Neuromodulation including magnetic stimulation

Abstract

A neuromodulation catheter includes an elongate body configured to transform from a relatively low profile configuration to an expanded configuration. A distal portion of the elongate body is configured to be positioned within an anatomical lumen of a patient. The neuromodulation catheter may further include a therapy delivery element disposed on the elongate body and configured to deliver neuromodulation therapy to tissue proximate the anatomical lumen. The neuromodulation catheter may further include a magnetic stimulation element disposed on the elongate body. The magnetic stimulation element is configured to generate a magnetic field in response to delivery of a stimulation signal to the magnetic stimulation element. The magnetic field has a strength sufficient to induce a stimulation current at a target tissue site adjacent the magnetic stimulation element.

Description

NEUROMODULATION INCLUDING MAGNETIC STIMULATIONCROSS-REFERENCE TO RELATED APPLICATION S)

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 672,989, filed July 18, 2024, which is incorporated herein by reference in its entirety.TECHNICAL FIELD

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

[0003] A denervation procedure may include ablating target nerves, for example, by delivering ablative energy to a target tissue site via a catheter. For example, a denervation procedure may include ablating renal nerves, hepatic nerves, or other nerves.Neuromodulation therapy may be monitored by measuring a physiological response to nerve stimulation.SUMMARY

[0004] In general, the present disclosure describes neuromodulation catheters including an elongate body including a therapy delivery element and a magnetic stimulation element.

[0005] Neuromodulation catheters may be used to deliver neuromodulation therapy, for example, by delivering energy to ablate a nerve via at least one therapy delivery element (e.g., an ablation electrode). In some examples, a neuromodulation catheter includes a distal portion configured to transform from a relatively low-profile configuration to a deployed configuration. In the deployed configuration, the distal portion may define a loop, a helical, or a spiral configuration. An electrode array is disposed on the distal portion.

[0006] In some examples, devices, systems, and techniques according to the present disclosure deliver ablative energy using therapy delivery elements, and determine effectiveness of ablation at a target tissue site based on a physiological response to magnetic stimulation at the target tissue site. For example, a catheter including a magnetic stimulation element may generate a magnetic field (e.g., in response to a stimulation signal generated by processing circuitry and delivered to the magnetic stimulation element) at a target tissue site. The magnetic field may have a strength that is sufficient to induce a stimulation current at the target tissue site (e.g., by generating a voltage potential that induces the stimulation current).The effect of the stimulation current at the target tissue site may differ on the extent of ablation of nerves at the target tissue site. For example, a physiological response to the stimulation current may be influenced by extent of innervation at the target tissue site, and in course of ablation, the target tissue site may get denervated. Thus, the physiological response to the stimulation current may be different before and after ablation. Thus, the processing circuitry may determine an efficacy of the ablation based by comparing the physiological response to magnetic stimulation before and after ablation.

[0007] Certain neuromodulation systems are configured to determine efficacy of ablation by applying a direct current (DC) signal to stimulate nerves and sensing a response to the DC signal. However, such DC stimulation may create a film of organic material during stimulation. The formation or geometry of the film (e.g., film thickness) may depend on stimulation parameters and electrode material. While the film of organic material may not affect the stimulation itself, the layer may interfere with ablation performed after stimulation. For example, ablation temperature may be affected by the organic material. Using magnetic stimulation may generate little to no organic material, and magnetic stimulation may not interfere with ablation, in contrast with application of a DC current.

[0008] In some examples, a neuromodulation catheter includes an elongate body configured to transform from a relatively low profile configuration to an expanded configuration. A distal portion of the elongate body is configured to be positioned within an anatomical lumen of a patient. The neuromodulation catheter may further include a therapy delivery element disposed on the elongate body and configured to deliver neuromodulation therapy to tissue proximate the anatomical lumen. The neuromodulation catheter may further include a magnetic stimulation element disposed on the elongate body. The magnetic stimulation element is configured to generate a magnetic field in response to delivery of a stimulation signal to the magnetic stimulation element. The magnetic field has a strength sufficient to induce a stimulation current at a target tissue site adjacent the magnetic stimulation element.

[0009] In some examples, a neuromodulation system includes a neuromodulation catheter and processing circuitry. The neuromodulation catheter includes an elongate body configured to transform from a relatively low profile configuration to an expanded configuration. A distal portion of the elongate body is configured to be positioned within an anatomical lumen of a patient. The neuromodulation catheter may further include a therapy delivery element disposed on the elongate body and configured to deliver neuromodulation therapy to tissue proximate the anatomical lumen. The neuromodulation catheter may further include amagnetic stimulation element disposed on the elongate body. The magnetic stimulation element is configured to generate a magnetic field in response to delivery of a stimulation signal to the magnetic stimulation element. The magnetic field has a strength sufficient to induce a stimulation current at a target tissue site. The processing circuitry is configured to generate a therapy signal configured to cause the therapy delivery element to deliver the neuromodulation therapy for a neuromodulation procedure. The processing circuitry is further configured to generate the stimulation signal to cause the magnetic stimulation element to generate the magnetic field having the strength sufficient to induce the stimulation current at the target tissue site.

[0010] In some examples, a neuromodulation system includes a neuromodulation catheter, a magnetic resonance imaging system, and processing circuitry. The neuromodulation catheter includes an elongate body configured to transform from a relatively low profile configuration to an expanded configuration. A distal portion of the elongate body is configured to be positioned within an anatomical lumen of a patient. The neuromodulation catheter may further include a therapy delivery element disposed on the elongate body and configured to deliver neuromodulation therapy to tissue proximate the anatomical lumen. The neuromodulation catheter may further include a magnetic stimulation element disposed on the elongate body. The magnetic stimulation element is configured to generate a magnetic field in response to delivery of a stimulation signal to the magnetic stimulation element. The magnetic field has a strength sufficient to induce a stimulation current at a target tissue site adjacent the magnetic stimulation element. The magnetic resonance imaging system is configured to generate a static magnetic field. The static magnetic field has a strength sufficient to induce alignment in ion channels at the target tissue site. The magnetic stimulation element of the neuromodulation catheter includes a radio-frequency coil configured to output a gradient magnetic field to induce relaxation of ions in the ion channels. The processing circuitry is configured to generate a therapy signal configured to cause the therapy delivery element to deliver the neuromodulation therapy for a neuromodulation procedure. The processing circuitry is further configured to generate the stimulation signal to cause the magnetic stimulation element to generate the gradient magnetic field.

[0011] In some examples, a method includes introducing a neuromodulation catheter in a blood vessel. The neuromodulation catheter includes an elongate body configured to transform from a relatively low profile configuration to an expanded configuration. A distal portion of the elongate body is configured to be positioned within an anatomical lumen of a patient. The neuromodulation catheter may further include a therapy delivery elementdisposed on the elongate body and configured to deliver neuromodulation therapy to tissue proximate the anatomical lumen. The neuromodulation catheter may further include a magnetic stimulation element disposed on the elongate body. The magnetic stimulation element is configured to generate a magnetic field in response to delivery of a stimulation signal to the magnetic stimulation element. The magnetic field has a strength sufficient to induce a stimulation current at a target tissue site adjacent the magnetic stimulation element. The method further includes, generating, by processing circuitry, a therapy signal to cause the therapy delivery element to deliver the neuromodulation therapy for a neuromodulation procedure. The method further includes generating, by the processing circuitry, the stimulation signal to cause the magnetic stimulation element to generate the magnetic field to induce the stimulation current at the target tissue site.

[0012] Further disclosed herein is a neuromodulation catheter that includes an elongate body configured to transform from a relatively low profile configuration to an expanded configuration, wherein a distal portion of the elongate body is configured to be positioned within an anatomical lumen of a patient, wherein the neuromodulation catheter may further include a therapy delivery element disposed on the elongate body and configured to deliver neuromodulation therapy to tissue proximate the anatomical lumen, wherein the neuromodulation catheter may further include a magnetic stimulation element disposed on the elongate body, wherein the magnetic stimulation element is configured to generate a magnetic field in response to delivery of a stimulation signal to the magnetic stimulation element, andwherein the magnetic field has a strength sufficient to induce a stimulation current at a target tissue site adjacent the magnetic stimulation element.

[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 A is a diagram illustrating an example system including a catheter configured to deliver neuromodulation therapy and including a magnetic stimulation element, a computing device, and a medical device.

[0015] FIG. IB is a diagram illustrating a partial side view of catheter of FIG. 1 A in an expanded configuration.

[0016] FIG. 2 is a diagram illustrating a partial exposed side view of a catheter including a magnetic coil and an electrode introduced in a blood vessel.

[0017] FIG. 3 A is a diagram illustrating a partial front view of a catheter in an expanded configuration including a plurality of magnetic stimulation elements including wire loops.

