Neuromodulation catheter having stimulation and ablation electrodes

Abstract

A neuromodulation system includes a neuromodulation catheter and a controller. The neuromodulation catheter includes an elongate body and an ablation electrode along the elongate body. The ablation electrode includes a plurality of electrode segments. Each electrode segment of the plurality of electrode segments may be electrically isolated from other respective electrode segments of the plurality of electrode segments. The controller may be configured to determine an impedance from a signal sensed by at least one electrode segment of the plurality of electrode segments and a reference pad, when the elongate body is placed in a vessel of a patient. The controller may be further configured to generate an ablation signal configured to be delivered by all electrode segments of the plurality of electrode segments, when the elongate body is placed in the vessel.

Description

NEUROMODULATION CATHETER HAVING STIMULATION AND ABLATIONELECTRODES

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 571,946, filed March 29, 2024, the entire content of which is incorporated herein by reference.TECHICAL 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 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. 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 detect impedance using an ablation electrode. For example, the ablation electrode may include a plurality of electrode segments, and at least one ablation electrode of the plurality of ablation electrode may be oriented toward or contact tissue. This way,contribution of or interference from blood to the measured impedance is reduced. Thus, the impedance detected may substantially correspond to tissue impedance. By using an electrode segment of the ablation electrode to determine impedance, complexity of the catheter may be reduced, for example, compared to a catheter using dedicated electrodes for sensing impedance and different electrodes for delivering ablation. Further, an ablation signal may be delivered by all electrode segments. By delivering the ablation signal from all electrode segments, a spatial profile of neuromodulation therapy delivered by the ablation electrode including a plurality of electrode segments may be the same, substantially the same, or functionally the same as an ablation electrode that does not include multiple segments. Thus, the ablation electrode may be used to detect impedance, without substantially changing an ablative function of the ablation electrode.

[0007] In some examples, an example neuromodulation system includes a neuromodulation catheter and a controller. The neuromodulation catheter includes an elongate body and an ablation electrode along the elongate body. The ablation electrode includes a plurality of electrode segments. Each electrode segment of the plurality of electrode segments may be electrically isolated from other respective electrode segments of the plurality of electrode segments. The controller may be configured to determine an impedance from a signal sensed by at least one electrode segment of the plurality of electrode segments and a reference pad, when the elongate body is placed in a vessel of a patient. The controller may be further configured to generate an ablation signal configured to be delivered by all electrode segments of the plurality of electrode segments, when the elongate body is placed in the vessel.

[0008] In some examples, an example neuromodulation catheter includes an elongate body including a distal portion. The distal portion may be configured to transform from a relatively low profile configuration to a deployed configuration. The neuromodulation catheter further includes an ablation electrode along the elongate body, the ablation electrode including a plurality of electrode segments. Each electrode segment of the plurality of electrode segments may be electrically isolated from other respective electrode segments of the plurality of electrode segments. Each electrode segment of the plurality of segments is arranged at approximately a same longitudinal position along the elongate body about a perimeter of the elongate body.

[0009] In some examples, an example technique includes determining, by processing circuitry, an impedance based on a signal from at least one electrode segment of a plurality ofelectrode segments of a neuromodulation catheter, the neuromodulation catheter being placed in a vessel of a patient. The technique may further include delivering, by all electrode segments of the plurality of electrode segments, an ablation signal to a target site, the neuromodulation catheter being placed in the vessel of the patient.

[0010] Further disclosed herein is a neuromodulation system that includes a neuromodulation catheter and a controller, wherein the neuromodulation catheter includes an elongate body and an ablation electrode along the elongate body, wherein the ablation electrode includes a plurality of electrode segments, wherein each electrode segment of the plurality of electrode segments may be electrically isolated from other respective electrode segments of the plurality of electrode segments, wherein the controller may be configured to determine an impedance from a signal sensed by at least one electrode segment of the plurality of electrode segments and a reference pad, when the elongate body is placed in a vessel of a patient, and wherein the controller may be further configured to generate an ablation signal configured to be delivered by all electrode segments of the plurality of electrode segments, when the elongate body is placed in the vessel.

[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 magnified partial view of the catheter of FIG. 1 A including an ablation electrode.

[0014] FIG. 1C is a diagram illustrating a top view of the ablation electrode of the catheter of FIG. IB.

[0015] FIG. 2 is a diagram illustrating a top view of an example ablation electrode including a plurality of uniform electrode segments.

[0016] FIG. 3 is a diagram illustrating a top view of an example ablation electrode including insulating material between neighboring electrode segments.

[0017] FIG. 4 is a diagram illustrating an example system including a multiplex wiring arrangement for an ablation electrode including a plurality of electrode segments.

[0018] FIG. 5 is a timing diagram illustrating comparing an example scheme for neuromodulation including sessions for detecting impedance and delivering ablation.

[0019] FIG. 6 is a block diagram illustrating an example configuration of the computing device of FIG. 1A.

[0020] FIG. 7 is a flow diagram illustrating an example technique for neuromodulation.

