 1340 and one or more first electrodes 1310 and second electrodes 1320 may be formed from nitinol or any other feasible material. In addition, the helical member 1340 may extend away from the elongated catheter body 1330 (e.g., distally) while spiraling from the outer circumference to the inner circumference, thereby forming an inverted cone shape (relative to applicator 1200). This inverted cone shape may allow one or more first electrodes 1310 and second electrodes 1320 to make uniform contact with a portion of the tissue surface.

[0131] One or more first electrodes 1310 and second electrodes 1320 can be formed from any feasible conductive material. In some examples, one or more first electrodes 1310 and second electrodes 1320 can be spirally wound around a helical member 1340. In other examples, one or more first electrodes 1310 and second electrodes 1320 may be individual bands electrically coupled together. Furthermore, especially if the helical member 1340 is conductive, an insulator (not shown) may be disposed between one or more first electrodes 1310 and second electrodes 1320 and the helical member 1340. One or more first electrodes 1310 and second electrodes 1320 and the helical member 1340 can be folded and retracted into a delivery sheath (not shown), or in some implementations, into an elongated catheter body 1330, allowing for placement of the applicator 1300 over the treatment area.

[0132] The applicator 1300 can be configured for bipolar operation. Pulse energy can be transmitted between one or more first electrodes 1310 and one or more second electrodes 1320. Thus, one or more first electrodes 1310 may be configured as anodes, and one or more second electrodes 1320 may be configured as cathodes (or vice versa). In another example, the applicator 1300 can be configured for unipolar operation.

[0133] Figure 14 shows another applicator 1400 configured to deliver nanosecond pulsed energy therapy to a body vascular system. 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 second electrodes 1420 may be electrically coupled to a system 100 (not shown) through the elongated catheter body 1430. The helical member 1440 and the plurality of first electrodes 1410 and second electrodes 1420 may be formed from nitinol or any other feasible material. In addition, the helical member 1440 may spiral outward from the elongated catheter body 1430 while simultaneously extending away from the elongated catheter body 1430 (e.g., distally therefrom), thereby forming a conical shape. This conical shape may allow the multiple first electrodes 1410 and second electrodes 1420 to make uniform contact with a portion of the tissue surface.

[0134] Multiple first electrodes 1410 and second electrodes 1420 can 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 pulsed energy therapy. Furthermore, especially if the helical member 1440 is conductive, an insulator (not shown) may be disposed between the multiple first electrodes 1410 and second electrodes 1420 and the helical member 1440.

[0135] The applicator 1400 can be configured for bipolar operation. Pulse energy can be transmitted between a plurality of first electrodes 1410 and a plurality of second electrodes 1420. Thus, the plurality of first electrodes 1410 may be configured as anodes, and the plurality of second electrodes 1420 may be configured as cathodes. In another example, the applicator 1400 can be configured for unipolar operation.

[0136] Figure 15 shows another applicator 1500 configured to deliver nanosecond pulsed energy therapy to a body blood vessel. 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, the second electrode 1520, the third electrode 1540, and the fourth electrode 1550 may be electrically coupled to a system 100 (not shown) through the elongated catheter body 1530. The helical member 1560, as well as the first electrode 1510, the second electrode 1520, the third electrode 1540, and the fourth electrode 1550, may be formed from nitinol or any other feasible material. In addition, the helical member 1560 can spiral outward from the elongated catheter body 1530 while simultaneously extending away from the elongated catheter body 1530 (for example, distally therefrom), thereby forming a conical shape. This conical shape can enable the first and second electrodes to make uniform contact with a portion of the tissue surface.

[0137] The first electrode 1510, the second electrode 1520, the third electrode 1540, and the fourth electrode 1550 can be formed from any feasible conductive material. In some examples, the first electrode 1510, the second electrode 1520, the third electrode 1540, and the fourth electrode 1550 can be spirally wound around the spiral member 1560. Furthermore, especially if the spiral member 1560 is conductive, an insulator (not shown) may be disposed between the first electrode 1510, the second electrode 1520, the third electrode 1540, and the fourth electrode 1550. In some examples, the first electrode 1510 and the third electrode 1540 may be electrically coupled together, and the second electrode 1520 and the fourth electrode 1550 may be electrically coupled together.

[0138] The applicator 1500 can be configured for bipolar operation. Pulse energy can be transmitted between two sets of electrodes. For example, the first electrode 1510 and the third electrode 1540 may be configured as a single cathode, and the second electrode 1520 and the fourth electrode 1550 may be configured as a single anode (or vice versa). In another example, the applicator 1500 can be configured for unipolar operation.

[0139] Figure 16 shows another applicator 1600 configured to deliver nanosecond pulsed energy therapy to the body's blood vessels. Applicator 1600 may include a first electrode 1610, a second electrode 1620, an elongated catheter body 1630, a third electrode 1640, a fourth electrode 1650, a support member 1660, and a connecting member 1670. The first electrode 1610, the second electrode 1620, the third electrode 1640, and the fourth electrode 1650 may be electrically coupled to a system 100 (not shown) through the elongated catheter body 1630. The first electrode 1610, the second electrode 1620, the third electrode 1640, and the fourth electrode 1650 may be arranged on a support member 1660 that may emerge from the elongated catheter body 1630. In some examples, particularly when the support member 1660 is conductive, an insulator (not shown) may be disposed between the first electrode 1610, the second electrode 1620, the third electrode 1640, and the fourth electrode 1650. A connecting member 1670 can connect both ends of the support member 1660. Although only four electrodes are shown, in other examples, the applicator 1600 may include any feasible number of electrodes.

[0140] The first electrode 1610, the second electrode 1620, the third electrode 1640, and the fourth electrode 1650, the support member 1660, and the connecting member 1670 may be formed from nitinol or any other feasible material. The connecting member 1670 may be smaller and / or more flexible than the support member 1660 so that the support member 1660 and the first electrode 1610, the second electrode 1620, the third electrode 1640, and the fourth electrode 1650 can be more easily drawn into the elongated catheter body 1630, allowing for the placement of the applicator 1600 relative to the treatment area.

[0141] Applicator 1600 can be configured for bipolar operation. Pulse energy can be transmitted between two sets of electrodes. For example, pulse energy may be transmitted between a first electrode 1610 and a third electrode 1640 forming a coupled anode, and between a second electrode 1620 and a fourth electrode 1650 forming a coupled cathode, or vice versa. In another example, applicator 1600 can be configured for unipolar operation.

[0142] Figure 17A shows another applicator 1700 configured to deliver treatment to a body vascular system. Applicator 1700 may include a first insulating conductor 1710, a second insulating conductor 1720, and an elongated catheter body 1730. The first and second insulating conductors 1710 and 1720, as well as the elongated catheter body 1730, may be formed from 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 within the distal section of the basket (as shown, the distal section is closer circumferentially to the shaft 1730). The double-blade region of the basket is shown in the enlarged region 1740. The basket formed by the first insulating conductor 1710 and the second insulating conductor can be folded and retracted into a delivery catheter (not shown), allowing for the placement of the applicator 1700 relative to the treatment area.

[0143] Figure 17B shows another diagram of the applicator 1700 of Figure 17A. The insulating regions of the first insulating conductor 1710 and the second insulating conductor 1720 can be selectively removed to expose the corresponding bare conductors. Thus, the insulator removed from the first insulating conductor 1710 can form the first electrode 1711, and the insulator removed from the second insulating conductor 1720 can form the second electrode 1721.

[0144] The applicator 1700 can be configured for bipolar operation. Pulse energy can be transmitted between two sets of electrodes. For example, pulse energy may be transmitted between the first electrode 1711 and the second electrode 1721. Thus, the first electrode 1711 may be configured as the anode and the second electrode 1721 may be configured as the cathode (or vice versa). In another example, the applicator 1700 can be configured for unipolar operation.

[0145] Figure 18 shows an example of a fixture 1800 for manufacturing the applicator 1700 of Figure 17A. The fixture 1800 may include a cylinder 1810, a first group of pins 1820, a second group of pins 1830, and a third group of pins 1840. To manufacture the applicator 1700, the first insulating conductor 1710 is selectively wound between the first group of pins 1820 and the third group of pins 1840. Similarly, the second insulating conductor 1720 is selectively wound between the first group of pins 1820 and the second group of pins 1830. After the first insulating conductor 1710 and the second insulating conductor 1720 are wound around the cylinder 1810, the insulator can be selectively removed from the first insulating conductor 1710 and the second insulating conductor 1720 to form the first electrode 1711 and the second electrode 1721.

[0146] Figure 19 shows another applicator 1900 configured to deliver nanosecond pulsed energy therapy to a body vascular system. Applicator 1900 may include a first electrode 1910, a second electrode 1920, a blade member 1925, and an elongated catheter body 1930. The first electrode 1910, the second electrode 1920, and the blade member 1925 may be formed from nitinol or any other feasible material. In some examples, the blade member 1925 may be or be made from a non-conductive material. The blade member 1925 can be extended (as shown) so that the first electrode 1910 can form a distal circular electrode and the second electrode 1920 can form a proximal circular electrode, thus unfolding the first electrode 1910 and the second electrode 1920. Although only two electrodes are shown, in other examples, applicator 1900 may include any feasible number of electrodes. The blade member 1925 can be folded and retracted into the delivery sheath, allowing for the placement of the applicator 1900 relative to the treatment area.

[0147] The applicator 1900 can be configured for bipolar operation. Pulse energy can be transmitted between two sets of electrodes. For example, pulse energy may be transmitted between the first electrode 1910 and the second electrode 1920. Thus, the first electrode 1910 may be configured as the cathode and the second electrode 1920 may be configured as the anode (or vice versa). In another example, the applicator 1900 can be configured for unipolar operation.

