Neuromodulation catheters

Abstract

In some examples, a neuromodulation catheter includes an elongate body extending along a longitudinal axis, at least one therapy delivery element, and at least one stiffening wire. The at least one therapy delivery element may be disposed on an expandable portion of the elongate body. The expandable portion may be configured to transform from a relatively low-profile configuration to an expanded, deployed configuration. The at least one stiffening wire includes a shape memory material and extends at least partially along the expandable portion.

Description

NEUROMODULATION CATHETERS

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 579,690, filed 30 August 2023, the entire content of which is incorporated herein by reference.TECHNICAL FIELD

[0002] The present disclosure generally relates to neuromodulation catheters, and to catheters including at least one therapy delivery element for neuromodulation.BACKGROUND

[0003] Catheters have been proposed for use with various medical procedures. For example, a catheter can be configured to deliver neuromodulation therapy to a target tissue site to modify the activity of nerves at or near the target tissue site. The nerves can be, for example, sympathetic nerves. The sympathetic nervous system (SNS) is a primarily involuntary bodily control system typically associated with stress responses. Chronic overactivation of the SNS is a maladaptive response that can drive the progression of many disease states. For example, excessive activation of the renal SNS has been identified experimentally and in humans as a likely contributor to the complex pathophysiology of arrhythmias, hypertension, states of volume overload (e.g., heart failure), and progressive renal disease.SUMMARY

[0004] In general, this disclosure describes system, techniques, and devices for neuromodulation, and neuromodulation catheters including at least one stiffening wire configured to facilitate a substantially commensurate movement of at least one therapy delivery element.

[0005] A neuromodulation catheter, e.g., for use in a renal denervation procedure, may be configured to transform from a relatively low-profile delivery configuration to a radially expanded (deployed) configuration. For example, an expandable portion of the catheter can be configured to transform from a substantially straight configuration to a helical or spiral configuration that places at least one therapy delivery element of the catheter in apposition to a vessel wall. The at least one therapy delivery element may include one or more electrodes or another energy delivery element. A proximal portion of the catheter may be coupled to ahandle, which can be used to manipulate the expandable portion. For example, a clinician may translate or rotate the handle to cause a translation or rotation of the expandable portion.

[0006] The at least one stiffening wire is configured to facilitate a controlled or predictable rotation of the expandable portion, for example, in response to rotating a proximal catheter portion of the neuromodulation catheter relative to a central longitudinal axis of an elongate body of the neuromodulation catheter. Compared to a catheter that does not include at least one stiffening wire, a neuromodulation catheter according to the present disclosure may enable better rotational control of the expandable portion. For example, the at least one stiffening wire may transmit torque to the expandable portion from a proximal portion and / or resist deformation of the expandable portion, such that rotating the proximal catheter portion results in a substantially commensurate rotation of the distal catheter portion. Thus, a clinician may be able to exercise control over the orientation of the at least one therapy delivery element, for example, relative to a target therapy site. In some examples, the clinician may orient the at least one therapy delivery element multiple times during a medical procedure, and deliver therapy using multiple orientations or location of the at least one electrode during the medical procedure. For example, delivering therapy at different orientations of the at least one electrode may generate a circumferential (e.g., spiral or circular), arced, or semi-circular therapy delivery pattern.

[0007] Devices, systems, and techniques according to the present disclosure may facilitate delivery of a predetermined pattern of neuromodulation therapy at a target site, for example, by providing a clinician with sufficient control over an orientation and a location of at least one therapy delivery element relative to the target site.

[0008] In some examples according to the present disclosure, an example neuromodulation catheter includes an elongate body extending along a longitudinal axis, at least one therapy delivery element, and at least one stiffening wire. The at least one therapy delivery element may be disposed on an expandable portion of the elongate body. The expandable portion may be configured to transform from a relatively low-profile configuration to an expanded configuration. The at least one stiffening wire may include a shape memory material and extend at least partially along the expandable portion.

[0009] In some examples according to the present disclosure, a neuromodulation system includes the neuromodulation catheter, and a control circuitry configured to control the neuromodulation catheter to cause the neuromodulation catheter to deliver neuromodulation therapy.

[0010] In some examples according to the present disclosure, a method of forming a neuromodulation catheter includes forming an elongate body including at least one therapy delivery element disposed on an expandable portion. The expandable portion is configured to transform from a relatively low-profile configuration to an expanded configuration. The method may further include coupling at least one stiffening wire including a shape memory material to the elongate body such that the at least one stiffening wire extends at least partially along the expandable portion.

[0011] In some examples according to the present disclosure, a method includes advancing a neuromodulation catheter through vasculature to a target tissue site within a blood vessel of a patient. The neuromodulation catheter includes an elongate body extending along a longitudinal axis, at least one therapy delivery element disposed on an expandable portion of the elongate body, and at least one stiffening wire. The expandable catheter portion is configured to transform from a relatively low-profile configuration to an expanded configuration. The at least one stiffening wire may include a shape memory material and extending at least partially along the expandable portion. The method may further include expanding the expandable portion to place the at least one therapy delivery element in apposition to a vessel wall of the blood vessel at a location. The method may further include delivering, via the at least one therapy delivery element, a therapy to tissue of the patient through the vessel wall at the location.

[0012] Further disclosed herein is a neuromodulation catheter that includes an elongate body extending along a longitudinal axis, at least one therapy delivery element, and at least one stiffening wire, wherein the at least one therapy delivery element may be disposed on an expandable portion of the elongate body, wherein the expandable portion may be configured to transform from a relatively low-profile configuration to an expanded, deployed configuration, and wherein at least one stiffening wire includes a shape memory material and extends at least partially along the expandable portion.

[0013] 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

[0014] FIG. 1 illustrates a front elevation view of an example system including a neuromodulation catheter including at least one therapy delivery element and at least one stiffening wire.

[0015] FIG. 2A illustrates a partial front view of an expandable portion of the neuromodulation catheter of FIG. 1 in a radially expanded (deployed) configuration.

[0016] FIG. 2B illustrates a partial top view of the expandable portion of the neuromodulation catheter of FIG. 2 A in the radially expanded configuration.

[0017] FIG. 3 illustrates a partial front view of an example neuromodulation catheter including an expandable portion extending along a first helical path and at least one stiffening wire extending along a second helical path clockwise about the first helical path.

[0018] FIG. 4 illustrates a partial front view of an example neuromodulation catheter including an expandable portion extending along a first helical path and at least one stiffening wire extending along a second helical path anticlockwise about the first helical path.

[0019] FIG. 5 illustrates a partial front view of an example neuromodulation catheter including a plurality of therapy delivery elements and at least one stiffening wire extending between endmost therapy delivery elements.

[0020] FIG. 6 illustrates a partial front view of an example neuromodulation catheter including a plurality of therapy delivery elements and at least one stiffening wire extending between intermediate elements of the plurality of therapy delivery elements and not between endmost therapy delivery elements.

[0021] FIG. 7 illustrates a partial front view of an example neuromodulation catheter including at least one therapy delivery element and at least one stiffening wire extending proximally from the at least one therapy delivery element.

[0022] FIG. 8 illustrates a cross-sectional view of an example neuromodulation catheter including at least one stiffening wire surrounded by a polymer jacket, the cross-section being taken in a direction orthogonal to a longitudinal axis of the neuromodulation catheter.

[0023] FIG. 9 illustrates a cross-sectional view of an example neuromodulation catheter including at least one stiffening wire within a polymer jacket about an elongate body, the cross-section being taken in a direction orthogonal to a longitudinal axis of the neuromodulation catheter.

[0024] FIG. 10 illustrates a cross-sectional view of an example neuromodulation catheter including at least one stiffening wire between first polymer jacket and a second polymer jacket about an elongate body.

[0025] FIG. 11 illustrates a front view of an example system including a neuromodulation catheter including at least one therapy delivery element and at least one electrically actuatable stiffening wire.

[0026] FIG. 12 illustrates a cross-sectional view of an example neuromodulation catheter including a helical hollow strand including at least one stiffening wire, the cross-section being taken in a direction orthogonal to a longitudinal axis of the neuromodulation catheter.

[0027] FIG. 13 is a flow diagram of an example technique for forming a neuromodulation catheter.

[0028] FIG. 14 is a flow diagram of an example technique for delivering neuromodulation therapy using a neuromodulation catheter.

