Multi-strut ablation and sensing catheter device and method - Patent Application 20070122997

Abstract

Methods and devices are disclosed for delivering pulsed electrical therapy (including high-voltage, sub-microsecond pulsed electrical energy) to tissue, including cardiac tissue. The devices may include deployable electrodes that conform to a transition surface. These devices may include single or multi-layered wire loops forming petal-like electrodes and sensing (e.g., mapping, navigation, etc.) electrodes, including sensing electrodes radially disposed on either side of the electrodes used to apply the therapy.

Description

[Technical Field]

[0001] Priority claim This patent application claims priority to U.S. Patent Application No. 18 / 353,867, entitled "MULTI-STRUT ABLATION AND SENSING CATHETER DEVICES AND METHODS," filed July 17, 2023, and U.S. Patent Application No. 18 / 046,784, entitled "CIRCUMFERENTIAL ABLATION DEVICES AND METHODS," filed October 14, 2022 (now U.S. Patent Application Publication No. US2023 / 0068059), each of which is incorporated by reference in its entirety herein. [Background technology]

[0002] Short, high-field-strength electric pulses are used for the electrical manipulation of biological tissues and cells. For example, electric pulses can be used to treat human cells and tissues. The voltage induced in the cell membrane depends on the pulse length and pulse amplitude. Pulses longer than approximately 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 approximately 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.

[0003] In some cases, two or more electrodes are used to deliver electrical pulses, such as high field strength electrical pulses, to a selected treatment site. 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 constant and uniform contraction.

[0004] Therefore, it would be beneficial to provide an electrode that can conform to varying and / or irregularly shaped treatment areas. Summary of the Invention

[0005] 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.

[0006] 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, blood vessels, heart, trachea, pharynx, larynx, bronchi, ureters, urethras, fallopian tubes, cervix, uterus, intestines (large and / or small intestines), gallbladder, pancreas, rectum, liver, esophagus, stomach, nasal cavities, 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 vessels are referred to herein as body vessels. For convenience of description, all such anatomical structures, cavities, ducts, lumens, passageways, or vessels are referred to herein as body vessels. In particular, the methods and devices described herein may be configured to selectively treat body vessels having varying, transitioning, and / or irregular surfaces. In particular, the methods and devices described herein can be configured to selectively treat body vessels with varying, transitional, and / or irregular surfaces. An electrode that can conform to a body vessel can include a first electrode and a second electrode, which are configured to deploy from a catheter and conform to, for example, 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. Generally, the electrodes described herein are also referred to as electrode assemblies, and these electrodes (e.g., electrode assemblies) can include one or more active regions configured to apply energy to tissue and one or more insulating regions.

[0007] The methods and devices described herein are not limited to vascular treatments such as angioplasty procedures, but can also 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, by applying sub-microsecond (e.g., nanosecond) pulsed electric fields to ducts 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.

[0008] 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. 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.

[0009] 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.

[0010] 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.

[0011] 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 the lumen through which the applicator tool is inserted and can improve tissue access and contact for the electrode. For example, the contact protrusions can be inflatable elements (e.g., balloons) or mechanical elements (e.g., a pair of plates or a set of arms).

[0012] In one embodiment, the applicator may include an elongate body, such as an elongate catheter body, a first electrode formed of one or more loops and having a first diameter coupled to the elongate catheter body, and a second electrode formed of one or more different loops and 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. Any of these devices may include mapping and / or sensing electrodes, which may be positioned distal and / or radially outward of the first and second electrodes.

[0013] In some examples, 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 examples, the first and second electrodes may include two or more lobes.

[0014] 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.

[0015] In some examples, the first electrode and the second electrode are configured to 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.

[0016] In some examples, the first conductor and the second conductor are configured to vary the distance therebetween.

[0017] For example, described herein is a device for delivering pulsed electric fields, the device comprising: an elongate body; a plurality of arms configured to extend obliquely from the elongate body in a deployed state; a first plurality of electrode lengths extending between the plurality of arms to form a first treatment electrode; a second plurality of electrode lengths extending between the plurality of arms to form a second treatment electrode radially outward from the first treatment electrode in the deployed state; one or more mapping and / or sensing electrodes on an extension region of each of the plurality of arms radially outward from the second treatment electrode; and one or more mapping and / or sensing electrodes on an intermediate region of each of the plurality of arms between the first treatment electrode and the second treatment electrode.

[0018] Any of these devices may include a central electrode. For example, the central electrode may include a mapping electrode and / or a sensing electrode. The central electrode may be configured to extend distally from the distal end of the elongate body. In some examples, the central electrode further includes a central treatment electrode, the central treatment electrode configured to operate with a different polarity than at least one of the first or second treatment electrodes.

[0019] In any of these devices, the one or more mapping and / or sensing electrodes on the extension region may include an electromagnetic sensor coupled to the extension region of one or more of the multiple arms.

[0020] At least some of the arms may include a hollow insulating member through which at least a portion of the first or second electrode and / or electrical connector extends. In some of these devices, each of the first plurality of electrode lengths forms an arc, and the arcs of the first plurality of electrode lengths together encircle the elongate body. The arms may be pre-bent or biased so that they bend obliquely relative to the longitudinal axis of the elongate body when extended from the elongate body. For example, at least one of the arms may be configured to bend at a different angle than at least one other arm of the plurality of arms. The arms may include at least three arms, and the device may further include a third plurality of electrode lengths extending between the three arms to form a third treatment electrode.

[0021] In some embodiments, a device for delivering pulsed electric fields comprises an elongate body, a first plurality of arms configured to extend obliquely from the elongate body in the deployed state, a second plurality of arms configured to extend obliquely from the elongate body in the deployed state, a first plurality of electrode lengths extending between the first plurality of arms to form a first treatment electrode, a second plurality of electrode lengths extending between the second plurality of arms to form a second treatment electrode axially separated from the first treatment electrode by a plurality of struts, the plurality of struts extending between the first treatment electrode and the second treatment electrode substantially parallel to a distal end region of the elongate body, and one or more mapping and / or sensing electrodes on at least some of the plurality of struts.

[0022] The one or more mapping and / or sensing electrodes may include a plurality of mapping and / or sensing electrodes, at least some of which may be positioned on either or both of the first plurality of arms and the second plurality of arms.

[0023] Some of the struts can be coupled to at least one of the first and second plurality of arms. For example, the first plurality of arms can be rotationally offset from the second plurality of arms. In some cases, some of the arms of the first and second plurality of arms are configured to transition from an undeployed state in which each arm of the plurality of arms is at least partially within the elongate body to a deployed state in which each arm of the first and second plurality of arms extends obliquely from the elongate body.

[0024] In any of these devices, some of the arms of the first plurality of arms and / or the second plurality of arms are configured to extend from the elongate body at an angle between 20 degrees and 90 degrees relative to the elongate body in the deployed state.

[0025] Any of these devices can include a central electrode configured to extend distally from the distal end of the elongate body, the central electrode including a mapping electrode and / or a sensing electrode. For example, the device can include a central electrode configured to extend distally from the distal end of the elongate body, the central electrode including a central treatment electrode. In some examples, the device is configured to apply bipolar energy between 1) the central electrode and at least one of the first plurality of electrode lengths, 2) the central electrode and at least one of the second plurality of electrode lengths, and / or 3) at least one of the first plurality of electrode lengths and at least one of the second plurality of electrode lengths. In any of these devices, the portion substantially parallel to the distal end region of the elongate body can be within plus or minus 10 degrees of the longitudinal axis of the distal end region of the elongate body.

[0026] Also described herein is a device for delivering a pulsed electric field, the device including: an elongate body; a balloon on the elongate body; a first electrode including a first plurality of wire loops, each wire loop of the first plurality extending from the elongate body to form a petal around the balloon, each wire loop of the first plurality having a first active region extending along at least a portion of the length of each first wire loop; and a second electrode including a second plurality of wire loops, each wire loop of the second plurality extending from the elongate body and each wire loop of the second plurality having a second active region extending along at least a portion of the length of each second wire loop, the first electrode being laterally offset from the second electrode along the length of the balloon, and the first active region and the second active region each including a flexible bend, the angle of the flexible bend configured to expand as the balloon expands.

[0027] At least one or both of the first and second plurality of wire loops can include 2 to 5 loops. In any of these examples, each wire loop of the first and second plurality of wire loops can be coupled to the outer surface of the balloon at one or more locations. For example, each wire loop of the first and second plurality of wire loops can be slidably coupled to the outer surface of the balloon. In some examples, each of the first and second active regions is bounded on both sides by insulating regions.

[0028] The first active region of each wire loop of the first plurality of wire loops can be spaced a distance from the second active region of each wire loop of the second plurality of wire loops. The first electrode and the second electrode can each be formed of a wire having a diameter of less than 0.2 mm. In some examples, the first electrode is configured to have a first polarity and the second electrode is configured to have a second polarity.

[0029] It can be particularly useful to include distal (e.g., most distal) hinge regions in the electrodes. For example, the plurality of wire loops of the first electrode and the plurality of wire loops of the second electrode can include distal regions configured as hinges that expand or contract with the expansion or contraction of the balloon.

[0030] In some cases, it may be particularly useful to place loop electrodes (including an electrically continuous anodic electrode and a separately electrically continuous cathodic electrode) around the entire circumference of the balloon, for example, multiple wire loops of a first electrode and multiple wire loops of a second electrode may be placed around the entire circumference of the balloon.

[0031] 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, contacting the two or more electrodes with tissue within the specified treatment area, and applying pulsed electrical therapy via the two or more electrodes. These methods may be performed using any of the devices described herein. In some examples, placing the two or more electrodes in contact with tissue may include deploying two or more electrodes from an elongated catheter body. In other examples, the two or more electrodes may include a first electrode and a second electrode. The first electrode may include multiple electrode lengths extending between two or more arms extending from the elongated catheter body and in electrical communication with each other. The second electrode may include multiple electrode lengths extending between two or more arms extending from the elongated catheter body and in electrical communication with each other. Any of these methods may include sensing electrical signals from the tissue using one or more mapping and / or sensing electrodes on an extension region of each of the multiple arms radially outward from the second treatment electrode and / or one or more mapping and / or sensing electrodes on an intermediate region of each of the multiple arms between the first treatment electrode and the second treatment electrode.