[0018] FIG. 3B is a diagram illustrating a partial perspective view showing a wire loop of a magnetic stimulation element of the catheter of FIG. 3 A.

[0019] FIG. 4 is a diagram illustrating a partial exposed side view of a catheter including a first magnetic stimulation element including a pair of permanent magnets introduced in a blood vessel and a second magnetic stimulation element including a radio frequency coil.

[0020] FIG. 5 is a diagram illustrating a partial exposed side view of a catheter including a first magnetic stimulation element including a pair of wire loops and a second magnetic stimulation element including a radio frequency coil.

[0021] FIG. 6 is a diagram illustrating an example system including a catheter configured to deliver neuromodulation therapy and including a magnetic stimulation element, a magnetic resonance imaging system.

[0022] FIG. 7 is a block diagram illustrating an example configuration of the computing device of FIG. 1A.

[0023] FIG. 8 is a flow diagram illustrating an example technique for neuromodulation.

[0024] FIG. 9 illustrates an example technique for accessing a renal artery and modulating renal nerves with a neuromodulation catheter in accordance with some examples of the present disclosure.

[0025] FIG. 10 is a conceptual illustration of an example sympathetic nervous system (SNS) illustrating how the brain communicated with the body via the SNS.

[0026] FIG. 11 is an enlarged anatomic view of nerves innervating a left kidney to form the renal plexus surrounding the left renal artery.

[0027] FIG. 12 is an anatomic view of a human body depicting neural efferent and afferent communication between the brain and kidneys.

[0028] FIG. 13 is a conceptual view of a human body depicting neural efferent and afferent communication between the brain and kidneys.

[0029] FIG. 14 is an anatomic view of the arterial vasculature of a human.

[0030] FIG. 15 is an anatomic view of the venous vasculature of a human.DETAILED DESCRIPTION

[0031] The present disclosure describes neuromodulation catheters including stimulation and ablation electrodes.

[0032] 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.

[0033] The present disclosure relates to a neuromodulation system that assesses efficacy of nerve ablation by monitoring a physiological response to magnetic stimulation at a target tissue site.

[0034] In some examples, a neuromodulation catheter includes an elongate body configured to transform from a relatively low profile configuration to an expanded configuration in which the distal catheter portion defines a loop, a helical, or a spiral configuration. The elongate body includes at least one therapy delivery element disposed on the elongate body. The therapy delivery element(s) may be configured to deliver electrically induced (e.g., radiofrequency), ultrasound induced, chemically induced, or thermally induced ablation therapy.

[0035] At least one magnetic stimulation element is positioned along the elongate body. For example, the at least one magnetic stimulation element may be used to deliver magnetic stimulation to a target tissue site before and after neuromodulation therapy, and the response to the stimulation may be sensed to determine whether neuromodulation of nerves in the target tissue site was achieved. For example, the neuromodulation catheter is introduced in a blood vessel such that the at least one magnetic stimulation element is configured to generate a magnetic field at a target tissue site. The magnetic field may induce a stimulation current at the target tissue site adjacent the magnetic stimulation element. That is, the magnetic field may have a strength sufficient to induce a stimulation current at the target tissue site. Stated another way, the magnetic stimulation element may deliver a magnetic stimulation signal, where the magnetic stimulation signal has a magnetic field with sufficient strength to induce a stimulation current at a target tissue site. Ablation of a nerve at the target tissue site may affect an extent of a physiological response to the stimulation current, and a change in the physiological response to the stimulation current before and after ablation may be sensed to determine the efficacy of the ablation.

[0036] FIG. 1 A is a diagram illustrating an example system 10 including a catheter 12 configured to deliver neuromodulation therapy and including a magnetic stimulation element 14, a computing device 16, and a medical device 18. In FIG. 1A, catheter 12 is in a relatively low profile configuration. FIG. IB is a diagram illustrating a partial side view of catheter 12 of FIG. 1 A in an expanded configuration 12A. Catheter 12 is also referred to as neuromodulation catheter 12.

[0037] Computing device 16 may be configured to send a control signal to medical device 18 or otherwise control the operation of one or both of catheter 12 or medical device 18. In some examples, the control signal sent by computing device 16 to medical device 18 is configured to cause medical device 18 to, based on the control signal received from computing device 16, generate a therapy signal. Medical device 18 may generate the therapy signal sent to catheter 12 to cause catheter 12 to deliver neuromodulation therapy. For example, the neuromodulation therapy may include renal neuromodulation, hepatic neuromodulation, or any other neuromodulation therapy, for a neuromodulation procedure.

[0038] Medical device 18 may be configured to generate an electrical signal comprising the therapy signal configured to be delivered by catheter 12. For example, medical device 18 may include a controller 40 and a therapy generation circuitry 42, and controller 40 may be configured to control therapy generation circuitry 42 to generate the therapy signal. Medical device 18 may also include stimulation generation circuitry 44, and controller 40 may be further configured to control stimulation generation circuitry 44 to generate a stimulation signal to test an extent of denervation in response to the therapy signal. For instance, the therapy signal may perform the denervation, and a separate stimulation signal may be used to determine the extent of the denervation.

[0039] In accordance with one or more examples described in this disclosure, the stimulation signal (e.g., used to determine the extent of the denervation) may be a magnetic stimulation signal having a strength sufficient to induce a stimulation current (or a stimulation charge) at a target tissue site (e.g., where the denervation occurs). A change in a physiological response to the stimulation current before and after denervation may be indicative of the extent of denervation (e.g., determining stimulation current before denervation and then after denervation).

[0040] As an example, controller 40 may control stimulation generation circuitry 44 to deliver the stimulation signal to magnetic stimulation element 14. The stimulation signal is configured to cause magnetic stimulation element 14 to generate a magnetic field at a target tissue site. The magnetic field may have a strength sufficient to induce a stimulation currentat the target tissue site adjacent magnetic stimulation element 14. For example, the magnetic field may induce a voltage potential along the target tissue site, and the voltage potential may induce the stimulation current. In some examples, the stimulation signal (e.g., a time-varying stimulation signal) delivered to magnetic stimulation element 14 creates the magnetic field around magnetic stimulation element 14 (e.g., extending to or across the target tissue site). A pulse of the magnetic field may pass to or through the target tissue site and induce a voltage difference between two points at the target tissue site. This voltage difference creates an electric field, which in turn induces electrons to flow between the two points. Unlike electrical stimulation, magnetic stimulation does not need passage of electric current through one or more of electrodes, skin, or a tissue interface. For example, the magnetic field itself may induce a flow of ions (and thus, the stimulation current). The flow of ions may cause nerve stimulation by axon depolarization and an initiation of an action potential. In some examples, cell bodies at the target tissue site have a relatively high stimulation threshold compared to axons, and the magnetic stimulation may be sufficient to stimulate axons without stimulating cell bodies.

[0041] Inducing a stimulation current (or a stimulation charge) at the target tissue site using a magnetic field may be beneficial over other techniques that induce a stimulation current or charge using an electric field. For example, delivery of a stimulation current by a stimulation electrode (e.g., direct current stimulation) may result in formation of a film of organic material during stimulation. The film of organic material may interfere with a subsequent delivery of a therapy signal. For example, the film may act as a thermal barrier and cause an increase in temperature during nerve ablation caused by the therapy signal. In contrast, there may be little to no film formation associated with a stimulation current locally induced by a magnetic field, for example, because there may be no contact between a stimulation electrode and tissue.

[0042] Depending on the frequency components of the therapy signal or the stimulation signal, therapy generation circuitry 42 or stimulation generation circuitry 44 may include one or both of an alternating current (AC) generator or a direct current (DC) generator. In some examples, stimulation generation circuitry 44 includes circuitry configured to rectify an AC signal to generate a DC signal. For example, stimulation generation circuitry 44 may generate the stimulation signal including solely the DC signal. In other examples, one or both of the therapy signal or the stimulation signal may include an AC signal and a DC signal, but differ in the frequency band of the AC signal, or the amplitude of the DC signal. For example, the therapy signal may have a significantly higher frequency than the stimulation signal.

[0043] Catheter 12 includes a handle 20 and an elongate body 22 attached to handle 20. That is, handle 20 is positioned at a proximal portion of elongate body 22. Elongate body 22 extends in a direction along a longitudinal axis L of catheter 12. Elongate body 22 may have any suitable outer diameter, and the diameter can be constant along the length of elongate body 22 or may vary along the length of elongate body 22. In some examples, elongate body 22 may be 2, 3, 4, 5, 6, or 7 French or another suitable size. Elongate body 22 extends along a central longitudinal axis L, and includes a distal catheter portion 22A and a proximal catheter portion 22B. Distal catheter portion 22A includes an expandable portion 24.

