Neuromodulation catheter with stimulating and ablation electrodes

Abstract

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

Description

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 571,946, filed March 29, 2024, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This disclosure relates in general to neural modulation. Background Technology

[0003] Denervation procedures may include, for example, ablating a target nerve by delivering ablation energy to the target site via a catheter. For example, renal denervation may include ablation of the renal nerve. Summary of the Invention

[0004] Generally speaking, this disclosure describes a neuromodulation conduit that includes stimulating electrodes and ablation electrodes.

[0005] Neuromodulation catheters can be used to deliver neuromodulation therapies, such as ablating nerves via at least one ablation electrode by delivering energy. In some examples, a neuromodulation catheter includes a distal portion configured to transition from a relatively low-profile configuration to an expanded configuration. In this expanded configuration, the distal portion may define a loop, a spiral, or a helical configuration. An array of electrodes is disposed on this distal portion. Impedance can be used to monitor and guide denervation procedures. For example, electrode impedance can be measured during denervation, for example, to determine lesion development during denervation. In this expanded configuration, the at least one electrode contacts blood and blood vessels. Because blood has a higher conductivity than blood vessels, impedance measured in the expanded configuration can exhibit greater sensitivity to blood contact than to blood vessel contact.

[0006] In some examples, the apparatus, systems, and techniques according to this disclosure use an ablation electrode to detect impedance. For example, the ablation electrode may include multiple electrode segments, and at least one of the multiple ablation electrodes may be oriented toward or in contact with tissue. This reduces the contribution or interference of blood to the measured impedance. Therefore, the detected impedance can substantially correspond to tissue impedance. For example, compared to catheters that use dedicated electrodes to sense impedance and different electrodes to deliver ablation, determining impedance by using electrode segments of an ablation electrode reduces catheter complexity. Furthermore, the ablation signal can be delivered by all electrode segments. By delivering the ablation signal from all electrode segments, the spatial profile of a neuromodulation therapy delivered by an ablation electrode including multiple electrode segments can be the same, substantially the same, or functionally the same as an ablation electrode that does not include multiple segments. Therefore, the ablation electrode can be used to detect impedance without substantially altering the ablation function of the ablation electrode.

[0007] In some examples, an exemplary neuromodulation system includes a neuromodulation catheter and a controller. The neuromodulation catheter includes an elongated body and an ablation electrode along the elongated body. The ablation electrode includes multiple electrode segments. Each of the multiple electrode segments is electrically isolated from other corresponding electrode segments of the multiple electrode segments. The controller is configured to determine impedance based on signals sensed by at least one of the multiple electrode segments and a reference pad when the elongated body is placed in a patient's blood vessel. The controller is also configured to generate an ablation signal, which is configured to be delivered by all of the multiple electrode segments when the elongated body is placed in the blood vessel.

[0008] In some examples, the example neuromodulation conduit includes an elongated body comprising a distal portion. This distal portion can be configured to transition from a relatively low-profile configuration to an expanded configuration. The neuromodulation conduit also includes an ablation electrode along the elongated body, the ablation electrode comprising multiple electrode segments. Each of the multiple electrode segments is electrically isolated from other corresponding electrode segments. Each of the multiple electrode segments is arranged at approximately the same longitudinal position along the periphery of the elongated body.

[0009] In some examples, one exemplary technique includes: determining impedance by processing circuitry based on signals sensed by at least one of a plurality of electrode segments of a neuromodulation catheter placed in a patient's blood vessel. The technique may also include: delivering ablation signals to a target site by all of the plurality of electrode segments in the patient's blood vessel.

[0010] This document also discloses a neuromodulation system comprising a neuromodulation catheter and a controller, wherein the neuromodulation catheter includes an elongated body and an ablation electrode along the elongated body, wherein the ablation electrode includes a plurality of electrode segments, wherein each of the plurality of electrode segments is electrically isolated from other corresponding electrode segments of the plurality of electrode segments, wherein the controller is configured to determine impedance based on signals sensed by at least one of the plurality of electrode segments and a reference pad when the elongated body is placed in a patient's blood vessel, and wherein the controller is further configured to generate an ablation signal, which is configured to be delivered by all of the plurality of electrode segments when the elongated body is placed in the blood vessel.

[0011] Details of one or more examples of the technology disclosed herein are set forth in the accompanying drawings and the following description. Other features, objectives, and advantages of these technologies will be apparent from the specification, drawings, and claims. Attached Figure Description

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

[0013] Figure 1B This example includes an ablation electrode. Figure 1A A magnified partial view of the catheter.

[0014] Figure 1C This is an example Figure 1B A top view of the ablation electrode in the catheter.

[0015] Figure 2 This is a top view illustration of an example ablation electrode comprising multiple uniform electrode segments.

[0016] Figure 3 This is a top view illustration of an example ablation electrode containing insulating material between adjacent electrode segments.

[0017] Figure 4 This is a diagram illustrating an example system including a multiplexed wiring arrangement for an ablation electrode, which includes multiple electrode segments.

[0018] Figure 5 This is a timing diagram illustrating a comparative example protocol for neuromodulation, which includes a session for detecting impedance and delivering ablation.

[0019] Figure 6 This is an example Figure 1A A block diagram of an example configuration of a computing device.

[0020] Figure 7 This is a flowchart illustrating an example technique used for neuromodulation.

[0021] Figure 8 Examples of techniques for accessing the renal artery and modulating the renal nerve using a neuromodulation catheter are illustrated according to some examples of this disclosure.

[0022] Figure 9 This is a conceptual illustration of the sympathetic nervous system (SNS), illustrating how the brain communicates with the body via the SNS.

[0023] Figure 10 This is an enlarged anatomical view of the nerves that innervate the left kidney to form the renal plexus surrounding the left renal artery.

[0024] Figure 11 It is an anatomical view of the human body, depicting the efferent and afferent neural communication between the brain and kidneys.

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

[0026] Figure 13 It is an anatomical view of the human arterial vascular system.

[0027] Figure 14 This is an anatomical view of the human venous system. Detailed Implementation

[0028] This disclosure describes a neuromodulation conduit that includes stimulating electrodes and ablation electrodes.

[0029] As used herein, the terms “distal” and “proximal” define a location or orientation relative to the treating clinician or the clinician’s control device (e.g., a handle assembly). “Distal” or “distally” can refer to a location remote from or in a direction remote from the clinician or the clinician’s control device. “Proximal” and “proximal” can refer to a location near or toward the clinician or the clinician’s control device.

[0030] In some examples, a neuromodulation conduit includes a distal portion configured to transition from a relatively low-profile configuration to an expanded configuration. In this expanded configuration, the distal portion may define a circumferential, helical, or spiral configuration. An electrode array (e.g., comprising multiple ablation electrodes) is disposed on this distal portion. At least one ablation electrode includes multiple electrically isolating electrode segments. For example, the at least one electrode may have a generally cylindrical configuration including isolating barriers defining an electrically isolating electrode region.

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

[0032] All electrode segments can be used to deliver denervation therapy, for example, to deliver radiofrequency (RF) energy. In this way, the ablation profile and current density remain substantially similar to denervation delivered by unsegmented electrodes (e.g., cylindrical electrodes).

[0033] Figure 1AThis is a diagram illustrating an example system including a catheter 12 configured to deliver neuromodulation therapy, a computing device 14, and a controller 16. The catheter 12 is also referred to as a neuromodulation catheter 12. The computing device 14 may be configured to send control signals to the controller 16 or otherwise control the operation of one or both of the catheter 12 and the controller 16. In some examples, the control signals sent from the computing device 14 to the controller 16 are configured to cause the controller 16 to generate electrical signals based on the control signals received from the computing device 14. The controller 16 may generate electrical signals to be sent to the catheter 12 to cause the catheter 12 to deliver the neuromodulation therapy. For example, the neuromodulation therapy may include renal neuromodulation, hepatic neuromodulation, or any other neuromodulation therapy.