[0032] In some examples, the first electrode may be disposed on the same plane as the second electrode or on a different plane, while in other examples, the first electrode may be disposed on the same plane as the second electrode.

[0033] In some examples, the pulsed electrical therapy may include an electric field between the first and second electrodes (e.g., between the first and second plurality of electrode lengths). In other examples, the pulsed electrical therapy may include an electric field between at least one of the two or more electrodes (e.g., between the first and / or second plurality of electrode lengths) and a third electrode.

[0034] 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 a high peak voltage of 1 to 5 kilovolts per centimeter (kV / cm), 10 kV / cm, 20 kV / cm, 100 kV / cm, or even higher. 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 can be a patient (human or non-human, including animals). A user can operate the devices described herein on a subject. The user may be a medical practitioner (doctor, surgeon, etc.), medical technician, nurse, or other health care provider.

[0035] 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.

[0036] 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 extend one or more electrodes. The distal end may be steerable (e.g., articulate) in some examples. The devices described herein include devices that may be referred to as applicator tools, and typically include an applicator (or applicator region) for applying energy at or near the distal end region.

[0037] As mentioned above, any of these devices may be configured so 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.

[0038] In some examples, as described above, the device may 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 may be adjustable so that the distance between the circumferentially arranged electrodes can be increased or decreased. In some cases, the applicator may be adjustable to adjust the separation between the circumferentially arranged electrodes, for example, to be between 5 mm and 40 mm (e.g., 10 mm and 20 mm, etc.). The circumferentially arranged electrodes may be multiple, petal-shaped electrode wire rings (extending circumferentially or partially extending circumferentially) or multiple individual electrodes circumferentially arranged around the applicator. Adjusting the spacing between the electrodes may allow the user to adjust and / or correct placement and fit within an interior wall or sinus, especially when the diameter / size of a blood vessel changes (including rapidly changing) depending on 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 adjusted in some instances.

[0039] 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.

[0040] 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 (e.g., 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. In any of these devices, one or more mapping and / or sensing electrodes may be positioned radially outward from the first and second active regions, and one or more additional mapping and / or sensing electrodes may be positioned radially between the different electrodes.

[0041] In any of the devices described herein, each electrode of the device may include an elongated active region through 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 therefore 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 therefore all of the loop subregions) forming the second electrode (and therefore all of the loop subregions) are electrically coupled together as a single anode or a single cathode.

[0042] 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.

[0043] Generally, the first active region of the first electrode can have a diameter 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.

[0044] Any of these devices may include an expandable frame. The expandable frame may be a balloon, a strut assembly, 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 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.

[0045] 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.).

[0046] Generally, the first and second electrodes are configured to flexibly conform to the 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 340 degrees or more, about 360 degrees, etc. around the circumference of the lumen). In some cases, the first active area is configured to encircle the body lumen in a nearly complete circle.

[0047] Any of these devices may include an outer catheter or guide sheath (e.g., an introducer or 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.

[0048] 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, or vice versa.

[0049] 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).

[0050] 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.

[0051] 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.

[0052] 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 rely on 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 thermal energy applied by the applied electric field is very small, preventing damage to noncellular tissue.

[0053] 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.

[0054] 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 (i.e., a non-deployed state) to a deployed configuration (i.e., a deployed state). 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.

[0055] 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). 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.

[0056] Also described herein are apparatus (e.g., devices, systems, etc.) for delivering pulsed energy as point-by-point treatments or as single-shot treatments. Point-by-point treatments generally involve applying an area between two smaller electrically active regions, while single-shot treatments generally treat a larger area with multiple electrically coupled active regions.

[0057] 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.

[0058] 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.).

[0059] 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 mapping and / or sensing electrodes on the first electrode outside the first active region and / or on the second electrode outside the second active region.

[0060] 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 having one or more first loops and a second electrode of the applicator having one or more second 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.

[0061] Also described herein are methods of using any of these devices. 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 a first one or more loops and a second electrode of the applicator including 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 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.

[0062] Also described herein are devices for delivering pulsed electric fields, including an elongate body, an expandable member (e.g., a balloon) that may be at a distal end region of the elongate body, a first electrode assembly including a first plurality of wire loops, each wire loop of the first plurality forming a petal having a first active region, the first active region of each wire loop of the first plurality of wire loops disposed about the expandable member and extending around all or at least a portion of the circumference of the expandable member, and a second electrode assembly including a second plurality of wire loops, the each wire loop of the second plurality of wire loops forms a petal having a second active region, the second active region of each wire loop of the second plurality of wire loops being disposed around the expandable member and extending around all or at least a portion of the circumference of the expandable member; and a second electrode assembly, the first electrode assembly being laterally offset from the second electrode assembly along the length of the expandable member, the first electrode assembly and the second electrode assembly being configured to expand radially outward when the expandable member is expanded.

[0063] For example, a device for delivering a pulsed electric field may include an elongate body, a balloon on the elongate body, a first electrode assembly including a first plurality of wire loops, each wire loop of the first plurality forming a petal having a first active region disposed on the balloon, and a second electrode assembly including a second plurality of wire loops, each wire loop of the second plurality forming a petal having a second active region disposed on the balloon, each of the first and second active regions having a flexible bend whose angle (oriented distal to proximal / proximal to distal) is configured to expand with balloon expansion such that the first and second electrode assemblies expand radially outward upon balloon expansion, and further wherein the first electrode assembly is laterally offset from the second electrode assembly along the length of the balloon. In some examples, the first and second electrode assemblies may be configured to return to a radially collapsed or contracted configuration when the balloon is deflated.

[0064] In any of these devices, the expandable member may include an expandable balloon. The first and second electrode assemblies may extend from the elongate body over the expandable member.

[0065] The first plurality of wire loops can include any number of loops (e.g., 2 to 10 loops, 2 to 8 loops, 2 to 5 loops, 2 to 4 loops, etc.), and the second plurality of wire loops can include any number of loops (which may be equal to the number of loops in the first plurality, e.g., 2 to 10 loops, 2 to 8 loops, 2 to 5 loops, 2 to 4 loops, etc.).

[0066] Each of the first and second active regions can include one or more flexible bends, and in some examples, the angle of the flexible bends can be configured to expand as the balloon expands.

[0067] Each wire loop of the first plurality of wire loops and each wire loop of the second plurality of wire loops can be coupled to the outer surface of the expandable balloon at one or more locations. For example, each wire loop of the first plurality of wire loops and each wire loop of the second plurality of wire loops can be slidably coupled to the outer surface of the expandable balloon. In some examples, each of the first active region and the second active region can be bounded on both sides by insulating regions. In some examples, the first and second electrode assemblies can be positioned adjacent to the expandable member (e.g., balloon) rather than attached to the expandable member. In any of these examples, the first and second electrode assemblies can be configured into a radially collapsed or contracted configuration, such that expanding the expandable member (e.g., balloon) radially expands the electrode assemblies and contracting the expandable member can return the first and second electrode assemblies to the radially collapsed (or contracted) configuration.

[0068] A first active region of each wire loop of the first plurality of wire loops can be spaced a distance from a second active region of a wire loop of the second plurality of wire loops. The first electrode assembly and the second electrode assembly can be configured to flexibly conform to a wall of the anatomical structure.

[0069] As noted above, in any of these devices, the first and second electrode assemblies can each be formed of wire having a diameter of, for example, less than 0.2 mm, and the first electrode assembly can be configured to have a first polarity and the second electrode assembly can be configured to have a second polarity.

[0070] Further described herein is a device for delivering pulsed electric fields, comprising an elongate body, a plurality of arms configured to extend obliquely from the elongate body (e.g., in a deployed state), a first plurality of electrode lengths extending between the plurality of arms to form a first treatment electrode, a second plurality of electrode lengths extending between the plurality of arms to form a second treatment electrode (e.g., in a deployed state) radially outward of the first treatment electrode, and one or more mapping and / or sensing electrodes on the plurality of arms. It should be understood that in some embodiments, the device is configured to convert from a non-deployed state (e.g., a non-expanded configuration) to a deployed state (e.g., an expanded or treatment configuration), while in other embodiments, the device is configured to already be in a deployed state (e.g., a treatment configuration) and does not convert to the non-deployed state. The mapping and / or sensing electrodes may be positioned radially outward of the first treatment electrode, and in some examples, at least some of the mapping and / or sensing electrodes are positioned radially outward of the second treatment electrode. The structure including the multiple arms, the treatment electrodes, and the mapping and / or sensing electrodes is also referred to herein as the applicator of the device.

[0071] Any of these devices may include an extension region in the arm. The extension region may extend radially outward of all of the treatment electrodes when the device is in the deployed state. In some examples, one of the arms may be a hollow insulating member through which at least a portion of the first and second electrodes and / or electrical connectors (e.g., wires) may extend. This configuration allows the applicator to fold and expand while ensuring that the treatment electrodes maintain a consistent shape and spacing in the deployed or deployed state, which may be particularly useful for providing consistent and complete treatment.

[0072] The devices described herein have a deployed state in which the arms extend diagonally from the elongate body, and a retracted (undeployed) configuration in which all or a portion of the arms are retracted into the elongate body and folded or bent so as to be at least partially within the elongate body, and electrode lengths forming the first and second (or more) treatment electrodes may be folded and at least partially within the elongate body in the undeployed state. In some examples, the treatment electrodes may be formed as lengths of wire or other conductor that slide relative to the arms to enable relatively easy transition between the deployed and undeployed states. In some examples, the device may be configured so that the applicator is always deployed and never converted to the undeployed state.

[0073] For example, described herein is a device for delivering a pulsed electric field that may include an elongate body, a plurality of arms extending diagonally from the elongate body, a first plurality of electrode lengths extending between the plurality of arms to form a first treatment electrode, a second plurality of electrode lengths extending between the plurality of arms to form a second treatment electrode radially outward of the first treatment electrode, and one or more mapping and / or sensing electrodes on the plurality of arms.