[0148] Figure 20 shows another applicator 2000, similar to the applicator in Figure 19, configured to deliver treatment to a body blood vessel. Applicator 2000 may include a first electrode 2010, a second electrode 2020, a blade member 2025, and an elongated catheter body 2030. The first electrode 2010, the second electrode 2020, and the blade member 2025 may be formed from nitinol or any other feasible material. The blade member 2025 can be extended (as shown) so that the first electrode 2010 can form a proximal electrode and the second electrode 2020 can form a distal electrode, thereby unfolding the first electrode 2010 and the second electrode 2020. Although only two electrodes are shown, in other examples, applicator 2000 may include any feasible number of electrodes. The first and second electrodes 2010 and 2020 and the blade member 2025 can be folded to allow placement of the applicator 2000 on the treatment area.

[0149] Applicator 2000 can be configured for bipolar operation. Pulse energy can be transmitted between two sets of electrodes. For example, pulse energy may be transmitted between the first electrode 2010 and the second electrode 2020. Thus, the first electrode 2010 may be configured as the anode and the second electrode 2020 may be configured as the cathode (or vice versa). In another example, applicator 2000 can be configured for unipolar operation.

[0150] Figure 21 shows another applicator 2100 configured to deliver nanosecond pulsed energy therapy to a body blood vessel. 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 from nitinol or any other feasible material. In some examples, the expandable member 2140 may be a balloon that can be inflated 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 be folded to allow placement of the applicator 2100 relative to the treatment area.

[0151] The applicator 2100 can be configured for bipolar operation. Pulse energy can be transmitted between two sets of electrodes. For example, pulse energy may be transmitted between the first electrode 2110 and the second electrode 2120. In another example, the applicator 2100 can be configured for unipolar operation.

[0152] Also described herein are devices (e.g., applicators, applicator devices, etc.) configured to apply bipolar electrical energy, particularly sub-microsecond (e.g., nanosecond) pulsed electrical energy, into tubular structures such as lumens of the body (also referred to as bodily vessels). As described above, tubular structures can generally be lumens such as blood vessels (veins, arteries, etc.), airways such as the nasal cavity, oral cavity, sinuses, larynx, trachea, bronchi, etc., and organs such as the heart (atria, ventricles, etc.), lungs, and bladder. 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 containing a plurality of longitudinally extending ribs configured to expand outward. In any of these examples, the elongated body may be a catheter. The elongated body may contain one or more channels, including a guidewire lumen. The ribs may be part of an expansion / contraction frame. A plurality of these ribs may be arranged radially around the distal end region of the device. Each of the ribs may correspond to an electrode. In some examples, the device can be configured as a bipolar device in which a first subset of ribs has a first polarity and a second subset of ribs has a second polarity. In some examples, ribs of opposite polarities may alternate.

[0153] The 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 may be extended (e.g., by deploying the device) by sliding the first elongated member relative to (or vice versa) the second elongated member, thereby shortening the distance between the distal and proximal ends of the rib. Similarly, the rib may be retracted (e.g., by contracting the device) by sliding the first elongated member relative to (or vice versa) the second elongated member, thereby increasing the distance between the distal and proximal ends of the rib. In some examples, the rib may be biased (or communicated with bias) to tend to extend outward. Alternatively, in some examples, the rib may be biased (or communicated with bias) to tend to fold inward. For example, the ribs may be formed from a shape memory alloy (e.g., a nickel-titanium alloy such as Nitinol) that is shaped to be in an extended configuration or, alternatively, a folded configuration. In some examples, the ribs may be in communication with a biasing force such as a leaf spring or balloon.

[0154] The ribs do not need to be insulated over a portion of the length of each rib, from which energy can be applied. For example, each rib does not need to be insulated over an intermediate region of the rib extending for a length F, this length F may be referred to as the active length or active region of each rib. In some examples, only the outward-facing side of each rib is not insulated. Any suitable electrical insulator can be used, including polymer insulators, particularly biocompatible polymer insulators.

[0155] For example, Figure 22A illustrates an example of a device, such as those described herein, configured to deliver sub-microsecond (e.g., nanosecond) pulsed energy into a tubular structure. In Figure 22A, the device 2200 includes an elongated body 2203 extending proximal to distal. The elongated body is configured to be inserted into a body lumen. In some examples, the elongated body may be flexible. In some examples, the elongated body is rigid. The elongated body may be bendable or maneuverable (e.g., using one or more tendons). The device also includes an applicator region 2201 in the distal end region of the elongated body. In Figures 22A and 22B, the applicator region is shown in a folded (non-expandable) configuration. The applicator region may include a number of expandable ribs 2221, each configured to expand outward in the lumen from a folded configuration. For example, in Figure 22B, the folded rib is shown folded such that the cross-sectional diameter of the applicator area is approximately the same as the diameter of the rest of the elongated body.

[0156] Figure 22C shows an applicator region 2201 in an extended configuration in which multiple ribs curve and extend radially outward. In this example, eight ribs 2221 are shown, but any suitable number (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, etc.) can be used. Each rib contains a non-insulating active region 2225 in which the conductive material is exposed. The ribs may be formed from any suitable material, including, for example, stainless steel, nickel-titanium (e.g., nitinol), etc. In Figure 22C, each rib 2221 contains a centrally located active region flanked on both sides by insulating regions 2223, 2223'. The active region can be any suitable length, such as 1 mm to 3 cm (e.g., 1 mm to 2 cm, 1 mm to 1.5 cm, 1 mm to 10 mm, 1 mm to 8 mm, 2 mm to 10 mm, 2 mm to 8 mm, 2 mm to 7 mm, etc.).

[0157] Generally, multiple ribs may comprise two subsets, each having a different polarity. In some examples, a first subset of multiple ribs within an active region is configured to have a first polarity, and a second subset of ribs is configured to have a second polarity. Thus, energy (e.g., pulsed submicrosecond energy) can be applied between the two subsets of ribs. In this example, every other rib (or spline) radially arranged around the active region can have different polarities, and ribs with the same polarity can be electrically coupled together. Thus, the polarities alternate around the active region.

[0158] In Figures 22A to 22C, a plurality of ribs forming an expandable active region are connected to a pair of elongated members, which form an elongated body extending proximal to distal, such that relative movement of the first and second elongated members can cause expansion or contraction of the active region. For example, the proximal end of each of the plurality of ribs may be connected to the first (e.g., in some examples, outer) elongated member 2205, and the distal ends of the plurality of ribs may be connected to the second (e.g., in some examples, inner) elongated member 2207. The second elongated member is positioned coaxially with respect to the first elongated member and may slide proximal to distal within the first elongated member to expand or contract the active region.

[0159] The apparatus also includes a pair of electrical connectors coupled to a pulse generator to supply power to the apparatus. For example, in Figure 22A, a first electrical connector 2215 is shown coupled to a first elongated member and may be coupled to a first subset of ribs (having a first polarity). A second electrical connector 2217 can be connected to a second elongated member and coupled to a second subset of ribs (having a second polarity).

[0160] Alternatively, in some examples, the same applicator may be used to apply a single polarity from all of the ribs, and a separate return pad (e.g., a grounding pad such as pad 133 shown in Figure 1) may be used (not shown).

[0161] The exemplary devices shown in Figures 22A to 22C each include eight stainless steel ribs, each measuring approximately 0.015 inches × 0.005 inches (e.g., 0.38 mm × 0.13 mm). Each rib is insulated with a polymer insulator such as polyimide to prevent arc discharge and provide electrical insulation by exposing only the rib (also referred to herein as a spline or strut) of the length necessary for energy delivery.

[0162] Figures 23A to 23F illustrate another example of a device similar to the one shown in Figures 22A to 22C. In this example, the distal active region of the device 2301 is shown in a folded configuration as in Figure 22A. The device also includes an elongated body 2303 which includes a first elongated member (an outer elongated member 2305) and a second (e.g., an inner) elongated member 2307. The first elongated member is coupled to the proximal end of the active region, and the second elongated member is coupled to the distal end of the active region. Thus, by pulling the second elongated member proximal and / or pushing the first elongated member distally, the distance between the proximal and distal ends of the active region (e.g., a rib or spline) can be shortened, and the rib can be extended outward.

[0163] Figure 23B shows an enlarged view of the active region 2301, which includes multiple ribs 2321, shown in a folded (non-extended) configuration. Figures 23C and 23D show enlarged end views of the ribs forming the active region described above, and Figures 23E and 23F illustrate the end views of the distal and proximal ends, respectively. Figures 23E and 23F illustrate an example of electrical connections between ribs of the same polarity that alternate around the outer circumference. In Figure 23E, which shows the end view of the distal end of the active region, every other rib or spline is electrically coupled (2335) to form a first subset of splines. Figure 23F shows the end view of the proximal end of the active region, showing the electrical connections 2337 of a second subset of splines. In the examples of Figures 23A to 23F, each spline 2321 includes a pair of insulating regions 2323, a central active region 2325 with 2323' located on the sides. In Figures 23A to 23F, the electrical distribution can be configured using high-voltage and return-voltage wires. Figure 23E shows the distal ends of four flat wires forming a first subset of splines, which are bent and soldered together for one polarity. The proximal ends of four flat wires forming a second subset of splines can be bent and soldered together to form the other polarity, as shown in Figure 23F.