[0044] Expandable portion 24 is configured to transform from a relatively low-profile configuration (shown in FIG. 1 A) to a radially expanded deployed configuration 24 A (shown in FIG. IB). Elongate body 22 is configured to expand from a respective relatively low- profile configuration (shown in FIG. 1 A) to expanded configuration 24A (shown in FIG. IB), such as a spiral, loop, or helical configuration. In some examples, elongate body 22 includes a helical hollow strand configured to expand from a relatively low-profile configuration into an expanded helical configuration. The helical hollow strand may include a plurality of shape memory wires, the plurality collectively defining a lumen, the lumen being helical in an expanded configuration.

[0045] Catheter 12 further includes a therapy delivery element 26 disposed on elongate body 24 and configured to deliver neuromodulation therapy to tissue proximate an anatomical lumen. In some examples, therapy delivery element 26 includes at least one electrode configured to deliver a therapy signal. For example, controller 40 may be configured to control therapy generation circuitry 42 to generate the therapy signal configured to be delivered by therapy delivery element 26, and control stimulation generation circuitry 44 to generate the stimulation signal configured to be delivered by magnetic stimulation element 14.

[0046] Therapy generation circuitry 42 may be configured to deliver therapy to tissue of a patient via therapy delivery element 26, for example, to modulate a target nerve of the patient. For example, therapy delivery element 26 may be coupled to therapy generation circuitry 42, and therapy generation circuitry 42 may deliver a therapy signal to tissue, or to a target tissue site via therapy delivery element 26. Catheter 12 may thus deliver denervation therapy via therapy delivery element 26, and computing device 16 or controller 40 may control catheter 12 to deliver denervation therapy.

[0047] Stimulation generation circuitry 44 may be configured to deliver stimulation via magnetic stimulation element 14, for example, to assess efficacy of neuromodulation therapy.For example, a change in physiological response of the patient to stimulation before and after ablation may be indicative of an effect of neuromodulation therapy on nerve activity. Catheter 12 may thus deliver denervation therapy via therapy delivery element 26, deliver stimulation via magnetic stimulation element 14, and computing device 16 or controller 40 may control catheter 12 to deliver and assess denervation therapy. For example, the extent to which the stimulation current induced by the magnetic field affects a physiological parameter may be influenced by an extent of innervation of nerves at the target tissue site. Thus, a response of the physiological parameter to the stimulation current may change in course of neuromodulation therapy. In some examples, a response of the physiological parameter to the stimulation current reduces in magnitude when nerves get denervated. For example, a reduction in magnitude of the response of the physiological parameter to the stimulation current greater than a predetermined threshold may be indicative of efficacious neuromodulation therapy and sufficient denervation.

[0048] Therapy delivery element 26 may have any suitable shape, size, or form. In some examples, each therapy delivery element 26 consists of one electrode. In other examples, at least one therapy delivery element 26 includes more than one electrode, for example, a split electrode. In some examples, at least one electrode of at least one therapy delivery element 26 is a ring electrode. In some such examples, each therapy delivery element 26 consists of a ring electrode. In some examples, each of therapy delivery elements 26 is identical to other therapy delivery elements 26. For example, each of therapy delivery element 26 may have a same length along longitudinal axis L of elongate body 24. In some such examples, all therapy delivery elements 26 are identical in shape, size, and form. In other examples, therapy delivery elements 26 differ from each of in at least one of shape, size, or form.

[0049] In some examples, at least one therapy delivery element 26 includes gold, iridium oxide, or platinum iridium alloy. For example, gold may promote thermal dissipation and reduce thermal buildup in course of ablation. Iridium oxide may have a high electrical conductivity. Platinum iridium alloy may be less susceptible than gold to effects of electrode polarization. In some examples, at least one therapy delivery element 26 includes gold with a coating of iridium oxide. In some examples, at least one therapy delivery element 26 configured to deliver a therapy signal includes, consists of, or consists essentially of (excepting for minor impurities) gold. In some examples, each therapy delivery element 26 includes, consists of, or consists essentially of gold.

[0050] At least one electrode of therapy delivery element 26 may be coupled to a respective thermocouple. For example, controller 40 may sense a respective temperature ofthe at least one electrode via the thermocouple. In some examples, controller 40 may be configured to terminate ablation therapy in response to a temperature sensed by the thermocouple, for example, to avoid excessive heating of catheter 12 or neighboring tissue.

[0051] Magnetic stimulation element 14 is configured to generate a magnetic field in response to delivery of a stimulation signal (e.g., the stimulation signal generated by stimulation generation circuitry 44) to magnetic stimulation element 14. For example, stimulation generation circuitry 44 is configured to output the stimulation signal, and passing the signal through magnetic stimulation element 14 generates the magnetic field. Magnetic stimulation element 14 may include one or more of a permanent magnet, an electromagnet, a coil, a wire loop, or any other element capable of generating a magnetic field.

[0052] Magnetic stimulation element 14 may be positioned or oriented along elongate body 22 to direct the magnetic field at any suitable spacing, location, or orientation relative to magnetic stimulation element 14 and / or elongate body 22. For example, magnetic stimulation element 14 may be configured to generate the magnetic field along a direction transverse to the elongate body (e.g., transverse to longitudinal axis L). In such examples, when elongate body 22 is placed within a blood vessel, magnetic stimulation element 14 may generate the magnetic field in a direction radially outward with respect to the blood vessel.

[0053] Magnetic stimulation element 14 may be configured to generate one or more of a static, dynamic, or gradient magnetic field, and magnetic field may have a direction or magnitude that may be constant or vary with time (e.g., increasing, decreasing, periodic, or any other temporal or spatial pattern). In turn, the characteristics of the magnetic field F may affect the magnitude and direction of the stimulation current.

[0054] FIG. 2 is a diagram illustrating a partial exposed side view of a catheter 112 including a magnetic coil 114 and an electrode 126 introduced in a blood vessel. Catheter 112 is substantially similar to catheter 10 described with reference to FIGS. 1 A and IB, with magnetic element 114 being an example of magnetic element 14, and electrode 126 being an example of therapy delivery element 26. Magnetic coil 114 may include a coil including a metal or an alloy, and have a composition, a geometry (e.g., length, coil width, wire width, lumen diameter, number of turns) that affects characteristics of a magnetic field F generated by magnetic coil 114 in response to a stimulation signal. In some examples, magnetic coil 114 includes a metal or an alloy described with reference to magnetic stimulation element 14. In some examples, magnetic coil 114 surrounds a ferritic core.

[0055] The stimulation signal may be received by magnetic coil 114 through a signal wire 121, and generated, for example, by stimulation generation circuitry 44 described withreference to FIG. 1 A. In some examples, magnetic coil 114 is electrically coupled to electrode 126, for example, via signal wire 121. Thus, the same signal wire can be used to transit a stimulation signal to magnetic coil 114 and a therapy signal to electrode 126. For example, the stimulation signal and the therapy signal may be alternated, or delivered in different frequency bands, or otherwise multiplexed along signal wire 121. In some such examples, the same signal may serve as both the stimulation signal and the therapy signal. In other examples, magnetic coil 114 and electrode 126 are not electrically coupled, and separate wiring is used to respectively deliver the stimulation signal to magnetic coil 114 and the therapy signal to electrode 126.

[0056] As seen in FIG. 2, in some examples, magnetic coil 114 is oriented transverse relative to longitudinal axis L such that a magnetic field F generated by magnetic coil 114 is oriented transverse to longitudinal axis L and radially outward the blood vessel toward a target tissue site T. Cells 125 at the target tissue site may get electrically polarized in response to magnetic field F. In some examples, a magnitude of the magnetic field F is sufficient to generate neural cell membrane potentials to depolarize neurons at the target tissue site T. Magnetic field F may induce a voltage potential (e.g., Vhighto Viow) in a direction across target tissue site T, and the voltage potential may induce a stimulation current along the target tissue site.

[0057] Turning back to FIG. 1 A, a physiological response to the stimulation current may vary based on the extent of denervation at the target tissue site T. For example, computing device 16 may compare a first sensor signal received from at least one sensor (not shown in the figures) indicative of a first magnitude associated with a physiological parameter before ablation with a second sensor signal indicative of a second magnitude associated with the physiological parameter after ablation. For example, the first sensor signal may be indicative of a first value of a physiological response (e.g., a change in a magnitude of physiological parameter) to a stimulation current before denervation, while the second sensor signal may be indicative of a second value of the physiological response after denervation. Based on the comparison of the first and second sensor signals (and thus, the first and second values of the physiological response), computing device 16 may determine an efficacy of the ablation.

[0058] In some examples, catheter 12 includes a plurality of magnetic stimulation elements 14 disposed along elongate body 24, for example, aligned with a direction along longitudinal axis L of catheter 12. Although FIG. 1 A illustrates four magnetic stimulation elements 14, in other examples, catheter 12 may include one, two, three, five, or more magnetic stimulation elements 14.

