WO2021097448A1

WO2021097448A1 - Methods and devices for renal neuromodulation

Info

Publication number: WO2021097448A1
Application number: PCT/US2020/060780
Authority: WO
Inventors: Thomas James OXLEY; Nicholas Lachlan Opie
Original assignee: Synchron Australia Pty Limited
Priority date: 2019-11-15
Filing date: 2020-11-16
Publication date: 2021-05-20

Abstract

Devices, methods and systems for using an electrically conductive stent structure to initially apply non-ablative stimulation energy within a renal artery to affect a blood pressure in an individual.

Description

METHODS AND DEVICES FOR RENAL NEUROMODULATION

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a non-provisional application of U.S. Provisional Application no. 62/935,901 filed November 15, 2020. This application is also a continuation-in-part of PCT Application no. PCT/US2020/059509, filed on November 6, 2020. The entirety of both applications is incorporated by reference.

TECHNICAL FIELD OF THE INVENTION

[0002] The present invention relates to medical devices for treatment of hypertension through renal sympathetic neuromodulation (RSN) or renal artery sympathetic denervation (RASN), which produces a transient and reversable stimulation for a therapeutic effect. The present disclosure can also affect hypotension through a similar mechanism that treats hypertension.

BACKGROUND OF THE INVENTION

[0003] Hypertension, or elevated blood pressure, is generally considered a major modifiable risk factor associated with cardiovascular morbidity and mortality. It is known that renal denervation or renal sympathetic denervation (RSDN), is a minimally invasive, endovascular catheter-based procedure that requires ablation of the arterial wall using heat from radio frequency-based ablation or ultrasound ablation. RSDN is aimed at treating resistant hypertension (high blood pressure not controlled by medication).

[0004] It is believed that RSDN ablates nerves in the wall of the renal artery. This causes reduction of sympathetic afferent and efferent activity to the kidney decreases blood pressure. While early clinical trials demonstrated that RSDN could produce significant blood pressure reductions in patients with treatment-resistant hypertension. It was found during additional clinical trials that there is too much variability in the outcome of RSDN to allow confirmation of repeatable beneficial effect on blood pressure.

[0005] Because conventional RSDN is often a catheter-based approach that is highly dependent on the medical practitioner, ablation of the renal arteries in widescale RSDN could be variable due to operator variability. Furthermore, care must be taken in RSDN procedures since ablation of renal arterial tissue produces therapeutic lesions in the arteries. Therefore, repeat treatments are impractical. [0006] Recently, stents and stent type devices have been discussed for use in restoring control to individuals that suffer from various neuromuscular disorders where control of limbs is severely impaired. In many of these patients, however, the portion of the brain responsible for movement remains intact, and it is disease and trauma to the spinal cord, nerves and muscles that limit mobility, function and independence. For these people, the ability to restore lost control at even a rudimentary level could lead to a greatly improved quality of life.

[0007] For example, commonly assigned U.S. patent application nos. 15/957,574 and 16/164,482 (incorporated by reference herein) disclose stent-based devices that can record and stimulate cortical tissue when placed in the vasculature of the brain. Such devices use blood vessels as a conduit to the brain and provide for improved intravascular electrodes, telemetry circuitry and implantation positions that are capable of more efficiently transmitting and receiving electrical energy between vessels and external circuitry, while minimizing the occlusion of blood flow. While such devices are demonstrating promise in improving BCI for control of external devices. The stent-based devices can offer therapeutic advantages to meet a number of surgical needs.

[0008] The stent-based devices described herein can deliver either therapeutic ablative and/or non-ablative energy, which can be controlled by a physician or a computerized system. The ability to deliver such energy presents additional opportunities to provide therapies that were previously limited to surgical ablation of tissue.

[0009] Therefore, there remains a need to deliver energy in a controlled manner where the results can be titrated to achieve consistent and effective results across multiple operators/physicians. RSDN is just one example of a therapy that could benefit from the controlled delivery of energy which produces a therapeutic effect via neuromodulation, which produces a transient and reversable stimulation, as opposed to a procedure that produces irreversible changes to the body through affecting a nerve or other tissue.

SUMMARY OF THE INVENTION

[0010] The methods, devices, and systems described herein relate to therapies for renal artery sympathetic neuromodulation (RASN), which produces a transient and reversable stimulation as opposed to a procedure that produces irreversible changes. The RASN procedure can be made long term through settings and/or continual application of the therapy. According to the present invention, medical devices are used for applying non-ablative energy to an artery to alleviate elevated blood pressure within the arterial system. In one example, the methods described herein include methods of treating a human patient to affect an initial blood pressure of the patient. One variation of such a method can include positioning an energy delivery device within a renal artery of at least one kidney of the patient; applying a regimen of non-ablative energy from the energy delivery device to the renal artery to affect the kidney to produce an altered blood pressure of the patient; monitoring the altered blood pressure for a period of time; assessing the altered blood pressure after the period of time to determine an effect of the regimen of non-ablative energy; and adjusting at least one parameter of the regimen of non-ablative energy based on the assessment of the altered blood pressure.

[0011] The methods described herein can produce altered blood pressure that is lower than the initial blood pressure in order to treat hypertension. Alternatively, the methods described herein can produce altered blood pressure that is higher than the initial blood pressure in order to treat hypotension.

[0012] In an additional variation of the method, the energy delivery device is electrically coupled to an implanted pulse generator located in a body of the patient and controls the regimen of non-ablative energy. The implanted pulse generator can be coupled to the energy delivery using a conductive lead. Variations of the method can include extending the conductive lead through a vasculature of the patient.

[0013] In another variation of the method, assessing the altered blood pressure after the period of time and adjusting the regimen of non-ablative energy based on the assessment of the altered blood pressure is automatically performed by a monitoring device in electrical communication with the implanted pulse generator. Alternatively, or in combination, assessing the altered blood pressure after the period of time and adjusting the regimen of non-ablative energy based on the assessment of the altered blood pressure is manually performed by a physician. [0014] Monitoring of the altered blood pressure can occur through traditional modes of monitoring blood pressure. Alternatively, or in combination, monitoring the altered blood pressure can comprise monitoring the altered blood pressure using one or more sensors positioned within a vasculature of the patient. In such cases, one or more sensors can be positioned on or adjacent to the energy delivery device.

[0015] The devices described herein can be implanted using a vascular approach.

[0016] Any energy transfer devices are within the scope of this disclosure. However, variations of the method include an energy delivery device that is an expandable stent structure, such as a stent-device. For example, the expandable stent structure can comprise a frame stmcture forming a plurality of struts, where the frame structure is moveable between a reduce profile and an expanded profile in which a diameter of the frame structure increases; where at least one of the plurality of struts forming the frame structure comprises an electrically conductive material on a support material, the electrically conductive material extending along at least a portion of the strut and being covered with a non-conductive material.

[0017] In another variation of the method, the expandable stent stmcture comprises; at least one electrode formed by an opening in the non-conductive material on the portion of the stmt. For example, the electrical effect can comprise at least a portion of the non-conductive material creating a capacitive effect between at least a portion of the electrically conductive material and the blood vessel.

[0018] The present disclosure also includes one or more systems for affecting an autonomous nervous system in a human patient to affect an initial blood pressure of the patient. For example, such a system can include a first energy delivery device configured for positioning within a renal artery of at least one kidney of the patient; a blood pressure monitoring device configured to monitor a blood pressure of the patient; a controller configured to apply a regimen of non-ablative energy from the energy delivery device to the renal artery to affect the kidney to produce an altered blood pressure of the patient, and to monitor the altered blood pressure for a period of time, the controller further configured to assess the altered blood pressure after the period of time to determine an effect of the regimen of non-ablative energy and adjust at least one parameter of the regimen of non-ablative energy based on the assessment of the altered blood pressure.

[0019] In one variation, the controller applies the regimen in a closed loop system using a monitoring device that provides one or more signals based on biological activity (e.g., blood pressure, heart rate, or any other cardiovascular indicator).

[0020] The controller described herein can be configured to produce the altered blood pressure to be lower than the initial blood pressure in order to treat hypertension. Additionally, the controller can be configured to produce the altered blood pressure to be higher than the initial blood pressure in order to treat hypotension.

[0021] In an additional variation, the controller is configured to automatically assess the altered blood pressure after the period of time and adjust the regimen of non-ablative energy based on the assessment of the altered blood pressure. Alternatively, or in combination, the controller can be configured to permit manual adjustment of the regimen of non-ablative energy. [0022] Variations of the system include one or more blood pressure monitoring devices having one or more sensors configured to be positioned within a vasculature of the patient. The one or more sensors can be positioned on or adjacent to the energy delivery device.

[0023] A variation of the system includes a energy delivery device that is an expandable stent structure/endovascular carrier.

[0024] In another variation, the expandable stent structure comprises a frame structure forming a plurality of struts, where the frame structure is moveable between a reduce profile and an expanded profile in which a diameter of the frame structure increases; where at least one of the plurality of struts forming the frame structure comprises an electrically conductive material on a support material, the electrically conductive material extending along at least a portion of the strut and being covered with a non-conductive material.

[0025] The system can further include a controller that comprises an implanted pulse generator configured to be implanted located in a body of the patient. In addition, the system can include a first conductive lead coupling the implanted pulse generator to the energy delivery, where the conductive lead is configured to extend through a vasculature of the patient. The system can further comprise at least one additional energy delivery device configured for positioning within the vasculature of the patient and where the controller is configured to apply the regimen of non-ablative energy from the energy device and the at least one additional energy delivery device into the renal artery to affect the kidney to produce the altered blood pressure of the patient.

[0026] The system can have a second conductive lead coupling the controller to the at least one additional energy delivery device. Alternatively, or in addition, the system can have a common conductive lead having a bifurcation section separating the first conductive lead from the second conductive lead.

[0027] Variations of the system include one or more extracorporeal devices configured to communicate with the implanted pulse generator.

[0028] In an additional variation, a pulse generator can include a first magnetic component, and wherein the extracorporeal device comprises a second magnetic component configured to be magnetically coupled to the first magnetic component, and wherein the pulse generator is configured to be charged by the extracorporeal device via electromagnetic induction when the extracorporeal device is placed in proximity to the pulse generator.

[0029] Alternate variations of the system include a first energy delivery device that comprises a wire or cable configured to be wound or coiled comprising an electrode array coupled to the wire or cable. Variations can also include an energy delivery device having a wire or cable comprising a sharp distal end for penetrating through the renal artery wall.