[0034] Figure 1B This example illustrates a device including an ablation electrode 18. Figure 1A A magnified partial view of the conduit 12. Figure 1C This is an example Figure 1B A top view of the ablation electrode 18 of the catheter 12. For example, the catheter 12 may include the ablation electrode 18, and the electrical signals sent to the catheter 12 may include ablation signals delivered to the target site by the ablation electrode 18.

[0035] The controller 16 may be configured to generate an electrical signal including an ablation signal configured to be delivered by the ablation electrode 18. For example, the controller 16 may include a generator 40 configured to generate the ablation signal. The controller 16 may also include a stimulator 42 configured to generate a stimulation signal in response to the ablation signal to test the degree of denervation. Depending on the frequency component of the ablation signal or the stimulation signal, the generator 40 or the stimulator 42 may include one or both of an AC generator or a DC generator. In some examples, the stimulator 42 includes circuitry configured to rectify the AC signal to generate a DC signal. For example, the stimulator 42 may generate a stimulation signal that includes only a DC signal. In other examples, one or both of the ablation signal or the stimulation signal may include both AC and DC signals, but differ in the frequency band of the AC signal or the amplitude of the DC signal. For example, the ablation signal may have a significantly higher frequency than the stimulation signal.

[0036] The catheter 12 includes a handle 20 and an elongated body 22 attached to the handle 20. That is, the handle 20 is positioned at the proximal portion of the elongated body 22. The elongated body 22 may have any suitable outer diameter, and this outer diameter may be constant along the length of the elongated body 22 or may vary along the length of the elongated body 22. In some examples, the elongated body 22 may be 2 French, 3 French, 4 French, 5 French, 6 French, or 7 French, or other suitable sizes. The elongated body 22 extends along a central longitudinal axis L and includes a distal portion 22A and a proximal portion 22B. The distal portion 22A includes an expandable portion 24. The expandable portion 24 is configured to extend from a relatively low profile configuration ( Figure 1A (As shown in the image) Transformation to a radially expanding unfolded configuration ( Figure 1A (not shown in the image), such as spiral, annular, or helical configurations, or expanded sac-like configurations.

[0037] The ablation electrode 18 may be segmented. For example, the ablation electrode 18 may include a plurality of electrode segments 26. The ablation electrode 18 and the plurality of electrode segments 26 may have any suitable shape, size, or form. Each of the plurality of electrode segments 26 may be arranged at substantially the same longitudinal position along the periphery of the elongated body 22. In some examples, the ablation electrode 18 is an annular electrode, and the electrode segments 26 include an annular segment surrounding at least a portion of the elongated body 22. For example, the ablation electrode 18 may be cylindrical, and each of the plurality of electrode segments 26 may be a cylindrical segment arranged circumferentially around the elongated body.

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

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

[0040] exist Figure 1A and Figure 1B In the example shown, the ablation electrode 18 is disposed on the expandable portion 24 of the elongated body 22. Although Figure 1A The catheter 12 is illustrated as having four ablation electrodes, but other example catheters may include one, two, three, five, or more ablation electrodes. The generator 40 may be configured to deliver therapy to a patient's tissue via the ablation electrodes 18, for example, to modulate a target nerve in the patient. For example, all of the plurality of electrode segments 26 of the ablation electrode 18 may be coupled together, and the generator 40 may deliver ablation signals to the tissue or target site via all electrode segments (e.g., because the electrode segments 26 are coupled together). Thus, the catheter 12 may deliver denervation therapy via the ablation electrodes 18 (e.g., via the plurality of electrode segments 26), and the computing device 14 or controller 16 may control the delivery of denervation therapy by the catheter 12.

[0041] In some examples, the ablation electrode 18 (e.g., at least one electrode segment of electrode segment 26) comprises gold, platinum, or iridium oxide. For example, gold can promote heat dissipation and reduce heat buildup during the ablation process. Iridium oxide can have high electrical conductivity. In some examples, the ablation electrode 18 comprises gold coated with an iridium oxide coating.

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

[0043] In other examples, at least two of the multiple electrode segments 26 differ in surface area. For example, as... Figure 1C As shown, the plurality of electrode segments 26 include a first electrode segment 26A and a second electrode segment 26B. The first electrode segment 26A defines a first electrode segment area (e.g., radial outer surface area along the longitudinal axis L), and the second electrode segment 26B may define a second electrode segment area larger than the area of ​​the first electrode segment. In some examples, the first electrode segment 26A is configured to contact or be oriented toward tissue within a blood vessel. In some examples, the ablation electrode includes a total of two electrode segments 26A and 26B, for example, no more than two electrode segments.

[0044] Figure 2 This is a top view illustration of an example ablation electrode 118 comprising multiple uniform electrode segments 126A, 126B, 126C, and 126D (collectively, "uniform electrode segments 126"). The ablation electrode 118 and the multiple uniform electrode segments 126 are similar to those in the reference numerals. Figures 1A to 1C The ablation electrode 18 and multiple electrode segments 26 are described, but differ in geometry. Specifically, each of the multiple electrode segments 126 is identical in composition, size, and shape. In some examples, the ablation electrode 118 comprises four electrode segments. In some examples, the ablation electrode 118 comprises a total of four electrode segments, for example, no more than four electrode segments 126.

[0045] Back Figures 1A to 1C Each of the plurality of electrode segments 26 may be electrically isolated from the other corresponding electrode segments of the plurality of electrode segments 26. For example, corresponding pairs of adjacent electrode segments 26 may be separated by corresponding electrically insulating regions 28. The electrically insulating regions 28 define air gaps or may be occupied by materials (e.g., insulating materials). In some examples, each of the plurality of electrode segments 26 is laterally spaced from the other corresponding electrode segments of the plurality of electrode segments 26 along the surface of the elongated body 22. In some examples, the electrically insulating regions 28 may be occupied by materials, as referenced Figure 3 As described.

[0046] Figure 3 This is a top view illustrating an example ablation electrode 218 containing insulating material 230 between adjacent electrode segments. The ablation electrode 218 may be similar to the reference figure. Figure 1A The described ablation electrode 18 or reference Figure 1B The ablation electrode 118 is described, but differs in that an insulating material 230 is present in the electrically insulating region 228. The insulating material 230 may include at least one of a metal, an alloy, or a polymer. In some examples, the metal or alloy includes at least one of bismuth, tungsten, or titanium. In some examples, the polymer comprises at least polyimide.

[0047] Back Figure 1A The distal portion 22A of the elongated body 22 is configured to advance within an anatomical lumen of a human patient to position the ablation electrode 18 within or otherwise adjacent to a target tissue site within the anatomical lumen. For example, the elongated body 22 may be configured to position the distal portion 22A within a blood vessel, ureter, urethra, conduit, airway, or another naturally occurring lumen within the human body. The examples described herein focus on anatomical lumens as blood vessels, such as renal vessels; however, it should be understood that similar techniques can be used for other anatomical lumens.

[0048] The catheter 12 can be configured for delivery via a guiding member to a target tissue site within a patient's vascular system, the guiding member including, for example, one or more guidewires or external sheaths. In some examples, intravascular delivery of the distal portion 22A includes placing a guidewire ( Figure 1A(Not shown in the image) The catheter 12 is percutaneously inserted into a patient's blood vessel and the elongated body 22 (e.g., at least the expandable portion 24) is moved along the guidewire until the expandable portion 24 reaches the target tissue site (e.g., the renal artery). For example, the distal portion 22A of the elongated body 22 may define a lumen configured to receive the guidewire for delivery of the expandable portion 24 to the target tissue site using an overall over-the-knee (OTW) or rapid over-the-knee (RX) technique. In other examples, the catheter 12 may be a manipulable or non-manipulable device configured for use without a guidewire. In still other examples, the catheter 12 may be configured to be used via a guiding member (e.g., a guiding catheter, an outer sheath) Figure 1A Delivery into the cavity of (not shown in the image) or other guiding devices.