[0164] As described above, the inner second elongated member can be moved relative to the first elongated member (e.g., pulled / pushed) to expand and contract the spline (and thus the diameter of the active area). For example, the selected diameter may be set by the user (to expand within the lumen of a blood vessel), and the expanded state of the device may be locked in place, for example, using a locking or latching mechanism that secures the first elongated member to the second elongated member. Once in place, energy can be applied.

[0165] For example, Figures 24A to 24E illustrate an example of the apparatus, such as the apparatus shown in Figures 22A to 22C and 23A to 23F, which applies pulsed submicrosecond energy to an example tissue during operation. In this example, the sample tissue is a potato, in which a lumen is formed for the insertion of an example of the apparatus. Figure 24A shows an end view of the lumen 2402 through the sample tissue into which the apparatus 2401 is inserted and expanded, as described above. In this example, eight ribs are expanded until they just touch the wall of the simulated lumen. The bipolar apparatus was constructed as described above and inserted into the lumen and expanded. Figures 24B and 24D illustrate a lumen diameter of 20 mm, and Figures 24C and 24E show a lumen diameter of 14 mm.

[0166] As shown in Figures 24B–24E, all tested parameters and devices resulted in circumferential treatment around the lumen. All of these examples were tested using pulses in the nanosecond range (e.g., 1–1000 ns) and a voltage of approximately 2,500 V.

[0167] In the examples shown in Figures 22A-22C and 23A-23F, the apparatus includes an exposed (active) portion of each rib (e.g., spline) located in the center of the 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 from a shape memory material such as nitinol, the ribs can be shaped to a preferred configuration.

[0168] For example, Figures 25 and 26 illustrate examples of apparatus 2500 and 2600 in which the exposed active regions of the ribs of an expandable / foldable frame forming the applicator region are biased toward the distal end. In Figure 25, the applicator region has a substantially teardrop shape in longitudinal cross-section. Thus, the applicator region is configured to expand outward with respect to the long axis of the applicator region, having a larger cross-sectional area distal to the proximal end. Each rib (spline) 2521 has a curved shape in the expanded configuration, and the inclination of the distal opposing region is greater (steeper) than the inclination of the proximal portion. As described above, each rib also includes an exposed active region 2525 where the insulating region 2623, 2623' is located on the side. Figure 26 is similar to the example shown in Figure 25, but the entire distal end region of each rib 2621 is exposed (uninsulated) (2625), and only the proximal end of the rib is insulated (2623).

[0169] The devices shown in Figures 22A–22C, 23A–23F, 25, and 26 can be expanded by connecting the applicator region proximal to a first elongated member that is axially slidable with respect to a second elongated member coupled to the distal end of the applicator region, as described above. Alternatively, or additionally, one of these devices may be expanded by pushing it distally from the catheter or sleeve so that the applicator region expands (e.g., self-expands), and the ribs of the applicator region may be biased to expand radially outward as driven distally from the catheter / sleeve. Similarly, the applicator region can be folded by pulling it proximal to the catheter / sleeve. The examples shown in Figures 25 and 26 are thus configured such that the elongated body does not necessarily extend within 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 a second subset of the active region to a second polarity, and in some examples, the ribs having the first polarity may alternate with the ribs having the second polarity.

[0170] Any of the devices described herein may be configured to treat the lateral wall of a lumen and / or to treat the anterior (distal) opposing region of tissue. For example, the devices described herein may be configured to treat the tissue surrounding the pulmonary vein (PV) sinus in the left atrium (LA) of the heart in order to treat atrial fibrillation (AFIB) via PV isolation (PVI). An example of this treatment using a device such as the one shown in Figure 26 is illustrated in Figure 27.

[0171] For example, to gain access to the LA of the heart, femoral vein puncture may be performed using a needle under fluoroscopy and / or ultrasound guidance. After puncture under fluoroscopy guidance, a guidewire (e.g., a 0.032-inch J-tip guidewire) may be advanced. The needle may be removed, and then a sheath introducer (e.g., an 8-12F introducer) may be inserted into the vein and flushed. The transseptal sheath and dilator may be advanced over the guidewire to the superior vena cava (SVC). When the sheath reaches 3-4 cm above the vena cava-atrial junction, the wire can be removed. The transseptal puncture needle may be advanced under fluoroscopy guidance until it reaches the tip of the sheath. The needle may then be advanced together with the inserted stylet until it reaches 4 cm from the tip. The stylet prevents the needle tip from rubbing against the inner lumen of the sheath. The stylet can then be removed. Next, a puncture may be performed and the sheath may be advanced into the LA. A device including an electrode formed as part of the applicator region (e.g., a catheter including device 2600 shown in Figure 26) may be introduced into the LA through the sheath. The active region of the expanded or partially expanded rib (e.g., the electrode) may be pressed against the wall of the LA 2718 surrounding the pulmonary vein 2719, as shown in Figure 27. In any of the devices described herein, the distal end of the device may be deflectable or fully articulated. For example, an elongated body may include one or more tendons for articulating the distal end (applicator region). Thus, electrode positioning can be assisted by the deflectable or fully articulated distal end of the catheter, controlled via a steering mechanism in the handle and a pull wire (tendon) located in the shaft of the elongated body.

[0172] The position of the catheter within the body can be verified using fluoroscopy and / or ultrasound (e.g., ICE), as well as impedance and / or magnetic localization enabled by additional electrodes and / or magnetic sensors on the catheter. Contact between the active area of ​​the device (e.g., electrodes) and the tissue (e.g., LA) wall 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 the desired position and contact of the electrodes are confirmed, energy (e.g., sub-microsecond pulsing, microsecond pulsing, RF, etc.) may be applied to achieve the desired therapeutic effect, including, in some cases, non-thermal ablation of all or selected portions of the target tissue. Active electrodes and / or electrodes used for impedance-based localization and / or contact evaluation before ablation can be used for signal acquisition after ablation. In some cases, tissue contact electrodes can be used for impedance-based localization and contact evaluation. For example, the absence of electrical signals from cardiac tissue may indicate a valid acute effect from ablation. The device may be repositioned one or more times, and energy application may be repeated over additional areas of tissue (e.g., the LA area surrounding other pulmonary veins). For example, when treating in the LA, complete PVI can be achieved.

[0173] In some examples, the ribs may be configured to form substantially flat regions, such as regions where the non-insulating region is substantially parallel to the long axis of the distal end region, such as regions extending through multiple ribs (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.). For example, each rib may include hinge regions adjacent to one or both ends of the non-insulating (active) region, allowing the rib to bend so that the non-insulating region is substantially flat.

[0174] For example, Figures 28A–28C illustrate an example in which ribs forming an expandable frame of the applicator region may be shaped substantially parallel to the long axis of the midline of the applicator region so that they appear substantially "flat" and can align with the lumen wall when expanded radially outward. In Figure 28A, the device 2800 is similar to those shown in Figures 22A–22C and 23A–23F in that it includes a plurality of ribs (splines) 2821 arranged radially around a central midline 2855. Each rib includes an insulating region 2823 and an active (electrode) region 2825 with 2823' located laterally. In this example, eight ribs are arranged radially around the midline. The central midline may be formed from an inner elongated member that is coupled to the distal end region of the ribs and can slide distally or proximal to expand / contract the applicator region.

[0175] In Figure 28A, each rib is shaped such that the active region 2825 extends substantially flat (without bending) and exposes an active region (electrode) of approximately the same size regardless of the amount of expansion of the applicator region (e.g., frame). For example, in Figure 28B, the lumen is narrower than the lumen shown in Figure 28C, and the applicator region expands less than in Figure 28C and may contact the wall of the lumen. 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 lumen 2866, as shown in Figures 28B and 28C. Furthermore, the length of the active region in contact with the tissue is substantially the same.

[0176] Therefore, in some cases, the ribs can be shaped or formed to ensure that the length of contact between the exposed active (electrode) section of each rib and the tissue does not change significantly, regardless of the ID of the lumen, including organs such as bronchi, esophagus, and blood vessels. For example, the device 2800 may be introduced inside a lumen (organ) having an ID of approximately 20 mm (e.g., Figure 28C). The same device may be used in a lumen having an ID of approximately 10 mm (e.g., Figure 28B). In the device shown in Figure 28A, the ribs may be formed from a shape memory alloy (such as nitinol) and may have, for example, an active (exposed electrode) area of ​​approximately 10 mm in length. Generally, the length of the exposed portion can be varied depending on the application.

[0177] In any of these devices, the ribs can be hinged to include more flexible regions to allow preferential bending on both sides of the active region, similar to the configuration shown in Figure 28A. The hinges may be living hinges. In some examples, the hinges are formed by constricted or cutout regions on one or both sides of the rib. The hinges can act as stress concentration points that allow contact bending along the exposed, non-insulating active region of the rib.

[0178] Figure 29A illustrates an example of a rib that does not contain one or more hinges. In this example, rib 2921 includes a pair of insulating regions 2923, and a non-insulating active region (electrode) 2925 with 2923' located on the side. The rib extends in an arc shape. Figure 29B shows a similar rib that includes a hinge region 2970. In this example, the hinge region is formed by two cutout regions 2971 that provide preferential bending in the hinge region. In some examples, the hinge region can be formed by the use of one or more different materials in the hinge region, such as thinning the thickness of the rib in the hinge region, perforation in the hinge region, shaping bends in the hinge region, and / or regions that bend preferentially over 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 extend within the insulating region 2923, within the non-insulating region 2925, or both regions. In Figure 29B, the hinge region is located within the insulating region 2923. The insulating material provides support for the hinge region and can prevent damage to the ribs in the hinge region.