[0074] In some examples, a device for delivering pulsed electric fields includes an elongate body, a plurality of arms configured to extend obliquely from the elongate body when the device is in a deployed state, a first plurality of electrode lengths extending between the plurality of arms to form a first treatment electrode, a second plurality of electrode lengths extending between the plurality of arms to form a second treatment electrode radially outward from the first treatment electrode in the deployed state, and a plurality of mapping electrodes on an extension region of each of the plurality of arms radially outward from the second treatment electrode in the deployed state and on an intermediate region of each of the plurality of arms between the first treatment electrode and the second treatment electrode.

[0075] Thus, the plurality of mapping electrodes may include a mapping electrode on an extension region of each of the plurality of arms, the extension region being radially outward from all of the treatment electrodes in the deployed state. The arms of the plurality of arms may be configured to extend from the elongate body in the deployed state at an angle between about 20 degrees and about 90 degrees relative to the elongate body. For example, in some embodiments, some of the arms may be configured to transition from a collapsed or undeployed configuration when constrained by an introducer sheath or other suitable device during delivery to a treatment site to an extended configuration in which each arm of the plurality of arms extends at an angle relative to the longitudinal axis of the elongate body in the deployed state. The arms of the devices described herein may be housed in a sheath or sleeve that can be removed during insertion into a delivery catheter, and the delivery catheter may hold the arms in the undeployed configuration until extended out of the delivery catheter. This may facilitate insertion and loading into a delivery catheter for use within the body.

[0076] Any of these devices may include a spacer at the distal end region of the elongate body configured to maintain spacing between the arms within the distal end region of the elongate body. The spacer may be axially movable relative to the distal end region of the elongate body. The elongate body may be configured as a sheath, as described above.

[0077] The first plurality of electrode lengths may include a first plurality of arcs extending between the arms, and the second plurality of electrode lengths may include a second plurality of arcs extending between the arms. The first plurality of electrode lengths may include a first ring or loop forming a first treatment electrode, and the second plurality of electrode lengths may include a second ring or loop forming a second treatment electrode.

[0078] Any of these devices may include a central electrode configured as a treatment electrode, a mapping electrode, and / or a sensing electrode. The central electrode may be integral with the spacer or may be separate from the spacer. In some examples, the device includes a central electrode without a spacer or a spacer without a central electrode. The central electrode may be configured to extend distally from the distal end of the elongate body.

[0079] Any of the devices described herein may include one or more electromagnetic (EM) sensors coupled to one or more of the multiple arms, including coupled to or positioned at an extension region of one or more of the multiple arms. For example, the device may include an EM sensor within an extension region of one or more of the multiple arms.

[0080] The devices described herein may include a third (or more, e.g., fourth, fifth, etc.) plurality of electrode lengths extending between the plurality of arms and forming a third treatment electrode radially outward of the first and second treatment electrodes (e.g., when the device is deployed). The mapping / sensing electrode may be comprised of a cylindrical electrode. In some examples, the mapping / sensing electrode may be on the outer surface of some of the plurality of arms. The first and second plurality of electrode lengths may each be formed of wire having a diameter of 0.2 mm or less.

[0081] In some examples, the device can be configured to apply energy between first and second treatment electrodes, e.g., the first treatment electrode includes an anode, the second treatment electrode includes a cathode, and the device is configured to deliver pulsed energy between the first and second treatment electrodes.

[0082] The first treatment electrode and the second treatment electrode may each be 5 cm or longer.

[0083] Also described herein are devices in which a first treatment electrode can form a circumferential loop longitudinally spaced from a second treatment electrode. The first and second treatment electrodes can have approximately the same radius. In some instances, the first and second treatment electrodes can have different radii.

[0084] For example, a device for delivering a pulsed electric field may include an elongate body, a first plurality of arms configured to extend obliquely from the elongate body (e.g., in a deployed state), a second plurality of arms configured to extend obliquely from the elongate body (e.g., in a deployed state), a first plurality of electrode lengths extending between the first plurality of arms to form a first treatment electrode, a second plurality of electrode lengths extending between the second plurality of arms to form a second treatment electrode axially separated from the first treatment electrode, and a plurality of mapping and / or sensing electrodes.

[0085] In any of these examples, the spacing between the first and second treatment electrodes may be maintained by multiple struts extending between the first and second treatment electrodes (even when using a retractable / foldable configuration). For example, a device for delivering a pulsed electric field may include an elongate body, a first plurality of arms configured to extend obliquely from the elongate body, a second plurality of arms configured to extend obliquely from the elongate body, a first plurality of electrode lengths extending between the first plurality of arms to form a first treatment electrode, a second plurality of electrode lengths extending between the second plurality of arms to form a second treatment electrode axially separated from the first treatment electrode by multiple struts, the multiple struts extending between the first and second treatment electrodes substantially parallel to a distal end region of the elongate body, and multiple mapping and / or sensing electrodes on some of the multiple struts.

[0086] Any of the devices described herein may include one or more electrodes on the shaft (e.g., immediately proximal to the arms). In particular, these devices may include one or more (e.g., two or more) sensing electrodes on the shaft of the device (as shown in FIG. 3B).

[0087] For example, each strut may include one or more mapping / sensing electrodes. Alternatively, only some of the struts may include mapping / sensing electrodes. In some examples, the mapping / sensing electrodes are on a first plurality of arms. Some of the struts may extend from at least one of the first plurality of arms and the second plurality of arms. In some examples, the first plurality of arms are rotationally offset from the second plurality of arms.

[0088] As described above, some of the arms of the first and second pluralities of arms can be configured to extend from the elongate body at an angle, e.g., between 20 and 90 degrees, relative to the elongate body. In some embodiments, the arms of the first and second pluralities of arms are configured to transition from a configuration extending at least partially longitudinally within the elongate body to an extended or deployed state in which each arm of the first and second pluralities extends obliquely from the elongate body when extended distally from the elongate body.

[0089] Also, as described above, any of these devices may include a spacer or guide in the distal end region of the elongate body to maintain spacing between each arm of the first and second plurality of arms within the distal end region of the elongate body.

[0090] The first plurality of electrode lengths may include a first plurality of arcs extending between the first plurality of arms, and the second plurality of electrode lengths may include a second plurality of arcs extending between the second plurality of arms. The first plurality of electrode lengths may include a first loop or ring forming a first treatment electrode, and the second plurality of electrode lengths may include a second loop or ring forming a second treatment electrode.

[0091] Any of these devices may include a central electrode, which may be configured to extend distally from the distal end of the elongate body, and which may include a mapping electrode and / or a sensing electrode.

[0092] In some examples, the first and second plurality of electrode lengths are each formed of wire having a diameter of 0.2 mm or less, the first treatment electrode includes an anode, the second treatment electrode includes a cathode, and the device is configured to deliver pulsed energy between the first and second treatment electrodes.

[0093] 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]

[0094] 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 and accompanying drawings that set forth illustrative embodiments. [Figure 1] FIG. 1 illustrates one example of a system for delivering high-voltage, high-rate pulses of electrical energy. [Figure 2] Figure 2A is an example of a device for delivering energy (e.g., nanosecond pulsed electrical energy) into a body vessel either in a single shot or point-by-point manner. Figure 2B is another example of a device for delivering energy (e.g., nanosecond pulsed electrical energy) into a body vessel either in a single shot or point-by-point manner. Figure 2C is another example of a device for delivering energy (e.g., nanosecond pulsed electrical energy) into a body vessel. [Figure 3] 3A-3B illustrate one example of an applicator including treatment electrodes and sensing / mapping sensors, with Fig. 3A showing a distal end view and Fig. 3B showing a side perspective view. [Figure 4]4A-4C show examples of devices for delivering pulsed electric fields. FIG. 4A shows an example of a device including first and second treatment electrodes and multiple mapping and / or sensing electrodes provided on extension regions of arms supporting the first and second treatment electrodes. FIG. 4B shows a device for delivering pulsed electric fields including a central electrode. FIG. 4C shows an example of a device including various features of FIGS. 4A-4B, with one of the arms shown transparent. [Figure 5] FIG. 5 is another example of a device for delivering pulsed electric fields that includes multiple mapping and / or sensing electrodes. [Figure 6] FIG. 6 shows an example of a device for delivering a multi-stage pulsed electric field. [Figure 7] FIG. 7 shows an example of animal model tissue demonstrating the ablation of discrete regions of tissue using a device similar to that shown in FIGS. 4A-4C. [Figure 8] Figures 8A and 8B show an example of a single wire loop having an active region forming part of an electrode assembly described herein, illustrating the expansion of the active region of the wire loop at a flexible bend. Figure 8C shows an example of a portion of a device including a small diameter wire electrode assembly formed of multiple wire loops having active regions with flexible bends disposed on an expandable member (e.g., a balloon). Figures 8D-8E show the expansion of a device such as that shown in Figure 8C. [Figure 9] Figures 9A-9C show examples of devices similar to those shown in Figures 8C-8E. Figure 9A shows an example using a transparent expandable member (e.g., a balloon). Figure 9B shows an example using an opaque expandable member. Figure 9C is an enlarged view of an example active area of ​​a portion of the wire loop of the electrode assembly of Figure 9B. [Figure 10] FIG. 10 is a flow chart illustrating an example method for delivering pulsed electrical therapy to a selected treatment site on a patient. DETAILED DESCRIPTION OF THE INVENTION

[0095] 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.).

[0096] 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. On these body vessel surfaces, it may be difficult for electrodes to establish effective contact to provide therapy. Described herein are various electrodes that can easily adapt and conform to irregular and / or changing shapes and provide reliable contact with body vessels.

[0097] Pulsed electric therapy can be microsecond pulse therapy or submicrosecond pulse therapy, including nanosecond pulses. For example, nanosecond pulsed electric field therapy can refer to the application of relatively high voltages (possibly 5 kV or more) for relatively short periods of time (possibly 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.

[0098] 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 the treatment of 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 abruptly changing diameters.

[0099] Alternatively, or in addition, 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 stent or angioplasty procedures. Thus, in some cases, these methods can be performed within the first 2-4 days after angioplasty and / or stenting. Untreated 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.