[0059] In some examples, catheter 12 includes a plurality of therapy delivery elements 26 disposed along elongate body 24, for example, aligned with a direction along longitudinal axis L of catheter 12. Although FIG. 1 A illustrates four therapy delivery elements 26, in other examples, catheter 12 may include one, two, three, five, or more therapy delivery elements 26. The number of magnetic stimulation elements 14 or therapy delivery elements 26 may be the same or different, and may independently be odd or even. In some examples, a plurality of magnetic stimulation elements 14 is interleaved with a plurality of therapy delivery elements 26, for example, along elongate body 22. In other examples, a plurality of magnetic stimulation elements 14 is spaced relative to a plurality of therapy delivery elements 26, for example, along elongate body 22.

[0060] FIG. 3A is a diagram illustrating a partial front view of a catheter 212 in an expanded configuration including a plurality of magnetic stimulation elements 214 including wire loops. FIG. 3B is a diagram illustrating a partial perspective view showing a wire loop of a magnetic stimulation element 214 of catheter 212 of FIG. 3A. Catheter 212 may be substantially similar to catheter 10 described with reference to FIG. 1 A, including a plurality of therapy delivery elements 226, and with plurality of magnetic stimulation elements 214 being examples of magnetic stimulation element 14 including wire loops.

[0061] In some examples, each magnetic stimulation element of plurality of magnetic stimulation elements 214 includes a respective wire loop. Each wire loop of respective magnetic stimulation elements of plurality of magnetic stimulation elements 214 may be identical or differ in one or more of shape, size, or composition. In some examples, each wire loop includes a metal or an alloy described with reference to magnetic stimulation element 14. Plurality of magnetic stimulation elements 214 may be configured to radially surround plurality of therapy delivery elements 26 relative to an elongate body 222 in an expanded configuration of the elongate body 222.

[0062] Plurality of magnetic stimulation elements 214 may be oriented and positioned relative to elongate body 222 or plurality of therapy delivery elements 226 to generate a magnetic field having a predetermined geometry, spacing, or orientation. For example, each magnetic stimulation element of plurality of magnetic stimulation elements 214 may generate a respective sub-field contributing to a combined magnetic field generated by an entirety of plurality of magnetic stimulation elements 214. One or more magnetic stimulation elements of plurality of magnetic stimulation elements 214 may be individually controlled by respective stimulation signals to deliver periodic, varying, static, or gradient magnetic fields, having any suitable temporal or spatial pattern.

[0063] In some examples, as described with reference to FIGS. 4 and 5, a catheter may include two types of magnetic stimulation elements. For example, the catheter may include a first magnetic stimulation element configured to generate a static magnetic field, and a second magnetic stimulation element configured to generate a gradient magnetic field.

[0064] FIG. 4 is a diagram illustrating a partial exposed side view of a catheter 312 including a first magnetic stimulation element 314A including a pair of permanent magnets and a second magnetic stimulation element 314B including a radiofrequency (RF) coil. The RF coil may be similar to magnetic coil 114 described with reference to FIG. 2. First magnetic stimulation element 314A may be configured to generate a static magnetic field to induce alignment in ion channels (e.g., in cells) at a target tissue site, and second magnetic stimulation element 314B may be configured to generate a gradient magnetic field to induce relaxation of ions in the ion channels. While first magnetic stimulation element 314A may include a pair of permanent magnets as shown in FIG. 4, in other examples, first magnetic stimulation element 314A may include one, three, or more permanent magnets or pairs of permanent magnets.

[0065] In some examples, catheter 312 further includes one or more therapy delivery elements, similar to therapy delivery element 26 described with reference to FIG. 1 A. In other examples, catheter 312 does not itself include any therapy delivery element, and catheter 312 is used to deliver magnetic stimulation, while another catheter (e.g., similar to or same as catheter 10) is used to deliver neuromodulation therapy.

[0066] FIG. 5 is a diagram illustrating a partial exposed side view of a catheter 412 including a first magnetic stimulation element 414A including a radiofrequency (RF) coil and a second magnetic stimulation element 414B including a pair of wire loops. The RF coil may be similar to magnetic coil 114 described with reference to FIG. 2. The wire loops may be similar to wire loops of magnetic stimulation element 214 described with reference to FIGS. 3A and 3B. While first magnetic stimulation element 414A may include a pair of wire loops as shown in FIG. 4, in other examples, first magnetic stimulation element 414A may include one, three, or more wire loops or pairs of wire loops.

[0067] In some examples, catheter 412 further includes one or more therapy delivery elements, similar to therapy delivery element 26 described with reference to FIG. 1 A. In other examples, catheter 412 does not itself include any therapy delivery element, and catheter 412 is used to deliver magnetic stimulation, while another catheter (e.g., similar to or same as catheter 10) is used to deliver neuromodulation therapy.

[0068] FIG. 6 is a diagram illustrating an example system 500 including catheter 512 configured to deliver neuromodulation therapy and including magnetic stimulation element 314A and a magnetic resonance imaging (MRI) system 515. Catheter 512 may be any catheter according to the present disclosure, including any of catheters 10, 212, 312, or 412, or another catheter. In some examples, catheter 512 is similar to catheter 312, and includes one or both of first magnetic element 314A or second magnetic element 314B. MRI system 515 includes a static magnetic element 514 configured to generate a static field. Other magnetic elements of MRI system 515 may be maintained switched off or dormant during operation of system 500. One or both of first magnetic element 314A or second magnetic element 314B may be used to generate a gradient field. Thus, catheter 512 may be used in combination with an existing MRI system 515 (e.g., in a clinical environment) to generate magnetic stimulation at a target tissue site.

[0069] Turning back to FIG. 1 A, distal catheter portion 22A of catheter 12 is configured to be positioned and / or advanced within an anatomical lumen of a human patient to locate at least one electrode of therapy delivery element 26 at a target tissue site within or otherwise proximate to the anatomical lumen. For example, catheter 12 may be configured to position distal catheter portion 22A within a blood vessel, a ureter, a urethra, a duct, an airway, or another naturally occurring lumen within the human body. The examples described herein focus on the anatomical lumen being a blood vessel, such as a renal vessel, but it will be understood that similar techniques may be used with other anatomical lumens.

[0070] Catheter 12 can be configured for delivery to a target tissue site within vasculature of a patient via a guide member, which can include, for example, one or more of a guidewire or an outer sheath. In certain examples, intravascular delivery of distal catheter portion 22A includes percutaneously inserting a guidewire (not shown in FIG. 1 A) into a vessel of a patient and moving at least elongate body 22 (for example, at least expandable portion 24) along the guidewire until expandable portion 24 reaches a target tissue site (for example, a renal artery). For example, distal catheter portion 22A of elongate body 22 (e.g., elongate body 24) may define a lumen configured to receive a guidewire for delivery of distal catheter portion to a target tissue site using over-the-wire (OTW) or rapid exchange (RX) techniques. In other examples, catheter 12 can be a steerable or non-steerable device configured for use without a guidewire. In still other examples, catheter 12 can be configured for delivery via an inner lumen of a guide member, for example, a guide catheter, an outer sheath (not shown in FIG. 1 A), or other guide device.

[0071] A distal end of elongate body 22 defines distal tip 28. Distal tip 28 is configured to facilitate navigation of distal catheter portion 22A within the vasculature of the patient to a blood vessel. In some examples, distal tip 28 may be atraumatic, for example, to resist or avoid puncturing a vessel of a blood vessel during navigation of distal catheter portion 22A within the blood vessel.

[0072] In the example illustrated in FIG. 1 A, catheter 12 is in a relatively low-profile delivery configuration, in which distal catheter portion 22A defines a relatively smaller radial extent (a relatively low-profile, such as a relatively linear configuration) relative to expanded (also referred to as a radially expanded and / or deployed) configuration 12A in which expandable portion 24 of distal catheter portion 22A defines a relatively larger radial extent. In some examples, the radial extent is measured in a direction orthogonal to central longitudinal axis L. Distal catheter portion 22A may be delivered through vasculature of the patient to the target tissue site in the low-profile configuration. In some examples, expandable portion 24 is configured to self-expand within a blood vessel of a patient, e.g., via a shape-memory element (e.g., a shape memory tube or a hollow helical strand) of elongate body 24. In some examples, expandable portion 24 (e.g., elongate body 22) extends along a straight line aligned with longitudinal axis L in the relatively low-profile configuration shown in FIG. 1 A. Expandable portion 24 may be constrained or restrained in the low-profile configuration by a guide member. The clinician may retract the guide member proximally relative to expandable portion 24 to un-constrain expandable portion 24 and cause or allow expandable portion 24 to transform from the low-profile configuration to an expanded configuration. Thus, expandable portion 24 may be configured to radially expand to the expanded configuration 24A shown in FIG. IB.

