Endovascular neuromodulation therapy programming

Abstract

A system includes processing circuitry configured to: receive, via sensing circuitry, a plurality of evoked compound action potential (ECAP) signals elicited by electrical stimulation and sensed via a first electrode combination including at least a first electrode of an array of electrodes disposed within a blood vessel; receive, via the sensing circuitry, a plurality of physiological signals via a second electrode combination including at least a second electrode of the array of electrodes; determine an ECAP characteristic value for each ECAP signal of the plurality of ECAP signals; determine a physiological signal characteristic value for each physiological signal of the plurality of physiological signals; and select, based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, one or more stimulation parameters that at least partially define subsequent electrical stimulation therapy.

Description

ENDOVASCULAR NEUROMODULATION THERAPY PROGRAMMINGCROSS-RELATED CLAIMS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 659,176, filed June 24, 2024, which is incorporated herein by reference in its entirety.TECHNICAL FIELD

[0002] This disclosure generally relates to electrical stimulation therapy.BACKGROUND

[0003] Medical devices such as electrical stimulation devices, may be used in different therapeutic applications, such as vagus nerve stimulation (VNS) and / or deep brain stimulation (DBS). A medical device may be used to deliver therapy to a patient to treat a variety of symptoms or patient conditions. In some therapy systems, an external or an implantable electrical stimulator delivers electrical stimulation therapy to a target tissue site within a patient via one or more electrodes and / or senses one or more patient parameters via one or more electrodes.SUMMARY

[0004] In general, the disclosure describes devices, systems, and techniques for selecting one or more stimulation parameters that define electrical stimulation therapy. For example, this disclosure describes selecting one or more stimulation parameters, e.g., sense and / or stimulation electrode combinations, based on a sensed evoked compound action potential (ECAP) signal and a physiological signal. The physiological signal may be different than the ECAP signal and may include signals such as an electromyogram (EMG) signal.

[0005] Endovascular neuromodulation is an emerging therapy in which a neuromodulation device is configured to be implanted within vasculature of a patient to provide electrical stimulation therapy and / or to sense various signals, such as ECAPs and physiological signals (e.g., EMGs), from within the vasculature. The techniques of this disclosure are directed to facilitating less invasive stimulation delivery techniques (e.g., implantation of a medical device within a lumen of an anatomical structure such as a blood vessel or duct) such as by selecting astimulation electrode combination and a sense electrode combination pair, and / or by identifying patient-specific dosing needs. In some examples, devices may be implanted and configured as described to provide endovascular neuromodulation therapy.

[0006] As an example, a system may be configured to select one or more stimulation parameters that at least partially define electrical stimulation deliverable via at least one electrode of an array of electrodes disposed within a blood vessel. In some examples, the array of electrodes is disposed on an expandable structure, such as a stent or a stent-like structure. In some examples, selecting the one or more stimulation parameters includes selecting at least a sense electrode combination and / or a stimulation electrode combination. In one example, to select the electrode pair for sensing and / or delivering stimulation, the system may be configured to identify which electrode pair is associated with a relatively high ECAP (e.g., a signal indicative of desirable neural activity) and a relatively low electromyogram (EMG) signal (e.g., a signal indicative of unwanted electrical activity). In examples in which the sensing electrode combination is the same for the ECAP signal and the EMG signal, the system may differentiate between ECAP and EMG components of the signal by identifying a latency shift of the signal resulting from propagation delay of the nerve fibers. If the ECAP signal meets one or more criteria, e.g., a signal to noise ratio (SNR) criterion, the system may select the electrode pair for therapy.

[0007] In one example, a system includes: processing circuitry configured to: receive, via sensing circuitry, a plurality of evoked compound action potential (ECAP) signals elicited by electrical stimulation and sensed via a first electrode combination including at least a first electrode of an array of electrodes disposed within a blood vessel; receive, via the sensing circuitry, a plurality of physiological signals via a second electrode combination including at least a second electrode of the array of electrodes disposed within the blood vessel; determine an ECAP characteristic value for each ECAP signal of the plurality of ECAP signals; determine a physiological signal characteristic value for each physiological signal of the plurality of physiological signals; and select, based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, one or more stimulation parameters that at least partially define subsequent electrical stimulation therapy deliverable via at least one electrode of the array of electrodes disposed within the blood vessel.

[0008] In another example, a method includes receiving, by processing circuitry of a system and from sensing circuitry of the system, a plurality of evoked compound action potential (ECAP) signals elicited by electrical stimulation and sensed via a first electrode combination including at least a first electrode of an array of electrodes disposed within a blood vessel; receiving, by the processing circuitry, a plurality of physiological signals via a second electrode combination including at least a second electrode of the array of electrodes disposed within the blood vessel; determining, by the processing circuitry, an ECAP characteristic value for each ECAP signal of the plurality of ECAP signals; determining, by the processing circuitry, a physiological signal characteristic value for each physiological signal of the plurality of physiological signals; and selecting, by the processing circuitry and based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, one or more stimulation parameters that at least partially define subsequent electrical stimulation therapy deliverable via at least one electrode of the array of electrodes disposed within the blood vessel.

[0009] In another example, a non-transitory computer-readable medium comprises instructions that, when executed, cause processing circuitry to: receive, via sensing circuitry, a plurality of evoked compound action potential (ECAP) signals elicited by electrical stimulation and sensed via a first electrode combination including at least a first electrode of an array of electrodes disposed within a blood vessel; receive, via the sensing circuitry, a plurality of physiological signals via a second electrode combination including at least a second electrode of the array of electrodes disposed within the blood vessel; determine an ECAP characteristic value for each ECAP signal of the plurality of ECAP signals; determine a physiological signal characteristic value for each physiological signal of the plurality of physiological signals; and select, based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, one or more stimulation parameters that at least partially define subsequent electrical stimulation therapy deliverable via at least one electrode of the array of electrodes disposed within the blood vessel.

[0010] The details of one or more examples of the techniques of this disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques will be apparent from the description and drawings, and from the claims.BRIEF DESCRIPTION OF DRAWINGS

[0011] FIG. 1 is a conceptual diagram illustrating an example therapy system including an endovascular device configured to sense an evoked compound action potential (ECAP) signal and a physiological signal and / or deliver electrical stimulation therapy to a target tissue site, in accordance with one or more techniques of this disclosure.

[0012] FIG. 2 is a functional block diagram illustrating components of an example medical device of the therapy system of FIG. 1 , in accordance with one or more techniques of this disclosure.

[0013] FIG. 3 is a block diagram of the example external programmer of FIG. 1, in accordance with one or more techniques of this disclosure.

[0014] FIG. 4 is a graph of an example ECAP signal sensed elicited by an electrical stimulation pulse, in accordance with one or more techniques of this disclosure.

[0015] FIG. 5 is a timing diagram illustrating one example of electrical stimulation pulses and respective sensed ECAPs, in accordance with one or more techniques of this disclosure.

[0016] FIG. 6 is a graph of example growth curves derived from sensed ECAPs by respective electrode combinations of an array of electrodes, in accordance with one or more techniques of this disclosure.

[0017] FIG. 7 is a graph of an example electromyogram (EMG) signal sensed by an electrode combination of the array of electrodes, in accordance with one or more techniques of this disclosure.

[0018] FIG. 8 is a flowchart illustrating an example operation for selecting a stimulation electrode combination and a sense electrode combination pair, in accordance with one or more techniques of this disclosure.

[0019] FIG. 9 is a flowchart illustrating an example operation for selecting one or more stimulation parameters to define electrical stimulation therapy, in accordance with one or more techniques of this disclosure.

[0020] FIG. 10 is a flowchart illustrating an example operation for selecting a sense electrode combination based on a selected stimulation electrode combination, in accordance with one or more techniques of this disclosure.

[0021] FIG. 11 is a flowchart illustrating an example operation for adjusting a therapeutic dose of electrical stimulation, in accordance with one or more techniques of this disclosure.

[0022] FIG. 12 is a flowchart illustrating an example operation for adjusting one or more stimulation parameters based on one or more physiological responses, in accordance with one or more techniques of this disclosure.

[0023] FIG. 13 is a flowchart illustrating an example operation for determining to reposition the array of electrodes, in accordance with one or more techniques of this disclosure.DETAILED DESCRIPTION

[0024] This disclosure describes example devices, systems, and techniques for selecting one or more stimulation parameters for electrical stimulation therapy, and related methods.Parameters of the electrical stimulation therapy (e.g., electrode combination, voltage or current amplitude, pulse width, pulse frequency, etc.) can be selected by a clinician and / or the patient to provide relief from various symptoms, such as pain, nervous system disorders, muscle disorders, etc. In some examples, the example devices, systems, techniques, and methods relate to delivery of electrical stimulation therapy, e.g., vagus nerve stimulation (VNS), phrenic nerve stimulation, or pudendal nerve stimulation, from an endovascular location.

[0025] Endovascular neuromodulation is an emerging therapy in which a neuromodulation device is configured to be implanted within vasculature of a patient to provide electrical stimulation therapy and / or to sense ECAPs and physiological signals, i.e., physiological signals other than ECAP signals, such as EMGs, from within the vasculature (e.g., within a blood vessel such as an artery or a vein. Traditional neuromodulation therapy can involve a relatively invasive implantation procedure that includes implantation of leads within tissue via tunnelling.Endovascular neuromodulation therapy can include a less invasive implantation procedure that includes passing medical devices through the lumen of blood vessels, which may involve less tissue damage and provide related benefits for both patients and clinicians. In addition, blood vessels, or other lumens within a hollow anatomical structure, may be positioned spatially near a target tissue (e.g., one or more nerves). However, configuring the neuromodulation device to be implanted within the vasculature or other hollow anatomical structure can be challenging. For example, due to the innervation of vasculature (e.g., smooth muscle in some vessel walls), bloodflow, or other movement, endovascular neuromodulation devices can be more susceptible to noise than traditional neuromodulation therapy devices implanted within other tissue.

[0026] As described herein, systems, devices, techniques, and methods can facilitate selection of one or more stimulation parameters, e.g., based on an ECAP signal and a physiological signal, e.g., an EMG signal. This process may provide a solution to various problems, such as identifying stimulation parameters for electrodes disposed within a hollow anatomical structure such as a blood vessel. Due to the innervation of vasculature with various types of patient tissue, electrodes of endovascular neuromodulation devices may sense different types of signals, such as ECAP signals and EMG signals. In some examples, a system may select one or more stimulation parameters based on an ECAP signal and an EMG signal. These stimulation parameters that may be selected include a sense electrode combination and / or a stimulation electrode combination based on the ECAP signal and the EMG signal. The system may select the sense electrode combination and / or the stimulation electrode combination based on a relationship between the ECAP signal and the EMG signal. This relationship could be an inverse relationship, such as a desired relationship between the ECAP signal and the EMG signal in which an ECAP characteristic value is high (indicating desired nerve activity) and the EMG characteristic value is relatively low amplitude (indicating that muscle activity from the stimulation is relatively low). Other relationships between ECAP signals and one or more physiological signals may be used in other examples. The sense electrode combination can be a single electrode combination that senses both the ECAP signal and the EMG signal. In some examples, the sense electrode combination includes two different electrode combinations, with one of the electrode combinations sensing the ECAP signal and the other electrode combination sensing the EMG signal. These different sense electrode combinations may have one or more common electrodes or use completely distinct electrodes.

[0027] In some examples, the system may monitor the EMG signal and employ the EMG signal as a signature that the system can use to differentiate between signal components associated with the ECAP signal and signal components associated with the EMG signal.

[0028] ECAPs are a measure of neural recruitment because each ECAP signal represents the superposition of electrical potentials generated from a population of axons firing in response to an electrical stimulus (e.g., a stimulation pulse). Changes in a characteristic (e.g., an amplitude of a portion of the signal or area under the curve of the signal) of an ECAP signals occur as afunction of how many axons have been activated by the delivered stimulation pulse. For a given set of parameter values that define the stimulation pulse and a given distance between the electrodes and target nerve, the detected ECAP signal may have a certain characteristic value (e.g., amplitude, or area under a curve).