[0100] 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).

[0101] 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 thereof, 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.

[0102] 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 can be varied. The microcontroller can 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 rather than mains-powered.

[0103] 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.

[0104] 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 is configured to have one or more lengths or loops and includes an electrically active region ("active region") formed on one or more lengths or loops. The active region is configured to contact the target tissue and is a conductive region 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, for example, to form 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.

[0105] Patent Publication WO2022 / 231726, "Circumferential Ablation Devices and Methods", provides examples of treatment applicators configured to deliver pulsed energy therapy into a body vessel. The methods and devices described herein can be used with any variations shown in WO2022 / 231726. For example, see FIGS. 2A-2C and FIGS. 3A-C.

[0106] FIGS. 2A-2C show examples of applicators that can be used to deliver pulsed therapy, such as nanosecond pulsed electrical energy therapy, into body vasculature. These applicators can include multiple rings of electrodes that can be selectively actuated to apply energy (e.g., bipolar energy) for treating tissue. These devices can also be referred to as conformable ring devices that can be used to apply energy to tissue within the body. In one non-limiting example, the devices shown herein, including FIGS. 2A-2C, 3A-3B, can be used for bipolar application of electrical energy onto myocardial tissue, including but not limited to, cavities, fenestrations, and inner / outer walls (such as treatment of pulmonary veins).

[0107] In some embodiments, the device includes 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 a cavity and / or ostium. In some examples, additional rings can be used. For example, FIG. 2A shows a device including three rings, and FIG. 2B shows an example having four rings. FIG. 2C illustrates an example having two rings with a central electrode. These configurations can also enable adaptability to the patient's anatomy and assist in achieving both single-shot therapy (e.g., treatment of an entire region such as around a blood vessel in one treatment, including ablation) and point-by-point therapy (e.g., treating small portions of a body vasculature one by one, including ablation).

[0108] FIG. 2A shows an example of an applicator 260 device configuration with three rings of electrodes, including an outer ring 261 having a diameter of approximately 30 mm. The outer electrode may be formed from multiple subregions (e.g., petals) that can be electrically coupled together to apply a first polarity. In some examples, the individual subregions can be activated independently. FIG. 2C also includes a second ring 263 that is smaller than the first ring and arranged concentrically with respect to the first ring. In FIG. 2A, 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 265 that can similarly 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. 2A, 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.

[0109] For example, in FIG. 2B, the device includes four concentrically arranged rings. The outer electrode (ring 281) 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. The second ring 283 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). The third ring 285, 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, the fourth electrode (ring 287), of an even smaller circumference, is concentrically arranged with respect to the third ring.

[0110] Any of these devices can provide a small (e.g., point) central electrode, as shown in Figure 2C. Figure 2C shows two concentrically arranged electrode rings. The first ring electrode 291 can be formed from multiple sub-region electrodes, each formed from a wire with an exposed electrically active area. As with any of these examples, in some configurations, each sub-region can be individually controlled and / or they can all be electrically coupled together to form a single electrode. The second ring electrode 293 is concentrically arranged relative to the first ring electrode and, like the first ring electrode, can be formed from multiple sub-regions. Finally, the example shown in Figure 2C 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 sub-region of the outer ring) or inner ring (or sub-region of the inner ring).

[0111] Any of the applicators described herein may include additional electrodes to enable visualization of the device in combination with a mapping system. For example, Figures 3A-3B (taken from WO 2023 / 231726, incorporated herein by reference) show an example of a device including treatment electrodes 311, 321 and mapping electrodes 350, 350'. In Figure 3A, ten individual mapping electrodes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 are positioned on the distal, outward-facing side of the applicator. The mapping electrodes may also be referred to as sensing electrodes. As described above, the applicator 300 may be configured to deliver nanosecond pulsed energy therapy. The applicator 300 includes an inner proximal ring 320 and an outer distal ring 310. The inner ring 320 and the outer ring 310 each include five lobes formed by lengths of wire forming the treatment electrodes 311, 321. Additionally, the applicator 300 includes five arms 330 that (e.g., flexibly) couple the inner and outer rings to the elongated catheter body 340. As previously mentioned, the inner and outer rings may have more lobes (e.g., more treatment electrodes) and / or fewer lobes.

[0112] 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., the largest dimension may be 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. The sensing or mapping electrodes 4350, 4350′ of FIG. 3A 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 330 of the device. 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 insulated from the treatment electrodes.

[0113] In operation, sensing and / or mapping electrodes (e.g., sensing / mapping electrodes) can be used to isolate the location 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.

[0114] Generally, sensing / mapping electrodes may be used (in place of, or in addition to, treatment electrodes) to monitor the progress of treatment. For example, sensing / mapping electrodes can be used to determine whether the 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 the 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.

[0115] The device may also include one or more magnetic sensors 342 (e.g., magnetic coils, rods, etc.). In the example of Figure 3A, the magnetic sensors are attached to the distal section of the catheter body 340 and are centered relative to the treatment electrodes. This can increase the accuracy of the catheter location.

[0116] 3B shows a side view of applicator 300. Inner ring 320, outer ring 310, and arms 330 are shown coupled to elongate body 340. In this example, one or more (e.g., two 11, 12) additional sensing / mapping electrodes may be positioned on the shaft of elongate body 340 and may be used in combination with one or more of the other sensing / mapping electrodes described above.

[0117] The devices shown in Figures 2A-2C and 3A-3B may include sensing and / or mapping electrodes. Additionally, these examples may be modified as described herein. For example, sensing and / or mapping electrodes may be coupled between loops (e.g., on portions of loops extending radially inward, or between electrode active regions) and / or on one or more extensions extending radially outward from the electrode active regions.

[0118] 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 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.

[0119] In some implementations, the first and second rings (or any additional rings) of applicator 260, 280, or 290 may be approximately coplanar. This coplanar arrangement may allow the electrodes (e.g., the first and second rings) to provide better contact with planar tissue and / or tissue shaped similarly to the sinuses of the pulmonary veins. In some examples, the electrodes may have a "funnel" configuration that faces away from the sinuses of the pulmonary veins.

[0120] Any of the applicators described herein can be configured to provide therapy, such as nanosecond pulsed energy therapy, within a body vessel. The body vessel can be any feasible vessel, including, but not limited to, the sinus of a pulmonary vein or the pulmonary vein itself. In some examples, the applicator can include a proximal ring, a distal ring, and an elongated catheter body. The applicator can include three rings, and in some embodiments, the applicator can include any feasible number of rings, such as two (see FIGS. 2C, 4A-4B), four (FIG. 2B), etc. The term "distal" may generally refer to the portion of the applicator closest to the distal end (and closest to the treatment tissue / surface), and the term "proximal" may generally refer to the portion of the applicator relatively far from the distal end and the treatment tissue / surface. However, those skilled in the art will recognize that other terms can be used to identify and distinguish features of the applicator, including the proximal and distal rings. For example, the proximal and distal rings may be referred to as the first and second rings.

[0121] These rings (proximal and distal rings) may be formed from any suitable material. In at least one example, the proximal and distal rings may be formed from nitinol (e.g., nickel titanium). However, any other feasible material, such as stainless steel, may be used. As shown in the exemplary applicator, the proximal ring may have a larger diameter than the distal ring. In other examples, the proximal ring may have a smaller diameter than the distal ring.

[0122] The proximal and distal rings (and any intermediate rings) 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 ring may be an active area (e.g., electrically continuous), so that the outer circumference of the ring, rather than the inner arms (which may be insulated), forms the active area for applying electrical energy. In some examples, the proximal and distal rings may be retracted into the catheter body (not shown). An applicator may then be positioned at the treatment area. After applicator placement is confirmed, the proximal and distal rings may be deployed from the catheter.

[0123] In some examples, the ring electrode is not deployed from within the catheter body, but may be housed with the catheter body within the delivery catheter, and the distal end of the device (e.g., in this example, the ring electrode) 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 electrode) 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's body, with the distal end of the sheath positioned near the target area (e.g., in or near the left atrium, right atrium, in some examples). The elongated catheter body and electrode (e.g., ring electrode) may be inserted into the proximal valve of the guide sheath using an introducer (e.g., a plastic tube), and the device may slide distally within the sheath. In some examples, the delivery catheter holding the distal end (e.g., ring electrode) may be advanced to the target tissue and then held in place while the distal end is driven from the delivery catheter.

[0124] The proximal ring may include two or more lobes. Five lobes (petals) are shown in Figures 2A-2C. The proximal ring may be divided into two or more semicircular portions joined to the arms (see, for example, Figures 4A-4B). In some examples, the arms may be insulated. Similarly, the distal ring may include two lobes joined to the arms. In other examples, the proximal and distal rings may include any number of lobes and arms. In some cases, increasing the number of lobes can increase the flexibility of the proximal and distal rings, allowing them to more easily conform to different shapes of body vessels and allow the ring electrodes to better appose with the target tissue. In some examples, the arms and can be formed of nitinol or any other feasible material. The arms and can flexibly couple the proximal and distal rings to the elongated catheter body. 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, shaft, or elongated body shaft. 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.

[0125] In some examples, the applicator may be guided to the identified treatment area by an elongated catheter body and a proximal handle (such as the handle portion of the elongated applicator tool 102 shown in FIG. 1 ). In some examples, the applicator may also be guided by the use of a guidewire (not shown for simplicity) and / or fluoroscopy equipment. The devices (e.g., applicators) described herein may include a central lumen (e.g., through the elongated catheter body) that may allow for operation of the device over a guidewire. Alternatively, a rapid-exchange lumen may be present on the side of the applicator distal end.

[0126] 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 and distal rings) can be expanded. The proximal and distal rings (and any intermediate rings) can be flexibly coupled to and emerge from the elongate catheter body 230, and can be juxtaposed with the body vessel. The correct position of the applicator, including the ring electrodes, can be verified and / or the device can be repositioned before applying energy.

