Circumferential ablation devices and methods

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

[0002] (Incorporated by reference) All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. [Background technology]

[0003] Short, high-field-strength electric pulses have been described for the electronic manipulation of biological cells. For example, electric pulses can be used in the treatment of human cells and tissues. The voltage induced in the cell membrane can depend on the pulse length and pulse amplitude. Pulses longer than about 1 microsecond can charge the outer cell membrane, resulting in permanent opening of pores. Permanent opening can result in instantaneous or near-instantaneous cell death. Pulses shorter than about 1 microsecond can affect the interior of cells without adversely or permanently affecting the outer cell membrane, delaying cell death with intact cell membranes. For example, such short pulses, with field strengths ranging from 10 kV / cm to 100 kV / cm, can induce apoptosis (i.e., programmed cell death) in some or all cells exposed to the described field strengths and pulse durations. These higher field strengths and shorter electric pulses can be useful in manipulating intracellular structures such as the nucleus, endoplasmic reticulum, and mitochondria. For example, such sub-microsecond (eg, 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 strength electrical pulses, to a selected treatment area. The two electrodes can be configured for bipolar operation. The electrodes are placed in contact with tissue within the area to be treated. In some cases, the treatment area can have a varying or irregular shape. For example, the treatment area can transition from a first diameter to a second diameter. The varying diameter and / or irregular shape can make it difficult for the electrodes to maintain a consistent and uniform contraction.

[0005] Therefore, it may be beneficial to provide an electrode that can conform to treatment areas of varying and / or irregular shapes. Summary of the Invention

[0006] Described herein are medical apparatus (e.g., devices, systems, etc.) and methods that can be used to perform medical procedures to treat patients. Specifically, the apparatus and methods described herein can be used to deliver short, high-field electrical pulses to perform ablation, such as circumferential ablation, on body vessels, including blood vessels and other lumens.

[0007] For example, described herein are devices and methods for treating walls of anatomical structures such as body passageways, cavities, or vessels (e.g., veins, arteries, ducts, heart, trachea, pharynx, larynx, bronchi, ureters, urethra, fallopian tubes, 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, microsecond pulsed electric fields, etc. For convenience of description, all such anatomical structures, cavities, ducts, lumens, passageways, 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 devices described herein can be configured to selectively treat body vessels with varying, transitioning, and / or irregular surfaces. The electrodes that can be conformed to the body vessel can include a first electrode and a second electrode that are configured to deploy from a catheter and conform, for example, to a portion of the wall of the body vessel and provide a sub-microsecond (e.g., nanosecond) pulsed electric field in a localized manner that limits or prevents 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, lungs (airways), gastric cavities, ducts, etc. may be treated as described herein. In some examples, the instruments and methods described herein are configured for otolaryngological use, for example, for insertion and treatment by applying sub-microsecond (e.g., nanosecond) pulsed electric fields within 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 glands, and structures connecting the throat (pharynx) to the stomach. These instruments and devices may be configured for insertion into these structures, for example, as elongated applicator tools, including catheters, tubing, etc., sized and shaped to fit within the ear, nose, or throat and / or to treat associated anatomical structures (e.g., nasal turbinates, tonsils, tongue, soft palate, parotid glands, etc.). For example, described herein are methods and devices configured for delivery of sub-microsecond (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, colon, etc. Also described herein are methods and devices configured for delivery of sub-microsecond (e.g., nanosecond) pulsed electric fields to portions of the respiratory tract, including the trachea, pharynx, larynx, bronchi, and bronchioles. The methods and devices described herein are also particularly useful in cardiac applications, including, but not limited to, the treatment of atrial fibrillation, among others.

[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.), the esophagus, ear, nose, throat, trachea, pharynx, larynx, small intestine, large intestine, duodenum, colon, etc. These applicator tools may include an elongated, flexible body extending in a proximal to distal direction. One or more (e.g., multiple) electrodes configured for delivery of electrical pulses (e.g., nanosecond pulses) to target tissue may be present at an end region of the flexible body.

[0010] The applicator ("applicator tool") may be configured to removably couple to a pulse generator configured to generate sub-microsecond (e.g., nanosecond) pulsed energy, for example, via a handle proximal to a distal end region containing the electrodes. The electrodes may be deployable and may be on an expansion member that expands to contact the vessel wall. The handle can control this deployment. Alternatively, in some cases, the applicator tool (also referred to herein as an apparatus or device) can be configured to couple directly to the pulse generator without the need for a handle. According to one example, the apparatus described herein includes medical devices and instruments for use in procedures in which the applicator tool is inserted into a lumen. These devices can be introduced into a blood vessel, for example, through an outer delivery catheter or guide sheath.

[0011] Any of the devices described herein can be configured to function within regions of the body having varying diameters (e.g., from wide to narrow or from narrow to wide), including regions having a tapered or funnel shape. For example, some of the devices described herein may include at least two ring-shaped (e.g., oval, circular, etc.) electrodes having different diameters. In some examples, these ring-shaped 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 protrusions (e.g., ribs, wires, springs, contact plates, contact posts, balloons, etc.) that can be manipulated to extend from the proximal end of the applicator, for example, by operation of a proximal handle to which the applicator tool is coupled. The contact protrusions typically contact the wall of a lumen through which the applicator tool is inserted and can improve access and contact of the electrode with tissue. For example, the contact protrusions may be expandable elements (e.g., balloons) or mechanical elements (e.g., a pair of plates or arms). In some examples, multiple contact protrusions may be positioned along the length of the applicator and may be moved closer or farther apart along the length of the applicator distal end region. In some examples, the contact protrusions flank the electrode. In some examples, the contact protrusions comprise the electrode. The contact protrusions may be retractable / removable into or simply relative to the applicator tool.

[0013] In one example, the applicator may include an elongate body, such as an elongate catheter body, a first electrode formed from one or more loops and having a first diameter flexibly coupled to the elongate catheter body, and a second electrode formed from one or more different flexible loops having a second diameter flexibly coupled to the elongate catheter body. The first and second electrodes may contact a body vessel, particularly a body vessel with an irregular, varying, or transitioning surface.

[0014] In some cases, the first and second electrodes may be divided into lobes, with each lobe coupled to an elongate body (e.g., an elongate catheter body) with an arm. In some cases, the first and second electrodes may include two or more lobes.

[0015] In some examples, the first and second electrodes are coupled to a distal end region of the elongate body (which may be referred to as an elongate catheter body). In further examples, the first and second electrodes may be movable within the elongate catheter body and may be configured to collapse when extending out from the elongate catheter body and retracted into the elongate catheter body. In some other examples, one of the first diameter and the second diameter is smaller than the other. In still other examples, the first electrode is positioned distal to an end of the elongate catheter body (e.g., the distal end of the elongate catheter body), and the second electrode is disposed between the first electrode and the distal end of the elongate catheter body.

[0016] In some examples, the first electrode and the second electrode are configured to flexibly contact sinuses associated with pulmonary veins. In some other examples, the first conductor and the second conductor are configured to deliver pulsed electrical therapy, and pulsed energy is transferred between the first conductor and the second conductor. In another example, the first conductor and the second conductor are configured to deliver pulsed electrical therapy, and energy is transferred between the first conductor and a third conductor or between the second conductor and a third conductor.

[0017] In some examples, the first conductor and the second conductor are configured to vary the distance therebetween.

[0018] In another example, a device for delivering nanosecond pulsed electric fields may include an elongate catheter body, a shape support member coupled to the elongate catheter body and configured to form a shape, a conductive braid circumferentially surrounding the shape support member and configured to form a first electrode, and one or more conductive bands circumferentially surrounding the conductive braid 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 braid.

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

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

[0021] A method for delivering a sub-microsecond pulsed electric field to a body vessel may include positioning an applicator including 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 electrical therapy via the two or more electrodes. In some examples, placing the two or more electrodes in contact with tissue may include deploying the two or more electrodes from an elongate catheter body. In some other examples, the two or more electrodes may include a first shaped electrode and a second shaped electrode. The first shaped electrode may have a first diameter and the second shaped electrode may have a second diameter, the first diameter being different from the second diameter.

[0022] In some examples, the first shaped electrode may be disposed on a different plane than the second shaped electrode. In some other examples, the first shaped electrode may be coplanar with the second shaped electrode.

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

[0024] The devices described herein can generally be configured to safely and reliably deliver microsecond, nanosecond, or picosecond pulses, including electric fields with pulse widths of 0.1 nanoseconds (ns) to less than 1000 nanoseconds, or even shorter, such as 1 picosecond, sometimes referred to as submicrosecond pulsed electric fields. This pulse energy can have high peak voltages, such as 1-5 kilovolts per centimeter (kV / cm), 10 kV / cm, 20 kV / cm, or even 100 kV / cm or more. In some applications, the pulse energy can be less than 1 kV / cm. Treatment of living cells can use multiple cyclic pulses at frequencies ranging from 0.1 Hz to 100,000 Hz, for example, to induce apoptosis in ingrowth tissue causing restenosis. Selective treatment of the vascular wall with high-voltage, submicrosecond pulsed energy can induce apoptosis in cells causing restenosis without substantially affecting normal cells in the surrounding tissue due to its non-thermal nature. The subject may be a patient (human or non-human, including animals). A user may operate the devices described herein on the subject. The user may be a medical practitioner (doctor, surgeon, etc.), medical technician, nurse, or other health care provider.

[0025] Thus, applying high-voltage, high-rate (e.g., microsecond or sub-microsecond) electrical pulses can include, for example, applying a train of electrical pulses having pulse widths of 0.1 nanoseconds (ns) to 1000 nanoseconds. Applying high-voltage, high-rate electrical pulses can include, for example, applying a train of sub-microsecond electrical pulses having peak voltages of 1 kilovolt per centimeter (kV / cm) to 500 kV / cm. Applying high-voltage, high-rate electrical pulses can include, for example, applying a train of sub-microsecond electrical pulses at frequencies of 0.1 Hz to 100,000 Hz.

[0026] Any of these devices can be used with a pulse generator. For example, systems for treating tissue are described herein that may include 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 the 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 connect to the high-voltage connector. In some examples, the applicator tool includes an elongated body having a distal end region configured to have one or more electrodes extending therefrom. The distal end, in some examples, may be steerable (e.g., articulatable).

[0027] As mentioned above, any of these devices may be configured such that the proximal end of the applicator tool is adapted to be coupled to a robotic or movable arm, for example, for computer-controlled actuation of the set of electrodes. Alternatively, or additionally, the proximal end of the applicator tool may be adapted to couple to a handle of a pulse generator, which may in turn 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 therapy at the distal end region of the applicator. In some examples, the applicator includes at least two circumferentially arranged electrodes, each circumferentially arranged around the support. The longitudinal position of one or both of the circumferentially arranged electrodes can be adjustable so 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, for example, to be between 5 mm and 40 mm (e.g., between 10 mm and 20 mm, etc.). The circumferentially arranged electrodes can be an electrode ring (extending completely or partially circumferentially around the periphery) or multiple separate electrodes circumferentially arranged around the applicator. Adjusting the spacing between the electrodes can allow the user to adjust and / or correct placement and fit within an interior wall or sinus, especially when the diameter / size of the blood vessel changes (including rapidly changing) with longitudinal position. One electrode ring may fit around one circumference, and the other electrode ring may fit around a larger or smaller circumference, and the spacing between them may be adjustable in some instances.

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

[0030] For example, described herein are apparatus (e.g., devices, systems, etc., including an electrode applicator) for delivering a pulsed electric field into a body lumen. These apparatus may include an elongate body (having an elongate flexible body), a first electrode comprising a first one or more loops and having a first active area formed on the first one or more loops, the first active area being positioned to surround the body lumen, and the first one or more loops being flexibly coupled to a distal end region of the elongate body, and a second electrode comprising a second one or more loops and having a second active area formed from the second one or more loops, the second active area being positioned to surround the body lumen, and the second one or more loops being flexibly coupled to the distal end region of the elongate body, and the first electrode being laterally offset from the second electrode along the distal end region of the elongate 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-insulated) region of a conductive material (e.g., a conductive wire, etc.) configured to emit electrical energy. Generally, the devices described herein may include a first electrode with a first conductive region extending over multiple lengths of different loops forming the first electrode (or, in some examples, a second electrode). All of the loops of the first electrode (and thus all of the loop subregions forming the active region) may be electrically coupled together to form a single anode or a single cathode, and all of the loops (and thus all of the loop subregions) forming the second electrode (and thus all of the loop subregions) are electrically coupled together as a single anode or a single cathode.

[0032] In some cases, the first electrode comprises a single loop. In other cases, the first electrode comprises multiple loops forming the first electrode, the loops being in electrical communication. Similarly, the second electrode can 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 elongate body, and / or the second electrode may traverse the distal end region of the elongate body. In any of these devices, the first electrode and / or the second electrode may include a first plurality of loops arranged as petals around the distal end region of the elongate body. The outer portion of each petal may form an active area for a single electrode. This configuration may enable more robust treatment around the entire circumference of the vessel without requiring multiple repositioning steps of the electrode pair to cover the same larger area around the circumference of the vessel.

[0034] Generally, the first active region of the first electrode can have a diameter that is smaller than the diameter of the second active region (e.g., the diameter of the loops forming the first electrode can be different from the diameter of the loops forming the second active region of the second electrode). In some examples, the diameters of the loops forming the first electrode and the second electrode can 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), or the like. Generally, the first and second electrodes may be coupled to the outer periphery of the expandable member, thereby at least partially surrounding the circumference of the blood vessel. The expandable frame may support the first and second active electrodes. Thus, the first and second electrodes may be disposed on the expandable frame. For example, the first and second electrodes may be disposed on an expandable balloon.

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

[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 circumference of the lumen. As used herein, "disposed or configured to surround a body lumen" can refer to extending at least partially around the circumference of the body lumen (e.g., traveling an arc of 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, a first active region disposed to surround a body lumen can include an active region that extends completely or nearly 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 360 degrees around the circumference of the lumen, etc.). In some cases, the first active area is configured to encircle the body lumen in a nearly complete circle.

[0038] Any of these devices may include an outer catheter or guide sheath (e.g., a delivery catheter), and an elongate body forming or carrying the first and second electrodes may be slidably disposed within the outer catheter, the first and second electrodes configured to collapse when retracted or introduced into the outer catheter and / or configured to expand radially outward when extended from the distal end of the delivery (outer) catheter.

[0039] The first electrode may be positioned distally relative to the end region of the elongate 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., may vary). For example, the first electrode may be configured to slide axially proximally or distally relative to the second electrode.