[0029] FIG. 15 illustrates an example technique for accessing a renal artery and modulating renal nerves with the system of FIG. 1 in accordance with some examples of the present disclosure.

[0030] FIG. 16 is a conceptual illustration of an example sympathetic nervous system (SNS) illustrating how the brain communicated with the body via the SNS.

[0031] FIG. 17 is an enlarged anatomic view of nerves innervating a left kidney to form the renal plexus surrounding the left renal artery.

[0032] FIG. 18 is an anatomic view of a human body depicting neural efferent and afferent communication between the brain and kidneys.

[0033] FIG. 19 is a conceptual view of a human body depicting neural efferent and afferent communication between the brain and kidneys.

[0034] FIG. 20 is an anatomic view of the arterial vasculature of a human.

[0035] FIG. 21 is an anatomic view of the venous vasculature of a human.DETAILED DESCRIPTION

[0036] The present disclosure describes catheters, methods for forming catheters, and methods for delivering therapy, that can be used for any suitable medical procedure, including neuromodulation (e.g., renal neuromodulation). Although neuromodulation and renal denervation are primarily described herein, devices, systems, and techniques described herein may be applied to other types of therapy, including other types of neuromodulation, such asneuromodulation performed on nerves other than the renal nerves, at sites other than within a renal vessel, or both. In general, the devices, systems, and techniques described herein may be used to perform neuromodulation from within any suitable anatomical lumen that has nerves adjacent to the anatomical lumen. In addition, the systems, devices, and methods described herein may be useful for neuromodulation within a body lumen other than a vessel, for extravascular neuromodulation and / or for use in therapies other than neuromodulation.

[0037] 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.

[0038] Neuromodulation, such as renal denervation, may be accomplished using one or more of a variety of treatment modalities, including delivery of radiofrequency (RF) energy, microwave energy, ultrasound energy, thermal energy (e.g., direct thermal energy), optical energy, cryogenic cooling, a chemical agent, or the like. To perform intravascular neuromodulation, a neuromodulation catheter may be delivered to a blood vessel, such as a renal artery, of a patient. In some examples, a neuromodulation catheter includes an elongate body and at least one therapy delivery element disposed on a radially expandable portion of the elongate body. The at least one therapy delivery element may include, for example, an electrode, an ultrasound transducer, a needle configured to deliver a chemical agent, or a fluid injection port. While the at least one therapy delivery element may be disposed on a distal portion of the elongate body of the neuromodulation catheter, in other examples, other portions of the elongate body may include the at least one therapy delivery element.

[0039] The expandable portion of the catheter body is configured to deploy from a relatively low-profile configuration to a radially expanded configuration (e.g., a helical, a spiral, a loop, or the like). In the radially expanded configuration, which is also referred to herein as a deployed configuration, the expandable portion is configured to position the at least one therapy delivery element in apposition to a vessel wall to facilitate delivery of therapy to tissue of the patient, e.g., surrounding the vessel wall, perivascular tissue, or the like. In the expanded configuration, at least some parts of the neuromodulation catheter are expanded radially away from a central longitudinal axis of a more proximal portion of the neuromodulation catheter, such as a proximal portion of an elongate catheter body. Suchradial movement away from the central longitudinal axis can bring the at least one therapy delivery element into contact with a vessel wall or other tissue of interest.

[0040] A clinician may introduce the expandable portion of the catheter within anatomy of a patient, with a proximal portion of the elongate body remaining outside the patient, and available to be maneuvered by the clinician. The clinician may move and orient the at least one therapy delivery element by at least manipulating the neuromodulation catheter, for example, to orient the at least one therapy delivery element relative to a target therapy site. This can include, for example, positioning the expandable portion of the catheter at the target therapy site. After the clinician has placed the expandable portion at a target tissue site within a patient and deployed the expandable portion to the radially expanded state, the clinician may deliver therapy to tissue of the patient via the at least one therapy delivery element, for example, for a denervation procedure or other therapy.

[0041] In the deployed configuration of the catheter, the at least one therapy delivery element may initially be placed at one location of multiple target locations. The clinician may need to re-position (for example, distally advance, proximally retract, and / or rotate about the central longitudinal axis) the neuromodulation catheter to deliver the therapy to other locations of the multiple target locations. Thus, the clinician may deliver the therapy at multiple locations along and / or around a blood vessel to increase the efficacy of the therapy. In some examples, the multiple locations are circumferentially distributed about the vessel wall, e.g., separated by a predetermined angle (for example, 90°, 120°, or 180°, or any other suitable angle). In some examples, the multiple locations are longitudinally distributed along the vessel wall. The clinician may also seek to deliver therapy to different locations, for example, to increase efficacy of the therapy, reduce a likelihood of occurrence of an unintended effect, or to deliver uniform therapy at different locations or orientations. In such examples, the clinician may rotate the catheter within the blood vessel to place the therapy delivery elements at the different locations around the perimeter (for example, circumference) of the blood vessel. Thus, the clinician may translate or rotate the proximal portion, in turn, causing translation or rotation of the expandable portion, and thus, the at least one therapy delivery element.

[0042] The clinician may expect or seek commensurate movement of the expandable portion (or of the at least one therapy delivery element) in response to a corresponding movement of the proximal portion, so that the clinician may exercise adequate control over the orientation of the at least one therapy delivery element relative to the target therapy site.For example, the commensurate movement may result in a 1 : 1 correspondence of rotation or translation of the expandable portion relative in response to a rotation or translation of the proximal portion. In some examples, the commensurate movement may not result in an 1 : 1 correspondence between movement of the proximal portion and the expandable portion, but another predetermined or predictable correspondence, for example, a 2: 1, 3:2, 4:3, 5:4, or 3: 1 correspondence, or any other correspondence.

[0043] The clinician may rotate a handle coupled to the elongate body (e.g., at a proximal portion of the elongate body) to rotate the expandable portion within the blood vessel. The clinician may apply a torque to the handle and / or the proximal portion by at least rotating the handle and / or the proximal portion about a central longitudinal axis of the handle and / or the proximal portion. The elongate body may propagate the applied torque along a length of elongate body to the expandable portion of the catheter body to rotate the expandable portion and the at least one therapy delivery element within the blood vessel (for example, relative to a central longitudinal axis along which the elongate body extends). However, the material characteristics and the placement of the catheter through relatively tortuous vasculature may make it relatively difficult for the clinician to transfer rotational force from a proximal portion of the catheter to the expandable portion of the catheter or to control the rotation of the expandable portion within the blood vessel in a predictable manner. Rotating the proximal portion of the elongate body may not result in a commensurate rotation of the expandable portion. For example, the expandable portion may lag in rotation relative to the proximal portion because of insufficient torque transfer from the proximal portion to the expandable portion.

[0044] The handle may be of a different material than the elongate body, and the transmission of torque across different materials with different material properties may lead to under-rotation of the expandable portion and / or a reduction in the ability to sufficiently control the rotation of the expandable portion of the catheter body. In addition, the elongate body may be relatively flexible to allow for navigation of the elongate body through vasculature of the patient. The flexibility of the elongate body may cause the elongate body to resist transmission of the torque along the elongate body. Thus, the insufficient torque transfer may arise from a relatively flexible or compliant material of the elongate body, which may resist rotation at the expandable portion in response to a rotation at the proximal portion. When deployed through a guide catheter, the neuromodulation catheter may also encounterrotational resistance within or relative to the guide catheter, making it more difficult to predictably rotate the at least one therapy delivery element.

[0045] In such examples, the clinician may need to over-rotate the handle and / or the proximal portion of the elongate body to rotate the expandable portion within the blood vessel by a predetermined amount. Therefore, to achieve a predetermined rotation of the expandable portion (and thus the at least one therapy delivery element), the clinician may need to rotate the proximal portion significantly beyond the target rotation of the expandable portion. For example, the clinician may need to turn the proximal portion beyond 90°, 120°, or 180°, to respectively achieve 90°, 120°, or 180° rotation of the expandable portion.