[0127] Nanosecond pulsed energy treatment of the body vessel can then be initiated. In some examples, the system 100 and applicator can be configured for bipolar operation, for example, between the proximal ring and the distal ring. In some examples, the proximal ring may be referred to as the cathode and the distal ring as the anode (or vice versa). In other examples, the proximal ring may be associated with a signal having a negative signal, and the distal ring may be associated with a signal having a positive signal. The proximal and distal rings can function as electrodes for delivering nanosecond pulsed energy. Electrodes carrying signals of opposite polarity can enable an electric field associated with pulsed therapy to be generated between the electrodes. In some examples, the system 100 (including the applicator) can be configured for monopolar operation. For example, the proximal and distal rings can be electrically coupled to each other, and a signal can be applied between the proximal and distal rings and a return electrode (e.g., another conductor, such as a portion of the elongated catheter body, or a conductive pad or electrode) that may contact the patient.

[0128] After delivery of the nanosecond pulsed energy treatment, the applicator can be moved to another area of ​​the body vessel or removed from the patient.

[0129] 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. Any of the devices described herein may be configured to treat the sidewall of a lumen and / or to treat a forward (distal) facing region of tissue, as described in more detail below.

[0130] Point-by-point treatment The devices described herein can be used for point-by-point treatment. For example, any of these devices can include a smaller electrode (e.g., a central electrode) or a subsection of the applicator area. For example, the devices described herein can be used to perform cardiac ablation to address various problems, such as atrial fibrillation, ventricular tachycardia, thickening of the ventricular wall, and the like, as well as ablation in other organs, such as the esophagus (e.g., Barrett's esophagus), the bronchi (e.g., chronic bronchitis, asthma, etc.). The same device can be configured to apply a larger area of ​​treatment, for example, using the entire applicator area, or a subsection of the applicator area can be used to apply a smaller treatment area appropriate for point-by-point treatment.

[0131] 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.

[0132] In general, the devices described herein may have radially separated active regions (and in some examples, a central electrode). These active regions may be formed of flexible wire that is exposed (uninsulated) along all or part of its circumferential length, forming a "petal" or loop shape. The applicator may be any suitable size; for example, the length of each petal's active region may be 5 mm to 3 cm (e.g., 7 mm to 1.5 cm, 8 mm to 12 mm, etc.), and the diameter of the (optional) central electrode may be 0.5 mm to 5 mm (e.g., 1 mm to 3 mm, etc.). Each of the curved active regions ("petals") in an example with three petals may extend approximately 120 degrees around a central region that includes the optional central electrode. In some examples, a central electrode, if present, may be configured to operate with a different polarity than one or more (or all) of the radially curved active regions, applying energy in a bipolar manner (between the central electrode and one or more active regions). In some examples, a central electrode is not included or used, and bipolar energy may be applied between any two of the curved active regions.

[0133] 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 during surgery, such as 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.

[0134] In any of these devices, the distance between the electrodes can be constant or variable, which determines the strength of the pulsed field at any given voltage, and therefore the size of the treatment area.

[0135] These devices and methods can be used in conjunction with cardiac mapping and navigation systems. For example, any of these devices and methods may be part of an ablation method for treating cardiac regions, including, but not limited to, pulmonary veins (or sinuses associated with pulmonary veins), and may 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.

[0136] 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.

[0137] Sensors including sensing electrodes may be used for navigation in addition to or instead of mapping. References contained herein to mapping or mapping / sensing electrodes may also refer to, and are intended to refer to, navigation (e.g., mapping / navigation). Thus, these devices and methods include using sensed electrical activity to create a map of tissue, such as the heart, and sensing electrodes may be used to assist in navigating an instrument to a treatment location.

[0138] 4A-4C illustrate an example of a device for delivering pulsed electric fields that may include mapping ("sensing") electrodes in addition to treatment electrodes according to the present disclosure. The devices described herein may be particularly well-suited for providing improved sensing (e.g., mapping, navigation, etc.) using multiple electrodes spanning a relatively large area while maintaining a small footprint. Notably, these devices may provide sensing electrodes on either side (outer and inner loops or lengths) of the treatment electrodes. The instruments described herein include an elongated body 403, the distal end of which is shown in FIG. 4A. The elongated body may be an elongated catheter body. In some examples, the elongated body may be part of an outer delivery catheter. In a non-deployed state (not shown), the applicator 400 may be configured to be fully or partially retained within the elongated body, which has a low profile that allows for easy insertion into the body and allows it to extend from and / or be expanded by retracting the elongated catheter body. For example, the applicator may include a plurality of arms 430, 430', 430" configured to extend diagonally from the elongate body when in a deployed state. The device also includes a first plurality of electrode lengths 411, 411', 411" extending between the plurality of arms and forming a first treatment electrode 410. In some examples, the first treatment electrode is also referred to as an "inner electrode" or "inner ring electrode" (when the applicator is deployed). Each of the first plurality of electrode lengths forms an arc that together form a ring that may be generally transverse to the longitudinal axis of the elongate body in FIGS. 4A-4C. The device also includes a second plurality of electrode lengths 421, 421', 421" that extend between the plurality of arms, e.g., in an arc, and form a second treatment electrode 420 located radially outward of the first treatment electrode when the applicator is expanded or deployed. In some examples, the second treatment electrode is also referred to as an "outer electrode" or "outer ring electrode." The device also includes multiple mapping electrodes 450 and / or sensing electrodes 450' disposed on the multiple arms. The mapping / sensing electrodes may be positioned radially outward of the first treatment electrode (e.g., between the first and second treatment electrodes) as shown.In some examples, the second plurality of electrode lengths may be oriented generally transverse to the longitudinal axis of the elongate body and form a ring located radially inward from the first treatment electrode when the applicator is deployed.

[0139] 4A-4B, the applicator arms of the device may include extension regions 431, 431′, 431″. The applicator arms of the device may be hollow (or solid) cylinders that are pre-bent, curved, and / or biased so that they bend at an angle relative to the longitudinal axis of the elongate body 403 when extended relative to the distal opening of the elongate body 403, as shown in FIGS. 4A-4C. In some examples, the arms may house portions of the electrical lengths that form the treatment electrodes. The multiple electrode lengths that form the first treatment electrode (and the multiple electrode lengths that form the second treatment electrode) may each be individually coupled to an electrical connector (e.g., wire, trace, etc.) or may be electrically coupled together. Each electrode of each of the multiple electrode lengths may be formed as a wire electrode, e.g., as a portion of a wire electrode that is uninsulated along all or a portion of its length.

[0140] When deployed, the extension regions of the device's arms may extend radially outward beyond the outer (e.g., second) treatment electrode, as shown. These extension regions may provide support or contact, along with additional space for one or more sensing (e.g., mapping) electrodes. In the example shown in Figures 4A-4C, mapping and / or sensing electrodes are positioned radially outward from the outer (deployed) treatment electrode between the first and second treatment electrode rings, on the arms, and on the extension regions of the arms.

[0141] The device may also include one or more central electrodes. For example, as shown in FIG. 4B, the device may include a central electrode 491 extending distally from the elongate body when the applicator is deployed, with the arms and first and second electrodes (or, in some embodiments, any additional electrodes forming an electrode ring similar to the first and second electrodes) surrounding the central electrode. The central electrode may be a treatment electrode. In some examples, the central electrode may be a mapping / sensing electrode or may be both a mapping / sensing electrode and a treatment electrode.

[0142] FIG. 4C shows an example of a device having the features of FIGS. 4A-4B, but with one of the arms 430′ shown transparent to illustrate example internal components, including one or more electrical connectors (e.g., wires) 483 connected to and / or forming the first electrode length 411 of the first treatment electrode 410, one or more electrical connectors (e.g., wires) 483′ connected to and / or forming the second electrode length 421 of the second treatment electrode 420, and one or more wires 485 coupled to the mapping electrodes 450, 450′. For example, each electrode length of each of the multiple electrode lengths may be coupled to or formed from an exposed or uninsulated portion of the wire 483, 483′. Generally, the arms 430, 430′, 430″ may be insulated and / or formed of a polymeric material. The arms may include one or more openings through which the internal wire forming the treatment electrode can pass. The wires within the arms are configured to slide at least slightly within the arms, allowing the wires to move longitudinally relative to one another to prevent breakage and relieve mechanical stress when the arms are transformed between a delivery configuration in which they are held straight within the elongate body 403, for example, and a deployed state in which they are angled relative to the elongate body.

[0143] In the deployed state, the arms may extend at an angle between about 20 degrees and 90 degrees relative to the longitudinal axis of the elongate body at the distal end region. In Figures 4A-4C, the arms (three arms are shown in this embodiment) extend at an angle of about 85 degrees relative to the longitudinal axis. In some examples, the angle may be between 30 degrees and 90 degrees, between 40 degrees and 90 degrees, between 45 degrees and 90 degrees, etc. In this example, all three arms are deployed at approximately the same angle, but in some examples, the arms may be configured to bend / deploy at different angles to "steer" the face of the applicator in a desired direction. In Figures 4A-4C, three arms are shown. As mentioned above, in some examples, fewer (e.g., two arms) or more than three (e.g., four arms, five arms, six arms, etc.) arms may be used. Any of these devices may include one or more spacers or guides 481 within the distal end region of the elongate body to maintain spacing between the arms and, in some embodiments, to accommodate movement of the arms, including insertion / removal of the arms into and / or from the distal end region of the elongate body. The guide / spacer may include a central region that couples to or engages with a central electrode 491, shown in FIGS. 4B-4C. The central electrode 491 may be configured as a post that forms additional mapping, sensing, and / or treatment electrodes. The guide / spacer may include one or more channels for each arm to allow longitudinal movement while preventing radial displacement of the arms within the elongate body.

[0144] The extension region 431, 431', 431'' of each arm may be configured to extend beyond the outer radius of the treatment electrode, allowing for a larger mapping area. In general, the use of dedicated tubular arms in which connectors (e.g., wires) and / or additional sensors (e.g., EM sensors) are located can be particularly beneficial, protecting the applicator, insulating the wires, and increasing the overall robustness of the device.

[0145] In any of these examples, the device may include at least one sensor (eg, electromagnetic sensor 487) in the arm, including, for example, in one or more (eg, all) extension regions 431, 431', 431'' of the arm.