[0040] In some examples, the first electrode may comprise an anode and the second electrode may comprise 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 greater 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 pulsed electric fields, the device comprising: an elongate catheter body; a first electrode comprising a first wire loop, the first wire loop flexibly extending from the elongate catheter body, the first electrode having a first active area comprising at least a portion of the first wire loop and extending a length of greater than 5 cm; and a second electrode comprising a second wire loop, the second wire loop flexibly extending from the elongate catheter body, the second electrode having a second active area comprising at least a portion of the second wire loop and extending a length of greater than 5 cm.

[0043] The first and second active regions can be separated by a fixed distance along the longitudinal axis of the elongate catheter body. The first and second electrodes can be configured to flexibly conform to a body vessel. The first loop can 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 elongate catheter body, and the second electrode may be positioned between the first electrode and the distal end of the elongate catheter body.

[0045] Generally, the devices described herein are advantageously configured to 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 overcomes the problem of many other electrical delivery systems that respond to multiple separate active regions, which can leave gaps. The devices described herein are particularly well-suited for applying nanosecond pulses, but are not limited to such use. Nanosecond pulse energy can enter cells nonthermally and act by altering the function of internal organelles, including mitochondria and the endoplasmic reticulum. For example, nanosecond pulsed electric fields can cause intracellular disruption, resulting in controlled cell death. In examples where the applied energy is a nanosecond (or faster) pulsed electric field, the active region of each electrode can be long and thin, e.g., formed from a wire, so that the applied electric field applies very little thermal energy, preventing damage to noncellular tissue.

[0046] For example, also described herein is a method for delivering a pulsed electric field to a wall of a body vessel within a subject's body, the method including positioning a first electrode including a first one or more wire loops and a second electrode including a second one or more wire loops within the body vessel such that first active regions of the first one or more wire loops are in electrical communication with a first circumference of the wall and second active regions of the second one or more wire loops are in electrical communication with a second circumference of the wall longitudinally separated from the first circumference of the wall, and applying pulsed electrical therapy 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 elongate body coupled to the first and second electrodes, expanding at least one of the first and second electrodes from a delivery configuration to a deployed configuration. In some examples, deploying the first electrode includes contacting a wall with a plurality of electrically continuous wire lengths of the first one or more wire loops. In some examples, deploying the second electrode includes contacting a wall with a plurality of electrically continuous wire lengths of the second one or more wire loops. Deploying the first electrode may include expanding the first electrode to have a larger diameter than the second electrode. In some examples, deploying includes deploying within an antrum of a pulmonary vein. For example, deploying may include deploying the first electrode such that the first electrode is coplanar with the second electrode.

[0048] As described above, applying pulsed electrical therapy can include applying an electric field between the first active region and the second active region. In particular, applying pulsed electrical therapy can include applying pulses having nanosecond durations (less than 1000 ns durations).

[0049] Also described herein is a device comprising: an elongate body extending proximally to distally, the elongate body configured to be inserted into a body vessel; and an applicator region at a distal end region of the elongate body, the applicator region comprising a plurality of expandable ribs configured to expand outwardly within the body vessel from a folded configuration, each rib comprising a non-insulated active region; and further, 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-insulated active area of ​​each of the plurality of ribs can be configured to be substantially straight and parallel to the longitudinal axis of a portion of the applicator area. In some implementations, the non-insulated active flat area of ​​each rib is also configured to remain the same length during rib expansion, regardless of how much each rib is expanded. Each of the plurality of ribs can include a hinge area on each side of the non-insulated active area. The hinge areas can be covered by flexible insulation.

[0051] In some examples, the elongate body can include a first elongate member coupled to a proximal end of each rib and a second elongate member coupled to a distal end of each rib, the first elongate member and the second elongate member configured to slide axially relative to each other to transform the applicator region between a collapsed configuration and an expanded configuration in which the plurality of 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 elongate body can be a flexible elongate body. The plurality of expandable ribs can be substantially flat.

[0053] Any of these devices may include an expandable member within the applicator region, configured to expand outwardly to drive the expansion of the plurality of ribs.

[0054] In some cases, the applicator region is configured to expand outwardly into a shape having a larger cross-sectional area relative to a long axis of the applicator region, for example, distally more than proximally, or in some cases, proximally more than distally. For example, the applicator region may include a teardrop shape.

[0055] The uninsulated active area of ​​each rib may be within a distal portion of the applicator region such that the uninsulated active area faces distally in the expanded configuration.

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

[0057] In some examples described herein, a device may comprise: an elongate body extending proximally to distally, the elongate body configured to be inserted into a body vessel; an applicator region at a distal end region of the elongate body comprising: a first wire extending distally from the elongate body, the first wire having a first active region adjacent a first insulating region of the first wire; and a second wire extending distally from the elongate body, the second wire having a second active region adjacent 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 a length of the first active region; and further wherein the first active region is configured to have a first polarity and the second active region is configured to have a second polarity. The first wire may include a first loop, and the second wire may include a second loop positioned concentrically with or within the first loop. In any of these devices, the first and second wires may extend from the elongate body in a plane. In some examples, the insulating region and / or the elongate body may include a bend such that the first and second wires extend at an angle relative to the longitudinal axis of the elongate body.

[0058] Also described herein are apparatus (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 treats a larger area with multiple electrically coupled active regions. For example, the apparatus may include an elongate body; a plurality of loops or ribs extending radially outward from the elongate body at a first circumferential position, each loop or rib comprising a non-insulated electrically active region facing radially outward such that the non-insulated electrically active region surrounds the first circumferential position of the elongate body; and an electrical connector configured to switch between a first configuration in which the multiple non-insulated electrically active regions are electrically coupled together to apply energy at a first polarity and a second configuration in which the non-insulated electrically active regions are separately activated.

[0059] In some examples, the electrical connector can be configured to electrically couple all of the non-insulated electrically active area loops or ribs of the plurality of loops or ribs in a first configuration, where the connector electrically couples a first subset of the non-insulated electrically active area loops or ribs of the plurality of loops or ribs and applies energy with a first polarity, and a second plurality of loops or ribs alternating with the loops or ribs of the first plurality of loops or ribs and applies energy with a second polarity.

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

[0061] For example, described herein is a device for delivering a pulsed electric field to a wall of an anatomical structure, the device comprising: an elongate body; a first electrode comprising a first one or more loops and having a first active area formed on the first one or more loops, the first active area configured to surround a first region of the wall of the anatomical structure, the first one or more loops being flexibly coupled to a distal end region of the elongate body; and a second electrode comprising a second one or more loops and having a second active area formed from the second one or more loops, the second active area configured to surround a second region of the wall of the anatomical structure, the second one or more loops being flexibly coupled to the distal end region of the elongate body, the first electrode being radially offset, laterally offset, or both radially and laterally offset from the second electrode.

[0062] Any of the devices described herein may be configured such that at least one of the first active area and the second active area is configured to surround the wall of the anatomical structure in a partial, near-complete, or complete circle.

[0063] Any of these devices may include multiple mapping and / or sensing electrodes on a portion of the first and / or second electrodes. For example, the sensing and / or mapping electrodes may be radially inward of the first and / or second active regions. The sensing and / or mapping electrodes may have a total surface area that is smaller than the surface area of ​​either the first and / or second electrically active regions (e.g., 80% or less, 70% or less, 60% or less, 50% or less, 40% or less, 30% or less, 20% or less, 10% or less, 5% or less, etc.). The sensing and / or mapping electrodes may be electrically isolated from the electrically active regions and may each be connected or connectable to a mapping system and / or subsystem via one or more lines (e.g., wires, traces, etc.).

[0064] Also described herein are devices for delivering pulsed electric fields, comprising an elongate body, a first electrode comprising a first wire loop, the first wire loop flexibly extending from the elongate body, the first electrode having a first active region extending along the length of the first wire loop, and a second electrode comprising a second wire loop, the second wire loop flexibly extending from the elongate body, the second electrode having a second active region extending along the length of the second wire loop, the first electrode being radially offset, laterally offset, or both radially and laterally offset from the second electrode. As noted above, any of these devices may include multiple 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 of delivering a pulsed electric field to a wall of an anatomical structure within a subject's body using an applicator, the methods including: positioning a first electrode of the applicator comprising first one or more loops and a second electrode of the applicator comprising second one or more loops within the subject's body such that a first active area of ​​the first one or more loops forms a first contact loop in electrical communication with a first region of the anatomical wall and a second active area of ​​the second one or more loops forms a second contact loop in electrical communication with a second region of the anatomical wall, the second contact loop being radially and / or longitudinally separated from the first region of the anatomical wall; and applying pulsed electric therapy between the first and second active areas. 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 include sensing one or more electrical properties of the wall of the anatomical structure using one or more sensors on the applicator before applying the pulsed electrical therapy, and / or during application of the pulses of the pulsed electrical therapy, and / or after applying the pulsed electrical therapy.

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

[0067] Also described herein is a device comprising: an elongate body extending proximally to distally; and an applicator region at a distal end region of the elongate body, the applicator region comprising: a first wire extending distally from the elongate body, the first wire having a first active region adjacent a first insulating region of the first wire; and a second wire extending distally from the elongate body, the second wire having a second active region adjacent a second insulating region of the second wire, the first active region separated from the second active region by a minimum distance d that is substantially constant along a 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 device can include an elongate body extending proximally to distally and an applicator region at a distal end region of the elongate body, the applicator region comprising an expandable member configured to expand radially relative to the elongate body; a first wire on the expandable member, the first wire having a first active region adjacent to a first insulating region of the first wire; and a second wire on the expandable member, the second wire having a second active region adjacent to a second insulating region of the second wire, the first active region separated from the second active region by a minimum distance d that is substantially constant along a length of the first active region, the first wire and the second wire having a thickness that is less than or equal to 0.38 mm, and further wherein the first active region is configured to have a first polarity and the second active region is configured to have a second polarity.

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

[0070] A better understanding of the features and advantages of the methods and apparatus described herein will be obtained by reference to the following detailed description that sets forth exemplary embodiments and the accompanying drawings. [Figure 1] FIG. 1 illustrates one example of a system for delivering high-voltage, high-rate pulses of electrical energy. [Figure 2] FIG. 2 illustrates one example of an applicator configured to deliver electrical therapy, such as nanosecond pulsed energy therapy, into a body vessel. [Figure 3A] FIG. 3A shows an example of an applicator configured to deliver energy treatment within a body vessel either circumferentially or point-by-point. [Figure 3B] FIG. 3B illustrates an example of an applicator configured for delivering energy treatment within a body vessel and configured for "head-on" and "side-on" energy application. [Figure 4A] FIG. 4A illustrates another example of an applicator configured to deliver nanosecond pulsed energy therapy within a body vessel. [Figure 4B] FIG. 4B illustrates another example of an applicator configured to deliver nanosecond pulsed energy therapy within a body vessel. [Figure 4C] FIG. 4C is another example of a device for delivering energy (eg, nanosecond pulsed electrical energy) into a body vessel either in a single shot or point-by-point manner. [Figure 4D] FIG. 4D is another example of a device for delivering energy (eg, nanosecond pulsed electrical energy) into a body vessel either in a single shot or point-by-point manner. [Figure 4E] FIG. 4E is another example of a device for delivering energy (eg, nanosecond pulsed electrical energy) into a body vessel. [Figure 5] FIG. 5 shows a view of the applicator of FIG. 4 disposed within a pulmonary vein. [Figure 6A] FIG. 6A illustrates another applicator configured to deliver nanosecond pulsed energy therapy within a body vessel. [Figure 6B] FIG. 6B shows an example of the effect of treatment using an applicator similar to that of FIG. 6A. [Figure 7] FIG. 7 illustrates another applicator similar to the applicator shown in FIG. 4A configured to deliver nanosecond pulsed energy therapy within a body vessel. [Figure 8A] FIG. 8A illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 8B] FIG. 8B illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 8C] FIG. 8C shows another example of an applicator in which the spacing between the electrodes is adjustable. [Figure 9] FIG. 9 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 10] FIG. 10 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 11] FIG. 11 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 12] FIG. 12 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 13] FIG. 13 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 14] FIG. 14 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 15] FIG. 15 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 16] FIG. 16 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 17A]FIG. 17A illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 17B] FIG. 17B shows further details of the applicator of FIG. 17A. [Figure 18] FIG. 18 shows an example of a fixture for manufacturing the applicator of FIG. 17A. [Figure 19] FIG. 19 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 20] FIG. 20 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 21] FIG. 21 illustrates another applicator configured to deliver nanosecond pulsed energy therapy to a body vessel. [Figure 22A] FIG. 22A illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 22B] FIG. 22B illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 22C] FIG. 22C illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 23A] FIG. 23A illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 23B] FIG. 23B illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 23C] FIG. 23C illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 23D] FIG. 23D illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 23E] FIG. 23E illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 23F] FIG. 23F illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 24A]FIG. 24A illustrates the treatment of model tissue using a device such as the device shown in FIGS. 22A-22C. [Figure 24B] FIG. 24B illustrates the treatment of model tissue using a device such as the device shown in FIGS. 22A-22C. [Figure 24C] FIG. 24C illustrates the treatment of model tissue using a device such as the device shown in FIGS. 22A-22C. [Figure 24D] FIG. 24D illustrates the treatment of model tissue using a device such as the device shown in FIGS. 22A-22C. [Figure 24E] FIG. 24E illustrates the treatment of model tissue using a device such as the device shown in FIGS. 22A-22C. [Figure 25] FIG. 25 is an example of a device for delivering pulsed electrical energy into a lumen. [Figure 26] FIG. 26 shows a device for delivering pulsed electrical energy into a lumen. [Figure 27] FIG. 27 illustrates the device of FIG. 26 applying energy around the pulmonary veins. [Figure 28A] FIG. 28A illustrates one example of a device for delivering pulsed electrical energy into a lumen. [Figure 28B] FIG. 28B shows the device of FIG. 28A within a lumen of narrow (FIG. 28B) and larger (FIG. 28C) diameter. [Figure 28C] FIG. 28C shows the device of FIG. 28A within a narrow (FIG. 28B) diameter and a larger (FIG. 28C) diameter lumen. [Figure 29A] FIG. 29A shows an example of a rib in the applicator region that bends in a curve. [Figure 29B] FIG. 29B shows an example of ribs in the applicator region that are hinged as described herein. [Figure 30A] FIG. 30A shows a device for delivering pulsed electrical energy into a body vessel (lumen). [Figure 30B] FIG. 30B shows an enlarged view of the hinge region of the device of FIG. 30A. [Figure 31]FIG. 31 shows a device for delivering pulsed electrical energy into a lumen, including a balloon for expanding the applicator region. [Figure 32] FIG. 32 shows a device for delivering pulsed electrical energy into a lumen. [Figure 33] FIG. 33 shows another view of the device of FIG. [Figure 34A] FIG. 34A shows an example of a paddle-shaped device for delivering pulsed electrical energy into a lumen. [Figure 34B] FIG. 34B shows an example of a paddle-shaped device for delivering pulsed electrical energy into a lumen. [Figure 34C] FIG. 34C shows an example of a paddle-shaped device for delivering pulsed electrical energy into a lumen. [Figure 35] FIG. 35 is an example of a device for delivering pulsed electrical energy into a lumen. [Figure 36A] FIG. 36A illustrates a further example of a device for delivering pulsed electrical energy into a lumen. [Figure 36B] FIG. 36B illustrates a further example of a device for delivering pulsed electrical energy into a lumen. [Figure 36C] FIG. 36C illustrates a further example of a device for delivering pulsed electrical energy into a lumen. [Figure 36D] FIG. 36D illustrates a further example of a device for delivering pulsed electrical energy into a lumen. [Figure 37] FIG. 37 illustrates the difficulty in positioning a device to treat a pulmonary vein. [Figure 38A] FIG. 38A shows an apparatus for delivering pulsed electrical energy into a lumen, including a centering guide. [Figure 38B] FIG. 38B shows a device for delivering pulsed electrical energy into a lumen, including a centering guide. [Figure 39] FIG. 39 is an example of a device for delivering pulsed electrical energy into a lumen, including a centering guide. [Figure 40A] FIG. 40A illustrates a method of using the device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 40B] FIG. 40B illustrates a method of using the device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 40C] FIG. 40C illustrates a method of using the device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 40D] FIG. 40D illustrates a method of using the device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 41A] FIG. 41A illustrates a method of using the device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 41B] FIG. 41B illustrates a method of using the device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 41C] FIG. 41C illustrates a method of using the device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 41D] FIG. 41D illustrates a method of using the device to deliver pulsed electrical energy into a lumen using a centering guide. [Figure 42] FIG. 42 is a flow diagram illustrating one example of a method for delivering pulsed electrical therapy to a selected treatment area of ​​a patient. [Figure 43A] Figure 43A illustrates an example of an applicator including treatment electrodes and sensing / mapping sensors, with Figure 43A showing a distal end view and Figure 43B showing a side perspective view. [Figure 43B] Figure 43B illustrates an example of an applicator including treatment electrodes and sensing / mapping sensors, with Figure 43A showing a distal end view and Figure 43B showing a side perspective view. [Figure 43C] FIG. 43C illustrates schematically one example of a system including an applicator such as that shown in FIGS. 43A-B. [Figure 44A] FIG. 44A shows an example of a device including a small diameter wire electrode as described herein. [Figure 44B] FIG. 44B shows an example of a device including a small diameter wire electrode as described herein. [Figure 44C] FIG. 44C shows an example of a device including a small diameter wire electrode as described herein. [Figure 44D] FIG. 44D shows an example of a device including a small diameter wire electrode as described herein. DETAILED DESCRIPTION OF THE INVENTION