[0021] 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.

[0022] FIG. 9 is a conceptual illustration of an example sympathetic nervous system (SNS) illustrating how the brain communicated with the body via the SNS.

[0023] FIG. 10 is an enlarged anatomic view of nerves innervating a left kidney to form the renal plexus surrounding the left renal artery.

[0024] FIG. 11 is an anatomic view of a human body depicting neural efferent and afferent communication between the brain and kidneys.

[0025] FIG. 12 is a conceptual view of a human body depicting neural efferent and afferent communication between the brain and kidneys.

[0026] FIG. 13 is an anatomic view of the arterial vasculature of a human.

[0027] FIG. 14 is an anatomic view of the venous vasculature of a human.DETAILED DESCRIPTION

[0028] The present disclosure describes neuromodulation catheters including stimulation and ablation electrodes.

[0029] 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 the clinician 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.

[0030] 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. An electrode array (for example, including a plurality of ablation electrodes) is disposed on the distal portion. At least one ablation electrode includes a plurality of electrically isolated electrode segments. For example, the at least one electrode may have agenerally cylindrical configuration including isolation barriers that define the electrically isolated electrode regions.

[0031] One electrically isolated electrode segment may define an impedance sensing region. For example, the neuromodulation catheter may be oriented so that the impedance sensing region contacts the vessel, or a particular electrode segment in contact with the vessel may be selected as the sensing region for an impedance measurement. In some examples, the impedance is determined based on signals sensed by only the sensing region and a reference pad, to determine impedance associated with the vessel, and reduce interference from blood with impedance measurement. For example, a controller may be configured to determine an impedance based on a signal sensed by at least one electrode segment of the plurality of electrode segments and a reference pad. The controller may be further configured to generate an ablation signal configured to be delivered by all electrode segments of the plurality of electrode segments.

[0032] Denervation therapy may be delivered using all electrode segments, for example, to deliver radiofrequency (RF) energy. In this way, the ablation profile and current density remains substantially similar to denervation delivered by an unsegmented electrode (for example, a cylindrical electrode).

[0033] 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. 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 by computing 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.

[0034] FIG. IB is a diagram illustrating a magnified partial view of catheter 12 of FIG.1A including an ablation electrode 18. FIG. 1C is a diagram illustrating a top view of ablation electrode 18 of catheter 12 of FIG. IB. For example, catheter 12 may include an ablation electrode 18, and the electrical signal sent to catheter 12 may include an ablation signal delivered by ablation electrode 18 to a target site.

[0035] Controller 16 may be configured to generate an electrical signal comprising the ablation signal configured to be delivered by ablation electrode 18. 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 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 AC generator or a 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 20 and an elongate body 22 attached to handle 20. That is, handle 20 is positioned at a proximal portion of elongate body 22. Elongate body 22 may have any suitable outer diameter, and the diameter can be constant along the length of elongate body 22 or may vary along the length of elongate body 22. In some examples, elongate body 22 may be 2, 3, 4, 5, 6, or 7 French or another suitable size. Elongate body 22 extends along a central longitudinal axis L, and includes a distal portion 22A and a proximal portion 22B. Distal portion 22A includes an expandable portion 24. Expandable portion 24 is configured to transform from a relatively low-profile configuration (shown in FIG. 1 A) to a radially expanded deployed configuration (not shown in FIG. 1 A), such as a spiral, loop, or helical configuration, or an expanded balloon configuration.

[0037] Ablation electrode 18 may be segmented. For example, ablation electrode 18 may include a plurality of electrode segments 26. Ablation electrode 18, and plurality of electrode segments 26, may have any suitable shape, size, or form. Each electrode segment of plurality of segments 26 may be arranged at approximately a same longitudinal position along elongate body 22 about a perimeter of elongate body 22. In some examples, ablation electrode 18 is a ring electrode, and electrode segments 26 include ring segments surrounding at least a portion of elongate body 22. For example, ablation electrode 18 may be cylindrical, and each electrode segment of plurality of electrode segments 26 may be a cylindrical segment circumferentially disposed about the elongate body.

[0038] Ablation electrode 18 may be disposed along elongate body 24, for example, aligned with a direction along a longitudinal axis L of catheter 12. In some examples, catheter 12 includes a plurality of ablation electrodes including ablation electrode 18, for example, disposed along elongate body 24. For example, catheter 12 may include two, three, four, or more ablation electrodes. In some examples, each ablation electrode of the plurality of ablation of electrodes is identical in one or more of shape, size, or form, for example, the same as ablation electrode 18. For example, each ablation electrode of the plurality of ablation electrodes may have a same ablation electrode length along longitudinal axis L of elongate body 22, for example, as ablation electrode 18. In some examples, each ablation electrode of the plurality of ablation electrodes includes a respective plurality of electrode segments, for example, similar to electrode segments 26 of ablation electrode 18.

[0039] In other examples, at least one ablation electrode of the plurality of electrodes differs from ablation electrode 18 in one or more of shape, size, or form. For example, ablation electrode 18 may be segmented, while at least one other electrode of the plurality of electrodes may not be segmented. In some examples, catheter 12 does not include any ablation electrode other than ablation electrode 18.