[0029] In some examples, effective stimulation therapy may rely on a certain level of neural recruitment at a target nerve. This effective stimulation therapy may provide relief from one or more conditions (e.g., patient perceived pain) without an unacceptable level of side effects (e.g., overwhelming perception of stimulation). An example of endovascular neuromodulation therapy is VNS. VNS can be used to manage one or more patient conditions, such as to control an inflammatory response in patients. Stimulating the vagus nerve may dampen the inflammatory response and associated cytokine response. In some examples, inflammatory cytokines are modulated up or down via stimulation. In addition, VNS may assist in stroke rehabilitation and limit ischemia reperfusion injury. After a myocardial infarction or stroke, reperfusion therapies (surgery or drugs) are given to restore blood flow. However, due to the restoration of blood, flow induced local damage occurs, including ischemia reperfusion injury. This injury may induce local accumulations of chemical mediators such as reactive oxygen species (ROS) production, inflammatory cytokines, bradykinin, etc., which can further affect inflammation. Such inflammatory compounds may trigger sensory signaling, which can lead to a reduced organ vagus activity and sympathetic overdrive. VNS may treat reperfusion damage as the inflammatory state may be lowered by increasing parasympathetic drive.

[0030] While this disclosure primarily describes examples of VNS and / or sensing via applicable endovascular locations (e.g., the internal jugular vein), it should be understood that the devices, systems, and techniques may be adapted for DBS, other kinds of brain stimulation, peripheral nerve stimulation, e.g., phrenic nerve stimulation, pudendal nerve stimulation, or electrical stimulation, and / or sensing of any nerve tissue that can be done via a location within a hollow anatomical structure. An endovascular location is an example of a hollow anatomical structure location, but other hollow anatomical structures such as ducts, tubes, or lymph vessels may be used in other examples. Additionally, the techniques may be adapted for chronic implantation or for acute implantation. The techniques may be adapted for acute implantation to trial a device before a more invasive procedure or to determine therapy efficacy beforeimplanting a permanent implant. As one example, the devices, systems, and techniques may be adapted for renal denervation, e.g., before or after ablation.

[0031] Inaccurate sensing of ECAP signals can lead to loss of effective therapy and / or side effects. As disclosed, in some examples, due to the innervation of the vasculature with various patient tissue type, the system including the endovascular neuromodulation device may be more susceptible to sensing physiological signals, such as EMG signals, in addition to ECAP signals. In some examples, if the system is not configured to monitor for both ECAPs and the EMG signal to, e.g., identify components of the ECAP signal and the EMG signal, the system may sense ECAP signals inaccurately. Therefore, it may be beneficial to maintain effective therapy by the system determining one or more stimulation parameters based on both ECAP signals and EMG signals.

[0032] In one example, a system may determine an ECAP characteristic value for each ECAP signal of a plurality of ECAPs signals, determine a physiological signal characteristic value for each physiological signal of a plurality of physiological signals, and select one or more stimulation parameters, e.g., a sense electrode combination and a stimulation electrode combination, that defines electrical stimulation therapy deliverable via at least one electrode of an array of electrodes, e.g., disposed on a stent and configured for endovascular neuromodulation.

[0033] In some examples, the physiological signal may be an EMG signal. In some examples, the system may additionally or alternatively be configured to monitor one or more of an electroencephalogram (EEG) signal, a local field potential (LFP) signal, an electrocardiogram (ECG) signal, a heart rate (HR) signal, a signal indicative of cytokine activity, or a signal indicative of neurotransmitter activity. In this manner, the physiological signal may be an electrical, chemical, mechanical, or other indication of events associated with the patient.

[0034] In some examples, to select the one or more parameters, the system may select a stimulation electrode combination and select a plurality of sense electrode combinations to generate a plurality of stimulation electrode combination and sense electrode combination pairs. For each pair of these electrode combinations, the system may determine one or more ECAP characteristic values and one or more physiological characteristic values based on sense ECAP signals and sensed physiological signals, e.g., EMG signals. The system may select a pair with, e.g., a relatively high ECAP signal and a relatively low EMG signal. If a signal quality value,e.g., a signal to noise ratio (SNR) associated with the pair meets a signal quality threshold, the system may select the pair. In some examples, the SNR is a 10 to 1 ratio. Otherwise, the system may select a new stimulation electrode combination, or, in some examples, may determine to generate an output to reposition the device.

[0035] In some examples, for the selected pair, the system may determine a therapeutic dose, e.g., one or more stimulation parameters, such as a pulse amplitude, a pulse width, and / or a current amplitude, for the patient based on a plurality of growth curves determined. In some examples, the therapeutic dose may refer to a time aspect (e.g., on or off time, or duration or number of consecutive pulses before a break in pulses). The system may additionally monitor one or more physiological signals, e.g., in response to delivery of the therapeutic dose. Based on one or more physiological responses associated with the one or more physiological signals, the system may determine to adjust the therapeutic dose.

[0036] FIG. l is a conceptual diagram illustrating an example system 10 configured to deliver electrical stimulation therapy to a target tissue site of a patient 12 and / or sense an ECAP signal and one or more physiological signals (e.g., an EMG signal, an EEG signal, an LFP signal, an ECG signal, a HR signal, a BP signal, a signal indicative of cytokine activity, and / or a signal indicative of neurotransmitter activity) from an endovascular location. Patient 12 ordinarily will be a human patient. In some cases, however, system 10 is applied to other mammalian or nonmammalian non-human patients. System 10 includes a medical device 14 and an endovascular device 16 (e.g. a lead or other device configured to be disposed within a hollow anatomical structure). In the example shown in FIG. 1, medical device 14 is configured to deliver electrical stimulation therapy (e.g., VNS) to a vagus nerve 21 of patient 12 and sense an ECAP signal and one or more physiological signals via electrodes 17, and in some examples, another electrode located separate from electrodes 17, such as one or more electrodes on medical device 14.However, in other examples, system 10 is configured to deliver electrical stimulation therapy (e.g., DBS) to brain 18 of patient 12 and / or sense physiological brain signals in brain 18 via electrodes 17.

[0037] Medical device 14 may be configured to sense ECAP signals and the one or more physiological signals using a monopolar sensing electrode configuration, a bipolar sensing electrode configuration, a tripolar sensing electrode configuration, or any other electrode configurations. Medical device 14 may be configured to deliver stimulation pulses in analternating polarity paradigm (e.g., an anode first in one pulse and then a cathode first in the next pulse) which can function to reduce stimulation artifacts in sensed signals. In some examples, medical device 14 may determine an average ECAP signal and / or an average of each of the one or more physiological signals based on a plurality of sensed signals over time and / or via multiple electrode combinations.

[0038] Endovascular device 16 is shown to be positioned in a jugular vein 13 of patient 12 in the example of FIG. 1 such that one or more electrodes 17 are located proximate to a target tissue site. In particular, electrodes 17 are positioned to deliver electrical stimulation therapy to and / or sense signals from nerves surrounding jugular vein 13, including (but not limited to) vagus nerve 21. Endovascular device 16 includes an expandable structure 19 at a distal portion 15 of endovascular device 16 which may be configured to dispose electrodes 17 in apposition with a vessel wall (e.g., the wall of jugular vein 13). In some examples, expandable structure 19 is at a distalmost end of endovascular device 16. Medical device 14 can provide electrical stimulation to one or more regions surrounding jugular vein 13 configured to manage a condition of patient 12, such as to mitigate the severity or duration of the patient condition. In some examples, endovascular device 16 includes fifteen electrodes 17 disposed over a 90 degree segment of surface area of endovascular device 16. Put another way, the area of endovascular device 16 that contains electrodes 17 may be only over a portion that is closest to the desired target tissue (e.g., vagus nerve 21). Endovascular device 16 may include as few as one electrode or more than fifteen electrodes, and the electrodes may be disposed on endovascular device 16 in a plurality of different configurations, e.g., on a larger or smaller segment of endovascular device 16. An endovascular device with fewer electrodes may be relatively easier to manufacture, reduce cost, and may be more flexible than an endovascular device with more electrodes. However, a larger number of electrodes may enable more stimulation and sensing flexibility by having more electrode configuration options.

[0039] Endovascular device 16 includes any suitable medical device configured to deliver electrical stimulation signals to tissue proximate electrodes 17. For example, endovascular device 16 can be a medical lead, a catheter, a guidewire, or another elongated body carrying electrodes 17 and configured to be electrically coupled to medical device 14 via an electrically conductive pathway that runs between medical device 14 and electrodes 17. Endovascular device 16 has any suitable length that enables connection to medical device 14 either directly orindirectly, e.g., a length in a range of 150 centimeters (cm) to 250 cm, such as 200 cm in one example. Further, endovascular device 16 has a suitable length (e.g., a suitable length as measured along a longitudinal axis of endovascular device 16) for accessing a target tissue site within patient 12 from a vascular access point. In examples in which endovascular device 16 accesses the jugular vein 13 and / or vasculature in a brain 18 of patient 12 from a femoral artery access point at the groin of patient 12, endovascular device 16 has a length of about 100 cm to about 200 cm, although other lengths may be used. As used herein, “about” may indicate the exact value or nearly the exact value to the extent permitted by manufacturing tolerances. “About” can also refer to a certain percentage of the recited value (e.g., within about 1%, 5%, or 10%).

[0040] Endovascular device 16 is configured to be introduced in the vasculature of patient 12, such as to access jugular vein 13 and / or relatively more distal locations in a patient, such as the middle cerebral artery (MCA) in a brain of a patient. Endovascular device 16 may include an elongated body that is structurally configured to be relatively flexible, pushable, and relatively kink- and buckle-resistant, so that it may resist buckling when a pushing force is applied to a relatively proximal portion to advance endovascular device 16 distally through vasculature, and so that it may resist kinking when traversing around a tight turn in the vasculature. Kinking and / or buckling of may hinder a clinician’s efforts to push the elongated body distally, e.g., past a turn. In some examples, the elongated body of endovascular device 16 may be constructed of one or more different types of polymers that enable flexibility. Endovascular device 16 may include one more reinforcement elements in the elongated body that reduce kinking or buckling, such as a metal or polymer braid or helical coil. In some examples, endovascular device 16 includes one or more radiopaque components (e.g., platinum bands) proximate electrodes 17 and / or expandable structure 19, e.g., to provide an indication to the clinician during implantation of the location of electrodes 17 relative to the target tissue, e.g., using X-ray imaging techniques. One or more markers (e.g., radiopaque markers) may be provided at a particular circumferential position(s) of endovascular device 16 that the user can identify the location (e.g., axial position and / or rotational position) of electrodes 17 within the hollow anatomical structure. In some examples, the clinician may additionally obtain images, e.g., magnetic resonance imaging (MRI) images or computed tomography (CT) images, prior to implantation to ascertain a location of vasculature, e.g., jugular vein 13, of patient 12 relative to a target tissue site, e.g., vagus nerve21. In some examples, the clinician may additionally or alternatively obtain images, e.g., MRI, CT, or fluoroscopy, intraoperatively to ascertain a location of the vasculature of patient 12 relative to the target tissue site.

[0041] Instead of or in addition to the elongated body of endovascular device 16 being configured for intravascular navigation to a cerebral blood vessel to deliver electrical stimulation therapy or sense a physiological signal, endovascular device 16 can be navigated through vasculature (e.g., through jugular vein 13, brain 18, or other target tissue sites) with the aid of a guide member. The guide member can include an outer catheter, an inner catheter, a guide extension catheter, a guidewire, or the like or combination thereof.

[0042] In some examples, more than one endovascular device 16 can be implanted within patient 12 to provide stimulation to and / or sense multiple anatomical regions, including one or more of both the left and right jugular veins, as well as in locations of brain 18. For example, two or more of endovascular device 16, which may be paired with one or more of medical device 14, may be configured of bilateral stimulation and / or sensing (e.g., of the left jugular vein and a right jugular vein). Endovascular device 16, including electrodes 17 and / or expandable structure 19, can be implanted in a blood vessel for chronic therapy delivery and / or chronic sensing (e.g., on the order of months or even years) or for more temporary therapy delivery and / or sensing (e.g., on the order of days, such as less than a month or less than 6 months). Temporary therapy delivery may include one or more trial periods, such as to determine, evaluate, or confirm an efficacy of stimulation and / or sensing.

[0043] The electrical stimulation therapy described herein (e.g., VNS, phrenic nerve stimulation, or pudendal nerve stimulation) may be used to treat various patient conditions, such as, a variety of illnesses including, but not limited to: reperfusion damage, cardiac ischemia, heart failure (HF), brain ischemia, stroke, traumatic brain injury, surgical or non-surgical acute kidney injury, inability of the intestine (bowel) to contract normally and move waste out of the body, postoperative ileus, postoperative cognitive decline or postoperative delirium, asthma, sepsis, bleeding control, myocardial infarction reduction, dysmotility, and obesity. Treating any of these diseases may improve patient outcomes by shortening length of hospital stays and reducing medical costs.