[0071] Described herein are systems and methods for treating the body, including body lumens such as body vessels, with pulsed electric fields using electrodes adapted for insertion into body vessels, such as arteries, veins, sinuses, and any other blood vessels in the body as described above. Generally, the devices and methods described herein can be positioned inside any body chamber, including, but not limited to, a body lumen such as a tubular body member or vessel, against any wall of an organ, and / or within a transition area (e.g., sinus, ostium, etc.).

[0072] In some cases, body vessels may have irregular or variable shapes. For example, the sinuses of pulmonary veins may transition from a relatively large area or diameter to a relatively small area or diameter. It may be difficult for electrodes to establish effective contact to provide therapy on these body vessel surfaces. Described herein are various electrodes that can easily adapt and conform to irregular and / or changing shapes and provide reliable contact with body vessels.

[0073] Pulsed electric therapy can be microsecond pulse therapy or sub-microsecond pulse therapy, including nanosecond pulses. For example, nanosecond pulsed electric field therapy can refer to the application of relatively high voltages (potentially 5 kV or more) for relatively short periods of time (potentially about 1 nanosecond to 999 ns). These high voltages and short durations create pulsed electric fields in the area to which the voltage is applied. In some cases, nanosecond pulses can induce apoptosis in cellular structures, which can reduce cellular inflammatory responses.

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

[0075] Alternatively, or additionally, these devices and methods can be used to treat the walls of blood vessels or other lumens that are not necessarily tapered or that 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 a stent or angioplasty procedure. Thus, in some cases, these methods can be performed within the first 2-4 days after angioplasty and / or stenting. Naive smooth muscle cells (SMCs) at the luminal surface in areas where the endothelium has been removed may continue to proliferate at a low rate. The methods and devices described herein can prevent or reduce this.

[0076] FIG. 1 illustrates one example of a system 100 for delivering rapid pulses of electrical energy (also referred to herein, by way of example, as a sub-microsecond generation system). 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 enclose electronic components) through 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 through 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) that may be configured to hold the elongated applicator tool 102. In some examples, the system may be configured for monopolar treatment and may optionally include a dispersive electrode 133 (e.g., a return electrode pad).

[0077] The applicator tool may be any of the devices for delivering pulsed electric fields within a body vessel, as described in detail herein. These devices may generally include an elongated, flexible body (generally referred to herein as an elongated body, catheter, or elongated catheter body) having one or more electrodes at the end, including electrodes forming one or more loops that can apply a pulsed electric field 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 side-facing. The system 100 may be configured to display (in real time and / or recorded) images captured by the elongated applicator tool 102 to identify a target treatment area and / or region.

[0078] A human operator may select the number of pulses, amplitude, pulse duration, and frequency information, for example, by entering such parameters into a numeric keypad or touchscreen of the user interface 104. In some examples, the pulse width may be varied. A microcontroller may send signals to pulse control elements within the system 100. In some examples, fiber optic cables are used to allow control signal transmission while electrically isolating the contents of the sub-microsecond pulse generation system 100, e.g., a metal cabinet (e.g., housing 105) containing high-voltage circuitry, 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 hand-held (e.g., by a user) or may be attached to a movable arm of a robotic system, the operation of which may be at least partially automated or fully automated, including computer-controlled operation.

[0080] FIG. 2 illustrates one example of an applicator 200 configured to deliver a therapy, such as a nanosecond pulsed energy therapy, into a body vessel. The body vessel may be any feasible vessel, including, but not limited to, the sinus of a pulmonary vein or the pulmonary vein itself. 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, one skilled in the art will recognize that other terms may be used to identify and distinguish features of the applicator 200, including the proximal ring 210 and the distal ring 220. For example, the proximal ring 210 and the distal ring 220 may be referred to as the first ring and the second ring.

[0081] The proximal ring 210 and the distal ring 220 may be formed from any suitable material. In at least one example, the proximal ring 210 and the distal ring 220 may be formed from nitinol (e.g., nickel titanium), although any other viable 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 the 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 circumference of each of the rings 220, 210 may be the active area (e.g., electrically continuous), so that the outer circumference of the ring, rather than the inner arms 211, 221 (which may be insulated), forms the active area for applying electrical energy. In some examples, the proximal ring 210 and the distal ring 220 may be retracted into the catheter body 230. The applicator 200 may then be positioned at the treatment area. After placement of the applicator 200 is confirmed, the proximal ring 210 and the distal ring 220 may be deployed from the catheter 230.

[0083] In some examples, the ring electrodes 210 and 220 are not deployed from within the catheter body 230, but may be housed with the catheter body 230 within a delivery catheter, and the distal end of the device (e.g., in this example, the ring electrodes) may be deployed from the delivery catheter once at or near the target treatment location within 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 to herein as a guide sheath). The guide sheath may already be within the patient, with the distal end of the sheath positioned near the target area (e.g., in some examples, at or near the left atrium). The elongated catheter body and electrodes (e.g., ring electrodes) may be inserted into a 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 examples, the delivery catheter holding the distal end (e.g., the ring electrodes) may be advanced to the target tissue and then 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 joined to the arms 211. In some examples, the arms 211 may be insulated. Similarly, the distal ring 220 may include two lobes joined to the arms 221. In other examples, the proximal ring 210 and the 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 the distal ring 220, allowing them to more easily conform to different shapes of body vessels and allowing the electrodes of the rings to be better apposed to 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 couple the proximal ring 210 and the distal ring 220 to the elongated catheter body 230. It should be noted that 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 electrodes extending from the distal end of the elongated catheter body may be movable relative to the distal end of the elongated catheter body, or may be fixed relative to the distal end.

[0085] 2 illustrates a distance 240 separating the proximal ring 210 and the distal ring 220. For example, the distance 240 may represent the distance between a plane generally containing the proximal ring 210 and a plane generally containing the distal ring 220. The distance 240 may be predetermined or may be variable and determined by a user when the proximal ring 210 and the distal ring 220 are deployed. In some examples, the potential between the proximal ring 210 and the distal ring 220 and the distance 240 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 examples, the applicator 200 can be guided to a specified treatment area by the elongate catheter body 230 and a proximal handle (such as the handle portion of the elongate applicator tool 102 shown in FIG. 1 ). In some examples, the applicator 200 can also be guided by the use of a guidewire (not shown for simplicity) and / or fluoroscopy equipment. The devices described herein (e.g., the applicator 200) can include a central lumen (e.g., through the elongate catheter body) that can allow for operation of the device over a guidewire. Alternatively, a rapid-exchange lumen can be present on the side of the applicator distal end.

[0087] The distal end of the device can be positioned within the approximate region of tissue to be treated (target tissue region), and the ring electrodes (e.g., proximal ring 210 and distal ring 220) can be expanded as shown in FIG. 3A. The proximal ring 210 and distal ring 220 can be flexibly coupled to and emerge from an elongate catheter body 230 into apposition with a body vessel. The correct position of the applicator 200, including the ring electrodes, can be verified and / or the device can be repositioned before applying energy.

[0088] Nanosecond pulsed energy treatment of the body vessel can then begin. In some examples, the system 100 and applicator 200 can be configured for bipolar operation, for example, between the proximal ring 210 and the distal ring 220. In some examples, the proximal ring 210 may be referred to as the cathode and the distal ring 220 may be referred to 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 the distal ring 220 can function as electrodes for delivering nanosecond pulsed energy. Electrodes carrying signals of opposite polarity can enable an electric field associated with pulsed treatment to be generated between the electrodes. In some examples, the system 100 (including the applicator 200) can be configured for monopolar operation. For example, the proximal ring 210 and the distal ring 220 may be electrically coupled to each other, and a signal may be applied between the proximal ring 210 and the distal ring 220 and a return electrode (e.g., another conductor, such as a portion of the elongate catheter body 230, or a conductive pad or electrode) that may be in contact with the patient.

[0089] After delivery of the nanosecond pulsed energy treatment, the applicator 200 can be moved to another area of ​​the body vessel or removed from the patient.

[0090] Any of the devices described herein can also be configured for use in regions of the body that are elastically resilient and may expand and contract, e.g., during diastole / systole, breathing, etc. For example, as described herein, the electrodes may be formed as rings (or partial rings) that can be flexibly coupled to the distal end region of the catheter body. The flexible coupling may be via wires or other members that can allow the ring to flex with tissue movement while remaining in place on the tissue.

[0091] 3A shows another example of an applicator 300 configured to deliver a treatment, such as a nanosecond pulsed energy treatment, into a body vessel. Similar to the applicator 200 of FIG. 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 disposed distally on the elongated catheter body 230 relative to the distal ring 220. In some examples, the point-by-point ablation tip 310 can provide a targeted treatment separately and independently from the proximal ring 210 and the distal ring 220. Accordingly, the point-by-point ablation tip 310 may include one or more electrodes (not shown for simplicity) for delivering nanosecond pulsed energy. Alternatively, in some instances, point-by-point ablation may be achieved by using a subset of ring or petal electrodes extending outward from the elongate body (elongate catheter body) 230, as described in more detail below with reference to Figures 7 and 32-33.

[0092] FIG. 3B is another example of a device configured to apply either circumferential treatment over a large area or point-by-point treatment in a smaller area by using either a “head-on” or “side-on” approach, as described below. The device shown in FIG. 3B is configured as a tripolar ablator (device) in which an electric field can be applied either between a distal ring 314, which can be held at a first polarity (polarity 1), and a central electrode 310, which can be held at a second polarity (polarity 2). The distal end or “front” of the device can “face” the tissue. Alternatively, energy can be applied between the distal ring 314 (e.g., polarity 1) and the proximal ring 312, which can be set to polarity 2. The side of the device can also 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 to a larger area.

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

[0094] The applicator 300, 300′ in FIGS. 3A and 3B is shown in a deployed mode relative to a body vessel 320, for example. One example of a body vessel 320 may be a pulmonary vein, which may include a sinus 325. The sinus 325 may transition in size from a first diameter to a second diameter. Thus, the different diameters of the proximal and distal rings 210, 220 may advantageously allow the applicator 300 to conform to the changing shapes of the sinus 325. In some examples, the diameters of the proximal and distal rings are different (e.g., the proximal ring is larger than the distal ring). In some examples, one (or both) of the proximal and distal rings are configured to have an adjustable diameter, which may allow the device to ascertain different shapes and diameters.

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

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

[0097] FIG. 4A illustrates another example of an applicator 400 configured to deliver nanosecond pulsed energy therapy within a body vessel. 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. Additionally, the applicator 400 may include five arms 430 for flexibly coupling the proximal and distal rings 410 and 420 to an elongated catheter body (not shown). As discussed above, the proximal and distal rings 410 and 420 having relatively more lobes may be more flexible than the proximal and distal rings having fewer lobes. FIG. 4B illustrates a side view of the applicator 400. The proximal and distal rings 410 and 420 and the arms 430 are shown coupled to an elongated catheter body 440.

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

[0099] As discussed above with respect to FIGS. 4A-4B, in some examples, the devices described herein include two electrode rings, an inner ring and an outer ring, which can be used to treat tissue, including (but not limited to) myocardial tissue within the sinuses and / or sinus ostia. In some examples, additional rings can be used. For example, FIG. 4C shows a device including three rings, and FIG. 4D shows an example having four rings. FIG. 4E illustrates an example having two rings with a central electrode. These configurations can also allow for adaptability to patient anatomy and can help achieve both single-shot treatments (e.g., treating an entire area, such as around a blood vessel, in one treatment, including ablation) and point-by-point treatments (e.g., treating small portions of a body vessel one at a time, including ablation).