[0049] The distal end of the elongated body 22 defines a distal end 30. The distal end 30 is configured to facilitate navigation of the distal portion 22A to a blood vessel within the patient's vascular system. In some examples, the distal end 30 may be non-invasive, for example, to resist or avoid puncturing the blood vessel during navigation of the distal portion 22A within the blood vessel.

[0050] exist Figure 1A In the illustrated examples, catheter 12 is in a relatively low-profile delivery configuration in which the distal portion 22A defines a relatively small radial range relative to an expansion (also referred to as radial expansion and / or unfolding) configuration (relatively low profile, such as a relatively linear configuration), in which the expandable portion 24 of the distal portion 22A defines a relatively large radial range. In some examples, the radial range is measured in a direction orthogonal to the central longitudinal axis L. The distal portion 22A can be delivered to the target tissue site via the patient's vascular system in a low-profile configuration. In some examples, the expandable portion 24 is configured to self-expand within the patient's blood vessels, for example, via a shape memory element (e.g., a shape memory tube or hollow spiral strand) of the elongated body 22. In some examples, the expandable portion is... Figure 1A The relatively low-profile configuration shown extends along a straight line aligned with the longitudinal axis L. The expandable portion 24 can be constrained or limited within the low-profile configuration by a guide member. The clinician can retract the guide member proximally relative to the expandable portion 24 to release the constraint on the expandable portion 24, thereby allowing or enabling the expandable portion 24 to transition from the low-profile configuration to the expanded configuration. Thus, the expandable portion 24 can be configured to expand radially away from the straight line into the expanded configuration.

[0051] In some examples, in the expansion configuration, the expandable portion 24 defines a ring-shaped, spiral, or helical shape, or a basket-shaped or scaffold-like configuration. In the expansion configuration, the expandable portion 24 is configured to position one or more electrodes (including the ablation electrode 18) near the vessel wall, for example, juxtaposed with the vessel wall.

[0052] In some examples, the expandable portion 24 can be expanded or self-expanding as the guide member retracts proximally from the distal portion 22A. Clinicians can retract the guide member to a position along the distal portion 22A near the expandable portion 24 to induce or allow expansion of the expandable portion 24. In an expansion configuration, the expandable portion 24 can position at least one electrode (e.g., ablation electrode 18) at a first position relative to the vessel wall (e.g., corresponding to a first rotational position). Clinicians can control the therapy delivery device to deliver, provide, or facilitate neuromodulation therapy at a target tissue site, for example, through the vessel wall to a target tissue adjacent to a vessel. Neuromodulation therapy may include, but is not limited to, radiofrequency (RF) energy.

[0053] Clinicians can rotate handle 20 or otherwise rotate the proximal portion 22B to apply torque to the distal portion 22A and cause the expandable portion 24 to rotate about the central longitudinal axis L from a first rotational position to a second rotational position. For example, applying torque from handle 20 or the proximal portion 22B to the expandable portion 24 can cause the expandable portion 24 to rotate about the longitudinal axis L, for example, in the same direction as the torque. Clinicians can control system 10 to deliver ablation therapy or stimulation at the second rotational position or after other successive rotational positions of the expandable portion 24.

[0054] The catheter 12 may be connected to the controller 16 (e.g., a therapy delivery device). The controller 16 may include control circuitry and a therapy source (e.g., an electrical signal generator, etc.) via at least one electrical conductor and / or at least one lumen defined by the handle 20 and the elongated body 22. Figure 1A (Not shown in the image).

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

[0056] System 10 also includes a reference pad 34. Impedance can be determined based on signals sensed by the ablation electrode 18 and the reference pad 34 (e.g., based on the voltage across the ablation electrode 18 and the reference pad 34). In some examples, the catheter 12 includes, for example, a reference pad 34 along the elongated body 22. In other examples, the reference pad 34 is spaced apart from the catheter 12 (or otherwise from the ablation electrode 18), for example, positioned relative to the catheter 12 or the ablation electrode 18 at any suitable location. In some examples, system 10 does not include a separate reference pad 34, and an electrode or electrode segment of the catheter 12 can be used as a reference pad. For example, an electrode segment among a plurality of electrode segments 26 can be used as a reference pad. In some examples, the reference pad 34 includes an electrode.

[0057] The controller 16 is configured to determine impedance based on signals sensed by at least one of the plurality of electrode segments 26 and a reference pad 34. The controller 16 can also be configured to generate an ablation signal, which is, for example, configured to be delivered by all of the plurality of electrode segments 26. In this way, the controller 16 can use the ablation electrode 18 (e.g., one of the electrode segments 26) to detect impedance and can determine impedance without the need for additional or dedicated electrodes.

[0058] In some examples, controller 16 is also configured to adjust the ablation signal based on at least impedance. For example, controller 16 may alternately determine impedance and deliver the ablation signal, and may adjust the ablation signal (e.g., change the intensity of the ablation signal, start or stop the ablation signal). In some examples, the determined impedance may indicate that heating of the tissue exceeds a predetermined threshold, and controller 16 may respond to such impedance by reducing the intensity of the ablation signal or stopping ablation.

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

[0060] In some examples, the identity of the electrode segment 26 that contacts or is closest to the tissue may not be initially known. In some examples, the controller 16 is configured to determine a corresponding impedance based on signals sensed by the corresponding electrode segment 26 and the reference pad 34. In some such examples, the controller 16 is configured to select the maximum impedance from the corresponding impedances to determine the impedance. For example, the maximum impedance may be associated with a corresponding electrode segment that contacts, is closest to, or is oriented toward the tissue, compared to corresponding impedances associated with other electrode segments that may not contact or are further away from the tissue. In some such examples, the controller 16 is configured to generate a selection signal that indicates the corresponding electrode segment 26 associated with the maximum impedance. A clinician may reposition the catheter 12 in response to the selection signal. In some examples, the controller 16 is configured to select the minimum impedance, an impedance greater than a threshold impedance, an impedance less than a threshold impedance, or an impedance within a predetermined range from the corresponding impedances to determine the impedance.

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

[0062] Back Figure 2 In some examples, controller 16 is configured to determine a corresponding impedance based on signals sensed by pairs of corresponding electrode segments of the plurality of uniform electrode segments 126. For example, controller 16 may determine the impedance based on signals sensed by a pair of adjacent uniform electrode segments or a pair of spaced-apart or opposite uniform electrode segments of the plurality of uniform electrode segments 126. In some examples, controller 16 is configured to determine the corresponding impedance for each pair of corresponding adjacent uniform electrode segments 126 (e.g., 126A and 126B, 126B and 126C, 126C and 126D, and 126D and 126A) and select the largest impedance among the corresponding impedances to determine the impedance.

[0063] Figure 4 This is a diagram illustrating an example system 300 including a multiplexed wiring arrangement 300 for an ablation electrode 118, which includes multiple electrode segments. Although Figure 4The ablation electrode 118 is shown, but in other examples, the multiplexing wiring arrangement 300 may be coupled to any ablation electrode according to this disclosure. The multiplexing wiring arrangement 300 may be carried on a catheter (e.g., catheter 12 or a catheter similar to catheter 12). For example, the multiplexing wiring arrangement 300 may be positioned along an elongated body of the catheter (e.g., elongated body 12) or some other component. The multiplexing wiring arrangement 300 is configured to split the ablation signal into a corresponding ablation signal sent to each electrode segment of the ablation electrode 118.

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

[0065] Figure 5 This is a timing diagram illustrating a comparative example protocol for neuromodulation, which includes a session for impedance detection and ablation delivery. Figure 5 In the illustrated protocol, impedance is detected during a first duration t1, followed by ablation during a second duration t2. In some examples, impedance is further detected during a third duration t3, allowing for assessment of the ablation's impact on the tissue. Ablation can be continued, modified, or terminated in response to impedance.

[0066] Therefore, controller 16 can control catheter 12 to deliver neuromodulation therapy including interleaved ablation and impedance detection. In some examples, computing device 14 controls controller 16 to deliver ablation via catheter 12. For example, computing device 14 can be configured to generate control signals and send them to controller 16, and controller 16 can be configured to generate electrical signals sent to catheter 12 based on the control signals.