[0046] In some examples, rotation of the handle and / or the proximal portion of the elongate body by the clinician may cause the release of stress within the catheter and cause over-rotation of the expandable portion or “whipping,” e.g., a delayed response by the catheter to rotational movement by the clinician, which can be caused by spring torsion. The under-rotation or over-rotation of the expandable portion and / or the reduction in the ability to precisely control the rotation of the expandable portion may lead to one or more difficulties with the neuromodulation procedure. For example, the clinician may need to spend a relatively long period of time to position the expandable portion to a desired location due to the increase difficulty in precisely manipulating the expandable portion. While the neuromodulation may still be effective, there may be a reduction in the efficacy of the neuromodulation therapy if the therapy is not delivered to an intended location (e.g., a location in the blood vessel proximate the target nerves for ablation) and / or delivered therapy to an unintended location (for example, non-target nerves or other non-target tissue). The delivery of neuromodulation therapy to the non-target tissue may lead to unintended outcomes.

[0047] In some examples according to the present disclosure, an example neuromodulation catheter includes an elongate body extending along a central longitudinal axis, at least one therapy delivery element, and at least one stiffening wire. The at least one therapy delivery element may be disposed on an expandable portion of the elongate body, which can be at a distal portion of the elongate body in some examples. The expandable portion is configured to transform from a relatively low-profile configuration to a radially expanded configuration. In some examples, the at least one stiffening wire includes a shape memory material and extends at least partially along the expandable portion. The at least one stiffening wire itself or alone is not sufficient to cause the expandable portion to expand,deploy, or transform from the relatively low-profile configuration to a radially expanded configuration. Without being bound by theory, the at least one stiffening wire may facilitate transferring force or torque between a proximal portion of the elongate body and the expandable portion, such that the expandable portion moves (for example, one or both of translates or rotates) substantially commensurately with a corresponding movement of the proximal portion. Thus, neuromodulation catheters according to the present disclosure may provide a clinician with better control of the position of the expandable portion (when deployed into the radially expanded deployed configuration) within a blood vessel, as well as better control of the orientation of the at least one therapy delivery element within the blood vessel. As a result, the neuromodulation catheters described herein that include at least one stiffening wire may enable the respective neuromodulation catheter to be positioned within a blood vessel with fewer adjustments, compared to a neuromodulation catheter does not include the at least one stiffening wire.

[0048] In some examples, the at least one stiffening wire may provide a 1 : 1 correspondence of movement between the proximal portion and the expandable portion, such that a particular magnitude of one or both of translation or rotation of the proximal portion results in the same magnitude of one or both of translation or rotation of the expandable portion (or the at least one therapy delivery element). In other examples, the commensurate movement may not result in a 1 : 1 correspondence of movement, but some other predictable, predetermined, or otherwise known correspondence of movement between the proximal portion and the expandable portion, such that a clinician may nonetheless be able to move the expandable portion to a predetermined orientation by moving a proximal portion with a sufficient compensatory movement. The at least one stiffening wire may facilitate predictable movement or orientation of the expandable portion in one or both of the relatively low-profile configuration or the expanded configuration.

[0049] Thus, the at least one stiffening wire may allow for relatively precise control of the placement of at least one therapy delivery element at one or more locations, for example, by removing resistance to the rotation from the material characteristics or the tortuosity of the elongate body. The control of the placement of at least one therapy delivery element may lead to increased efficacy of the neuromodulation therapy and decreased likelihood of the occurrence of unintended effects as a result of the neuromodulation therapy.

[0050] The at least one stiffening wire may provide a sufficient mechanical coupling between the proximal and distal portions of the catheter, such that a movement of theproximal portion results in a predetermined or known corresponding movement of the distal portion. The at least one stiffening wire may provide better torque transmission without impacting the electrode positions or ability to straighten the catheter, compared to a catheter that does not include at least one stiffening wire. In some examples, the at least one stiffening wire includes a shape memory material (for example, nitinol) and mirrors a shape of a shape memory member (for example, a helical member or a helical hollow strand member) present in a distal portion of the catheter, providing better torque transfer from a proximal portion through the distal portion compared to a catheter that does not include at least one stiffening wire. In some examples, the shape memory member in the distal portion that shapes the expandable portion (for example, in a helical shape in a deployed configuration) is sensitive to a torsional direction. In some such examples, at least one stiffening wire including a single strand wire may transfer torque more predictably than the shape memory member itself. Thus, providing the at least one stiffening wire in addition to the shape memory member results in a more commensurate movement of the expandable portion relative to the proximal portion, compared to a catheter that includes the shape memory member but not at least one stiffening wire.

[0051] FIG. 1 illustrates a front elevation view of an example system 10 including a neuromodulation catheter 12 including at least one therapy delivery element 14 and at least one stiffening wire 16.

[0052] Catheter 12 further includes a handle 18 and an elongate body 20 attached to handle 18. That is, handle 18 is positioned at a proximal portion of elongate body 20. Elongate body 20 may have any suitable outer diameter, and the diameter can be constant along the length of elongate body 20 or may vary along the length of elongate body 20. In some examples, elongate body 20 may be 2, 3, 4, 5, 6, or 7 French or another suitable size. Elongate body 20 extends along a central longitudinal axis L, and includes a distal portion 20A and a proximal portion 20B. Distal portion 20A includes an expandable portion 22. Expandable portion 22 is configured to transform from a relatively low-profile configuration (shown in FIG. 1) to a radially expanded deployed configuration (shown in FIGS. 2A and 2B).

[0053] In the example shown in FIG. 1, at least one therapy delivery element 14 is disposed on expandable portion 22 of elongate body 20. At least one therapy delivery element 14 is configured to deliver therapy to tissue of a patient, for example, to neuromodulate a target nerve of the patient. At least one therapy delivery element 14 mayinclude, but is not limited to, one or more electrodes, one or more ultrasound transducers, one or more needles configured to deliver a therapeutic agent directly or indirectly, one or more heat or cryo-therapy delivery devices (for example, balloons), one or more injection ports configured to deliver a therapeutic agent, or any combination thereof. In some examples, each therapy delivery element of at least one therapy delivery element 14 is an electrode. In some examples, at least one therapy delivery element 14 includes a ring electrode surrounding a portion of elongate body 20. At least one therapy delivery element 14 may be connected to a therapy delivery device, which includes control circuitry and therapy source (for example, an electrical signal generator, a source of a therapeutic agent, a cryogenic therapeutics source, or the like; not shown in FIG. 1) via at least one electrical conductor and / or at least one lumen defined by elongate body 20 and / or handle 18. Although FIG. 1 illustrates catheter 12 as having four therapy delivery elements 14, other example catheters may include one, two, three, five, or more therapy delivery elements 14. In some examples, as shown in FIG. 1, at least one therapy delivery element 14 includes four electrodes, for example, four ring electrodes.

[0054] Distal portion 20A of elongate body 20 is configured to be advanced within an anatomical lumen of a human patient to locate at least one therapy delivery element 14 at a target tissue site within or otherwise proximate to the anatomical lumen. For example, elongate body 20 may be configured to position distal portion 20A within a blood vessel, a ureter, a urethra, a duct, an airway, or another naturally occurring lumen within the human body. The examples described herein focus on the anatomical lumen being a blood vessel, such as a renal vessel, but it will be understood that similar techniques may be used with other anatomical lumens.

[0055] Neuromodulation 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 20 A includes percutaneously inserting a guidewire (not shown in FIG. 1) into a vessel of a patient and moving elongate body 20 (for example, at least expandable portion 22) along the guidewire until expandable portion 22 reaches a target tissue site (for example, a renal artery). For example, distal portion 20A of elongate body 20 may define a lumen configured to receive a guidewire for delivery of expandable portion 20 to a target tissue site using over- the-wire (OTW) or rapid exchange (RX) techniques. In other examples, neuromodulation catheter 12 can be a steerable or non-steerable device configured for use without a guidewire.In still other examples, neuromodulation 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), or other guide device.

[0056] A distal end of elongate body 20 defines distal tip 26. Distal tip 26 is configured to facilitate navigation of distal portion 20A within the vasculature of the patient to a blood vessel. In some examples, distal tip 26 may be atraumatic, for example, to resist or avoid puncturing a vessel of a blood vessel during navigation of distal portion 20A within the blood vessel.