[0179] Figures 30A and 30B illustrate another example of a device including an applicator region having multiple ribs 3021, each of which is configured to have an active region 3025 (electrode) that remains substantially flat and parallel to the central longitudinal axis of the applicator region 3055 in any extended configuration. Figure 30B shows an enlarged view of section B of Figure 30A, showing a hinge region 3070 of one of the ribs. In this example, the hinge region is similar to that shown in Figure 29B and is covered by an electrically insulating material in the form of an insulating region 3023.

[0180] As described above, any of these devices may additionally or alternatively include a balloon to help expand the applicator region. For example, the balloon may be positioned within an expandable frame formed by the applicator region, as shown in Figure 31. In this example, device 3100 includes a balloon 3185, shown inflated within an applicator region formed by eight ribs, which can drive (or assist in driving) the expansion of the applicator region. The balloon can be inflated by injecting a fluid, such as saline solution, into the balloon through an elongated body 3103. Each rib includes an active region 3125, shown in this example as an active region (electrode) located in the center with a pair of insulating regions 3123, 3123' positioned on the sides. In some examples, the applicator region may be shaped to fold, so that the deflation of the balloon may self-fold so that the ribs return to a non-expandable configuration. In some examples, the applicator region may also fold by pulling it proximal to a catheter or sleeve. The applicator region may also include one or more elongated members to assist with expansion / contraction, in addition to the balloon, as previously mentioned. The balloon, such as the one shown in Figure 31, can also act as an insulator, preventing arc discharge between electrodes of different polarities. For example, the balloon may be formed of an electrically insulating material. The device shown in Figure 31 also includes a non-traumatic distal tip 3186, which can be used additionally or alternatively, in some examples, as a centering guide.

[0181] Point-by-point treatment The devices described herein can be used for point-by-point treatment as described above. For example, any of these devices may include smaller electrodes, or subsections of the applicator area, as described with reference to Figures 3B and 7, for example, with reference to Figure 3A or 3B (showing the central electrode). In some examples, such as the devices shown in Figures 22A to 22C, a single pair of ribs of different polarities may be used to apply treatment to a smaller area of ​​tissue. Thus, a subsection or sub-area of ​​a larger set of circumferential electrodes may be used. For example, the devices described herein may be used for cardiac ablation to address various problems, such as atrial fibrillation, ventricular tachycardia, and ventricular wall thickening, as well as for ablation in other organs, such as the esophagus (e.g., Barrett's esophagus) and bronchi (e.g., chronic bronchitis, asthma). The same device may be configured, for example, to apply a larger area of ​​treatment using the entire applicator area, or to apply a smaller treatment area suitable for point-by-point treatment using a subsection of the applicator area.

[0182] The apparatus described herein can be configured to create a treatment area (e.g., the ablation area in some cases) of approximately 5–15 mm. In some cases, a larger treatment area may not be necessary or recommended. For example, excessive ablation of the proximal wall or roof of the left atrium (LA) of the heart may lead to loss of myocardial function or interference with the proper pathway for the propagation of electrical impulses in the heart. Depending on the distance between electrodes, the apparatus described herein can limit the ablation "footprint" to, for example, approximately 5–15 mm and generate an electric field strong enough to achieve a transwall effect.

[0183] Figures 32 and 33 illustrate another example of an applicator device in which the applicator region includes a distal ring 3214 having three independently addressable electrodes 3214', 3214'', and 3214'''', and a proximal ring 3212 having three independently addressable electrodes 3212', 3212'', and 3212''''. Therapeutic energy may be applied between the entire distal ring and the proximal ring to treat the lumen circumferentially (e.g., to ablate), or the energy may be applied between only a subset of the distal ring electrodes and the proximal ring electrodes (e.g., only between 3214' and 3212'). Thus, treatment can be applied only when the sides of the applicator region are facing the tissue.

[0184] Figures 34A–34C, 35, and 36A–36D illustrate examples of applicators that may be configured as described herein. Figures 34A–34C show examples of flat “paddle” applicators including an outer electrode (wire electrode) and an inner electrode (wire electrode). For example, Figure 34A shows an example of a substantially flat paddle applicator including 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 wire electrode and the inner wire electrode is substantially the same along their lengths. Each electrode is insulated proximal (3405) but formed by an uninsulated wire over the active region. Similarly, the wire paddle-shaped apparatus of Figure 34B 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 positioned such that the minimum distance d' between the outer and inner wire electrodes is substantially the same along their lengths. Figure 34C illustrates another example of a wire paddle-shaped device, 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 positioned such that the minimum distance d between the outer wire electrode and the inner wire electrode is substantially the same along their lengths. In Figure 34C, the overall shape is semicircular.

[0185] Figure 35 shows another example of a paddle-type applicator formed by two parallel wires arranged longitudinally. The insulating portion of the wire 3505 forming the elongated body and / or electrode can be L-shaped so that the electrode can be placed flat against the target tissue without the elongated body coming into contact with the tissue. In Figure 35, the first wire 3503 is separated from the second wire 3501 by a fixed distance along the active (non-insulated) length of the electrode.

[0186] Figures 36A to 36D show an example of an applicator having electrodes facing forward (distal). Figure 36A includes a plurality of ribs (e.g., six in this example), each containing a distal counter electrode 3603. In this example, the active regions (electrodes) are formed from the non-insulating portions of each rib (spline), and each of these active regions can be electrically coupled together to form a unipolar electrode. The central electrode 3605 is positioned on the distal end face of the electrode. As in the apparatus shown in Figures 22A to 22C and 23A to 23F above, the apparatus shown in Figure 36A may be expandable and foldable, which includes coupling the distal end of each rib to an axially slidable elongated member that can slide relative to the proximal end of the rib.

[0187] Figure 36B shows an example of a device configured as a distally facing applicator, including a pair of wings 3613, 3615 that can be energized with different polarities to apply energy between them. An example of an applicator shown in Figure 36C is similar to that shown in Figure 36B, and also includes a pair of wings 3613', 3615', which can be energized with different polarities to apply energy between them. In this example, the electrodes maintain a constant distance between them over their length, which may be beneficial when applying a uniform energy density to the tissue.

[0188] Figure 36D illustrates an example of a device having radially separated active regions (electrodes) 3661, 3662, 3663, and 3664 that form a distally facing circle. The first active region 3661 and the third active region 3663, separated by the second active region 3662 and the fourth active region 3664, may have a first polarity (and may be electrically coupled to each other), while the second active region 3662 and the fourth active region 3664 may have a second polarity and may be electrically coupled to each other. In some examples, only two of the four electrodes may be used, with each electrode applying energy of opposite polarity, for example, to the first and second active regions.

[0189] Any of these devices can be used as the distal part of a device or apparatus, including an elongated body (e.g., a catheter), for intraluminal treatment of the body, such as (but not limited to) atrial fibrillation, ventricular tachycardia, or other cardiac ablations. For example, these devices may be used to apply nanosecond pulsed electric fields to substantially any part of the human body. For example, in some implementations, these devices may be used to apply other types of energy, such as RF or microsecond pulsed energy. These applicators may be part of a catheter used during minimally invasive procedures, or part of a device used during surgery, such as cardiac surgery. In some cases, the method of using the device may be performed as an incidental procedure, if necessary, and the device may not be catheter-based.

[0190] In any of these devices, the distance between electrodes can be varied, thereby determining the intensity of the pulse field at any given voltage, and therefore the size of the treatment area.

[0191] Centering mechanism Any of the devices described herein may also include a centering guide (centering feature) to assist in positioning the device within tissue. Therefore, any of these devices may include a centering guide to assist in positioning the device so that the electrode (e.g., in a single-shot configuration) is oriented relative to the tissue. In some examples, the device may include a centering guide for positioning the device's electrode relative to various vascular sinus / foramen regions, such as the pulmonary veins of the heart, enabling proper positioning and more efficient ablation while achieving pulmonary vein isolation (PVI).

[0192] Figure 37 illustrates the difficulty of centering a device 3700, such as the applicator device described herein, relative to target tissue. In this example, the target tissue is the left atrium (LA) 3706 of the pulmonary vein (PV) 3708. Positioning the device relative to the LAPV can be difficult, especially if 3D visualization is not performed. Many facilities performing procedures to address atrial fibrillation (AFIB) lack 3D mapping capabilities and rely on fluoroscopy to implant their devices. Therefore, navigating the device toward the PV can be difficult. In certain cases, the device may be implanted off-center from the sinus of the PV, as shown in Figure 37, preventing circumferential ablation from being achieved.

[0193] Accordingly, any of the devices described herein may include one or more additional centering guides, which may be part of the device or additional devices that can be used in conjunction with the device, to enable centering to the lumen to which treatment is applied, such as (but not limited to) the sinus of the PV. Generally, the centering guides may be expandable, non-traumatic projections that may extend distally to the distal end of the device. Figure 38A illustrates an example of an applicator device 3800 described herein, which includes a centering guide 3840. 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.

[0194] Figure 38B shows another example of a device including a centering guide 3842 extending from the distal end of the device 3800', distal to a first ring 3814 and a second ring 3812 that form an active region (electrode) extending from an elongated body 3803. In Figure 38A, the centering guide is an expandable and foldable balloon, while in Figure 38B, the centering guide is formed by multiple splines that can be expanded and folded. The centering guide is generally initially positioned within a lumen and can be expanded to traumatically guide positioning within the tissue. Any of these devices may further or additionally use a guidewire for positioning the device. For example, the balloon or spline may have an integrated guidewire or a lumen for a guidewire that can be used to introduce the device. For example, the balloon or spline (centering guide) may be integrated with the ablation device and introduced together on a guidewire. Figure 39 illustrates an example of a device 3900 that includes a pair of ring electrodes 3912 and 3914, a centering guide 3942, and a guide wire 3945. The guide wire extends through a lumen within an elongated body 3903.

