Neuromodulation catheter including stimulation and ablation electrodes

Abstract

A neuromodulation system includes a neuromodulation catheter and a controller. The neuromodulation catheter includes a distal catheter portion configured to transform from a relatively low profile configuration to an expanded configuration. The distal catheter portion includes a first elongate body and a second elongate body. The second elongate body is configured to be spaced from the first elongate body in the expanded configuration. The neuromodulation catheter further includes a first electrode array disposed on the first elongate body, and a second electrode array disposed on the second elongate body. The controller is configured to generate an ablation signal configured to be delivered by the first electrode array, and generate a stimulation signal configured to be delivered by the second electrode array.

Description

NEUROMODULATION CATHETER INCLUDING STIMULATION AND ABLATION ELECTRODES

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 644,052, filed May 8, 2024, the entire content of which is incorporated herein by reference.TECHNICAL FIELD

[0002] The present disclosure generally relates to neuromodulation.BACKGROUND

[0003] A denervation procedure may include ablating target nerves, for example, by delivering ablative energy to a target site via a catheter. For example, renal denervation may include ablating renal nerves.SUMMARY

[0004] In general, the present disclosure describes neuromodulation catheters including a dual-body distal portion including stimulation and ablation electrodes.

[0005] Neuromodulation catheters may be used to deliver neuromodulation therapy, for example, by delivering energy to ablate a nerve via at least one ablation electrode. In some examples, a neuromodulation catheter includes a distal portion configured to transform from a relatively low-profile configuration to a deployed configuration. In the deployed configuration, the distal portion may define a loop, a helical, or a spiral configuration (e.g., one or more loops, helices, or spirals). An electrode array is disposed on the distal portion. Impedance may be used to monitor and guide a denervation procedure. For example, an electrode impedance may be measured in course of denervation, for example, to determine lesion development during denervation. In the deployed configuration, the at least one electrode contacts blood and vessels. Because blood has a higher conductance than vessels, impedance measured in the deployed configuration may exhibit a greater sensitivity to blood contact than to vessel contact.

[0006] In some examples, devices, systems, and techniques according to the present disclosure deliver ablative energy and stimulation using a combined apparatus. For example, an example neuromodulation catheter may include a first electrode array and a second electrode array. At least one electrode of the first electrode array is configured to deliver an ablation signal, and at least one electrode of the second electrode array is configured todeliver a stimulation signal. An extent of denervation may be determined by detecting a physiological response or a change in physiological response to the stimulation signal after ablation. The first electrode array is disposed on a first elongate body, and the second electrode array is disposed on a second elongate body spaced from the first elongate body. The first electrode array may be offset from the second electrode array. Spacing and / or offsetting the electrodes may prevent or reduces effects of polarization on ablation electrodes, which in turn may shorten procedure time by delivering stimulation during or interleaved with ablation. The first electrode array and the second electrode array may be used to deliver a variety of stimulation patterns, for example, to incorporate a stimulation period within an ablation pattern. Further, the first elongate body and second elongate body may be positioned to deliver a stimulation signal from electrodes relatively close to electrodes used to deliver an ablation signal. Thus, the stimulation signal may be delivered to target nerves substantially within an ablation region to which an ablation signal is delivered.

[0007] In some examples, a neuromodulation system includes a neuromodulation catheter and a controller. The neuromodulation catheter includes a distal catheter portion configured to transform from a relatively low profile configuration to an expanded configuration. The distal catheter portion includes a first elongate body and a second elongate body. The second elongate body is configured to be spaced from the first elongate body in the expanded configuration. The neuromodulation catheter further includes a first electrode array disposed on the first elongate body, and a second electrode array disposed on the second elongate body. The controller is configured to generate an ablation signal configured to be delivered by the first electrode array, and generate a stimulation signal configured to be delivered by the second electrode array.

[0008] In some examples, a neuromodulation catheter includes a distal catheter portion configured to transform from a relatively low profile configuration to an expanded configuration. The distal catheter portion includes a first elongate body and a second elongate body. The second elongate body is configured to be spaced from the first elongate body in the expanded configuration. The neuromodulation catheter further includes a first electrode array disposed on the first elongate body, and a second electrode array disposed on the second elongate body. The neuromodulation catheter further includes a first electrode array disposed on the first elongate body and configured to deliver an ablation signal, and a second electrode array disposed on the second elongate body and configured to deliver a stimulation signal.

[0009] In some examples, a method includes delivering, by a first electrode array disposed on a first elongate body of a neuromodulation catheter, an ablation signal to a targetsite, the neuromodulation catheter being placed in a vessel of a patient. The method further includes delivering, by a second electrode array disposed on a second elongate body of the neuromodulation catheter, a stimulation signal to the target site, the neuromodulation catheter being placed in the vessel of the patient. The method further includes determining, by processing circuitry, a physiological response to the stimulation signal.

[0010] Further disclosed herein is a neuromodulation system that includes a neuromodulation catheter and a controller, wherein the neuromodulation catheter includes a distal catheter portion configured to transform from a relatively low profile configuration to an expanded configuration, wherein the distal catheter portion includes a first elongate body and a second elongate body, wherein the second elongate body is configured to be spaced from the first elongate body in the expanded configuration, wherein the neuromodulation catheter further includes a first electrode array disposed on the first elongate body, and a second electrode array disposed on the second elongate body, and wherein the controller is configured to generate an ablation signal configured to be delivered by the first electrode array, and generate a stimulation signal configured to be delivered by the second electrode array.

[0011] The details of one or more examples of the techniques of this disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques will be apparent from the description and drawings, and from the claims.BRIEF DESCRIPTION OF DRAWINGS

[0012] FIG. 1 A is a diagram illustrating an example system including a catheter configured to deliver neuromodulation therapy, a computing device, and a controller.

[0013] FIG. IB is a diagram illustrating a partial side view of the catheter of FIG. 1 A in an expanded configuration.

[0014] FIG. 2A is a diagram illustrating a side view of an example monopolar delivery configuration of the second electrode array in the expanded configuration of the catheter of FIG. IB.

[0015] FIG. 2B is a diagram illustrating a side view of an example bipolar delivery configuration of the second electrode array in the expanded configuration of the catheter of FIG. IB.

[0016] FIG. 2C is a diagram illustrating a side view of an example bipolar delivery configuration of the first electrode array and the second electrode array in the expanded configuration of the catheter of FIG. IB.

[0017] FIG. 3 is a diagram illustrating a cross-sectional view of an example elongate body including a shape memory wire defining a groove.

[0018] FIG. 4 is a timing diagram illustrating comparing an example scheme for delivering ablation and stimulation for neuromodulation including separate ablation and stimulation sessions.

[0019] FIG. 5 is a timing diagram illustrating comparing an example scheme for delivering ablation and stimulation for neuromodulation including combining ablation and stimulation sessions.

[0020] FIG. 6 is a block diagram illustrating an example configuration of the computing device of FIG. 1.

[0021] FIG. 7 is a flow diagram illustrating an example technique for neuromodulation.

[0022] FIG. 8 illustrates an example technique for accessing a renal artery and modulating renal nerves with a neuromodulation catheter in accordance with some examples of the present disclosure.

[0023] FIG. 9 is a conceptual illustration of an example sympathetic nervous system (SNS) illustrating how the brain communicated with the body via the SNS.

[0024] FIG. 10 is an enlarged anatomic view of nerves innervating a left kidney to form the renal plexus surrounding the left renal artery.

[0025] FIG. 11 is an anatomic view of a human body depicting neural efferent and afferent communication between the brain and kidneys.

[0026] FIG. 12 is a conceptual view of a human body depicting neural efferent and afferent communication between the brain and kidneys.

[0027] FIG. 13 is an anatomic view of the arterial vasculature of a human.

[0028] FIG. 14 is an anatomic view of the venous vasculature of a human.DETAILED DESCRIPTION

[0029] The present disclosure describes neuromodulation catheters including stimulation and ablation electrodes.

[0030] As used herein, the terms “distal” and “proximal” define a position or direction with respect to the treating clinician or clinician’s control device (e.g., a handle assembly). “Distal” or “distally” can refer to a position distant from or in a direction away from theclinician or clinician’s control device. “Proximal” and “proximally” can refer to a position near or in a direction towards the clinician or clinician’s control device.

[0031] In some examples, a neuromodulation catheter includes a distal catheter portion including a first elongate body and a second elongate body. The distal catheter portion is configured to transform from a relatively low-profile configuration to a deployed configuration. For example, each of the first elongate body and a second elongate body may be respectively configured to transform from a respective relatively low-profile configuration to a respective deployed configuration. In the deployed configuration, the first elongate body or the second elongate body may define a loop, a helical, or a spiral configuration. The second elongate body is configured to be spaced from the first elongate body in the expanded configuration. A first electrode array is disposed on the first elongate body and is configured to deliver an ablation signal, and second electrode array is disposed on the second elongate body and is configured to deliver a stimulation signal, for example, from a controller or a generator.

[0032] In some examples, respective electrodes of the second electrode array are longitudinally offset from corresponding electrodes of the first electrode array, but in the same vessel quadrant in the expanded configuration. In some examples, the second electrode array is spaced in a range of from 0.1 inch to 0.2 inch from the first electrode array.