[0100] FIG. 4C shows an example of an applicator 460 device configuration 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 subregions (e.g., petals or loops) that can be electrically coupled together to apply a first polarity. In some examples, the individual subregions can be activated independently. FIG. 4C also includes a second ring 463 that is smaller than the first ring and arranged concentrically with respect to the first ring. In FIG. 4C, the second ring has a diameter of approximately 23 mm and can be formed from multiple subregions that can be electrically coupled to provide a second polarity. The multiple subregions can also be activated separately in some examples. The same device can also include a third ring 465 that can also be formed from multiple subregions that are arranged concentrically with respect to the second ring and can be electrically coupled to provide a first polarity. In FIG. 4C, the third ring has a diameter of approximately 16 mm. The outer and middle rings can be used to treat larger sinuses and / or ostia, while a second configuration can use the second and third rings to apply treatment in smaller sinuses and / or ostia. Varying the size of the diameter and / or number of rings can allow the system to select which pair of rings to designate (in what polarity) to provide better adjustment and fit when treating tissue areas of different sizes, such as (but not limited to) sinuses and / or ostia.

[0101] For example, in FIG. 4D , the device includes four concentrically arranged rings. The outer electrode (ring 481) can be formed from multiple subregions that can be electrically coupled together to apply a first polarity. In some examples, individual subregions can be independently activated. A second ring 483 can be formed from multiple subregions 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 of a smaller circumference can be formed from multiple subregions that are concentrically arranged with respect to the second ring and can also be electrically coupled to provide a first polarity. Finally, a fourth electrode (ring 487) of 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 FIG. 4E. FIG. 4E is similar to FIGS. 4A and 4B in that it has two concentrically arranged electrode rings. The first ring electrode 491 can be formed from multiple subregion electrodes, each formed from a wire with an exposed electrically active area. As with any of these examples, in some configurations, each subregion can be individually controlled and / or they can all be electrically coupled together to form a single electrode. The second ring electrode 493 is concentrically arranged relative to the first ring electrode and, like the first ring electrode, can be formed from multiple subregions. Finally, the example shown in FIG. 4E can also include a single central electrode 495 that can be configured to apply a polarity opposite to that applied to either the larger outer ring (or subregion of the outer ring) or inner ring (or subregion of the inner ring).

[0103] Any of these devices can be used as the distal portion of an elongate body (e.g., a catheter) and may be used, for example, in the treatment of atrial fibrillation. Treatment of atrial fibrillation can involve various target sites, including, but not limited to, pulmonary vein (PV) sinuses, PV ostia, 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 pulsed energy), for example, treating pulmonary vein sinuses / ostia of various sizes, and / or providing point-by-point tissue treatment (e.g., ablation) throughout the cardiac anatomy. These devices can also be used to apply sub-microsecond treatments to other parts of the body. For example, a larger diameter outer ring can be used for single-shot treatment of the sinuses and ostia, while a smaller inner ring can be used for point-by-point ablation of the target tissue. Due to the adaptability and adjustability of these configurations, treatment can be achieved more efficiently while being able to adjust / conform to anatomy of varying sizes.

[0104] Figure 5 shows a view 500 of the applicator 400 of Figure 4 disposed within the sinus 510 of a pulmonary vein. The proximal ring 410 and the distal ring 420 can conform to the surface of the pulmonary vein.

[0105] FIG. 6A illustrates another applicator 600 configured to deliver a treatment, such as a nanosecond pulsed energy treatment, into a body vessel. The applicator 600 may include a first ring 610, a second ring 620, an elongated catheter body 630, and an arm 640. The arm 640 may electrically and flexibly couple the first ring 610 and the second ring 620 to the system 100 (not shown) through the elongated catheter body 630. The first ring 610, the second ring 620, and the arm 640 may be formed from nitinol or any other feasible material. Additionally, the first ring 610 may have a first diameter, and the second ring 620 may have a second diameter that is different from the first diameter. The different diameters may at least partially determine the density of the electric field associated with the nanosecond pulsed energy treatment. Although shown with two lobes, the first ring 610 and the second ring 620 may include any feasible number of lobes. 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 to allow placement of the applicator 600 relative to the treatment area.

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

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

[0108] FIG. 6B shows an example illustrating the use of an applicator similar to that shown in FIG. 6A to treat model tissue 651. In FIG. 6B, nanosecond pulsed electrical treatment is applied to model tissue (a potato immersed in saline) using an applicator similar to that of FIG. 6A, showing the treatment of two regions 653, 653′ (e.g., two applications of the device). In particular, the applicator is used to apply pulsed electrical treatment to two target regions. 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 show 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), approximately 320 degrees of treatment is performed, with a small gap indicated at 357 that is not covered by the active area of ​​the electrodes.

[0109] FIG. 7 illustrates another applicator 700 configured to deliver nanosecond pulsed energy treatment within a body vessel. The applicator 700 may include a first ring 710, a second ring 720, an elongated catheter body 730, and an arm 740. The arm 740 may electrically and flexibly couple the first ring 710 and the second ring 720 to the system 100 (not shown) through the elongated catheter body 730. The first ring 710, the second ring 720, and the arm 740 may be formed from nitinol or any other feasible material. Additionally, the first ring 710 may have a first diameter, and the second ring 720 may have a second diameter that is different from the first diameter. The different diameters may at least partially determine the density of the electric field associated with the nanosecond pulsed energy treatment.

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

[0111] 6A , first ring 710 and second ring 720 may be substantially coplanar. Accordingly, the function and use of applicator 700 may be similar to that of applicator 600. While applicator 700 is shown with five lobes, other numbers of lobes are possible in other examples. As noted above, applicators with a relatively large number of lobes are more flexible than applicators with a relatively small number of lobes and, therefore, may more easily conform to some body vessels.

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

[0113] 8A and 8B show another applicator 800 configured to deliver energy, such as nanosecond pulsed energy therapy, to a body vessel. The 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 couple the proximal ring 810 and the distal ring 820 to the 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. Additionally, the proximal ring 810 may have a first diameter, and the distal ring 820 may have a second diameter different from the first diameter. The different diameters can at least partially determine the density of the electric field associated with the nanosecond pulsed energy therapy. The proximal and distal rings 810 and 820 may be folded and retracted into the elongate catheter body 830 to allow placement of the applicator 800 against the treatment area.

[0114] The proximal and distal rings 810 and 820 may be separated by a distance 840. In some examples, the proximal and distal rings 810 and 820 may be elastic relative to the elongate catheter body 830 and / or relative to each other. Thus, the distance 840 can be varied by elasticating either or both of the proximal ring 810 and the distal ring 820. In some examples, the elongate applicator tool 102 can control the distance 840 by moving a control wire, push rod, tendon, cable, etc. to elasticate (position) the proximal ring 810 and / or the distal ring 820.

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

[0116] In some examples, the proximal ring 810 and the distal ring 820 may not form a continuous circle. Region 850 of the distal ring 820 is enlarged in FIG. 8B to show detail. The distal arm 821 may be bent to form the distal ring 820. For example, the distal ring 820 is bent toward the right, as shown in region 850. However, the tip of the distal ring 820 is not connected 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 view of an applicator 800 similar to the applicator of Figure 8A. In this view, the distance 840 between the proximal ring 810 and the distal ring 820 is shown as increased relative to the distance 840 of the applicator 800 of Figure 8A. For example, the proximal ring 810 and / or the distal ring 820 may be moved to increase the distance 840 between the respective rings. As discussed above, varying the distance 840 can affect the density of the electric field associated with nanosecond pulsed energy treatment.

[0118] FIG. 9 illustrates another applicator 900 configured to deliver nanosecond pulsed energy treatment to a body vessel. The applicator 900 may include a proximal ring 910, a proximal arm 911, a distal ring 920, a distal arm 921, and an elongated catheter body 930. The proximal and distal rings 910 and 920 and the proximal and distal arms 911 and 921 may be formed from nitinol or any other feasible material. Additionally, the proximal ring 910 may have a first diameter, and the distal ring 920 may have a second diameter that is 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 treatment. While shown with six lobes, the proximal ring 910 and the distal ring 920 may include any feasible number of lobes.

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

[0120] 10 illustrates another applicator 1000 configured to deliver sub-microsecond pulsed energy therapy to a body vessel. The applicator 1000 may include a proximal ring 1010, a distal ring 1020, an expandable sphere 1025, and an elongated catheter body 1030. The proximal and distal rings 1010 and 1020 may be coupled to the system 100 (not shown) through conductors (not shown) and the 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 may be disposed on and / or coupled to the expandable sphere 1025. Thus, the expandable sphere 1025 and the proximal and distal rings 1010 and 1020 may be folded and retracted into a delivery catheter or sheath, allowing positioning of the applicator 1000 relative to the treatment area.

[0122] Additionally, the proximal ring 1010 may have a first diameter and the distal ring 1020 may have a second diameter that is 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 treatment. While shown with six lobes, the proximal ring 1010 and the distal ring 1020 may include any feasible number of lobes.

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

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

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

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

[0127] 12 shows another applicator 1200 configured to deliver nanosecond pulsed energy therapy to a body vessel. The applicator 1200 may include one or more first electrodes 1210, one or more second electrodes 1220, an elongate catheter body 1230, and a helical member 1240. The one or more first electrodes 1210 and the one or more second electrodes 1220 may be electrically coupled to the system 100 (not shown) through the elongate catheter body 1230. The helical member 1240 and the one or more first electrodes 1210 and second electrodes 1210 may be formed from nitinol or any other feasible material. Additionally, the helical member 1240 may spiral outward from the elongate catheter body 1230 while simultaneously extending away from (e.g., distally therefrom) the elongate catheter body 1230, thereby forming a conical shape. This conical shape may allow the one or more first electrodes 1210 and second electrodes 1220 to contact some tissue surface uniformly.

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

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

[0130] 13 shows another applicator 1300 configured to deliver nanosecond pulsed energy therapy to a body vessel. The 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. The one or more first electrodes 1310 and the one or more second electrodes 1320 may be electrically coupled to the system 100 (not shown) through the elongated catheter body 1330. The helical member 1340 and the one or more first electrodes 1310 and second electrodes 1320 may be formed from nitinol or any other feasible material. Additionally, the helical member 1340 may spiral from the outer circumference to the inner circumference while simultaneously extending away (e.g., distally) from the elongated catheter body 1330, thereby forming an inverted cone shape (relative to the applicator 1200). This inverted cone shape may allow one or more first electrodes 1310 and second electrodes 1320 to contact some tissue surface uniformly.

[0131] The one or more first electrodes 1310 and second electrodes 1320 can be formed from any feasible conductive material. In some examples, the one or more first electrodes 1310 and second electrodes 1320 can be helically wound around the helical member 1340. In other examples, the one or more first electrodes 1310 and second electrodes 1320 can be individual bands electrically coupled together. Furthermore, particularly if the helical member 1340 is conductive, an insulator (not shown) can be disposed between the one or more first electrodes 1310 and second electrodes 1320 and the helical member 1340. The 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 the elongated catheter body 1330, allowing placement of the applicator 1300 relative to the treatment area.

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

[0133] 14 shows another applicator 1400 configured to deliver nanosecond pulsed energy therapy to a body vessel. The applicator 1400 may include a plurality of first electrodes 1410, a plurality of second electrodes 1420, an elongate catheter body 1430, and a helical member 1440. The plurality of first electrodes 1410 and second electrodes 1420 may be electrically coupled to the system 100 (not shown) through the elongate 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. Additionally, the helical member 1440 may spiral outward from the elongate catheter body 1430 while simultaneously extending away from (e.g., distally therefrom) the elongate catheter body 1430, thereby forming a conical shape. This conical shape may allow the plurality of first electrodes 1410 and second electrodes 1420 to contact a portion of the tissue surface uniformly.

[0134] The plurality of first electrodes 1410 and second electrodes 1420 may be arranged in an alternating pattern on the helical member 1440. Varying the spacing between the plurality of first electrodes 1410 and the plurality of second electrodes 1420 may affect the density of the electric field associated with nanosecond pulsed energy treatment. Furthermore, an insulator (not shown) may be arranged between the plurality of first electrodes 1410 and second electrodes 1420 and the helical member 1440, particularly if the helical member 1440 is conductive.

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

[0136] 15 shows another applicator 1500 configured to deliver nanosecond pulsed energy therapy to a body vessel. The 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 the system 100 (not shown) through the elongated catheter body 1530. The helical member 1560 and 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. Additionally, the helical member 1560 can spiral outward from the elongate catheter body 1530 while simultaneously extending away from (e.g., distally away from) the elongate catheter body 1530, thereby forming a conical shape that can allow the first and second electrodes to uniformly contact 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 a spiral member 1560. Furthermore, particularly if the spiral member 1560 is conductive, an insulator (not shown) can 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 can be electrically coupled together, and the second electrode 1520 and the fourth electrode 1550 can be electrically coupled together.

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

[0139] 16 shows another applicator 1600 configured to deliver nanosecond pulsed energy therapy to a body vessel. The 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 the 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 disposed on a support member 1660, which 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 may join opposite 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 retracted into the elongated catheter body 1630, allowing placement of the applicator 1600 relative to the treatment area.

[0141] The applicator 1600 can be configured for bipolar operation. Pulse energy can be transmitted between two sets of electrodes. For example, pulse energy can be transmitted between the first electrode 1610 and the third electrode 1640, which form a combined anode, and the second electrode 1620 and the fourth electrode 1650, which form a combined cathode, or vice versa. In another example, the applicator 1600 can be configured for monopolar operation.

[0142] 17A shows another applicator 1700 configured to deliver therapy to a body vessel. The applicator 1700 may include a first insulated conductor 1710, a second insulated conductor 1720, and an elongated catheter body 1730. The first and second insulated conductors 1710 and 1720 and the elongated catheter body 1730 may be formed from nitinol or any other feasible material. Furthermore, the first insulated conductor 1710 and the second insulated conductor 1720 may be woven into a basket. In some examples, the first insulated conductor 1710 and the second insulated conductor 1720 may be woven together within the distal section of the basket (as shown, the distal section is circumferentially closer to the shaft 1730). A double-braided region of the basket is shown in the enlarged region 1740. The basket formed by the first insulated conductor 1710 and the second insulated conductor may be collapsed and retracted into a delivery catheter (not shown), allowing placement of the applicator 1700 relative to the treatment area.

[0143] Figure 17B shows another view of the applicator 1700 of Figure 17A. Insulated regions of first insulated conductors 1710 and second insulated conductors 1720 can be selectively removed to expose associated bare conductors. Thus, the insulation removed from first insulated conductors 1710 can form first electrode 1711, and the insulation removed from second insulated conductors 1720 can form 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 can be transmitted between a first electrode 1711 and a second electrode 1721. Thus, the first electrode 1711 can be configured as an anode, and the second electrode 1721 can be configured as a cathode (or vice versa). In another example, the applicator 1700 can be configured for monopolar operation.

[0145] FIG. 18 illustrates an example fixture 1800 for manufacturing the applicator 1700 of FIG. 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 insulated conductors 1710 are selectively wound between the first group of pins 1820 and the third group of pins 1840. Similarly, the second insulated conductors 1720 are selectively wound between the first group of pins 1820 and the second group of pins 1830. After the first and second insulated conductors 1710 and 1720 are wound around the cylinder 1810, insulation can be selectively removed from the first and second insulated conductors 1710 and 1720 to form the first and second electrodes 1711 and 1721.