[0030] In an additional variation, the energy delivery device comprises an anchor, and wherein the anchor is at least one of a barbed anchor and a radially-expandable anchor.

[0031] The systems described herein can further include a controller having a telemetry unit, wherein the telemetry unit is configured to analyze the electrophysiological signal detected by comparing the electrophysiological signal against one or more signal thresholds or patterns. [0032] Any number of energy-based devices are within the scope of this disclosure. For example, the method can include placing at least one additional energy delivery device within the vasculature of the patient and where applying a regimen of non-ablative energy from the energy delivery device into the renal artery to affect the kidney to produce the altered blood pressure of the patient comprises applying the regimen using the energy delivery device and the at least one additional energy delivery device. The additional energy delivery devices can be placed within a second renal artery. Alternatively, or in combination, additional energy delivery devices can be positioned in other arteries within the body.

BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Preferred embodiments of the present invention are hereafter described, by way of non-limiting example only, with reference to the accompanying drawing.

[0034] Figure 1 is a diagrammatic illustration of a system for controlling use of apparatus coupled to an animal or a human.

[0035] Figure. 2 illustrates an example of a device implanted within a renal artery where the device includes one or more sensors configured to detect blood pressure within the vasculature. [0036] Figure 3 a diagrammatic illustration showing parts of the system shown in Figure 1. [0037] Figure 4 illustrates a variation of an endovascular neuromodulation system.

[0038] Figures 5A to 5D illustrate various embodiments of endovascular carriers.

[0039] Figure 6 illustrates a variation of a system having a neuromodulation unit and one endovascular carrier implanted within the subject for treatment of renal nerves.

[0040] Figures 7 A to 7E are diagrammatic illustrations of medical device of the system shown in Figure 1.

[0041] Figures 8A to 8D illustrate examples of stents or scaffoldings having a plurality of electrodes disposed about the stent body. [0042] Figures 9A to 9C illustrate an example of integrated or embedded electrodes.

[0043] Figures. 10A to 10B show an example of a stent structure fabricated with dimensional variation to impart specific characteristics to the stent.

[0044] Figure 11 illustrates a number of conductive tracks extending in a strut of a stent.

[0045] Figures 12A to 12C illustrate one embodiment of a transmission lead used to connect an electrode array to another electrode array or to the neuromodulation unit.

[0046] Figures 13A to 13C illustrate an example method of implanting an embodiment of an electrode array.

[0047] Figure 14 illustrates an embodiment of a delivery catheter comprising a bifurcated transmission lead.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

[0048] As shown in FIG. 1 , a system as described herein includes a medical system that includes an energy delivery device or component 108 that is designed for placement within a vessel 202 of an animal or human 10. In this particular variation, energy delivery device 108 comprises a stent-structure and the can be a renal artery 6 associated with a kidney 2. Placement of the stent-structure 108 is shown for purposes of illustration only. Variations of the concept can include a stent that is positioned so that partially or entirely extends into a descending aorta 3 or that extends into opposite renal artery 6 associated with a second kidney. Regardless of position, one variation of the concept includes placement of the device 108 such that it can apply (at least) non-ablative energy into the renal artery 6 in a manner similar to a renal denervation procedure. However, as discussed herein, the device 108 is part of a closed-loop neuromodulation system that allows for a gradual or titrated treatment utilizing real time feedback of blood pressure that allows for observation of an initial effect of energy delivery into the renal artery 6 and adjustment of one or more parameters of the energy delivery to maximize the therapeutic effect and/or to minimize any adverse effects of the treatment. The ability to treat, observe, and titrate the treatment in a reversible manner is believed to reduce variability of the effect of the renal denervation procedure across multiple patients and/or increase the effectiveness of the treatment for each particular patient where denervation is often a one-time irreversible ablative procedure.

[0049] FIG. 1 also illustrates the system includes a lead 106 structure that couples the energy delivery component or endovascular carrier 108 to a component 234 that can serve as a pulse generator, power supply, controller, communications, unit, or any other structure that allows a medical practitioner to control the application of energy at the treatment site in the artery. The lead 106 can comprise a wire, bundle of wires, and/or other structure that allows for electrical coupling between the endovascular carrier 108 and component 234. For example, the lead 106 can comprise a multi-lumen tubing that facilitates delivery of energy at the endovascular carrier 108 as well as allows for other functions necessary for the procedure (including but not limited to blood pressure measurement at or near the stent site).

[0050] In most variations, placement of the component 234 will occur exterior to the vasculature but subcutaneously on the patient 10. In some variations, the component can remain within the vasculature, but more frequently, positioning of the component 234 subcutaneously on the chest and/or abdomen, legs, arms, back, sacro-iliac (same as location for spinal cord stimulators) etc. will allow the patient 10 to perform every day activities without interference by the presence of the component. Additional variations of the disclosure include components 234 that are not subcutaneous but are located on an external surface of the body.

[0051] In one example, the present system allows for a method of treating a human 10 patient to affect an initial blood pressure where the patient is experiencing resistant hypertension. Additional variations of the method can include treatment of non-resistant hypertension as well as hypotension. For example, the system can use machine learning to identify ideal stimulation parameters (duration of stimulation, time of stimulation, pattern of stimulation) that may either achieve hypertension or hypotension. In any case, a first variation of the method includes positioning an energy delivery device, illustrated in FIG. 1 as an endovascular carrier 108, within a renal artery 6 of at least one kidney 2 of the patient 10. The endovascular carrier 108 is coupled to a lead 106 where both are advanced through a vasculature such that the stent 202 is ultimately positioned at a desired target site. In one variation, the lead 106 also extends through the vasculature so that a controller device 234 can be located as desired. In the illustrated example, the lead must exit the vasculature for positioning of the controller 234. However, alternate variations allow for capacitive coupling of a lead that remains within the vasculature and a controller that is subcutaneously implanted or positioned on a surface of the body.

[0052] In practice, the system will cause application of a regimen of non-ablative energy to the renal artery 6 using the energy delivery device 108 in an effort to produce an altered blood pressure of the patient. Again, in cases of hypertension, the desired outcome is to reduce blood pressure. As noted herein, the device 108 will deliver a non-ablative energy that is intended to produce the desired outcome. [0053] Next, the patient’s 10 blood pressure is monitored to determine the effect of the application of energy to proceed an altered blood pressure. In those cases where the application of energy has no effect on the patient’s blood pressure, the altered blood pressure will be the same as the previous blood pressure that gave rise to the medical condition. However, when the application of energy within the renal artery 6 produces a reduction in blood pressure, the altered blood pressure is reduced as compared to the initial blood pressure. The monitoring of blood pressure can be performed with a conventional blood pressure monitor 310. Alternatively, as discussed below, the system can incorporate blood pressure monitoring in any component (e.g., in the device 108, the lead 106, and/or the control unit 234). In most cases, monitoring of the altered blood pressure occurs over a period of time or during a specified interval. For example, monitoring may occur continually over a period of time. In another variation of the method, the monitoring of blood pressure may occur at night or during the day. In yet another variation, an accelerometer can be incorporated into the system such that the monitoring occurs during a period of rest or activity.

[0054] Once sufficient data is observed via monitoring of the altered blood pressure an assessment of the altered blood pressure takes place to determine an effect of the regimen of non ablative energy at the implant site. In one variation, the assessment occurs via a physician that monitors data produced by the system. Alternatively, the data can be streamed to a networked communication device. The assessment of data will typically determine whether the results of the procedure have produced effects that are within an acceptable range (e.g., that the patient’s blood pressure was reduced by a clinically effective amount). The parameters of the regimen of non ablative energy delivered by the implant 200 can be adjusted based on the assessment of the altered blood pressure system. In yet another example, the data is monitored in a closed feedback system such that the system continually updates the parameters of the regimen of non-ablative energy to ensure that the delivery of non-ablative energy produces a sufficiently acceptable clinical result. The system can also take into account other parameters for stimulation, including but not limited to, a degree of physical activity, a time of physical activity, duration of exposure to sunlight, eating habits, or other medicines and/or treatments taken by the patient.

[0055] FIG. 2 illustrates a device 108 implanted within a renal artery 6 where the stent includes one or more sensors 236 that are configured to detect blood pressure within the vasculature. In the illustrated variation, the sensors 109 are positioned proximate to the endovascular carrier 108. While the figure shows two sensors 236, one placed at the endovascular carrier 108 and one placed at the lead 106, any number of sensors are within the scope of this disclosure. Moreover, a blood pressure detecting apparatus and/or sensor can be positioned in any portion of the body.

[0056] FIG. 2 also illustrates the controller/modulation unit 104 communicating with an external device 300 via a non-wired connection. For example, the communication 262 can occur through capacitive coupling between the implanted unit 104and the external device 300. In another variation, communication 262 can occur through any known wireless communication mode. The use of an external device 300 allows a physician or other medical caregiver to review data relating to the operation of the device (e.g., historical adjusted blood pressure data, device parameters, energy delivered, frequency of energy delivery, and/or other energy delivery parameters). The external device 300 can adjust any number of parameters of the regimen of non ablative energy based being applied to the renal artery 6. As noted above, this adjustment can occur via a medical caregiver and/or can be performed on an automatic basis where the external device 300 maintains somewhat frequent or regular communication with the implanted controller 104.

[0057] FIG. 3 illustrates another variation of the system in which multiple energy transfer devices 108A, 108B are implanted within multiple arterial sites 6, 7. In the illustrated variation, a first endovascular carrier 108 A is positioned in a first renal artery 6 and a second endovascular carrier 108B is positioned in a second renal artery 7. Both devices 108A and 108B can be coupled in a parallel manner to a single control unit 104 using leads 106A and 106B. Alternatively, the devices 108A and 108B can be wired sequentially. In yet another variation, multiple controllers 104 can be used where each controller 104 is coupled to at least one energy transfer device.

[0058] Fig. 4 illustrates a variation of neuro modulation system 100 useful for renal artery sympathetic neuromodulation. This neuromodulation system 100 comprises a plurality of electrode arrays 102 electrically coupled to a neuromodulation unit 104 via transmission leads 106 or wires. For example, the neuromodulation system 100 can comprise a first electrode array 102A and a second electrode array 102B electrically coupled to the neuromodulation unit 104. While two endovascular carriers 108A and 108B are show, alternate variations include the use of a single endovascular carrier.