[0033] Denervation therapy may be delivered using the first electrode array, while nerve stimulation to monitor the denervation therapy may be sent using the second electrode array. For example, a monopolar stimulation performed by the second electrode array could be incorporated into an ablation pattern delivered from the first electrode array. The ablation may be paused for a predetermined interval of time during the stimulation. Alternatively, bipolar stimulation may be performed using electrode pairs of the second electrode array, or using electrode pairs between the first electrode array and the second electrode array. Stimulation with electrode pairs between the first electrode array and the second electrode array may be performed before and after ablation.

[0034] FIG. 1 A is a diagram illustrating an example system including a catheter 12 configured to deliver neuromodulation therapy, a computing device 14, and a controller 16. In FIG. 1 A, catheter 12 is in a relatively low profile configuration. FIG. IB is a diagram illustrating a partial side view of catheter 12 of FIG. 1 A in an expanded configuration 12 A. Catheter 12 is also referred to as neuromodulation catheter 12. Computing device 14 may be configured to send a control signal to controller 16 or otherwise control the operation of one or both of catheter 12 or controller 16. In some examples, the control signal sent bycomputing device 14 to controller 16 is configured to cause controller 16 to, based on the control signal received from computing device 14, generate an electrical signal. Controller 16 may generate the electrical signal sent to catheter 12 to cause catheter 12 to deliver neuromodulation therapy. For example, the neuromodulation therapy may include renal neuromodulation, hepatic neuromodulation, or any other neuromodulation therapy.

[0035] Controller 16 may be configured to generate an electrical signal comprising the ablation signal configured to be delivered by catheter 12. For example, controller 16 may include a generator 40 configured to generate the ablation signal. Controller 16 may also include a stimulator 42 configured to generate a stimulation signal to test an extent of denervation in response to the ablation signal. Depending on the frequency components of the ablation signal or the stimulation signal, generator 40 or stimulator 42 may include one or both of an alternating current (AC) generator or a direct current (DC) generator. In some examples, stimulator 42 includes circuitry configured to rectify an AC signal to generate a DC signal. For example, stimulator 42 may generate the stimulation signal including solely the DC signal. In other examples, one or both of the ablation signal or the stimulation signal may include an AC signal and a DC signal, but differ in the frequency band of the AC signal, or the amplitude of the DC signal. For example, the ablation signal may have a significantly higher frequency than the stimulation signal.

[0036] Catheter 12 includes a handle 18 and a catheter body 20 attached to handle 18. That is, handle 18 is positioned at a proximal portion of catheter body 20. Catheter body 20 may have any suitable outer diameter, and the diameter can be constant along the length of catheter body 20 or may vary along the length of catheter body 20. In some examples, catheter body 20 may be 2, 3, 4, 5, 6, or 7 French or another suitable size. Catheter body 20 extends along a central longitudinal axis L, and includes a distal catheter portion 20A and a proximal catheter portion 20B. Distal catheter portion 20A includes an expandable portion 22.

[0037] Expandable portion 22 is configured to transform from a relatively low-profile configuration (shown in FIG. 1 A) to a radially expanded deployed configuration 22 A (shown in FIG. IB). Expandable portion 22 includes a first elongate body 24 and a second elongate body 26. In some examples, first elongate body 24 and second elongate body 26 each extend in a direction along a longitudinal axis L of catheter 12. Each of first elongate body 24 and second elongate body 26 are configured to expand from a respective relatively low-profile configuration (shown in FIG. 1 A) to a radially expanded deployed configuration 24 A and 26A (shown in FIG. IB), such as a spiral, loop, or helical configuration. In some examples,one or both of first elongate body 24 or second elongate body 26 include a helical hollow strand configured to expand from a relatively low-profile configuration into an expanded helical configuration. The helical hollow strand may include a plurality of shape memory wires, the plurality collectively defining a lumen, the lumen being helical in an expanded configuration. For example, first elongate body 24 may include a first helical hollow strand, and second elongate body 26 may include a second helical hollow strand. In some examples, second elongate body 26 includes, instead of the helical hollow strand, a shape memory wire. For example, the shape memory wire may include a nickel titanium alloy. In some examples, first elongate body 24 includes a helical hollow strand, and the second elongate body includes a shape memory wire.

[0038] Second elongate body 26A is configured to be spaced from first elongate body 24A when catheter 12 is in expanded configuration 12A shown in FIG. IB. In the relatively low-profile configuration of catheter 12 shown in FIG. 1 A, at least a portion of second elongate body 26 may contact first elongate body 24. In some examples, a first distal tip of first elongate body 24 is distal to a second distal tip of second elongate body 26, as shown in FIG. 1 A. In other examples, the first distal tip of first elongate body 24 is proximal to the second distal tip of second elongate body 26. The first distal tip or the second distal tip may be secured or coupled to each other, or the first distal tip may be secured or coupled to a portion of second elongate body 26, or the second distal tip may be secured or coupled to a portion of first elongate body 24. For example, middle portions of first elongate body 24 and second elongate body 26 may be movable apart in the expanded configuration 12 A, while distal and proximal portions may remain coupled to each other or secured to each other (e.g., by an overmold, a weld, a heat bond, an adhesive, or a friction fit). In some examples, a distal portion of first elongate body 24 defines an opening, and the second distal tip of second elongate body 26 is inserted and retained in the opening in first elongate body.

[0039] Catheter 12 further includes a first electrode array 28 disposed on first elongate body 24, and a second electrode array 30 disposed on second elongate body 26. At least one electrode of first electrode array 28 is configured to deliver an ablation signal, and at least one electrode of second electrode array 30 is configured to deliver a stimulation signal. For example, controller 16 may be configured to generate the ablation signal configured to be delivered by first electrode array 28, and generate the stimulation signal configured to be delivered by second electrode array 30. In some examples, each electrode of first electrode array 28 is configured to deliver the ablation signal. In some examples, the stimulation signal is a monopolar stimulation signal configured to be delivered by each electrode of secondelectrode array 30. In some examples, the stimulation signal is a bipolar stimulation signal configured to be delivered by at least one electrode pair of second electrode array 30.

[0040] First electrode array 28 may be disposed along first elongate body 24, for example, aligned with a direction along longitudinal axis L of catheter 12. Although FIG. 1 A illustrates first electrode array 28 and second electrode array 30 each as having four electrodes, in other examples, one or both of first electrode array 28 or second electrode array 30 may include one, two, three, five, or more electrodes. The number of electrodes in first electrode array 28 or second electrode array 30 may be the same or different, and may independently be odd or even. In some examples, second electrode array 30 includes more electrodes than first electrode array 28. For example, second electrode array 30 may include five electrodes, while first electrode array 28 may include four electrodes. In some such examples, second electrode array 30 includes at least one electrode proximal to first electrode array 28, and controller 16 is configured to detect an efferent response to the stimulation signal. In other such examples, second electrode array 30 includes at least one electrode distal to first electrode array 28, and controller 16 is configured to detect an afferent response to the stimulation signal. In some examples, first electrode array 28 and second electrode array 30 include a same number of electrodes, and second elongate body 30 is proximal to first elongate body 28 to detect an efferent response, and distal to first elongate body 28 to detect an afferent response.

[0041] Electrodes of first electrode array 28 and second electrode array 30 may have any suitable shape, size, or form. In some examples, at least one electrode of at least one of first electrode array 28 or second electrode array 30 is a ring electrode. In some such examples, each electrode of both first electrode array 28 or second electrode array 30 is a ring electrode. In some examples, each electrode of first electrode array 28 is identical to other electrodes of first electrode array 28, and each electrode of second electrode array 30 is identical to other electrodes of second electrode array 30. For example, each electrode of first electrode array 28 may have a same electrode length along longitudinal axis L of first elongate body 24. In some such examples, all electrodes of first electrode array 28 and second electrode array 30 are identical in shape, size, and form. In other examples, electrodes of first electrode array 28 differ from electrodes of second electrode array 30 in at least one of shape, size, or form.

[0042] In some examples, at least one electrode of first electrode array 28 or second electrode array 30 includes gold, iridium oxide, or platinum iridium alloy. For example, gold may promote thermal dissipation and reduce thermal buildup in course of ablation. Iridium oxide may have a high electrical conductivity. Platinum iridium alloy may be less susceptible than gold to effects of electrode polarization. In some examples, at least one electrode of firstelectrode array 28 or second electrode array 30 includes gold with a coating of iridium oxide. In some examples, at least one electrode of first electrode array 28 configured to deliver an ablation signal includes, consists of, or consists essentially of (excepting for minor impurities) gold. In some examples, each electrode of first electrode array 28 includes, consists of, or consists essentially of gold. In some examples, at least one electrode of second electrode array 30 configured to deliver a stimulation signal includes, consists of, or consists essentially of (excepting for minor impurities) platinum iridium alloy. In some examples, each electrode of second electrode array 30 includes, consists of, or consists essentially of platinum iridium alloy.