[0073] In some examples, in expanded configuration 24A shown in FIG. IB, expandable portion 24A defines a loop, a helix, or a spiral shape, or a basket, or a stent-like configuration. In the expanded configuration, expandable portion 24A is configured to position one or more therapy delivery elements 26 near a vessel wall, for example, in apposition with the vessel wall.

[0074] In some examples, expandable portion 24 may be expanded or may self-expand as a result of proximal retraction of a guide member from distal catheter portion 22A. The clinician may retract the guide member to a location along distal catheter portion 22A proximal to expandable portion 24 to cause or allow expandable portion 24 to expand. In the expanded configuration, expandable portion 24 may place at least one therapy delivery element 26 at a first location relative to the vessel wall, for example, corresponding to a firstrotational location. A clinician may control a therapy delivery device to deliver, provide, or facilitate neuromodulation therapy at the target tissue site, for example, through the vessel wall at the target tissue site to target tissue adjacent to the blood vessel. The neuromodulation therapy may include, but is not limited to, radiofrequency (RF) energy, microwave energy, or the like.

[0075] The clinician may rotate handle 20, or otherwise proximal portion 22B, to apply a torque to distal portion 22A and cause expandable portion 24 to rotate about central longitudinal axis L from the first rotational location to a second rotational location. For example, the application of torque from handle 20 or proximal portion 22B to expandable portion 24 may cause expandable portion 24 to rotate about longitudinal axis L, for example, in a same direction as the torque. The clinician may control system 10 to deliver ablation therapy or stimulation at the second rotational location, or after further successive rotational locations of expandable portion 24.

[0076] Catheter 12 may be connected to controller 40 (e.g., a therapy delivery device or within medical device 18). Controller 40 may include processing circuitry and a therapy source (for example, an electrical signal generator, or the like), or may control therapy generation circuitry 42 via at least one electrical conductor.

[0077] Wiring to deliver the therapy signal or the stimulation signal along catheter 12 may be positioned along an exterior or interior of catheter 12. For example, in catheter 12, wiring may extend from a port (e.g., electrically coupled to controller 40) in handle 20 along proximal catheter portion 22B to distal catheter portion 22A, and may include a first wiring extending through or along elongate body 24 and configured to deliver the therapy signal, and a second wiring extending through or along elongate body 24 and configured to deliver the stimulation signal. In other examples, both the therapy signal and the stimulation signal may be delivered via a same wiring.

[0078] System 10 and / or catheter 12 may be used to deliver ablation and stimulation for neuromodulation according to any appropriate scheme. For example, computing device 16 or controller 40 may control catheter 12 to deliver a neuromodulation therapy including ablation and stimulation. In some examples, computing device 16 controls controller 40 to deliver ablation and stimulation via catheter 12. For example, computing device 16 may be configured to generate and send a control signal to controller 40, and controller 40 may be configured to generate, based on the control signal, an electrical signal sent to catheter 12.

[0079] FIG. 7 is a block diagram illustrating an example configuration of computing device 16 of FIG. 1 A. In some examples, controller 40 may include computing device 16, orinclude one or more components described with reference to computing device 16, or otherwise perform functions described with reference to computing device 16. Computing device 16 may include a workstation, a tablet computer, a laptop computer, or a desktop computer. Computing device 16 or a similar computing device may be used to control any example system or catheter according to the present disclosure.

[0080] As shown in the example of FIG. 2, computing device 16 includes processing circuitry 170, storage device 172, communication circuitry 174, and a user interface 176. While computing device 16 may be a stand-alone device as shown in FIG. 7, in other examples, computing device 16 may be any component or system that includes processing circuitry or other suitable computing environment for executing software instructions and, for example, need not necessarily include one or more elements shown in FIG. 7 (e.g., in some examples components such as storage device 172 may not be co-located or in the same housing or structure as other components).

[0081] Processing circuitry 170, in some examples, is configured to implement functionality and / or process instructions for execution within at least one computing device 16. For example, processing circuitry 170 may be capable of processing instructions, including at least one application 180, stored in storage device 172. Examples of processing circuitry 170, as well as other processors, processing circuitry, controllers, control circuitry, and the like, described herein, may include any combination of integrated circuitry, discrete logic circuitry, analog circuitry, such as one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), or field-programmable gate arrays (FPGAs). In some examples, processing circuitry 170 includes multiple components, such as any combination of one or more microprocessors, one or more DSPs, one or more ASICs, or one or more FPGAs, as well as other discrete or integrated logic circuitry, and / or analog circuitry.

[0082] Storage device 172 (which can also be referred to as a memory) may be configured to store information within computing device 16, including at least one application 180 and data 190. Storage device 172, in some examples, is a computer-readable storage medium. In some examples, storage device 172 includes a temporary memory or a volatile memory. Storage device 172, in one example, is used by at least one application 180 running on computing device 16 to temporarily store information during program execution. Storage device 172, in some examples, also includes one or more memories configured for long-term storage of information, e.g., including non-volatile storage elements. Examples of such nonvolatile storage elements include any volatile, non-volatile, magnetic, optical, or electricalmedia, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital media.

[0083] Computing device 16 utilizes communication circuitry 174 to communicate with other devices, such as catheter 12, controller 40, other computing devices, and system 10 of FIG. 1 A. Communication circuitry 174 may include a network interface card, such as an Ethernet card, an optical transceiver, a radio frequency transceiver, or any other type of device that can send and receive information. Other examples of such network interfaces may include 3G, 4G, 5G, and WiFi radios.

[0084] Computing device 16 may include a user interface 176. User interface 176 may be configured to provide output to a user using tactile, audio, or video stimuli and receive input from a user through tactile, audio, or video feedback. User interface 176 may include, as examples, a presence-sensitive display, a mouse, a keyboard, a voice responsive system, video camera, microphone, or any other type of device for detecting a command from a user, a sound card, a video graphics adapter card, or any other type of device for converting a signal into an appropriate form understandable to humans or machines, a speaker, a display device, such as, but not limited to, cathode ray tube (CRT) monitor, a liquid crystal display (LCD), or any other type of device that can generate intelligible output to a user. In some examples, a presence-sensitive display includes a touch-sensitive screen.

[0085] At least one application 180 executable by processing circuitry 170 of computing device 16 may include a stimulation interface application 182 and a monitoring system 184 that may utilize physiological data or other data obtained during neuromodulation to monitor the progress of neuromodulation and effects of ablation. At least one application 180 further may include an ablation interface application 186 that controls delivery of ablation via controller 40 and / or catheter 12.

[0086] Execution of stimulation interface 182 and ablation interface 186 by processing circuitry 170 configures computing device 16 to interface with system 10 or controller 40 (or catheter 12). For example, stimulation interface 82 configures computing device 16 to communicate with controller 40 via communication circuitry 174. Processing circuitry 170 may receive a signal from a physiological sensor indicative of a physiological parameter, and store the physiological data 192 in storage device 172. Physiological parameters may include, but are not limited to, electrical conduction, electrical impedance, tissue response (e.g., blood pressure), heat response (e.g., heart rate), or any other physiological parameter that may change as a result of ablation and be stimulated through stimulation. Stimulation interface182 and / or ablation interface 186 also configures user interface 176 for a user to interact with controller 40 (or catheter 12). One or more of stimulation interface 182, monitoring system 184, or ablation interface 186 may cause processing circuity 170 and computing device 16 to perform any of the techniques described herein related to neuromodulation by system 10.

[0087] FIG. 8 is a flow diagram illustrating an example technique for neuromodulation. The example technique of FIG. 8 is described with reference to processing circuitry 170 of computing device 16 and system 10 of FIG. 1A. However, the example technique may be implemented by any suitable computing device, controller, catheter, or system alone or in combination with processing circuitry 170.

[0088] The technique includes delivering, by therapy delivery element 26 disposed on elongate body 24 of neuromodulation catheter 12, neuromodulation therapy to a target tissue site (600). Neuromodulation catheter 12 is placed in a vessel of a patient. For example, processing circuitry 170 may send the therapy signal to neuromodulation catheter 12. In some examples, processing circuitry 170 causes controller 40 to generate the therapy signal, and to send the therapy signal to therapy delivery element 26 of neuromodulation catheter 12. Therapy delivery element 26 delivers neuromodulation therapy in response to the therapy signal. For example, therapy delivery element 26 may cause denervation at the target tissue site in response to the therapy signal.

[0089] The technique further includes delivering, by magnetic stimulation element 14 disposed on elongate body 24 of neuromodulation catheter 12, magnetic stimulation to the target tissue site (602). For example, processing circuitry 170 may send a stimulation signal to magnetic stimulation element 14 of neuromodulation catheter 12, and magnetic stimulation element 14 may generate a magnetic field at the target tissue site based on the stimulation signal. The magnetic field has a strength sufficient to induce a stimulation current at the target tissue site. In some examples, processing circuitry 170 causes controller 40 to generate the stimulation signal, and to send the stimulation signal to magnetic stimulation element 14 of neuromodulation catheter 12.