[0040] In the example shown in FIGS. 1A and IB, ablation electrode 18 is disposed on expandable portion 24 of elongate body 22. Although FIG. 1 A illustrates catheter 12 as having four ablation electrodes, other example catheters may include one, two, three, five, or more ablation electrodes. Generator 40 may be configured to deliver therapy to tissue of a patient via ablation electrode 18, for example, to modulate a target nerve of the patient. For example, all electrode segments of plurality of electrode segments 26 of ablation electrode 18 may be coupled together, and generator 40 may deliver an ablation signal to tissue, or to a target site via all electrode segments (e.g., since electrode segments 26 are coupled together). Catheter 12 may thus deliver denervation therapy via ablation electrode 18 (for example, via the plurality of electrode segments 26), and computing device 14 or controller 16 may control catheter 12 to deliver denervation therapy.

[0041] In some examples, ablation electrode 18 (for example, at least one of electrode segments 26) includes gold, platinum, or iridium oxide. For example, gold may promote thermal dissipation and reduce thermal buildup in course of ablation. Iridium oxide may have a high electrical conductivity. In some examples, ablation electrode 18 includes gold plated with a coating of iridium oxide.

[0042] Electrode segments of plurality of electrode segments 26 may be identical, similar, or different in composition or geometry. For example, two or more electrode segments of plurality of electrode segments 26 may be similar to each other, or differ from each other in composition or geometry. In some examples, each electrode segment of plurality of electrode segments 26 defines a same electrode segment area. In some examples, each electrode segment of plurality of electrode segments 26 defines a same electrode segment shape.

[0043] In other examples, at least two electrode segments of plurality of electrode segments 26 differ in surface area. For example, as shown in FIG. 1C, plurality of electrode segments 26 includes a first electrode segment 26 A and a second electrode segment 26B. First electrode segment 26A defines a first electrode segment area (for example, a radially exterior surface area in a direction along longitudinal axis L), and a second electrode segment 26B may define a second electrode segment area greater than the first electrode segment area. In some examples, first electrode segment 26A is configured to contact or be oriented toward tissue within a vessel. In some examples, ablation electrode includes a total of two electrode segments 26A and 26B, for example, no more than two electrode segments.

[0044] FIG. 2 is a diagram illustrating a top view of an example ablation electrode 118 including a plurality of uniform electrode segments 126A, 126B, 126C, and 126D (collectively referred to as “uniform electrode segments 126”). Ablation electrode 118 and plurality of uniform electrode segments 126 are similar to ablation electrode 18 and plurality of electrode segments 26 described with reference to FIGS. 1 A to 1C, but differ in the geometry of electrode segments. In particular, each electrode segment of plurality of electrode segments 126 is identical in composition, size, and shape. In some examples, ablation electrode 118 includes four electrode segments. In some examples, ablation electrode 118 includes a total of four electrode segments, for example, no more than four electrode segments 126.

[0045] Turning back to FIGS. 1 A to 1C, each electrode segment of plurality of electrode segments 26 may be electrically isolated from other respective electrode segments of plurality of electrode segments 26. For example, respective pairs of neighboring electrode segments 26 may be separated by a respective electrically insulating region 28. The electrically insulating region 28 define an air-gap, or may be occupied by material, for example, insulating material. In some examples, each electrode segment of plurality of electrode segments 26 is laterally spaced along a surface of elongate body 22 from other respective electrode segments ofplurality of electrode segments 26. In some examples, electrically insulating region 28 may be occupied with material, as described with reference to FIG. 3.

[0046] FIG. 3 is a diagram illustrating a top view of an example ablation electrode 218 including insulating material 230 between neighboring electrode segments. Ablation electrode 218 may be similar to ablation electrode 18 described with reference to FIG. 1 A or ablation electrode 118 described with reference to FIG. IB, but differ in the presence of insulating material 230 in an electrically insulating region 228. Insulating material 230 may include at least one of a metal, an alloy, or a polymer. In some examples, the metal or the alloy includes at least one of bismuth, tungsten, or titanium. In some examples, the polymer includes at least a polyimide.

[0047] Turning back to FIG. 1 A, distal portion 22A of elongate body 22 is configured to be advanced within an anatomical lumen of a human patient to locate ablation electrode 18 at a target tissue site within or otherwise proximate to the anatomical lumen. For example, elongate body 22 may be configured to position distal portion 22A 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.

[0048] 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 portion 22A includes percutaneously inserting a guidewire (not shown in FIG. 1 A) into a vessel of a patient and moving elongate body 22 (for example, at least expandable portion 24) along the guidewire until expandable portion 24 reaches a target tissue site (for example, a renal artery). For example, distal portion 22A of elongate body 22 may define a lumen configured to receive a guidewire for delivery of expandable portion 24 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.