[0195] In some examples, the centering guide may also function as an electrode for applying pulsed energy to the tissue, or may include an electrode. For example, in Figure 39, the basket 3942 (formed with splines / ribs) may include an electrode that can apply treatment to the tissue, such as by applying sub-microsecond (e.g., nanosecond) pulses between the ring electrodes and the basket, when one or both of the ring electrodes 3912, 3914 are used in a second polarity and the basket is used in a first polarity.

[0196] For example, Figures 40A to 40D illustrate the use of a centering guide configured as an expandable balloon as part of the apparatus. In Figure 40A, apparatus 4000, including a deflated balloon 4040, is introduced and positioned near LA4006. The centering guide (e.g., balloon) 4040 is partially inflated to have an OD smaller than the ID of PV4008, as shown in Figure 40B. In Figure 40C, the centering guide (balloon) is moved inside the PV until the ring electrode contacts the cavity, as shown. Finally, the balloon is inflated, as shown in Figure 40D.

[0197] Figures 41A to 41D illustrate a similar use when the centering guide is an expandable basket formed by splines (ribs), for example, as shown in Figure 38B. In Figure 41A, the apparatus 4100, including the folded basket 4140, is introduced and positioned near the LA4106. The centering guide (e.g., basket) 4140 is partially expanded to have an OD smaller than the ID of the PV4108, as shown in Figure 41B. In Figure 41C, the centering guide (basket) is moved inward of the PV until the ring electrode contacts the cavity, as shown. Finally, the balloon is inflated, as shown in Figure 41D.

[0198] How to treat cardiac ablation In general, the methods and apparatus described herein can be used to treat atrial fibrillation, ventricular tachycardia, and other cardiac ablations using pulsed electrical energy (e.g., pulsed electrical energy such as microseconds, submicroseconds, or nanoseconds). The applicators described herein can be used to deliver pulsed electrical energy to a desired treatment area during minimally invasive procedures or during surgery, such as cardiac surgery.

[0199] For example, cardiac ablation may be treated by using these methods and apparatus to deliver pulsed energy to the coronary arteries as well as peripheral arteries and veins. For example, pulsed energy may be delivered to the pulmonary venous sinus using any of the applicators described herein. In particular, the applicator can be adapted to a sinus transition region that starts in a relatively larger area (relative to the distal region of the applicator) and transitions to a relatively smaller area. A first or distal electrode having a relatively smaller diameter can contact the smaller area, while a second or proximal electrode having a relatively larger diameter can contact the larger area.

[0200] In another example, the diameters of the first and second electrodes can be reversed so that the diameter of the first electrode is relatively larger than the diameter of the second electrode. The use of such an applicator may be very suitable for treating areas of tissue, starting with a relatively small area and progressing to a relatively large area.

[0201] One exemplary use of the applicators described herein is to deliver a single-shot ablation for pulmonary vein isolation in the left atrium to treat atrial fibrillation. To gain access to the left atrium, a femoral vein can be punctured using a needle under fluoroscopy and / or ultrasound guidance. After puncture, a 0.032-inch J tip guidewire can be advanced under fluoroscopy guidance. The needle may be removed, and a sheath introducer (typically 8-12F in size) may be inserted into the vein and then flushed. A transseptal sheath (which may carry one of the applicators described herein) is advanced across the guidewire to the superior vena cava (SVC). Alternatively, the device of this disclosure may be advanced through the inferior vena cava (IVC) if the primary puncture is performed in the femoral vein.

[0202] Once the sheath is positioned within 3-4 centimeters (cm) above the vena cava-atrial junction, the wire is removed. The transseptal puncture needle is advanced under fluoroscopic guidance until it reaches the tip of the sheath. With the stylet inserted, the needle is advanced until it reaches 4 cm from the tip. The stylet prevents the needle tip from rubbing against the inner lumen of the sheath. The stylet can then be removed. The puncture is performed and the sheath is advanced into the left atrium. The catheter with electrodes can be introduced into the left atrium through the sheath.

[0203] The electrodes may be pressed against the left atrium wall, particularly surrounding the pulmonary veins. Proper positioning of the electrodes can be assisted by the deflectable or fully articulated distal end of the elongated catheter body, which is controlled via a mechanism in the elongated handle and pull wire located within the shaft of the elongated catheter body. The proper positioning of the catheter can be verified using fluoroscopy and / or ultrasound (TEE and / or ICE), as well as impedance and / or magnetic localization enabled by additional electrodes and / or magnetic sensors on the catheter. Proper contact between the applicator electrodes and the left atrium wall can be verified via impedance readings, which can be done, for example, by transmitting a low-amplitude non-therapeutic electrical "test" signal. After proper positioning and contact of the electrode bipolar pair are confirmed, energy (nanosecond pulses, microsecond pulses, RF) can be applied to achieve the desired ablation effect. Complete pulmonary vein isolation can then be achieved by repositioning the catheter and distal bipolar pair and repeating energy application over additional left atrium areas surrounding other pulmonary veins.

[0204] Pulsed electrical (e.g., nanosecond pulses) therapy may include pulse profiles having rise and / or fall times that 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, about 5 kV to 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 10 A, about 10 A, about 25 A, about 40 A, about 50 A, about 60 A, about 75 A, about 100 A, about 125 A, about 150 A, about 175 A, about 200 A, or greater than 200 A. 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 more than 5 ps. The apparatus (e.g., system) described herein may include, in addition to the instrument (e.g., elongated applicator tool), a pulse generator, such as the one schematically shown in Figure 1, configured to emit pulses in the sub-microsecond range.

[0205] Generally, the systems of this disclosure may include additional elements such as a power supply and / or a high-voltage connector for securely connecting an elongated applicator tool device to a high-voltage power supply. As described above, these systems and devices are configured to apply high-voltage, sub-microsecond pulsed electrical energy.

[0206] Figure 42 is a flowchart illustrating an example of one method 4200 for delivering pulsed electrotherapy to a selected treatment area of ​​a patient. Some examples may perform the operations described herein with additional actions, fewer actions, actions in a different order, parallel actions, and some actions differently. Method 4200 can be used to treat atrial fibrillation, ventricular tachycardia, or other cardiac ablations. Method 4200 is not limited to cardiac applications and, rather, can be used to treat various systemic blood vessels.

[0207] In Figure 42, method 4200 can be initiated once the treatment area is identified in block 4202. Block 4202 may be of any choice, as indicated by the dashed line in Figure 42. For example, one or more diagnostic tests for a patient may identify an area of ​​a vein, artery, or other bodily vascular vessel to be treated with pulsed electrotherapy. In other examples, the treatment area may be any technically feasible lumen, passage, or structure. Diagnostic tests may include radiography, vascular examination, ultrasound, or any other feasible test that allows for the identification of the treatment area.

[0208] In block 4204, the applicator is positioned within a specified treatment area. For example, the system 100 in Figure 1 may be used to position the applicator (such as any of the applicators in Figures 2 to 41D, but not limited to) within a specified treatment area. For example, the applicator can be positioned by extending spaced-apart fist electrodes (e.g., a first ring electrode having one or more loops) and a second electrode (e.g., a second ring electrode having one or more loops).

[0209] In block 4206, the electrodes of the applicator can be placed in contact with target tissue within a specified treatment area. The electrodes can be positioned such that an active area on a first electrode, which may extend circumferentially (fully or partially) over the target tissue, is separated from an active area on a second electrode, which may similarly extend circumferentially (fully or partially) over the target tissue. The area between the active areas of the first and second electrodes can be treated. In some cases, the first active area of ​​the first electrode and the second active area of ​​the second electrode may be placed circumferentially around a lumen (e.g., a vascular wall), and in some cases, the first active area of ​​the first electrode and the second active area of ​​the second electrode may be placed circumferentially around a portion of a body vascular system, such as a pulmonary sinus, in one non-limiting example. In some cases, the electrodes can be positioned through an elongated catheter body to which they are attached, so that the electrodes are in contact with the tissue. In some other cases, the electrodes may emerge from the elongated catheter body and expand to allow the electrodes to enter the treatment area. After dilation, the applicator may be moved to place the electrode in contact with the tissue.

[0210] When electrodes are placed in contact with tissue, in some cases the spacing between electrodes on the applicator (e.g., the set of electrodes) (e.g., the longitudinal spacing) can be adjusted. For example, referring particularly to the applicators described with respect to Figures 2, 3, 8, and 9, the spacing between electrodes on the applicator can be adjusted to change the density of the pulsed electric field or to accommodate the changing shape and topology of the tissue.

[0211] In an optional block 4207, contact with tissue may be confirmed by any suitable method (e.g., impedance testing, electrography, imaging, etc.). In this optional step, a low-level or low-amplitude signal (e.g., voltage and / or current) may be provided to the electrode. Based on the signal provided to and returned from the electrode, the system 100 may determine and / or measure the impedance associated with the electrode. Contact with tissue may be confirmed when the impedance is within the expected range.

[0212] In block 4208, pulsed electrotherapy is applied to a specified treatment area through an applicator. For example, system 100 may deliver energy through the applicator (e.g., between the active area of ​​the first electrode and the active area of ​​the second electrode). In some examples, the energy can be provided by a pulse generator configured to provide electrical pulses having an amplitude greater than 0.1 kV and a duration of less than 1000 nanoseconds.