[0057] In the example illustrated in FIG. 1, catheter 12 is in a relatively low-profile delivery configuration, in which distal portion 20A 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 22 of distal portion 20A defines a relatively larger radial extent (shown in FIGS. 2A and 2B). In some examples, the radial extent is measured in a direction orthogonal to central longitudinal axis L. Distal portion 20A may be delivered through vasculature of the patient to the target tissue site in the low-profile configuration. In some examples, expandable portion 22 is configured to self-expand within a blood vessel of a patient, e.g., via a shape-memory element (e.g., a shape memory tube or a hollow helical strand) of elongate body 20. 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. Expandable portion 22 may be constrained or restrained in the low-profile configuration by a guide member. The clinician may retract the guide member proximally relative to expandable portion 22 to unconstrain expandable portion 22 and cause or allow expandable portion 22 to transform from the low- profile configuration to an expanded configuration. Thus, expandable portion 22 may be configured to radially expand away from the straight line to the expanded configuration.

[0058] FIG. 2A illustrates a partial front view of expandable portion 22 of neuromodulation catheter 12 of FIG. 1 in an expanded configuration 22A. FIG. 2B illustrates a partial top view of expandable portion 22 in expanded configuration 22A. In some examples, in expanded configuration 22A, expandable portion 22 defines a loop, a helix, or a spiral shape, or a basket, or a stent-like configuration. In expanded configuration 22A, expandable portion 22 is configured to position one or more therapy delivery elements of at least one therapy delivery element 14 near a vessel wall, for example, in apposition with the vessel wall.

[0059] In some examples, expandable portion 22 may be expanded or may self-expand as a result of proximal retraction of a guide member from distal portion 20A. The clinician may retract the guide member to a location along distal portion 20A proximal to expandable portion 22 to cause or allow expandable portion 22 to expand. In the expanded configuration, expandable portion 22 may place at least one therapy delivery elements 14 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 the target tissue site to target tissue adjacent to the blood vessel. The neuromodulation therapy may include, but is not limited to, radiofrequency (RF) energy, microwave energy, ultrasound energy, a therapeutic agent (e.g., a chemical ablation agent), cryogenic energy, or the like.

[0060] The clinician may rotate handle 18, or otherwise proximal portion 20B, to apply a torque to distal portion 20A and cause expandable portion 22 to rotate about central longitudinal axis L from the first rotational location to a second rotational location. The second rotational location is spaced from the first rotational location by a predetermined angle. In some examples, the second rotational location is at least 15°, 30°, 45°, 60°, 75°, 90°, 120°, 150°, or 180° along the vessel wall from the first rotational location. The second rotational location may be longitudinally aligned with the first rotational location (for example, resulting from a pure rotation of expandable portion 22 without any relative longitudinal translation of expandable portion 22), or may be longitudinally spaced from the first rotational location (for example, resulting from a combination of a rotation and longitudinal translation of expandable portion 22). Rotation of expandable portion 22 to the second rotational location may cause at least one therapy delivery element 14 to be rotated to a different location along an inner perimeter of the vessel wall spaced from an initial location associated with the first rotational location of expandable portion 22. For example, the application of torque from handle 18 or proximal portion 20B to expandable portion 22 may cause expandable portion 22 to rotate about longitudinal axis L, for example, in a same direction as the torque. The clinician may control system 10 to delivery therapy at the second rotational location, or after further successive rotational locations of expandable portion 22.

[0061] At least one stiffening wire 16 is configured to facilitate sufficient control over rotation of expandable portion 22 by the clinician, for example, by transmitting torque in a substantially commensurate or predictable manner from handle 18 or proximal portion 20B to distal portion 20A (and thus to expandable portion 22). Thus, a rotation Ri of handle 18 mayresult in a substantially conforming rotation R2of expandable portion 22. For example, R2may be substantially the same as R or within a predetermined range of deviation (for example, under-rotation) relative to R, . In some examples, R2is in a range of 5°, or 7°, or 10°, or 15°, or 25° from R, .

[0062] In some examples, at least one stiffening wire 16 includes a shape memory material and extends at least partially along expandable portion 22. For example, the shape memory material may include a metal, an alloy, a plastic, or combinations thereof. In some examples, the shape memory material includes nitinol. At least one stiffening wire 16 may include one, two, three, four, five, or more wires. In some examples, at least one stiffening wire 16 defines a single coil. In some examples, at least one stiffening wire 16 includes at least one single-strand shape memory wire. In some such examples, at least one stiffening wire 16 consists of at least one single-strand shape memory wire. In some examples, catheter 10 includes only one stiffening wire 16. For example, catheter 10 may not include any stiffening member extending along the expandable portion other than the single-strand shape memory wire.

[0063] As shown in FIG. 1, at least one stiffening wire 16 may extend along longitudinal axis L, for example, along substantially a same path as expandable portion 22. However, in other examples, at least one stiffening wire 16 may follow a different path. For example, at least one stiffening wire 16 may follow a zig-zag, undulating, curved, helical, spiral, piecewise linear, or piecewise curved path, or combinations thereof, relative to a path along which expandable portion 22 extends. Thus, the helical path of expandable portion 22 in expanded configuration 22 A may be a first helical path, and at least one stiffening wire 16 may extend along a second helical path different from the first helical path. In some examples, the second helical path extends about the primary helical path of expandable portion 22 in expanded configuration 22A.

[0064] FIG. 3 illustrates a partial front view of an example neuromodulation catheter 112 including expandable portion 22 extending along a first helical path P and at least one stiffening wire 116 extending along a second helical path SI clockwise (represented by the letter “C”) about first helical path P. In particular, second helical path SI is clockwise in a distal direction about expandable portion 22. Neuromodulation catheter 112 is substantially similar to neuromodulation catheter 12, and at least one stiffening wire 116 is substantially similar to at least one stiffening wire 16, but differs in the path it traverses relative to expandable portion 22.

[0065] FIG. 4 illustrates a partial front view of an example neuromodulation catheter 212 including an expandable portion 22 extending along a first helical path P and at least one stiffening wire 216 extending along a secondary helical path S2 anticlockwise (represented by the letter “A”) about the first helical path P. In particular, second helical path S2 is clockwise in a distal direction about expandable portion 22. Neuromodulation catheter 212 is substantially similar to neuromodulation catheter 12, and at least one stiffening wire 216 is substantially similar to at least one stiffening wire 16, but differs in the path it traverses relative to expandable portion 22.

[0066] In FIGS. 3 or 4, first helical path P itself may be clockwise or anticlockwise, in a distal direction along expandable portion 22. Thus, a chirality of second helical path (SI or S2) may be aligned with or opposed to a chirality of first helical path. In some examples, the first helical path SI has a same chirality as the second helical path S2. For example, both SI and S2 may be clockwise or anticlockwise in a distal direction along expandable portion 22. In case of a relatively highly compliant expandable portion 22, an aligned chirality may reduce kinks or folds in expandable portion in response to torque transfer from handle 18 or proximal portion 20B. In contrast, in case of a relatively less compliant expandable portion 22, an opposing chirality may facilitate retraction of expandable portion 22 by transformation from expanded configuration 22A into the relatively low-profile configuration, while still transmitting sufficient torque to support or facilitate commensurate rotation of expandable portion 22 relative to handle 18 or proximal portion 20B. Thus, in some examples, the first helical path SI has an opposite chirality as the second helical path S2, with one of first helical path SI and second helical path S2 being clockwise, and the other of first helical path SI and second helical path S2 being anticlockwise, in a distal direction along expandable portion 22.

[0067] In some examples, at least one stiffening wire 16 may extend along a linear path relative to expandable member 22 in a first section or segment, and along a non-linear path (for example, a helical path) in a second section or segment. For example, a proximal portion of at least one stiffening wire 16 may extend along a linear path relative to expandable member 22, and a distal portion of least one stiffening wire 16 may extend along a helical path relative to expandable member 22.

[0068] Turning back to FIG. 1, at least one stiffening wire 16 may extend along different portions of elongate body 20 in different examples. For example, as shown in FIG. 1, at least one stiffening wire 16 may extend distally along distal portion 20A to distal tip 26. Thus, a distal end of at least one stiffening wire 16 may terminate at distal tip 26, while a proximalend of at least one stiffening wire 16 may terminate at a location proximal to expandable portion 22. However, in other examples, a distal end of at least one stiffening wire 16 may terminate at a position proximal to distal tip 26 or proximal to one or more therapy delivery elements of the at least one therapy delivery element 14. A proximal end of at least one stiffening wire 16 may terminate at handle 18, at a position distal to handle 18, at a position along proximal portion 20B, at a position along distal portion 20A, at a position proximal to at least one therapy delivery element 14, or at a position distal to at least one therapy delivery element. In some examples, in which at least one therapy delivery element 14 includes two or more therapy delivery elements, the proximal and / or distal end of at least one stiffening wire 16 may terminate at a position between the two or more therapy delivery elements, or at a position distal or proximal to any of the two or more therapy delivery elements. Thus, the position and length of at least one stiffening wire may be modified along elongate body 20 to provide a predetermined rotational stiffness to one or more sections of elongate body 20.