[0049] A distal end of elongate body 22 defines distal tip 30. Distal tip 30 is configured to facilitate navigation of distal portion 22A within the vasculature of the patient to a blood vessel. In some examples, distal tip 30 may be atraumatic, for example, to resist or avoidpuncturing a vessel of a blood vessel during navigation of distal portion 22A within the blood vessel.

[0050] In the example illustrated in FIG. 1 A, catheter 12 is in a relatively low-profile delivery configuration, in which distal portion 22A defines a relatively smaller radial extent (a relatively low-profile, such as a relatively linear configuration) relative to an expanded (also referred to as a radially expanded and / or deployed) configuration in which expandable portion 24 of distal portion 22A defines a relatively larger radial extent. In some examples, the radial extent is measured in a direction orthogonal to central longitudinal axis L. Distal portion 22A may be delivered through vasculature of the patient to the target tissue site in the low-profile configuration. In some examples, expandable portion 24 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 hollow helical strand) of elongate body 22. In some examples, expandable portion extends along a straight line aligned with longitudinal axis L in the relatively low-profile configuration shown in FIG. 1 A. Expandable portion 24 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 24 to un-constrain expandable portion 24 and cause or allow expandable portion 24 to transform from the low-profile configuration to an expanded configuration. Thus, expandable portion 24 may be configured to radially expand away from the straight line to the expanded configuration.

[0051] In some examples, in an expanded configuration, expandable portion 24 defines a loop, a helix, or a spiral shape, or a basket, or a stent-like configuration. In the expanded configuration, expandable portion 24 is configured to position one or more electrodes (including ablation electrode 18) near a vessel wall, for example, in apposition with the vessel wall.

[0052] In some examples, expandable portion 24 may be expanded or may self-expand as a result of proximal retraction of a guide member from distal portion 22A. The clinician may retract the guide member to a location along distal portion 22A proximal to expandable portion 24 to cause or allow expandable portion 24 to expand. In the expanded configuration, expandable portion 24 may place at least one electrode (for example, ablation electrode 18) at a first location relative to the vessel 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 thetarget tissue site to target tissue adjacent to the blood vessel. The neuromodulation therapy may include, but is not limited to, radiofrequency (RF) energy, or the like.

[0053] The clinician may rotate handle 20, or otherwise proximal portion 22B, to apply a torque to distal portion 22A and cause expandable portion 24 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 20 or proximal portion 22B to expandable portion 24 may cause expandable portion 24 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 24.

[0054] 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 20 and elongate body 22.

[0055] Ablation electrode 18 may be coupled to a thermocouple 32. For example, controller 16 may sense a respective temperature of ablation electrode 18 (or of an electrode segment of plurality of electrode segments 26) via thermocouple 32. In some examples, controller 16 may be configured to terminate ablation therapy in response to a temperature sensed by thermocouple 32, for example, to avoid excessive heating of catheter 12 or neighboring tissue. In some examples, a same electrode segment of plurality of electrode segments 26 used to determine impedance is coupled to thermocouple 32. In other examples, a different electrode segment of plurality of electrode segments 26 from an electrode segment used to determine impedance is coupled to thermocouple 32.

[0056] System 10 further includes a reference pad 34. Impedance may be determined based on signals sensed by ablation electrode 18 and reference pad 34, for example, based on a voltage across ablation electrode 18 and reference pad 34. In some examples, catheter 12 includes reference pad 34, for example, along elongate body 22. In other examples, reference pad 34 is spaced from catheter 12 (or otherwise from ablation electrode 18), for example, being positioned in any suitable position relative to catheter 12 or ablation electrode 18. In some examples, system 10 does not include a separate reference pad 34, and an electrode or electrode segment of catheter 12 may function as a reference pad. For example, an electrode segment of plurality of electrode segments 26 may function as a reference pad. In some examples, reference pad 34 includes an electrode.

[0057] Controller 16 is configured to determine an impedance from a signal sensed by at least one electrode segment of plurality of electrode segments 26 and reference pad 34. Controller 16 may be further configured to generate the ablation signal, for example, configured to be delivered by all electrode segments of plurality of electrode segments 26. In this way, controller 16 may use ablation electrode 18 (for example, one of electrode segments 26) to detect impedance, and may not need additional electrodes or dedicated electrodes for determining impedance.

[0058] In some examples, controller 16 is further configured to modulate the ablation signal based on at least the impedance. For example, controller 16 may alternate determining the impedance and delivering the ablation signal, and may modulate the ablation signal (for example, change the intensity of, start, or stop, the ablation signal). In some examples, the determined impedance may be indicative of heating of tissue beyond a predetermined threshold, and controller 16 may reduce the intensity of the ablation signal, or stop ablation in response to such an impedance.

[0059] In some examples, controller 16 is configured to determine the impedance based on the signal from no more than one electrode segment of plurality of electrode segments 26 (for example, from a single electrode segment). In some such examples, a clinician may initially position catheter 12 so that the single electrode segment from which controller 16 receives the signal contacts tissue, is oriented toward tissue, or has a relatively low contact with blood. In this way, contribution of blood to or interference of blood with impedance, which may otherwise affect the sensed impedance, can be reduced or prevented.