[0044] The vasculature into which endovascular device 16 may be inserted and / or guided includes, but is not limited to, veins or arteries. For example, endovascular device 16 can benavigated from a vasculature access site (e.g., in the femoral artery, the radial artery, or another suitable access site) to one or more of a jugular vein (e.g., internal jugular vein and / or external jugular vein), a carotid artery (e.g., internal carotid artery, external carotid artery, and / or common carotid artery), as well as brain targets including the thalamostriate vein, the internal cerebral vein, the basal vein of Rosenthal, the inferior / superior sagittal sinus, the anterior choroidal artery, or any related combinations thereof.

[0045] A clinician can also select a particular blood vessel to position electrodes 17 within, such as to avoid certain regions to minimize or even eliminate adverse effects. For example, electrodes 17 can be oriented or positioned relative to vagus nerve 21 to avoid inadvertently providing electrical stimulation to anatomical regions (e.g., undesired anatomical regions) near the targeted anatomical region.

[0046] In some examples, endovascular device 16 is configured to be delivered to one or more target sites in vasculature of patient 12. Thus, rather than introducing endovascular device16 into tissue in close proximity with vagus nerve 21 through an incision in the neck or chest area of patient 12, endovascular device 16 is configured to be navigated proximate to a target electrical stimulation site via vasculature of patient 12. The endovascular delivery of endovascular device 16 to target sites can help reduce the invasiveness of system 10.

[0047] In some examples, electrodes 17 are positioned on (e.g., coupled to, defined by, or otherwise carried by) expandable structure 19 of endovascular device 16, which is configured to expand radially outwards from a relatively low-profile (e.g., radially compressed or collapsed) delivery configuration to a deployed configuration. By expanding expandable structure 19, the deployed configuration may enable electrodes 17 to be held in apposition with a blood vessel wall, promote tissue ingrowth around electrodes 17 along the vessel wall (while still leaving a patent lumen to enable blood flow through the blood vessel, through expandable structure 19, despite implantation of endovascular device 16), which can reduce the overall power needed to deliver efficacious electrical stimulation therapy to a target tissue site, and help secure electrodes17 in place in the blood vessel for chronic therapy delivery.

[0048] Medical device 14 can be an external medical device or an implantable medical device that includes electrical stimulation circuitry configured to generate and deliver electrical stimulation therapy to patient 12 and / or sensing circuitry configured to sense a patient parameter (e.g., a physiological signal) via one or more electrodes 17 of endovascular device 16. In theexample shown in FIG. 1, endovascular device 16 is directly or indirectly mechanically and electrically coupled to medical device 14 via a header 11 of medical device 14, which defines a plurality of electrical contacts in one or more feedthrough portions for electrically coupling electrodes 17 to electrical stimulation generation circuitry and / or sensing circuitry within medical device 14. In some examples, header 11 includes multiple feedthrough portions, which may be respectively configured for receiving one of multiple portions of endovascular device 16. Header 11 may also be referred to as a connector block or connector of medical device 14. Endovascular device 16 may be coupled to header 11 with the aid of a lead extension. However, in some examples, a lead extension is not used between header 11 and endovascular device 16, and endovascular device is directly mechanically and / or electrically connected to medical device 14 via header 11.

[0049] In some examples, medical device 14 is configured to be implanted in patient 12 in any suitable location, such as a location in a pectoral region. In other examples, medical device 14 is configured to be external to patient 12. Endovascular device 16 may be, for example, implanted within a vein (e.g., jugular vein 13) and one or more proximal wires / leads can remain within the venous system until they exit the venous system, such as through the subclavian vein in the chest or the internal jugular vein in the neck for implant in the pectoral region. In yet other examples, some or all of medical device 14 is configured to be implanted in the vasculature, e.g., as part of endovascular device 16.

[0050] As shown in FIG. 1, system 10 may also include a programmer 20, which may be a handheld device, portable computer, or workstation that provides a user interface to a user, for example a clinician or other user, such as a patient. The user may interact with the user interface to program electrical stimulation parameters for medical device 14. Programmer 20 is a device that may be described as an external programmer because it remains external from patient 12.

[0051] With the aid of programmer 20 or another computing device, a clinician may select values for stimulation parameters for controlling therapy delivery by system 10. The values for the therapy parameters may be organized into a group of parameter values referred to as a “therapy program” or “stimulation parameter set.” “Therapy program” and “stimulation parameter set” are used interchangeably herein. In the case of electrical stimulation, the stimulation parameters may include an electrode combination, a power, and an amplitude, which may be a current or voltage amplitude, and, if medical device 14 delivers electrical pulses, apulse width, and a pulse rate (or pulse frequency) for stimulation signals to be delivered to patient 12. Other example stimulation parameters include a slew rate, duty cycle, and phase of the electrical stimulation signal. In some examples, medical device 14 or endovascular device 16 may select one or more stimulation parameters, e.g., a sense electrode combination and a stimulation electrode combination, and / or may propose one or more stimulation parameter for user approval via programmer 20.

[0052] An electrode combination may include a selected subset of one or more electrodes 17 located on one or more implantable endovascular devices 16 coupled to medical device 14. Generally, an electrode combination identifies at least two electrodes between current can flow and / or a voltage potential can be detected. If only one electrode of electrodes 17 is selected, another electrode on medical device 14 or elsewhere may also be selected to be part of the electrode combination. The electrode combination may also refer to the polarities of the electrodes in the selected subset. By selecting particular electrode combinations, the user may target particular tissue sites (e.g., anatomic structures) within patient 12. Additionally, by selecting a sense electrode combination and a stimulation electrode combination pair with a relatively high ECAP signal amplitude and a relatively low EMG signal amplitude, endovascular device 16 may more accurately sense patient signals, which may lead to more efficacious therapy delivery. In addition, by selecting values for pulse width, current amplitude, slew rate, duty cycle, phase amplitude, and / or pulse rate, the user can attempt to generate an efficacious therapy for patient 12 that is delivered via the selected electrode subset.

[0053] Whether programmer 20 is configured for clinician or patient use, programmer 20 may be configured to communicate with medical device 14 or any other computing device via wireless or a wired communication. Programmer 20, for example, may communicate via wireless communication with medical device 14 using radio frequency (RF) telemetry techniques. Programmer 20 may also communicate with another programmer or computing device via a wired or wireless connection using any of a variety of local wireless communication techniques, such as RF communication according to the 802.11 or Bluetooth specification sets, infrared communication according to the Infrared Data Association (IRDA) specification set, or other standard or proprietary telemetry protocols. Programmer 20 may also communicate with another programming or computing device via a wired or wireless communication technique.

[0054] Medical device 14 or another device senses one or more physiological signals, either using electrodes 17 or other types of sensors that are carried by endovascular device 16. In some examples, sensed physiological signals are used as part of continuous feedback system in which medical device 14 adjusts one or more stimulation parameter values and / or a therapeutic dose based on sensed physiological signals. Example physiological signals are described in further detail below with reference to FIG. 2.

[0055] In some examples, medical device 14 is configured to generate and deliver a suitable electrical stimulation signal, which can be a continuous time signal (e.g., a sinusoidal waveform or the like) or a plurality of pulses. In some examples, the electrical stimulation waveform generated by medical device 14 and delivered by one or more of electrodes 17 is a charge balanced, biphasic waveform. In some examples, such an electrical stimulation waveform consists of periodic pulses or otherwise include periodic pulses or can include a continuous time waveform. A stimulation pulse may include one or more phases. For example, a biphasic pulse may include an anodic phase and a cathodic phrase which may be separated by an interphase delay. In some examples, a pulse may include an anodic or cathodic phase followed by a passive recharge phase in which remaining charge is balanced at the electrodes. Although pulses are generally charge balanced, it is possible to deliver two or more consecutive pulses of the same polarity without delivering a balancing pulse (e.g., active recharge phase or passive recharge phase) until after the two or more consecutive pulses of the same polarity are delivered.

[0056] As noted above, in some examples, one or more electrodes 17 are positioned on expandable structure 19. In some examples, one or more sensors that are different from electrodes 17 are positioned on the same expandable structure (e.g., expandable structure 19) as one or more electrodes 17 or on a different expandable structure (e.g., a structure similar to or different from expandable structure 19) of endovascular device 16. Expandable structure 19 can have any suitable configuration that enables endovascular device 16 to assume a relatively low- profile configuration (also referred to herein as a “delivery,” “compressed,” or “collapsed” configuration in some examples) to facilitate delivery through vasculature to a target tissue site and expand radially outwards (relative to a central longitudinal axis of endovascular device 16) to position the one or more electrodes 17 closer to target tissue.

[0057] In some examples, expandable structure 19 is configured to expand radially outwards with sufficient force and to a cross-sectional dimension (e.g., a diameter) sufficient to positionthe one or more electrodes 17 in apposition with a blood vessel wall. Positioning one or more electrodes 17 in apposition with a blood vessel wall may help promote tissue ingrowth around electrodes 17, which can reduce the impedance and the overall power needed to deliver efficacious electrical stimulation therapy to a target tissue site and help secure electrodes 17 in place in the blood vessel for chronic (e.g., on the order of months or even years) therapy delivery. Fixing endovascular device 16 in place within the blood vessel via the tissue ingrowth or, in some examples, using another fixation structures / anchoring mechanisms, such as tines, coils barbs, or the like, can also help reduce the possibility of thrombosis.

[0058] Expandable structure 19 can be configured to expand radially outwards using any suitable technique and configuration. In some examples, expandable structure 19 includes a shape memory (e.g., nitinol) material that enables the expandable structure to assume a predetermined shape in the absence of a force (e.g., a compressive or tensile force) holding expandable structure 19 in a relatively low- profile delivery configuration. For example, expandable structure 19 can be configured to expand radially outwards upon deployment from an outer sheath (e.g., an outer catheter), or upon the proximal withdrawal of a straightening element (e.g., a guidewire or a mandrel) positioned in an inner lumen of the endovascular device 16. In some examples, expandable structure 19 is configured to expand radially outwards in response to proximal withdrawal of a pull member attached to a distal portion of the endovascular device 16, in response to a distal movement of an elongated control member attached to the expandable structure, or with the aid of a balloon or the like. Alternatively, a shape memory material may expand in the body due to the increased body temperature compared to lower temperature out of the body. In some examples, expandable structure 19 may be similar to a “stent” that includes a plurality of repeating structures.

[0059] Expandable structure 19 can have any suitable configuration in its deployed (e.g., expanded) configuration. In some examples herein, expandable structure 19 includes a plurality of interconnected struts to form a structure configured to expand radially outward (e.g., from a central longitudinal axis of expandable structure 19) similar to a “stent.” For example, expandable structure 19 can include a tubular member, a basket, include one or more splines or arms configured to expand radially outwards, define one or more loops, define a helical or spiral element, or the like or combinations thereof, when in the deployed configuration. One or more expandable structures 19 may be disposed at various positions along endovascular device 16(e.g., at one or more longitudinal positions along endovascular device 16). Expandable structure 19 can be formed from a plurality of structural elements (e.g., braided or coupled together) or can be a unitary structure (e.g., a laser cut nitinol tube).

[0060] In addition to, or instead of, chronic therapy delivery and / or chronic sensing, example devices, systems, and methods described herein can be used for more temporary applications. In some examples, a first endovascular device (e.g., configured like endovascular device 16 or having another configuration) is configured to be operated in an acute (e.g., temporary) trial mode for a trial period to determine, evaluate, or confirm an efficacy of stimulation and / or sensing. For example, endovascular device 16 (as well as electrodes 17, medical device 14, processing circuitry, etc.) may be configured to operate in the trial mode to determine the efficacy of one or more stimulation parameter values and / or one or more sensing parameters. After the acute trial period, the first endovascular device may be removed, and a second endovascular device (e.g., configured like endovascular device 16 or having another configuration) configured to operate in a chronic mode may be implanted for a chronic period for chronic (e.g., long term, or permanent) stimulation therapy or sensing. In some examples, a first endovascular device (e.g., for use in the acute trial mode) is configured to be implanted and subsequently removed after the trial period.