[0090] The technique further includes determining, by processing circuitry 170, a physiological response to the stimulation signal (604). Processing circuitry 170 may determine, based on the physiological response, an effectiveness of ablation at the target tissue site induced by the therapy signal. For example, attenuation of the physiological response may be indicative of a reduction in neural activity, and thus, successful ablation. A physiological response may include any physiological parameter of a biological that may be affected by the stimulation signal (e.g., the stimulation current) to the biological system. Forexample, the stimulation signal is a first stimulation signal preceding the therapy signal, and magnetic stimulation element 14 may deliver a second stimulation signal to the target tissue site after the therapy signal, and processing circuitry 170 may compare a physiological parameter after the first stimulation signal and a physiological parameter after the second stimulation signal.

[0091] Processing circuitry 170 may initiate, continue, or terminate ablation in response to the comparison. For example, processing circuitry 170 may cause controller 40 to initiate, continue, or terminate ablation in response to the comparison. For example, if the comparison indicates that neural traffic is attenuated, or that the target tissue site has been sufficiently ablated or denervated, processing circuitry 170 may cause controller 40 to terminate ablation. However, if the comparison indicates that neural traffic is not attenuated, or that the target tissue site has not been sufficiently ablated or denervated, processing circuitry 170 may cause controller 40 to initiate or continue ablation.

[0092] In some examples, processing circuitry 170 may further generate an output indicative of the efficacy of the neuromodulation procedure. In some examples, processing circuitry 170 may further generate a notification in response to determining that the efficacy of the neuromodulation procedure is lower than a threshold value. In some examples, processing circuitry 170 may further control medical device 18 to adjust the neuromodulation procedure based on the efficacy. In some examples, processing circuitry 170 may further automatically adjust the neuromodulation procedure based on the efficacy.

[0093] Thus, example systems and techniques according to the present disclosure may be used to deliver, monitor, or control neuromodulation therapy.

[0094] FIG. 9 illustrates an example technique for accessing a renal artery and modulating renal nerves with a neuromodulation catheter. While FIG. 9 illustrates the use of catheter 12 for renal neuromodulation, catheter 12 may be used for other therapies and treatments within another blood vessel or other hollow anatomical body within the human body. Catheter 12 is configured to deliver energy (e.g., RF energy, ultrasound energy, electrical stimulation energy, or the like) to one or more target tissue sites within a renal vessel. Catheter 12 provides access to the renal plexus (RP) through an intravascular path (P), such as a percutaneous access site in the femoral (illustrated), brachial, radial, or axillary artery to the target tissue sites within a respective renal artery (RA). By manipulating proximal portion 22B or elongate body 22 from outside the intravascular path (P), a clinician may advance distal portion 22A of elongate body 22 through the sometimes-tortuous intravascular path (P)and remotely manipulate distal portion 22A (FIG. 1 A) of elongate body 22. Distal portion 22A may be remotely manipulated by the clinician using handle 20.

[0095] In the example illustrated in FIG. 9, distal portion 22A is delivered intravascularly to the treatment site using an inner member 123 in an over-the-wire (OTW) technique. Inner member 123 may be internal to catheter 12 (e.g., a guide wire, inner catheter, or the like) or external to catheter 12 (e.g., an outer sheath or the like). In some examples, inner member 123 is a navigation wire. Catheter 12 may define a passageway for receiving inner member 23 for delivery of catheter 12 using either an OTW or an RX technique. At the treatment site, inner member 123 can be at least partially withdrawn or removed relative to catheter 12 and distal portion 22A can transform into an expanded configuration (for example, a helical configuration, a spiral configuration, or the like) for delivering ultrasound energy. In other examples, elongate body 22 is self-steerable such that therapy may be delivered to the target tissue site without the aid of inner member 123.

[0096] In some examples, catheters described herein may be used to perform renal modulation. Renal modulation is the partial or complete incapacitation or other effective disruption of nerves of the kidneys (e.g., nerves terminating in the kidneys or in structures closely associated with the kidneys). In particular, renal neuromodulation can include inhibiting, reducing, or blocking neural communication along neural fibers (e.g., efferent or afferent neural fibers) of the kidneys. Such incapacitation can be long-term (e.g., permanent or for a period of months, years, or decades) or short-term (e.g., for periods of minutes, hours, days, or weeks). Renal neuromodulation is expected to contribute to the systemic reduction of sympathetic tone or drive or benefit at least some specific organs or other bodily structures innervated by sympathetic nerves. Accordingly, renal neuromodulation is expected to 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.

[0097] 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 ofthe 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 22A within the renal artery, delivering the therapy to targeted tissue, or effectively modulating the renal nerves with the therapy delivery device.

[0098] As noted previously, the sympathetic nervous system (SNS) is a branch of the autonomic nervous system along with the enteric nervous system and parasympathetic nervous system. It is always active at a basal level (called sympathetic tone) and becomes more active during times of stress. Like other parts of the nervous system, the sympathetic nervous system operated through a series of interconnected neurons. Sympathetic neurons are frequently considered part of the peripheral nervous system (PNS), although many lie within the central nervous system (CNS). Sympathetic neurons of the spinal cord (which is part of the CNS) communicate with peripheral sympathetic neurons via a series of sympathetic ganglia. Within the ganglia, spinal cord sympathetic neurons are therefore called presynaptic (or preganglionic) neurons, while peripheral sympathetic neurons are called postsynaptic (or postganglionic neurons).

[0099] 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.

[0100] 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.

[0101] 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.

[0102] FIG. 10 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.10, 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.

[0103] 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.

[0104] 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.

[0105] 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.

[0106] FIG. 11 is an enlarged anatomic view of nerves innervating a left kidney to form the renal plexus surrounding the left renal artery. As FIG. 11 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.

[0107] 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.

[0108] 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.

[0109] 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.

[0110] 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.[OHl] Activation of cardiorenal sympathetic nerve activity is even more pronounced in heart failure, as demonstrated by an exaggerated increase of NE overflow from the heart and the kidneys to plasma in this patient group. In line with this notion is the recent demonstration of a strong negative predictive value of renal sympathetic activation on allcause mortality and heart transplantation in patients with congestive heart failure, which is independent of overall sympathetic activity, glomerular filtration late, and left ventricular ejection fraction. These findings support the notion that treatment regimens that are designed to reduce renal sympathetic stimulation have the potential to improve survival in patients with heart failure.

[0112] 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.

[0113] Sympathetic nerves to the kidneys terminate in the blood vessels, the juxtaglomerular apparatus, and the renal tubules. Stimulation of the renal sympathetic nervescause increased renin release, increased sodium (Na+) reabsorption, and a reduction of renal blood flow. These components of the neural regulation of renal function are considerably stimulated in disease states characterized by heightened sympathetic tone and clearly contribute to the rise in blood pressure in hypertensive patients. The reduction of renal blood flow and glomerular filtration rate as a result of renal sympathetic efferent stimulation may be a cornerstone of the loss of renal function in cardio-renal syndrome, which is renal dysfunction as a progressive complication of chronic heart failure, with a clinical course that typically fluctuates with the patient’s clinical status and treatment. Pharmacologic strategies to thwart the consequences of renal efferent sympathetic stimulation include centrally acting sympatholytic drugs, beta blockers (intended to reduce renin release), angiotensin converting enzyme inhibitors and receptor blockers (intended to block the action of angiotensin II and aldosterone activation consequent to renin release), and diuretics (intended to counter the renal sympathetic mediated sodium and water retention). However, the current pharmacologic strategies can have significant limitations including limited efficacy, compliance issues, side effects, and others.

[0114] 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.

[0115] FIG. 12 is an anatomic view of a human body depicting neural efferent and afferent communication between the brain and kidneys. FIG. 13 is a conceptual view of a human body depicting neural efferent and afferent communication between the brain and kidneys. As shown in FIGS. 12 and 13, 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.

[0116] The physiology therefore suggests that (i) modulation of tissue with efferent sympathetic nerves will reduce inappropriate renin release, salt retention, and reduction ofrenal 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.

[0117] As provided above, renal denervation is likely to be valuable in the treatment of several clinical conditions characterized by increased overall and particularly renal sympathetic activity such as hypertension, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic end state renal disease, inappropriate fluid retention in heart failure, cardio-renal syndrome and sudden death. Since the reduction of afferent neural signals contributing to the systemic reduction of sympathetic tone / drive, renal denervation might also be useful in treating other conditions associate with systemic sympathetic hyperactivity. Accordingly, renal denervation may also benefit other organs and bodily structures innervated by sympathetic nerves, including those identified in FIG. 13. 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.

[0118] 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. 14 is an anatomic view of the arterial vasculature of a human. As FIG. 14 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.