[0060] In some examples, the identity of an electrode segment contacting tissue or closest to tissue from plurality of electrode segments 26 may not be initially known. In some examples, controller 16 is configured to determine respective impedances from signals sensed by respective electrode segments of plurality of electrode segments 26 and reference pad 34. In some such examples, controller 16 is configured to select a maximum impedance from the respective impedances to determine the impedance. For example, the maximum impedance may be associated with a respective electrode segment that is in contact with tissue, or closest to tissue, or oriented toward tissue, in comparison with respective impedances associated with other electrode segments that may not contact the tissue or be more distant from the tissue. In some such examples, controller 16 is configured to generate a selection signal indicative of a respective electrode segment of plurality of electrode segments 26 being associated with the maximum impedance. The clinician may re-position catheter 12 in response to the selectionsignal. In some examples, controller 16 is configured to select a minimum impedance, an impedance greater than a threshold impedance, an impedance lower than a threshold impedance, or an impedance within a predetermined range, from the respective impedances, to determine the impedance.

[0061] In some examples, controller 16 is configured to determine the impedance from the signal sensed by only a first electrode segment 26A of two electrode segments 26. In some examples, first electrode segment 26A is configured to contact or be oriented toward tissue within a vessel.

[0062] Turning back to FIG. 2, in some examples, controller 16 is configured to determine respective impedances from signals sensed by pairs of respective electrode segments of plurality of uniform electrode segments 126. For example, controller 16 may determine impedance from signals sensed by a pair of neighboring uniform electrode segments, or a pair of spaced or opposed uniform electrode segments, of plurality of uniform electrode segments 126. In some examples, controller 16 is configured to determine respective impedances for each respective pair of neighboring uniform electrode segments 126 (e.g., 126A and 126B, 126B and 126C, 126C and 126D, and 126D and 126A), and select a maximum impedance of the respective impedances to determine the impedance.

[0063] FIG. 4 is a diagram illustrating an example system 300 including a multiplex wiring arrangement 300 for ablation electrode 118 including a plurality of electrode segments. While ablation electrode 118 is shown in FIG. 4, in other examples, multiplex wiring arrangement 300 may be coupled to any ablation electrode according to the present disclosure. Multiplex wiring arrangement 300 may be carried on a catheter (for example, catheter 12 or a catheter similar to catheter 12). For example, multiplex wiring arrangement 300 may be positioned along an elongate body (for example, elongate body 12) or some other component of the catheter. Multiplex wiring 300 is configured to split an ablation signal into respective ablation signals sent to each electrode segment of ablation electrode 118.

[0064] System 10, catheter 12, and / or controller 16 may be used to deliver ablation and stimulation for neuromodulation according to any appropriate scheme.

[0065] FIG. 5 is a timing diagram illustrating comparing an example scheme for neuromodulation including sessions for detecting impedance and delivering ablation. In the scheme shown in FIG. 5, impedance is detected for a first time duration ti, followed by delivering ablation in a second time duration t2. In some examples, impedance is furtherdetected in a third time duration t3and the effect of ablation on tissue may be assessed. Ablation may be continued, modified, or termination in response to the impedance.

[0066] Thus, controller 16 may control catheter 12 to deliver a neuromodulation therapy including interleaved ablation and impedance detection. In some examples, computing device 14 controls controller 16 to deliver ablation 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.

[0067] FIG. 6 is a block diagram illustrating an example configuration of computing device 14 of FIG. 1A. 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.

[0068] 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 processing circuitry 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).

[0069] 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.

[0070] 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.

[0071] 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.

[0072] 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.

[0073] At least one application 180 executable by processing circuitry 170 of computing device 14 may include an impedance interface application 182 and a monitoring system 184 that may utilize physiological data or other data obtained during neuromodulation to monitorthe 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.

[0074] Execution of impedance 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, impedance interface 182 configures computing device 14 to communicate with controller 16 via communication circuitry 184. Processing circuitry 170 may determine an impedance from a signal sensed by ablation electrode 18, and store the impedance data 192 in storage device 172. Impedance 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 impedance 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.

[0075] 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 FIGS. 1 A to 1C. However, the example technique may be implemented by any suitable computing device, controller, or system alone or in combination with processing circuitry 170.

[0076] The technique may include positioning of neuromodulation catheter 12 in a vessel (400). For example, a clinician may position neuromodulation catheter 12 such that first electrode segment 26A contacts or is relatively close to tissue. In other examples, the clinician may not be able to ascertain an orientation of plurality of electrode segments 26, and the positioning 400 may include positioning catheter 12 in the vessel without regard for orientation of electrode segments 26, but toward a target site.

[0077] The technique may include determining, by processing circuitry 170, an impedance from a signal sensed by at least one electrode segment of plurality of electrode segments 26 of neuromodulation catheter 12 and reference pad 34 (402). In some examples, determining the impedance (402) includes determining the impedance from the signal sensed by no more than one electrode segment of plurality of electrode segments 26.