[0146] The applicators described herein can be configured for bipolar operation. Pulse energy can be transferred, for example, between a first ring and a second ring. Thus, the first ring 410 can be associated with a signal having a first polarity (e.g., a positive signal), and the second ring 420 can be associated with a signal having a second polarity (e.g., a negative signal). In another example, the first ring 410 can be associated with a signal having a negative signal, and the second ring 420 can be associated with a signal having a positive signal. In another example, the applicator 400 can be configured for monopolar operation. For example, the first ring 410 and the second ring 420 can both be electrically coupled together, and a return electrode (e.g., on the elongated catheter body 403 or a conductive pad) can be used.

[0147] The applicator devices described herein may also be configured to include two or more treatment electrodes, as described above. For example, FIG. 5 shows an example of a device configured as a three-armed applicator similar to FIGS. 4A-4C, with a mapping and / or sensing electrode coupled to each arm 530, 530', 530''. The three treatment electrodes 510, 520, 540 form inner, middle, and outer electrode rings, respectively. As described above, each treatment electrode may be formed with multiple electrode lengths 511, 521, 541. In this configuration, mapping and / or sensing electrodes 550, 550', 550'' are positioned radially inward on each arm between the inner ring 510 and the middle ring 520, between the middle ring 520 and the outer ring 540, and radially outward from the outer ring 540, e.g., on the extended arm region 531. The example shown in FIG. 5 may (optionally) include a central electrode 591 and / or a spacer / guide 581.

[0148] The examples shown in Figures 4A-4C and 5 are depicted as single-layer (even funnel-shaped) ablation devices including six or more mapping electrodes or sensors, e.g., for detecting intracardiac electrograms (EGMs). In some examples, the device may instead be configured to include multiple layers, such as a two-layer applicator as shown in Figure 6. A two-layer structure may include multiple treatment electrodes positioned longitudinally offset from one another but having the same or nearly the same (e.g., not substantially different) radii. A multi-layer device may include multiple struts (e.g., lateral or connecting struts) extending between a first (e.g., upper or more distal) treatment electrode and a second (e.g., lower or more proximal) treatment electrode. Figure 6 also illustrates example locations of sets or subsets of sensing electrodes (e.g., mapping electrodes). Sensing electrodes can be provided in various locations, including around the periphery of the device. These devices shown in the example of FIG. 6 may include multiple mapping electrodes 650, 650', 650'', 650''', 650''', 650'''', 650'''', 650'''' on the laterally facing sides of the applicator, e.g., posts 635, 635', 635'', 635'''', 635'''', and may also include multiple sensing / mapping electrodes 651, 651' on, e.g., a first (e.g., upper) set of arms, thereby allowing for more accurate rendering in 3D.

[0149] In some examples, the struts 635, 635', 635", 635'", 635"" extend from the first (e.g., upper) set of arms 630, 630', 630" and / or the second (e.g., lower) set of arms 631, 631', 631". The multiple electrode lengths 614, 614', 614", 614'", 614"", 614"", 614"" forming the distal treatment electrodes and the multiple electrode lengths 612, 612', 612", 612'", 612"", 612"", 612"" forming the proximal treatment electrodes may be connected at either end of a corresponding connecting strut.

[0150] For example, the device for delivering pulsed electric fields shown in FIG. 6 may include an elongate body 603 the same or similar to those described above, and in some embodiments, may be configured such that an applicator (including electrodes) can be at least partially retracted within a distal end region of the elongate body for delivery to or navigation to the heart or other target body region. The device may also include a first plurality of arms 630, 630', 630" configured to extend obliquely from the elongate body when deployed, and a second plurality of arms 631, 631', 631" configured to extend obliquely from the elongate body when deployed. In some examples, the upper arms may be rotationally offset from the lower arms, as shown in FIG. 6. The device may also include a first plurality of electrode lengths 614, 614', 614'', 614''', 614'''', 614'''', 614''''' extending between the first plurality of arms 630, 630', 630'' to form the first treatment electrode 610, and a second plurality of electrode lengths 612, 612', 612'', 612'''', 612'''', 612'''', 612'''''' extending between the second plurality of arms 631, 631', 631'' to form the second treatment electrode 620 axially spaced (e.g., axially spaced) from the first treatment electrode 610. The multiple struts may extend between the first and second treatment electrodes, for example, parallel or substantially parallel (e.g., within ±1°, 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°, 10°, etc.) to the distal end region of the elongate body. As previously described, the device may include multiple mapping and / or sensing electrodes, and in some examples, these mapping electrodes may be on struts of the multiple struts. In the example shown in FIG. 6, the device also includes a central electrode 691, which may be configured as, for example, a sensing electrode (e.g., a mapping electrode), and a spacer (not shown) integrally formed with the device and which may be similar to the spacer shown in FIG. 5. Alternatively, this central electrode 691 may be used for therapy or treatment applications (e.g., in combination with the first and second treatment electrodes).

[0151] The struts 635 in the example of FIG. 6 can stabilize the spacing and / or shape between the treatment electrodes 610, 620.

[0152] In operation, the above-described device can be used to ablate relatively large regions of tissue (e.g., the heart). FIG. 7 illustrates an example of tissue ablation using a device similar to that shown in the examples of FIGS. 4A-4C, 5, or 6 and described above. For example, FIG. 7 shows an example of porcine heart tissue that has been treated by application of energy as described herein to form ablated regions. Three exemplary ablated regions 742, 742', and 742'' are shown. Energy was applied to the surface of the tissue and was applied via bipolar application between a central electrode and one or more circumferential treatment electrodes, or between two (or more) circumferential treatment electrodes.

[0153] These devices may be configured for magnetic sensing, electrical property (e.g., impedance-based) sensing, or both. As mentioned above, sensing may be utilized for navigation and / or mapping. In some examples, the applicator may be coupled to a third-party mapping and / or navigation system (e.g., the Carto™ system, the Navx™ system, etc.), for example, by directly or indirectly providing input to the mapping system from sensing / mapping electrodes. The applicators described herein may be used in conjunction with a separate mapping catheter. For example, tissue may be mapped using a mapping catheter and system that can generate a map or model of tissue, such as cardiac tissue, including a target 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 may 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 / navigate 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 examples, the devices described herein may include a mapping system or subsystem integrated into the device.

[0154] For example, the device may include an applicator similar to that described above, including both multiple treatment electrodes and sensing / mapping electrodes. The applicator may be coupled to a nanosecond pulsed energy treatment system, 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 may be separate from the mapping system and / or an output, which may include one or more displays, that 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, the device may include a pulsed energy treatment system and an output that may be used in combination with a separate mapping system / subsystem. Alternatively, in some examples, the mapping system / subsystem may be included as part of the device. In any of these devices, a separate mapping catheter may be coupled to the mapping system / subsystem.

[0155] 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.

[0156] 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.

[0157] For example, in contrast to the bulky tubular electrodes used with RF ablation, the use of such low-profile wires of the present disclosure allows the devices described herein to have a relatively smaller crossing profile, which may allow 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, thereby simplifying and / or enabling certain procedures.

[0158] 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.

[0159] As described above, in any of these devices, the electrode assembly may include multiple petals formed of wire loops arranged around an expandable member, such as a balloon or an expandable frame, which may be expandable itself or may be part of the expandable frame. Each petal may include an active region of the electrode assembly. The wire loops forming the petals may include insulated leg regions on either side of the active region, which may extend generally longitudinally. These legs are also referred to herein as ribs. The active regions of each petal may be at least partially circumferentially arranged around the expandable member such that all of the active regions of the electrode assembly together surround (or at least partially surround) the expandable member. Each active region is flexible and configured to change shape, such that as the expandable member expands (and / or contracts), the active region increases (and / or decreases) its circumferential length, and the radial circumference defined by the active regions of the electrode assembly increases and / or decreases with the expansion or contraction of the expandable member. This radial expansion enables treatment of anatomical structures (lumens, walls, etc.) of various sizes. As previously mentioned, in any of these examples, the active regions may each include a hinge region, hi some examples, the hinge region may be formed as a flexible bend in the active region of the loop of the electrode assembly.

[0160] For example, FIGS. 8A and 8B show a single loop (or petal) 800 of an electrode assembly, with FIG. 8A showing the loop in an unexpanded configuration and FIG. 8B showing the same loop in an expanded configuration. In FIG. 8A, the loop includes an active region 822, which is an exposed (uninsulated) wire extending between two insulating regions 871, 871′. The active region 822 may be flexible, for example, including or configured to provide a flexible bend 812, 812′. The active region of the loop may be disposed on and / or at least partially attached to the expandable member. As the expandable member expands, the loop may transition from the narrow shape shown in FIG. 8A to the wide shape shown in FIG. 8B. The flexible bend 812 may have an initial angle (e.g., between about 90 degrees and 160 degrees) and may increase as the expandable member expands to an expanded angle greater than the initial angle (e.g., up to about 180 degrees). Specifically, as shown in Figures 8A-8B, the active area changes shape to increase the effective radial circumferential distance 860, 860' of the electrode assembly of which it forms a part.

[0161] In any of these devices, the electrode assembly can include multiple circumferentially arranged petals, as shown in FIG. 8C. Additionally, as described above, the electrode assemblies can be positioned adjacent to one another along the length of the expandable member. The spacing between adjacent active regions of the electrode assemblies can be approximately the same along the length of the active regions in both the unexpanded and expanded configurations, for example, as the expandable member is expanded.

[0162] In FIG. 8C, the device includes four electrode assemblies 822, 823, 824, and 825 formed from multiple small diameter wires (e.g., wires having a diameter of 0.015 inches or less). In FIG. 8C, the wires are disposed on an expandable balloon 828. Each electrode assembly forms three petals disposed on the balloon. In FIG. 8C, four electrode assemblies are shown with three active areas, one for each petal. The active area of ​​each electrode assembly includes a flexible bend 812 approximately midway between the active areas. In this example, the electrode assemblies are paired, such that the first electrode assembly 822 and the third electrode assembly 824 have a first polarity, and the second electrode assembly 823 and the fourth electrode assembly 825 have a second polarity. In some examples, the first electrode assembly and the third electrode assembly may be electrically coupled, and the second electrode assembly 823 and the fourth electrode assembly 852 may be electrically coupled. Alternatively, the first, second, third, and fourth electrode assemblies may be separately addressable. The balloon is disposed at an end region of an elongate body (not shown in FIG. 8C), such as the elongate body of a catheter. The balloon can be deflated to reduce the radial profile (e.g., diameter) of the device, and inflated to increase the radial profile. In FIG. 8C, the device is shown with the balloon in a relatively deflated state. The laterally spaced active regions of the electrode assemblies 822, 823, 824, 825 may be separated by, for example, about 1 mm or less (e.g., 0.5 mm) to 10 mm. The active regions in this example are surrounded on both sides by insulators 871, 871′.