[0146] FIG. 19 shows another applicator 1900 configured to deliver nanosecond pulsed energy therapy to a body vessel. The 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 expand (as shown) to deploy the first electrode 1910 and the second electrode 1920, such that the first electrode 1910 can form a distal circular electrode and the second electrode 1920 can form a proximal circular electrode. Although only two electrodes are shown, in other examples, the applicator 1900 may include any feasible number of electrodes. The blade members 1925 may be folded and retracted into the delivery sheath, allowing 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 can be transmitted between a first electrode 1910 and a second electrode 1920. Thus, the first electrode 1910 can be configured as a cathode and the second electrode 1920 can be configured as an anode (or vice versa). In another example, the applicator 1900 can be configured for monopolar operation.

[0148] FIG. 20 illustrates another applicator 2000 similar to the applicator of FIG. 19 and configured to deliver therapy to a body vessel. The 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 may expand (as shown) to deploy the first electrode 2010 and the second electrode 2020, such that the first electrode 2010 may form the proximal electrode and the second electrode 2020 may form the distal electrode. Although only two electrodes are shown, in other examples, the applicator 2000 may include any feasible number of electrodes. The first and second electrodes 2010 and 2020 and the blade member 2025 may be folded to allow placement of the applicator 2000 against the treatment area.

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

[0150] 21 shows another applicator 2100 configured to deliver nanosecond pulsed energy therapy to a body vessel. The 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 and 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 delivered between two sets of electrodes. For example, pulse energy can be delivered between a first electrode 2110 and a second electrode 2120. In another example, the applicator 2100 can be configured for monopolar operation.

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

[0153] The ribs may be attached at their proximal ends to a first elongate member forming the elongate body. In some examples, the ribs may be attached at their distal ends to a second elongate member that is axially slidable within the first elongate member. The ribs may be expanded (e.g., deploying the device) by sliding the first elongate member relative to the second elongate member (or vice versa) and shortening the distance between the distal and proximal ends of the ribs. Similarly, the ribs may be retracted (e.g., contracting the device) by sliding the first elongate member relative to the second elongate member (or vice versa) and increasing the distance between the distal and proximal ends of the ribs. In some examples, the ribs may be biased (or may be in communication with a bias) to tend to expand the ribs outward. Alternatively, in some examples, the ribs may be biased (or may be in communication with a bias) to tend to collapse the ribs 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 expanded configuration or, alternatively, a collapsed configuration. In some examples, the ribs may be in communication with a bias such as a leaf spring, balloon, or the like.

[0154] The ribs may be uninsulated over a portion of each rib's length through which energy may be applied. For example, each rib may be uninsulated over a mid-region of the rib extending a length F, which may be referred to as the active length or active region of each rib. In some instances, only the outward-facing side of each rib is uninsulated. Any suitable electrical insulator may be used, including polymeric insulators, particularly biocompatible polymeric insulators.

[0155] For example, FIG. 22A illustrates one example of a device as described herein configured to deliver sub-microsecond (e.g., nanosecond) pulsed energy within a tubular structure. In FIG. 22A, the device 2200 includes an elongate body 2203 extending from proximally to distally. The elongate body is configured to be inserted into a body lumen. In some examples, the elongate body can be flexible. In some examples, the elongate body is rigid. The elongate body can be bent or steerable (e.g., using one or more tendons). The device also includes an applicator region 2201 at a distal end region of the elongate body. In FIGS. 22A and 22B, the applicator region is shown in a collapsed (unexpanded) configuration. The applicator region can include a plurality of expandable ribs 2221, each configured to expand outward within the lumen from the collapsed configuration. For example, in FIG. 22B, the folded ribs are shown folded such that the cross-sectional diameter of the applicator region has approximately the same diameter as the remainder of the elongate body.

[0156] FIG. 22C shows the applicator region 2201 in an expanded configuration with multiple ribs extending radially outward in a curved manner. 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 includes a non-insulated active region 2225 in which 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 FIG. 22C, each rib 2221 includes a centrally positioned active region flanked on either side 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, the plurality of ribs can include two subsets, each having a different polarity. In some examples, a first subset of the plurality of ribs in the active region is configured to have a first polarity, and a second subset of ribs is configured to have a second polarity. Thus, energy (e.g., pulsed sub-microsecond energy) can be applied between the two subsets of ribs. In this example, every other rib (or spline) radially disposed around the active region can have a different polarity, and ribs of the same polarity can be electrically coupled together. Thus, polarity alternates around the active region.

[0158] 22A-22C, the ribs forming the expandable active region are coupled to a pair of elongate members that form an elongate body extending proximally to distally such that relative movement of the first and second elongate members can result in expansion or contraction of the active region. For example, a proximal end of each of the ribs may be connected to a first (e.g., in some examples, outer) elongate member 2205, and a distal end of the ribs may be connected to a second (e.g., in some examples, inner) elongate member 2207. The second elongate member may be coaxially positioned relative to the first elongate member and slid proximally to distally within the first elongate member to expand or contract the active region.

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

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

[0161] The exemplary device shown in Figures 22A-22C includes eight stainless steel ribs, each approximately 0.015 inches by 0.005 inches (e.g., 0.38 mm by 0.13 mm). Each rib is insulated by a polymer insulator, such as polyimide, to prevent arcing and expose only the length of the rib (also referred to herein as splines or struts) necessary for energy delivery to provide electrical insulation.

[0162] 23A-23F illustrate another example of a device similar to the device shown in FIGS. 22A-22C. In this example, the distal active region of the device 2301 is shown in a folded configuration as in FIG. 22A. The device also includes an elongate body 2303 including a first elongate member (outer elongate member 2305) and a second (e.g., inner) elongate member 2307. The first elongate member is coupled to a proximal end of the active region, and the second elongate member is coupled to a distal end of the active region. Thus, pulling the second elongate member proximally and / or pushing the first elongate member distally can shorten the distance between the proximal and distal ends of the active region (e.g., ribs or splines) and cause the ribs to expand outward.

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

[0164] As previously described, the inner, second elongate member can be moved (e.g., pulled / pushed) relative to the first elongate member to expand and contract the spline (and thus the diameter of the active region). For example, a selected diameter may be set by the user (to expand within the lumen of the 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 elongate member relative to the second elongate member. Once in place, energy can be applied.

[0165] For example, FIGS. 24A-24E illustrate an example device, such as those shown in FIGS. 22A-22C and 23A-23F, that, during operation, applies pulsed sub-microsecond energy to example tissue. In this example, the sample tissue is a potato, within which a lumen has been formed for insertion of an example device. FIG. 24A shows an end view of lumen 2402 through the sample tissue into which device 2401 has been inserted and expanded, as described above. In this example, the eight ribs are expanded until they just touch the walls of the simulated lumen. A bipolar device was constructed as described above, inserted into the lumen, and expanded. FIGS. 24B and 24D illustrate a lumen diameter of 20 mm, and FIGS. 24C and 24E show a lumen diameter of 14 mm.

[0166] As shown in Figures 24B-24E, all of the parameters and devices tested resulted in circumferential treatment around the lumen 2404. All of these examples were tested using pulses in the nanosecond range (e.g., 1-1000 ns) and voltages of approximately 2,500 V.

[0167] 22A-22C and 23A-23F, the device 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 can 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 shape-set into a preferred configuration.

[0168] For example, FIGS. 25 and 26 illustrate examples of devices 2500, 2600 in which the exposed active areas of the ribs of the expandable / collapsible frame forming the applicator region are biased toward the distal end. In FIG. 25, the applicator region has a generally teardrop shape in longitudinal cross-section. Thus, the applicator region is configured to expand outward to a shape with a larger cross-sectional area distally than proximally relative to the long axis of the applicator region. Each rib (spline) 2521 has a curved shape in the expanded configuration, with the slope of the distal facing region being greater (steeper) than the slope of the proximal portion. As described above, each rib also includes an exposed active area 2525 flanked by insulating regions 2623, 2623′. FIG. 26 is similar to the example shown in FIG. 25, except that 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 coupling the applicator region proximally to a first elongate member that is axially slidable relative to a second elongate member coupled to the distal end of the applicator region, as described above. Alternatively, or additionally, any of these devices may be expanded by pushing the applicator region distally out of a catheter or sleeve so that it expands (e.g., self-expands), and the ribs of the applicator region can be biased to expand radially outward as they are driven distally out of the catheter / sleeve. Similarly, the applicator region can be collapsed by pulling it proximally back into the catheter / sleeve. The examples shown in Figures 25 and 26 are thus configured so that the elongate body does not necessarily extend into the expandable applicator region. In this example, the active areas of each rib (spline) may be electrically coupled at the proximal end, including electrically coupling a first subset of the active areas to a first polarity and a second subset of the active areas to a second polarity, and in some examples, ribs having the first polarity may alternate with ribs having the second polarity.

[0170] Any of the devices described herein may be configured to treat the sidewall of a lumen and / or treat anterior (distal) facing regions of tissue. For example, the devices described herein may be configured to treat tissue surrounding the sinuses of the pulmonary veins (PV) in the left atrium (LA) of the heart, e.g., to treat atrial fibrillation (AFIB) via PV isolation (PVI). An example of this treatment using a device such as that shown in FIG. 26 is illustrated in FIG. 27.

[0171] For example, puncture of the femoral vein may be performed using a needle under fluoroscopic and / or ultrasound guidance to gain access to the LA of the heart. After puncture under fluoroscopic 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. A transseptal sheath and dilator may be advanced over the guidewire to the superior vena cava (SVC). Once the sheath is 3-4 cm above the cavoatrial junction, the wire can be removed. The transseptal puncture needle may be advanced under fluoroscopic guidance until it reaches the sheath tip. The needle may then be advanced with a stylet inserted until it is 4 cm from the tip. The stylet prevents the needle tip from rubbing against the inner lumen of the sheath. The stylet may then be removed. The puncture may then 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 FIG. 26) may be introduced through the sheath into the LA. The active region (e.g., electrode) of the expanded or partially expanded ribs may be pushed against the wall of the LA 2718 surrounding the pulmonary vein 2719, as shown in FIG. 27. In any of the devices described herein, the distal end of the device may be deflectable or fully articulatable. For example, the elongate body may include one or more tendons for articulating the distal end (applicator region). Thus, electrode positioning may be aided by a deflectable or fully articulated distal end of the catheter, controlled via a steering mechanism in the handle and pull wires (tendons) located in the shaft of the elongate 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 device's active region (e.g., electrode) and the tissue (e.g., LA) wall can be verified, for example, by acquiring signals generated by the cardiac tissue. Electrodes incorporated into the catheter design for impedance-based localization can also be used for this purpose. After the desired electrode position and contact are confirmed, energy (e.g., sub-microsecond pulsing, microsecond pulsing, RF, etc.) can be applied to achieve the desired therapeutic effect, including, in some cases, non-thermal ablation of all or selected portions of the target tissue. The active electrode and / or electrodes used for pre-ablation impedance-based localization and / or contact assessment can be used for post-ablation signal acquisition. In some cases, tissue-contacting electrodes can be used for impedance-based localization and contact assessment. For example, the absence of electrical signals from cardiac tissue may indicate a positive acute effect from the ablation. The device may be repositioned one or more times and the application of energy may be repeated over additional regions of tissue (e.g., the LA area surrounding other pulmonary veins). For example, when treating in the LA, complete PVI may be achieved.

[0173] In some examples, the ribs can be configured to form a substantially flat region, such as a region where the non-insulated region is substantially parallel (e.g., within about + / - 8 degrees, within about + / - 5 degrees, within about + / - 4 degrees, within about + / - 3 degrees, within about + / - 2 degrees, within about + / - 1 degree, etc.) to the major axis of the distal end region, such as a region extending through multiple ribs. For example, each rib may include a hinge region adjacent one or both ends of the non-insulated (active) region that allows the rib to flex so that the non-insulated region is substantially flat.

[0174] For example, FIGS. 28A-28C illustrate an example in which the ribs forming the expandable frame of the applicator region may be shaped to be substantially parallel to the long axis of the applicator region's midline so that they appear substantially "flat" and may align with the lumen wall when expanded radially outward. In FIG. 28A, the device 2800 is similar to that shown in FIGS. 22A-22C and 23A-23F in that it includes multiple ribs (splines) 2821 arranged radially around a central midline 2855. Each rib includes an active (electrode) region 2825 flanked by insulating regions 2823, 2823′. 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 regions of the ribs and can slide distally or proximally to expand / contract the applicator region.

[0175] In Figure 28A, each of the ribs is shaped so that the active area 2825 extends substantially flat (without bending) and exposes approximately the same sized active area (electrode) 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 may expand less and contact the walls of the lumen than in Figure 28C. As the applicator region expands outward, the active area of ​​the rib remains substantially parallel to the central midline and also substantially parallel to the walls of the lumen 2866, as shown in Figures 28B and 28C. Furthermore, the length of the active area in contact with tissue is substantially similar.

[0176] Thus, in some examples, the ribs can be shaped or formed to ensure that the length of contact between the exposed active (electrode) section of each rib and tissue does not significantly vary, regardless of the ID of the lumen, including organs such as the bronchi, esophagus, and blood vessels. For example, device 2800 may be introduced inside a lumen (organ) with an ID of approximately 20 mm (e.g., FIG. 28C). The same device may be used in a lumen with an ID of approximately 10 mm (e.g., FIG. 28B). In the device shown in FIG. 28A, the ribs may be formed from a shape memory alloy (such as Nitinol) and may have an active (exposed electrode) region with a length of approximately 10 mm, for example. Generally, the length of the exposed portion can vary 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 either side of the active area, similar to the configuration shown in FIG. 28A. The hinges can be living hinges. In some cases, the hinges are formed by narrowed or cutout regions on one or both sides of the rib. The hinges can act as stress concentrators to allow contact bending along the exposed, non-insulated active area of ​​the rib.

[0178] FIG. 29A illustrates one example of a rib that does not include one or more hinges. In this example, rib 2921 includes a non-insulated active area (electrode) 2925 flanked by a pair of insulating regions 2923, 2923′. The rib extends in an arc. FIG. 29B shows a similar rib that includes a hinge region 2970. The hinge region in this example 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 thinning the rib thickness in the hinge region, perforations in the hinge region, shape-set bending in the hinge region, and / or using one or more different materials in the hinge region, such as a region that bends preferentially over the active region. A second hinge region can be included on the opposite side of the active region 2925 (not shown). In any of these examples, the hinge region can be within the insulating region 2923, the non-insulating region 2925, or span two regions. In Figure 29B, the hinge region is within insulating region 2923. The insulating material can provide support for the hinge region and prevent breakage of the ribs in the hinge region.