[0043] Generator 40 may be configured to deliver therapy to tissue of a patient via at least one electrode of first electrode array 28, for example, to modulate a target nerve of the patient. For example, all electrodes of first electrode array 28 may be coupled together or otherwise to generator 40, and generator 40 may deliver an ablation signal to tissue, or to a target site via all electrodes of first electrode array 28. Catheter 12 may thus deliver denervation therapy via first electrode array 28, and computing device 14 or controller 16 may control catheter 12 to deliver denervation therapy.

[0044] Generator 40 may be configured to deliver a stimulation signal via at least one electrode of second electrode array 30, for example, to assess efficacy of neuromodulation therapy. For example, a change in physiological response of the patient to stimulation before and after ablation may be indicative of an effect of neuromodulation therapy on nerve activity. In some examples, generator 40 is configured to deliver a monopolar stimulation signal using individual electrodes of second electrode array 30, such that electrical current flows from the individual electrode to a large dispersive electrode (e.g., a ground pad) external to catheter 12. In other examples, generator 40 is configured to deliver a bipolar stimulation signal using at least one pair of electrodes of second electrode array 30 (or at least one electrode pair including a first electrode of first electrode array 28 and a second electrode of second electrode array 30), such that electrical current flows from an electrode of first or second electrode array 28 or 30 to another electrode of second electrode array 30 on catheter 12. Catheter 12 may thus deliver denervation therapy via first electrode array 28, deliver a stimulation signal via second electrode array 30, and computing device 14 or controller 16 may control catheter 12 to deliver and assess denervation therapy.

[0045] At least one electrode of first electrode array 28 may be coupled to a respective thermocouple. For example, controller 16 may sense a respective temperature of the at least one electrode via the thermocouple. In some examples, controller 16 may be configured toterminate ablation therapy in response to a temperature sensed by the thermocouple, for example, to avoid excessive heating of catheter 12 or neighboring tissue.

[0046] Distal catheter portion 20A of catheter 12 is configured to be advanced within an anatomical lumen of a human patient to locate at least one electrode of first electrode array 28 at a target tissue site within or otherwise proximate to the anatomical lumen. For example, catheter 12 may be configured to position distal catheter portion 20A within a blood vessel, a ureter, a urethra, a duct, an airway, or another naturally occurring lumen within the human body. The examples described herein focus on the anatomical lumen being a blood vessel, such as a renal vessel, but it will be understood that similar techniques may be used with other anatomical lumens.

[0047] Catheter 12 can be configured for delivery to a target tissue site within vasculature of a patient via a guide member, which can include, for example, one or more of a guidewire or an outer sheath. In certain examples, intravascular delivery of distal catheter portion 20A includes percutaneously inserting a guidewire (not shown in FIG. 1 A) into a vessel of a patient and moving at least catheter body 20 (for example, at least expandable portion 22) along the guidewire until expandable portion 22 reaches a target tissue site (for example, a renal artery). For example, distal catheter portion 20A of catheter body 20 (e.g., first elongate body 24) may define a lumen configured to receive a guidewire for delivery of distal catheter portion to a target tissue site using over-the-wire (OTW) or rapid exchange (RX) techniques. In other examples, catheter 12 can be a steerable or non-steerable device configured for use without a guidewire. In still other examples, catheter 12 can be configured for delivery via an inner lumen of a guide member, for example, a guide catheter, an outer sheath (not shown in FIG. 1 A), or other guide device.

[0048] A distal end of catheter body 20 defines distal tip 32. Distal tip 32 is configured to facilitate navigation of distal catheter portion 20A within the vasculature of the patient to a blood vessel. In some examples, distal tip 32 may be atraumatic, for example, to resist or avoid puncturing a vessel of a blood vessel during navigation of distal catheter portion 20A within the blood vessel.

[0049] In the example illustrated in FIG. 1 A, catheter 12 is in a relatively low-profile delivery configuration, in which distal catheter portion 20A defines a relatively smaller radial extent (a relatively low-profile, such as a relatively linear configuration) relative to expanded (also referred to as a radially expanded and / or deployed) configuration 12A in which expandable portion 22 of distal catheter portion 20A defines a relatively larger radial extent. In some examples, the radial extent is measured in a direction orthogonal to centrallongitudinal axis L. Distal catheter portion 20A may be delivered through vasculature of the patient to the target tissue site in the low-profile configuration. In some examples, expandable portion 22 is configured to self-expand within a blood vessel of a patient, e.g., via a shape-memory element (e.g., a shape memory tube or a helical hollow strand) of one or both of first elongate body 24 or second elongate body 26. In some examples, expandable portion 22 (e.g., both first elongate body 24 and second elongate body 26) extend along a straight line aligned with longitudinal axis L in the relatively low-profile configuration shown in FIG. 1 A. Expandable portion 22 may be constrained or restrained in the low-profile configuration by a guide member. The clinician may retract the guide member proximally relative to expandable portion 22 to un-constrain expandable portion 22 and cause or allow expandable portion 22 to transform from the low-profile configuration to an expanded configuration. Thus, expandable portion 22 may be configured to radially expand to the expanded configuration 22A.

[0050] In some examples, in the expanded configuration shown in FIG. IB, one or each of first elongate body 24A or second elongate body 26A defines a loop, a helix, or a spiral shape, or a basket, or a stent-like configuration. In the expanded configuration, first elongate body 24A is configured to position one or more electrodes of first electrode array 28 near a vessel wall, for example, in apposition with the vessel wall. Likewise, in the expanded configuration, second elongate body 26A is configured to position one or more electrodes of second electrode array 30 near the vessel wall, for example, in apposition with the vessel wall, but offset longitudinally, radially, or circumferentially from respective electrodes of first electrode array 28. For example, as shown in FIG. IB, respective electrodes of second electrode array 30 are longitudinally offset from corresponding electrodes of first electrode array 28 in a same quadrant about longitudinal axis L defined by distal catheter portion 20A in the expanded configuration 12 A. Respective electrodes of second electrode array 30 may be spaced from corresponding electrodes of first electrode array 28 by any suitable distance in expanded configuration 12 A. In some examples, respective electrodes of second electrode array 30 are spaced from corresponding electrodes of first electrode array 28 by a distance in a range from 0.1 inch to 0.2 inch in expanded configuration 12 A.

[0051] In some examples, expandable portion 22 may be expanded or may self-expand as a result of proximal retraction of a guide member from distal catheter portion 20A. The clinician may retract the guide member to a location along distal catheter portion 20A proximal to expandable portion 22 to cause or allow expandable portion 22 to expand. In the expanded configuration, expandable portion 22 may place at least one electrode (for example, of first electrode array 28 or of second electrode array 30) at a first location relative to thevessel wall, for example, corresponding to a first rotational location. A clinician may control a therapy delivery device to deliver, provide, or facilitate neuromodulation therapy at the target tissue site, for example, through the vessel wall at the target tissue site to target tissue adjacent to the blood vessel. The neuromodulation therapy may include, but is not limited to, radiofrequency (RF) energy, microwave energy, or the like.

[0052] The clinician may rotate handle 18, or otherwise proximal portion 20B, to apply a torque to distal portion 20A and cause expandable portion 22 to rotate about central longitudinal axis L from the first rotational location to a second rotational location. For example, the application of torque from handle 18 or proximal portion 20B to expandable portion 22 may cause expandable portion 22 to rotate about longitudinal axis L, for example, in a same direction as the torque. The clinician may control system 10 to deliver ablation therapy or stimulation at the second rotational location, or after further successive rotational locations of expandable portion 22.

[0053] Catheter 12 may be connected to controller 16 (e.g., a therapy delivery device). Controller 16 may include control circuitry and therapy source (for example, an electrical signal generator, or the like; not shown in FIG. 1 A) via at least one electrical conductor and / or at least one lumen defined by handle 18 and catheter body 20.

[0054] First electrode array 28 and second electrode array 30 may be used to deliver an ablation signal and a stimulation signal (e.g., from controller 16) using any suitable electrode or combination of electrodes.

[0055] FIG. 2A is a diagram illustrating a side view of an example monopolar delivery configuration of second electrode array 30 in the expanded configuration of catheter 12A of FIG. IB. In this configuration, respective electrodes 30A, 30B, 30C, and 30D of second electrode array 30 are each configured to deliver a monopolar stimulation signal (e.g., generated by controller 16). For example, electrodes 30A, 30B, 30C, and 30D are coupled to each other or otherwise to controller 16, and a monopolar stimulation signal received from controller 16 is delivered by each of electrodes 30A, 30B, 30C, and 30D.

[0056] FIG. 2B is a diagram illustrating a side view of an example bipolar delivery configuration of second electrode array 30 in the expanded configuration of catheter 12A of FIG. IB. In this configuration, first pair of electrodes 30A and 30B, and second pair of electrodes 30C and 30D each deliver a bipolar stimulation signal (e.g., generated by controller 16).

[0057] FIG. 2C is a diagram illustrating a side view of an example bipolar delivery configuration of first electrode array 28 and second electrode array 30 in the expandedconfiguration of catheter 12A of FIG. IB. In this configuration, respective electrodes 28A, 28B, 28C, and 28D of first electrode array 28 form electrode pairs with corresponding electrodes 30A, 30B, 30C, and 30D of second electrode array 30. Thus, pairs of electrodes 28 A and 30 A, 28B and 3 OB, 28C and 30C, and 28D and 30D each deliver a bipolar stimulation signal (e.g., generated by controller 16).