[0069] In some examples, at least one therapy delivery element 14 includes a first therapy delivery element and a second therapy delivery element, and at least one stiffening wire 16 extends from the first therapy delivery element to the second therapy delivery element.

[0070] FIG. 5 illustrates a partial front view of an example neuromodulation catheter 312 including a plurality of therapy delivery elements 14A, 14B, 14C, and 14D and at least one stiffening wire 316 extending between endmost therapy delivery elements 14A and 14D. Plurality of therapy delivery elements 14 may include intermediate delivery elements 14B and 14C between endmost therapy delivery elements 14A and 14D in a direction along a central longitudinal axis L of catheter 312. For example, first therapy delivery element 14A is a proximal -most therapy delivery element of catheter 312, and second therapy delivery element 14D is a distal-most therapy delivery element of catheter 312. Neuromodulation catheter 312 is substantially similar to neuromodulation catheter 12, and at least one stiffening wire 316 is substantially similar to at least one stiffening wire 16, but differs in length (measured along longitudinal axis L). For example, no portion of at least one stiffening wire 316 extends beyond endmost therapy delivery elements 14A and 14D.

[0071] FIG. 6 illustrates a partial front view of an example neuromodulation catheter 412 including a plurality of therapy delivery elements 14 and at least one stiffening wire 416 extending between intermediate elements 14B and 14C of plurality of therapy delivery elements 14. In the example shown in FIG. 6, at least one stiffening wire 416 does not extend distally past intermediate element 14B or proximally past intermediate element 14C. In otherexamples, at least one stiffening element 416 extend distally past intermediate element 14B and / or proximally past intermediate element 14C, but not all the way to the adjacent therapy delivery elements 14A and 14D, respectively. Neuromodulation catheter 412 is substantially similar to neuromodulation catheter 12, and at least one stiffening wire 416 is substantially similar to at least one stiffening wire 16, but differs in length. For example, no portion of at least one stiffening wire 416 extends beyond intermediate therapy delivery elements 14B and 14C.

[0072] FIG. 7 illustrates a partial front view of an example neuromodulation catheter 512 including a plurality of therapy delivery elements 14 and at least one stiffening wire 516 extending proximally from at least one therapy delivery element of plurality of therapy delivery elements 14. Neuromodulation catheter 512 is substantially similar to neuromodulation catheter 12, and at least one stiffening wire 516 is substantially similar to at least one stiffening wire 16, but differs in length. For example, no portion of at least one stiffening wire 516 extends distally beyond therapy delivery element 14C. In other examples, no portion of at least one stiffening wire 516 extends distally beyond therapy delivery element 14B, or distally beyond therapy delivery element 14D. In these examples, a proximal end of at least one stiffening wire 516 may terminate at a position along expandable portion 22, or at a position proximal to expandable portion 22.

[0073] Turning back to FIG. 1, at least one stiffening wire 16 can be connected to elongate body 20 using any suitable technique. For example, at least one stiffening wire 16 may be positioned at a surface of expandable portion 22 and / or within an interior of expandable portion 22. In some examples, at least one layer, for example, a coating or a jacket, may surround at least one stiffening wire 16. Further positions of at least one stiffening wire are described with reference to FIGS. 8 to 10.

[0074] FIG. 8 illustrates a cross-sectional view of an example neuromodulation catheter 612 including at least one stiffening wire 16 surrounded by a polymer jacket 625, which is positioned about elongate body 20 (e.g., radially outwards of elongate body 20), the crosssection being taken in a direction orthogonal to central longitudinal axis L. In some examples, polymer jacket 625 is an outer layer of elongate body 20, for example, radially outer than another layer or component of elongate body 20. In some examples, polymer jacket 625 is an outermost layer of elongate body 20. Polymer jacket 625 may include any suitable polymer, for example, a biocompatible polymer or a medical grade polymer. In some examples, polymer jacket 625 includes polyethylene terephthalate (PET). At least onetherapy delivery element (for example, at least one therapy delivery element 14 described with reference to FIG. 1) may be positioned exterior to, within a bulk of, or interior to polymer jacket 625. In some examples, polymer jacket 625 promotes retention of at least one stiffening wire 16 along a predetermined path relative to expandable portion 22, and resists or reduces separation of at least one stiffening wire 16 from expandable portion 22.

[0075] FIG. 9 illustrates a cross-sectional view of an example neuromodulation catheter 712, the cross-section being taken in a direction orthogonal to central longitudinal axis. Catheter 712 includes at least one stiffening wire 16 within polymer jacket 625, which is about elongate body 20. For example, at least one stiffening wire 16 may be positioned within a bulk of polymer jacket 625.

[0076] FIG. 10 illustrates a cross-sectional view of an example neuromodulation catheter 812, the cross-section being taken in a direction orthogonal to central longitudinal axis. Catheter 812 includes at least one stiffening wire 16 between a first polymer jacket 625 and a second polymer 627 jacket positioned about elongate body 20. Second polymer jacket 627 may include any suitable material described with reference to polymer jacket 625. The composition of second polymer jacket 627 may be identical to, or differ from, the composition of polymer jacket 625. As shown in FIG. 10, at least one stiffening wire 16 may be positioned at an interface of first polymer jacket 625 and second polymer jacket 627. In other examples, at least one stiffening wire 16 may be positioned within a bulk of second polymer jacket 627.

[0077] In some examples, different stiffening wires of at least one stiffening wire 16 may be positioned at an interface of, or within a bulk of, one or both of first polymer jacket 625 or second polymer jacket 627. In some examples, a first portion, for example, a distal portion or a proximal portion, of at least one stiffening wire 16 may be embedded or surrounded by second polymer jacket 627, and a second portion of at least one stiffening wire 16 may be embedded or surrounded by first polymer jacket 625. In some examples, a first portion of at least one stiffening wire 16 may be embedded or surrounded by first polymer jacket 625 or second polymer jacket 627, and a second portion of at least one stiffening wire 16 may be free of one or both of first polymer jacket 625 or second polymer jacket 627.

[0078] Turning back to FIG. 1, at least one stiffening wire 16 may be passively actuatable, for example, via shape-memory effect in response to a change in ambient temperature. In other examples, as described with reference to FIGS. 11 and 12, at least one stiffening wire 16 may be actively actuatable, for example, in response to an electrical stimulus. For example,the electrical stimulus may generate resistive heating along the at least one stiffening wire 16 to heat a shape memory material in at least one stiffening wire 16 above a threshold temperature to induce transformation to a predetermined memory shape. In some examples, the threshold temperature is an austenite finish temperature.

[0079] FIG. 11 illustrates a front view of an example system 900 including a neuromodulation catheter 912 including at least one therapy delivery element 14 and at least one electrically actuatable stiffening wire 916. System 900 is substantially similar to system 10, neuromodulation catheter 912 is substantially similar to neuromodulation catheter 12, and at least one stiffening wire 916 is substantially similar to at least one stiffening wire 16, but differs in that it is configured to be electrically actuatable. System 900 further includes a control circuitry 950. Control circuitry 950 is configured to send an electrical signal to at least one stiffening wire 916 to cause at least one stiffening wire 916 to change shape. For example, at least one stiffening wire 916 may be electrically actuatable from an initial shape to a stiffening shape in response to a signal from control circuitry 950. In some examples, at least one stiffening wire 916 may include two, three, or more stiffening wires that are individually actuatable. For example, individually actuating different stiffening wires may allow inducing different overall catheter shapes or curvatures, or allow progressively stiffening one or more portions of neuromodulation catheter 912. In these examples, the stiffening wires can have respective stiffening shapes, which can be the same (e.g., the same stiffening shape, but having different rotational orientations) or different from other stiffening wires. In some examples, one of the initial shape and the stiffening shape may be a linear shape, and another of the initial shape and the stiffening shape may be a loop shape, a helical shape, or a spiral shape. Control circuitry 950 may be the same as, or different than, the control circuitry that controls delivery of therapy to via at least one therapy delivery element 14.