[0061] A trial period has a shorter intended duration than a chronic period, though the ultimate length of the chronic period may be less than an intended duration due to one or more factors, such as a patient response that requires shortening the chronic period relative to the intended duration of the chronic period. In some examples, the trial period includes a trial period length on the order of minutes (e.g., 1 minute, 2 minutes, 3 minutes, 5 minutes, 30 minutes, 45 minutes, etc.), on the order of hours (e.g., 1 hour, 2 hours, 5 hours, 12 hours, etc.), on the order of days (e.g., 1 day, 2 days, 3 days, etc.), on the order of weeks (e.g., 1 week, 2 weeks, 3 weeks, etc.) on the order of months (e.g., 1 month, 2 months, 3 months, etc.), or longer. In some examples, one or more endovascular devices may be used for multiple trial periods (e.g., successive trial periods) for determining an efficacy of one or more stimulation parameters and / or one or more sensing parameters.

[0062] Endovascular device 16 may have any suitable configuration for delivering electrical stimulation to a target tissue site in patient 12 or sensing a patient parameter from an endovascular location (e.g., jugular vein 13). In some examples, endovascular device includes afirst subset of electrodes of electrodes 17 configured for delivering electrical stimulation therapy and a second subset of electrodes of electrodes 17 configured to for sensing one or more patient parameters. In some examples, some or all electrodes of electrodes 17 are configured for both electrical stimulation therapy and for sensing one or more patient parameters. Endovascular device 16 can include any suitable number of electrodes 17 and / or combination of different kinds of electrodes. In some examples, electrodes 17 include electrodes formed via one or more manufacturing processes. For example, electrodes 17 can include a first electrode type (e.g., one or more stamped electrodes), a second electrode type (e.g., one or more machined electrodes), or any suitable combination thereof.

[0063] FIG. 2 is a functional block diagram illustrating components of an example medical device 14, which is configured to generate and deliver electrical stimulation therapy to patient 12 and sense one or more physiological signals. Medical device 14 may control electrical stimulation therapy using one or more of these sensed physiological signals. Medical device 14 includes processing circuitry 208, memory 212, stimulation generation circuitry 202, sensing circuitry 204, telemetry circuitry 206, and power source 210.

[0064] Stimulation generation circuitry 202 includes any suitable configuration (e.g., hardware) configured to generate and deliver electrical stimulation signals to target tissue (e.g., vagus nerve 21) in patient 12. Processing circuitry 208 is configured to control stimulation generation circuitry 202 to generate and deliver electrical stimulation therapy via electrodes 17 of endovascular device 16. The therapy parameter values may be selected based on the patient condition being addressed, as well as the target tissue site in patient 12 for the electrical stimulation therapy. The electrical stimulation therapy can be provided via stimulation signals of any suitable form, such of stimulation pulses or continuous-time signals (e.g., sine waves), delivered via one or more of electrodes 17.

[0065] There can be greater or fewer electrodes 17 than depicted in FIG. 2. In the example of FIG. 2, endovascular device 16 includes 15 electrodes. In some examples, endovascular device 16 may include anywhere from 8 to 16 electrodes. However, different numbers of electrodes are also possible. A greater number of electrodes may enable more programming flexibility to deliver stimulation to target tissue and / or sense desired signals with an appropriate sensing vector. In some examples, including relatively fewer electrodes may reduce manufacturing complexity and may improve flexibility of endovascular device 16. In some examples, includingmore electrodes may reduce a complexity associated with implanting and configuring endovascular device 16. Additionally, electrodes 17 can be disposed on endovascular device 16 in various configurations. In the example of FIG. 2, electrodes 17 are disposed on a 90 degree segment (e.g., only a 90 degree perimeter or circumference) of endovascular device 16. In other examples, electrodes 17 may be disposed around the full perimeter or circumference of endovascular device 16, on a 180 degree segment, a 120 degree segment, a 60 degree segment, a 30 degree segment, a 15 degree segment, or a smaller segment. In some examples, including electrodes on a relatively large segment of endovascular device 16 may reduce the complexity of implantation by enabling sensing and / or stimulation at any rotational implantation, and including electrodes on a relatively small segment of endovascular device 16 may reduce a manufacturing complexity (e.g., fewer electrodes) and an overall device complexity. Electrodes 17 may be configured in 3 axial rows as depicted or in greater or fewer rows. For example, in an example in which there are 8 electrodes 17, electrodes 17 may be configured in 4 axial rows, 2 axial rows, or 1 axial row. The pattern of electrodes 17 may be any pattern appropriate for the desired stimulation or sensing. In some examples, electrodes 17 may be placed in pairs at different locations or in different patterns that may match the location of target nerves or other tissues.

[0066] Sensing circuitry 204 is configured to sense a physiological parameter of a patient. Sensing circuitry 204 may include any sensing hardware configured to sense a physiological parameter of a patient, such as, but not limited to, one or more electrodes, e.g., one or more electrodes 17, optical receivers, pressure sensors, or the like. The one or more sensing electrodes can be the same or different from electrodes 17 configured to deliver electrical stimulation therapy. In some examples, processing circuitry 208 stores the sensed physiological parameters in memory 212 or transmits the sensed parameters to another device via telemetry circuitry 206. In addition, in some examples, processing circuitry 208 can use the sensed physiological signals as feedback (e.g., in a closed-loop control system) to control therapy delivery by stimulation generation circuitry 202, e.g., one or more stimulation parameters, of the electrical simulation signal generated by stimulation generation circuitry 202.

[0067] In some examples, sensing circuitry 204 is configured to sense an ECAP and one or more physiological signals via one or more electrodes 17 (e.g., all or a subset of electrodes 17). While an ECAP is an example of a physiological signal, for the purposes of this disclosure, physiological signals include physiological signals other than ECAPs when combined withECAP sensing. Thus, electrodes 17 can be configured to receive or transmit energy (e.g., current). In some examples, the one or more physiological signals include EMG, muscle activation signals (e.g., laryngeal muscle activation), ECG, HR, intracardiac electrogram (EGM), BP, EEG, electrocorti cogram (ECoG), action potentials from single cells within brain 18 (referred to as “spikes”), signals indicative of cytokine activity, and / or signals indicative of neurotransmitter activity.

[0068] In some examples, sensing circuitry 204 is configured to sense both the ECAP and the one or more physiological signals via the same electrode combination of electrodes 17. In some examples, sensing circuitry 204 is configured to sense the ECAP signal and the one or more physiological signals via different electrode combinations of electrodes 17. In some examples, the different electrodes combinations can include one or more of the same electrodes. In some cases, the particular combination of electrodes for sensing ECAPs and / or the one or more physiological signal includes different electrode combinations of electrodes 17 used to deliver stimulation pulses. Alternatively, in other cases, the particular combination of electrodes used for sensing ECAPs and / or the one or more physiological signals includes at least one of the same electrodes as a set of electrodes used to deliver stimulation pulses to patient 102.

[0069] In some examples, sensing circuitry 204 and / or processing circuitry 208 includes signal processing circuitry configured to perform any suitable analog conditioning of the sensed physiological signals. For example, sensing circuitry 204 may communicate to processing circuitry 208 an unaltered (e.g., raw) signal. Processing circuitry 208 may be configured to modify a raw signal to a usable signal by, for example, filtering (e.g., low pass, high pass, band pass, notch, or any other suitable filtering), amplifying, performing an operation on the received signal (e.g., taking a derivative, averaging), performing any other suitable signal conditioning (e.g., converting a current signal to a voltage signal), or any combination thereof. In some examples, the conditioned analog signals are processed by an analog-to-digital converter of processing circuitry 208 or other component to convert the conditioned analog signals into digital signals. In some examples, processing circuitry 208 operates on the analog or digital form of the signals to separate out different components of the signals. In some examples, sensing circuitry 204 and / or processing circuitry 208 performs any suitable digital conditioning of the converted digital signals, such as low pass, high pass, band pass, notch, averaging, or any other suitable filtering, amplifying, performing an operation on the signal, performing any othersuitable digital conditioning, or any combination thereof. Additionally or alternatively, sensing circuitry 204 may include signal processing circuitry to modify one or more raw signals and communicate to processing circuitry 208 one or more modified signals.

[0070] In some examples, processing circuitry 208, alone or in combination with stimulation generation circuitry 202 and / or sensing circuitry 204, is configured to operate medical device 14 (including electrodes 17, endovascular device 16, etc.) in a trial mode for a trial period to determine an efficacy of electrical stimulation or sensing. As described above, a trial mode can include a trial period of stimulation and / or sensing to determine, evaluate, or confirm an efficacy of stimulation and / or sensing. In some examples, processing circuitry 208, alone or in combination with stimulation generation circuitry 202 and / or sensing circuitry 204, is configured to deliver electrical stimulation therapy and / or sense an ECAP and one or more physiological signals during the trial period. In some examples, processing circuitry 208 is configured to determine, evaluate, or confirm an efficacy of stimulation and / or sensing. For example, processing circuitry 208 may determine one or more therapy parameters for chronic stimulation and / or sensing based on the trial period.

[0071] Although shown as part of medical device 14 in FIG. 2, in other examples, sensing circuitry 204 is part of a device separate from medical device 14. For example, sensing circuitry 204 can be part of an implantable sensing device implanted in patient 12.

[0072] Processing circuitry 208, as well as other processors, processing circuitry, controllers, control circuitry, and the like, described herein, may include any combination of integrated circuitry, discrete logic circuity, analog circuitry, such as one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), or field-programmable gate arrays (FPGAs). In some examples, processing circuitry 208 includes multiple components, such as any combination of one or more microprocessors, one or more DSPs, one or more ASICs, or one or more FPGAs, as well as other discrete or integrated logic circuitry, and / or analog circuitry.

[0073] Memory 212 is configured to store program instructions, such as software, which may include one or more program modules, which are executable by processing circuitry 208. When executed by processing circuitry 208, such program instructions may cause processing circuitry 208 to provide the functionality ascribed to processing circuitry 208 herein. The program instructions may be embodied in software and / or firmware. Memory 212 may include anyvolatile, non-volatile, magnetic, optical, or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital media.

[0074] Memory 212 stores stimulation parameter settings 214, characteristic values 216, and growth curve data 218. Each stored stimulation parameter setting 214 defines values for a set of electrical stimulation parameters (e.g., a stimulation parameter set or therapy program), such as pulse amplitude, pulse width, pulse frequency, sense electrode combination, stimulation electrode combination, pulse burst rate, pulse burst duration, and / or waveform shape. Stimulation parameter settings 220 may also include additional information such as instructions regarding delivery of electrical stimulation signals based on stimulation parameter relationship data, which can include relationships between two or more stimulation parameters based upon data from electrical stimulation signals delivered to patient 102 or data transmitted from external programmer 104. Stimulation parameter settings 214 may define electrical stimulation therapy to be delivered via electrodes 17 of endovascular device 16.

[0075] Characteristic values 216 may include, for example, a plurality of ECAP characteristic values based on a plurality of ECAP signals and a plurality of physiological signal characteristic values, e.g., EMG characteristic values based on a plurality of physiological signals, e.g., EMG signals. Characteristic values 216 may additionally include target ECAP characteristic values and / or threshold ECAP characteristic values and target physiological characteristic values and / or threshold physiological characteristic values determined for patient 12 and / or a history of measured ECAP characteristic values and physiological characteristic values for patient 12. Memory 212 may also store growth curve data 218 in separate areas from or as part of patient stimulation parameter settings. Instead of, or in addition to, growth curve data 218, memory 212 may include gain values that processing circuitry 208 may use to modulate stimulation pulses as described herein. In other examples, growth curve data 218 may include information regarding relationships between ECAP characteristic values and physiological characteristic values and stimulation parameters.

[0076] Processing circuitry 208 is configured to control telemetry circuitry 206 to send and receive information. Telemetry circuitry 206, as well as telemetry modules in other devices described herein, such as programmer 20 (FIG. 1), may accomplish communication by any suitable communication techniques, such as RF communication techniques. In addition,telemetry circuitry 206 may communicate with external medical device programmer 20 via proximal inductive interaction of medical device 14 with programmer 20. Accordingly, telemetry circuitry 206 may send information to external programmer 20 on a continuous basis, at periodic intervals, or upon request from medical device 14 or programmer 20.