[0058] Wiring to deliver the ablation signal or the stimulation signal along a catheter may be positioned along an exterior or interior of the catheter. For example, in catheter 12, wiring may extend from a port (e.g., electrically coupled to controller 16) in handle 18 along proximal catheter portion 20B to distal catheter portion 20A, and may include a first wiring extending through or along first elongate body 24 and configured to deliver the ablation signal, and a second wiring extending through or along second elongate body 26 and configured to deliver the stimulation signal.

[0059] FIG. 3 is a diagram illustrating a cross-sectional view of an example elongate body 100 including a shape memory wire 102 defining a groove 104. Elongate body 100 may be an example of first elongate body 24 or second elongate body 26, or any elongate body of any catheter according to the present disclosure. For example, groove 104 may extend in a longitudinal direction along a length of shape memory wire 102, and be configured to a plurality of electrode wires 106 extending along groove 104. Plurality of electrode wires 106 is configured to deliver a signal to an electrode, for example, the stimulation signal to at least one electrode of second electrode array 30. In some such examples, each electrode wire of plurality of electrode wires 106 consists of a single filar wire. Elongate body 100 may further include a polymer jacket 108 surrounding shape memory wire 102. Polymer jacket 108 may include any suitable polymeric material, for example, a biocompatible polymer. In some examples, polymer jacket 108 includes thermoplastic urethane (TPU). In some examples, at least one electrode (not shown in FIG. 3) is positioned on an exterior surface defined by polymer jacket 108.

[0060] System 10 and / or catheter 12 may be used to deliver ablation and stimulation for neuromodulation according to any appropriate scheme.

[0061] FIG. 4 is a timing diagram illustrating an example scheme for delivering ablation and stimulation for neuromodulation including separate ablation and stimulation sessions. In the scheme shown in FIG. 4, the ablation waveform is delivered in a single, relatively long session (e.g., 88 ms), followed by a relatively long impedance measurement session (e.g., 12 ms). For example, a bipolar stimulation signal delivered by the electrode configuration described with reference to FIG. 2C, may be used to perform the scheme shown in FIG. 4. Insome such examples, the stimulation signal is a first stimulation signal, and controller 16 is configured to generate the first stimulation signal before the ablation signal and a second stimulation signal after the ablation signal.

[0062] FIG. 5 is a timing diagram illustrating an example scheme for delivering ablation and stimulation for neuromodulation including combining ablation and stimulation sessions. The scheme of FIG. 5 is achieved by modifying the scheme of FIG. 4 to split the ablation waveform into two shorter waveforms (“Ablation waveform A” and “Ablation waveform B” having shorter durations of time than the “Ablation waveform” of FIG. 4), and introduce a relatively short time of stimulation (first instance of “Stim”) between the split ablation waveforms A and B. Further, the impedance measurement is shortened in time (“Impedance meas ”), and a second stimulation is delivered after the shortened impedance measurement (second instance of “Stim”). For example, a monopolar stimulation signal delivered by the electrode configuration described with reference to FIG. 2A, or a bipolar stimulation signal delivered by the electrode configuration described with reference to FIG. 2B, may be used to perform the scheme shown in FIG. 4. In some such examples, controller 16 is configured to generate the stimulation signal (e.g., “Stim”) in a period of time at least partially overlapping with the ablation signal (e.g, an ablation signal including a first “Ablation waveform A” and a second “Ablation Waveform B” with “Stim” in between).

[0063] Thus, controller 16 may control catheter 12 to deliver a neuromodulation therapy including ablation and stimulation. In some examples, computing device 14 controls controller 16 to deliver ablation and stimulation via catheter 12. For example, computing device 14 may be configured to generate and send a control signal to controller 16, and controller 16 may be configured to generate, based on the control signal, an electrical signal sent to catheter 12.

[0064] FIG. 6 is a block diagram illustrating an example configuration of computing device 14 of FIG. 1. In some examples, controller 16 may include computing device 14, or include one or more components described with reference to computing device 14, or otherwise perform functions described with reference to computing device 14. Computing device 14 may include a workstation, a tablet computer, a laptop computer, or a desktop computer.

[0065] As shown in the example of FIG. 6, computing device 14 includes processing circuitry 170, storage device 172, communication circuitry 174, and a user interface 176. While computing device 14 may be a stand-alone device as shown in FIG. 6, in other examples, computing device 14 may be any component or system that includes processingcircuitry or other suitable computing environment for executing software instructions and, for example, need not necessarily include one or more elements shown in FIG. 6 (e.g., in some examples components such as storage device 172 may not be co-located or in the same housing or structure as other components).

[0066] Processing circuitry 170, in some examples, is configured to implement functionality and / or process instructions for execution within at least one computing device 14. For example, processing circuitry 170 may be capable of processing instructions, including at least one application 180, stored in storage device 172. Examples of processing circuitry 170, as well as other processors, processing circuitry, controllers, control circuitry, and the like, described herein, may include any combination of integrated circuitry, discrete logic circuitry, analog circuitry, such as one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), or field-programmable gate arrays (FPGAs). In some examples, processing circuitry 170 includes multiple components, such as any combination of one or more microprocessors, one or more DSPs, one or more ASICs, or one or more FPGAs, as well as other discrete or integrated logic circuitry, and / or analog circuitry.

[0067] Storage device 172 (which can also be referred to as a memory) may be configured to store information within computing device 14, including at least one application 180 and data 190. Storage device 172, in some examples, is a computer-readable storage medium. In some examples, storage device 172 includes a temporary memory or a volatile memory. Storage device 172, in one example, is used by at least one application 180 running on computing device 14 to temporarily store information during program execution. Storage device 172, in some examples, also includes one or more memories configured for long-term storage of information, e.g., including non-volatile storage elements. Examples of such nonvolatile storage elements include any volatile, non-volatile, magnetic, optical, or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital media.

[0068] Computing device 14 utilizes communication circuitry 174 to communicate with other devices, such as catheter 12, controller 16, other computing devices, and system 10 of FIG. 1. Communication circuitry 174 may include a network interface card, such as an Ethernet card, an optical transceiver, a radio frequency transceiver, or any other type of device that can send and receive information. Other examples of such network interfaces may include 3G, 4G, 5G, and WiFi radios.

[0069] Computing device 14 may include a user interface 176. User interface 176 may be configured to provide output to a user using tactile, audio, or video stimuli and receive input from a user through tactile, audio, or video feedback. User interface 176 may include, as examples, a presence-sensitive display, a mouse, a keyboard, a voice responsive system, video camera, microphone, or any other type of device for detecting a command from a user, a sound card, a video graphics adapter card, or any other type of device for converting a signal into an appropriate form understandable to humans or machines, a speaker, a display device, such as, but not limited to, cathode ray tube (CRT) monitor, a liquid crystal display (LCD), or any other type of device that can generate intelligible output to a user. In some examples, a presence-sensitive display includes a touch-sensitive screen.

[0070] At least one application 180 executable by processing circuitry 170 of computing device 14 may include a stimulation interface application 182 and a monitoring system 184 that may utilize physiological data or other data obtained during neuromodulation to monitor the progress of neuromodulation and effects of ablation. At least one application 180 further may include an ablation interface application 186 that controls delivery of ablation via controller 16 and / or catheter 12.

[0071] Execution of stimulation interface 182 and ablation interface 186 by processing circuitry 170 configures computing device 14 to interface with system 10 or controller 16 (or catheter 12). For example, stimulation interface 82 configures computing device 14 to communicate with controller 16 via communication circuitry 174. Processing circuitry 170 may receive a signal from a physiological sensor indicative of a physiological parameter, and store the physiological data 192 in storage device 172. Physiological parameters may include, but are not limited to, electrical conduction, electrical impedance, tissue response (e.g., blood pressure), heat response (e.g., heart rate), or any other physiological parameter that may change as a result of ablation and be stimulated through stimulation. Stimulation interface 182 and / or ablation interface 186 also configures user interface 176 for a user to interact with controller 16 (or catheter 12). One or more of stimulation interface 182, monitoring system 184, or ablation interface 186 may cause processing circuity 170 and computing device 14 to perform any of the techniques described herein related to neuromodulation by system 10.

[0072] FIG. 7 is a flow diagram illustrating an example technique for neuromodulation. The example technique of FIG. 7 is described with reference to processing circuitry 170 of computing device 14 and system 10 of FIG. 1A. However, the example technique may be implemented by any suitable computing device, controller, or system alone or in combination with processing circuitry 170.

[0073] The technique includes delivering, by first electrode array 28 disposed on first elongate body 24 of neuromodulation catheter 12, an ablation signal to a target site (200). Neuromodulation catheter 12 is placed in a vessel of a patient. For example, processing circuitry 170 may send the ablation signal to neuromodulation catheter 12. In some examples, processing circuitry 170 causes controller 16 to generate the ablation signal, and to send the ablation signal to first electrode array 28 of neuromodulation catheter 12.