[0059] In the illustrated example, a first electrode array 102A is coupled to a first endovascular carrier 108A configured to be implanted endovascularly within the subject. A second electrode array 102B can be coupled to a second endovascular carrier 108B configured to be implanted endovascularly within the subject.

[0060] In some embodiments, the first endovascular carrier 108A and the second endovascular carrier 108B can be implanted within different vessels (e.g., different veins, arteries, or sinuses) of the subject. In other embodiments, the first endovascular carrier 108A and the second endovascular carrier 108B can be implanted within the same vessel or within different segments of the same vessel.

[0061] In certain embodiments, the first electrode array 102A can be configured to detect or record an electrophysiological signal of a subject and the second electrode array 102B can be configured to stimulate an intracorporeal target (e.g., a target nerve, a target brain region or area, or other target tissue, such as nerves in the proximity of the renal arteries) of the subject. In these embodiments, the neuromodulation unit 104 can be configured to analyze the electrophysiological signal detected or recorded by a sensing unit that measures blood pressure and transmit an electrical impulse to one or more electrode arrays 102A electrode array 102B via a pulse generator 110 in response to the electrophysiological signal detected or recorded.

[0062] In other embodiments, the first electrode array 102A and the second electrode array 102B can both be configured to stimulate one or more intracorporeal targets of the subject. The intracorporeal target(s) will be discussed in more detail in later sections.

[0063] The first electrode array 102A can comprise a plurality of electrodes 112 coupled to the first endovascular carrier 108A. For example, the first electrode array 102A can comprise between 2 and 16 electrodes. In other embodiments, the first electrode array 102A can comprise between 16 and 20 electrodes or more than 20 electrodes.

[0064] A second optional electrode array 102B can comprise a plurality of electrodes 112 coupled to the second endovascular carrier 108B. For example, the second electrode array 102B can comprise between 2 and 16 electrodes. In other embodiments, the second electrode array 102B can comprise between 16 and 20 electrodes or more than 20 electrodes. Again, the systems and methods described herein can use any number of endovascular carriers as needed.

[0065] In variations of the device, when the electrode arrays 102 (e.g., any of the first electrode array 102A or the second electrode array 102B) are used to detect or record an electrophysiological signal of the subject, the electrode arrays can be referred to as recording electrode arrays. Moreover, when the electrode arrays (e.g., any of the first electrode array 102A or the second electrode array 102B) are used to stimulate an intracorporeal target of the subject, the electrode arrays can be referred to as stimulating electrode arrays.

[0066] In some embodiments (for example, the embodiment shown in Fig. 4), the first endovascular carrier 108A and the second endovascular carrier 108B can be expandable stents or endovascular scaffolds. The endovascular carrier and the electrode arrays coupled to such a carrier can be referred to as a stent-electrode array 109. Stent-electrode arrays 109 will be discussed in more detail in later sections.

[0067] In other embodiments, at least one of the first endovascular carrier 108A and the second endovascular carrier 108B can be a biocompatible coiled wire 200, a biocompatible anchored wire 208 , or a combination thereof (as discussed below). In yet additional variations, both endovascular carriers can be coiled or anchored.

[0068] In certain embodiments, the first endovascular carrier 108A can be the same as the second endovascular carrier 108B (e.g., both the first endovascular carrier 108A and the second endovascular carrier 108B can be stent-electrode arrays 109, coiled wires 200, or anchored wires 208). In other embodiments, the first endovascular carrier 108A can be different from the second endovascular carrier 108B (e.g., the first endovascular carrier 108A can be a stent-electrode array 109 and the second endovascular carrier 108B can be a coiled wire 200).

[0069] Although Fig. 4 illustrates the neuromodulation system 100 comprising two electrode arrays 102 and two endovascular carriers 108, it is contemplated by this disclosure that the neuromodulation system 100 can comprise between three to five electrode arrays 102 and endovascular carriers 108. In additional embodiments, the neuromodulation system 100 can comprise between five to ten electrode arrays 102 and endovascular carriers 108.

[0070] The neuromodulation unit 104 can be configured to be implanted within the subject.

In some embodiments, the neuromodulation unit 104 can be configured to be implanted within any region of the body. In the variations shown in FIGS. 1 to 3, the unit 104 is positioned in a lower portion of the body. However, alternatively, or additionally, the unit 104 can be implanted within a pectoral region of the subject (see below). However, variations of the devices, systems and methods allow for implantation in any portion of the body.

[0071] Each of the first electrode array 102A and the second electrode array 102B can be coupled via one or more transmission leads 106 or lead wires to the neuromodulation unit 104. In some embodiments, the transmission leads 106 can be inserted or otherwise coupled to a header portion 114 of the neuromodulation unit 104. [0072] The header portion 114 can comprise a different plug receptor for leads or plugs coming from different electrode arrays. For example, the header portion 114 can comprise a 0.9 mm plug receptor for receiving a plug or connector from a first transmission lead 106 A connected or coupled to the first electrode array 102A serving as the recording electrode array and a 1.3 mm plug receptor for receiving a plug or connector from a second transmission lead 106B connected or coupled to the second electrode array 102B serving as the stimulation electrode array.

[0073] The neuromodulation unit 104 can comprise a unit housing 116. The unit housing 116 can be a hermetically sealed housing or casing such that electronic components within the neuromodulation unit 104 are encapsulated by the unit housing 116. The unit housing 116 can be made of a biocompatible material. For example, the unit housing 116 can be made in part of a metallic material (e.g., titanium, stainless steel, platinum, or a combination thereof), a polymeric material, or a combination thereof.

[0074] In some embodiments, the pulse generator 110 can be part of the neuromodulation unit 104 or contained within the unit housing 116. In some embodiments, the implantable neuromodulation unit 104 can comprise one or more batteries (e.g., rechargeable or non- rechargeable batteries). In certain embodiments, the batteries of the neuromodulation unit 104 can be recharged via wireless inductive charging.

[0075] In other embodiments, the neuromodulation unit 104 can be powered and/or activated by an extracorporeal device 300 (see, for example, Figs. 2 and 3). As shown in FIG. 4, the neuromodulation unit 104 can comprise a first magnetic component 118 and the extracorporeal device 300 can comprise a second magnetic component 302 (discussed below) configured to be magnetically coupled to the first magnetic component 118. The neuromodulation unit 104, including the pulse generator 110, can be configured to be charged by the extracorporeal device 300 via electromagnetic induction or activated by the extracorporeal device 300 when the extracorporeal device 300 is placed in proximity to the neuromodulation unit 104, such as by holding the extracorporeal device 300 close to an implantation site of the neuromodulation unit 104. In these embodiments where the neuromodulation unit 104 and the pulse generator 110 are the same device, any reference to the neuromodulation unit 104 can also refer to the pulse generator 110.

[0076] In other embodiments, the pulse generator 110 can be a separate device or apparatus from the neuromodulation unit 104. In these embodiments, the pulse generator 110 can be implanted within the subject and the neuromodulation unit 104 can be an extracorporeal unit located and operating outside of the body of the subject. In these embodiments, the neuromodulation unit 104 can serve as the extracorporeal device 300 and can process data received wirelessly or via physical leads from the first electrode array 102A, the second electrode array 102B, or a combination thereof.

[0077] In further embodiments, the implantable pulse generator 110 can comprise one or more batteries (e.g., rechargeable or non-rechargeable batteries). The batteries of the pulse generator 110 can be recharged via wireless inductive charging.

[0078] When the pulse generator 110 is a separate device implanted within the subject, the pulse generator 110 can be powered and activated by the extracorporeal device 300 (see, e.g.,

Figs. 2 and 3). The pulse generator 110 can be configured to be charged by the extracorporeal device 300 via electromagnetic induction when the extracorporeal device 300 is placed in proximity to the pulse generator 110, such as by holding the extracorporeal device 300 close to an implantation site of the pulse generator 110.

[0079] FIG. 4 also shows a neuromodulation unit 104 having a telemetry unit 120 or telemetry module (e.g., a telemetry hardware module, a telemetry software module, or a combination thereof). The telemetry unit 120 can be configured to analyze the electrophysiological signal detected or recorded by an electrode array by comparing the electrophysiological signal against one or more predetermined signal thresholds or patterns. For example, the neuromodulation unit 104 (or the telemetry unit 120 within the neuromodulation unit 104) can comprise one or more processors and one or more memory units. The one or more processors can be programmed to execute instructions stored in the one or more memory units to compare the electrophysiological signal against one or more predetermined signal thresholds or patterns as part of the analysis. Alternatively, or in addition, the telemetry unit 120 can receive a signal from an external monitor (e.g., 310 in FIG. 1), which is then used by the control unit 104 to control signals delivered to the endovascular carriers.

[0080] In further embodiments, the electrophysiological signal can be a signal indicating a heart rate or change in heart rate of the subject or any other measurement associated with cardiac activity. For example, the electrophysiological signal can be an electrocardiogram (ECG/EKG) signal measured by the neuromodulation unit 104 when the neuromodulation unit 104 is implanted within a pectoral region or implanted within a subclavian space of the subject.

[0081] The neuromodulation unit 104 (or the telemetry unit 120) can adjust or vary one or more signal thresholds. Moreover, the neuromodulation unit 104 can also select from different signal thresholds. For example, the neuromodulation unit 104 can raise or lower a signal threshold based the various cardiac/blood pressure measurements discussed herein.

[0082] The neuromodulation system 100 can be considered to operate in a closed-loop mode or to provide “responsive neurostimulation” when the intracorporeal target is stimulated in response to a detected measured signal. In some embodiments, the system 100 can also classify or stratify the electrophysiological signals detected or recorded into low risk, medium risk, or high risk and only generate the electrical impulse when the signal is considered medium risk or high risk.

[0083] The neuromodulation unit 104 can be configured to analyze the electrophysiological signal detected or recorded by at least one of the electrode arrays (e.g., any of the first electrode array 102A, the second electrode array 102B, or a combination thereof) and transmit an electrical impulse to the same electrode array or another electrode array via the pulse generator 110 in response to the electrophysiological signal detected or recorded.

[0084] The electrical impulse can be biphasic, monophasic, sinusoidal, or a combination thereof. The pulse generator 110 can generate the electrical impulse by increasing a current amplitude of the electrical impulse from 0 mA to up to 10 mA in 0.1 mA steps and increasing a voltage of the electrical impulse from 0 V to up to 10 V in 0.25 V steps. The electrical impulse generated can have a pulse width of between 25 pS to about 600 pS. A timing parameter of the electrical impulse can also be adjusted to allow for different stimulation timing patterns.