[0119] FIG. 15 is an anatomic view of the venous vasculature of a human. As FIG. 15 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 isconveyed into the left atrium. From the left atrium, the oxygenated blood is conveyed by the left ventricle back to the aorta.

[0120] 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.

[0121] The wrist, upper arm, and shoulder region provide other locations for introduction of catheters into the arterial system. For example, catheterization of either the radial, brachial, or axillary artery may be utilized in select cases. Catheters (e.g., catheter 12) introduced via these access points may be passed through the subclavian artery on the left side (or via the subclavian and brachiocephalic arteries on the right side), through the aortic arch, down the descending aorta and into the renal arteries using standard angiographic techniques. Other access sites can also be used to access the arterial system.

[0122] 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.

[0123] 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-patientvariation 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.

[0124] In addition to complicating renal arterial access, specifics of the renal anatomy also complicate establishment of stable contact between neuromodulatory apparatus and a luminal surface or wall of a renal artery. For example, navigation can be impeded by the tight space within a renal artery, as well as tortuosity of the artery. Furthermore, establishing consistent contact is complicated by patient movement, respiration, or the cardiac cycle because these factors may cause significant movement of the renal artery relative to the aorta, and the cardiac cycle may transiently distend the renal artery (i.e., cause the wall of the artery to pulse).

[0125] The neuromodulation system may also be configured to allow for adjustable positioning and repositioning of distal portion 22A (FIG. 1 A) within the renal artery since location of treatment may also impact clinical efficacy. Additionally, variable positioning and repositioning of the neuromodulatory apparatus may prove to be useful in circumstances where the renal artery is particularly tortuous or where there are proximal branch vessels off the renal artery main vessel, making treatment in certain locations challenging.

[0126] As noted above, an apparatus positioned within a renal artery may be configured so that distal portion 22A of catheter 12 may intimately contact the vessel wall or extend at least partially through the vessel wall. Renal artery vessel diameter, DRA, typically is in a range of about 2-10 mm, with most of the patient population having a DRA of about 4 mm to about 8 mm and an average of about 6 mm. Renal artery vessel length, LRA, between its ostium at the aorta / renal artery juncture and its distal branchings, generally is in a range of about 5-70 mm, and a significant portion of the patient population is in a range of about 20-50 mm. Since the target renal plexus is embedded within the adventitia of the renal artery, 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.

[0127] An additional property of the renal artery that may be of interest is the degree of renal motion relative to the aorta induced by respiration or blood flow pulsatility. A patient’s kidney, which is located at the distal end of the renal artery, may move as much as 10 centimeters cranially with respiratory excursion. This may impart significant motion to the renal artery connecting the aorta and the kidney, thereby requiring from the neuromodulatory apparatus a unique balance of stiffness and flexibility to maintain contact between the energy delivery element and the vessel wall during cycles of respiration. Furthermore, the take-off angle between the renal artery and aorta may vary significantly between patients, and also may vary dynamically within a patient, e.g., due to kidney motion. The take-off angle generally may be in a range of about 30°-135°.

[0128] In general, the devices, systems, and techniques described herein may be used in conjunction with neuromodulation performed from within any suitable anatomical lumen that has nerves adjacent to the anatomical lumen. Example anatomical lumens include the celiac trunk and its branches (including the common hepatic artery and its branches, the gastroduodenal artery and its branches, the right gastric artery and its branches, and the proper hepatic artery and its branches, the left gastric artery and its branches, and the splenic artery and its branches), the superior mesenteric artery and its branches, the gonadal artery and its branches, the inferior mesenteric artery and its branches, and the like. Further, although the disclosure primarily describes neuromodulation from within one or more arteries, the devices, systems, and techniques of the disclosure also may be applied to neuromodulation from within one or more veins, such as a renal vein and its branches, a hepatic vein and its branches, an intercostal vein and its branches, or the like.

[0129] In some implementations, the devices, systems, and techniques described herein may be used to perform neuromodulation from within two or more anatomical lumens, e.g., in the renal arteries and the common hepatic artery, or any other combination of two or more anatomical lumens, either simultaneously or sequentially. In addition, the systems, devices, and methods described herein may be useful in conjunction with neuromodulation within a body lumen other than a vessel, for extravascular neuromodulation and / or for use in conjunction with therapies other than neuromodulation.

[0130] The following enumerated clauses describe examples according to the present disclosure.

[0131] Clause 1 : A neuromodulation catheter comprising: an elongate body configured to transform from a relatively low profile configuration to an expanded configuration, wherein a distal portion of the elongate body is configured to be positioned within an anatomical lumenof a patient; a therapy delivery element disposed on the elongate body and configured to deliver neuromodulation therapy to tissue proximate the anatomical lumen; and a magnetic stimulation element disposed on the elongate body, and wherein the magnetic stimulation element is configured to generate a magnetic field, in response to delivery of a stimulation signal to the magnetic stimulation element, having a strength sufficient to induce a stimulation current at a target tissue site adjacent the magnetic stimulation element.

[0132] Clause 2: The neuromodulation catheter of clause 1, wherein the strength of the magnetic field is sufficient to generate neural cell membrane potentials to depolarize neurons at the target tissue site.

[0133] Clause 3 : The neuromodulation catheter of clauses 1 or 2, wherein the elongate body is configured to define a loop, a helix, or a spiral in the expanded configuration.

[0134] Clause 4: The neuromodulation catheter of any of clauses 1 to 3, wherein the distal portion of the elongate body is configured to be placed in a blood vessel, and wherein a direction of the magnetic field is transverse to the elongate body and radially outward with respect to the blood vessel.

[0135] Clause 5: The neuromodulation catheter of any of clauses 1 to 4, wherein the magnetic stimulation element comprises a magnetic coil surrounding a ferritic core.

[0136] Clause 6: The neuromodulation catheter of any of clauses 1 to 5, wherein the magnetic stimulation element is electrically coupled to the therapy delivery element.

[0137] Clause 7: The neuromodulation catheter of any of clauses 1 to 5, wherein the magnetic stimulation element comprises a first magnetic stimulation element, wherein the magnetic field comprises a static magnetic field, wherein the strength of the static magnetic field is sufficient to induce alignment in ion channels at the target tissue site, and wherein the neuromodulation catheter further comprises a second magnetic stimulation element comprising a radio-frequency coil configured to output a gradient magnetic field to induce relaxation of ions in the ion channels.

[0138] Clause 8: The neuromodulation catheter of clause 7, wherein the first magnetic stimulation element comprises a pair of permanent magnets.

[0139] Clause 9: The neuromodulation catheter of clause 7, wherein the first magnetic stimulation element comprises a pair of wire loops.

[0140] Clause 10: The neuromodulation catheter of any of clauses 1 to 9, further comprising a plurality of therapy delivery elements disposed on the elongate body, the plurality of therapy delivery elements comprising the therapy delivery element.

[0141] Clause 11 : The neuromodulation catheter of clause 10, further comprising a plurality of magnetic stimulation elements disposed on the elongate body, the plurality of magnetic stimulation elements comprising the magnetic stimulation element.

[0142] Clause 12: The neuromodulation catheter of clause 11, wherein the plurality of magnetic stimulation elements is interleaved with the plurality of therapy delivery elements.

[0143] Clause 13: The neuromodulation catheter of clause 11, wherein the plurality of magnetic stimulation elements is spaced relative to the plurality of therapy delivery elements.

[0144] Clause 14: The neuromodulation catheter of clause 13, wherein the plurality of magnetic stimulation elements is configured to radially surround the plurality of therapy delivery elements relative to the elongate body in the expanded configuration of the elongate body.

[0145] Clause 15: The neuromodulation catheter of clause 14, wherein each magnetic stimulation element of the plurality of magnetic stimulation elements comprises a respective wire loop.

[0146] Clause 16: A neuromodulation system comprising: a neuromodulation catheter of any of clauses 1 to 15 configured to be introduced in a blood vessel; and processing circuitry configured to: generate a therapy signal configured to cause the therapy delivery element to deliver the neuromodulation therapy for a neuromodulation procedure; and generate the stimulation signal to cause the magnetic stimulation element to generate the magnetic field having the strength sufficient to induce the stimulation current at the target tissue site.

[0147] Clause 17: The neuromodulation system of clause 16, wherein the control circuitry is further configured to determine an efficacy of the neuromodulation procedure based on a signal indicative of a physiological response to the stimulation current.

[0148] Clause 18: The neuromodulation system of clause 17, wherein the processing circuitry is configured to generate the stimulation signal before and after the neuromodulation procedure and compare the physiological response before and after the neuromodulation procedure to determine the efficacy of the neuromodulation procedure.

[0149] Clause 19: The neuromodulation system of clauses 17 or 18, further comprising at least one sensor configured to generate the signal indicative of the physiological response.