[0077] Power source 210 is configured to deliver operating power to various components of medical device 14. Power source 210 may include a small rechargeable or non- rechargeable battery and a power generation circuit to produce the operating power. Recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within medical device 14. In some examples, power requirements may be small enough to allow medical device 14 to utilize patient motion and implement a kinetic energy-scavenging device to trickle charge a rechargeable battery. In other examples, traditional batteries may be used for a limited period of time. In some examples, processing circuitry 208 may monitor the remaining charge (e.g., voltage) of power source 210 and select stimulation parameter values that may deliver similarly effective therapy at lower power consumption levels when needed to extend the operating time of power source 210. In some examples, endovascular device 16 is configured to be a standalone electrical stimulation device and can include one or more elements of medical device 14 shown in FIG. 2.

[0078] FIG. 3 is a block diagram of the example programmer 20. Although programmer 20 may generally be described as a hand-held device, programmer 20 may be a larger portable device or a more stationary device. In addition, in some examples, programmer 20 may be included as part of an external charging device or include the functionality of an external charging device. As illustrated in FIG. 3, programmer 20 may include a processing circuitry 302, memory 304, user interface 306, telemetry circuitry 308, and power source 310. Storage device 304 may store instructions that, when executed by processing circuitry 302, cause processing circuitry 302 and programmer 20 to provide the functionality ascribed to programmer 20 throughout this disclosure. Each of these components, circuitry, or modules, may include electrical circuitry that can perform some, or all of the functionality described herein. For example, processing circuitry 302 may include processing circuitry to perform the processes discussed with respect to processing circuitry 302.

[0079] In general, programmer 20 comprises any suitable arrangement of hardware, alone or in combination with software and / or firmware, to perform the techniques attributed toprogrammer 20, and processing circuitry 302, user interface 306, and telemetry circuitry 308 of programmer 20. In various examples, programmer 20 may include one or more processors, such as one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. Programmer 300 also, in various examples, may include a memory 304, such as RAM, ROM, PROM, EPROM, EEPROM, flash memory, a hard disk, a CD-ROM, comprising executable instructions for causing the one or more processors to perform the actions attributed to them. Moreover, although processing circuitry 302 and telemetry circuitry 308 are described as separate, in some examples, processing circuitry 302 and telemetry circuitry 308 are functionally integrated. In some examples, processing circuitry 302 and telemetry circuitry 308 correspond to individual hardware units, such as ASICs, DSPs, FPGAs, or other hardware units.

[0080] Memory 304 (e.g., a storage device) may store instructions that, when executed by processing circuitry 302, cause processing circuitry 302 and programmer 20 to provide the functionality ascribed to programmer 20 throughout this disclosure. For example, memory 304 may include instructions that cause processing circuitry 302 to obtain a stimulation parameter setting from memory, select a spatial electrode movement pattern, or receive a user input and send a corresponding command to programmer 20, or instructions for any other functionality. In addition, memory 304 may include a plurality of stimulation parameter settings, where each setting includes a parameter set that defines electrical stimulation. Memory 304 may also store data received from a medical device (e.g., medical device 14 and / or endovascular device 16). For example, memory 304 may store ECAP related data and physiological signal recording data recorded at a sensing circuitry of the medical device, and memory 304 may also store data from one or more sensors of the medical device.

[0081] User interface 306 may include a button or keypad, lights, a speaker for voice commands, a display, such as a liquid crystal (LCD), light-emitting diode (LED), or organic light-emitting diode (OLED). In some examples the display may be a touch screen. User interface 306 can display any information related to the delivery of electrical stimulation, identified patient behaviors, sensed patient parameter values, patient behavior criteria, or any other such information. Programmer 20 may receive user input via user interface 306. The input may be, for example, in the form of pressing a button on a keypad or selecting an icon from a touch screen. The input may request starting or stopping electrical stimulation, the input mayrequest a new spatial electrode movement pattern or a change to an existing spatial electrode movement pattern, of the input may request some other change to the delivery of electrical stimulation. In other examples, user interface 306 may receive input from patient 12 and / or clinician regarding efficacy of the therapy, such as binary feedback, numerical ratings, textual input, etc. In some examples, processing circuitry 302 may interpret patient requests to change therapy as negative feedback regarding the current parameter values used to define therapy.

[0082] Telemetry circuitry 308 may support wireless communication between the medical device and programmer 20 under the control of processing circuitry 302. Telemetry circuitry 308 can communicate with another computing device via wireless communication techniques, or direct communication through a wired connection. In some examples, telemetry circuitry 308 provides wireless communication via an RF or proximal inductive medium. In some examples, telemetry circuitry 308 includes an antenna, which may take on a variety of forms, such as an internal or external antenna.

[0083] Examples of local wireless communication techniques that may be employed to facilitate communication between programmer 20 and IMD 110 include RF communication according to the 902.11 or Bluetooth specification sets or other standard or proprietary telemetry protocols. In this manner, other external devices may be capable of communicating with programmer 20 without needing to establish a secure wireless connection. As described herein, telemetry circuitry 308 can transmit a spatial electrode movement pattern or other stimulation parameter values to IMD 110 for delivery of electrical stimulation.

[0084] In some examples, selection of stimulation parameter settings may be transmitted to the medical device for delivery to patient 12. In other examples, stimulation parameter settings may include medication, activities, or other instructions that patient 12 must perform themselves or a caregiver perform for patient 102. In some examples, programmer 20 may provide visual, audible, and / or tactile notifications that indicate there are new instructions. Programmer 20 may require receiving user input acknowledging that the instructions have been completed in some examples.

[0085] According to the techniques of the disclosure, user interface 306 of programmer 20 receives an indication from a clinician instructing a processor of the medical device to update one or more stimulation parameter settings. Updating the stimulation parameter settings may include changing one or more stimulation parameter values of the electrical stimulation signaldelivered by the medical device according to the settings, such as pulse amplitude, pulse width, pulse frequency, sense electrode combination, stimulation electrode combination, and / or waveform shape. User interface 306 may also receive instructions from the clinician commanding any electrical stimulation.

[0086] Power source 310 can deliver operating power to various components of programmer 20. Power source 310 may be the same as or substantially similar to power source 214. Power source 310 may include a battery and a power generation circuit to produce the operating power. In some examples, the battery is rechargeable to allow extended operation. Recharging may be accomplished by electrically coupling power source 310 to a cradle or plug that is connected to an alternating current (AC) outlet. In addition, recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within programmer 20. In other examples, traditional batteries (e.g., nickel cadmium or lithium ion batteries) may be used. In addition, external programmer 20 may be directly coupled to an alternating current outlet to operate.

[0087] The architecture of programmer 20 illustrated in FIG. 3 is shown as an example. The techniques as set forth in this disclosure may be implemented in the example external programmer 20 of FIG. 3, as well as other types of systems not described specifically herein. Nothing in this disclosure should be construed so as to limit the techniques of this disclosure to the example architecture illustrated by FIG. 3.

[0088] FIG. 4 is a graph 400 of an example ECAP signals sensed for respective electrical stimulation pulses. As shown in FIG. 3, graph 400 shows example ECAP signal 402 (dotted line) and ECAP signal 404 (solid line). Each of ECAP signals 402 and 404 may be sensed from pulses that were delivered from a guarded cathode and bi-phasic pulses including an interphase interval between each positive and negative phase of the pulse. ECAP signal 402 illustrates the voltage amplitude sensed as a result from a sub-threshold stimulation pulse. Peaks 406 of ECAP signal 402 are detected and represent the artifact of the delivered pulse. However, no propagating signal is detected after the artifact in ECAP signal 404 because the pulse was sub-threshold.

[0089] In contrast to ECAP signal 402, ECAP signal 404 represents the voltage amplitude detected from a supra- threshold stimulation pulse. Peaks 406 of ECAP signal 404 are detected and represent the artifact of the delivered pulse. After peaks 406, ECAP signal 404 also includes peaks Pl, Nl, and P2, which are three peaks representative of propagating action potentials froman ECAP. The example duration of the artifact and peaks Pl, Nl, and P2 is approximately 1 millisecond (ms). When detecting the ECAP of ECAP signal 404, different characteristics may be identified. For example, the characteristic of the ECAP may be the amplitude between Nl and P2. This N1-P2 amplitude can be detected even if the artifact impinges on Pl, a relatively large signal, and the N1-P2 amplitude may be minimally affected by electronic drift in the signal. In other examples, the characteristic of the ECAP used to control pulses may be an amplitude of Pl, Nl, or P2 with respect to neutral or zero voltage. In some examples, the characteristic of the ECAP used to control pulses may be a sum of two or more of peaks Pl, Nl, or P2. In other examples, the characteristic of ECAP signal 404 may be the area under one or more of peaks Pl, Nl, and / or P2. In other examples, the characteristic of the ECAP may be a ratio of one of peaks Pl, Nl, or P2 to another one of the peaks. In some examples, the characteristic of the ECAP may be a slope between two points in the ECAP signal, such as the slope between Nl and P2. In other examples, the characteristic of the ECAP may be the time between two points of the ECAP, such as the time between Nl and P2. The time between two points in the ECAP signal may be referred to as a latency of the ECAP and may indicate the types of fibers being captured by the pulse. The latency may be determined from sensing of artifact 406 or between two peaks, such as between Pl and Nl or Nl and P2. ECAP signals with lower latency (i.e., smaller latency values) indicate a higher percentage of nerve fibers that have faster propagation of signals, whereas ECAP signals with higher latency (i.e., larger latency values) indicate a higher percentage of nerve fibers that have slower propagation of signals. Other characteristics of the ECAP signal may be used in other examples.

[0090] The amplitude of the ECAP signal increases with increased amplitude of the pulse, as long as the pulse amplitude is greater than the threshold such that nerves depolarize and propagate the signal. In some examples, the pulse amplitude is between 0 milliamps and 25 milliamps. The target ECAP characteristic (e.g., the target ECAP amplitude) may be determined from the ECAP signal detected from a pulse when pulses are determined to deliver effective therapy to patient 12. The ECAP signal thus is representative of the distance between the stimulation electrodes and the nerves appropriate for the stimulation parameter values of the pulses delivered at that time. Therefore, IMD 110 may attempt to use detected changes to the measured ECAP characteristic value to change stimulation pulse parameter values and maintain the target ECAP characteristic value during stimulation pulse delivery. Alternatively, IMD 110may attempt to prevent undesirable stimulation intensity by decreasing stimulation pulse intensity in response to the ECAP characteristic value exceeding a threshold ECAP characteristic value. As used herein, a stimulation intensity may refer to a “charge” applied to the target tissue, which may be a function of current or voltage amplitude, pulse width, pulse shape, and / or pulse frequency.

[0091] FIG. 5 is a timing diagram 500A illustrating one example of electrical stimulation pulses and respective sensed ECAPs, in accordance with one or more techniques of this disclosure. For convenience, FIG. 5 is described with reference to medical device 14 of FIG. 2. As illustrated, timing diagram 500A includes first channel 502, a plurality of control pulses 504A-504N (collectively “control pulses 504”), second channel 506, a plurality of respective ECAPs 508A-508N (collectively “ECAPs 508”), and a plurality of stimulation interference signals 509A-509N (collectively “stimulation interference signals 509”). In the example of FIG. 5, stimulation pulses 504 may or may not contribute to therapy for patient 12. In any case, stimulation pulses 504 may elicit respective ECAPs 508 for the purpose of determining relative neural recruitment due to the stimulation pulses 504, which may be indicated by a growth curve specific to a pulse width and current amplitude associated with a respective stimulation pulse of stimulation pulses 504.

[0092] First channel 502 is a time / voltage (and / or current) graph indicating the voltage (or current) of at least one electrode of electrodes 17. In one example, the stimulation electrodes of first channel 502 may be located on the opposite side of the lead as the sensing electrodes of second channel 506. Stimulation pulses 504 may be electrical pulses delivered to tissue of patient 12 by at least one of electrodes 17 and stimulation pulses 504 may be balanced biphasic square pulses with an interphase interval. In other words, each of control pulses 504 are shown with a negative phase and a positive phase separated by an interphase interval. For example, a control pulse 504 may have a negative voltage for the same amount of time and amplitude that it has a positive voltage. It is noted that the negative voltage phase may be before or after the positive voltage phase. Stimulation pulses 504 may be delivered according to instructions stored in stimulation parameter settings 214 of memory 212.