[0078] In some examples, the determining (402) further includes determining, by processing circuitry 170, a respective impedances from signals sensed by respective electrode segments of plurality of electrode segments 26 and reference pad 34. The determining (402)may further include selecting, by processing circuitry 170, a maximum impedance from the respective impedances to determine the impedance.

[0079] The technique may include delivering, by all electrode segments of plurality of electrode segments 26, an ablation signal to a target site (404). For example, processing circuitry 170 may cause controller 16 to generate the ablation signal, and to send the ablation signal to neuromodulation catheter 12.

[0080] In some examples, the delivering (404) may further include, or be preceded by, positioning the neuromodulation catheter such that an electrode segment which senses the impedance with reference pad 34, is oriented toward the target site.

[0081] In some examples, the impedance determined (402) is a first impedance, and the technique further includes determining, by processing circuitry 170, a second impedance from the signal sensed by the at least one electrode segment after delivering the ablation signal (404).

[0082] The technique may further include modulating, by processing circuitry 170, the ablation signal based on the impedance. For example, one or more of the positioning (400), determining the impedance (402), and delivering the ablation signal (404) may be repeated, with processing circuitry 170 changing an intensity or magnitude of the ablation signal, for example, in response to the impedance.

[0083] Thus, example systems and techniques according to the present disclosure may be used to deliver, monitor, or control neuromodulation therapy.

[0084] 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 delivery 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 22B or elongate body 22 from outside the intravascular path (P), a clinician may advance distal portion 22A of elongate body 22 through the sometimes-tortuous intravascular path (P) and remotely manipulate distal portion 22A (FIG. 1 A) of elongate body 22. Distal portion 22A may be remotely manipulated by the clinician using handle 20.

[0085] In the example illustrated in FIG. 8, distal portion 22A 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 22A can transform into an expanded configuration (for example, a helical configuration, a spiral configuration, or the like) for delivering ultrasound energy. In other examples, elongate body 22 may be self-steerable such that therapy may be delivered to the target tissue site without the aid of inner member 123.

[0086] 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 be useful 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.

[0087] 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 theadventitia 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 22A within the renal artery, delivering the therapy to targeted tissue, or effectively modulating the renal nerves with the therapy delivery device.

[0088] 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).

[0089] 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.

[0090] 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.

[0091] 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.

[0092] 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 (which lie near the vertebral column) or prevertebral (which lie near the aortic bifurcation) ganglia extending alongside the spinal column.

[0093] 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.

[0094] 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 locatedbetween 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.

[0095] 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.

[0096] 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.

[0097] 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 celiac ganglion, the superior mesenteric ganglion, and the aorticorenal ganglion to the renal plexus (RP) and are distributed to the renal vasculature.

[0098] 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.

[0099] 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 theprogression 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.

[0100] 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.

[0101] 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 designed to reduce renal sympathetic stimulation have the potential to improve survival in patients with heart failure.

[0102] 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.

[0103] 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.

[0104] 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.

[0105] 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.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] 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 theiliac 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.

[0110] 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.[OHl] 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.

[0112] 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 specific patient 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.

[0113] 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 someother 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.

[0114] 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).

[0115] The neuromodulation system may also be configured to allow for adjustable positioning and repositioning of distal portion 22A (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.

[0116] As noted above, an apparatus positioned within a renal artery may be configured so that distal portion 22A 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, thecomposite 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.

[0117] 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°.

[0118] 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.

[0119] 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 in the 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.

[0120] 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 adifferent 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.

[0121] 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).

[0122] 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.

[0123] 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.

[0124] The following enumerated clauses describe examples according to the present disclosure.

[0125] Clause 1 : A neuromodulation system including: a neuromodulation catheter including: an elongate body; an ablation electrode along the elongate body, the ablation electrode including a plurality of electrode segments, each electrode segment of the plurality of electrode segments being electrically isolated from other respective electrode segments of the plurality of electrode segments; and a controller configured to: determine an impedance from a signal sensed by at least one electrode segment of the plurality of electrode segments and a reference pad, when the elongate body is placed in a vessel of a patient; and generate an ablation signal configured to be delivered by all electrode segments of the plurality of electrode segments, when the elongate body is placed in the vessel.

[0126] Clause 2: The neuromodulation system of clause 1, where the controller is further configured to modulate the ablation signal based on at least the impedance.

[0127] Clause 3: The neuromodulation system of clauses 1 or 2, where the controller is configured to determine the impedance from the signal sensed by no more than one electrode segment of the plurality of electrode segments and the reference pad.

[0128] Clause 4: The neuromodulation system of clauses 1 or 2, where the controller is configured to determine respective impedances from signals sensed by respective electrode segments of the plurality of electrode segments and the reference pad, and where to determine the impedance, the controller is configured to select a maximum impedance from the respective impedances.

[0129] Clause 5: The neuromodulation system of clause 4, where the controller is configured to generate a selection signal indicative of a respective electrode segment of the plurality of electrode segments being associated with the maximum impedance.