[0213] Additional treatments may be performed, including repeated application of energy to the tissue through the first and second electrodes, allowing for evaluation of the effect of each pulse of electrotherapy. If the treatment is sufficient, further treatment may not be necessary (as determined, for example, by imaging, impedance testing, electrophoresis, etc.). In some cases, it may be advantageous to apply energy in a circumferential pattern as described herein (see, for example, Figure 6B) without having to move the apparatus in order to obtain nearly complete or complete circumferential treatment.

[0214] In block 4210, the applicator electrode is withdrawn from the tissue. In some cases, the catheter may be moved to the surface of the treated tissue to provide further treatment. The applicator may be moved to another treatment area or removed from the patient.

[0215] Use with cardiac mapping As described above, any of these devices and methods can be used in conjunction with a cardiac mapping system. For example, any of these devices and methods may be part of an ablation method for the treatment of a cardiac region, including, but not limited to, pulmonary veins (or sinuses associated with pulmonary veins), and may also include coordinating the position of the energy application (e.g., submicrosecond pulsed energy application) electrodes of the applicator with mapping, such as 3D electroanatomical mapping / mapping of the associated tissue.

[0216] As described above, the device may include one or more sensors, including electrical sensors (e.g., sensing electrodes) and / or imaging sensors. The device can integrate data from these one or more sensors with one or more maps of the tissue being treated. These electroanatomical maps may be generated by a separate mapping system, including a commercially available mapping system, or the device described herein may include a mapping system or subsystem integrated into the device. In some examples, the sensors are configured in combination with one or more patches that can be applied to a patient and connected to the mapping system / subsystem, and can be used as electrodes for a mapping (e.g., 3D electroanatomical mapping) system or subsystem.

[0217] Any of the applicators described herein may include additional electrodes for enabling visualization of the device in combination with a mapping system.

[0218] For example, Figures 43A to 43B illustrate an example of an apparatus similar to those shown in Figures 4A to 4E and Figure 7, including both treatment electrodes 4311, 4321 and mapping electrodes 4350, 4350', in which Figure 43A, ten individual mapping electrodes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 are positioned on the distal outward side of the applicator. 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. The inner ring 4320 and the outer ring 4310 each include five lobes formed by the length of the wires forming the treatment electrodes 4311, 4321. In addition, the applicator 4300 includes five arms 4330 that flexibly connect the inner ring and the outer ring to the elongated catheter body 4340. As described above, the inner ring and the outer ring may have more lobes (e.g., more therapeutic electrodes) and / or fewer lobes.

[0219] The sensing electrode or mapping electrode is typically smaller than the treatment electrode, which in this example is an elongated wire. For example, the sensing electrode or mapping electrode may have a length and / or width of 5 mm or less (for example, it may have maximum dimensions such as 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). The mapping electrode may be electrically insulated from the treatment electrode. In the example shown in Figure 43A, the sensing electrode or mapping electrode 4350, 4350' is formed from a band or cuff of conductive material (e.g., metal) that is crimped or otherwise bonded over an insulating material on the arm 4330 of the device. Some examples of insulating materials or coatings include polyimide, PET, etc. Each sensing electrode or mapping electrode may include a conductor (e.g., wire) extending from the sensing electrode or mapping electrode through a catheter to a coupling site (not shown) for coupling to a sensing or reading subassembly and / or to a separate mapping system or subsystem. The sensing electrode or mapping electrode may be electrically separated and insulated from the treatment electrode.

[0220] During operation, sensing electrodes and / or mapping electrodes (e.g., sensing / mapping electrodes) can be used to isolate the applicator's position from or from tissue. For example, sensing / mapping electrodes 1, 3, 5, 7, and 9 may provide the outline of the outer ring, while sensing / mapping electrodes 2, 4, 6, 8, and 10 may provide the outline of the inner ring. Combinations of sensing / mapping electrodes (e.g., 1-2, 3-4, 5-6, 7-8, 9-10, or other combinations) may also be used, or alternatively, to improve signal acquisition and / or for more reliable tissue contact. In some examples, sensing / mapping electrodes can be used to detect position without requiring tissue contact.

[0221] In general, sensing / mapping electrodes may be used (in place of or in addition to therapeutic electrodes) to monitor the progress of treatment. For example, sensing / mapping electrodes can be used to determine whether a target tissue has changed one or more electrical properties and / or electrical activity. For example, sensing / mapping electrodes may be used before and / or during the application of pulsed (e.g., nanosecond pulses) energy from therapeutic electrodes to determine or monitor electrical activity on or adjacent to the target tissue. For example, tissue ablation using the methods described herein, by the application of non-thermal treatment such as nanosecond pulsed electrical energy, may be expected to reduce the electrical activity of an underlying target, such as cardiac tissue. In general, the methods described herein can apply submicrosecond (e.g., nanosecond) pulses ranging from 0.1 / sec (Hz) to 100,000 Hz. Even at faster (e.g., kHz) frequencies, nanosecond pulses can provide relatively long periods during which no energy is applied to the tissue, during which time the sensing / mapping electrodes can detect electrical activity on the tissue. In some examples, sensing / mapping electrodes can be used to determine the impedance of underlying tissue and / or changes in impedance over time.

[0222] The apparatus described herein may also include one or more magnetic sensors 4342 (e.g., magnetic coils, rods, etc.). In this example, the magnetic sensor is attached to the distal section of the catheter body 4340 and is centrally located relative to the therapeutic electrode. This allows for increased precision in the placement of the catheter.

[0223] Figure 43B shows a side view of the applicator 4300. The inner ring 4320, the outer ring 4310, and the arm 4330 are shown coupled to the elongated body 4340. In this example, one or more (e.g., two 11, 12) additional sensing / mapping electrodes may be positioned on the shaft of the elongated body 4340 and used in combination with one or more of the other sensing / mapping electrodes described above.

[0224] These devices may be configured for magnetic sensing, electrical property (e.g., impedance-based) sensing, or both. For example, the devices shown in Figures 43A-43B include both mapping electrodes 4350, 4350' and a magnetic sensor 4342 in addition to the treatment electrodes. In some examples, the applicator may be coupled to a third-party mapping system (e.g., the Carto® system, the Navx® system, etc.) by directly or indirectly providing input from the sensing / mapping electrodes to the mapping system, for example. The applicators described herein may be used in conjunction with a separate mapping catheter. For example, tissue may be mapped using a mapping catheter and system that can generate a map or model of tissue, such as cardiac tissue, including a target area to be treated, and one or more sensors, including electrodes, may be introduced to locate the applicator on the map or model of tissue. The device can display an image of the map or model and, at the same time, indicate the position of the applicator on the image of the map or model to help guide the user, e.g., a physician, surgeon, etc., when treating the target tissue. Alternatively, the applicators described herein may be used for both mapping and ablation. In some examples, the apparatus described herein may include a mapping system or subsystem integrated into the apparatus.

[0225] For example, Figure 43C schematically illustrates an example of an apparatus as described herein, which includes both mapping and treatment. In a first embodiment of this example, the apparatus includes an applicator 4394 similar to those described above, which includes both multiple treatment electrodes and sensing / mapping electrodes. The applicator is coupled to a nanosecond pulsed energy treatment system 4392, which may include a pulse generator and a controller (including one or more processors) as described above (for example, as shown in Figure 1). The system 4392 may be separate from the mapping system 4393 and / or output 4395, the output may include one or more displays that show a map of tissue, including the location of the applicator, based on inputs from one or more sensing / mapping electrodes (or other mapping sensors) on the applicator. In some examples, as shown by the dashed line 4390'', the apparatus may include the nanosecond pulsed energy treatment system 4392 and output 4395, which can be used together with a separate mapping system / subsystem 4393. Alternatively, in some examples, the mapping system / subsystem may be included as part of the device, as indicated by the dashed box 4390'. In any of these devices, a separate mapping catheter 4396 may be coupled to the mapping system / subsystem 4393, as illustrated.

[0226] Wire-based bipolar electrodes for nanosecond pulsed energy application Any of the methods and apparatus described herein may be for the application of bipolar submicrosecond (e.g., nanosecond) pulses using electrodes formed using thin (small-profile) wires. These small-profile wires may have a maximum diameter of 0.015 inches (e.g., 0.38 mm) or less (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 less). The wires may be formed from any conductive material. Smaller-profile wires are particularly suitable for emitting the electromagnetic fields described herein. Typically, such small-profile wires are avoided in systems that generate thermal energy because the thinner the profile, the more limited the ablation area and the more fragile they may be.

[0227] For example, most energy-based therapeutic devices, such as radio frequency (RF) devices, employ electrodes with a diameter of approximately 2-3 mm or more. RF thermal ablation, for instance, relies on two types of heating: resistive and conductive. Tissue in direct contact with the electrode is heated via resistive heating, based on the voltage applied to the electrode and electrode material, as well as the impedance between the electrode and the tissue. Tissue away from the electrode can be heated as a result of conductive heating, either directly from the electrode or through heat conduction from already "hot" parts of the tissue to "colder" areas. Electrode size is crucial in this scenario because larger electrodes cover a larger area of ​​tissue, thus increasing "direct" conductive heat transfer between the electrode and the tissue. In addition, when multiple electrodes are used (e.g., bipolar RF systems), larger electrode sizes reduce the distance between them, thus decreasing the volume of tissue that needs to be heated by "indirect" conductive heat transfer. Even in some applications involving pulsed signals (e.g., millisecond pulses, microsecond pulses), the highest energy concentration is at the electrodes, and since the electric field generated by a typical 2-3 kV (e.g., the voltage used by almost all microsecond pulse devices) is not high enough to be therapeutic, larger electrodes are considered advantageous. As a result, most microsecond-based devices typically require electrode repositioning to generate adjacent therapeutic zones.