[0067] Figure 6 This is an example Figure 1A A block diagram of an example configuration of the computing device 14. In some examples, the controller 16 may include the computing device 14, or include one or more components described with reference to the computing device 14, or otherwise perform the functions described with reference to the computing device 14. The computing device 14 may include a workstation, tablet computer, laptop computer, or desktop computer.

[0068] like Figure 6 As shown in the example, external device 14 includes processing circuitry 170, storage device 172, communication circuitry 174, and user interface 176. While computing device 14 can be as follows... Figure 6 The computing device 14 is a standalone device as shown, but in other examples, it can be any component or system including processing circuitry or other suitable computing environment for executing software instructions, and need not, for example, include... Figure 6One or more of the components shown (e.g., in some examples, components such as storage device 172 may not be in the same location as other components or are located in the same housing or structure).

[0069] In some examples, processing circuitry 170 is configured to perform functionality and / or process instructions for execution within at least one computing device 14. For example, processing circuitry 170 may be able to process instructions (including at least one application program 180) stored in storage device 172. Examples of processing circuitry 170 described herein, as well as other processors, processing circuits, controllers, control circuits, etc., may include any combination of integrated circuits, discrete logic circuits, analog circuits, 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, and other discrete or integrated logic circuits and / or analog circuits.

[0070] Storage device 172 (also referred to as memory) may be configured to store information (including at least one application 180 and data 190) within computing device 14. In some examples, storage device 172 is a computer-readable storage medium. In some examples, storage device 172 includes temporary memory or volatile memory. In one example, storage device 172 is used by at least one application 180 running on computing device 14 to temporarily store information during program execution. In some examples, storage device 172 also includes one or more memories configured for long-term storage of information, such as non-volatile storage elements. Examples of such non-volatile storage elements include any volatile memory, non-volatile memory, magnetic memory, optical memory, or dielectric memory, such as random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, or any other digital medium.

[0071] The computing device 14 communicates with other devices, such as conduit 12, controller 16, other computing devices, and system 10 of FIG. 1, using communication circuitry 174. 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 capable of transmitting and receiving information. Other examples of such network interfaces may include 3G, 4G, 5G, and WiFi radio components.

[0072] The computing device 14 may include a user interface 176. The user interface 176 may be configured to provide output to a user using tactile, audio, or video stimuli, and to receive input from the user via tactile, audio, or video feedback. As examples, the user interface 176 may include a presence-sensitive display, a mouse, a keyboard, a voice response system, a camera, a microphone, or any other type of device for detecting commands from the user, a sound card, a video graphics adapter card, or any other type of device for converting signals into an appropriate form that can be understood by humans or machines, a speaker, a display device such as, but not limited to, a cathode ray tube (CRT) monitor, a liquid crystal display (LCD), or any other type of device capable of generating understandable output to the user. In some examples, the presence-sensitive display includes a touchscreen.

[0073] At least one application 180, executable by the processing circuitry 170 of the computing device 14, may include an impedance interface application 182 and a monitoring system 184 that can monitor the progress of neuromodulation and the effects of ablation using physiological or other data acquired during neuromodulation. At least one application 180 may also include an ablation interface application 186 that controls the delivery of ablation via a controller 16 and / or catheter 12.

[0074] The execution of the impedance interface 182 and ablation interface 186 by the processing circuitry 170 configures the computing device 14 to interface with the system 10 or the controller 16 (or catheter 12). For example, the impedance interface 182 configures the computing device 14 to communicate with the controller 16 via the communication circuitry 184. The processing circuitry 170 can determine the impedance based on the signal sensed by the ablation electrode 18 and store the impedance data 192 in the storage device 172. The impedance interface 182 and / or the ablation interface 186 also configure a user interface 176 for user interaction with the controller 16 (or catheter 12). One or more of the impedance interface 182, the monitoring system 184, or the ablation interface 186 can enable the processing circuitry 170 and the computing device 14 to perform any of the techniques described herein related to the neuromodulation of the system 10.

[0075] Figure 7 This is a flowchart illustrating an example technique used for neuromodulation. (Reference) Figures 1A to 1C The computing device 14 and the processing circuitry 170 of the system 10 are described in terms of their respective characteristics. Figure 7 The example technology is as described above. However, the example technology can be implemented by any suitable computing device, controller, or system, either alone or in combination with processing circuitry 170.

[0076] The technique may include positioning the neuromodulation catheter 12 within a blood vessel (400). For example, a clinician may position the neuromodulation catheter 12 such that the first electrode segment 26A is in contact with or relatively close to tissue. In other examples, a clinician may not be able to determine the orientation of the multiple electrode segments 26, and positioning 400 may include positioning the catheter 12 within a blood vessel regardless of the orientation of the electrode segments 26, but rather towards the target site.

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

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

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

[0080] In some examples, delivery (404) may also include positioning the neuromodulation conduit or positioning the neuromodulation conduit prior to delivery such that the electrode segment sensing impedance using the reference pad 34 is oriented toward the target site.

[0081] In some examples, the determined impedance (402) is a first impedance, and the technique also includes: a second impedance (404) determined by the processing circuit 170 based on a signal sensed by at least one electrode segment after the delivery of the ablation signal.

[0082] The technique may also include: adjusting the ablation signal based on impedance by the processing circuit 170. For example, one or more of positioning (400), determining impedance (402), and delivering the ablation signal (404) may be repeated, wherein the processing circuit 170 changes the intensity or magnitude of the ablation signal, for example, in response to impedance.

[0083] Therefore, the example systems and techniques according to this disclosure can be used to deliver, monitor, or control neuromodulation therapies.

[0084] Figure 8 An example technique for accessing the renal artery and modulating the renal nerve using a neuromodulation catheter is illustrated. Although Figure 8The use of catheter 12 for renal neuromodulation is illustrated, but catheter 12 can also be used for other therapies and treatments in another blood vessel or other hollow anatomy within the human body. Catheter 12 is configured to deliver energy (e.g., RF energy, ultrasound energy, electrical stimulation energy, etc.) to one or more target tissue sites within the renal vessels. Catheter 12 provides a pathway through the intravascular pathway (P) into the renal plexus (RP), such as a percutaneous entry point in the femoral artery (illustrated), brachial artery, radial artery, or axillary artery, to a target tissue site within the corresponding renal artery (RA). By manipulating the proximal portion 22B or the elongated body 22 from outside the intravascular pathway (P), clinicians can advance the distal portion 22A of the elongated body 22 through the sometimes tortuous intravascular pathway (P) and remotely manipulate the distal portion 22A of the elongated body 22. Figure 1A The distal portion 22A can be remotely operated by a clinician using the handle 20.

[0085] exist Figure 8 In the illustrated examples, an inner member 123 is used in an overall over-the-water (OTW) technique to deliver a distal portion 22A intravascularly to the treatment site. The inner member 123 may be internal to or external to a catheter 12 (e.g., a guidewire or inner catheter). In some examples, the inner member 123 is a navigation line. The catheter 12 may define a channel for receiving the inner member 23 to deliver the catheter 12 using an OTW or RX technique. At the treatment site, the inner member 123 may be at least partially withdrawn or removed relative to the catheter 12, and the distal portion 22A may be converted into an expanded configuration (e.g., a helical or spiral configuration) for delivering ultrasound energy. In other examples, the elongated body 22 may be maneuverable, allowing the therapy to be delivered to the target tissue site without the aid of the inner member 123.

[0086] Renal neuromodulation is the partial or complete incapacitation or other effective disruption of the nerves of the kidney (e.g., nerves terminating in or closely associated with the kidney). Specifically, renal neuromodulation may involve inhibiting, reducing, or blocking neural communication along nerve fibers (e.g., efferent or afferent nerve fibers) of the kidney. Such incapacitation can be long-term (e.g., permanent or lasting for months, years, or decades) or short-term (e.g., lasting for minutes, hours, days, or weeks). Renal neuromodulation is expected to contribute to a systemic reduction of sympathetic tone or activity or benefit at least some specific organs or other body structures innervated by the sympathetic nervous system. Therefore, renal neuromodulation holds promise for treating clinical conditions associated with excessive central sympathetic stimulation. For example, renal neuromodulation holds promise for effectively treating hypertension, heart failure, acute myocardial infarction, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic and end-stage renal disease, inappropriate fluid retention in heart failure, cardiorenal syndrome, polycystic kidney disease, polycystic ovary syndrome, osteoporosis, erectile dysfunction, and sudden death, among other conditions.