[0085] The electrical impulse generated can have a frequency between 1 Hz and 400 Hz. For example, a frequency of the electrical impulse can be set at a low frequency (between about 1 Hz to 10 Hz), a medium frequency (between about 10 Hz to 150 Hz), and a high frequency (between about 150 Hz to 400 Hz).

[0086] In other embodiments, the neuromodulation system 100 can operate in an open-loop mode or configuration such that the intracorporeal target is stimulated via an electrode array intermittently or periodically based on a pre-set schedule.

[0087] Figs. 5A-5D illustrates various other embodiments of endovascular carriers 108 that can be used to carry an electrode array 102 and secure the electrode array 102 to an implantation site within a vasculature of the subject.

[0088] As previously discussed, an endovascular carrier 108 can be an expandable stent or endovascular scaffold comprising an electrode array 102 coupled to the expandable stent or endovascular scaffold. The expandable stent or endovascular scaffold can comprise multiple filaments woven into a tubular-like structure.

[0089] In some embodiments, the stent or scaffold is configured to be self-expandable. For example, the stent or scaffold can self-expand from a collapsed or crimped configuration to an expanded configuration when deployed within a vasculature of the subject. For example, the stent or scaffold can self-expand into a shape or diameter pre-set to fit a particular vein, artery, or another vessel. In other embodiments, the stent or scaffold can be expanded by a balloon catheter. [0090] The electrodes 112 of the electrode array 102 can be affixed, secured, or otherwise coupled to an external boundary or radially outward portion of the expandable stent or scaffold. For example, the electrodes 112 of the electrode array 102 can be arranged along filaments making up the external boundary or radially outward portion of the expandable stent or scaffold (i.e., the part of the stent or scaffold configured to be in contact with the vessel lumen).

[0091] In some embodiments, the filaments of the expandable stent or endovascular scaffold can be made in part of a shape-memory alloy. For example, the filaments of the expandable stent or endovascular scaffold can be made in part of Nitinol (e.g., Nitinol wire). The filaments of the expandable stent or endovascular scaffold can also be made in part of stainless steel, gold, platinum, nickel, titanium, tungsten, aluminum, nickel-chromium alloy, gold-palladium-rhodium alloy, chromium-nickel-molybdenum alloy, iridium, rhodium, or a combination thereof. The filaments of the expandable stent or endovascular scaffold can also be made in part of a shape memory polymer.

[0092] When the endovascular carrier 108 is an expandable stent or endovascular scaffold carrying an electrode array 102, the entire carrier and array assembly can be referred to as a stent- electrode array 109.

[0093] The stent-electrode arrays 109 disclosed herein can be any of the stents, scaffolds, stent-electrodes, or stent-electrode arrays disclosed in U.S. Patent Pub. No. US 2014/0288667; U.S. Patent Pub. No. 2020/0078195; U.S. Patent Pub. No. 2019/0336748; U.S. Patent Pub. No. 2020/0016396; U.S. Pat. No. 10,575,783; U.S. Pat. No. 10,485,968; U.S. Pat. No. 10,729,530, U.S. Pat. No. 10,512,555; U.S. Pat. App. No. 16/457,493 filed on June 28, 2019; U.S. Pat. App. No. 62/927,574 filed on October 29, 2019; U.S. Pat. App. No. 62/932,906 filed on November 8, 2019; U.S. Pat. App. No. 62/932,935 filed on November 8, 2019; U.S. Pat. App. No. 62/935,901 filed on November 15, 2019; U.S. Pat. App. No. 62/941,317 filed on November 27, 2019; U.S. Pat. App. No. 62/950,629 filed on December 19, 2019; U.S. Pat. App. No. 63/003,480 filed on April 1, 2020; U.S. Pat. App. No. 63/057,379 filed on July 28, 2020, the contents of which are incorporated herein by reference in their entireties.

[0094] Fig. 5A illustrates another embodiment of the endovascular carrier 108 as a coiled wire 200. The coiled wire 200 can be used in vessels that are too small to accommodate the stent- electrode array 109.

[0095] The coiled wire 200 can be a biocompatible wire 202 or microwire configured to wind itself into a coiled pattern or a substantially helical pattern. The electrodes 112 of the electrode array 102 can be scattered along a length of the coiled wire 200. More specifically, the electrodes 112 of the electrode array 102 can be affixed, secured, or otherwise coupled to distinct points along a length of the coiled wire 200. The electrodes 112 of the electrode array 102 can be separated from one another such that no two electrodes 112 are within a predetermined separation distance (e.g., at least 10 pm, at least 100 pm, or at least 1.0 mm) from one another.

[0096] In some embodiments, the wire 202 or microwire can be configured to automatically wind itself into a coiled configuration (e.g., helical pattern) when the wire 202 or microwire is deployed out of a delivery catheter. For example, the coiled wire 200 can automatically attain its coiled configuration via shape memory when the delivery catheter or sheath is retracted. The coiled configuration or shape can be a preset or shape memory shape of the wire 202 or microwire prior to the wire 202 or microwire being introduced into a delivery catheter. The preset or pre trained shape can be made to be larger than the diameter of the anticipated deployment or implantation vessel to enable the radial force exerted by the coils to secure or position the coiled wire 200 in place within the deployment or implantation vessel.

[0097] In other embodiments, the coiled wire 200 can attain the coiled configuration when a pushing force is applied to the wire 202 or microwire to compel or otherwise bias the wire 202 or microwire into the coiled configuration.

[0098] As shown in Fig. 5A, the coiled wire 200 can have a wire diameter 204 and a coil diameter 206. The wire diameter 204 can be a diameter of the underlying wire 202 or microwire used to form the endovascular carrier 108. In some embodiments, the wire diameter 204 can be between about 25 pm to about 1.0 mm. In other embodiments, the wire diameter 204 can be between about 100 pm to about 500 pm.

[0099] The coil diameter 206 can be between 1.0 mm to 15.0 mm. More specifically, the coil diameter 206 can be between about 3.0 mm to about 8.0 mm (e.g., about 6.0 mm or 7.0 mm). In some embodiments, the coil diameter 206 can be between 15.0 mm to about 25.0 mm. The coil diameter 206 can be set based on a diameter of a target vessel or deployment vessel.

[0100] The wire 202 or microwire can be made in part of a shape-memory alloy, a shape- memory polymer, or a combination thereof. For example, wire 202 or microwire can be made in part of Nitinol (e.g., Nitinol wire). The wire 202 or microwire can also be made in part of stainless steel, gold, platinum, nickel, titanium, tungsten, aluminum, nickel-chromium alloy, gold- palladium-rhodium alloy, chromium-nickel-molybdenum alloy, iridium, rhodium, or a combination thereof.

[0101] Fig. 5B illustrates that a first electrode array 102A can be carried by a first coiled wire 200A and a second electrode array 102B can be carried by a second coiled wire 200B connected to the first coiled wire 200A. In this embodiment, the first coiled wire 200A can serve as the first endovascular carrier 108 A and the second coiled wire 200B can serve as the second endovascular carrier 108B. Each of the first coiled wire 200A and the second coiled wire 200B can be the same as the coiled wire 200 (see Fig. 5A) previously discussed.

[0102] The first coiled wire 200A can be connected to the second coiled wire 200B by an uncoiled segment of the wire 202 or microwire. For example, the first coiled wire 200A can be connected to the second coiled wire 200B by an uncoiled segment of the same wire 202 or micro wire used to make the first coiled wire 200A and the second coiled wire 200B.

[0103] As will be discussed in more detail in later sections, the first coiled wire 200A serving as the first endovascular carrier 108 A and the second coiled wire 200B serving as the second endovascular carrier 108B can be implanted along different segments of the same vessel or implanted within different vessels.

[0104] In some embodiments, the first electrode array 102A carried by the first coiled wire 200A can serve as a recording electrode array and the second electrode array 102B carried by the second coiled wire 200B can serve as the stimulating electrode array. In other embodiments, both the first electrode array 102A carried by the first coiled wire 200A and the second electrode array 102B carried by the second coiled wire 200B can serve as the recording electrode arrays and/or the stimulating electrode arrays.

[0105] Fig. 5C illustrates a further embodiment of the endovascular carrier 108 as an anchored wire 208. The anchored wire 208 can be used in vessels that are too small or too tortuous to accommodate either the coiled wire 200 or the stent-electrode array 109. [0106] The anchored wire 208 can comprise a biocompatible wire 202 or microwire attached or otherwise coupled to an anchor or another type of endovascular securement mechanism.

[0107] Fig. 5C illustrates that the anchored wire 208 can comprise a barbed anchor 210, a radially expandable anchor 212, or a combination thereof (both the barbed anchor 210 and the radially expandable anchor 212 are shown in broken or phantom lines in Fig. 5C).

[0108] In some embodiments, the barbed anchor 210 can be positioned at a distal end of the anchored wire 208. In other embodiments, the barbed anchor 210 can be positioned along one or more sides of the wire 202 or microwire. The barbs of the barbed anchor 210 can secure or moor the anchored wire 208 to an implantation site within the subject.

[0109] The radially expandable anchor 212 can be a segment of the wire 202 or microwire shaped as a coil or loop. The coil or loop can be sized to allow the coil or loop to conform to a vessel lumen and to expand against a lumen wall to secure the anchored wire 208 to an implantation site within the vessel. For example, the coil or loop can be sized to be larger than the diameter of the anticipated deployment or implantation vessel to enable the radial force exerted by the coil or loop to secure or position the anchored wire 208 in place within the deployment or implantation vessel.

[0110] In some embodiments, the radially expandable anchor 212 can be positioned at a distal end of the anchored wire 208. In other embodiments, the radially expandable anchor 212 can be positioned along a segment of the anchored wire 208 proximal to the distal end.

[0111] The electrodes 112 of the electrode array 102 can be scattered along a length of the coiled wire 200. More specifically, the electrodes 112 of the electrode array 102 can be affixed, secured, or otherwise coupled to distinct points along a length of the anchored wire 208. The electrodes 112 of the electrode array 102 can be separated from one another such that no two electrodes 112 are within a predetermined separation distance (e.g., at least 10 pm, at least 100 pm, or at least 1.0 mm) from one another.