[0228] For example, in contrast to the bulky tubular electrodes used with RF ablation, the use of such small-profile wires in this disclosure allows the devices described herein to have a relatively smaller cross-profile. This makes it possible to retract any of these devices, for example, into the working channel of a bronchoscope / gastroscopy or the lumen of a delivery sheath for cardiac applications, thereby simplifying and / or enabling certain procedures.

[0229] The bipolar submicrosecond (e.g., nanosecond) pulse energies described herein can be applied at voltages high enough (e.g., 12–15 kV or higher) to generate a therapeutic electric field, even when the electrodes are constructed from small diameter (e.g., 0.005 inches to 0.015 inches or less) wires. Surprisingly, studies using such small diameter wires have been found to be highly effective for tissue ablation, without requiring repositioning for tissue ablation between them.

[0230] For example, Figures 44A to 44D illustrate examples of different configurations of wire-based designs for devices for delivering pulsed electrical energy. The small diameter of the wire electrodes in all these designs enhances the capabilities of these configurations, making them easily foldable and adaptable to smaller lumens of delivery devices. For example, such devices can be more easily fitted into the 2.8 mm or 3.7 mm working channels of therapeutic bronchoscopes and gastroscopes with inner diameters (ID: inner diameter) of 8.5 Fr, 9 Fr, and 12 Fr, such as cardiovascular induction sheaths. Catheters carrying such electrodes may be deflectable and / or maneuverable. For example, in Figure 44D, described below, delivery can be made through the working channel of a bronchoscope and / or gastroscope, and contact with target tissue can be made by deflecting the distal end of the bronchoscope or gastroscope.

[0231] Examples shown in Figures 44A to 44D can be used as distal portions of catheters used for the treatment of tubular areas of human or animal biological structures. Such tubular areas may include, but are not limited to, the esophagus, bronchi, pulmonary veins, and other parts of the venous and arterial systems. These devices can be used to apply submicrosecond pulse fields to other parts of the human body. For example, these devices can be used as part of a catheter used during minimally invasive procedures or as part of a device used during surgery.

[0232] For example, Figure 44A shows a first example of a device as described herein, comprising several small-diameter wires (e.g., wires having a diameter of 0.015 inches or less). In Figure 44A, the wires are positioned on an expandable member such as a balloon 4485. Three pairs of wires are shown, one of first polarity 4463 and the other of second polarity 4465, separated laterally. The balloon is positioned at the end of an elongated body, such as an elongated body 4460 of a catheter. The device may include a distal tip region 4469 extending distally from the balloon. The balloon may be deflated to fold the radial shape of the device (not shown) or inflated to expand the radial shape, and in Figure 44A, the device is shown with the device expanded. The laterally separated wires (electrodes or wire electrodes) may be separated by only, for example, 1 mm or less (e.g., 0.5 mm) to 10 mm.

[0233] Figure 44B shows another example of an expandable device including a single pair of small-diameter wires (e.g., wires with a diameter of 0.015 inches or less). In this example, as in Figure 44A, the wire electrodes 4463', 4465' are positioned on an expandable member (e.g., balloon 4485) which is coupled to, for example, a catheter 4460', and the device includes a distal region 4469' that extends beyond the expandable member and electrodes. In Figure 44B, the pair of wire electrodes includes a first-polarity wire 4463' that is laterally separated from a second-polarity wire 4465'. As in Figure 44A, the electrodes extend partially (or, in some examples, completely) radially around the expandable member, such as over approximately 45–235 degrees (e.g., 90–135 degrees, etc.). Figures 44A and 44B show wire electrodes extending laterally with respect to the long axis of the expandable member, but in some examples the electrodes may extend longitudinally along the length of the expandable member and may be located at separate radial positions, as shown in Figure 44C.

[0234] In Figure 44C, the device includes an expandable member 4485 (e.g., a balloon, basket, etc., shown as a balloon in Figure 44C), on which multiple wire electrodes, which may have different polarities, are arranged extending longitudinally along the length of the expandable member from different radial positions. For example, the active region of a first-polarity wire electrode 4463'' extends over part or all of the length of the balloon 4485 and is radially separated from the active region of a second wire electrode 4465'' by about 40–60 degrees (2–5 mm in this example). The device includes an elongated catheter body 4460'' and a distal end region 4469''. The active region of each electrode typically refers to the exposed region of the wire electrode, and the non-exposed (e.g., insulated) regions 4467 may be positioned closer to each other, as shown in Figure 44C. As in the examples shown in Figures 44A–44B, the expandable member in Figure 44C may transition between a folded configuration (not shown) and an expanded configuration (shown). Therefore, the spacing between wire electrodes can be controlled by controlling the expansion of the expandable member.

[0235] Alternatively, in some examples, the apparatus may not include an expandable member, as shown in Figure 44D. In this example, the apparatus includes an elongated body 4460''' from which a pair of wire electrodes 4463''', 4465''' extend. The wire electrodes may be supported by insulating regions 4467', as shown, and may be separated from each other by a radial (and / or optionally longitudinal) spacing distance. The wires may be folded from a folded configuration (not shown) to an extended configuration (shown), or vice versa.

[0236] Method of using the apparatus disclosed herein The devices described herein can include, or be included as part of, a portion of a catheter used during minimally invasive procedures or a portion of a device utilized during surgery. As described above, the devices described herein, including (but not limited to) those shown in FIGS. 22A-22C, FIGS. 23A-23F, FIG. 25, and FIG. 26, can be used to treat body lumens by applying pulsed sub-microsecond (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.

[0237] Generally, sub-sub-microsecond (e.g., nanosecond) pulsed energy can be applied using the methods and devices described herein. However, any of the devices described herein can also be configured to apply other types of energy, such as RF or micro-pulse-based electric field energy.

[0238] In some cases, the devices described herein may be inserted through a catheter or other delivery device and / or used in conjunction with them. For example, any of these devices may be inserted through the working channel of an endoscope, such as a bronchoscope or gastroscopy. In some cases, the device may include, for example, a catheter with an expandable active area including electrodes, which may be used in conjunction with an expandable frame (e.g., struts, ribs, etc.) and / or a balloon, and may be used in the bronchial system or esophagus, and may be introduced through the working channel of a bronchoscope or gastroscopy. The endoscope (e.g., bronchoscope or gastroscopy) may be placed adjacent to the treatment site, which may be visualized (imaged) through a scope or camera, such as a bronchoscope view (camera built into the scope). The device can then be introduced through the working channel of the scope. The device (e.g., frame and / or balloon) can then be expanded, and thus expanded, the electrodes on the surface of the frame / balloon are placed in contact with the tissue at the treatment site. Energy can then be delivered to the electrodes. The device can then be folded (for example, by deflating the balloon or frame) and repositioned to the next treatment site where active area expansion and energy application can be repeated, either by moving the device or the scope and device together.

[0239] For example, the devices of the present disclosure may be used to treat luminal cancers by inserting the device of the present disclosure through a body vasculature (using a catheter or, where applicable, a laparoscopic device) and expanding the device at the treatment site (e.g., within or adjacent to a luminal cancer) and applying energy, specifically nanosecond pulsed electrical energy, to treat the tissue. In some examples, these devices described herein may be used to treat the prostate, such as to treat prostate cancer and / or benign prostatic hyperplasia. For example, described herein is a method of treating the prostate by inserting a device as 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 insertion of a luminal catheter through the penis, through the urethra, into the prostate where energy delivery can be applied.

[0240] Other examples of tissues that may be treated can include the lung (e.g., to treat lung cancer), the pancreas (e.g., pancreatic cancer), and the like. Other exemplary tissues (body vasculatures) and treatment methods are described herein.

[0241] The methods and devices described above are, for purposes of illustration, described with an example of arterial treatment using pulsed electrical therapy. However, other treatments are contemplated.

[0242] As described above, any of the devices described herein can be implemented in a robotic system that can be used to position and / or control electrodes during treatment. For example, the robotic system may include a movable (robot) arm to which an elongated applicator tool is coupled. Various motors and other moving devices can be incorporated to enable fine movement of the working end of the elongated applicator tool in multiple directions. The robotic system and / or the elongated applicator tool may further include at least one image acquisition device (and preferably two or more for stereoscopic viewing) that can be mounted in a fixed position or coupled (directly or indirectly) to the robotic arm or other controllable moving device. In some examples, the image acquisition device may be incorporated into the elongated applicator tool.

[0243] Examples of the methods described herein can be implemented using computer software, firmware, or hardware. Various programming languages ​​and operating systems can be used to implement the disclosure. A program that runs the methods and systems may include separate program code containing a set of instructions for performing a desired operation, or may include multiple modules that perform such suboperations of the operation, or may be part of a single module of a larger program that provides the operation. The modular structure facilitates the addition, deletion, updating, and / or modification of internal modules and / or features within modules.

[0244] In some examples, the user can select a specific method or example of this application, and the processor executes the program or algorithm associated with the selected method. In some examples, various types of position sensors can be used. For example, in certain examples, a non-optical encoder can be used, which can adjust the voltage level or polarity as a function of encoder signal feedback to achieve a desired angle, velocity, or force.

[0245] Specific examples may relate to machine-readable media (e.g., computer-readable media) or computer program products containing program instructions and / or data (including data structures) for performing various computer implementations. Machine-readable media can be used to store software and data that cause a system to perform the methods of this disclosure. The machine-readable media described above may include any suitable medium that can store and transmit information in a form accessible by a processing device, such as a computer. Some examples of machine-readable media include, but are not limited to, hard disks, floppy disks, magnetic disk storage devices such as magnetic tapes. This may also include flash memory devices, optical memory devices, random access memory, and the like. Data and program instructions may also be embodied on a carrier wave or other carrier medium. Examples of program instructions include both machine language, such as that generated by a compiler, and files containing high-level code that can be executed using an interpreter program.