[0150] Clause 20: The neuromodulation system of any of clauses 17 to 19, wherein the processing circuitry is further configured to generate an output indicative of the efficacy of the neuromodulation procedure.

[0151] Clause 21: The neuromodulation system of any of clauses 17 to 20, wherein the processing circuitry is further configured to generate a notification in response to determining that the efficacy of the neuromodulation procedure is lower than a threshold value.

[0152] Clause 22: The neuromodulation system of any of clauses 17 to 21, wherein the processing circuitry is further configured to control a medical device to adjust the neuromodulation procedure based on the efficacy.

[0153] Clause 23: The neuromodulation system of any of clauses 17 to 22, wherein the processing circuitry is further configured to automatically adjust the neuromodulation procedure based on the efficacy.

[0154] Clause 24: A neuromodulation system comprising: a neuromodulation catheter of any of clauses 1 to 6 and 10 to 15 configured to be introduced in a blood vessel; a magnetic resonance imaging system configured to generate a static magnetic field, wherein the strength of the static magnetic field is sufficient to induce alignment in ion channels at the target tissue site, and wherein the magnetic stimulation element of the neuromodulation catheter comprises a radio-frequency coil configured to output a gradient magnetic field to induce relaxation of ions in the ion channels; and processing circuitry configured to: generate a therapy signal configured to cause the therapy delivery element to deliver the neuromodulation therapy for a neuromodulation procedure; and generate the stimulation signal to cause the magnetic stimulation element to generate the gradient magnetic field.

[0155] Clause 25: A method comprising: introducing a neuromodulation catheter of any of clauses 1 to 15 in a blood vessel; generating, by processing circuitry, a therapy signal to cause the therapy delivery element to deliver the neuromodulation therapy for a neuromodulation procedure; and generating, by the processing circuitry, the stimulation signal to cause the magnetic stimulation element to generate the magnetic field having the strength sufficient to induce the stimulation current at the target tissue site adjacent the magnetic stimulation element.

[0156] Clause 26: The method of clause 25, further comprising determining, by the processing circuitry, an efficacy of the neuromodulation procedure based on a signal indicative of a physiological response to the stimulation current.

[0157] Clause 27: The method of clause 26, further comprising: generating, by the processing circuitry, the stimulation signal before and after the neuromodulation procedure; and comparing, by the processing circuitry, the physiological response before and after the neuromodulation procedure to determine the efficacy of the neuromodulation procedure.

[0158] Clause 28: The method of any of clauses 26 or 27, further comprising generating, by the processing circuitry, an output indicative of the efficacy of the neuromodulation procedure.

[0159] Clause 29: The method of any of clauses 26 to 28, further comprising generating, by the processing circuitry, a notification in response to determining that the efficacy of the neuromodulation procedure is lower than a threshold value.

[0160] Clause 30: The method of any of clauses 26 to 29, further comprising controlling, by the processing circuitry, a medical device to adjust the neuromodulation procedure based on the efficacy.

[0161] Clause 31 : The method of any of clauses 26 to 28, further comprising automatically adjusting, by the processing circuitry, the neuromodulation procedure based on the efficacy.

[0162] 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.

[0163] Moreover, unless the word “or” is expressly limited to mean only a single term exclusive from the other items in reference to a list of two or more items, then the use of “or” in such a list is to be interpreted as including (a) any single item in list, (b) all of the items in the list, or (c) any combination of the items in the list. Additionally, the term “comprising” is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and / or additional types of other features are not precluded.

[0164] It should be understood that various aspects disclosed herein may be combined in different combinations than the combinations specifically presented in the description and accompanying drawings. It should also be understood that, depending on the example, certain acts or events of any of the processes or methods described herein may be performed in a different sequence, may be added, merged, or left out altogether (e.g., all described acts or events may not be necessary to carry out the techniques). In addition, while certain aspects of this disclosure are described as being performed by a single module, unit, or circuit for purposes of clarity, it should be understood that the techniques of this disclosure may beperformed by a combination of units, modules, or circuitry associated with, for example, a medical device.

[0165] In one or more examples, the described techniques may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored as one or more instructions or code on a computer-readable medium and executed by a hardware-based processing unit. Computer-readable media may include non-transitory computer-readable media, which corresponds to a tangible medium such as data storage media (e.g., RAM, ROM, EEPROM, flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer).

[0166] Instructions may be executed by one or more processors that include processing circuitry, such as one or more digital signal processors (DSPs), general purpose microprocessors, application specific integrated circuits (ASICs), field programmable logic arrays (FPGAs), or other equivalent integrated or discrete logic circuitry. Accordingly, the term “processor” or “processing circuitry” as used herein may refer to any of the foregoing structure or any other physical structure suitable for implementation of the described techniques. Also, the techniques could be fully implemented in one or more circuits or logic elements.

[0167] 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.

[0168] 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.

[0169] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

CLAIMS1. A neuromodulation catheter comprising: an elongate body configured to transform from a relatively low profile configuration to an expanded configuration, wherein a distal portion of the elongate body is configured to be positioned within an anatomical lumen of a patient; a therapy delivery element disposed on the elongate body and configured to deliver neuromodulation therapy to tissue proximate the anatomical lumen; and a magnetic stimulation element disposed on the elongate body, and wherein the magnetic stimulation element is configured to generate a magnetic field, in response to delivery of a stimulation signal to the magnetic stimulation element, having a strength sufficient to induce a stimulation current at a target tissue site adjacent the magnetic stimulation element.

2. The neuromodulation catheter of claim 1, wherein the strength of the magnetic field is sufficient to generate neural cell membrane potentials to depolarize neurons at the target tissue site.

3. The neuromodulation catheter of any one of claims 1 or 2, wherein the elongate body is configured to define a loop, a helix, or a spiral in the expanded configuration.

4. The neuromodulation catheter of any one of claims 1 to 3, wherein the distal portion of the elongate body is configured to be placed in a blood vessel, and wherein a direction of the magnetic field is transverse to the elongate body and radially outward with respect to the blood vessel.

5. The neuromodulation catheter of any one of claims 1 to 4, wherein the magnetic stimulation element comprises a magnetic coil surrounding a ferritic core.

6. The neuromodulation catheter of any one of claims 1 to 5, wherein the magnetic stimulation element comprises a first magnetic stimulation element, wherein the magnetic field comprises a static magnetic field, wherein the strength of the static magnetic field is sufficient to induce alignment in ion channels at the target tissue site, and wherein the neuromodulation catheter further comprises a second magnetic stimulation element comprising a radio-frequency coil configured to output a gradient magnetic field to induce relaxation of ions in the ion channels.

7. The neuromodulation catheter of claim 6, wherein the first magnetic stimulation element comprises a pair of permanent magnets or a pair of wire loops.

8. The neuromodulation catheter of any one of claims 1 to 7, further comprising: a plurality of therapy delivery elements disposed on the elongate body, the plurality of therapy delivery elements comprising the therapy delivery element; and a plurality of magnetic stimulation elements disposed on the elongate body, the plurality of magnetic stimulation elements comprising the magnetic stimulation element.

9. The neuromodulation catheter of claim 8, wherein the plurality of magnetic stimulation elements is interleaved with the plurality of therapy delivery elements or spaced relative to the plurality of therapy delivery elements.

10. The neuromodulation catheter of any one of claims 8 or 9, wherein the plurality of magnetic stimulation elements is configured to radially surround the plurality of therapy delivery elements relative to the elongate body in the expanded configuration of the elongate body, and wherein each magnetic stimulation element of the plurality of magnetic stimulation elements comprises a respective wire loop.

11. A neuromodulation system comprising: the neuromodulation catheter of any one of claims 1 to 10; and processing circuitry configured to: generate a therapy signal configured to cause the therapy delivery element to deliver the neuromodulation therapy for a neuromodulation procedure; and generate a stimulation signal configured to cause the magnetic stimulation element, in response to delivery of the stimulation signal to the magnetic stimulation element, to generate the magnetic field having a strength sufficient to induce a stimulation current at a target tissue site adjacent the magnetic stimulation element.

12. The neuromodulation system of claim 11, wherein the control circuitry is further configured to determine an efficacy of the neuromodulation procedure based on a signal indicative of a physiological response to the stimulation current.

13. The neuromodulation system of claim 12, wherein the processing circuitry is configured to generate the stimulation signal before and after the neuromodulation procedure and compare the physiological response before and after the neuromodulation procedure to determine the efficacy of the neuromodulation procedure.

14. The neuromodulation system of any one of claims 12 or 13, further comprising at least one sensor configured to generate the signal indicative of the physiological response.

15. The neuromodulation system of any one of claims 12 to 14 , wherein the processing circuitry is further configured to generate an output indicative of the efficacy of the neuromodulation procedure or to automatically adjust the neuromodulation procedure based on the efficacy.

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