[0087] Renal neuromodulation can be induced electrically or otherwise by delivering energy (RF energy, ultrasound energy, microwave energy, etc.). Target tissue sites may be located within or near the renal lumen (e.g., the renal artery, ureter, renal pelvis, major calyces, minor calyces, or another suitable structure), and target tissue sites may include tissue at least adjacent to the renal lumen wall. For example, regarding the renal artery, treatment protocols may include modulating nerves in the renal plexus that are closely located within or adjacent to the adventitia of the renal artery. The following discussion provides further details regarding patient anatomy and physiology, as these may relate to renal denervation therapy. This section aims to supplement and expand upon the preceding discussion of the relevant anatomy and physiology and to provide additional context regarding the disclosed techniques and the therapeutic benefits associated with renal denervation. For example, several properties of the renal vascular system can influence the design of target tissue devices and associated methods for achieving renal neuromodulation via endovascular access, and impose specific design requirements on such devices. Specific design requirements may include access to the renal artery, positioning the distal portion 22A within the renal artery, delivering therapy to the target tissue, or utilizing a therapy delivery device to effectively modulate the renal nerve.

[0088] As previously noted, the sympathetic nervous system (SNS) is a branch of the autonomic nervous system, as well as the enteric and parasympathetic nervous systems. It is always active at a basal level (known as sympathetic tension) and becomes more active during periods of stress. Like other parts of the nervous system, the sympathetic nervous system operates through a network of interconnected neurons. Sympathetic neurons are frequently considered part of the peripheral nervous system (PNS), although many reside within the central nervous system (CNS). The spinal cord's sympathetic neurons (which are part of the CNS) communicate with peripheral sympathetic neurons via a series of sympathetic ganglia. Within the ganglia, spinal sympathetic neurons are called presynaptic (or preganglionic) neurons, while peripheral sympathetic neurons are called postsynaptic (or postganglionic) neurons.

[0089] At the synapses within the sympathetic ganglia, preganglionic sympathetic neurons release acetylcholine, a chemical messenger that binds to and activates nicotinic acetylcholine receptors on postganglionic neurons. In response to this stimulation, postganglionic neurons primarily release norepinephrine. Prolonged activation may trigger the release of adrenaline from the adrenal medulla.

[0090] Once released, norepinephrine and epinephrine bind to adrenergic receptors in peripheral tissues. Binding to these receptors triggers neuronal and hormonal responses. Physiological manifestations include pupillary dilation, increased heart rate, occasional vomiting, and elevated blood pressure. Increased sweating is also due to the binding of cholinergic receptors in sweat glands.

[0091] The sympathetic nervous system is responsible for upregulating and downregulating many homeostatic mechanisms within living organisms. Fibers from the SNS innervate tissues in almost every organ system, providing regulation of at least some physiological characteristics, as diverse as pupil diameter, intestinal motility, and urine output. This response is also known as the body's sympathetic-adrenal response because preganglionic sympathetic fibers terminating in the adrenal medulla (along with all other sympathetic fibers) secrete acetylcholine, which activates the secretion of adrenaline and, to a lesser extent, norepinephrine. Thus, this response, primarily acting on the cardiovascular system, is directly mediated by impulses transmitted through the sympathetic nervous system and indirectly mediated by catecholamines secreted by the adrenal medulla.

[0092] Figure 9 This is a conceptual diagram illustrating the sympathetic nervous system (SNS), demonstrating how the brain communicates with the body via the SNS. Figure 9As shown, the SNS provides a neural network that allows the brain to communicate with the body. The sympathetic nervous system originates within the spinal column, for example, in the middle lateral column (or lateral angle) of cells facing the middle of the spinal cord, beginning in the first thoracic segment and believed to extend to the second or third lumbar segment. Because SNS cells originate in the thoracic and lumbar regions of the spinal cord, the SNS is said to have thoracolumbar outflow. The axons of the sympathetic nerves leave the spinal cord via anterior small roots / roots. The axons pass near the spinal (sensory) ganglia, where they enter the anterior branches of the spinal nerves. However, unlike somatic innervation, the axons separate via white branch connectors, which connect to the paravertebral ganglia (located near the spinal column) or prevertebral ganglia (located near the aortic bifurcation) extending along the sides of the spine.

[0093] To reach target organs and glands, axons must travel long distances within the body, and to accomplish this, many axons relay their messages to second cells via synaptic transmission. The ends of the axons span the space, forming synapses, which connect to the dendrites of the second cell. The first cell (presynaptic cell) sends neurotransmitters across the synaptic cleft, where they activate the second cell (postsynaptic cell). The message is then transmitted to its final destination.

[0094] In the SNS and other components of the peripheral nervous system, these synapses form at sites discussed above called ganglia. Cells that send their fibers to the ganglia are called preganglionic cells, while those whose fibers leave the ganglia are called postganglionic cells. As previously mentioned, preganglionic cells of the SNS are located between the first thoracic (T1) and third lumbar (L3) segments of the spinal cord. Postganglionic cells have their cell bodies located within the ganglia and send their axons to target organs or glands.

[0095] Ganglia include not only the sympathetic trunk, but also the cervical ganglia (upper, middle, and lower) that send sympathetic nerve fibers to the head and thoracic organs, and the abdominal and mesenteric ganglia that send sympathetic nerve fibers to the intestines.

[0096] Figure 10 This is an enlarged anatomical view of the nerves that innervate the left kidney to form the renal plexus surrounding the left renal artery. (Example) Figure 10 As shown, the kidney is innervated by the renal plexus (RP), which is closely associated with the renal artery. The renal plexus (RP) is an autonomic nerve plexus that surrounds the renal artery and is embedded in the adventitia of the renal artery. The renal plexus (RP) extends along the renal artery and is embedded in the adventitia of the renal artery. Fibers contributing to the renal plexus (RP) originate from the celiac ganglion, superior mesenteric ganglion, aortic renal ganglion, and aortic plexus. The renal plexus (RP), also known as the renal nerve, mainly contains the sympathetic component. There is no (or at least very little) parasympathetic innervation of the kidney.

[0097] Preganglionic neuron cell bodies are located in the middle lateral cell column of the spinal cord. Preganglionic axons pass through the paravertebral ganglia to become smaller visceral nerves, the smallest visceral nerve, the first lumbar visceral nerve, the second lumbar visceral nerve, and proceed to the celiac ganglion, superior mesenteric ganglion, and aortorenal ganglion. Postganglionic neuron cell bodies exit the celiac ganglion, superior mesenteric ganglion, and aortorenal ganglion to reach the renal plexus (RP) and distribute to the renal vascular system.

[0098] Messages travel bidirectionally through social networks (SNS). Outgoing messages can trigger simultaneous changes in different parts of the body. For example, the sympathetic nervous system can increase heart rate, dilate bronchial passages, reduce bowel motility, constrict blood vessels, increase esophageal peristalsis, cause pupil dilation, goosebumps, and sweating, or raise blood pressure. Incoming messages carry signals from various organs and sensory receptors within the body to other organs, especially the brain.

[0099] Hypertension, heart failure, and chronic kidney disease are among many disease states caused by chronic activation of the SNS, particularly the renal sympathetic nervous system. Chronic SNS activation is an adaptive response that drives the progression of these disease states. Pharmacological management of the renin-angiotensin-aldosterone system (RAAS) has been a long-standing, but somewhat ineffective, approach to reducing SNS overactivity.