[0074] The technique further includes delivering, by second electrode array 30 disposed on second elongate body 26 of neuromodulation catheter 12, a stimulation signal to the target site (202). For example, processing circuitry 170 may send the stimulation signal to neuromodulation catheter 12. In some examples, processing circuitry 170 causes controller 16 to generate the stimulation signal, and to send the stimulation signal to second electrode array 30 of neuromodulation catheter 12.

[0075] The technique further includes determining, by processing circuitry 170, a physiological response to the stimulation signal (204). Processing circuitry 170 may determine, based on the physiological response, an effectiveness of ablation at the target site induced by the ablation signal. For example, attenuation of the physiological response may be indicative of a reduction in neural activity, and thus, successful ablation. A physiological response may include any physiological parameter of a biological that may be affected by the stimulation signal to the biological system. For example, the stimulation signal is a first stimulation signal preceding the ablation signal, and second electrode array 30 may deliver a second stimulation signal to the target site after the ablation signal, and processing circuitry 170 may compare a physiological parameter after the first stimulation signal and a physiological parameter after the second stimulation signal. Processing circuitry 170 may initiate, continue, or terminate ablation in response to the comparison. For example, processing circuitry 170 may cause controller 16 to initiate, continue, or terminate ablation in response to the comparison. For example, if the comparison indicates that neural traffic is attenuated, or that the target site has been sufficiently ablated or denervated, processing circuitry 170 may cause controller 16 to terminate ablation. However, if the comparison indicates that neural traffic is not attenuated, or that the target site has not been sufficiently ablated or denervated, processing circuitry 170 may cause controller 16 to initiate or continue ablation.

[0076] Thus, example systems and techniques according to the present disclosure may be used to deliver, monitor, or control neuromodulation therapy.

[0077] FIG. 8 illustrates an example technique for accessing a renal artery and modulating renal nerves with a neuromodulation catheter. While FIG. 8 illustrates the use of catheter 12 for renal neuromodulation, catheter 12 may be used for other therapies and treatments within another blood vessel or other hollow anatomical body within the human body. Catheter 12 is configured to deliver energy (e.g., RF energy, ultrasound energy, electrical stimulation energy, or the like) to one or more target tissue sites within a renal vessel. Catheter 12 provides access to the renal plexus (RP) through an intravascular path (P), such as a percutaneous access site in the femoral (illustrated), brachial, radial, or axillary artery to the target tissue sites within a respective renal artery (RA). By manipulating proximal portion 20B or catheter body 22 from outside the intravascular path (P), a clinician may advance distal portion 20A of catheter body 22 through the sometimes-tortuous intravascular path (P) and remotely manipulate distal portion 20A (FIG. 1 A) of catheter body 20. Distal portion 20A may be remotely manipulated by the clinician using handle 18.

[0078] In the example illustrated in FIG. 8, distal portion 20A is delivered intravascularly to the treatment site using an inner member 123 in an over-the-wire (OTW) technique. Inner member 123 may be internal to catheter 12 (e.g., a guide wire, inner catheter, or the like) or external to catheter 12 (e.g., an outer sheath or the like). In some examples, inner member 123 is a navigation wire. Catheter 12 may define a passageway for receiving inner member 23 for delivery of catheter 12 using either an OTW or an RX technique. At the treatment site, inner member 123 can be at least partially withdrawn or removed relative to catheter 12 and distal portion 20A can transform into an expanded configuration (for example, a helical configuration, a spiral configuration, or the like) for delivering ultrasound energy. In other examples, catheter body 22 is self-steerable such that therapy may be delivered to the target tissue site without the aid of inner member 123.

[0079] In some examples, catheters described herein may be used to perform renal modulation. Renal modulation is the partial or complete incapacitation or other effective disruption of nerves of the kidneys (e.g., nerves terminating in the kidneys or in structures closely associated with the kidneys). In particular, renal neuromodulation can include inhibiting, reducing, or blocking neural communication along neural fibers (e.g., efferent or afferent neural fibers) of the kidneys. Such incapacitation can be long-term (e.g., permanent or for a period of months, years, or decades) or short-term (e.g., for periods of minutes, hours, days, or weeks). Renal neuromodulation is expected to contribute to the systemic reduction of sympathetic tone or drive or benefit at least some specific organs or other bodily structures innervated by sympathetic nerves. Accordingly, renal neuromodulation is expected to beuseful in treating clinical conditions associated with central sympathetic overstimulation. For example, renal neuromodulation is expected to efficaciously treat hypertension, heart failure, acute myocardial infarction, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic and end state renal disease, inappropriate fluid retention in heart failure, cardio-renal syndrome, polycystic kidney disease, polycystic ovary syndrome, osteoporosis, erectile dysfunction, and sudden death, among other conditions.

[0080] Renal neuromodulation can be electrically induced or induced in another suitable manner through the delivery of energy (RF energy, ultrasound energy, microwave energy, or the like). The target tissue site can be within or otherwise proximate to a renal lumen (e.g., a renal artery, a ureter, a renal pelvis, a major renal calyx, a minor renal calyx, or another suitable structure), and the target tissue site can include tissue at least proximate to a wall of the renal lumen. For example, with regard to a renal artery, a treatment procedure can include modulating nerves in the renal plexus, which lay intimately within or adjacent to the adventitia of the renal artery. The following discussion provides further details regarding patient anatomy and physiology as it may relate to renal denervation therapy. This section is intended to supplement and expand upon the previous discussion regarding the relevant anatomy and physiology, and to provide additional context regarding the disclosed technology and the therapeutic benefits associated with renal denervation. For example, several properties of the renal vasculature may inform the design of the target tissue devices and associated methods for achieving renal neuromodulation via intravascular access and impose specific design requirements for such devices. Specific design requirements may include accessing the renal artery, positioning distal portion 20A within the renal artery, delivering the therapy to targeted tissue, or effectively modulating the renal nerves with the therapy delivery device.

[0081] As noted previously, the sympathetic nervous system (SNS) is a branch of the autonomic nervous system along with the enteric nervous system and parasympathetic nervous system. It is always active at a basal level (called sympathetic tone) and becomes more active during times of stress. Like other parts of the nervous system, the sympathetic nervous system operated through a series of interconnected neurons. Sympathetic neurons are frequently considered part of the peripheral nervous system (PNS), although many lie within the central nervous system (CNS). Sympathetic neurons of the spinal cord (which is part of the CNS) communicate with peripheral sympathetic neurons via a series of sympathetic ganglia. Within the ganglia, spinal cord sympathetic neurons are therefore called presynaptic(or preganglionic) neurons, while peripheral sympathetic neurons are called postsynaptic (or postganglionic neurons).

[0082] At synapses within the sympathetic ganglia, preganglionic sympathetic neurons release acetylcholine, a chemical messenger that binds and activates nicotinic acetylcholine receptors on postganglionic neurons. In response to this stimulus, postganglionic neurons principally release noradrenaline (norepinephrine). Prolonged activation may elicit the release of adrenaline from the adrenal medulla.

[0083] Once released, norepinephrine and epinephrine bind adrenergic receptors on peripheral tissues. Binding to adrenergic receptors causes a neuronal and hormonal response. The physiologic manifestations include pupil dilation, increased heart rate, occasional vomiting, and increased blood pressure. Increased sweating is also seen due to binding of cholinergic receptors of the sweat glands.

[0084] The sympathetic nervous system is responsible for up- and down-regulating many homeostatic mechanisms in living organisms. Fibers from the SNS innervate tissues in almost every organ system, providing at least some regulatory function to physiological features as diverse as pupil diameter, gut motility, and urinary output. This response is also known as sympatho-adrenal response of the body, as the preganglionic sympathetic fibers that end in the adrenal medulla (but also all other sympathetic fibers) secrete acetylcholine, which activates the secretion of adrenaline (epinephrine) and to a lesser extent noradrenaline (norepinephrine). Therefore, this response that acts primarily on the cardiovascular system is mediated directly via impulses transmitted through the sympathetic nervous system and indirectly via catecholamines secreted from the adrenal medulla.

[0085] FIG. 9 is a conceptual illustration of an example sympathetic nervous system (SNS) illustrating how the brain communicated with the body via the SNS. As shown in FIG. 9, the SNS provides a network of nerves that allows the brain to communicate with the body. Sympathetic nerves originate inside the vertebral column, e.g., toward the middle of the spinal cord in the intermediolateral cell column (or lateral horn), beginning at the first thoracic segment of the spinal cord and are thought to extend to the second or third lumbar segments. Because SNS cells begin in the thoracic and lumbar regions of the spinal cord, the SNS is said to have a thoracolumbar outflow. Axons of sympathetic nerves leave the spinal cord through the anterior rootlet / root. The axons pass near the spinal (sensory) ganglion, where the axons enter the anterior rami of the spinal nerves. However, unlike somatic innervation, the axons separate out through white rami connectors which connect to either the paravertebral (whichlie near the vertebral column) or prevertebral (which lie near the aortic bifurcation) ganglia extending alongside the spinal column.