[0163] 8A and 8B show an example of a device having an elongate member (e.g., shaft) 829 and four electrode assemblies 822, 823, 824, 825, each with four petals forming an active region, each including flexible bends 812, 813, 814, 815 disposed on an expandable balloon 828. The wires forming the electrode assemblies are shape-memory alloy (e.g., nitinol) wires that are looped circumferentially around a compliant or semi-compliant balloon 828 (forming petals). As shown in FIG. 8D, four identical petals are disposed around the balloon. In some embodiments, each loop of nitinol wire may be configured to form a V-shape (flexible bend), as shown in FIG. 8D. The V-shape has its smallest angle when the wire is resting on an uninflated or minimally inflated balloon (FIG. 8D). As the balloon inflates, the angle increases, and the wire straightens, as shown in FIG. 8E. The V-shape allows the wires to expand as the balloon inflates, thereby preventing the balloon from being restricted in inflation as would occur if the electrode assembly wires did not have flexible bends. In various examples, the balloon also acts as an insulator to prevent arcing between electrodes of opposite polarity. For example, the balloon may be formed of an electrically insulating material.

[0164] Figure 8E shows the same device as Figure 8D with balloon 828 inflated. As noted above, the active area of ​​each petal forming the electrode assembly transitions from a first bend angle 812, 813, 814, 815 shown in Figure 8D to an open (large) bend angle 812', 813', 814', 815' shown in Figure 8E.

[0165] The strength of the electric field between the active regions of the electrode assembly (e.g., wires) can be varied by varying the applied voltage and / or varying the distance between the wires. As shown in Figures 8D and 8E, in some embodiments, the distance between the active regions is fixed and cannot be changed, i.e., is not adjustable. Furthermore, the device may be configured such that the spacing or distance between the active regions remains constant along the length of the active regions, even as the shape of each active region changes, such as when a flexible flexure bends during balloon inflation / deflation.

[0166] Four petals are shown in Figures 8D-8E. Generally, any suitable number of petals can be used. For example, to create circumferential ablation without rotating the catheter, at least two petals are used. In some instances, three, four, five, or six (or more) petals may be used and positioned around the balloon. While a greater number of petals can better maintain the distance between the wires, a larger number of petals may increase the cross-sectional profile of the device and potentially increase the minimum size of the device due to the space required to fit within the device shaft 829.

[0167] 9A-9C illustrate other examples of devices described herein. For example, in FIG. 9A, device 900 includes an expandable balloon 928 at the distal end region of elongate member 929. Distal tip 931 extends distally from the balloon. In some examples (see, e.g., FIGS. 8C-8E), the elongate shaft may extend through the balloon. In this example, the balloon is transparent and has six electrodes (three pairs) 922, 923, 924, 925, 926, and 927 disposed on the balloon, forming four petals. The wires are organized into four ribs 939 and 940. FIGS. 9B and 9C illustrate another example of a device 900′ similar to that shown in FIG. 9A, except that balloon 928′ is opaque. In this example, six electrodes (three pairs) 922, 923, 924, 925, 926, and 927 also form four petals disposed on the balloon. Each of the six active areas of each electrode assembly includes flexible bends 912, 913, 914, 915, 916, and 917, as described above and shown in more detail in FIG. 9C. Any number of electrode assemblies (e.g., wires) can be used as appropriate. For example, if a larger area needs to be ablated, the number of electrode assemblies can be increased or the distance between the active areas of the electrode assemblies can be increased. For example, if the desired ablation area is 10 mm long and the distance between the active areas of the electrode assemblies is 1 mm, 11 electrode assemblies (wires) can be placed on the balloon. As will be appreciated by those skilled in the art, any suitable number of wires and distances between the wires can be implemented.

[0168] In any of these devices, the electrode assembly may be coupled to the balloon along all or part of the length of the electrode assembly wire. In some examples, the electrode assembly / wire loops of the assembly are attached to the balloon at several attachment regions, such as flexible bends and / or ribs. In some examples, the wire loops are slidably attached to the balloon (e.g., via screw attachments, etc.). In some examples, separate attachment regions connect first, second, etc. loops and / or ribs. In some examples, the electrode assembly is not attached to the expandable member. The electrode assembly may be shape-set, for example, into an expanded or unexpanded configuration.

[0169] Methods of using the devices of the present disclosure The device described herein can comprise or be included as part of the catheter used during minimally invasive procedures, or as part of the device utilized during surgery.As mentioned above, the device described herein can be used to treat body lumen by applying pulsed submicrosecond (for example, nanosecond) energy.For example, these devices can be used to treat arterial stenosis or restenosis.In some cases, these devices can be used to treat Barrett's esophagus.

[0170] Generally, the methods and devices described herein may be used to apply 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.

[0171] In some examples, the devices described herein may be inserted through and / or used with a catheter, introducer, 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.

[0172] 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, specifically nanosecond pulsed electrical energy, and treating the tissue. In some examples, the devices described herein may be used to treat the prostate, such as for treating 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.

[0173] Other examples of tissues that can 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.

[0174] Cardiac Ablation Methods The methods and devices described herein can use pulsed electrical energy (e.g., microsecond, submicrosecond, nanosecond, etc. pulsed electrical energy) to treat atrial fibrillation, ventricular tachycardia, and other heart-related diseases. 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.

[0175] For example, these methods and devices may be used to perform 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.

[0176] 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.

[0177] One exemplary use of the applicator 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.

[0178] 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.

[0179] The electrode may be pressed against the left atrial wall, particularly surrounding the pulmonary veins. Proper electrode positioning can be aided by the 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 electrode and the left atrial wall can be verified via impedance readings, for example, by transmitting low-amplitude non-therapeutic electrical "test" signals. The active electrode and / or electrodes used for impedance-based localization and / or contact assessment before ablation can be used for post-ablation signal acquisition. For example, the absence of an electrical signal from cardiac tissue may indicate an effective acute effect from the ablation. After proper electrode positioning and contact are confirmed, energy (nanosecond pulse, microsecond pulse, 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 the energy application over additional left atrial areas surrounding other pulmonary veins.

[0180] 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 μs or less, about 2 μs or less, about 3 μs or less, about 4 μs or less, about 5 μs or less, or more than 5 μs. 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.

[0181] 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.

[0182] 10 is a flow diagram illustrating one example of a method 1000 for delivering pulsed electrical therapy to a selected treatment area of ​​a patient. Some examples may implement the methods described herein with additional operations, fewer operations, operations in a different order, operations in parallel, and some operations differently. Method 1000 may be used to treat atrial fibrillation, ventricular tachycardia, or other cardiac disorders. Method 1000 is not limited to cardiac applications, but rather may be used to treat various body vessels.

[0183] In FIG. 10 , method 1000 can begin when a treatment area is identified in block 1002. Block 1002 may be optional, as indicated by the dashed line in FIG. 10 . 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.

[0184] In block 1004, 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. 4A-4C, 5A-5B) within the identified treatment area. For example, the applicator may be positioned by extending a spaced-apart first 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).

[0185] In block 1006, 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 active areas of the first and second electrodes 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 vascular 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 operatively connected to the elongate catheter body so that they 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.

[0186] Once the electrodes are placed in contact with tissue, in some cases, the spacing (e.g., longitudinal spacing) between the electrodes (e.g., sets of electrodes) on the applicator can be adjusted to vary the density of the pulsed electric field or to accommodate changing tissue shape and topology.

[0187] In optional block 1007, contact with tissue may be confirmed by any suitable method (e.g., impedance testing, electrogram, imaging, etc.). In this optional step, a low-level or low-amplitude signal (e.g., voltage and / or current) may be provided to the electrode. System 100 may determine and / or measure the impedance associated with the electrode based on the signal provided to and returned from the electrode. Contact with tissue may be confirmed when the impedance is within an expected value.

[0188] In any of these methods, tissue, particularly tissue surrounding an electrode (e.g., an electrode used to administer treatment), can be mapped 1011 using mapping electrodes on the device, including, for example, radially opposite the treatment electrode, as shown in Figures 3-6. At block 1008, 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.

[0189] 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 can 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 Figures 4A-4C, 5A-5B, etc.) without the need to move the device to achieve near-complete or complete circumferential treatment.

[0190] In block 1010, 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.

[0191] 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. All publications and patent applications mentioned herein are 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. Furthermore, it should be understood that all combinations of concepts described in this disclosure (provided those concepts are not mutually inconsistent) are contemplated as part of the inventive subject matter disclosed herein and can be used to achieve the advantages described herein.

[0192] 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.

[0193] 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. A program that executes the present methods and systems may include separate program code containing a set of instructions to perform a desired operation, or may include multiple modules that perform such sub-operations of the operation, or may be part of a single module of a larger program that provides the operation. The modular structure makes it easy to add, delete, update, and / or modify internal modules and / or features within the modules.

[0194] 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 polarities as a function of encoder signal feedback to achieve a desired angle, velocity, or force.

[0195] Particular examples may relate to machine-readable media (e.g., computer-readable media) or computer program products containing program instructions and / or data (including data structures) for performing various computer-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. The machine-readable media described above may include any suitable medium that can store and transmit information in a form accessible by a processing device, 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. 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.

[0196] 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.