[0112] Although Fig. 5C illustrates the anchored wire 208 having only one barbed anchor 210 and one radially expandable anchor 212, it is contemplated by this disclosure that the anchored wire 208 can comprise a plurality of barbed anchors 210 and/or radially expandable anchors 212. [0113] Fig. 5D illustrates an embodiment of an endovascular carrier 214 carrying different electrode arrays 102 (e.g., the first electrode array 102A and the second electrode array 102B). As shown in Fig. 5D, the endovascular carrier 214 can be the stent-electrode array 109 previously discussed. [0114] In this embodiment, two electrode arrays 102 can be coupled to the same expandable stent or endovascular scaffold. In other embodiments, three or more electrode arrays 102 can be coupled to the same expandable stent or endovascular scaffold.

[0115] Although Fig. 5D illustrates the electrodes 112 of the first electrode array 102A using dark circles and the electrodes 112 of the second electrode array 102B using white circles, it should be understood by one of ordinary skill in the art that the difference in color is only for ease of illustration.

[0116] The electrodes 112 of the first electrode array 102A can be used as dedicated recording or detection electrodes and the electrodes 112 of the second electrode array 102B can be used as dedicated stimulating electrodes. In this manner, only one endovascular carrier is needed to deploy both the recording electrode array and the stimulating electrode array. Moreover, in this embodiment, the electrodes 112 of the first electrode array 102A can record and communicate via different data or communication channels than electrodes 112 of the second electrode array 102B. [0117] Although Fig. 5D illustrates the endovascular carrier 214 as an expandable stent or scaffold, it is contemplated by this disclosure that any of endovascular carriers disclosed herein, including the coiled wire 200 and the anchored wire 208, can be used as an endovascular carrier for carrying the at least two types of electrode arrays 102.

[0118] The electrodes 112 of the electrode arrays 102 depicted in Figs. 2A-2D can be made in part of platinum, platinum black, another noble metal, or alloys or composites thereof. For example, the electrodes 112 of the electrode arrays 102 can be made of gold, iridium, palladium, a gold-palladium-rhodium alloy, rhodium, or a combination thereof. In some embodiments, the electrodes 112 can be made of a metallic composite with a high charge injection capacity (e.g., a platinum-iridium alloy or composite).

[0119] In some embodiments, the electrodes 112 can be shaped as circular disks having a disk diameter of between about 100 pm to 1.0 mm. In other embodiments, the electrodes 112 can have a disk diameter of between 1.0 mm and 1.5 mm. In additional embodiments, the electrodes 112 can be cylindrical, spherical, cuff-shaped, ring-shaped, partially ring-shaped (e.g., C-shaped), or semi -cylindrical,

[0120] The electrodes 112 can have their conductive properties enhanced by increasing the surface area of the electrodes 112 through surface roughening with chemical or electrochemical roughening methods or coating with a conductive polymeric coating such as poly(3,4- ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). [0121] Fig. 6 illustrates a variation of a system having a neuromodulation unit 104 and one endovascular carrier 108 that is implanted within the subject. The neuromodulation unit 104 have an internal power supply such as one or more rechargeable batteries. In these and other embodiments, the batteries of the neuromodulation unit 104 can be recharged by an extracorporeal device 300 via electromagnetic induction. In some embodiments, the neuromodulation unit 104 can also be activated or powered by the extracorporeal device 300 when the extracorporeal device 300 is placed in proximity to the neuromodulation unit 104 (e.g., when held up next to the implantation site of the neuromodulation unit 104).

[0122] For example, the neuromodulation unit 104 can comprise a first magnetic component 118 (e.g., a receiving or secondary coil) and the extracorporeal device 300 can comprise a second magnetic component 302 (e.g., a primary or transmission coil) configured to be magnetically coupled to the first magnetic component 118. The extracorporeal device 300 can charge or power the neuromodulation unit 104 via electromagnetic induction.

[0123] In some embodiments, the pulse generator 110 can be a standalone device separate from the neuromodulation unit 104. In these embodiments, the pulse generator 110 can also comprise a first magnetic component 118 (e.g., a receiving or secondary coil) configured to be magnetically coupled to a second magnetic component 302 (e.g., a primary or transmission coil) within the extracorporeal device 300. In these embodiments, the pulse generator 110 can be charged or powered by the extracorporeal device 300 via electromagnetic induction.

[0124] As shown in Fig. 6A, an endovascular carrier 108 is implanted within a renal artery 6 of the subject 10 where a transmission lead or cable 106 is passed from the implanted site of the pulse generator/controller 104 through a vessel wall and into the vessel. In the illustrated example, the transmission lead 106 passes into a subclavian artery 5 through a descending aorta 3 to the renal artery 6. This variation couples stent-electrode array on the carrier 108 directly to the neuromodulation unit 104 via its own transmission lead 106 or cable. In alternative variations, the stent-electrode array can be coupled to the neuromodulation unit 104 via a a wireless connection. [0125] Fig. 6 shows one variation of how a system under the present disclosure can operate as a closed-loop system. The implanted neuromodulation unit 104 can be receive signals from a monitoring device (e.g., 310 in FIG. 1 or a separate extracorporeal device 300, 302, 306, 308). In additional variations, a monitoring device (not shown) can be implanted and directly coupled to the pulse neuromodulation unit 104. Regardless, the neuromodulation unit 104 acts as a controller that applies a regimen of non-ablative energy from the energy delivery components of the endovascular carrier 108 to the renal artery 6 to affect the kidney(s) 2 to produce an altered blood pressure for the patient 10. The controller of the pulse generator 10 can continue to monitor the altered blood pressure for a period of time and then further assess the altered blood pressure after the period of time to determine an effect of the regimen of non-ablative energy. The neuromodulation unit 104 then adjusts at least one parameter of the regimen of non-ablative energy based on the assessment of the altered blood pressure. In this manner, the system operates as a closed loop system for manipulation of autonomic nervous system to cause a change in blood pressure.

[0126] Fig. 6 also illustrates that the extracorporeal device 300 can also be implemented as a portable handheld device 304, a wand 306, or a wearable device 308 (e.g., bracelet or watch). In addition to monitoring blood pressure, the extracorporeal device 300 can be used to recharge one or more batteries within the neuromodulation unit 104, the pulse generator 110, or a combination thereof. In some embodiments, the extracorporeal device 300 can be used to activate the pulse generator 110 to transmit an electrical impulse to the stimulating electrode array.

[0127] FIGS. 7 A to 7E show variations of an endovascular carrier 108 with a plurality of electrodes 131 in various patterns. In the arrangement shown in FIG. 7 A, the device 108 includes nine electrodes patterns on the stent lattice 128 in a linear pattern. As shown, the stent lattice 128 is illustrates in a planar view. The stent lattice 128 can be a closed cylindrical shape, where both longitudinal sides are joined to form a cylinder shape. Alternatively, the stent lattice 128 can be an open configuration, where the two longitudinal sides

[0128] Alternatively, an endovascular carrier 108 can have any number of electrode 131 patterns arranged in any desired configuration. For example, the electrodes can be configured as follows: the sinusoidal arrangement of electrodes 131 shown in FIG. 7B; the spiral arrangement of electrodes 131 shown in Fig. 7C to enable 360 degree contact of an electrode to the vessel wall once deployed; the reduced amplitude sinusoidal arrangement of electrodes 131 shown in Fig. 7D for increased coverage whilst still ensuring only one stent is at each vertical segment; and the dense arrangement of electrodes shown in Fig. 7E for increased coverage. The stent lattice 128 can be configured in a manner such that there is additional material or markers where the electrodes 131 are to be placed to assist with attachment of electrodes and uniformity of electrode locations. For example, if a stent lattice 128 is fabricated by laser cutting material away from a cylindrical tube (original form of stent), and, for example, electrodes are to be located at 5mm intervals on the one axis, then electrode mounting platforms can be created by not cutting these areas from the tube. Similarly, if the stent is made by wire wrapping, then additional material can be welded or attached to the stent wires providing a platform on which to attach the electrodes. Alternatively, stents can be manufactured using thin-film technology, whereby material (Nitinol and or platinum and or other materials or combinations of) is deposited in specific locations to grow or build a stent structure and/or electrode array

[0129] To enhance contact and functionality of the device 108, electrodes 131 include the attachment of additional material (shape memory alloy or other conducting material) through soldering, welding, chemical deposition and other attachment methods to the stent 128 including but not limited to: directly on or between the stent struts 128; to lead wires passing from the electrodes 131 to wireless telemetry links or circuitry; and directly to an lead 106on the distal aspect of the device 108.

[0130] The electrodes 131 can be made from electrically conductive material and attached to one or more stents, which form the device 108 and allow for multiple positions. In this embodiment, the electrodes 131 are made from common electrically active materials such as platinum, platinum-iridium, nickel-cobalt alloys, or gold, and may be attached by soldering, welding, chemical deposition and other attachment methods to one or more lead wires 141, which may be directly attached to the shape memory shaft(s). The electrodes 131 are preferably one or more exposed sections on the insulated lead wire 141 and the electrode lead wires may be wrapped around one or more shape memory backbones. There may be one or more electrodes and lead wires wrapped around a single shape memory backbone, and, where multiple shape memory backbones are used in the one device, the backbones may have different initial insertion and secondary deposition positions. Thus, they may be used for targeting multiple vessels simultaneously.