[0086] To reach the target organs and glands, the axons should travel long distances in the body, and, to accomplish this, many axons relay their message to a second cell through synaptic transmission. The ends of the axons link across a space, the synapse, to the dendrites of the second cell. The first cell (the presynaptic cell) sends a neurotransmitter across the synaptic cleft where it activates the second cell (the postsynaptic cell). The message is then carried to the final destination.

[0087] In the SNS and other component of the peripheral nervous system, these synapses are made at sites called ganglia, discussed above. The cell that sends its fiber to the ganglion is called a preganglionic cell, while the cell whose fiber leaves the ganglion is called a postganglionic cell. As mentioned previously, the preganglionic cell of the SNS is located between the first thoracic (Tl) segment and third lumbar (L3) segments of the spinal cord. Postganglionic cells have their cell bodies in the ganglia and send their axons to target organs or glands.

[0088] The ganglia include not just the sympathetic trunks but also the cervical ganglia(superior, middle, and inferior), which send sympathetic nerve fibers to the head and thorax organs, and the celiac and mesenteric ganglia, which send sympathetic fibers to the gut.

[0089] FIG. 10 is an enlarged anatomic view of nerves innervating a left kidney to form the renal plexus surrounding the left renal artery. As FIG. 10 shows, the kidney is innervated by the renal plexus (RP), which is intimately associated with the renal artery. The renal plexus (RP) is an autonomic plexus that surrounds the renal artery and is embedded within the adventitia of the renal artery. The renal plexus (RP) extends along the renal artery and is embedded within the adventitia of the renal artery. Fibers contributing to the renal plexus (RP) arise from the celiac ganglion, the superior mesenteric ganglion, the aorticorenal ganglion and the aortic plexus. The renal plexus (RP), also referred to as the renal nerve, is predominantly comprised of sympathetic components. There is no (or at least very minimal) parasympathetic innervation of the kidney.

[0090] Preganglionic neuronal cell bodies are located in the intermediolateral cell column of the spinal cord. Preganglionic axons pass through the paravertebral ganglia to become the lesser splanchnic nerve, the least splanchnic nerve, the first lumbar splanchnic nerve, the second lumbar splanchnic nerve, and travel to the celiac ganglion, the superior mesenteric ganglion, and the aorticorenal ganglion. Postganglionic neuronal cell bodies exit the celiacganglion, the superior mesenteric ganglion, and the aorticorenal ganglion to the renal plexus (RP) and are distributed to the renal vasculature.

[0091] Messages travel through the SNS in a bi-directional flow. Efferent messages may trigger changes in different parts of the body simultaneously. For example, the sympathetic nervous system may accelerate heart rate, widen bronchial passages, decrease motility (movement) of the large intestine, constrict blood vessels, increase peristalsis in the esophagus, cause pupil dilation, piloerection (goose bumps) and perspiration (sweating), or raise blood pressure. Afferent messages carry signals from various organs and sensory receptors in the body to other organs and, particularly, the brain.

[0092] Hypertension, heart failure, and chronic kidney disease are a few of the many disease states that result from chronic activation of the SNS, especially the renal sympathetic nervous system. Chronic activation of the SNS is a maladaptive response that drives the progression of theses disease states. Pharmaceutical management of the renin-angiotensin- aldosterone system (RAAS) has been a longstanding, but somewhat ineffective, approach for reducing over-activity of the SNS.

[0093] As mentioned above, the renal sympathetic nervous system has been identified as a major contributor to the complex pathophysiology of hypertension, states of volume overload (such as heart failure) and progressive renal disease, both experimentally and in humans. Studies employing radiotracer dilution methodology to measure overflow of norepinephrine from the kidneys to plasma revealed increased renal norepinephrine (NE) spillover rates in patients with essential hypertension, particularly so in young hypertensive subjects, which in concert with increased NE spillover from the heart, is consistent with the hemodynamic profile typically seen in early hypertension and characterized by an increased heart rate, cardiac output, and renovascular resistance. It is now known that essential hypertension is commonly neurogenic, often accompanied by pronounced sympathetic nervous system overactivity.

[0094] Activation of cardiorenal sympathetic nerve activity is even more pronounced in heart failure, as demonstrated by an exaggerated increase of NE overflow from the heart and the kidneys to plasma in this patient group. In line with this notion is the recent demonstration of a strong negative predictive value of renal sympathetic activation on allcause mortality and heart transplantation in patients with congestive heart failure, which is independent of overall sympathetic activity, glomerular filtration late, and left ventricular ejection fraction. These findings support the notion that treatment regimens that are designedto reduce renal sympathetic stimulation have the potential to improve survival in patients with heart failure.

[0095] Both chronic and end state renal disease in some patients are characterized by heightened sympathetic nervous activation. In patients with end state renal disease, plasma levels of norepinephrine above the media have been demonstrated to be predictive for both all-cause death and death from cardiovascular disease. This can also be true for patients suffering from diabetic or contrast nephropathy. There is compelling evidence suggesting that sensory afferent signals originating from the diseased kidneys are major contributors to initiating and sustaining elevated central sympathetic outflow in this patient group; this facilitates the occurrence of the well-known adverse consequences of chronic sympathetic over activity, such as hypertension, left ventricular hypertrophy, ventricular arrhythmias, sudden cardiac death, insulin resistance, diabetes, and metabolic syndrome.

[0096] Sympathetic nerves to the kidneys terminate in the blood vessels, the juxtaglomerular apparatus, and the renal tubules. Stimulation of the renal sympathetic nerves cause increased renin release, increased sodium (Na+) reabsorption, and a reduction of renal blood flow. These components of the neural regulation of renal function are considerably stimulated in disease states characterized by heightened sympathetic tone and clearly contribute to the rise in blood pressure in hypertensive patients. The reduction of renal blood flow and glomerular filtration rate as a result of renal sympathetic efferent stimulation may be a cornerstone of the loss of renal function in cardio-renal syndrome, which is renal dysfunction as a progressive complication of chronic heart failure, with a clinical course that typically fluctuates with the patient’s clinical status and treatment. Pharmacologic strategies to thwart the consequences of renal efferent sympathetic stimulation include centrally acting sympatholytic drugs, beta blockers (intended to reduce renin release), angiotensin converting enzyme inhibitors and receptor blockers (intended to block the action of angiotensin II and aldosterone activation consequent to renin release), and diuretics (intended to counter the renal sympathetic mediated sodium and water retention). However, the current pharmacologic strategies can have significant limitations including limited efficacy, compliance issues, side effects, and others.

[0097] The kidneys communicate with integral structures in the central nervous system via renal sensory afferent nerves. Several forms of “renal injury” may induce activation of sensory afferent signals. For example, renal ischemia, reduction in stroke volume or renal blood flow, or an abundance of adenosine enzyme may trigger activation of afferent neural communication.

[0098] FIG. 11 is an anatomic view of a human body depicting neural efferent and afferent communication between the brain and kidneys. FIG. 12 is a conceptual view of a human body depicting neural efferent and afferent communication between the brain and kidneys. As shown in FIGS. 11 and 12, the afferent communication might be from kidney to the brain or might be from one kidney to the other kidney (via the central nervous system). These afferent signals are centrally integrated and may result in increased sympathetic outflow. This sympathetic drive is directed towards the kidneys, thereby activating the RAAS and inducing increased renin secretion, sodium retention, volume retention, and vasoconstriction. Central sympathetic over activity also impacts other organs and bodily structures innervated by sympathetic nerves such as the heart and the peripheral vasculature, resulting in the described adverse effects of sympathetic activation, several aspects of which also contribute to the rise in blood pressure.

[0099] The physiology therefore suggests that (i) modulation of tissue with efferent sympathetic nerves will reduce inappropriate renin release, salt retention, and reduction of renal blood flow, and that (ii) modulation of tissue with afferent sensory nerves will reduce the systemic contribution to hypertension and other disease states associated with increased central sympathetic tone through its direct effect on the posterior hypothalamus as well as the contralateral kidney. In addition to the central hypotensive effects of afferent renal denervation, a desirable reduction of central sympathetic outflow to various other sympathetically innervated organs such as the heart and the vasculature is anticipated.

[0100] As provided above, renal denervation is likely to be valuable in the treatment of several clinical conditions characterized by increased overall and particularly renal sympathetic activity such as hypertension, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic end state renal disease, inappropriate fluid retention in heart failure, cardio-renal syndrome and sudden death. Since the reduction of afferent neural signals contributing to the systemic reduction of sympathetic tone / drive, renal denervation might also be useful in treating other conditions associate with systemic sympathetic hyperactivity. Accordingly, renal denervation may also benefit other organs and bodily structures innervated by sympathetic nerves, including those identified in FIG. 12. For example, as previously discussed, a reduction in central sympathetic drive may reduce the insulin resistance that afflicts people with metabolic syndrome and Type II diabetics. Additionally, patients with osteoporosis may also be sympathetically activated and might also benefit from the down regulation of sympathetic drive that accompanies renal denervation.