[0246] Any of the methods described herein (including user interfaces) may be implemented as software, hardware, or firmware, and may be described as a non-temporary computer-readable storage medium storing a set of instructions that can be executed by a processor (e.g., a computer, tablet, smartphone, etc.) to cause the processor to perform or control the execution of any of the steps, including but not limited to, displaying, communicating with a user, analyzing, changing parameters (including timing, frequency, intensity, etc.), determining, and warning. In some exemplary examples, hardware may be used in combination with software instructions to implement this disclosure.

[0247] Where a feature or element is referred to herein as "on top of" another feature or element, it may be directly on the other feature or element, or there may be intervening features and / or elements. In contrast, where a function or element is referred to as "directly present" on another function or element, there is no intervening function or element. Where a feature or element is referred to as "connected," "attached," or "combined" to another feature or element, it should also be understood that it may be directly connected, attached, or combined with the other feature or element, or there may be intervening functions or elements. In contrast, where a function or element is referred to as "directly connected," "directly attached," or "directly combined" to another function or element, there is no intervening function or element. Features and elements described or illustrated in part with respect to one example may apply to other examples. It will also be understood by those skilled in the art that a reference to a structure or feature positioned "adjacent" to another feature may overlap with or have a portion beneath the adjacent feature.

[0248] The terms used herein are for illustrative purposes only and are not intended to limit the inventions of this disclosure. For example, as used herein, the singular forms “a,” “an,” and “the” are intended to include the plural form unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and / or “comprising,” as used herein, specify the presence of the described features, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof. As used herein, the terms “and / or” include any combination of one or more of the related listed items and may be abbreviated as “ / .”

[0249] Spatially relative terms such as “under,” “below,” “lower,” “over,” and “upper” may be used herein to describe the relationship between one element or feature and another, as illustrated in the figures, for the sake of clarity. It will be understood that spatially relative terms are intended to encompass different orientations of a device in use or operation, in addition to the orientation depicted in the figures. For example, if the device in the figure is inverted, an element described as “under” or “beneath” another element or feature is oriented “over” that other element or feature. Thus, the illustrative term “under” can encompass both up and down directions. The device may be oriented in other ways (rotated 90 degrees or in other directions), and the spatially relative descriptors used herein may be interpreted accordingly. Similarly, terms such as “upwardly,” “downwardly,” “vertical,” and “horizontal” are used herein for illustrative purposes only, unless otherwise specified.

[0250] The terms “first” and “second” may be used herein to describe various features / elements (including steps), but unless the context indicates otherwise, these features / elements should not be limited by these terms. These terms may be used to distinguish one feature / element from another. Thus, 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.

[0251] Throughout this specification and the following claims, unless otherwise specified in the context, the word “comprise,” and variations such as “comprises” and “comprising,” mean that various components can be used together in methods and articles (e.g., compositions and apparatus including devices and methods). For example, the term “comprising” would be understood to mean including the element or step described, but not excluding other elements or steps.

[0252] In general, all apparatuses and methods described herein should be understood to be comprehensive; however, all or a subset of components and / or steps may be "consisting of" or, alternatively, "consisting essentially of" various components, steps, subcomponents, or substeps, which may be expressed as "consisting essentially of".

[0253] Where used in the specification and claims of this specification, and where used in the examples, unless otherwise specified, all numbers can be read as if preceded by the words “about” or “approximately,” even if the term is not explicitly stated. The phrases “about” or “approximately” may be used when describing size and / or location to indicate that the described value and / or location is within a reasonable expected range of the value and / or location. For example, a number may have values ​​such as + / -0.1% of the described value (or range of value), + / -1% of the described value (or range of value), + / -2% of the described value (or range of value), + / -5% of the described value (or range of value), + / -10% of the described value (or range of value), etc. Any number given herein should also be understood to include an approximate or approximate value unless the context indicates otherwise. For example, if the value “10” is disclosed, “about 10” is also disclosed. Any numerical range enumerated herein is intended to include all subranges contained therein. Furthermore, as those skilled in the art will understand, when a value is disclosed, the possible ranges between the value and the values ​​"less than or equal to", "greater than or equal to", and the values ​​themselves are also disclosed. For example, if the value "X" is disclosed, then "less than or equal to X" and "greater than or equal to X" (e.g., where X is a number) are also disclosed. Also, throughout this application, data is provided in several different formats, and this data also represents ranges of endpoints and starting points, as well as any combination of data points. For example, if a specific data point "10" and a specific data point "15" are disclosed, it is understood that the ranges between 10 and 15, greater than or equal to 10 and 15, greater than or equal to 10 and 15, less than or equal to 10 and 15, and equal to 10 and 15 are disclosed, as well as the range between 10 and 15. It is also understood that each unit between two specific units is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0254] While various illustrative examples are described above, any number of modifications can be made to these examples without departing from the scope of the invention as described in the claims. For example, the order in which the various described method steps are performed may often be changed in alternative examples, and in other alternative examples, one or more method steps may be skipped entirely. Optional features of the various device and system examples may be included in some examples and not in others. Therefore, the foregoing descriptions are provided primarily for illustrative purposes and should not be construed as limiting the scope of the invention as described in the claims.

[0255] The examples and illustrations contained herein illustrate, not limit, specific embodiments in which the subject matter may be implemented. As stated above, other examples and variations can be utilized and derived from therein, resulting in structural and logical substitutions and modifications without departing from the scope of this disclosure. Such examples of the subject matter of the present invention, when multiple are disclosed, may be referred to herein individually or collectively by the term “invention” simply for convenience, without the intention of voluntarily limiting the scope of this application to any single invention or concept of invention. Thus, while certain examples have been illustrated and described herein, any configuration calculated to achieve the same objective can be used in place of the specific embodiments shown. This disclosure is intended to cover all possible adaptations or variations of various examples. Combinations of some features of the examples described above or provided, and other examples not specifically described herein, will be apparent to those skilled in the art upon consideration of the above description.

Claims

1. In an ablation and mapping apparatus for applying electrical energy, The long, slender body, The device comprises an applicator region extending from the distal end region of the elongated main body, The aforementioned application area is A first arm and a second arm are configured to extend from the elongated main body, A first wire electrode extending between the first arm and the second arm, A second wire electrode extending between the first arm and the second arm, wherein the second wire electrode is substantially parallel to the first wire electrode, It has a plurality of mapping electrodes and / or sensing electrodes arranged on the first arm and the second arm and on the elongated body, The apparatus is characterized in that the applicator region is configured to deliver energy between the first wire electrode and the second wire electrode.

2. The apparatus according to claim 1, characterized in that the first wire electrode has a first active region, and the second wire electrode has a second active region arranged concentrically with respect to the first active region.

3. The apparatus according to claim 2, characterized in that the second wire electrode is substantially parallel to the first wire electrode within ±8 degrees along the length of the first active region.

4. The apparatus according to claim 1, characterized in that the first wire electrode is located at a minimum distance d from the second wire electrode along the length of the first wire electrode.

5. The apparatus according to claim 1, characterized in that the mapping electrode and / or sensing electrode are configured to receive a signal and generate a map of the shape and / or activity of the heart.

6. The apparatus according to claim 1, characterized in that the first wire electrode and the second wire electrode extend from the elongated body on the same plane.

7. The apparatus according to claim 1, characterized in that the length of the first wire electrode is between 2 mm and 8 mm, and the length of the second wire electrode is between 2 mm and 8 mm.

8. The apparatus according to claim 1, characterized in that the applicator area has a paddle-shaped applicator.

9. The apparatus according to claim 1, characterized in that the first wire electrode has a plurality of first wire loops and / or the second wire electrode has a plurality of second wire loops, and the plurality of first wire loops and the plurality of second wire loops are arranged as a petal around the distal end region of the elongated body.

10. The apparatus according to claim 1, characterized in that the first wire electrode and the second wire electrode have different circumferences.

11. The apparatus according to claim 1, wherein the apparatus is configured to be used for the treatment of atrial fibrillation, ventricular tachycardia, and other cardiac diseases, or for the application of electrical energy to the pulmonary venous sinuses, foramina, and / or other cardiac tissue walls.

12. The apparatus according to Claim 1, characterized in that the apparatus is configured for single-shot treatment and / or point-by-point treatment.

13. The apparatus according to claim 1, further characterized in that it has a central electrode at the distal end of the elongated body.

14. The apparatus according to claim 13, characterized in that the central electrode has a polarity opposite to the polarity of at least one of the first wire electrode and the second wire electrode.

15. The apparatus according to claim 1, further comprising one or more additional electrodes arranged concentrically with respect to the first wire electrode and the second wire electrode, and having a different circumference from that of the first wire electrode and the second wire electrode.

16. The apparatus according to claim 1, characterized in that the first wire electrode has a plurality of first active regions, the second wire electrode has a plurality of second active regions, and each of the plurality of first active regions and each of the plurality of second active regions are separated on both sides by an insulating region.

17. The apparatus according to claim 4, characterized in that the minimum distance d is substantially the same over the length of the first wire electrode.

18. The apparatus according to claim 1, characterized in that the first wire electrode and the second wire electrode are configured to flexibly conform to the wall of an anatomical structure.

19. The apparatus according to claim 1, characterized in that the first wire electrode and the second wire electrode are each formed from a wire with a diameter of less than 0.2 mm.

20. The apparatus according to claim 1, characterized in that the first wire electrode has a first polarity and the second wire electrode has a second polarity.

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