[0179] 30A and 30B illustrate another example of a device including an applicator region with a plurality of ribs 3021, each configured to have an active area 3025 (electrode) configured to remain substantially flat and parallel to a central longitudinal axis of the applicator region 3055 in any expanded configuration. FIG. 30B shows an enlarged view of section B of FIG. 30A, illustrating the hinge region 3070 of one of the ribs. In this example, the hinge region is similar to that shown in FIG. 29B and is covered by the electrically insulating material of insulating region 3023.

[0180] As mentioned above, any of these devices can 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 FIG. 31 . In this example, the device 3100 includes a balloon 3185, shown inflated within the applicator region formed by the eight ribs, which may drive (or help drive) the expansion of the applicator region. The balloon can be inflated by injecting a fluid, such as saline, into the balloon through the elongate body 3103. Each rib includes an active region 3125, shown in this example as a centrally located active region (electrode) flanked by a pair of insulating regions 3123, 3123′. In some examples, the applicator region may be shaped to fold, such that deflation of the balloon may allow the ribs to self-fold back to a non-expanded configuration. In some examples, the applicator region may also be folded by pulling it proximally back into the catheter or sleeve. The applicator region may also include one or more elongate members to assist in expansion / collapse in addition to the balloon, as described above. A balloon, such as that shown in FIG. 31, can also act as an insulator and prevent arcing between electrodes of different polarities. For example, the balloon may be formed of an electrically insulating material. The device shown in FIG. 31 also includes an atraumatic distal tip 3186, which may additionally or alternatively be used as a centering guide in some instances.

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

[0182] The devices described herein can be configured to create a treatment region (e.g., in some cases, a region of ablation) of approximately 5-15 mm. In some cases, a larger treatment region may not be necessary or advisable. For example, excessive ablation of the proximal wall or roof of the left atrium (LA) of the heart can lead to loss of myocardial function or disruption of the proper pathway for the propagation of cardiac electrical impulses. The devices described herein can limit the ablation "footprint" to, for example, approximately 5-15 mm, depending on the distance between electrodes, and can generate a sufficiently strong electric field to achieve a transmural effect.

[0183] 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″, 3214′″ and a proximal ring 3212 of three independently addressable electrodes 3212′, 3212″, 3212′″. Treatment energy may be applied between the entire distal ring and the proximal ring, for example, to circumferentially treat (e.g., ablate) the lumen, or energy may be applied between only a subset of the distal ring electrodes and the proximal ring electrode (e.g., only between 3214′ and 3212′). Thus, treatment may be applied only when the side of the applicator region faces the tissue.

[0184] FIGS. 34A-34C, 35, and 36A-36D illustrate examples of applicators that may be configured as described herein. FIGS. 34A-34C show an example of a flat "paddle" applicator including an outer electrode (wire electrode) and an inner electrode (wire electrode). For example, FIG. 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 positioned such that the minimum distance d between the outer and inner wire electrodes is substantially the same along their lengths. Each electrode is insulated proximally (3405), but is formed by uninsulated wire over the active region. Similarly, the wire paddle-shaped device of FIG. 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 that also includes an outer (more distal) active area electrode 3401" and an inner (more proximal) active area 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. In Figure 34C, the overall shape is semicircular.

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

[0186] Figures 36A-36D show an example of an applicator having a forward (distal) facing electrode. Figure 36A includes multiple (e.g., six in this example) ribs, each including a distal opposing electrode 3603. An active area (electrode) is formed in this example from the uninsulated portion of each rib (spline), and each of these active areas can be electrically coupled together to form a unipolar electrode. A central electrode 3605 is positioned on the distal end face of the electrode. As in the devices shown in Figures 22A-22C and 23A-23F above, the device shown in Figure 36A can be expandable and foldable, which includes coupling the distal end of each rib to an axially slidable elongate member that can slide relative to the proximal end of the rib.

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

[0188] 36D illustrates one example of a device having radially separated active regions (electrodes) 3661, 3662, 3663, 3664 that form a distally facing circle. The first and third active regions 3661, 3663, separated by the second and fourth active regions 3662, 3664, may be of a first polarity (and may be electrically coupled to each other), while the second and fourth active regions 3662, 3664 may be of 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, e.g., the first and second active regions.

[0189] Any of these devices can be used as a device or distal portion of a device, including an elongated body (e.g., a catheter), that can be used for treatment within a body lumen, such as (but not limited to) treating atrial fibrillation, ventricular tachycardia, or other cardiac-related ablation. For example, these devices may be used to apply nanosecond pulsed electric fields to virtually 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 may be part of a device used intraoperatively, e.g., during cardiac surgery. In some cases, methods using the device may be performed as an accompanying procedure, if desired, and the device need not be catheter-based.

[0190] In any of these devices, the distance between the electrodes can be varied, thereby determining the strength of the pulsed 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 centering guides (centering features) to aid in positioning the device within tissue. Thus, any of these devices may include a centering guide to aid 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 to position the device's electrode relative to the sinus / ostium region of various vessels, such as the pulmonary veins of the heart, allowing for proper positioning and more efficient ablation while achieving pulmonary vein isolation (PVI).

[0192] FIG. 37 illustrates the difficulty of centering a device 3700, such as the applicator device described herein, relative to a 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 that perform procedures to address atrial fibrillation (AFIB) do not have 3D mapping capabilities and rely on fluoroscopic imaging to place their devices. Therefore, navigating the device toward the PV can be difficult. In certain cases, the device can be placed off-center in the sinus of the PV, as shown in FIG. 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 may be additional devices that can be used in conjunction with the device to enable centering relative to the lumen to which the treatment is being applied, such as (but not limited to) the sinuses of a PV. Generally, a centering guide may be an expandable, atraumatic protrusion that may extend distally from the distal end of the device. FIG. 38A illustrates one example of an applicator device 3800 described herein that includes a centering guide 3840. The centering guide feature 3840, in this example, is integrated into the device and extends distally beyond the electrodes of the first (outer) ring 3814 and the second (inner) ring 3812.

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

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

[0196] For example, Figures 40A-40D illustrate the use of a centering guide configured as an expandable balloon as part of a device. In Figure 40A, device 4000 including a deflated balloon 4040 is introduced and positioned near LA 4006. Centering guide (e.g., balloon) 4040 is partially inflated to have an OD smaller than the ID of PV 4008, as shown in Figure 40B. In Figure 40C, the centering guide (balloon) is moved inside the PV until the ring electrode contacts the sinus, as shown. Finally, the balloon is inflated, as shown in Figure 40D.

[0197] 41A-41D illustrate a similar method of use when the centering guide is an expandable basket formed, for example, by splines (ribs) as shown in FIG. 38B. In FIG. 41A, the device 4100 including the folded basket 4140 is introduced and positioned near the LA 4106. The centering guide (e.g., basket) 4140 is partially expanded to have an OD smaller than the ID of the PV 4108, as shown in FIG. 41B. In FIG. 41C, the centering guide (basket) is moved inside the PV until the ring electrode contacts the sinus, as shown. Finally, the balloon is inflated, as shown in FIG. 41D.

[0198] How to Treat Cardiac Ablation Generally, the methods and devices described herein can use pulsed electrical energy (e.g., microsecond, sub-microsecond, nanosecond, etc. pulsed electrical energy) to treat atrial fibrillation, ventricular tachycardia, and other cardiac-related ablations. The applicators described herein can be used to deliver pulsed electrical energy to a desired treatment area during minimally invasive procedures or intraoperatively, such as during cardiac surgery.

[0199] For example, these methods and devices may be used to treat cardiac ablation by delivering pulsed energy to coronary arteries and peripheral arteries and veins. For example, any of the applicators described herein may be used to deliver pulsed energy to the pulmonary vein sinus. In particular, the applicator may fit into a transition region of the sinus, starting from a relatively larger area (relative to the distal region of the applicator) and transitioning to a relatively smaller area. A first or distal electrode having a relatively smaller diameter may contact the smaller area, while a second or proximal electrode having a relatively larger diameter may contact the larger area.

[0200] In another example, the diameter dimensions of the first and second electrodes can be reversed, such that the diameter of the first electrode is relatively larger than the diameter of the second electrode. Use of such an applicator can be well suited for treating areas of tissue that start with a relatively small area and transition to a relatively large area.

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

[0202] Once the sheath is positioned within 3-4 centimeters (cm) above the cavoatrial junction, the wire is removed. The transseptal needle is advanced under fluoroscopic guidance until it reaches the tip of the sheath. With the stylet inserted, the needle is advanced until it is 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. A puncture is made, and the sheath is advanced into the left atrium. A catheter with an electrode can be introduced through the sheath into the left atrium.

[0203] The electrodes may be pressed against the left atrial wall, particularly surrounding the pulmonary veins. Proper electrode positioning can be aided by a deflectable or fully articulated distal end of the elongated catheter body, controlled via mechanisms within the elongated handle and pullwire located within the shaft of the elongated catheter body. Proper catheter location 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 atrial wall can be verified via impedance readings, for example, by transmitting low-amplitude non-therapeutic electrical "test" signals. After proper location and contact of the electrode bipolar pair is confirmed, energy (nanosecond pulses, microsecond pulses, RF) can be applied to achieve the desired ablation effect. Complete pulmonary vein isolation treatment can then be achieved by repositioning the catheter and distal bipolar pair and repeating energy application over additional left atrial areas surrounding other pulmonary veins.

[0204] Pulsed electrical (e.g., nanosecond pulse) treatments can include pulse profiles with pulse rise and / or fall times that can 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 can 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 can 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. In addition to an instrument (e.g., an elongated applicator tool), the devices (e.g., systems) described herein may include a pulse generator, such as that shown schematically in FIG. 1 , configured to emit pulses in the sub-microsecond range, for example.

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

[0206] 42 is a flow diagram depicting one example of a method 4200 for delivering pulsed electrical therapy to a selected treatment area of ​​a patient. Some examples may perform the operations described herein with additional operations, fewer operations, operations in a different order, operations in parallel, and some operations differently. Method 4200 may be used to treat atrial fibrillation, ventricular tachycardia, or other cardiac ablation. Method 4200 is not limited to cardiac applications, but rather may be used to treat various body vessels.

[0207] In FIG. 42 , method 4200 can begin when a treatment area is identified in block 4202. Block 4202 may be optional, as indicated by the dashed line in FIG. 42 . For example, one or more diagnostic tests for the patient may identify a region of a vein, artery, or other body vessel that will receive pulsed electrical therapy. In other examples, the treatment area may be any technically feasible lumen, passageway, or structure. The diagnostic test may include a radiological test, a vascular test, an ultrasound test, or any other feasible test that allows for identification of the treatment area.

[0208] At block 4204, an applicator is positioned within the identified treatment area. For example, the system 100 of FIG. 1 may be used to position an applicator (such as, but not limited to, any of the applicators of FIGS. 2-41D) within the identified treatment area. For example, the applicator may be positioned by extending a spaced-apart fist electrode (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, electrodes of the applicator can be placed in contact with the target tissue within the identified treatment area. The electrodes can be positioned such that an active area on a first electrode, which can extend circumferentially (fully or partially) over the target tissue, is spaced apart from an active area on a second electrode, which can also extend circumferentially (fully or partially) over the target tissue. The area between the first and second electrode active areas can be treated. In some examples, the first active area of ​​the first electrode and the second active area of ​​the second electrode can be placed circumferentially around a lumen (e.g., a vessel wall), and in some examples, the first active area of ​​the first electrode and the second active area of ​​the second electrode can be placed circumferentially around a portion of a body vessel, such as a pulmonary vein sinus, in one non-limiting example. In some cases, the electrodes can be positioned through an attached elongate catheter body such that the electrodes contact the tissue. In some other cases, the electrodes can emerge from the elongate catheter body and expand to allow the electrodes to enter the treatment area. After expansion, the applicator can be moved to place the electrodes in contact with the tissue.

[0210] Once the electrodes are placed in contact with tissue, in some instances, the spacing (e.g., longitudinal spacing) between the electrodes (e.g., sets of electrodes) on the applicator may be adjusted. For example, with particular reference to the applicators described with respect to Figures 2, 3, 8, and 9, the spacing between the electrodes on the applicator may be adjusted to vary the density of the pulsed electric field or to accommodate changing tissue shape and topology.

[0211] In optional block 4207, contact with tissue may be confirmed by any suitable method (e.g., impedance testing, electrogram, imaging, etc.). In this optional step, low-level or low-amplitude signals (e.g., voltage and / or current) may be provided to the electrodes. System 100 may determine and / or measure impedance associated with the electrodes based on signals provided to and returned from the electrodes. Contact with tissue may be confirmed when the impedance is within expected values.

[0212] At block 4208, pulsed electrical therapy is applied to the identified treatment area through an applicator. For example, the 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 may be provided by a pulse generator configured to provide electrical pulses having an amplitude greater than 0.1 kV and a duration less than 1000 nanoseconds.

[0213] Additional treatments may be administered, including repeated application of energy to the tissue through the first and second electrodes, and the effectiveness of each pulsed electrical treatment may be assessed. If treatment is sufficient (e.g., as determined by imaging, impedance testing, electrograms, etc.), further treatments may not be necessary. In some cases, it may be advantageous to apply energy in a circumferential pattern as described herein (e.g., see FIG. 6B ), without the need to move the device, to achieve near-complete or complete circumferential treatment.

[0214] At block 4210, the applicator electrodes are withdrawn from the tissue. Optionally, the catheter may be moved relative 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 mentioned 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 can be part of an ablation method for treating cardiac regions, including, but not limited to, pulmonary veins (or sinuses associated with pulmonary veins), and can include coordinating the position of an applicator's energy application (e.g., sub-microsecond pulse energy application) electrodes with a mapping, such as a 3D electroanatomical mapping / map, of the relevant 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 may 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 commercially available mapping systems, or the devices described herein may include a mapping system or subsystem integrated into the device. In some examples, the sensors are configured as electrodes that can be used as sensors for a mapping (e.g., 3D electroanatomical mapping) system or subsystem, and in combination with one or more patches that can be applied to the patient and connected to the mapping system / subsystem.

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

[0218] For example, FIGS. 43A-43B illustrate an example of a device similar to that shown in FIGS. 4A-4E and 7 that includes both treatment electrodes 4311, 4321 and mapping electrodes 4350, 4350′, with ten individual mapping electrodes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 positioned on the distal, outward-facing side of the applicator in FIG. 43A. The mapping electrodes may also be referred to as sensing electrodes. As described above, the applicator 4300 is configured to deliver nanosecond pulsed energy treatment. 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 lengths of wire that form the treatment electrodes 4311, 4321. Additionally, the applicator 4300 includes five arms 4330 that flexibly couple the inner and outer rings to the elongate catheter body 4340. As previously mentioned, the inner and outer rings may have more lobes (e.g., more treatment electrodes) and / or fewer lobes.