[0197] When a feature or element is referred to herein as being "on" another feature or element, it can be directly on the other feature or element, or intervening features and / or elements may be present. In contrast, when a feature or element is described as being "directly on" another feature or element, there are no intervening features or elements present. Also, when a feature or element is referred to as being "connected," "attached," or "coupled" to another feature or element, it will be understood that it can be directly connected, attached, or coupled to the other feature or element, or that intervening features or elements may be present. In contrast, when a feature or element is referred to as being "directly connected," "directly attached," or "directly coupled" to another feature or element, there are no intervening features or elements present. Although described or illustrated with respect to one example, features and elements so described or illustrated may be applicable to other examples. Furthermore, those skilled in the art will understand that references to structures or features located "adjacent" to other features may have overlapping or underlying portions of the adjacent feature.

[0198] 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 unless the context clearly dictates otherwise. It will be further understood that as used herein, the terms "comprises" and / or "comprising" 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 " / ."

[0199] Spatially relative terms, such as "under," "below," "lower," "over," and "upper," may be used herein as illustrated to facilitate the description of one element or feature's relationship to another. It will be understood that spatially relative terms are intended to encompass various 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 were inverted, elements described as being "below" or "directly below" other elements or features would then be positioned "above" the other elements or features. Thus, the exemplary term "under" can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations), and the spatially relative descriptions used herein will be interpreted accordingly. Similarly, terms such as "upward," "downward," "vertical," and "horizontal" are used herein for descriptive purposes only, unless otherwise noted.

[0200] In this specification, the terms "first" and "second" may be used 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 described below may be referred to as a second feature / element, and similarly, a second feature / element described below may be referred to as a first feature / element without departing from the teachings of the present invention.

[0201] Throughout this specification and the claims that follow, unless the context dictates otherwise, the word "comprises" and variations such as "includes" and "comprising" mean that various components may be used jointly in methods and articles (e.g., devices and apparatuses that include methods). For example, the term "comprising" is understood to mean including the stated elements or steps, but not excluding other elements or steps.

[0202] Generally, any of the apparatuses 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.

[0203] As used in this specification and claims, including those used in the examples, and unless specifically stated otherwise, all numbers may be read as preceded by the word "about" or "approximately," even if the term does not explicitly state otherwise. When describing a size and / or location, the term "about" or "approximately" may be used to indicate that the stated value and / or location is within a reasonably expected range of values ​​and / or locations. For example, a numerical value may have a value of ±0.1% of the stated value (or numerical range), ±1% of the stated value (or numerical range), ±2% of the stated value (or numerical range), ±5% of the stated value (or numerical range), ±10% of the stated value (or numerical range), etc. Numerical values ​​provided herein should be understood to include approximate ranges or approximations of that value, unless the context dictates otherwise. For example, if a value of "10" is disclosed, then a value of "about 10" is also disclosed. Numeric ranges described herein are intended to include all subranges encompassed therein. It is also understood that where a value is disclosed, the value "less than or equal to" the value, the value "greater than or equal to" the value, and possible ranges between the values ​​are also disclosed, as would be understood by one of ordinary skill in the art. For example, if a value "X" is disclosed, not only is "less than or equal to X" disclosed, but also "greater than or equal to X" (e.g., if X is a numeric value). It is also understood that throughout this application, data is provided in many 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 not only values ​​between 10 and 15, but also values ​​greater than 10, greater than or equal to 10, less than 10, less than or equal to 10, and values ​​between 10 and 15 are considered disclosed. 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.

[0204] 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 described by 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, this description is provided primarily for illustrative purposes and should not be construed as limiting the scope of the invention to that described in the claims.

[0205] The examples and drawings included herein are by way of illustration, not limitation, and illustrate specific embodiments in which the 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 inventive subject matter, if more than one is in fact disclosed, may be individually or collectively referred to herein by the term "invention" for convenience only, without intending to intentionally limit the scope of this 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, comprising: A long, slender body and a plurality of arms configured to extend obliquely from the elongate body in a deployed state; a first plurality of electrode lengths extending between the plurality of arms and forming a first treatment electrode; a second plurality of electrode lengths extending between the arms and defining second treatment electrodes positioned radially outward of the first treatment electrodes in a deployed state; a first treatment electrode and a second treatment electrode, the first treatment electrode and the second treatment electrode being spaced apart from each other; and a second treatment electrode and a third treatment electrode and a fourth treatment electrode being spaced apart from each other; and a second treatment electrode and a fourth ...

2. The device of claim 1 further comprising a center electrode.

3. The device of claim 2 , wherein the central electrode comprises a mapping electrode and / or a sensing electrode, the central electrode being configured to extend distally from a distal end of the elongate body.

4. 4. The device of claim 2 or 3, wherein the central electrode further comprises a central treatment electrode, the central treatment electrode configured to operate at a different polarity than at least one of the first or second treatment electrodes.

5. The device of any one of claims 1 to 4, wherein the one or more mapping and / or sensing electrodes on the extension region include an electromagnetic sensor coupled to the extension region of one or more of the plurality of arms.

6. 6. The device of claim 1, wherein at least some of the plurality of arms include a hollow insulating member through which at least a portion of the first electrode or the second electrode and / or electrical connector extends or passes.

7. The apparatus of any preceding claim, wherein each of the first plurality of electrode lengths forms an arc, and the arcs of the first plurality of electrode lengths together encircle the elongate body.

8. The device of any preceding claim, wherein the arms are pre-bent or biased to bend obliquely relative to a longitudinal axis of the elongate body when extended from the elongate body.

9. The device of claim 8 , wherein at least one of the plurality of arms is configured to bend at a different angle than at least one other arm of the plurality of arms.

10. 10. The device of claim 1, wherein the plurality of arms includes at least three arms, and the device further includes a third plurality of electrode lengths extending between the three arms to form a third treatment electrode.

11. 1. A device for delivering a pulsed electric field, comprising: A long, slender body and a first plurality of arms configured to extend obliquely from the elongate body in a deployed state; a second plurality of arms configured to extend obliquely from the elongate body in a deployed state; a first plurality of electrode lengths extending between the first plurality of arms and forming a first treatment electrode; a second plurality of electrode lengths extending between the second plurality of arms and forming a second treatment electrode axially spaced from the first treatment electrode by a plurality of struts; wherein the plurality of struts extend substantially parallel to a distal end region of the elongate body between the first and second treatment electrodes; and one or more mapping and / or detection electrodes on at least some of the struts.

12. 12. The device of claim 11, wherein the one or more mapping and / or sensing electrodes comprise a plurality of mapping and / or sensing electrodes, at least some of the plurality of mapping and / or sensing electrodes being disposed on either or both of the first plurality of arms and the second plurality of arms.

13. 13. The apparatus of claim 11 or 12, wherein some of the plurality of struts are coupled to at least one of the first plurality of arms and the second plurality of arms.

14. An apparatus according to any of claims 11 to 13, wherein the first plurality of arms are rotationally offset from the second plurality of arms.

15. 15. The device of claim 11, wherein some of the first and second pluralities of arms are configured to transition from an undeployed state, in which each arm of the first and second pluralities is at least partially within the elongate body, to a deployed state, in which each arm of the first and second pluralities extends obliquely from the elongate body.

16. 16. The device of claim 11, wherein some of the first and / or second plurality of arms are configured to extend from the elongate body at an angle between 20 and 90 degrees relative to the elongate body in a deployed state.

17. The device of any of claims 11 to 16, further comprising a central electrode configured to extend distally from the distal end of the elongate body, the central electrode comprising a mapping electrode and / or a sensing electrode.

18. The device of any of claims 11-16, further comprising a central electrode configured to extend distally from the distal end of the elongate body, the central electrode comprising a central treatment electrode.

19. 20. The device of claim 18, wherein the device is configured to apply bipolar energy 1) between the central electrode and at least one of the first plurality of electrode lengths, 2) between the central electrode and at least one of the second plurality of electrode lengths, or 3) between at least one of the first plurality of electrode lengths and at least one of the second plurality of electrode lengths.

20. 20. The device of any one of claims 11 to 19, wherein substantially parallel to the distal end region of the elongate body is up to plus / minus 10 degrees from a longitudinal axis of the distal end region of the elongate body.

21. 1. A device for delivering a pulsed electric field, comprising: A long, slender body and a balloon on the elongate body; a first electrode including a first plurality of wire loops, each wire loop of the first plurality of wire loops extending from the elongate body to form a petal around the balloon, and further wherein each wire loop of the first plurality of wire loops has a first active region extending along at least a portion of the length of each first wire loop; a second electrode including a second plurality of wire loops, each wire loop of the second plurality of wire loops extending from the elongate body, and each wire loop of the second plurality of wire loops having a second active region extending along at least a portion of the length of each second wire loop; the first electrode is laterally offset from the second electrode along the length of the balloon, and further wherein the first active region and the second active region each include a flexible bend, the angle of the flexible bend configured to expand as the balloon expands.

22. 22. The apparatus of claim 21, wherein at least one or both of the first and second plurality of wire loops includes between 2 and 5 loops.

23. 23. The device of claim 21 or 22, wherein each wire loop of the first plurality of wire loops and each wire loop of the second plurality of wire loops is bonded to an outer surface of the balloon at one or more locations.

24. 24. The device of any one of claims 21 to 23, wherein each wire loop of the first plurality of wire loops and each wire loop of the second plurality of wire loops is slidably coupled to an outer surface of the balloon.

25. The device of any one of claims 21 to 24, wherein each of the first and second active regions is bounded on either side by an insulating region.

26. 26. The apparatus of claim 21, wherein a first active area of ​​each wire loop of the first plurality of wire loops is spaced a fixed distance from a second active area of ​​each wire loop of the second plurality of wire loops.

27. 26. The device of any one of claims 21 to 25, wherein the first electrode and the second electrode are each formed from a wire having a diameter of less than 0.2 mm.

28. 28. The apparatus of any one of claims 21 to 27, wherein the first electrode is configured to have a first polarity and the second electrode is configured to have a second polarity.

29. 29. The device of any of claims 21-28, wherein the first electrode wire loops and the second electrode wire loops include distal regions configured as hinges that expand or contract with expansion or contraction of the balloon.

30. 30. The device of any one of claims 21 to 29, wherein the plurality of wire loops of the first electrode and the plurality of wire loops of the second electrode are arranged around the entire circumference of the balloon.

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