[0130] Clause 6: The neuromodulation system of any of clauses 1 to 5, where each electrode segment of the plurality of segments is arranged at approximately a same longitudinal position along the elongate body about a perimeter of the elongate body.

[0131] Clause 7: The neuromodulation system of any of clauses 1 to 6, where each electrode segment of the plurality of electrode segments is laterally spaced along a surface of the elongate body from other respective electrode segments of the plurality of electrode segments.

[0132] Clause 8: The neuromodulation system of any of clauses 1 to 7, where the ablation electrode is cylindrical, and where each electrode segment of the plurality of electrode segments is a cylindrical segment circumferentially disposed about the elongate body.

[0133] Clause 9: The neuromodulation system of any of clauses 1 to 8, where each electrode segment of the plurality of electrode segments defines a same electrode segment area.

[0134] Clause 10: The neuromodulation system of any of clauses 1 to 9, where each electrode segment of the plurality of electrode segments defines a same electrode segment shape.

[0135] Clause 11 : The neuromodulation system of any of clauses 1 to 8, where the plurality of electrodes segments includes two electrode segments, and where a first electrode segment of the two electrode segments defines a first electrode segment area, and where a second electrode segment of the two electrode segments defines a second electrode segment area greater than the first electrode segment area.

[0136] Clause 12: The neuromodulation system of clause 11, where the controller is configured to determine the impedance from the signal sensed by only the first electrode segment.

[0137] Clause 13: The neuromodulation system of clauses 11 or 12, where the first electrode segment is configured to contact tissue within the vessel.

[0138] Clause 14: The neuromodulation system of any of clauses 1 to 13, where the ablation electrode includes a total of two electrode segments.

[0139] Clause 15: The neuromodulation system of any of clauses 1 to 13, where the ablation electrode includes a total of four electrode segments.

[0140] Clause 16: The neuromodulation system of any of clauses 1 to 15, where the ablation electrode includes at least one of gold, platinum, or iridium oxide.

[0141] Clause 17: The neuromodulation system of any of clauses 1 to 16, where each pair of electrode segments of the plurality of electrode segments is separated by a respective electrically insulating region.

[0142] Clause 18: The neuromodulation system of clause 17, further including an insulating material in the respective electrically insulating region.

[0143] Clause 19: The neuromodulation system of clause 18, where the insulating material includes at least one of a metal, an alloy, or a polymer.

[0144] Clause 20: The neuromodulation system of clause 19, where the metal or the alloy includes at least one of bismuth, tungsten, or titanium.

[0145] Clause 21 : The neuromodulation system of clause 19, where the polymer includes at least a polyimide.

[0146] Clause 22: The neuromodulation system of any of clauses 1 to 21, further including a thermocouple coupled to at least one electrode segment of the plurality of electrode segments.

[0147] Clause 23 : The neuromodulation system of any of clauses 1 to 22, where the neuromodulation catheter includes a plurality of ablation electrodes along the elongate body, the plurality of ablation electrodes including the ablation electrode.

[0148] Clause 24: The neuromodulation system of clause 23, where each ablation electrode of the plurality of ablation electrodes includes a respective plurality of electrode segments.

[0149] Clause 25: The neuromodulation system of any of clauses 1 to 24, further including a computing device configured to control the controller to deliver neuromodulation therapy via the neuromodulation catheter.

[0150] Clause 26: A neuromodulation catheter including: an elongate body including a distal portion, the distal portion configured to transform from a relatively low profile configuration to a deployed configuration; and an ablation electrode along the elongate body, the ablation electrode including a plurality of electrode segments, each electrode segment of the plurality of electrode segments being electrically isolated from other respective electrode segments of the plurality of electrode segments, where each electrode segment of the plurality of segments is arranged at approximately a same longitudinal position along the elongate body about a perimeter of the elongate body.

[0151] Clause 27: The neuromodulation catheter of clause 26, where the ablation electrode is cylindrical, and where each electrode segment of the plurality of electrode segments is a cylindrical segment circumferentially disposed about the elongate body.

[0152] Clause 28: The neuromodulation catheter of clauses 26 or 27, where the ablation electrode consists of two electrode segments, where a first electrode segment of the two electrode segments defines a first electrode segment area, and where a second electrode segment of the two electrode segments defines a second electrode segment area greater than the first electrode segment area.

[0153] Clause 29: The neuromodulation catheter of any of clauses 26 to 28, where the neuromodulation catheter includes a plurality of ablation electrodes along the elongate body, the plurality of ablation electrodes including the ablation electrode, and where each ablation electrode of the plurality of ablation electrodes includes a respective plurality of electrode segments.

[0154] Clause 30: A method for neuromodulation, the method including: determining, by processing circuitry, an impedance based on a signal sensed by at least one electrode segment of a plurality of electrode segments of a neuromodulation catheter of any of clauses 1 to 29 and a reference pad, the neuromodulation catheter being placed in a vessel of a patient; delivering, by all electrode segments of the plurality of electrode segments, an ablation signal to a target site, the neuromodulation catheter being placed in the vessel of the patient.