[0080] In some examples, expandable portion 22 includes at least one shape memory member configured to transform expandable portion 22 from the relatively low-profile configuration to expanded configuration 22A. The shape memory member may include a helical hollow strand, for example, a helical hollow strand tube (HHS®) available from Fort Wayne Metals Research Products, L.L.C. (Fort Wayne, Indiana).

[0081] In some examples, at least one stiffening wire 916 (or at least one stiffening wire 16) is radially spaced from the at least one shape memory member of expandable portion 22. Thus, at least one stiffening wire 916 (or at least one stiffening wire 16) may be separate anddistinct from the at least one shape memory member. In other examples, at least one stiffening wire 916 (or at least one stiffening wire 16) is part of the at least one shape memory member.

[0082] FIG. 12 illustrates a cross-sectional view of an example neuromodulation catheter 1012 including a helical hollow strand 1060 including at least one stiffening wire 916, the cross-section being take in a direction orthogonal to central longitudinal axis L. Neuromodulation catheter 1012 is an example of neuromodulation catheter 12 and illustrates an example helical hollow strand 1060. Helical hollow strand 1060 includes a plurality of strands 1062 including a shape memory material. In some examples, plurality of strands 1062 defines a hollow tubular body. At least one stiffening wire 916 may extend along strands 1062, or may form one of strands 1062. At least one stiffening wire 916 may be relatively stiffer than one more strands of, or all strands of, strands 1062. At least one stiffening wire 916 may differ in one or more of composition, a major diameter, or a cross-sectional shape relative to strands 1062. In some examples, strands 1062 are not electrically actuatable, and only at least one stiffening wire 916 is electrically actuatable. In some examples, strands 1062 include three stiffening wires 916. Catheter 1012 may include a liner or jacket 1064 in some examples. Helical hollow strand 1060 may be embedded within an expandable portion 1022 of neuromodulation catheter 1012, or spaced from, or in contact with, expandable portion 1022.

[0083] In some examples, at least one stiffening wire 916 is electrically actuatable. Control circuitry (for example, control circuitry 950) may send a control signal to at least one stiffening wire 96, which may in turn affect a conformation or shape of helical hollow strand 1060. In some examples, neuromodulation catheter 1012 includes a plurality of thermoelectric elements 1070, and the control circuitry is configured to control an energy source to send a control signal to thermoelectric elements 1070 to generate heat, which in turn may induce a thermal shape memory transformation in at least one stiffening wire 916.

[0084] Example catheters according to the disclosure may be formed using any suitable technique.

[0085] FIG. 13 illustrates an example technique for forming a neuromodulation catheter. While the technique of FIG. 13 is described with reference to catheter 12 of FIG. 1, the example technique may be used to form any catheter according to the present disclosure.

[0086] In some examples, the technique of FIG. 13 includes forming an elongate body 20 including at least one therapy delivery element 14 disposed on an expandable portion 22(1102). In some examples, forming elongate body 20 (1102) includes securing at least one shape memory member to elongate body 20, where the at least one shape memory member is configured to transform expandable portion 22 from the relatively low-profile configuration to the expanded configuration 22A.

[0087] The technique furthers include coupling at least one stiffening wire 16 including a shape memory material to elongate body 20 such that at least one stiffening wire 16 extends at least partially along expandable portion 22 (1104). The coupling (1104) may include applying an adhesive, a coating, a jacket, a weld, an extruded layer, to one or both of at least one stiffening wire 16 or elongate body 20, or any other suitable manner of joining at least one stiffening wire 16 to elongate body 16.

[0088] The technique may further include forming a polymer jacket surrounding at least one stiffening wire 16 (1106). For example, a polymer layer can be extruded about elongate body 20.

[0089] FIG. 14 illustrates an example technique for delivering neuromodulation therapy using a neuromodulation catheter. While FIG. 14 is described with reference to catheter 12 of FIG. 1, the technique may be performed using any catheter according to the present disclosure.

[0090] The technique of FIG. 14 includes advancing neuromodulation catheter 12 through vasculature to position at least one therapy delivery element 14 at a target tissue site within a blood vessel of a patient (1202). The technique further includes deploying expandable portion 22 of catheter 12 from the relatively low profile delivery configuration to radially expanded configuration 22 A to place the at least one therapy delivery element 14 in apposition to a vessel wall of the blood vessel at a location (1204). In some examples, expandable portion 22 is constrained in the low-profile configuration by a guidewire or a guide sheath, and expanding expandable portion 22 (1204) includes proximally retracting the guidewire or the guide sheath relative to elongate body 20 to a point proximal to expandable portion 22 to enable expandable portion 22 to deploy radially outwards.

[0091] The technique further includes delivering, via the at least one therapy delivery element 14, a therapy to tissue of the patient through the vessel wall at the location (1206).

[0092] In some examples, the location is a first location, and the technique further includes rotating expandable portion 22 relative to the longitudinal axis L to place the at least one therapy delivery element 14 in apposition to a vessel wall of the blood vessel at a second location (1208). The rotating the expandable portion (1208) may include rotating a proximalportion 20B of the elongate body 20 relative to the longitudinal axis L. In such examples, the technique further includes delivering, via the at least one therapy delivery element 14, therapy at the second location (1210).

[0093] FIG. 15 illustrates an example technique for accessing a renal artery and modulating renal nerves with system 10 of FIG. 1 in accordance with some examples of the present disclosure. While FIG. 15 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 20B or elongate body 20 from outside the intravascular path (P), a clinician may advance distal portion 20A of elongate body 20 through the sometimes-tortuous intravascular path (P) and remotely manipulate distal portion 20A (FIG. 1) of elongate body 20. Distal portion 20A may be remotely manipulated by the clinician using handle 18.

[0094] In the example illustrated in FIG. 15, distal portion 20A is delivered intravascularly to the treatment site using an inner member 23 in an over-the-wire (OTW) technique. Inner member 23 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 23 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 23 can be at least partially withdrawn or removed relative to catheter 12 and distal portion 20A can transform into an expanded configuration (for example, a helical configuration, a spiral configuration, or the like) for delivering ultrasound energy. In other examples, elongate body 200 may be self-steerable such that at least one therapy delivery element 14 may be delivered to the target tissue site without the aid of inner member 23.

[0095] 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 orafferent 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.

[0096] Renal neuromodulation can be electrically induced or induced in another suitable manner through the delivery of energy (RF energy, ultrasound energy, microwave energy, or the like). The target tissue site can be within or otherwise proximate to a renal lumen (e.g., a renal artery, a ureter, a renal pelvis, a major renal calyx, a minor renal calyx, or another suitable structure), and the target tissue site can include tissue at least proximate to a wall of the renal lumen. For example, with regard to a renal artery, a treatment procedure can include modulating nerves in the renal plexus, which lay intimately within or adjacent to the adventitia of the renal artery. The following discussion provides further details regarding patient anatomy and physiology as it may relate to renal denervation therapy. This section is intended to supplement and expand upon the previous discussion regarding the relevant anatomy and physiology, and to provide additional context regarding the disclosed technology and the therapeutic benefits associated with renal denervation. For example, several properties of the renal vasculature may inform the design of the target tissue devices and associated methods for achieving renal neuromodulation via intravascular access and impose specific design requirements for such devices. Specific design requirements may include accessing the renal artery, positioning distal portion 16a within the renal artery, delivering the therapy to targeted tissue, or effectively modulating the renal nerves with the therapy delivery device.

[0097] 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 sympatheticnervous 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).

[0098] 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.

[0099] 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.

[0100] 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.

[0101] FIG. 16 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. 16, 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.

[0102] 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.

[0103] In the SNS and other component of the peripheral nervous system, these synapses are made at sites called ganglia, discussed above. The cell that sends its fiber to the ganglion is called a preganglionic cell, while the cell whose fiber leaves the ganglion is called a postganglionic cell. As mentioned previously, the preganglionic cell of the SNS is located between the first thoracic (Tl) segment and third lumbar (L3) segments of the spinal cord. Postganglionic cells have their cell bodies in the ganglia and send their axons to target organs or glands.

[0104] 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.

[0105] FIG. 17 is an enlarged anatomic view of nerves innervating a left kidney to form the renal plexus surrounding the left renal artery. As FIG. 17 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.