[0100] As mentioned above, the renal sympathetic nervous system has been identified, both experimentally and in humans, as a major cause of the complex pathophysiology leading to hypertension, volume overload conditions such as heart failure, and progressive kidney disease. Studies using radioactive tracer dilution methods to measure the overflow of norepinephrine from the kidneys into the plasma have shown an increased rate of renal norepinephrine (NE) spillover in patients with idiopathic hypertension, particularly in younger hypertensive subjects. This increased renal norepinephrine spillover, along with an increased rate of cardiac NE spillover, is consistent with the hemodynamic profile commonly found in early hypertension and characterized by increased heart rate, cardiac output, and renal vascular resistance. It is now known that idiopathic hypertension is often neurogenic and is typically accompanied by significant sympathetic nervous system overactivity.

[0101] Activation of cardiorenal sympathetic activity is even more pronounced in heart failure, as demonstrated by the excessive increase in NE overflow from the heart and kidneys to the plasma in the patient group. Consistent with this view, recent studies have shown strong negative predictive value of renal sympathetic activation for all-cause mortality and heart transplantation in patients with congestive heart failure, independent of overall sympathetic activity, glomerular filtration rate, and left ventricular ejection score. These findings support the view that treatment regimens designed to reduce renal sympathetic stimulation have the potential to improve survival in patients with heart failure.

[0102] Some patients with both chronic kidney disease and end-stage renal disease exhibit elevated sympathetic activation. In patients with end-stage renal disease, above-median plasma norepinephrine levels have been shown to predict both all-cause mortality and mortality from cardiovascular disease. This is also true for patients with diabetes or contrast-induced nephropathy. There is compelling evidence that sensory afferent signals originating from the diseased kidney are a major contributor to the initiation and maintenance of elevated central sympathetic outflow in this patient group; this contributes to the known adverse consequences of chronic sympathetic hyperactivity, such as hypertension, left ventricular hypertrophy, ventricular arrhythmias, sudden cardiac death, insulin resistance, diabetes, and metabolic syndrome.

[0103] The renal sympathetic nerves terminate in blood vessels, the juxtaglomerular apparatus, and the renal tubules. Stimulation of the renal sympathetic nerves leads to increased renin release, increased sodium (Na+) reabsorption, and decreased renal blood flow. These components of the neural regulation of renal function are greatly stimulated in disease states characterized by increased sympathetic tone and significantly contribute to elevated blood pressure in hypertensive patients. The decrease in renal blood flow and glomerular filtration rate caused by renal sympathetic efferent stimulation may be the basis for renal dysfunction in cardiorenal syndrome, a form of renal impairment that presents as a progressive complication of chronic heart failure and has a clinical course that typically fluctuates with the patient's clinical condition and treatment. Pharmacological strategies to block the consequences of renal efferent sympathetic stimulation include centrally acting sympathetic drugs, beta-blockers (aimed at reducing renin release), angiotensin-converting enzyme inhibitors and receptor blockers (aimed at blocking angiotensin II and aldosterone activation caused by renin release), and diuretics (aimed at counteracting renal sympathetic-mediated sodium and water retention). However, current pharmacological strategies may have significant limitations, including limited efficacy, compliance issues, and side effects.

[0104] The kidneys communicate with the overall structure of the central nervous system via renal sensory afferent nerves. Several forms of "kidney injury" may induce activation of sensory afferent signals. For example, renal ischemia, stroke, reduced renal blood flow, or adenosine abundance can trigger activation of afferent nerve communication.

[0105] Figure 11 It is an anatomical view of the human body, depicting the efferent and afferent neural communication between the brain and kidneys. Figure 12 It is a conceptual view of the human body, depicting the neural efferent and afferent communication between the brain and kidneys. For example... Figure 11 and Figure 12As shown, afferent communication may originate from the kidneys to the brain, or from one kidney to another (via the central nervous system). These afferent signals are concentrated and integrated, potentially leading to increased sympathetic outflow. This sympathetic drive is directed directly at the kidneys, thereby activating the RAAS and inducing increased renin secretion, sodium retention, volume retention, and vasoconstriction. Central sympathetic hyperactivity also affects other organs and body structures innervated by the sympathetic nervous system, such as the heart and peripheral vascular system, resulting in the described side effects of sympathetic activation, several aspects of which also contribute to elevated blood pressure.

[0106] Therefore, physiology suggests that: (i) regulation of the tissues with efferent sympathetic nerves will reduce inappropriate renin release, salt retention, and decreased renal blood flow; and (ii) regulation of the tissues with afferent sensory nerves will reduce the systemic contribution to hypertension and other disease states associated with increased central sympathetic tension through their direct effects on the posterior hypothalamus and contralateral kidney. In addition to the central hypotensive effect of afferent renal denervation, a reduction in central sympathetic outflow to various other sympathetically innervated organs such as the heart and vascular system is expected.

[0107] As provided above, renal denervation may be valuable in the treatment of several clinical conditions characterized by increased overall activity, particularly renal sympathetic activity, such as hypertension, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic end-stage renal disease, inappropriate fluid retention in heart failure, cardiorenal syndrome, and sudden death. Since a reduction in afferent nerve signals contributes to a systemic decrease in sympathetic tension / excitation, renal denervation can also be used to treat other conditions associated with excessive systemic sympathetic activity. Therefore, renal denervation may also be beneficial for other organs and body structures innervated by the sympathetic nervous system, including… Figure 12 The organs and body structures identified in the text. For example, as previously discussed, a decrease in central sympathetic drive can reduce insulin resistance, which afflicts people with metabolic syndrome and type 2 diabetes. Additionally, patients with osteoporosis can be sympathetically activated and may also benefit from the downregulation of sympathetic drive accompanying renal denervation.

[0108] According to this technology, neural modulation of the left or right renal plexus (RP), which is closely associated with the left or right renal artery, can be achieved through an intravascular pathway. Figure 13 It is an anatomical view of the human arterial vascular system. For example... Figure 13 As shown, blood, propelled by the heart's contractions, is pumped from the left ventricle of the heart through the aorta. The aorta descends through the chest 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, passing through the left and right legs respectively, and connect with the left and right femoral arteries.

[0109] Figure 14This is an anatomical view of the human venous system. For example... Figure 14 As shown, blood pools in the veins and returns to the heart, passing through the femoral vein into the iliac vein and then into the inferior vena cava. The inferior vena cava branches into the left and right renal arteries. Above the renal veins, the inferior vena cava ascends to pump blood into the right atrium of the heart. Blood from the right atrium passes through the right ventricle and is pumped into the lungs, where it is oxygenated. Oxygenated blood from the lungs is pumped into the left atrium. Oxygenated blood from the left atrium passes through the left ventricle back into the aorta.

[0110] The femoral artery can be accessed and cannulated at the base of the femoral triangle, directly below the midpoint of the inguinal ligament. The catheter can be percutaneously inserted into the femoral artery through this access site, passing through the iliac artery and aorta, and placed into the left or right renal artery. This includes endovascular pathways that provide minimally invasive access to the corresponding renal artery or other renal vessels.

[0111] The wrist, upper arm, and shoulder regions offer other locations for catheter introduction into the arterial system. For example, catheterization via the radial, brachial, or axillary arteries can be used to select cases. Catheters introduced through these entry points (e.g., catheter 12) can be inserted using standard angiography techniques through the left superior subclavian artery (or via the right superior subclavian artery and brachiocephalic artery), through the aortic arch, down the descending aorta, and into the renal arteries. Other entry sites may also be used to access the arterial system.

[0112] Since neural modulation of the left or right renal plexus (RP) can be achieved via an endovascular pathway according to this technique, the properties and characteristics of the renal vascular system can constrain or guide the design of devices, systems, and methods used to achieve such renal neural modulation. Some of these properties and characteristics may vary over time across patient populations or within a specific patient, and may also vary in response to disease states such as hypertension, chronic kidney disease, vascular disease, end-stage renal disease, insulin resistance, diabetes, metabolic syndrome, etc. As explained herein, these properties and characteristics may influence the efficacy of the protocol and the specific design of the endovascular device. Properties of interest may include, for example, material / mechanical, spatial, hydrodynamic / hemodynamic, or thermodynamic properties.