[0101] In accordance with the present technology neuromodulation of a left or right renal plexus (RP), which is intimately associated with a left or right renal artery, may be achieved through intravascular access. FIG. 13 is an anatomic view of the arterial vasculature of a human. As FIG. 13 shows, blood moved by contractions of the heart is conveyed from the left ventricle of the heart by the aorta. The aorta descends through the thorax and branches into the left and right renal arteries. Below the renal arteries, the aorta bifurcates at the left and right iliac arteries. The left and right iliac arteries descend, respectively, through the left and right legs and join the left and right femoral arteries.

[0102] FIG. 14 is an anatomic view of the venous vasculature of a human. As FIG. 14 shows, the blood collects in veins and returns to the heart, through the femoral veins into the iliac veins and into the inferior vena cava. The inferior vena cava branches into the left and right renal veins. Above the renal veins, the inferior vena cava ascends to convey blood into the right atrium of the heart. From the right atrium, the blood is pumped through the right ventricle into the lungs, where it is oxygenated. From the lungs, the oxygenated blood is conveyed into the left atrium. From the left atrium, the oxygenated blood is conveyed by the left ventricle back to the aorta.

[0103] The femoral artery may be accessed and cannulated at the base on the femoral triangle just inferior to the midpoint of the inguinal ligament. A catheter may be inserted percutaneously into the femoral artery through this access site, passed through the iliac artery and aorta, and placed into either the left or right renal artery. This comprises an intravascular path that offers minimally invasive access to a respective renal artery or other renal blood vessels.

[0104] The wrist, upper arm, and shoulder region provide other locations for introduction of catheters into the arterial system. For example, catheterization of either the radial, brachial, or axillary artery may be utilized in select cases. Catheters (e.g., catheter 12) introduced via these access points may be passed through the subclavian artery on the left side (or via the subclavian and brachiocephalic arteries on the right side), through the aortic arch, down the descending aorta and into the renal arteries using standard angiographic techniques. Other access sites can also be used to access the arterial system.

[0105] Since neuromodulation of a left or right renal plexus (RP) may be achieved in accordance with the present technology through intravascular access, properties and characteristics of the renal vasculature may impose constraints upon or inform the design of apparatus, systems, and methods for achieving such renal neuromodulation. Some of these properties and characteristics may vary across the patient population or within a specificpatient across time, as well as in response to disease states, such as hypertension, chronic kidney disease, vascular disease, end-stage renal disease, insulin resistance, diabetes, metabolic syndrome, and the like. These properties and characteristics, as explained herein, may have bearing on the efficacy of the procedure and the specific design of the intravascular device. Properties of interest may include, for example, material / mechanical, spatial, fluid dynamic / hemodynamic or thermodynamic properties.

[0106] As discussed previously, a catheter may be advanced percutaneously into either the left or right renal artery via a minimally invasive intravascular path. However, minimally invasive renal arterial access may be challenging, for example, because as compared to some other arteries that are routinely accessed using catheters, the renal arteries are often extremely tortuous, may be of relatively small diameter, or may be of relatively short length.Furthermore, renal arterial atherosclerosis is common in many patients, particularly those with cardiovascular disease. Renal arterial anatomy also may vary significantly from patient to patient, which further complicates minimally invasive access. Significant inter-patient variation may be seen, for example, in relative tortuosity, diameter, length, or atherosclerotic plaque burden, as well as in the take-off angle at which a renal artery branches from the aorta. Further, some patients include multiple left renal arteries or right renal arteries. Apparatus, systems, and methods for achieving renal neuromodulation via intravascular access should account for these and other aspects of renal arterial anatomy and its variation across the patient population when minimally invasively accessing a renal artery.

[0107] In addition to complicating renal arterial access, specifics of the renal anatomy also complicate establishment of stable contact between neuromodulatory apparatus and a luminal surface or wall of a renal artery. For example, navigation can be impeded by the tight space within a renal artery, as well as tortuosity of the artery. Furthermore, establishing consistent contact is complicated by patient movement, respiration, or the cardiac cycle because these factors may cause significant movement of the renal artery relative to the aorta, and the cardiac cycle may transiently distend the renal artery (i.e., cause the wall of the artery to pulse).

[0108] The neuromodulation system may also be configured to allow for adjustable positioning and repositioning of distal portion 20A (FIG. 1 A) within the renal artery since location of treatment may also impact clinical efficacy. Additionally, variable positioning and repositioning of the neuromodulatory apparatus may prove to be useful in circumstances where the renal artery is particularly tortuous or where there are proximal branch vessels off the renal artery main vessel, making treatment in certain locations challenging.

[0109] As noted above, an apparatus positioned within a renal artery may be configured so that distal portion 20A of catheter 12 may intimately contact the vessel wall or extend at least partially through the vessel wall. Renal artery vessel diameter, DRA, typically is in a range of about 2-10 mm, with most of the patient population having a DRA of about 4 mm to about 8 mm and an average of about 6 mm. Renal artery vessel length, LRA, between its ostium at the aorta / renal artery juncture and its distal branchings, generally is in a range of about 5-70 mm, and a significant portion of the patient population is in a range of about 20-50 mm. Since the target renal plexus is embedded within the adventitia of the renal artery, the composite Intima-Media Thickness, IMT, (i.e., the radial outward distance from the artery's luminal surface to the adventitia containing target neural structures) also is notable and generally is in a range of about 0.5-2.5 mm, with an average of about 1.5 mm. Although a certain depth of treatment is important to reach the target neural fibers, the treatment should not be too deep (e.g., > 10 mm from inner wall of the artery) to avoid non-target tissue and anatomical structures such as anatomical structures of the digestive system of psoas muscle.

[0110] An additional property of the renal artery that may be of interest is the degree of renal motion relative to the aorta induced by respiration or blood flow pulsatility. A patient’s kidney, which is located at the distal end of the renal artery, may move as much as 10 centimeters cranially with respiratory excursion. This may impart significant motion to the renal artery connecting the aorta and the kidney, thereby requiring from the neuromodulatory apparatus a unique balance of stiffness and flexibility to maintain contact between the energy delivery element and the vessel wall during cycles of respiration. Furthermore, the take-off angle between the renal artery and aorta may vary significantly between patients, and also may vary dynamically within a patient, e.g., due to kidney motion. The take-off angle generally may be in a range of about 30°-135°.[OHl] Certain aspects of the present disclosure described in the context of particular examples may be combined or eliminated in other examples. Further, while advantages associated with certain examples have been described in the context of those examples, other examples may also exhibit such advantages, and not all examples need necessarily exhibit such advantages to fall within the scope of the present disclosure. Accordingly, the present disclosure and associated technology can encompass other examples not expressly shown or described herein.

[0112] Moreover, unless the word “or” is expressly limited to mean only a single term exclusive from the other items in reference to a list of two or more items, then the use of “or” in such a list is to be interpreted as including (a) any single item in list, (b) all of the items inthe list, or (c) any combination of the items in the list. Additionally, the term “comprising” is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and / or additional types of other features are not precluded.

[0113] It should be understood that various aspects disclosed herein may be combined in different combinations than the combinations specifically presented in the description and accompanying drawings. It should also be understood that, depending on the example, certain acts or events of any of the processes or methods described herein may be performed in a different sequence, may be added, merged, or left out altogether (e.g., all described acts or events may not be necessary to carry out the techniques). In addition, while certain aspects of this disclosure are described as being performed by a single module, unit, or circuit for purposes of clarity, it should be understood that the techniques of this disclosure may be performed by a combination of units, modules, or circuitry associated with, for example, a medical device.

[0114] In one or more examples, the described techniques may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored as one or more instructions or code on a computer-readable medium and executed by a hardware-based processing unit. Computer-readable media may include non-transitory computer-readable media, which corresponds to a tangible medium such as data storage media (e.g., RAM, ROM, EEPROM, flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer).

[0115] Instructions may be executed by one or more processors that include processing circuitry, such as one or more digital signal processors (DSPs), general purpose microprocessors, application specific integrated circuits (ASICs), field programmable logic arrays (FPGAs), or other equivalent integrated or discrete logic circuitry. Accordingly, the term “processor” or “processing circuitry” as used herein may refer to any of the foregoing structure or any other physical structure suitable for implementation of the described techniques. Also, the techniques could be fully implemented in one or more circuits or logic elements.

[0116] The above detailed descriptions of examples of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Although specific examples of the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. For example, while steps are presented in a given order,alternative examples may perform steps in a different order. The various examples described herein may also be combined to provide further examples. All references cited herein are incorporated by reference as if fully set forth herein.

[0117] From the foregoing, it will be appreciated that specific examples of the present disclosure have been described herein for purposes of illustration, but that various modifications may be made without deviating from the present disclosure.

[0118] Various examples have been described. These and other examples are within the scope of the following.

[0119] Example 1. A neuromodulation system comprising: a neuromodulation catheter comprising: a distal catheter portion configured to transform from a relatively low profile configuration to an expanded configuration, the distal catheter portion comprising a first elongate body and a second elongate body, the second elongate body configured to be spaced from the first elongate body in the expanded configuration; a first electrode array disposed on the first elongate body; and a second electrode array disposed on the second elongate body; and a controller configured to: generate an ablation signal configured to be delivered by the first electrode array; and generate a stimulation signal configured to be delivered by the second electrode array.