[0106] 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.

[0107] 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.

[0108] Hypertension, heart failure, and chronic kidney disease are a few of the many disease states that result from chronic activation of the SNS, especially the renal sympathetic nervous system. Chronic activation of the SNS is a maladaptive response that drives the progression of theses disease states. Pharmaceutical management of the renin-angiotensin- aldosterone system (RAAS) has been a longstanding, but somewhat ineffective, approach for reducing over-activity of the SNS.

[0109] 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.

[0110] 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 andthe 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.[OHl] 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.

[0112] 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 pharmacologicstrategies can have significant limitations including limited efficacy, compliance issues, side effects, and others.

[0113] 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.

[0114] FIG. 18 is an anatomic view of a human body depicting neural efferent and afferent communication between the brain and kidneys. FIG. 19 is a conceptual view of a human body depicting neural efferent and afferent communication between the brain and kidneys. As shown in FIGS. 18 and 19, 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.

[0115] 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.

[0116] 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 denervationmight 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. 18. 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.

[0117] 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. 20 is an anatomic view of the arterial vasculature of a human. As FIG. 20 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.

[0118] FIG. 21 is an anatomic view of the venous vasculature of a human. As FIG. 21 shows, the blood collects in veins and returns to the heart, through the femoral veins into the iliac veins and into the inferior vena cava. The inferior vena cava branches into the left and right renal veins. Above the renal veins, the inferior vena cava ascends to convey blood into the right atrium of the heart. From the right atrium, the blood is pumped through the right ventricle into the lungs, where it is oxygenated. From the lungs, the oxygenated blood is conveyed into the left atrium. From the left atrium, the oxygenated blood is conveyed by the left ventricle back to the aorta.

[0119] 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.

[0120] 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 thesubclavian 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.

[0121] 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.

[0122] As discussed previously, a catheter may be advanced percutaneously into either the left or right renal artery via a minimally invasive intravascular path. However, minimally invasive renal arterial access may be challenging, for example, because as compared to some other arteries that are routinely accessed using catheters, the renal arteries are often extremely tortuous, may be of relatively small diameter, or may be of relatively short length. Furthermore, renal arterial atherosclerosis is common in many patients, particularly those with cardiovascular disease. Renal arterial anatomy also may vary significantly from patient to patient, which further complicates minimally invasive access. Significant inter-patient variation may be seen, for example, in relative tortuosity, diameter, length, or atherosclerotic plaque burden, as well as in the take-off angle at which a renal artery branches from the aorta. Further, some patients include multiple left renal arteries or right renal arteries. Apparatus, systems, and methods for achieving renal neuromodulation via intravascular access should account for these and other aspects of renal arterial anatomy and its variation across the patient population when minimally invasively accessing a renal artery.

[0123] 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 cyclebecause 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).

[0124] The neuromodulation system may also be configured to allow for adjustable positioning and repositioning of distal portion 20A and at least one therapy delivery element 14 (FIG. 1) 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.

[0125] As noted above, an apparatus positioned within a renal artery may be configured so that distal portion 20A of catheter 12 may intimately contact the vessel wall or extend at least partially through the vessel wall. Renal artery vessel diameter, DRA, typically is in a range of about 2-10 mm, with most of the patient population having a DRA of about 4 mm to about 8 mm and an average of about 6 mm. Renal artery vessel length, LRA, between its ostium at the aorta / renal artery juncture and its distal branchings, generally is in a range of about 5-70 mm, and a significant portion of the patient population is in a range of about 20-50 mm. Since the target renal plexus is embedded within the adventitia of the renal artery, the composite Intima-Media Thickness, IMT, (i.e., the radial outward distance from the artery's luminal surface to the adventitia containing target neural structures) also is notable and generally is in a range of about 0.5-2.5 mm, with an average of about 1.5 mm. Although a certain depth of treatment is important to reach the target neural fibers, the treatment should not be too deep (e.g., > 10 mm from inner wall of the artery) to avoid non-target tissue and anatomical structures such as anatomical structures of the digestive system of psoas muscle.

[0126] 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 alsomay 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°.

[0127] 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.

[0128] 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.

[0129] 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.

[0130] Further, although techniques have been described in which a neuromodulation catheter is positioned at a single location within a single renal artery, in other examples, the neuromodulation catheter may be repositioned to a second treatment site within a single renal artery (e.g., proximal or distal of the first treatment site, may be repositioned in a branch of the single artery, may be repositioned within a different renal vessel on the same side of the patient (e.g., a renal vessel associated with the same kidney of the patient), may be repositioned in a renal vessel on the other side of the patient (e.g., a renal vessel associated with the other kidney of the patient), or any combination thereof. At each location where the neuromodulation catheter is positioned, renal neuromodulation may be performed using any of the techniques described herein or any other suitable renal neuromodulation technique or any combination thereof.

[0131] 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 terms “about” or approximately,” when preceding a value, should be interpreted to mean plus or minus 10% of the value, unless otherwise indicated. 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.

[0132] Various examples have been described. These and other examples are within the scope of the following claims.

[0133] Example 1. A neuromodulation catheter comprising: an elongate body extending along a longitudinal axis, the elongate body comprising an expandable portion configured to transform from a relatively low-profile configuration to a radially expanded configuration; at least one therapy delivery element disposed on the expandable portion; and at least one stiffening wire comprising a shape memory material and extending at least partially along the expandable portion.

[0134] Example 2. The neuromodulation catheter of Example 1, wherein the expandable portion extends along a straight line aligned with the longitudinal axis in the relatively low-profile configuration.

[0135] Example 3. The neuromodulation catheter of Example 2, wherein the longitudinal axis is a central longitudinal axis of the catheter, and wherein the expandable portion is configured to radially expand away from the central longitudinal axis to the radially expanded configuration.

[0136] Example 4. The neuromodulation catheter of any of Examples 1 to 3, wherein the expandable portion defines a loop, a helix, or a spiral shape in the radially expanded configuration.

[0137] Example 5. The neuromodulation catheter of any of Examples 1 to 4, wherein the expandable portion extends along a first helical path in the radially expanded configuration, and wherein the at least one stiffening wire extends along a second helical path about the first helical path.

[0138] Example 6. The neuromodulation catheter of Example 5, wherein the first helical path has a same chirality as the second helical path.

[0139] Example 7. The neuromodulation catheter of Example 5, wherein the first helical path has an opposite chirality as the second helical path.

[0140] Example 8. The neuromodulation catheter of any of Examples 1 to 7, wherein the expandable portion comprises a polymer jacket.

[0141] Example 9. The neuromodulation catheter of Example 8, wherein the at least one stiffening wire extends along the catheter body between the polymer jacket and the elongate body.

[0142] Example 10. The neuromodulation catheter of Example 8, wherein the polymer jacket is a first polymer jacket, wherein the expandable portion further comprises a second polymer jacket surrounding the first polymer jacket, and wherein the at least one stiffening wire extends along the catheter body between the first polymer jacket and the second polymer jacket.

[0143] Example 11. The neuromodulation catheter of any of Examples 1 to 10, wherein the at least one therapy delivery element comprises a first therapy delivery element and a second therapy delivery element, and wherein the at least one stiffening wire extends from the first therapy delivery element to the second therapy delivery element.

[0144] Example 12. The neuromodulation catheter of Example 11, wherein the first therapy delivery element is a proximal-most therapy delivery element of the neuromodulation catheter, and wherein the second therapy delivery element is a distal-most therapy delivery element of the neuromodulation catheter.

[0145] Example 13. The neuromodulation catheter of any of Examples 1 to 12, wherein the at least one therapy delivery element comprises an electrode.

[0146] Example 14. The neuromodulation catheter of Example 13, wherein the electrode is a ring electrode surrounding a portion of the elongate body.

[0147] Example 15. The neuromodulation catheter of any of Examples 1 to 14, wherein the at least one stiffening wire defines a single coil.

[0148] Example 16. The neuromodulation catheter of any of Examples 1 to 15, wherein the at least one stiffening wire comprises at least one single-strand shape memory wire.

[0149] Example 17. The neuromodulation catheter of any of Examples 1 to 16, wherein the at least one stiffening wire consists of a single-strand shape memory wire, and wherein the neuromodulation catheter does not comprise any stiffening member extending along the expandable portion other than the single-strand shape memory wire.