[0113] As previously discussed, catheters can be percutaneously advanced into the left or right renal artery via a minimally invasive endovascular approach. However, minimally invasive renal artery access can be challenging, for example, because renal arteries are often extremely tortuous, may have a relatively small diameter, or may have a relatively short length compared to some other arteries routinely accessed using catheters. Furthermore, renal artery atherosclerosis is common in many patients, especially those with cardiovascular disease. Renal artery anatomy can also vary significantly from patient to patient, further complicating the minimally invasive approach. For example, significant inter-patient variations can be seen in relative tortuosity, diameter, length, or atherosclerotic plaque burden, as well as in the angle of flight of the renal artery from its aortic branches. In addition, some patients have multiple left or right renal arteries. Devices, systems, and methods used to achieve renal neuromodulation via endovascular access should take into account these and other aspects of renal artery anatomy and their variations across patient populations when using minimally invasive access to the renal arteries.

[0114] In addition to complicating access to the renal artery, the details of renal anatomy also complicate establishing stable contact between the neurally modulated device and the luminal surface or wall of the renal artery. For example, the narrow spaces within the renal artery and its tortuosity can hinder guidance. Furthermore, establishing consistent contact is complicated by patient movement, breathing, or cardiac cycles, as these factors can cause significant movement of the renal artery relative to the aorta, and cardiac cycles can temporarily dilate the renal artery (i.e., cause pulsation of the arterial wall).

[0115] The neural modulation system is also configured to allow the distal portion 22A ( Figure 1A Adjustable localization and repositioning within the renal artery are crucial because the location of treatment can affect clinical efficacy. Furthermore, the variable localization and repositioning of neuromodulation devices has proven useful in cases of particularly tortuous renal arteries or where proximal branches of the main renal artery exist, making treatment at certain locations challenging.

[0116] As previously noted, the device positioned within the renal artery can be configured such that the distal portion 22A of the catheter 12 can closely contact or at least partially extend through the vessel wall. The renal artery diameter (DRA) typically ranges from approximately 2 mm to 10 mm, with the majority of patients having a DRA of approximately 4 mm to approximately 8 mm and an average of approximately 6 mm. The renal artery length (LRA) between the ostium at the aortorenal junction and its distal branches typically ranges from approximately 5 mm to 70 mm, with a significant portion of the patient population having a LRA of approximately 20 mm to 50 mm. Because the target renal plexus is embedded within the adventitia of the renal artery, the composite intima-media thickness (IMT) (i.e., the radially outward distance from the luminal surface of the artery to the adventitia containing the target neural structures) is also significant, typically ranging from approximately 0.5 mm to 2.5 mm, with an average of approximately 1.5 mm. While a certain depth of treatment is important for reaching the target nerve fibers, treatment should not be too deep (e.g., >10 mm from the inner wall of the artery) to avoid non-target tissues and anatomical structures, such as the digestive system anatomical structures of the psoas muscles.

[0117] An additional property of interest regarding the renal artery is the degree of kidney movement relative to the aorta induced by respiration or pulsatility of blood flow. The kidney, located at the distal end of the renal artery in a patient, can move up to 10 cm toward the skull with respiratory displacement. This can endow the renal artery, which connects the aorta and the kidney, with significant movement, thus requiring a unique balance of rigidity and flexibility in the neural modulation device to maintain contact between the energy delivery element and the vessel wall during the respiratory cycle. Furthermore, the fly-off angle between the renal artery and the aorta can vary significantly between patients and can also change dynamically within the patient, for example, due to kidney movement. The fly-off angle is typically around 30°. Up to 135 Within the range.

[0118] In other examples, certain aspects of this disclosure described in the context of a particular example may be combined or omitted. Furthermore, while advantages associated with some examples have been described in the context of those examples, other examples may also present such advantages, and not all examples must present such advantages to fall within the scope of this disclosure. Therefore, this disclosure and associated techniques may cover other examples not explicitly shown or described herein.

[0119] Furthermore, unless the word “or” is explicitly limited to referring only to a single item other than those in a list that refers to two or more items, its use in such lists may be interpreted as including: (a) any single item in the list, (b) all items in the list, or (c) any combination of items in the list. Additionally, the term “includes” throughout the text is used to mean that at least the enumerated features are included, without excluding any larger number of the same features and / or other features of additional types.

[0120] It should be understood that the various aspects disclosed herein can be combined with combinations different from those specifically presented in the specification and drawings. It should also be understood that, depending on the example, certain actions or events of any of the processes or methods described herein may be performed in a different order, or may be completely added, combined, or omitted (e.g., performing these techniques may not require all the described actions or events). Furthermore, although some aspects of this disclosure are described for clarity as being performed by a single module, unit, or circuit, it should be understood that the techniques of this disclosure can be performed by combinations of units, modules, or circuits associated with, for example, a medical device.

[0121] In one or more examples, the described techniques may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functionality may be stored as one or more instructions or code on a computer-readable medium and executed by a hardware-based processing unit. The computer-readable medium may include a non-transitory computer-readable medium that corresponds to a tangible medium, such as a data storage medium (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 is accessible by a computer).

[0122] Instructions can be executed by one or more processors including processing circuitry, such as one or more digital signal processors (DSPs), general-purpose microprocessors, application-specific integrated circuits (ASICs), field-programmable arrays (FPGAs), or other equivalent integrated or discrete logic circuits. Therefore, the terms "processor" or "processing circuitry" as used herein may refer to any of the foregoing structures or any other physical structure suitable for implementing the described techniques. Furthermore, these techniques can be fully implemented in one or more circuit or logic elements.

[0123] The above detailed description of the examples of this technology is not intended to be exhaustive or to limit the technology to the precise form disclosed above. While specific examples of the technology have been described above for illustrative purposes, those skilled in the art will recognize that various equivalent modifications can be made within the scope of this technology. For example, although the steps are presented in a given order, alternative examples may perform the steps in a different order. The various examples described herein may also be combined to provide other examples. All references cited herein are incorporated by way of citation as if they were listed entirely herein.

[0124] The following listed terms describe embodiments according to this disclosure.

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

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

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

[0128] Clause 4: The neuromodulation system according to Clause 1 or 2, wherein the controller is configured to determine a corresponding impedance based on signals sensed by the respective electrode segment of the plurality of electrode segments and the reference pad, and wherein, in order to determine the impedance, the controller is configured to select the maximum impedance from the corresponding impedance.

[0129] Clause 5: The neuromodulation system according to Clause 4, wherein the controller is configured to generate a selection signal that indicates the corresponding electrode segment among the plurality of electrode segments associated with the maximum impedance.

[0130] Clause 6: A neuromodulation system according to any one of Clauses 1 to 5, wherein each of the plurality of electrode segments is arranged at substantially the same longitudinal position along the periphery of the elongated body.

[0131] Clause 7: A neuromodulation system according to any one of Clauses 1 to 6, wherein each of the plurality of electrode segments is laterally spaced from the other corresponding electrode segments of the plurality of electrode segments along the surface of the elongated body.

[0132] Clause 8: A neuromodulation system according to any one of Clauses 1 to 7, wherein the ablation electrode is cylindrical, and wherein each of the plurality of electrode segments is a cylindrical segment arranged circumferentially around the elongated body.

[0133] Clause 9: A neuromodulation system according to any one of Clauses 1 to 8, wherein each of the plurality of electrode segments defines the same electrode segment area.

[0134] Clause 10: A neuromodulation system according to any one of Clauses 1 to 9, wherein each of the plurality of electrode segments defines the same electrode segment shape.

[0135] Clause 11: A neuromodulation system according to any one of Clauses 1 to 8, wherein the plurality of electrode segments includes two electrode segments, and wherein a first electrode segment of the two electrode segments defines a first electrode segment area, and wherein a second electrode segment of the two electrode segments defines a second electrode segment area larger than the area of ​​the first electrode segment.