[0131] Fig. 8A illustrates a variation of a endovascular carrier 128 that can be fabricated where stent structure comprises an integrated conductive layer that extends through a portion or more of the stent stmt 128 and where the electrode 131 is formed through an exposed portion of the integrated conductive layer. Such a stent configuration, as described in detail below, permits a stent 128 electrode 131 assembly, which embeds electrodes and conductive electrode tracks into the stent lattice or stmt itself. Such a constmction reduces or eliminates the requirement to use fixation methods (i.e., adhesives, glues, fasteners, welds, etc.) to mount electrodes to the body of the stent. Such a constmction further reduces or eliminates the need to further weld or electrically connect electrodes to wires. Another benefit is that conventional wire -connected-electrodes require accommodation of the wires about the stent struts and through the body of the stent. [0132] Fig. 8B illustrates a stent structure 128 with integrated electrodes 131, where the stent lattice 128 is coupled to a lead 106 at a distal end 146. The shaft, as described herein, can electrically couple the electrodes 131 to one or more control units (not shown) as described herein. In one example, the lead 106 can comprise a guidewire, push wire other tubular structure that contains wires or conductive members extending therein and are coupled to the conductive layer of the stent at the distal end 146. Alternatively, Figures 9C and 9D shows a variation of stents 128 that can be fabricated such that the lead 106 is part of or integral with the stent structure, where the conductive layer extends through a portion or all of the stent to the lead 106. Such a construction further eliminates the need for joining the shaft to the stent structure at the working end of the stent. Instead, the joining of the stent structure (forming the shaft) to a discrete shaft can be moved proximally along the device. Such a construction allows the working end of the stent and shaft to remain flexible. Fig. 8C further illustrates a hollow lead 106, which allows insertion of a stylet 123 therethrough to assist in positioning of the device or permits coupling of wires or other conductive members therethrough. Furthermore, the lead 106 can include any number of features 119 that improve flexibility or pushability of the shaft through the vasculature. [0133] The electrical connection of the electrodes 131 to leads extending through the device can be accomplished by the construction of one or more connection pads (similar in construction to the electrodes described below) where the size of the pads ensures sufficient contact with the wire/lead, the type of pads ensures robustness and reduces track fatigue when crimped and attached. The section containing the pads can be compressed into a tube at, for example, distal section 146 to enable insertion of a cable 121.

[0134] In certain variations, the connection pads should be able to feed through the catheter. Furthermore, the connection pads 132 can include one or more holes or openings that enable visual confirmation that the pads are aligned with contacts on the lead. These holes/openings also enables direct/laser welding or adhesion of the contact leads (inside tube 121) and the contact pads (on the inside of the tube spanning through the hole to the outside)

[0135] In one example, a coaxial-octofilar cable (i.e. an inner cable with 8 wires positioned inside an outer cable having 8 wires) is used to enhance fatigue resistance and to ensure that wires can fit within constraints (i.e., can be inserted through a sufficiently small catheter, and can have an internal stylet as required). [0136] Figs. 8A-8Dillustrate some examples of a stent lattice structure 128 constructed with an embedded electrode and conductive path. Fig. 8A illustrates an example of a stent structure 128 in a planar configuration with electrodes 131 in a linear arrangement for purposes of illustration only. Clearly, any configuration of electrodes is within the scope of this disclosure. Specifically, in those variations of stent structures useful for neurological applications, the stent structure can comprise a diameter that is traditionally greater than existing neurological stents. Such increased diameter can be useful due to the stent structure being permanently implanted and while requiring apposition of electrodes against the vessel/tissue wall. Moreover, in some variations, the length of such stent structures can include lengths up to and greater than 20mm to accommodate desired placement along the human motor cortex. For example, variations of the device require a stent structure that is sufficiently long enough to cover the motor cortex and peripheral cortical areas. Such lengths are not typically required for existing interventional devices aimed at restoring flow or addressing aneurysms or other medical conditions. In addition, in certain variations, the electrical path between certain electrodes can be isolated. In such a case, the electrically conductive material 50 can be omitted from certain stent struts to form a pattern that allows an electrode to have an electrical conduction path to a contact pad or other conductive element but the electrical conduction path is electrically isolated from a second electrode having its own second electrically conductive path.

[0137] Placement of the electrodes in a specific pattern (e.g., a corkscrew configuration or a configuration of three linear (or corkscrew oriented) lines that are oriented 120 degrees from each other) can ensure a deployed electrode orientation that directs electrodes towards the brain. Once implanted, orientation is not possible surgically (i.e., the device will be implanted and will be difficult if not impossible to rotate). Therefore, variations of the device will be desirable to have an electrode pattern that will face towards the desired regions of the brain upon delivery.

[0138] Electrode sizing should be of a sufficient size to ensure high quality recordings and give large enough charge injection limits (the amount of current that can be passed through the electrodes during stimulation without damaging the electrodes which in turn may damage tissue). The size should also be sufficient to allow delivery via a catheter system.

[0139] Fig. 9B and 9C illustrates a cross-sectional view of the stent structure of Fig. 9A taken along line 9B-9B to further illustrate one variation of a manufacturing technique of using MEMS (microelectrical mechanical systems) technology to deposit and structure thin film devices to fabricate a stent structure with electrodes and a conductive path embedded into the stent lattice or struts. The spacing of the struts in Figs. 9B and 9C are compressed for illustrative purposes only. [0140] As discussed above, embedding the electrode and conductive path presents advantages in the mechanical performance of the device. Furthermore, embedding of electrodes provides the ability to increase the number of electrodes mounted on the structure give that the conductive paths (30-50 pm x 200-500nm) can be smaller than traditional electrode wires (50-100 pm). [0141] Manufacture of thin-film stents can be performed by depositing Nitinol or other superelastic and shape memory materials (or other materials for deposition of electrodes and contacts (including but not limited to gold, platinum, iridium oxide) through magnetron sputtering in a specific pattern (56) using a sacrificial layer (58) as a preliminary support structure. Removal of the support structure (54) enables the thin film to be further structured using UV-lithography and structures can be designed with thicknesses corresponding with radial force required to secure the electrodes against a vessel wall.

[0142] Electrical insulation of electrodes is achieved by RF sputtering and deposition of a non-conductive layer (52) (eg, SiO) onto the thin-film structure (54). Electrodes and electrode tracks (50) are sputter deposited onto the non-conductive layer (using conductive and biomedically acceptable materials including gold, Pt, Ti, NiTi, Ptlr), with an additional non- conductive layer deposited over the conductive track for further electrical isolation and insulation. As shown, conducting path 50 is left exposed to form the electrode 131 (similarly, a contact pad area can remain exposed). Finally, the sacrificial layer 56 and substrate are removed leaving the stent structure 128 as shown in Fig. 9C.

[0143] In certain variations where the base structure 54 comprises superelastic and shape- memory materials (i.e. Nitinol), the stent structure 128 can be annealed in a high vacuum chamber to avoid oxidation during the annealing process. During heat treatment, the amorphous Nitinol structure 54 crystallizes to obtain superelasticity and can be simultaneously shape set into a cylindrical or other shape as desired. The structure 128 can then be heat treated.

[0144] Fig. 10A, which is a partial sectional view of taken along lines 10A-10A of FIG. 10B, illustrate an additional variation of a stent structure 128 fabricated via MEMS technology where one or more stent struts 128 can be dimensionally altered to impart desired structural or other aspects to the stent structure 128. For example, in the illustrated variation, certain stent struts 128 are dimensionally altered such that the support material 60 comprises a greater thickness than adjacent stent structures 128. However, such dimensional variation is not limited to thickness but can also include width, shape, etc.

[0145] Fig. 10B illustrates the stent structure 128 resulting from the dimensionally altered struts formed by 60 having a greater thickness than struts formed by 54 resulting in a sinusoidal pattern of the stent lattice 128 that comprises a greater stiffness (resulting from the increased thickness). Such a configuration allowing the stent device to be pushed through a catheter rather than conventional requirements to be unsheathed (where the sheath is pulled back over the stent). Conventional stents are made from a thin lattice of Nitinol diamonds or cells. This sinusoidal section can function like a backbone and gives forward pushing strength to the device without restricting super-elasticity and the ability for the stent to compress and expand. Clearly, any number of variations of dimensionally altered strut sections are within the scope of this disclosure. [0146] FIG. 11 illustrates an example of endovascular carrier 108 with a magnified view of struts 128 designed as discussed above. FIG. 11 also shows one or more electrically conductive channels 252, 254 that extend along a length of the strut 128. Although two channels 252, 254 are shown separated by an electrically insulative divider 256, a single channel can extend in a strut 128 or more than 2 channels.

[0147] In the variation shown in FIG. 11, the channels 252, 254 can function as electrode tracks such that any length of the stent (e.g., various portions as noted above, or the entire length of the endovascular carrier) can be used for attraction along the channels 252, 254, while the remainder of the endovascular carrier has on electrical charge. Such a construction increases the useful/usable length of the endovascular carrier. Again, the variation shown in FIG. 11 is one variation that allows a single or parallel tracks (where parallel tracks 252, 254 can opposite poles) through which to attract debris.

[0148] The tracks can remain uninsulated and be used to attract debris across the length of the stent and over the entire circumference of the stent. In another variation, a single track could be used or multiple tracks can be used.

[0149] Figs. 12A-12C illustrate one embodiment of a transmission lead 106 used to connect the electrode array 102 to the neuromodulation unit 104, the pulse generator 110, or a combination thereof. For example, the transmission lead 106 can be used to connect the first electrode array 102A or the second electrode array 102B to the neuromodulation unit 104, the pulse generator 110, or a combination thereof. [0150] As shown in Figs. 12A-12C, the transmission lead 106 can comprise at least one variable length segment 400 in between the endovascular carrier 108 and a transmission segment 402. A segment length 404 of the variable length segment 400 can be adjusted (e.g., shortened or lengthened) after the transmission lead 106 is deployed within a bodily vessel (e.g., vein, artery, or sinus) of the subject.

[0151] The transmission segment 402 can be a proximal segment of the transmission lead 106 configured to connect or plug in to the neuromodulation unit 104 (e.g., into the header portion 114 of the neuromodulation unit 104). The transmission segment 402 can be made of one or more conductive wires without shape memory. For example, the transmission segment 402 can be made in part of platinum wire or platinum-iridium wire. The transmission segment 402, along with other segments of the transmission lead 106, can be covered by an insulator (e.g., polyurethane) or insulating coating.

[0152] Figs. 12A-12C illustrate that the variable length segment 400 can be connected or coupled to a proximal end of the endovascular carrier 108. For example, the endovascular carrier 108 can be a coiled wire 200 and the variable length segment 400 can be connected or coupled directly to the proximal end of the coiled wire 200.