[0093] In some examples, each of stimulation pulses 504 may be a part of a sweep of pulses configured to determine a relationship between the stimulation parameter values of the pulses and a characteristic value of the resulting respective ECAPs 508. For example, the relationshipmay be a growth curve of ECAP voltage amplitude versus current amplitude for a plurality of pulse widths. In this manner, each of stimulation pulses 504 may differ from each other by a parameter value, such as an iteratively increasing current amplitude. Stimulation pulses 504 may vary and be up to 5 milliseconds to 10 milliseconds in examples in which medical device 14 is delivering renal denervation therapy. In examples in which medical device 14 is delivering VNS, the pulse width range may be shorter. In one example, stimulation pulses 504 may have a pulse width of less than approximately 300 microseconds (e.g., the total time of the positive phase, the negative phase, and the interphase interval is less than 300 microseconds). In another example, control pulses 504 may have a pulse width of approximately 100 microseconds for each phase of the bi-phasic pulse. In some examples, the pulse width of stimulation pulses 504 may be longer than 300 microseconds, as long as the pulse width does not interfere with the detection of the desired one or more features of the elicited ECAPs 508. In some examples, the pulse width of stimulation pulses 504 may be between 20 microseconds and 5 milliseconds. In some examples, the pulse width of stimulation pulses 504 may be between 50 microseconds and 1 millisecond. As illustrated in FIG. 5, stimulation pulses 504 may be delivered via channel 502. Delivery of stimulation pulses 504 may be delivered by one or more of electrodes 17.

[0094] Second channel 506 is a time / voltage (and / or current) graph indicating the voltage (or current) of at least one electrode of electrodes 17. ECAPs 508 are electrical signals which may propagate along a nerve away from the origination of stimulation pulses 504. In one example, ECAPs 508 are sensed by different electrodes than the electrodes used to deliver stimulation pulses 504. In some examples, a sense electrode combination includes one or more of electrodes 17, and, in some examples, an electrode located on a housing of medical device 14. As illustrated in FIG. 5, ECAPs 508 may be recorded on second channel 506. In some examples, ECAPs 508 may not be sensed after each stimulation pulse 504.

[0095] Stimulation interference signals 509A, 509B, and 509N (e.g., the artifact of the stimulation pulses) may be sensed by leads 230 and may be sensed during the same period of time as the delivery of stimulation pulses 504. Since the interference signals may have a greater amplitude and intensity than ECAPs 508, any ECAPs arriving at IMD 200 during the occurrence of stimulation interference signals 509 may not be adequately sensed by sensing circuitry 204 of medical device 14. However, ECAPs 508 may be sufficiently sensed by sensing circuitry 204 because each ECAP 508, or at least a portion of ECAP 508 that includes one or more desiredfeatures of ECAP 508 that is used as feedback for stimulation pulses 504, falls after the completion of each a stimulation pulse 504. As illustrated in FIG. 5, stimulation interference signals 509 and ECAPs 508 may be recorded on channel 506.

[0096] In some examples, medical device 14, for example, may deliver the entire group of stimulation pulses 504 (e.g., a sweep) consecutively and without any other intervening pulses in order to detect ECAPs 508 from which respective characteristic values are determined. Medical device 14 may then determine the relationship between the characteristic values from ECAPs 508 and the different parameter values of stimulation pulses 504. In one example, the sweep of pulses 504 may be delivered by medical device 14 during a break in delivery of other types of stimulation pulses.

[0097] FIG. 6 is a graph 600 of example growth curves 602, 604, and 606 of sensed ECAPs from respective stimulation pulse amplitudes, e.g., pulse amplitudes between 0 milliamps and 25 milliamps. Graph 600 illustrates example ECAPs shown as dots (growth curve 602), squares (growth curve 604), and triangles (growth curve 606) for respective different current amplitudes of stimulation pulses. The pulses may have the same pulse width, but in other examples, the x- axis may refer to pulse width changes, or intensity changes (which may include a combination of amplitude, pulse width, or other parameters that affect intensity). ECAPs will sometimes not be generated until the stimulation pulse amplitude reaches a threshold, approximately at 4.5 mA current in the example of FIG. 6. Then, as the current amplitude is increased, the ECAP amplitude also increases approximately linearly. This linear relationship is shown by growth curves 602, 604, 606. Besides growth curves varying based on the pulse widths, the slope may vary for each patient based on the type of electrodes implanted, where the electrodes are implanted, the sensitivity of patient 12’s neurons to stimulation, neurological dysfunction, or other factors.

[0098] For a given pulse width, sensed ECAPs may be detected for stimulation pulses with different current amplitudes. For example, each growth curve 602, 604, and 606 may be for a single pulse width. When pulse width changes, the corresponding growth curve can change as well. For example, growth curve 602 may be associated with a first pulse width, growth curve 604 may be associated with a second pulse width, and growth curve 606 may be associated with a third pulse width. In some examples, the pulse widths corresponding to growth curves 602,604, and 606 may range from 20 microseconds to 5 milliseconds. In some examples, pulse widths may range from 50 microseconds to 1 millisecond.

[0099] The slope of the growth curves 602, 604, and 606 that linearly increase may indicate the relationship between sensed ECAP amplitudes and pulse amplitudes. In some examples, the gain value used to increase or decrease stimulation parameter values may be inversely proportional to the slope of the growth curve of values of the characteristic of ECAP signals (e.g., an amplitude such as the N1-P2 amplitude or the amplitude of any peak of the ECAP signal) elicited from respective stimulation pulses delivered to patient 12 and at least partially defined by different values of a stimulation parameter (e.g., current amplitude, voltage amplitude, or pulse width). For example, the gain value for a patient may be used to dynamically adjust pulse amplitude based on the sensed ECAP amplitudes. In some examples, the gain may be approximated for a patient based on historical data for similar patients. In other examples, the system may generate a custom growth curve and gain specific to patient 12 before starting therapy with the system.

[0100] FIG. 7 is a graph of an example EMG signal 702 sensed by an electrode combination of electrodes 17, in accordance with one or more techniques of this disclosure. In examples in which sensing circuitry of medical device 14 is configured to sense one or more physiological signals, an electrode combination, e.g., one or more electrodes, of electrodes 17 can be configured to sense an EMG signal. In some examples, the same electrode combination of electrodes 17 that senses ECAP signal senses the EMG signal. In other examples, different electrode combinations sense the ECAP signal and the EMG signal. In some examples, the electrode combination may additionally include an electrode located on a housing of, e.g., medical device 14.

[0101] Contraction blocks 704 are indicative of muscle tissue activation, which can be stimulated by electrical stimulation, e.g., stimulation pulses 504, or by patient movement. Due to the innervation of vasculature with other patient tissue, endovascular neuromodulation devices may sense EMG signals of surrounding muscle tissue. Processing circuitry, e.g., processing circuitry 208, may be configured to differentiate between ECAP components and EMG components of a signal. In some examples, EMG signal 702 serves as a signature to facilitate the differentiation between the ECAP components and the EMG components. In examples in which the same electrode combination of electrodes 17, and, in some cases, an electrode on the housingof medical device 14, senses an ECAP signal and EMG signal 702, processing circuitry 208 differentiates between the ECAP signal components and the EMG signal components based on a latency shift of the signal.

[0102] FIG. 8 is a flowchart illustrating an example operation for selecting a stimulation electrode combination and a sense electrode combination pair, in accordance with one or more techniques of this disclosure. The example of FIG. 8 will be described with respect to processing circuitry 208 of medical device 14, but other processing circuitry of system 10, e.g., processing circuitry 302 of programmer 20, and / or other devices or systems may be used in other examples to facilitate placement of and stimulation parameter selection for endovascular device 16. In some examples, processing circuitry of different devices may be used to collectively perform this technique in a distributed computing model.

[0103] As shown in the example of FIG. 8, processing circuitry 208 selects a stimulation electrode combination and a sense electrode combination pair (802). The electrode combination may comprise one or more electrodes of electrodes 17, and, in some examples, an electrode located on a housing of medical device 14. In some examples, processing circuitry 208 selects the stimulation electrode combination based on a proximity of the one or more electrodes of electrodes 17 to a target tissue site. In some examples, processing circuitry 208 determines the proximity of the one or more electrodes to the target tissue site based on pre-procedural planning and / or based on a review of images, e.g., MRI images. In some examples, processing circuitry 208 may select the one or more electrodes of electrodes 17 based on intraoperative images, e.g., CT images, fluoroscopy images, or MRI images. In some examples, processing circuitry 208 selects the stimulation electrode combination and the sense electrode combination pair based on at least one ECAP characteristic value and at least one physiological characteristic value. The selection of the stimulation electrode combination and the sense electrode combination pair is further described in FIGS. 9 and 10. Processing circuitry 208 determines whether the pair meets one or more criterion, e.g., a signal quality criterion, such as a SNR criterion (804). If the pair does not meet the one or more criterion (“NO” branch of block 804), processing circuitry 208 determines to output an indication to the user, e.g., the clinician, to reposition endovascular device 16 (806). In examples in which endovascular device 16 comprises a stent or stent-like structure, electrodes 17 may be disposed on a 90 degree segment of the stent. Repositioning the stent may include rotating the stent to adjust the location of the 90 degree segment withelectrodes 17 or moving the stent to a different location within the vasculature to align the 90 degree segment of the stent with electrodes 17 with the target nerve, e.g., vagus nerve 21.

[0104] If the pair meets the one or more criterion (“YES” branch of block 804), processing circuitry 208 controls stimulation generation circuitry, e.g., stimulation generation circuitry 202, to perform a sweep to determine a neural threshold associated with the stimulation electrode combination and sense electrode combination pair (808). Based on the neural threshold, processing circuitry 208 determines a therapeutic dose, e.g., one or more stimulation parameters, such as pulse width, current amplitude, or pulse duration (810). Determining the neural threshold and the therapeutic dose is further described in FIG. 11.

[0105] Processing circuitry 208 controls stimulation generation circuitry 202 to provide electrical stimulation therapy according to the therapeutic dose and monitors a physiological response of patient 12. The physiological response may be based on one or more physiological signals, such as an EMG, an EEG, an ECG, an LFP, a HR, a BP, a signal indicative of cytokine activity, and / or a signal indicative of neurotransmitter activity, and / or an ECAP signal. In some examples, the physiological response may additionally include patient input, such as input regarding side effects associated with the electrical stimulation therapy at the therapeutic dose. If the physiological response meets one or more therapeutic dose criterion (“YES” branch of block 812), the process ends, and processing circuitry 208 continues to control stimulation generation circuitry 202 to provide electrical stimulation therapy according to the therapeutic dose and to monitor the physiological response (814). If the physiological response does not meet the one or more therapeutic dose criterion (“NO” branch of block 812), processing circuitry 208 may determine to select a new stimulation electrode combination and sense electrode combination pair and repeat the process with the new stimulation electrode combination and sense electrode combination pair (802). In some examples, before determining to select a new stimulation electrode combination and sense electrode combination pair, processing circuitry 208 may adjust a therapeutic dose to an adjusted therapeutic dose and determine whether a physiological response to the adjusted therapeutic dose meets the one or more criterion.

[0106] FIG. 9 is a flowchart illustrating an example operation for selecting one or more stimulation parameters, e.g., a sense electrode combination and a stimulation electrode combination pair, to define electrical stimulation therapy, in accordance with one or more techniques of this disclosure. In some examples, the example operation of FIG. 9 is a specificexample of step 802 of the example operation of FIG. 8. The example of FIG. 9 will be described with respect to processing circuitry 208 of medical device 14, but other processing circuitry of system 10, e.g., processing circuitry 302 of programmer 20, and / or other devices or systems may be used in other examples. In some examples, processing circuitry of different devices may be used to collectively perform this technique in a distributed computing model.