[0136] Clause 12: The neural modulation system according to Clause 11, wherein the controller is configured to determine the impedance based solely on the signal sensed by the first electrode segment.

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

[0138] Clause 14: A neuromodulation system according to any one of Clauses 1 to 13, wherein the ablation electrode comprises a total of two electrode segments.

[0139] Clause 15: A neuromodulation system according to any one of Clauses 1 to 13, wherein the ablation electrode comprises a total of four electrode segments.

[0140] Clause 16: A neuromodulation system according to any one of Clauses 1 to 15, wherein the ablation electrode comprises at least one of gold, platinum or iridium oxide.

[0141] Clause 17: A neuromodulation system according to any one of Clauses 1 to 16, wherein each pair of electrode segments in the plurality of electrode segments is separated by a corresponding electrically insulating region.

[0142] Clause 18: The neuromodulation system as described in Clause 17 further includes an insulating material in a corresponding electrically insulating region.

[0143] Clause 19: The neural modulation system as described in Clause 18, wherein the insulating material comprises at least one of a metal, an alloy, or a polymer.

[0144] Clause 20: The neuromodulation system as described in Clause 19, wherein the metal or alloy comprises at least one of bismuth, tungsten, or titanium.

[0145] Clause 21: The neural modulation system as described in Clause 19, wherein the polymer comprises at least polyimide.

[0146] Clause 22: The neuromodulation system according to any one of Clauses 1 to 21 further includes a thermocouple coupled to at least one of the plurality of electrode segments.

[0147] Clause 23: A neuromodulation system according to any one of Clauses 1 to 22, wherein the neuromodulation conduit includes a plurality of ablation electrodes along the elongated body, the plurality of ablation electrodes including the ablation electrodes.

[0148] Clause 24: The neuromodulation system as described in Clause 23, wherein each of the plurality of ablation electrodes comprises a corresponding plurality of electrode segments.

[0149] Clause 25: The neuromodulation system according to any one of Clauses 1 to 24, the neuromodulation system further comprising a computing device configured to control the controller to deliver neuromodulation therapy via the neuromodulation conduit.

[0150] Clause 26: A neuromodulation conduit comprising: an elongated body including a distal portion configured to transition from a relatively low-profile configuration to an expanded configuration; and an ablation electrode along the elongated body, the ablation electrode including a plurality of electrode segments, each of the plurality of electrode segments being electrically isolated from other corresponding electrode segments of the plurality of electrode segments, wherein each of the plurality of electrode segments is arranged at substantially the same longitudinal position along the periphery of the elongated body.

[0151] Clause 27: The neuromodulation conduit according to Clause 26, wherein the ablation electrode is cylindrical, and wherein each of the plurality of electrode segments is a cylindrical segment arranged circumferentially around the elongated body.

[0152] Clause 28: The neuromodulation conduit according to Clause 26 or 27, wherein the ablation electrode comprises two electrode segments, wherein a first electrode segment of the two electrode segments defines a first electrode segment area, and wherein a second electrode segment of the two electrode segments defines a second electrode segment area larger than the area of ​​the first electrode segment.

[0153] Clause 29: A neuromodulation conduit according to any one of Clauses 26 to 28, wherein the neuromodulation conduit includes a plurality of ablation electrodes along the elongated body, the plurality of ablation electrodes including the ablation electrode, and wherein each of the plurality of ablation electrodes includes a corresponding plurality of electrode segments.

[0154] Clause 30: A method for neuromodulation, the method comprising: determining impedance by a processing circuit based on signals sensed by at least one of a plurality of electrode segments of a neuromodulation catheter placed in a patient’s blood vessel; and delivering an ablation signal by all of the plurality of electrode segments to a target site, the neuromodulation catheter placed in the patient’s blood vessel.

[0155] Clause 31: The method according to Clause 30, wherein determining the impedance comprises: determining the impedance based on the signal sensed by no more than one of the plurality of electrode segments and the reference pad.

[0156] Clause 32: The method according to Clause 31 further comprises: positioning the neuromodulation conduit such that one electrode segment contacts at least one tissue in the blood vessel oriented toward the target site.

[0157] Clause 33: The method according to Clause 30 further comprises: determining a corresponding impedance by the processing circuit based on a signal sensed by a corresponding electrode segment of the plurality of electrode segments and the reference pad, and determining the impedance by the processing circuit by selecting the maximum impedance from the corresponding impedance.

[0158] Clause 34: The method according to any one of Clauses 30 to 33, further comprising: adjusting the ablation signal by the processing circuit based on at least the impedance.

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

[0160] Based on the foregoing, it should be understood that specific examples of this disclosure have been described herein for illustrative purposes, but various modifications may be made without departing from the scope of this disclosure.

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

Claims

1. A neural modulation system, the neural modulation system comprising: Neuromodulation conduit, the neuromodulation conduit comprising: Slender body; An ablation electrode, the ablation electrode extending along the elongated body, the ablation electrode comprising a plurality of electrode segments, each of the plurality of electrode segments being electrically isolated from other corresponding electrode segments of the plurality of electrode segments; and The controller is configured to: When the elongated body is placed in a patient's blood vessel, impedance is determined based on signals sensed by at least one of the plurality of electrode segments and a reference pad; and An ablation signal is generated, which is configured to be delivered by all of the plurality of electrode segments when the elongated body is placed in the blood vessel.

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

3. The neural modulation system of claim 1 or 2, wherein the controller is configured to determine the impedance based on the signal sensed by no more than one of the plurality of electrode segments and the reference pad.

4. The neural modulation system according to any one of claims 1 to 3, wherein the controller is configured to determine a corresponding impedance based on signals sensed by a corresponding electrode segment of the plurality of electrode segments and the reference pad. In order to determine the impedance, the controller is configured to select the maximum impedance from the corresponding impedances, and The controller is configured to generate a selection signal that indicates the corresponding electrode segment among the plurality of electrode segments associated with the maximum impedance.

5. The neuromodulation system according to any one of claims 1 to 4, wherein the ablation electrode is cylindrical, and wherein each of the plurality of electrode segments is a cylindrical segment arranged circumferentially around the elongated body.

6. The neural modulation system according to any one of claims 1 to 5, wherein the plurality of electrode segments comprises two electrode segments, The first electrode segment of the two electrode segments defines the area of ​​the first electrode segment. The second electrode segment of the two electrode segments is defined as having an area larger than that of the first electrode segment. The first electrode segment is configured to contact the tissue within the blood vessel, and The controller is configured to determine the impedance based solely on the signal sensed by the first electrode segment.

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

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

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

10. The neuromodulation system according to any one of claims 1 to 9, wherein the neuromodulation conduit includes a plurality of ablation electrodes along the elongated body, the plurality of ablation electrodes including the ablation electrodes.

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

12. A neuromodulation conduit, the neuromodulation conduit comprising: An elongated body, the elongated body including a distal portion, the distal portion being configured to transform from a relatively low profile configuration to an unfolded configuration; and An ablation electrode, extending along the elongated body, comprising a plurality of electrode segments, each of the plurality of electrode segments being electrically isolated from the other corresponding electrode segments of the plurality of electrode segments. Each of the plurality of electrode segments is arranged at approximately the same longitudinal position along the periphery of the elongated body.

13. The neuromodulation conduit of claim 12, wherein the ablation electrode is cylindrical, and wherein each of the plurality of electrode segments is a cylindrical segment arranged circumferentially around the elongated body.

14. The neuromodulation conduit of claim 12 or 13, wherein the ablation electrode comprises two electrode segments, wherein a first electrode segment of the two electrode segments defines a first electrode segment area, and wherein a second electrode segment of the two electrode segments defines a second electrode segment area larger than the area of ​​the first electrode segment.

15. The neuromodulation conduit according to any one of claims 12 to 14, wherein the neuromodulation conduit includes a plurality of ablation electrodes along the elongated body, the plurality of ablation electrodes including the ablation electrode, and wherein each of the plurality of ablation electrodes includes a corresponding plurality of electrode segments.

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