[0219] The sensing or mapping electrodes are typically smaller than the treatment electrodes, which in this example are elongated lengths of wire. For example, the sensing or mapping electrodes may be 5 mm or less in length and / or width (e.g., having a maximum dimension of 5 mm or less, 4.5 mm or less, 4 mm or less, 3.5 mm or less, 3 mm or less, 2.5 mm or less, 2 mm or less, 1.5 mm or less, 1 mm or less, etc.). The mapping electrodes may be electrically insulated from the treatment electrodes. In the example shown in FIG. 43A , the sensing or mapping electrodes 4350, 4350′ are formed from a band or cuff of conductive material (e.g., metal) that is crimped or otherwise bonded over insulating material on the arm 4330 of the device. Some examples of insulating materials or coatings include polyimide, PET, etc. Each sensing or mapping electrode may include a lead (e.g., wire) extending from the sensing or mapping electrode through the 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 or mapping electrodes may be electrically separated and isolated from the treatment electrodes.

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

[0221] Generally, sensing / mapping electrodes may be used (instead of, or in addition to, treatment electrodes) to monitor the progress of treatment. For example, sensing / mapping electrodes can be used to determine whether 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 application of pulsed (e.g., nanosecond pulsed) energy from treatment electrodes to determine or monitor electrical activity on or adjacent to the target tissue. For example, ablation of tissue using the methods described herein by application of non-thermal treatments such as nanosecond pulsed electrical energy can be expected to reduce the electrical activity of the underlying target, e.g., cardiac tissue. Generally, the methods described herein can apply sub-microsecond (e.g., nanosecond) pulses, e.g., at 0.1 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 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 the underlying tissue and / or changes in impedance over time.

[0222] The devices described herein may also include one or more magnetic sensors 4342 (e.g., magnetic coils, rods, etc.). In this example, the magnetic sensors are attached to the distal section of the catheter body 4340 and are centered relative to the treatment electrodes. This can increase the accuracy of the catheter location.

[0223] 43B shows a side view of the applicator 4300. The inner ring 4320, outer ring 4310, and arms 4330 are shown coupled to an elongate 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 elongate body 4340 and may be used in combination with one or more of the other sensing / mapping electrodes described above.

[0224] These devices may be configured for magnetic sensing or electrical property (e.g., impedance-based) sensing, or both. For example, the device shown in FIGS. 43A-43B includes both mapping electrodes 4350, 4350′ and a magnetic sensor 4342 in addition to treatment electrodes. In some examples, the applicator can be coupled to a third-party mapping system (e.g., the Carto™ system, the Navx™ system, etc.), for example, by providing input to the mapping system directly or indirectly from the sensing / mapping electrodes. The applicators described herein can 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 region to be treated, and any of the applicators described herein may be introduced, and one or more sensors, including electrodes, may be used to locate the applicator on the tissue map or model. The device can display an image of the map or model and simultaneously indicate the location of the applicator on the image of the map or model to help guide a user, e.g., a physician, surgeon, etc., in treating the target tissue. Alternatively, the applicators described herein may be used for both mapping and ablation. In some cases, the devices described herein may include a mapping system or subsystem integrated into the device.

[0225] For example, FIG. 43C schematically illustrates one example of a device as described herein that includes both mapping and therapy. In a first embodiment of this example, the device includes an applicator 4394 similar to that described above that includes both a plurality of 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 (e.g., as shown in FIG. 1). The system 4392 may be separate from the mapping system 4393 and / or output 4395, which may include one or more displays and may show a map of the tissue, including the location of the applicator, based on input from one or more sensing / mapping electrodes (or other mapping sensors) on the applicator. In some examples, as indicated by dashed line 4390″, the device may include the nanosecond pulsed energy treatment system 4392 and output 4395 and be used 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 pulse energy application Any of the methods and devices described herein may be for bipolar sub-microsecond (e.g., nanosecond) pulse application 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 of any conductive material. Smaller profile wires are particularly suitable for emitting the electromagnetic fields described herein. Typically, such small profile wires are avoided for use in systems that generate thermal energy because their thinner profile limits the ablation area and may be more susceptible to breakage.

[0227] Most energy-based treatment devices, such as radio frequency (RF) devices, employ electrodes approximately 2–3 mm in diameter or larger. RF thermal ablation, for example, 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 and the impedance between the electrode and tissue. Tissue further from the electrode can be heated as a result of conductive heating, either directly from the electrode or by conduction of heat from already “hot” tissue to “cooler” regions. Electrode size is crucial in this scenario because larger electrodes cover a larger area of ​​tissue, thereby increasing “direct” conductive heat transfer between the electrode and tissue. Additionally, when multiple electrodes are used (e.g., bipolar RF systems), larger electrode size reduces the distance between them and therefore reduces 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 location of highest energy concentration is at the electrode, and larger electrodes are considered advantageous because the electric field generated by a typical 2-3 kV (e.g., approximately the voltage used by most microsecond pulse devices) is not high enough for treatment. As a result, most microsecond-based devices typically require repositioning of the electrode to generate adjacent treatment zones.

[0228] For example, in contrast to the bulky tubular electrodes used with RF ablation, the use of such small profile wires of the present disclosure allows the devices described herein to have a relatively smaller crossing profile, which allows any of these devices to be pulled into, for example, the working channel of a bronchoscope / gastroscope or the lumen of a delivery sheath for cardiac applications, which may simplify and / or enable certain procedures.

[0229] The bipolar sub-microsecond (e.g., nanosecond) pulsed energy described herein can be applied at voltages high enough (e.g., 12-15 kV or greater) to generate therapeutic fields, even when the electrodes are constructed from small diameter (e.g., 0.005 inch to 0.015 inch or smaller) wire. Tests using such small diameter wires have surprisingly been found to be highly effective for tissue ablation, requiring no repositioning to ablate the tissue between them.

[0230] For example, Figures 44A-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 of these designs enhances the ability of these configurations to be easily foldable and fit into the small lumens of delivery devices. For example, such devices can more easily fit into the 2.8 mm or 3.7 mm working channels of therapeutic bronchoscopes and gastroscopes with 8.5 Fr, 9 Fr, and 12 Fr inner diameters (IDs), such as cardiovascular introducer sheaths. Catheters carrying such electrodes can be deflectable and / or steerable. For example, in Figure 44D, described below, they can be delivered through the working channel of a bronchoscope and / or gastroscope and contacted with target tissue by deflecting the distal tip of the bronchoscope or gastroscope.

[0231] The examples shown in Figures 44A-44D can be used as distal portions of catheters utilized for treatment of tubular areas of human or animal anatomy. Such tubular areas may include, but are not limited to, the esophagus, bronchi, pulmonary veins, other portions of the venous and arterial systems, and the like. These devices can also be used to apply sub-microsecond pulsed fields to other portions of the human body. For example, these devices can be used as part of catheters used during minimally invasive procedures or as part of devices utilized during surgery.

[0232] For example, FIG. 44A shows a first example of a device as described herein that includes a plurality of small diameter wires (e.g., wires having a diameter of 0.015 inches or less). In FIG. 44A, the wires are disposed on an expandable member, such as a balloon 4485. Three pairs of laterally spaced wires 4463 of a first polarity and wires 4465 of a second polarity are shown. The balloon is positioned at the end of an elongate body, such as elongate 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 collapse the radial profile of the device (not shown) or inflated to expand the radial profile, and in FIG. 44A, the device is shown with the device in an expanded state. The laterally spaced wires (electrodes or wire electrodes) may be separated, for example, by 1 mm or less (e.g., 0.5 mm) to 10 mm.

[0233] FIG. 44B shows another example of an expandable device including a single pair of small diameter wires (e.g., wires having a diameter of 0.015 inches or less). In this example, similar to FIG. 44A, wire electrodes 4463′, 4465′ are positioned on an expandable member (e.g., balloon 4485) coupled to, for example, a catheter 4460′, and the device includes a distal region 4469′ extending beyond the expandable member and electrodes. In FIG. 44B, the pair of wire electrodes includes a wire 4463′ of a first polarity that is laterally spaced from a wire 4465′ of a second polarity. As in FIG. 44A, the electrodes extend partially (or in some examples, completely) radially around the expandable member, such as over approximately 45 to 235 degrees (e.g., 90 to 135 degrees) of the circumference. Although FIGS. 44A and 44B show wire electrodes extending transversely to the long axis of the expandable member, in some instances the electrodes may extend longitudinally along the length of the expandable member or may be located at distinct radial positions, as shown in FIG. 44C.

[0234] In FIG. 44C , the device includes an expandable member 4485 (e.g., a balloon, basket, etc., shown in FIG. 44C as a balloon) on which multiple wire electrodes, which may have different polarities, are disposed extending longitudinally along the length of the expandable member from different radial locations. For example, the active region of a wire electrode 4463″ of a first polarity extends 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 approximately 40-60 degrees (in this example, 2-5 mm). The device includes an elongate 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, while the unexposed (e.g., insulated) region 4467 may be positioned closer to each other, as shown in FIG. 44C . As in the example shown in FIGS. 44A-44B , the expandable member of FIG. 44C may transition between a collapsed configuration (not shown) and an expanded configuration (shown). Thus, the spacing between the wire electrodes can be controlled by controlling the expansion of the expandable member.

[0235] Alternatively, in some examples, the device may not include an expandable member, as shown in FIG. 44D. In this example, the device includes an elongate body 4460'" from which extends a pair of wire electrodes 4463'", 4465'". The wire electrodes may be supported by insulating regions 4467' as shown and may be separated from one another by a radial (and / or, in some cases, longitudinal) spacing distance. The wires may be folded from a collapsed configuration (not shown) to an expanded configuration (shown), or vice versa.

[0236] Methods of using the devices of the present disclosure The devices described herein can include or be included as part of a catheter used during a minimally invasive procedure or a device utilized during surgery. As previously mentioned, the devices described herein, including (but not limited to) those shown in Figures 22A-22C, 23A-23F, 25, and 26, can be used to treat a body lumen 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, the methods and devices described herein can be used to apply sub-sub-microsecond (e.g., nanosecond) pulsed energy, however, any of the devices described herein can also be configured to apply other types of energy, such as RF or micropulse-based electric field energy.

[0238] In some examples, the devices described herein may be inserted through and / or used in conjunction with a catheter or other delivery device. For example, any of these devices may be inserted through the working channel of an endoscope, such as a bronchoscope or gastroscope. In some examples, the device may include, for example, a catheter with an expandable active region including electrodes, which may be used in conjunction with an expansion frame (e.g., struts, ribs, etc.) and / or balloon, may be used within the bronchial system or esophagus, and may be introduced through the working channel of the bronchoscope or gastroscope. An endoscope (e.g., a bronchoscope or gastroscope) may be placed adjacent to the treatment site, which may be visualized (imaged) through a scope or camera, such as a bronchoscope field (a camera built into the scope). The device may then be introduced through the working channel of the scope. Thereafter, the device (e.g., frame and / or balloon) may be expanded, so that the electrodes on the surface of the frame / balloon are placed in contact with tissue at the treatment site. Energy may then be delivered to the electrodes. The device can then be folded (e.g., by deflating the balloon, deflating the frame, etc.) 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 intraluminal cancers, for example, by inserting the device of the present disclosure through a body vessel (using a catheter, or, if applicable, a laparoscopic device), expanding the device at a treatment site (e.g., at or adjacent to the intraluminal cancer), applying energy, particularly nanosecond pulsed electrical energy, and treating the tissue. In some examples, the 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 are methods 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 involve the insertion of a luminal catheter through the penis, through the urethra, and into the prostate, where energy delivery may be applied.

[0240] Other examples of tissues that may be treated include the lung (e.g., treating lung cancer), pancreas (e.g., pancreatic cancer), etc. Other exemplary tissues (body vessels) and treatment methods are described herein.

[0241] The above-described methods and devices describe, for ease of explanation, an example of arterial treatment using pulsed electrical therapy, however, other treatments are contemplated.

[0242] As mentioned above, any of the devices described herein can be implemented into a robotic system that can be used to position and / or control electrodes during treatment. For example, the robotic system may include a movable (robotic) arm to which an elongated applicator tool is coupled. Various motors and other movement devices can be incorporated to enable fine movement of the working tip 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 vision), which may be mounted in a fixed position or coupled (directly or indirectly) to the robotic arm or other controllable movement device. In some examples, the image acquisition device may be incorporated into the elongated applicator tool.

[0243] Examples of the methods of the present disclosure can be implemented using computer software, firmware, or hardware. Various programming languages ​​and operating systems can be used to implement the present disclosure. Programs that execute the methods and systems may include separate program code containing sets of instructions to perform desired operations, or may include multiple modules that perform such sub-operations of an operation, or may be part of a single module of a larger program that provides the operations. The modular structure facilitates adding, deleting, updating, and / or modifying internal modules and / or features within the modules.

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

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

[0246] Any of the methods described herein (including the user interface) may be implemented as software, hardware, or firmware, and may be described as a non-transitory computer-readable storage medium storing a set of instructions executable by a processor (e.g., a computer, tablet, smartphone, etc.) that, when executed by a processor, 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, modifying parameters (including timing, frequency, intensity, etc.), making decisions, alerting, etc. In some illustrative examples, hardware may be used in combination with software instructions to implement the present disclosure.

[0247] When a feature or element is referred to herein as "on" another feature or element, it can be directly on the other feature or element, or intervening features and / or elements may also be present. In contrast, when a feature or element is referred to as "directly on" another feature or element, there are no intervening features or elements present. It should also be understood that when a feature or element is referred to as "connected," "attached," or "coupled" to another feature or element, it can be directly connected, attached, or coupled to the other feature or element, or there may be intervening features or elements present. In contrast, when a feature or element is referred to as "directly connected," "directly attached," or "directly coupled" to another feature or element, there are no intervening features or elements present. Although described or illustrated with respect to one example, the features and elements so described or illustrated can be applied to other examples. Those skilled in the art will also understand that a reference to a structure or feature disposed "adjacent" to another feature may have portions that overlap with or underlie the adjacent feature.

[0248] The terms used herein are for the purpose of describing particular examples only and are not intended to limit the invention of the present disclosure. For example, as used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. It will be further understood that the terms "comprises" and / or "comprising," as used herein, specify the presence of stated 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 term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ."

[0249] Spatially relative terms such as "under," "below," "lower," "over," "upper," and the like may be used herein to describe the relationship of one element or feature to another element or feature, as illustrated in the figures, for ease of explanation. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is inverted, an element described as "under" or "beneath" another element or feature would be oriented "over" the other element or feature. Thus, the exemplary term "under" can encompass both an orientation of above and below. The device may be otherwise oriented (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," "horizontal," etc. are used herein for descriptive purposes only, unless otherwise specified.