[0107] In the example of FIG. 9, processing circuitry 208 receives, e.g., from sensing circuitry 204, a plurality of ECAP signals elicited by electrical stimulation (902). In some examples, the electrical stimulation may be generated by stimulation generation circuitry 202 and delivered by one or more electrodes of electrodes 17, and the ECAP signals may be sensed via a first electrode combination including at least a first electrode of an array of electrodes disposed within a blood vessel of patient 12. Processing circuitry 208 receives a plurality of physiological signals, e.g., an EMG signal, via a second electrode combination including at least a second electrode of electrodes 17 (904). In some examples, the first electrode combination and the second electrode combination are the same. In other examples, the first and second electrode combinations are different. In some examples, the different first and second electrode combinations share one or more electrodes. Processing circuitry 208 determines an ECAP characteristic value for each ECAP signal of the plurality of ECAP signals (906). Processing circuitry 208 likewise determines a physiological signal characteristic value for each physiological signal of the plurality of physiological signals (908). In some examples, the ECAP characteristic values and the physiological signal characteristic values are based on ECAP signal amplitudes and physiological signal amplitudes, respectively. Processing circuitry 208 selects one or more stimulation parameters, e.g., a sense electrode combination and a stimulation electrode combination, based on at least one ECAP characteristic value and at least one physiological signal characteristic value (910). In some examples, to select the one or more stimulation parameters, processing circuitry 208 applies weights to the at least one ECAP characteristic value and the at least one physiological signal characteristic value. In some examples, processing circuitry 208 prioritizes the at least one ECAP characteristic value over the at least one physiological signal characteristic value. In some examples, the weight applied to the at least one ECAP characteristic value is larger than the weight applied to the at least one physiological signal characteristic value. The one or more stimulation parameters at least partially define subsequent electrical stimulation therapy deliverable via at least one electrode ofelectrodes 17, i.e., the selected stimulation electrode combination. In some examples, the selected sense electrode combination comprises one or more of the first electrode combination or the second electrode combination.

[0108] In some examples, processing circuitry 208 repeats the example operation for a plurality of stimulation electrode combinations and first and second electrode combinations before selecting the one or more parameters. In some examples, in response to selecting the one or more stimulation parameters, processing circuitry 208 performs an operation substantially similar or the same as the example operation illustrated in FIG. 8.

[0109] FIG. 10 is a flowchart illustrating an example operation for selecting a sense electrode combination based on a selected stimulation electrode combination, in accordance with one or more techniques of this disclosure. The example of FIG. 10 will be described with respect to processing circuitry 208 of medical device 14, but other processing circuitry of system 10, e.g., processing circuitry 302 of programmer 20, and / or other devices or systems may be used in other examples. In some examples, processing circuitry of different devices may be used to collectively perform this technique in a distributed computing model.

[0110] Processing circuitry 208 selects one or more electrodes of electrodes 17 for a potential stimulation electrode combination (1002). Processing circuitry 208 may select the one or more electrodes of electrodes 17 based on a proximity of the one or more electrodes to a target tissue site. In some examples, processing circuitry 208 determines the proximity of the one or more electrodes to the target tissue site based on pre-procedural planning and / or based on a review of images, e.g., MRI images. In some examples, processing circuitry 208 may select the one or more electrodes of electrodes 17 based on intraoperative images, e.g., CT images, fluoroscopy images, or MRI images. Processing circuitry 208 selects a plurality of sense electrode combinations including at least one electrode of electrodes 17, and, in some examples, an electrode on the housing of medical device 14 (1004). In some examples, processing circuitry 208 selects the sense electrode combinations based on a location of the at least on electrode of electrodes 17 relative to the one or more electrodes of electrodes 17 of the stimulation electrode combination. For each sense electrode combination of the plurality of sense electrode combinations, processing circuitry 208 controls stimulation generation circuitry 202 to deliver supra-neural threshold short pulse trains via the stimulation electrode combination and controls sensing circuitry 204 to sense an ECAP signal via the sense electrode combination and to sense aphysiological signal, e.g., an EMG signal, via either the sense electrode combination, i.e., in examples in which the electrode combination for sensing the ECAP signal and the EMG signal is the same, or another sense electrode combination of the plurality of sense electrode combination (1006). In some examples, processing circuitry 208 determines the neural threshold based on a plurality of growth curves at different pulse widths within a predefined range of current amplitude. An example operation for determining the neural threshold is described in FIG. 11.

[0111] Processing circuitry 208 determines which sense electrode combination(s) of the plurality of sense electrode combinations senses a relatively high amplitude ECAP signal and a relatively low amplitude EMG signal (1008). In some examples, processing circuitry 208 prioritizes selecting a sense electrode combination with a relatively high ECAP amplitude over selecting a sense electrode combination with a relatively low EMG amplitude. In some examples, processing circuitry 208 applies weights to the ECAP signal amplitude and to the EMG signal amplitude to determine the sense electrode combination(s).

[0112] Responsive to selecting the sense electrode combination(s), processing circuitry 208 determines whether a signal quality, e.g., an SNR, of the ECAP signal and / or the EMG signal meets a signal quality threshold. In some examples, the SNR is a 10 to 1 ratio, but other ratios may be used in other examples. If processing circuitry 208 determines the signal quality meets the signal quality threshold (“YES” branch of block 1010), the process ends, and processing circuitry 208 can control stimulation generation circuitry 202 to deliver therapy via the stimulation electrode combination and based on signals sensed via the sense electrode combination(s) (1014). If processing circuitry 208 determines the signal quality does not meet the signal quality threshold (“NO” branch of block 1010), processing circuitry 208 determines whether there are additional stimulation electrode combinations that have not been tested (1012). If there are additional stimulation electrode combinations (“YES” branch of block 1012), processing circuitry 208 selects one of the additional stimulation electrode combinations (1002) and repeats the example operation of FIG. 10. If there are no additional stimulation electrode combinations (“NO” branch of block 1012), processing circuitry 208 determines to output an indication to the user via user interface 306 of programmer 20, to reposition endovascular device 16 (1016). Processing circuitry 208 repeats the example operation of FIG. 10 in the new position.

[0113] FIG. 11 is a flowchart illustrating an example operation for adjusting a therapeutic dose of electrical stimulation, in accordance with one or more techniques of this disclosure. Insome examples, the example operation of FIG. 11 is a specific example of steps 808, 810, and 812 of FIG. 8. The example of FIG. 11 will be described with respect to processing circuitry 208 of medical device 14, but other processing circuitry of system 10, e.g., processing circuitry 302 of programmer 20, and / or other devices or systems may be used in other examples. In some examples, processing circuitry of different devices may be used to collectively perform this technique in a distributed computing model. In some examples, responsive to selecting a stimulation electrode combination and sense electrode combination pair based on at least one ECAP characteristic value and at least one physiological signal characteristic value, processing circuitry 208 performs the example operation of FIG. 11. In some examples, processing circuitry 208 selects the stimulation electrode combination and sense electrode combination pair via the example operation of FIG. 9 or FIG. 10.

[0114] Processing circuitry 208 determines, for a plurality of pulse widths and within a predefined range of current amplitude, a plurality of growth curves (1102). The growth curves may be substantially similar to the growth curves illustrated in FIG. 6. Based on the plurality of growth curves, processing circuitry 208 determines a neural threshold of patient 12 (1104). Then neural threshold may be the amplitude, or intensity, at which there is an inflection point in the growth curve. The inflection point may indicate that stimulation has started to induce detectable ECAP signals at the corresponding amplitude, or intensity, of stimulation.

[0115] Based on the neural threshold of patient 12, processing circuitry 208 selects a therapeutic dose for electrical stimulation therapy (1106). In some examples, processing circuitry 208 determines a pulse frequency, e.g., a pulse frequency between 2 Hertz (Hz) to 500 Hz, and On / Off cycle and fine-tunes the current amplitude and pulse width to select the therapeutic dose. In some examples, processing circuitry 208 may select the therapeutic dose in part based on determining a pulse amplitude and pulse width combination to preserve longevity of medical device 14 and / or endovascular device 16. As an example, processing circuitry 208 may select a therapeutic dose with a relatively wide pulse width and a relatively low amplitude to preserve longevity and to obtain longer recharge intervals for rechargeable devices. The therapeutic dose is based on a pulse width of the plurality of pulse widths and a current amplitude range within the predefined current amplitude range. Processing circuitry 208 controls therapy delivery circuitry, e.g., stimulation generation circuitry 202, to deliver stimulation at the therapeutic dosevia at least one electrode of an array of electrodes, e.g., the stimulation electrode combination comprising at least one electrode of electrodes 17 (1108).

[0116] Processing circuitry 208 controls sensing circuitry 204 to sense an ECAP signal and / or one or more physiological signals, such as an EMG signal, an EEG signal, an ECG signal, an LFP signal, a HR signal, a BP signal, a signal indicative of cytokine activity, and / or a signal indicative of neurotransmitter activity and determines one or more physiological responses based on the physiological signals (1110). In some examples, the one or more physiological responses additionally or alternatively include patient input, such as patient sensation of the stimulation at the therapeutic dose and / or side effects. In some examples, processing circuitry 208 monitors a physiological signal based on a condition for which the system is configured to provide therapy. For example, processing circuitry 208 may monitor one or more of the ECG signal, the HR signal, or the BP signal in examples in which patient 12 has cardiovascular disease. Processing circuitry 208 may monitor one or more of the EEG signal or the LFP signal in example in which patient 12 has epilepsy or depression. In examples in which patient 12 has inflammatory disease, processing circuitry 208 may monitor the signal indicative of cytokine activity and / or the signal indicative of neurotransmitter activity. In some examples, processing circuitry 208 controls sensing circuitry 204 to sense the ECAP signal and / or the one or more physiological signals in response to stimulation generation circuitry 202 delivering the therapeutic dose. In some examples, processing circuitry 208 controls sensing circuitry 204 to sense the ECAP signal and / or the one or more physiological responses continuously, e.g., on a periodic schedule. If the one or more physiological responses do not meet a criterion, processing circuitry 208 determines to adjust the therapeutic dose to an adjusted therapeutic dose based on the one or more physiological responses to the therapeutic dose (1112).

[0117] FIG. 12 is a flowchart illustrating an example operation for adjusting one or more stimulation parameters based on one or more physiological responses, in accordance with one or more techniques of this disclosure. The example of FIG. 12 will be described with respect to processing circuitry 208 of medical device 14, but other processing circuitry of system 10, e.g., processing circuitry 302 of programmer 20, and / or other devices or systems may be used in other examples. In some examples, processing circuitry of different devices may be used to collectively perform this technique in a distributed computing model.

[0118] In the example of FIG. 12, during therapy, e.g., during endovascular neuromodulation therapy delivered subsequent to selecting the one or more stimulation parameters and therapeutic dose, processing circuitry 208 monitors one or more physiological responses (1202). In some examples, endovascular device 16 may undergo endothelialization over time. Due to the endothelialization, the one or more physiological responses may change and may be indicative or changes in therapy efficacy and / or patient sensation. The one or more physiological responses may be based on one or more of the ECAP signal or the one or more physiological signals, e.g., an EMG signal, an EEG signal, an ECG signal, an LFP signal, a HR signal, a BP signal, a signal indicative of cytokine activity, or a signal indicative of neurotransmitter activity. In some examples, processing circuitry 208 controls sensing circuitry 204 to sense the ECAP signal and / or the one or more physiological signals continuously, e.g., on a periodic schedule. In some examples, processing circuitry 208 controls sensing circuitry 204 to sense the ECAP signal and / or the one or more physiological signals in response to a user request or sensed signal exceeding a threshold. The user, e.g., the clinician or patient 12, may input a user request via user interface 306, based on a change in symptoms and / or sensation of the stimulation therapy for patient 12. In some examples, processing circuitry 208 monitors the one or more physiological responses continuously, e.g., on a periodic schedule. In some examples, processing circuitry 208 monitors the one or more physiological responses in response to a user request, sensed signal exceeding a threshold, or other command. In response to identifying a change in the one or more physiological responses, processing circuitry 208 determines to adjust one or more of the one or more stimulation parameters, e.g., the stimulation electrode combination and / or the sense electrode combination (1204). In some examples, to adjust the one or more of the one or more stimulation parameters, processing circuitry 208 determines to perform the example operation of FIG. 9.

[0119] FIG. 13 is a flowchart illustrating an example operation for determining to reposition the array of electrodes, in accordance with one or more techniques of this disclosure. The example of FIG. 13 will be described with respect to processing circuitry 208 of medical device 14, but other processing circuitry of system 10, e.g., processing circuitry 302 of programmer 20, and / or other devices or systems may be used in other examples. In some examples, processing circuitry of different devices may be used to collectively perform this technique in a distributed computing model.

[0120] Processing circuitry 208 may determine an ECAP signal corresponding to the selected one or more stimulation parameters, e.g., an ECAP signal elicited by stimulation delivered via the stimulation electrode combination and sensed by the sense electrode combination, does not meet a signal quality criterion, e.g., a SNR criterion or amplitude criterion (1302). For example, if the system cannot detect ECAP signals from stimulus that previously elicited a detectable ECAP, processing circuitry 208 may determine that the stimulus electrodes and / or sensing electrodes have moved or otherwise are not acceptable for sensing ECAP signals. In response to determining the ECAP signal does not meet the signal quality criterion, processing circuitry 208 determines to output, e.g., via user interface 306, to the user to reposition the array of electrodes (1304). In some examples, processing circuitry 208 may automatically perform a screening process to deliver stimuli from different stimulation electrode combinations and / or sense ECAPs from different sensing electrode combinations in order to identify a new stimulation electrode combination and / or sensing electrode combination that enables detection of ECAPs. Processing circuitry 208 may control delivery of these new combinations to a user, via a user interface, for final selection or confirmation.