[0153] The variable length segment 400 of the transmission lead 106 can be made in part of a shape-memory alloy. The variable length segment 400 of the transmission lead 106 can also be made of a composite material comprising a shape-memory alloy. For example, the variable length segment 400 of the transmission lead 106 can be made in part of Nitinol (e.g., Nitinol wire). In some embodiments, the variable length segment 400 of the transmission lead 106 can be made of composite clad wire or a Nitinol wire having a conductive (e.g., gold or platinum) wire core. [0154] Fig. 12A illustrates the shape of the coiled wire 200 and the transmission lead 106 when constricted within a delivery catheter or sheath. Fig. 12B illustrates the shape of the coiled wire 200 and the transmission lead 106 when the coiled wire 200 and the transmission lead 106 are deployed out of the delivery catheter or when the delivery catheter or sheath is retracted. [0155] As shown Fig. 12B, the variable length segment 400 of the transmission lead 106 can be configured to automatically recover a preset or pretrained shape. In some embodiments, the preset or pretrained shape can be a coiled configuration having loosely wound coils or coils with a larger pitch or less turns than the coils of the coiled wire 200. The variable length segment 400 can automatically attain its loosely coiled configuration via shape memory when a delivery catheter or sheath carrying the variable length segment 400 is retracted. [0156] In certain embodiments, the preset or pretrained shape of the coils formed by the variable length segment 400 can have a coil diameter less or smaller than the diameter of the anticipated deployment or implantation vessel. This ensures that the radial forces exerted by the coils on the vessel lumen walls do not prevent the coils of the variable length segment 400 from shifting, contracting, or expanding within the bodily vessel of the subject. In some instances, this contraction and expansion can allow the segment length 404 of the variable length segment 400 to vary (e.g., shorten or lengthen). For example, the variable length segment 400 can lengthen by pulling on a proximal (or distal) end of the variable length segment 400. The variable length segment 400 can be shortened by pushing on a proximal end of the variable length segment 400 when an endovascular carrier 108 coupled to a distal end of the variable length segment 400 is implanted or otherwise secured within a deployment vessel. The variable length segment 400 can also be shortened by pushing on a distal end of the variable length segment 400 when an endovascular carrier 108 coupled to a proximal end of the variable length segment 400 is implanted or otherwise secured within a deployment vessel.

[0157] In some embodiments, the variable length segment 400 can attain a coiled configuration when or only when a pushing force is applied to the variable length segment 400 to compel or urge the variable length segment 400 into the coiled configuration.

[0158] In further embodiments, the variable length segment 400 can have little or no shape memory and the variable length segment 400 can be a segment of the transmission lead 106 configured to curl up or deform when a pushing force is applied to the variable length segment 400.

[0159] One technical problem faced by the applicants is how to design an implantable neuromodulation system comprising endovascular carriers connected or coupled by transmission leads when the distance between such endovascular carriers or the distance between such endovascular carriers and an implantable neuromodulation unit or pulse generator differs by patient or treatment regimen. For example, differences in neck and torso lengths among subjects and where such endovascular carriers are implanted within each subject requires a neuromodulation system that can adapt to different sized anatomy and different implantation requirements. One advantage of the neuromodulation system 100 disclosed herein is the unique transmission leads 106 comprising the variable length segment 400 disclosed herein that can allow the neuromodulation system 100 to be adapted to different sized patients and patients with different implantation requirements. [0160] In some embodiments, the transmission lead 106 can have a lead diameter of between 0.5 mm and 1.5 mm. More specifically, the transmission lead 106 can have a lead diameter of between 0.5 mm and 1.0 mm.

[0161] In some embodiments, the transmission lead 106, or segments thereof, can be covered by an insulator or insulating coating. For example, the transmission lead 106, or segments thereof, can be covered by polyurethane or a polyurethane coating.

[0162] In some embodiments, at least a segment of the transmission lead 106 can be a cable comprising multiple conductive wires or transmission wires coupled to the various electrodes 112 of the electrode array 102. For example, the transmission lead 106 can be a stranded cable comprising a plurality of conductive wires twisted and bundled together and covered by an insulator or insulating material.

[0163] Figs. 13A-13C illustrate an example method of implanting an embodiment of an electrode array 102 (e.g., any of the first electrode array 102A or the second electrode array 102B). The method can be used when an intracorporeal target 500 is close to but not adjacent to a vessel 502 used to deliver or deploy the electrode array 102.

[0164] As shown in Figs. 13A and 13B, when a delivery catheter 504 is moved into position near a vessel wall 506, an endovascular carrier 108 carrying the electrode array 102 can be deployed out of the delivery catheter 504. In the embodiment shown in Figs. 13A-13C, the endovascular carrier 108 can be an anchored wire 208 having the electrode array 102 coupled along a segment of a biocompatible wire 202 or microwire.

[0165] The wire 202 or microwire can comprise a sharp distal end in the form of a penetrating barb 508 or penetrating anchor coupled or detachably coupled to the distal end of the wire 202 or microwire. The penetrating barb 508 or penetrating anchor can allow the wire 202 or microwire to penetrate or create a puncture in the vessel wall 506 to allow the wire 202 or microwire to extend through the vessel wall 506. The wire 202 or microwire can then direct the electrode array 102 closer to the intracorporeal target 500 (e.g., the target nerve or brain region) such that the electrode array 102 is positioned at or in close proximity to the intracorporeal target 500.

[0166] Fig. 13C illustrates that once the delivery catheter 504 is retracted, a wire segment 510 proximal to the electrode array 102 can automatically take the shape of a coil. The coil shape of the wire segment 510 can be pre-set prior to being introduced into the delivery catheter 504. For example, the wire segment 510 can have a lead diameter of about 1.0 mm (or less than 1.0 mm) and the vessel 502 can have a vessel diameter of about 6.0 mm. Once the delivery catheter 504 is removed, the wire segment 510 can take the shape of a coil having a coil diameter of greater than 6.0 mm. The wire segment 510 can self-expand until the coil pushes against the internal vessel walls to secure the wire segment 510 to the internal vessel walls. In this embodiment, the wire segment 510 proximal to the electrode array 102 can be used to also secure the endovascular carrier 108. With the wire segment 510 and the electrode array 102 in place, the penetrating barb 508 can be removed by a stylet or other device extending through the delivery catheter 504.

[0167] Fig. 14 illustrates an embodiment of a delivery catheter 1300 comprising a first endovascular carrier 108A and a second endovascular carrier 108B connected by a bifurcated transmission lead 1302. As shown in Fig. 14, a first branch 1304 of the bifurcated transmission lead 1302 can be connected or coupled to the first endovascular carrier 108 A and a second branch 1306 of the bifurcated transmission lead 1302 can be connected or coupled to the second endovascular carrier 108B. At least one guide wire 1308 can extend alongside at least one of the branches of the bifurcated transmission lead 1302. The guide wire 1308 can extend through a lumen of one of the endovascular carriers 108 (e.g., the second endovascular carrier 108B) and be detachably coupled to a tip 1310 of the endovascular carrier 108.

[0168] Another method of deploying or delivering the endovascular carriers 108 (e.g., the first endovascular carrier 108A and the second endovascular carrier 108B) to their respective implantation sites can comprise deploying the delivery catheter 1300 through a jugular incision to the superior sagittal sinus 900. The delivery catheter 1300 can be deployed under angiographic guidance.

[0169] A first endovascular carrier 108 A carrying a first electrode array 102A (not shown in Fig. 13, see Fig. 1) can be deployed or otherwise delivered through the delivery catheter 1300. For example, the first endovascular carrier 108A can be a stent-electrode array 109 configured to self- expand into position within the superior sagittal sinus 900.

[0170] In some embodiments, the first electrode array 102A coupled to the first endovascular carrier 108A can be used as a recording electrode array. In other embodiments, the first electrode array 102A can be used as a stimulating electrode array or both a recording electrode array and a stimulating electrode array. Once the first endovascular carrier 108A is positioned in place, the delivery catheter 1300 can be retracted proximally and a second endovascular carrier 108B carrying a second electrode array can be deployed through the retracted delivery catheter 1300 into a second implantation site (e.g., the internal cerebral vein 926 overlying the anterior nucleus of thalamus 932 of the subject). The guidewire 1308 can be used to guide the second endovascular carrier 108 into place within the second implantation site.

[0171] For example, the second endovascular carrier 108B can be a stent-electrode array 109 configured to self-expand into position within a deployed vessel such as the internal cerebral vein 926. In some embodiments, the second electrode array 102B coupled to the second endovascular carrier 108B can be used as a stimulating electrode array. In other embodiments, the second electrode array 102B can be used as a recording electrode array or both a stimulating electrode array and a recording electrode array. Once the second endovascular carrier 108B is positioned in place, the delivery catheter 1300 and the guidewire 1308 can be removed from the vasculature of the subject.

[0172] Retracting the delivery catheter 1300 can expose the bifurcated transmission lead 1302 connecting the first endovascular carrier 108 A to the second endovascular carrier 108B. The transmission lead 1302 can extend through the neck of the subject (e.g., through a jugular vein) and a proximal end of the transmission lead 1302 can be inserted into a neuromodulation unit 104 implanted within the subject.

[0173] One technical advantage of the closed-loop neuromodulation system 100 disclosed herein is that the system 100 can be delivered through a minimally invasive procedure, via angiography, to a vessel near an intracorporeal/stimulation target (e.g., renal nerves) without physically contacting or potentially causing damage to the intracorporeal/stimulation target.

[0174] Yet another technical advantage of the neuromodulation system 100 disclosed herein is that the system 100 can provide a closed-loop or responsive stimulation whereby a signal from the subject is detected or otherwise acquired and used as the impetus to trigger the electrical stimulation. An added advantage of the system operating in a closed-loop or responsive mode is that the battery life of the various electronic components of the system can be extended such that such electronic components are only activated when a seizure is imminent or when the subject is observed to be in a high seizure risk state.

[0175] A number of embodiments have been described. Nevertheless, it will be understood by one of ordinary skill in the art that various changes and modifications can be made to this disclosure without departing from the spirit and scope of the embodiments. Elements of systems, devices, apparatus, and methods shown with any embodiment are exemplary for the specific embodiment and can be used in combination or otherwise on other embodiments within this disclosure. For example, the steps of any methods depicted in the figures or described in this disclosure do not require the particular order or sequential order shown or described to achieve the desired results. In addition, other steps operations may be provided, or steps or operations may be eliminated or omitted from the described methods or processes to achieve the desired results. Moreover, any components or parts of any apparatus or systems described in this disclosure or depicted in the figures may be removed, eliminated, or omitted to achieve the desired results. In addition, certain components or parts of the systems, devices, or apparatus shown or described herein have been omitted for the sake of succinctness and clarity.

[0176] Accordingly, other embodiments are within the scope of the following claims and the specification and/or drawings may be regarded in an illustrative rather than a restrictive sense. [0177] Each of the individual variations or embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other variations or embodiments. Modifications may be made to adapt a particular situation, material, composition of matter, process, process act(s) or step(s) to the objective(s), spirit or scope of the present invention.