[0250] The terms "first" and "second" may be used herein to describe various features / elements (including steps), but these features / elements should not be limited by these terms unless the context dictates otherwise. These terms may be used to distinguish one feature / element from another. Thus, a first feature / element discussed below could be referred to as a second feature / element, and similarly, a second feature / element discussed below could be referred to as a first feature / element, without departing from the teachings of the present invention.

[0251] Throughout this specification and the claims that follow, unless the context dictates otherwise, the word "comprise" and variations such as "comprises" and "comprising" mean that various components can be used jointly in methods and articles (e.g., compositions and apparatuses, including devices and methods). For example, the term "comprising" will be understood to mean the inclusion of stated elements or steps, but not the exclusion of other elements or steps.

[0252] Generally, any of the apparatus and methods described herein should be understood to be inclusive, although all or a subset of the components and / or steps may alternatively be exclusive when expressed as "consisting of" or alternatively "consisting essentially of" various components, steps, subcomponents, or substeps.

[0253] As used in the specification and claims herein, including in the examples, unless otherwise specified, all numbers can be read as if preceded by the word "about" or "approximately," even if that term is not explicitly stated. The phrase "about" or "approximately," when describing a size and / or location, can be used to indicate that the described value and / or location is within a reasonably expected range of values ​​and / or locations. For example, a numerical value can have a value of + / - 0.1% of the stated value (or range of values), + / - 1% of the stated value (or range of values), + / - 2% of the stated value (or range of values), + / - 5% of the stated value (or range of values), + / - 10% of the stated value (or range of values), etc. Any numerical value given herein should also be understood to include about or approximately that value unless the context dictates otherwise. For example, if the value "10" is disclosed, then "about 10" is also disclosed. Any numerical range recited herein is intended to include all subranges therein. It is also understood that when a value is disclosed, "less than or equal to" the value, "greater than or equal to" the value, and possible ranges between values ​​are also disclosed, as would be understood by one of ordinary skill in the art. For example, if a value "X" is disclosed, "less than or equal to X" as well as "greater than or equal to X" (e.g., where X is a number) are also disclosed. It is also understood that throughout this application, data is provided in several different formats, and this data represents endpoints and starting points, and ranges for any combination of the data points. For example, if a specific data point "10" and a specific data point "15" are disclosed, it is understood that greater than 10 and 15, greater than or equal to 10 and 15, less than 10 and 15, less than or equal to 10 and 15, and equal to 10 and 15 are considered to be disclosed, as well as between 10 and 15. It is also understood that each unit between two specified 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 have been described above, any number of modifications may be made to the various examples without departing from the scope of the invention as set forth in the claims. For example, the order in which 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 other examples. Therefore, the foregoing description has been provided primarily for illustrative purposes and should not be construed as limiting the scope of the invention, as set forth in the claims.

[0255] The examples and illustrations contained herein illustrate, by way of illustration and not limitation, specific embodiments in which the present subject matter may be practiced. As noted above, other examples and variations can be utilized and derived therefrom, such that structural and logical substitutions and changes can be made without departing from the scope of the present disclosure. Such examples of the present subject matter, if more than one is indeed disclosed, may be individually or collectively referred to herein by the term "invention" for convenience only, without intending to intentionally limit the scope of the present application to any single invention or inventive concept. Thus, while specific examples have been illustrated and described herein, any configuration calculated to achieve the same purpose may be substituted for the specific example shown. The present disclosure is intended to cover any and all adaptations or modifications of the various examples. Combinations of some features of the above examples or examples provided, as well as other examples not specifically described herein, will be apparent to those skilled in the art upon reviewing the above description.

Claims

1. 1. A device for delivering a pulsed electric field to a wall of an anatomical structure, said device comprising: A long, slender body and a first electrode comprising first one or more loops, the first electrode having a first active area formed on the first one or more loops, the first active area configured to surround a first region of the wall of the anatomical structure, and further wherein the first one or more loops are flexibly coupled to a distal end region of the elongate body; a second electrode comprising second one or more loops, the second electrode having a second active area formed from the second one or more loops, the second active area configured to surround a second region of the wall of the anatomical structure, the second one or more loops flexibly coupled to the distal end region of the elongate body; The apparatus further wherein the first electrode is radially offset, laterally offset, or both radially and laterally offset from the second electrode.

2. The device of claim 1 , wherein the first electrode, the second electrode, or both, comprise a single loop.

3. The device of claim 1 or 2, wherein at least one of the first electrode and the second electrode traverses the distal end region of the elongate body.

4. The device of claim 1 , wherein the first electrode comprises a first plurality of loops arranged as petals around the distal end region of the elongate body.

5. The device of claim 1 or 4, wherein the second electrode comprises a second plurality of loops arranged as petals around the distal end region of the elongate body.

6. The device of any one of claims 1 to 5, wherein the first active region has a diameter smaller than a diameter of the second active region.

7. The device of any one of claims 1 to 6, wherein the first electrode and the second electrode are disposed on an expandable frame.

8. The device of any one of claims 1 to 7, wherein the first electrode and the second electrode are disposed on an expandable balloon.

9. The device of any one of claims 1 to 8, wherein the first electrode and the second electrode are each formed from a wire having a diameter of less than 0.2 mm.

10. The device of any one of claims 1 to 9, wherein the first and second electrodes are configured to flexibly conform to the wall of the anatomical structure.

11. 11. The device of claim 1, further comprising an outer delivery catheter, the elongate body being slidably disposed within the outer delivery catheter, and the first electrode and the second electrode being configured to collapse when retracted into the outer delivery catheter.

12. 12. The device of claim 1, wherein the first electrode is positioned distally relative to the distal end region of the elongate body and the second electrode is positioned proximal to the first electrode.

13. The device of any preceding claim, wherein the first and second electrodes are configured to slide axially proximally or distally relative to one another.

14. 14. The apparatus of any one of claims 1 to 13, wherein the first electrode comprises an anode and the second electrode comprises a cathode, and the apparatus is configured to deliver pulsed energy between the first electrode and the second electrode.

15. The device of any preceding claim, wherein the first active region and the second active region each have a length greater than 5 cm.

16. The device of any preceding claim, wherein the first active region and the second active region each have a diameter of less than 0.2 mm.

17. 17. The device of any one of claims 1 to 16, wherein at least one of the first active area and the second active area is configured to surround the wall of the anatomical structure in a partial, near complete, or complete circle.

18. 18. Apparatus according to any preceding claim, further comprising a plurality of mapping and / or sensing electrodes on a portion of the first and / or second electrodes.

19. 1. A device for delivering a pulsed electric field, comprising: A long, slender body and a first electrode comprising a first wire loop, the first wire loop flexibly extending from the elongate body, the first electrode having a first active area extending along the length of the first wire loop; a second electrode comprising a second wire loop, the second wire loop flexibly extending from the elongate body, the second electrode having a second active area extending along the length of the second wire loop; The apparatus, wherein the first electrode is radially offset, laterally offset, or both radially and laterally offset from the second electrode.

20. 20. The device of claim 19, wherein the first active region and the second active region are spaced apart from each other by a fixed distance along the longitudinal axis of the elongated body.

21. 21. The device of claim 19 or 20, wherein the first electrode and the second electrode are configured to flexibly conform to a wall of an anatomical structure.

22. 22. The device of any one of claims 19 to 21, wherein the first electrode and the second electrode are configured to collapse when retracted into an outer delivery catheter within which the elongate body is axially movable.

23. The device of any one of claims 19 to 22, wherein the first loop is smaller than the second loop.

24. 24. The device of any one of claims 19 to 23, wherein either the first electrode or the second electrode, or both, comprise a single loop.

25. The device of any one of claims 19 to 24, wherein at least one of the first electrode and the second electrode traverses a distal end region of the elongate body.

26. 26. The device of any one of claims 19 to 25, wherein at least one or both of the first electrode and the second electrode comprise a plurality of wire loops arranged as petals around a distal end region of the elongate body.

27. The device of any one of claims 19 to 26, wherein the first active region has a diameter smaller than a diameter of the second active region.

28. The device of any one of claims 19 to 27, wherein the first electrode and the second electrode are disposed on an expandable frame.

29. 29. The device of any one of claims 19 to 28, wherein the first electrode and the second electrode are each formed from a wire having a diameter of less than 0.2 mm.

30. 30. The device of any one of claims 19 to 29, further comprising an outer catheter, the elongate body being slidably disposed within the outer catheter, and the first electrode and the second electrode being configured to collapse when retracted into the outer catheter.

31. 31. The device of any one of claims 19 to 30, wherein the first electrode is positioned distally relative to an end region of the elongate body and the second electrode is positioned proximal to the first electrode.

32. 32. The device of any one of claims 19 to 31, wherein the first electrode is configured to slide axially proximally or distally relative to the second electrode.

33. 33. The apparatus of any one of claims 19 to 32, further comprising a plurality of mappings and / or electrodes on the first electrode outside the first active area and / or on the second electrode outside the second active area.

34. 1. A method for delivering a pulsed electric field to a wall of an internal anatomical structure of a subject using an applicator, the method comprising: positioning a first electrode of the applicator comprising a first one or more loops and a second electrode of the applicator comprising a second one or more loops within the subject's body such that a first active area of ​​the first one or more loops forms a first contact loop in electrical communication with a first region of the wall of the anatomical structure and a second active area of ​​the second one or more loops forms a second contact loop in electrical communication 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; applying a pulsed electrical therapy between the first active area and the second active area.

35. To position it, 35. The method of claim 34, comprising deploying the first electrode and the second electrode from the delivery catheter by moving the delivery catheter relative to an elongate body coupled to the first and second electrodes to expand at least one of the first electrode and the second electrode from a delivery configuration to a deployed configuration.

36. 36. The method of claim 35, wherein deploying the first electrode and the second electrode comprises contacting a plurality of electrically continuous wire lengths of the first one or more loops with the wall to form the first contact loop.

37. 37. The method of claim 35 or 36, wherein deploying the first electrode and the second electrode comprises contacting a plurality of electrically continuous wire lengths of the second one or more loops with the wall to form the second contact loop.

38. 38. The method of any one of claims 35 to 37, wherein deploying the first electrode and the second electrode comprises expanding the first electrode to have a larger diameter than the second electrode.

39. The method of any one of claims 35 to 38, wherein deploying comprises deploying into an antrum of a pulmonary vein.

40. 36. The method of claim 35, wherein the deploying comprises deploying the first electrode such that the first electrode is coplanar with the second electrode.

41. 41. The method of any one of claims 34 to 40, wherein applying the pulsed electrical therapy comprises applying an electric field between the first active region and the second active region.

42. 42. The method of any one of claims 34 to 41, wherein applying the pulsed electrical therapy comprises applying pulses having nanosecond durations.

43. 43. The method of any one of claims 34 to 42, further comprising mapping the location of the applicator relative to the wall of the anatomical structure using one or more mapping sensors on the applicator.

44. 44. The method of any one of claims 34-43, further comprising sensing one or more electrical properties of the wall of the anatomical structure using one or more sensors on the applicator before applying the pulsed electrical therapy, and / or during the application of pulses of the pulsed electrical therapy, and / or after applying the pulsed electrical therapy.

45. 1. An apparatus comprising: an elongate body extending proximally to distally, the elongate body configured to be inserted into a body vessel; an applicator region at a distal end region of the elongate body, the applicator region comprising a plurality of expandable ribs configured to expand outwardly within the body vessel from a collapsed configuration; each rib having a non-insulating active area; The device further includes 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.

46. 46. ​​The device of claim 45, wherein the non-insulated active area of ​​each of the plurality of ribs is configured to be substantially straight and parallel to a longitudinal axis of a portion of the applicator area.

47. 47. The apparatus of claim 45 or 46, wherein each of the plurality of ribs comprises a hinge region on each side of the non-insulating active region.

48. 48. The device of claim 47, wherein the hinge region is covered by a flexible insulator.

49. 49. The device of any one of claims 45 to 48, wherein the elongate body comprises a first elongate member coupled to a proximal end of each rib and a second elongate member coupled to a distal end of each rib, the first elongate member and the second elongate member configured to slide axially relative to each other to transform the applicator region between the collapsed configuration and an expanded configuration in which the plurality of expandable ribs are expanded outward.

50. 50. The device of any one of claims 45 to 49, wherein each of the expandable ribs is biased to expand outwardly.

51. 51. The device of any one of claims 45 to 50, wherein the elongate body is a flexible elongate body.

52. 51. The device of any one of claims 45 to 50, wherein the plurality of expandable ribs are substantially flat, and wherein the substantially flat active portion of each rib does not change length regardless of the level of expansion of the plurality of expandable ribs.

53. 50. The device of claim 49, further comprising an expandable member within the applicator region, the expandable member configured to expand outwardly to drive expansion of the plurality of ribs.

54. 50. The device of claim 49, wherein the applicator region is configured to expand outwardly into a shape having a larger cross-sectional area relative to a longitudinal axis of the applicator region, and the shape is biased to be larger distally than proximally or larger proximally than distally.

55. 55. The device of claim 54, wherein the shape is a teardrop shape.

56. 56. The device of claim 54 or 55, wherein the non-insulated active area of ​​each rib is within a distal portion of the applicator region such that the non-insulated active area faces distally in the expanded configuration.

57. 57. The device of any one of claims 45 to 56, further comprising a centering guide extending distally from the applicator region.

58. 1. An apparatus comprising: an elongate body extending proximally to distally; an applicator region at a distal end region of the elongate body, the applicator region comprising: a first wire extending distally from the elongate body, the first wire having a first active region adjacent a first insulating region of the first wire; a second wire extending distally from the elongate body, the second wire having a second active region adjacent a second insulating region of the second wire; a device, wherein the first active region is separated from the second active region by a minimum distance d that is substantially constant along a length of the first active region, and further wherein the first active region is configured to have a first polarity and the second active region is configured to have a second polarity.

59. 59. The apparatus of claim 58, wherein the first wire comprises a first loop and the second wire comprises a second loop positioned concentrically within the first loop.

60. 60. The device of claim 58 or 59, wherein the first wire and the second wire extend from the elongate body in a plane.

61. 61. A device as claimed in any one of claims 58 to 60, wherein the insulating region and / or the elongate body comprises a bend such that the first and second wires extend at an angle to the longitudinal axis of the elongate body.

62. 62. The apparatus of any one of claims 58 to 61, wherein the first wire and the second wire have a thickness that is less than or equal to 0.38 mm.

63. 63. The device of any one of claims 58-62, further comprising an expandable member, the first wire and the second wire coupled to the expandable member such that expanding the expandable member causes the first wire and the second wire to expand radially relative to the elongate body.

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