[0155] Clause 31 : The method of clause 30, where determining the impedance includes determining the impedance from the signal sensed by no more than one electrode segment of the plurality of electrode segments and the reference pad.

[0156] Clause 32: The method of clause 31, further including positioning the neuromodulation catheter such that the one electrode segment is at least one of in contact with tissue in the vessel oriented toward the target site.

[0157] Clause 33: The method of clause 30, further including: determining, by the processing circuitry, respective impedances from signals sensed by respective electrode segments of the plurality of electrode segments and the reference pad, and determining, by the processing circuitry, the impedance by selecting a maximum impedance from the respective impedances.

[0158] Clause 34: The method of any of clauses 30 to 33, further including, modulating, by the processing circuitry, the ablation signal based on at least the impedance.

[0159] Clause 35: The method of any of clauses 30 to 34, where the impedance is a first impedance, the method further comprising determining, by the processing circuitry, a second impedance based on the signal sensed by the at least one electrode segment after delivering the ablation signal.

[0160] 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.

[0161] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

CLAIMS1. A neuromodulation system including: a neuromodulation catheter comprising: an elongate body; an ablation electrode along the elongate body, the ablation electrode comprising a plurality of electrode segments, each electrode segment of the plurality of electrode segments being electrically isolated from other respective electrode segments of the plurality of electrode segments; and a controller configured to: determine an impedance from a signal sensed by at least one electrode segment of the plurality of electrode segments and a reference pad, when the elongate body is placed in a vessel of a patient; and generate an ablation signal configured to be delivered by all electrode segments of the plurality of electrode segments, when the elongate body is placed in the vessel.

2. The neuromodulation system of claim 1, wherein the controller is further configured to modulate the ablation signal based on at least the impedance.

3. The neuromodulation system of claims 1 or 2, wherein the controller is configured to determine the impedance from the signal sensed by no more than one electrode segment of the plurality of electrode segments and the reference pad.

4. The neuromodulation system of any of claims 1 to 3, wherein the controller is configured to determine respective impedances from signals sensed by respective electrode segments of the plurality of electrode segments and the reference pad, wherein to determine the impedance, the controller is configured to select a maximum impedance from the respective impedances, and wherein the controller is configured to generate a selection signal indicative of a respective electrode segment of the plurality of electrode segments being associated with the maximum impedance.

5. The neuromodulation system of any of claims 1 to 4, wherein the ablation electrode is cylindrical, and wherein each electrode segment of the plurality of electrode segments is a cylindrical segment circumferentially disposed about the elongate body.

6. The neuromodulation system of any of claims 1 to 5, wherein the plurality of electrodes segments comprises two electrode segments, wherein a first electrode segment of the two electrode segments defines a first electrode segment area, wherein a second electrode segment of the two electrode segments defines a second electrode segment area greater than the first electrode segment area, wherein the first electrode segment is configured to contact tissue within the vessel, and wherein the controller is configured to determine the impedance from the signal sensed by only the first electrode segment.

7. The neuromodulation system of any of claims 1 to 6, wherein the ablation electrode comprises a total of two electrode segments.

8. The neuromodulation system of any of claims 1 to 6, wherein the ablation electrode comprises a total of four electrode segments.

9. The neuromodulation system of any of claims 1 to 8, wherein each pair of electrode segments of the plurality of electrode segments is separated by a respective electrically insulating region.

10. The neuromodulation system of any of claims 1 to 9, wherein the neuromodulation catheter comprises a plurality of ablation electrodes along the elongate body, the plurality of ablation electrodes comprising the ablation electrode.

11. The neuromodulation system of any of claims 1 to 10, further comprising a computing device configured to control the controller to deliver neuromodulation therapy via the neuromodulation catheter.

12. A neuromodulation catheter comprising: an elongate body comprising a distal portion, the distal portion configured to transform from a relatively low profile configuration to a deployed configuration; and an ablation electrode along the elongate body, the ablation electrode comprising a plurality of electrode segments, each electrode segment of the plurality of electrode segments being electrically isolated from other respective electrode segments of the plurality of electrode segments, wherein each electrode segment of the plurality of segments is arranged at approximately a same longitudinal position along the elongate body about a perimeter of the elongate body.

13. The neuromodulation catheter of claim 12, wherein the ablation electrode is cylindrical, and wherein each electrode segment of the plurality of electrode segments is a cylindrical segment circumferentially disposed about the elongate body.

14. The neuromodulation catheter of claims 12 or 13, wherein the ablation electrode consists of two electrode segments, wherein a first electrode segment of the two electrode segments defines a first electrode segment area, and wherein a second electrode segment of the two electrode segments defines a second electrode segment area greater than the first electrode segment area.

15. The neuromodulation catheter of any of claims 12 to 14, wherein the neuromodulation catheter comprises a plurality of ablation electrodes along the elongate body, the plurality of ablation electrodes comprising the ablation electrode, and wherein each ablation electrode of the plurality of ablation electrodes comprises a respective plurality of electrode segments.

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