[0178] Methods recited herein may be carried out in any order of the recited events that is logically possible, as well as the recited order of events. Moreover, additional steps or operations may be provided, or steps or operations may be eliminated to achieve the desired result.

[0179] Furthermore, where a range of values is provided, every intervening value between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. Also, any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein. For example, a description of a range from 1 to 5 should be considered to have disclosed subranges such as from 1 to 3, from 1 to 4, from 2 to 4, from 2 to 5, from 3 to 5, etc. as well as individual numbers within that range, for example 1.5, 2.5, etc. and any whole or partial increments therebetween.

[0180] All existing subject matter mentioned herein (e.g., publications, patents, patent applications) is incorporated by reference herein in its entirety except insofar as the subject matter may conflict with that of the present invention (in which case what is present herein shall prevail). The referenced items are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such material by virtue of prior invention. [0181] Reference to a singular item, includes the possibility that there are plural of the same items present. More specifically, as used herein and in the appended claims, the singular forms “a,” “an,” “said” and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements or use of a “negative” limitation. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0182] Reference to the phrase “at least one of’, when such phrase modifies a plurality of items or components (or an enumerated list of items or components) means any combination of one or more of those items or components. For example, the phrase “at least one of A, B, and C” means: (i) A; (ii) B; (iii) C; (iv) A, B, and C; (v) A and B; (vi) B and C; or (vii) A and C.

[0183] In understanding the scope of the present disclosure, the term “comprising” and its derivatives, as used herein, are intended to be open-ended terms that specify the presence of the stated features, elements, components, groups, integers, and/or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and/or steps. The foregoing also applies to words having similar meanings such as the terms, “including”, “having” and their derivatives. Also, the terms “part,” “section,” “portion,” “member” “element,” or “component” when used in the singular can have the dual meaning of a single part or a plurality of parts. As used herein, the following directional terms “forward, rearward, above, downward, vertical, horizontal, below, transverse, laterally, and vertically” as well as any other similar directional terms refer to those positions of a device or piece of equipment or those directions of the device or piece of equipment being translated or moved.

[0184] Finally, terms of degree such as “substantially”, “about” and “approximately” as used herein mean the specified value or the specified value and a reasonable amount of deviation from the specified value (e.g., a deviation of up to ±0.1%, ±1%, ±5%, or ±10%, as such variations are appropriate) such that the end result is not significantly or materially changed. For example,

“about 1.0 cm” can be interpreted to mean “1.0 cm” or between “0.9 cm and 1.1 cm.” When terms of degree such as “about” or “approximately” are used to refer to numbers or values that are part of a range, the term can be used to modify both the minimum and maximum numbers or values. [0185] This disclosure is not intended to be limited to the scope of the particular forms set forth, but is intended to cover alternatives, modifications, and equivalents of the variations or embodiments described herein. Further, the scope of the disclosure fully encompasses other variations or embodiments that may become obvious to those skilled in the art in view of this disclosure.

Claims

CLAIMS We Claim:

1. A system for affecting an autonomous nervous system in a human patient to affect an initial blood pressure of the patient, the system comprising: a first energy delivery device configured for positioning within a renal artery of at least one kidney of the patient; a blood pressure monitoring device configured to monitor a blood pressure of the patient; and a controller configured to apply a regimen of non-ablative energy from the energy delivery device to the renal artery to affect the kidney to produce an altered blood pressure of the patient, and to monitor the altered blood pressure for a period of time, the controller further configured to assess the altered blood pressure after the period of time to determine an effect of the regimen of non-ablative energy and adjust at least one parameter of the regimen of non ablative energy based on the assessment of the altered blood pressure.

2. The system of claim 1 , where the controller is further configured to apply the regimen in a closed loop system.

3. The system of claim 1, where the controller is configured to produce the altered blood pressure to be lower than the initial blood pressure in order to treat hypertension.

4. The system of claim 1 , where the controller is configured to produce the altered blood pressure to be higher than the initial blood pressure in order to treat hypotension.

5. The system of claim 1, where the controller is configured to automatically assess the altered blood pressure after the period of time and adjust the regimen of non-ablative energy based on the assessment of the altered blood pressure.

6. The system of claim 1, where the controller is configured to permit manual adjustment of the regimen of non-ablative energy.

7. The system of claim 1, where the blood pressure monitoring device comprises one or more sensors configured to be positioned within a vasculature of the patient.

8. The system of claim 7, wherein the one or more sensors are positioned on or adjacent to the energy delivery device.

9. The system of claim 1, wherein the energy delivery device is an expandable stent structure.

10. The system of claim 9, wherein the expandable stent structure comprises a frame structure forming a plurality of struts, where the frame structure is moveable between a reduce profile and an expanded profile in which a diameter of the frame structure increases; where at least one of the plurality of struts forming the frame structure comprises an electrically conductive material on a support material, the electrically conductive material extending along at least a portion of the strut and being covered with a non-conductive material.

11. The system of claim 10, wherein the expandable stent structure comprises at least one electrode located in an opening in the non-conductive material on the portion of the strut.

12. The system of claim 1, further wherein the controller comprises an implanted pulse generator configured to be implanted located in a body of the patient.

13. The system of claim 12, further comprising a first conductive lead coupling the implanted pulse generator to the energy delivery, where the conductive lead is configured to extend through a vasculature of the patient.

14. The system of claim 15, further comprising at least one additional energy delivery device configured for positioning within the vasculature of the patient and where the controller is configured to apply the regimen of non-ablative energy from the energy device and the at least one additional energy delivery device into the renal artery to affect the kidney to produce the altered blood pressure of the patient.

15. The system of claim 14, further comprising a second conductive lead coupling the controller to the at least one additional energy delivery device.

16. The system of claim 15, further comprising a common conductive lead having a bifurcation section separating the first conductive lead from the second conductive lead.

17. The system of claim 12, further comprising an extracorporeal device configured to communicate with the implanted pulse generator.

18. The system of claim 17, wherein the pulse generator comprises a first magnetic component, and wherein the extracorporeal device comprises a second magnetic component configured to be magnetically coupled to the first magnetic component, and wherein the pulse generator is configured to be charged by the extracorporeal device via electromagnetic induction when the extracorporeal device is placed in proximity to the pulse generator.

19. The system of claim 1, wherein the first energy delivery device comprises a wire or cable configured to be wound or coiled comprising an electrode array coupled to the wire or cable.

20. The system of claim 1 , wherein the first energy delivery device comprises a wire or cable comprising a sharp distal end for penetrating through the renal artery wall.

21. The system of claim 1, wherein the first energy delivery device comprises an anchor, and wherein the anchor is at least one of a barbed anchor and a radially-expandable anchor.

22. The system of claim 1 , wherein the controller further comprises a telemetry unit, wherein the telemetry unit is configured to analyze the electrophysiological signal detected by comparing the electrophysiological signal against one or more signal thresholds or patterns.

23. A method for treating a human patient to affect an initial blood pressure of the patient, the method comprising: positioning an energy delivery device within a renal artery of at least one kidney of the patient; applying a regimen of non-ablative energy from the energy delivery device to the renal artery to affect the kidney to produce an altered blood pressure of the patient; monitoring the altered blood pressure for a period of time; assessing the altered blood pressure after the period of time to determine an effect of the regimen of non-ablative energy; and adjusting at least one parameter of the regimen of non-ablative energy based on the assessment of the altered blood pressure.

24. The method of claim 23, where applying the regimen of non-ablative energy is performed as a closed loop system

25. The method of claim 23, wherein an implanted pulse generator delivers a signal to the energy delivery device for the regimen of non-ablative energy.

26. The method of claim 23, further comprising a first conductive lead coupling the implanted pulse generator to the energy delivery, where the first conductive lead extends through a vasculature of the patient.

27. The method of claim 23, wherein the implantable pulse generator is placed in the infraclavicular pectoral region, with the first conductive lead entering a subclavian artery and where the first conductive lead extends to the energy delivery device located in a renal artery, via an aortic arch and a descending aorta

28. The method of claim 23, wherein the altered blood pressure is lower than the initial blood pressure in order to treat hypertension.

29. The method of claim 23, wherein the altered blood pressure is higher than the initial blood pressure in order to treat hypotension.

30. The method of claim 23, wherein the energy delivery device is electrically coupled to an implanted pulse generator located in a body of the patient and controls the regimen of non ablative energy.

31. The method of claim 30, wherein the implanted pulse generator is coupled to the energy delivery using a conductive lead.

32. The method of claim 31 , where the conductive lead extends through a vasculature of the patient.

33. The method of claim 23, where assessing the altered blood pressure after the period of time and adjusting the regimen of non-ablative energy based on the assessment of the altered blood pressure is automatically performed by a monitoring device in electrical communication with the implanted pulse generator.

34. The method of claim 23, assessing the altered blood pressure after the period of time and adjusting the regimen of non-ablative energy based on the assessment of the altered blood pressure is manually performed by a physician.

35. The method of claim 23, where monitoring the altered blood pressure comprises monitoring the altered blood pressure using one or more sensors positioned within a vasculature of the patient.

36. The method of claim 35, wherein one or more sensors are positioned on or adjacent to the energy delivery device.

37. The method of claim 23, where the energy delivery device is implanted using a vascular approach.

38. The method of claim 37, wherein the energy delivery device is an expandable stent structure.

39. The method of claim 38, wherein the expandable stent structure comprises a frame structure forming a plurality of struts, where the frame structure is moveable between a reduce profile and an expanded profile in which a diameter of the frame structure increases; where at least one of the plurality of struts forming the frame structure comprises an electrically conductive material on a support material, the electrically conductive material extending along at least a portion of the strut and being covered with a non-conductive material.

40. The method of claim 39, wherein the expandable stent structure comprises; at least one electrode formed by an opening in the non-conductive material on the portion of the strut.

41. The method of claim 39, the electrical effect comprises at least a portion of the non- conductive material creating a capacitive effect between at least a portion of the electrically conductive material and the blood vessel.

42. The method of claim 23, further comprising placing at least one additional energy delivery device within the vasculature of the patient and where applying a regimen of non-ablative energy from the energy delivery device into the renal artery to affect the kidney to produce the altered blood pressure of the patient comprises applying the regimen using the energy delivery device and the at least one additional energy delivery device.

43. The method of claim 42, wherein placing at least one additional energy delivery device within the vasculature comprises positioning the at least one additional energy delivery device within a second renal artery.