[0150] Example 18. The neuromodulation catheter of any of Examples 1 to 17, wherein the at least one stiffening wire is electrically actuatable from an initial shape to a stiffening shape.

[0151] Example 19. The neuromodulation catheter of any of Examples 1 to 18, wherein the expandable portion comprises at least one shape memory member configured to transform the expandable portion from the relatively low-profile configuration to the expanded configuration.

[0152] Example 20. The neuromodulation catheter of Example 19, wherein the at least one stiffening wire is radially spaced from the at least one shape memory member of the expandable portion.

[0153] Example 21. The neuromodulation catheter of Examples 19 or 20, wherein the shape memory member comprises a helical hollow strand.

[0154] Example 22. The neuromodulation catheter of Example 21, wherein the helical hollow strand comprises the at least one stiffening wire.

[0155] Example 23. A neuromodulation catheter comprising: an elongate body extending along a longitudinal axis, the elongate body comprising an expandable portion configured to transform from a relatively low-profile configuration to a radially expanded configuration, the expandable portion configured to extend along a straight line aligned with the longitudinal axis in the relatively low-profile configuration, the expandable portion configured to extend along a helical path in the radially expanded configuration; at least one therapy delivery element disposed on the expandable portion; and at least one stiffening wire comprising a shape memory material and extending about the expandable portion along a second helical path.

[0156] Example 24. The neuromodulation catheter of Example 23, wherein the expandable portion comprises a polymer jacket.

[0157] Example 25. The neuromodulation catheter of Examples 23 or 24, wherein the at least one therapy delivery element comprises a ring electrode surrounding a portion of the elongate body.

[0158] Example 26. A neuromodulation system comprising: the neuromodulation catheter of any of claims 1 to 25; an energy source; and control circuitry configured to control the energy source to deliver neuromodulation therapy via the at least one therapy delivery element of the neuromodulation catheter.

[0159] Example 27. The neuromodulation system of Example 26, wherein the expandable portion defines an inner lumen configured receive a guidewire, wherein the expandable portion is configured to transform from the relatively low-profile configuration to the radially expanded configuration in response to proximal retraction of the guidewire out of the inner lumen of the expandable portion.

[0160] Example 28. The neuromodulation system of Examples 26 or 27, further comprising a guide sheath defining a guide lumen configured to receive the neuromodulation catheter in the low-profile configuration, and wherein the expandable portion catheter is configured to transform to the radially expanded configuration in response to removal of the guide sheath from around the expandable portion.

[0161] Example 29. A method of forming a neuromodulation catheter, the method comprising: forming an elongate body comprising at least one therapy delivery element disposed on an expandable portion, the expandable portion configured to transform from a relatively low-profile configuration to a radially expanded configuration; and coupling at least one stiffening wire comprising a shape memory material to the elongate body such that the at least one stiffening wire extends at least partially along the expandable portion.

[0162] Example 30. The method of Example 29, further comprising forming a polymer jacket about a central longitudinal axis of the elongate body.

[0163] Example 31. The method of Examples 29 or 30, wherein forming the elongate body comprises securing at least one shape memory member to the elongate body, wherein the at least one shape memory member is configured to transform the expandable portion from the relatively low-profile configuration to the radially expanded configuration.

[0164] Example 32. A method of forming a neuromodulation catheter according to the present disclosure.

[0165] Example 33. A method comprising: advancing a neuromodulation catheter through vasculature to a target tissue site within a blood vessel of a patient, wherein the neuromodulation catheter comprises: an elongate body extending along a longitudinal axis, the elongate body comprising an expandable portion configured to transform from a relatively low-profile configuration to a radially expanded configuration; at least one therapy delivery element disposed on the expandable portion; and at least one stiffening wire comprising a shape memory material and extending at least partially along the expandable portion; deploying the expandable portion to the radially expanded configuration to place the at least one therapy delivery element in apposition to a vessel wall of the blood vessel at a location; and delivering, via the at least one therapy delivery element, therapy to tissue of the patient through the vessel wall at the location.

[0166] Example 34. The method of Example 33, wherein the location is a first location, the method further comprising: rotating the expandable portion relative to the longitudinal axis to place the at least one therapy delivery element in apposition to the vessel wall of the blood vessel at a second location; and delivering, via the at least one therapy delivery element, therapy at the second location.

[0167] Example 35. The method of Example 34, wherein rotating the expandable portion comprises rotating a proximal portion of the elongate body relative to the longitudinal axis, wherein rotating the proximal portion causes the expandable portion to rotate.

[0168] Example 36. The method of any of Examples 33 to 35, wherein the expandable portion is constrained in the low-profile configuration by a guidewire or a guide sheath, and wherein deploying the expandable portion comprises retracting the guidewire or the guide sheath from the elongate body relative to the expandable portion.

[0169] Example 37. A method comprising delivering neuromodulation therapy via at least one therapy delivery element of a neuromodulation catheter according to the present disclosure.

Claims

CLAIMS1. A neuromodulation catheter comprising: an elongate body extending along a longitudinal axis, the elongate body comprising an expandable portion configured to transform from a relatively low-profile configuration to a radially expanded configuration; at least one therapy delivery element disposed on the expandable portion; and at least one stiffening wire comprising a shape memory material and extending at least partially along the expandable portion.

2. The neuromodulation catheter of claim 1, wherein the expandable portion extends along a straight line aligned with the longitudinal axis in the relatively low-profile configuration, wherein the longitudinal axis is a central longitudinal axis of the catheter, and wherein the expandable portion is configured to radially expand away from the central longitudinal axis to the radially expanded configuration.

3. The neuromodulation catheter of claims 1 or 2, wherein the expandable portion defines a loop, a helix, or a spiral shape in the radially expanded configuration.

4. The neuromodulation catheter of any one of claims 1 to 3, wherein the expandable portion extends along a first helical path in the radially expanded configuration, and wherein the at least one stiffening wire extends along a second helical path about the first helical path.

5. The neuromodulation catheter of any one of claims 1 to 4, wherein the expandable portion comprises a polymer jacket, and wherein the at least one stiffening wire extends along the catheter body between the polymer jacket and the elongate body.

6. The neuromodulation catheter of any one of claims 1 to 4, wherein the expandable portion comprises a first polymer jacket and a second polymer jacket surrounding the first polymer jacket, and wherein the at least one stiffening wire extends along the catheter body between the first polymer jacket and the second polymer jacket.

7. The neuromodulation catheter of any one of claims 1 to 6, wherein the at least one therapy delivery element comprises a first therapy delivery element and a second therapy delivery element, and wherein the at least one stiffening wire extends from the first therapy delivery element to the second therapy delivery element.

8. The neuromodulation catheter of any one of claims 1 to 7, wherein the at least one therapy delivery element comprises an electrode.

9. The neuromodulation catheter of any one of claims 1 to 8, wherein the at least one stiffening wire defines a single coil.

10. The neuromodulation catheter of any one of claims 1 to 9, wherein the at least one stiffening wire is electrically actuatable from an initial shape to a stiffening shape.

11. The neuromodulation catheter of any one of claims 1 to 10, wherein the expandable portion comprises at least one shape memory member configured to transform the expandable portion from the relatively low-profile configuration to the radially expanded configuration, and wherein the at least one stiffening wire is radially spaced from the at least one shape memory member.

12. The neuromodulation catheter of any one of claims 1 to 10, wherein the expandable portion comprises at least one shape memory member configured to transform the expandable portion from the relatively low-profile configuration to the radially expanded configuration, wherein the at least one shape memory member comprises a helical hollow strand, and wherein the helical hollow strand comprises the at least one stiffening wire.

13. A neuromodulation system comprising: the neuromodulation catheter of any one of claims 1 to 12; an energy source; and control circuitry configured to control the energy source to deliver neuromodulation therapy via the at least one therapy delivery element of the neuromodulation catheter.

14. A method of forming a neuromodulation catheter, the method comprising: forming an elongate body comprising at least one therapy delivery element disposed on an expandable portion, the expandable portion configured to transform from a relatively low-profile configuration to a radially expanded configuration; and coupling at least one stiffening wire comprising a shape memory material to the elongate body such that the at least one stiffening wire extends at least partially along the expandable portion.

15. The method of claim 14, further comprising forming a polymer jacket about a central longitudinal axis of the elongate body.

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