[0120] Example 2. The neuromodulation system of Example 1, wherein the first elongate body and the second elongate body are each configured to define a loop, a helix, or a spiral in the expanded configuration.

[0121] Example 3. The neuromodulation system of Examples 1 or 2, wherein each electrode of the first electrode array is configured to deliver the ablation signal.

[0122] Example 4. The neuromodulation system of any of Examples 1 to 3, wherein the stimulation signal is a monopolar stimulation signal configured to be delivered by each electrode of the second electrode array.

[0123] Example 5. The neuromodulation system of any of Examples 1 to 3, wherein the stimulation signal is a bipolar stimulation signal configured to be delivered by at least one electrode pair of the second electrode array.

[0124] Example 6. The neuromodulation system of Examples 4 or 5, wherein the controller is configured to generate the stimulation signal in a period of time at least partially overlapping with the ablation signal.

[0125] Example 7. The neuromodulation system of any of Examples 1 to 3, wherein the stimulation signal is a bipolar stimulation signal configured to be delivered by atleast one electrode pair comprising a first electrode of the first electrode array and a second electrode of the second electrode array.

[0126] Example 8. The neuromodulation system of any of Examples 1 to 7, wherein the stimulation signal is a first stimulation signal, and wherein the controller is configured to generate the first stimulation signal before the ablation signal and a second stimulation signal after the ablation signal.

[0127] Example 9. The neuromodulation system of any of Examples 1 to 8, wherein at least one electrode of the first electrode array comprises gold.

[0128] Example 10. The neuromodulation system of any of Examples 1 to 9, wherein at least one electrode of the second electrode array comprises a platinum iridium alloy.

[0129] Example 11. The neuromodulation system of any of Examples 1 to 10, wherein a first distal tip of the first elongate body is distal to a second distal tip of the second elongate body.

[0130] Example 12. The neuromodulation system of any of Examples 1 to 10, wherein a first distal tip of the first elongate body is proximal to a second distal tip of the second elongate body.

[0131] Example 13. The neuromodulation system of any of Examples 1 to 12, wherein respective electrodes of the second electrode array are longitudinally offset from corresponding electrodes of the first electrode array in a same quadrant about a longitudinal axis defined by the distal catheter portion in the expanded configuration.

[0132] Example 14. The neuromodulation system of Example 13, wherein respective electrodes of the second electrode array are spaced from corresponding electrodes of the first electrode array by a distance in a range from 0.1 inch to 0.2 inch in the expanded configuration.

[0133] Example 15. The neuromodulation system of any of Examples 1 to 14, wherein the second electrode array includes more electrodes than the first electrode array.

[0134] Example 16. The neuromodulation system of Example 15, wherein the second electrode array comprises at least one electrode proximal to the first electrode array, and wherein the controller is configured to detect an efferent response to the stimulation signal.

[0135] Example 17. The neuromodulation system of Examples 15 or 16, wherein the second electrode array comprises at least one electrode distal to the first electrode array, and wherein the controller is configured to detect an afferent response to the stimulation signal.

[0136] Example 18. The neuromodulation system of any of Examples 1 to 17, wherein the first elongate body comprises a helical hollow strand.

[0137] Example 19. The neuromodulation system of Example 18, wherein the helical hollow strand is a first helical hollow strand, and wherein the second elongate body comprises a second helical hollow strand.

[0138] Example 20. The neuromodulation system of any one of Examples 1 to 18, wherein the second elongate body comprises a shape memory wire.

[0139] Example 21. The neuromodulation system of Example 20, wherein the shape memory wire comprises a nickel titanium alloy.

[0140] Example 22. The neuromodulation system of Examples 20 or 21, wherein the shape memory wire defines a groove extending along the shape memory wire, wherein the groove is configured to receive a plurality of electrode wires extending along the groove and configured to deliver the stimulation signal to the second electrode array.

[0141] Example 23. The neuromodulation system of Example 22, wherein each electrode wire of the plurality of electrode wires consists of a single filar wire.

[0142] Example 24. The neuromodulation system of any of Examples 20 to 23, wherein the second elongate body further comprises a polymer jacket surrounding the shape memory wire.

[0143] Example 25. The neuromodulation system of any of Examples 1 to 24, wherein the controller is further configured to detect a physiological response to the stimulation signal.

[0144] Example 26. A neuromodulation catheter comprising: a distal catheter portion configured to transform from a relatively low profile configuration to an expanded configuration, the distal catheter portion comprising a first elongate body and a second elongate body, the second elongate body being configured to be spaced from the first elongate body in the expanded configuration; a first electrode array disposed on the first elongate body and configured to deliver an ablation signal; and a second electrode array disposed on the second elongate body and configured to deliver a stimulation signal.

[0145] Example 27. The neuromodulation catheter of Example 26, wherein the first elongate body and the second elongate body are each configured to define a loop, a helix, or a spiral in the expanded configuration, wherein the first elongate body comprises a helical hollow strand, and wherein the second elongate body comprises a shape memory wire.

[0146] Example 28. A method for neuromodulation, the method comprising: delivering, by a first electrode array disposed on a first elongate body of a neuromodulationcatheter of any of claims 1 to 27, an ablation signal to a target site, the neuromodulation catheter being placed in a vessel of a patient; delivering, by a second electrode array disposed on a second elongate body of the neuromodulation catheter, a stimulation signal to the target site, the neuromodulation catheter being placed in the vessel of the patient; and determining, by processing circuitry, a physiological response to the stimulation signal.

[0147] Example 29. The method of Example 28, further comprising, determining, by the processing circuitry, based on the physiological response, an effectiveness of ablation at the target site induced by the ablation signal.

[0148] Example 30. The method of Examples 28 or 29, wherein the stimulation signal is a first stimulation signal preceding the ablation signal, the method further comprising, delivering, by the second electrode array, a second stimulation signal to the target site after the ablation signal.

Claims

CLAIMS:

1. A neuromodulation system comprising: a neuromodulation catheter comprising: a distal catheter portion configured to transform from a relatively low profile configuration to an expanded configuration, the distal catheter portion comprising a first elongate body and a second elongate body, the second elongate body configured to be spaced from the first elongate body in the expanded configuration; a first electrode array disposed on the first elongate body; and a second electrode array disposed on the second elongate body; and a controller configured to: generate an ablation signal configured to be delivered by the first electrode array; and generate a stimulation signal configured to be delivered by the second electrode array.

2. The neuromodulation system of claim 1, wherein the first elongate body and the second elongate body are each configured to define a loop, a helix, or a spiral in the expanded configuration.

3. The neuromodulation system of claims 1 or 2, wherein each electrode of the first electrode array is configured to deliver the ablation signal.

4. The neuromodulation system of any of claims 1 to 3, wherein the stimulation signal is a monopolar stimulation signal configured to be delivered by each electrode of the second electrode array.

5. The neuromodulation system of any of claims 1 to 3, wherein the stimulation signal is a bipolar stimulation signal configured to be delivered by at least one electrode pair of the second electrode array.

6. The neuromodulation system of any of claims 1 to 3, wherein the stimulation signal is a bipolar stimulation signal configured to be delivered by at least one electrode paircomprising a first electrode of the first electrode array and a second electrode of the second electrode array.

7. The neuromodulation system of any of claims 1 to 6, wherein the stimulation signal is a first stimulation signal, and wherein the controller is configured to generate the first stimulation signal before the ablation signal and a second stimulation signal after the ablation signal.

8. The neuromodulation system of any of claims 1 to 7, wherein at least one electrode of the first electrode array comprises gold, and wherein at least one electrode of the second electrode array comprises a platinum iridium alloy.

9. The neuromodulation system of any of claims 1 to 8, wherein respective electrodes of the second electrode array are longitudinally offset from corresponding electrodes of the first electrode array in a same quadrant about a longitudinal axis defined by the distal catheter portion in the expanded configuration.

10. The neuromodulation system of any of claims 1 to 9, wherein the helical hollow strand is a first helical hollow strand, and wherein the second elongate body comprises a second helical hollow strand.

11. The neuromodulation system of any one of claims 1 to 10, wherein the second elongate body comprises a shape memory wire.

12. The neuromodulation system of claim 11, wherein the shape memory wire defines a groove extending along the shape memory wire, and wherein the groove is configured to receive a plurality of electrode wires extending along the groove and configured to deliver the stimulation signal to the second electrode array.

13. The neuromodulation system of any of claims 1 to 12, wherein the controller is further configured to detect a physiological response to the stimulation signal.

14. A neuromodulation catheter comprising:a distal catheter portion configured to transform from a relatively low profile configuration to an expanded configuration, the distal catheter portion comprising a first elongate body and a second elongate body, the second elongate body being configured to be spaced from the first elongate body in the expanded configuration; a first electrode array disposed on the first elongate body and configured to deliver an ablation signal; and a second electrode array disposed on the second elongate body and configured to deliver a stimulation signal.

15. The neuromodulation catheter of claim 14, wherein the first elongate body and the second elongate body are each configured to define a loop, a helix, or a spiral in the expanded configuration, wherein the first elongate body comprises a helical hollow strand, and wherein the second elongate body comprises a shape memory wire.

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