[0121] The following examples are described herein. Example 1. A system comprising: processing circuitry configured to: receive, via sensing circuitry, a plurality of evoked compound action potential (ECAP) signals elicited by electrical stimulation and sensed via a first electrode combination including at least a first electrode of an array of electrodes disposed within a blood vessel; receive, via the sensing circuitry, a plurality of physiological signals via a second electrode combination including at least a second electrode of the array of electrodes disposed within the blood vessel; determine an ECAP characteristic value for each ECAP signal of the plurality of ECAP signals; determine a physiological signal characteristic value for each physiological signal of the plurality of physiological signals; and select, based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, one or more stimulation parameters that at least partially define subsequent electrical stimulation therapy deliverable via at least one electrode of the array of electrodes disposed within the blood vessel.

[0122] Example 2. The system of example 1, further comprising an implantable medical device (IMD) comprising an array of electrodes configured for endovascular neuromodulation therapy.

[0123] Example 3. The system of example 2, wherein the endovascular neuromodulation therapy comprises vagus nerve stimulation (VNS).

[0124] Example 4. The system of any of examples 1 through 3, wherein the processing circuitry is configured to select the one or more stimulation parameters based on a comparison of each ECAP characteristic value to the plurality of ECAP characteristic values and each physiological signal feature to the plurality of physiological signal characteristic values.

[0125] Example 5. The system of any of examples 1 through 4, wherein the plurality of physiological signals comprises an electromyogram (EMG) signal.

[0126] Example 6. The system of example 5, wherein the first electrode combination and the second electrode combination are the same, and wherein the processing circuitry is further configured to: identify components of the ECAP signal and components of the EMG signal based on a latency shift of the signal.

[0127] Example 7. The system of any of examples 1 through 5, wherein the first electrode combination and the second electrode combination are the same.

[0128] Example 8. The system of any of examples 1 through 7, wherein the processing circuitry is configured to select the one or more stimulation parameters by at least selecting a stimulation electrode combination and a sensing electrode combination from the array of electrodes disposed within the blood vessel.

[0129] Example 9. The system of any of examples 1 through 8, wherein the processing circuitry is configured to select the one or more stimulation parameters by at least identifying the one or more stimulation parameters defining stimulation that elicits an ECAP signal with a high amplitude ECAP characteristic value relative to other ECAP signals and a low amplitude physiological signal characteristic value relative to other physiological signals.

[0130] Example 10. The system of any of examples 1 through 9, wherein to select the one or more stimulation parameters based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, the processing circuitry is configured to at least: apply a first weight value to each ECAP characteristic value; and apply a second weight value to each physiological signal characteristic value, wherein the first weight value is larger than the second weight value.

[0131] Example 11. The system of any of examples 1 through 10, wherein the array of electrodes is disposed on a stent.

[0132] Example 12. The system of any of examples 1 through 11, wherein the processing circuitry is configured to: determine, for a plurality of potential pulse widths (PW) and a predefined current amplitude range, a corresponding plurality of growth curves; determine, based on the plurality of growth curves, a neural threshold; select, based on the neural threshold, a therapeutic dose, wherein the therapeutic dose comprises a PW of the plurality of potential PWs and a current amplitude range within the predefined current amplitude range; control therapy delivery circuitry to deliver the therapeutic dose via at least one electrode of the array of electrodes disposed within the blood vessel; determine one or more physiological responses to the therapeutic dose based on one or more physiological signals sensed in response to delivery of the therapeutic dose; and adjust, based on the one or more physiological responses, the therapeutic dose to an adjusted therapeutic dose.

[0133] Example 13. The system of any of examples 1 through 12, wherein the plurality of physiological signals comprises one or more of: an electroencephalogram (EEG) signal; a local field potential (LFP) signal; an electrocardiogram (ECG) signal; an EMG signal; a heart rate (HR) signal; a blood pressure (BP) signal; a signal indicative of cytokine activity; or a signal indicative of neurotransmitter activity.

[0134] Example 14. The system of any of examples 1 through 13, wherein the processing circuitry is further configured to: determine an ECAP signal corresponding to the selected one or more stimulation parameters does not meet a signal quality criterion; and responsive to the ECAP signal not meeting the signal quality criterion, output an indication to a user to reposition the array of electrodes.

[0135] Example 15. The system of example 14, wherein the signal quality criterion comprises a signal to noise ratio (SNR).

[0136] Example 16. A method comprising: receiving, by processing circuitry of a system and from sensing circuitry of the system, a plurality of evoked compound action potential (ECAP) signals elicited by electrical stimulation and sensed via a first electrode combination including at least a first electrode of an array of electrodes disposed within a blood vessel; receiving, by the processing circuitry, a plurality of physiological signals via a second electrode combination including at least a second electrode of the array of electrodes disposed within theblood vessel; determining, by the processing circuitry, an ECAP characteristic value for each ECAP signal of the plurality of ECAP signals; determining, by the processing circuitry, a physiological signal characteristic value for each physiological signal of the plurality of physiological signals; and selecting, by the processing circuitry and based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, one or more stimulation parameters that at least partially define subsequent electrical stimulation therapy deliverable via at least one electrode of the array of electrodes disposed within the blood vessel.

[0137] Example 17. The method of example 16, wherein the system comprises an implantable medical device (IMD) comprising an array of electrodes configured for endovascular neuromodulation therapy.

[0138] Example 18. The method of example 17, wherein the endovascular neuromodulation therapy comprises vagus nerve stimulation (VNS).

[0139] Example 19. The method of any of examples 16 through 18, wherein selecting the one or more stimulation parameters comprises at least selecting the one or more stimulation parameters based on a comparison of each ECAP characteristic value to the plurality of ECAP characteristic values and each physiological signal feature to the plurality of physiological signal characteristic values.

[0140] Example 20. The method of any of examples 16 through 19, wherein the plurality of physiological signals comprises an electromyogram (EMG) signal.

[0141] Example 21. The method of example 20, wherein the first electrode combination and the second electrode combination are the same, the method further comprising: identifying components of the ECAP signal and components of the EMG signal based on a latency shift of the signal.

[0142] Example 22. The method of any of examples 16 through 20, wherein the first electrode combination and the second electrode combination are the same.

[0143] Example 23. The method of any of examples 16 through 22, wherein selecting the one or more stimulation parameters comprises selecting a stimulation electrode combination and a sensing electrode combination from the array of electrodes disposed within the blood vessel.

[0144] Example 24. The method of any of examples 16 through 23, wherein selecting the one or more stimulation parameters comprises identifying the one or more stimulation parameters defining stimulation that elicits an ECAP signal with a high amplitude ECAP characteristic value relative to other ECAP signals and a low amplitude physiological signal characteristic value relative to other physiological signals.

[0145] Example 25. The method of any of examples 16 through 24, wherein selecting the one or more stimulation parameters based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals comprises: applying a first weight value to each ECAP characteristic value; and applying a second weight value to each physiological signal characteristic value, wherein the first weight value is larger than the second weight value.

[0146] Example 26. The method of any of examples 16 through 25, wherein the array of electrodes is disposed on a stent.

[0147] Example 27. The method of any of examples 16 through 26, further comprising: determining, for a plurality of potential pulse widths (PW) and a predefined current amplitude range, a corresponding plurality of growth curves; determining, based on the plurality of growth curves, a neural threshold; selecting, based on the neural threshold, a therapeutic dose, wherein the therapeutic dose comprises a PW of the plurality of potential PWs and a current amplitude range within the predefined current amplitude range; controlling therapy delivery circuitry to deliver the therapeutic dose via at least one electrode of the array of electrodes disposed within the blood vessel; determining one or more physiological responses to the therapeutic dose based on one or more physiological signals sensed in response to delivery of the therapeutic dose; and adjusting, based on the one or more physiological responses, the therapeutic dose to an adjusted therapeutic dose.

[0148] Example 28. The method of any of examples 16 through 27, wherein the plurality of physiological signals comprises one or more of: an electroencephalogram (EEG) signal; a local field potential (LFP) signal; an electrocardiogram (ECG) signal; an EMG signal; a heart rate (HR) signal; a blood pressure (BP) signal; a signal indicative of cytokine activity; or a signal indicative of neurotransmitter activity.

[0149] Example 29. The method of any of examples 16 through 28, further comprising: determining an ECAP signal corresponding to the selected one or more stimulation parametersdoes not meet a signal quality criterion; and responsive to the ECAP signal not meeting the signal quality criterion, outputting an indication to a user to reposition the array of electrodes.

[0150] Example 30. The method of example 29, wherein the signal quality criterion comprises a signal to noise ratio (SNR).

[0151] Example 31. A non-transitory computer-readable medium comprising instructions that, when executed, cause processing circuitry to: receive, via sensing circuitry, a plurality of evoked compound action potential (ECAP) signals elicited by electrical stimulation and sensed via a first electrode combination including at least a first electrode of an array of electrodes disposed within a blood vessel; receive, via the sensing circuitry, a plurality of physiological signals via a second electrode combination including at least a second electrode of the array of electrodes disposed within the blood vessel; determine an ECAP characteristic value for each ECAP signal of the plurality of ECAP signals; determine a physiological signal characteristic value for each physiological signal of the plurality of physiological signals; and select, based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, one or more stimulation parameters that at least partially define subsequent electrical stimulation therapy deliverable via at least one electrode of the array of electrodes disposed within the blood vessel.

[0152] The techniques described in this disclosure may be implemented, at least in part, in hardware, software, firmware or any combination thereof. For example, various aspects of the described techniques may be implemented within one or more processors or processing circuitry, including one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. The term “processor” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry. A control unit including hardware may also perform one or more of the techniques of this disclosure.

[0153] Such hardware, software, and firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure. In addition, any of the described units, circuits or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different featuresas circuits or units is intended to highlight different functional aspects and does not necessarily imply that such circuits or units must be realized by separate hardware or software components. Rather, functionality associated with one or more circuits or units may be performed by separate hardware or software components or integrated within common or separate hardware or software components.

[0154] The techniques described in this disclosure may also be embodied or encoded in a computer-readable medium, such as a computer-readable storage medium, containing instructions that may be described as non-transitory media. Instructions embedded or encoded in a computer-readable storage medium may cause a programmable processor, or other processor, to perform the method, e.g., when the instructions are executed. Computer readable storage media may include random access memory (RAM), read only memory (ROM), programmable read only memory (PROM), erasable programmable read only memory (EPROM), electronically erasable programmable read only memory (EEPROM), flash memory, a hard disk, a CD-ROM, a floppy disk, a cassette, magnetic media, optical media, or other computer readable media.

[0155] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

1. WHAT IS CLAIMED IS:

1. A system comprising: processing circuitry configured to: receive, via sensing circuitry, a plurality of evoked compound action potential (ECAP) signals elicited by electrical stimulation and sensed via a first electrode combination including at least a first electrode of an array of electrodes disposed within a blood vessel; receive, via the sensing circuitry, a plurality of physiological signals via a second electrode combination including at least a second electrode of the array of electrodes disposed within the blood vessel; determine an ECAP characteristic value for each ECAP signal of the plurality of ECAP signals; determine a physiological signal characteristic value for each physiological signal of the plurality of physiological signals; and select, based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, one or more stimulation parameters that at least partially define subsequent electrical stimulation therapy deliverable via at least one electrode of the array of electrodes disposed within the blood vessel.

2. The system of claim 1 , further comprising an implantable medical device (IMD) comprising an array of electrodes configured for endovascular neuromodulation therapy.

3. The system of claim 2, wherein the endovascular neuromodulation therapy comprises vagus nerve stimulation (VNS).

4. The system of any of claims 1 through 3, wherein the plurality of physiological signals comprises an electromyogram (EMG) signal.

5. The system of claim 4, wherein the first electrode combination and the second electrode combination are the same, and wherein the processing circuitry is further configured to: identify components of the ECAP signal and components of the EMG signal based on a latency shift of the signal.

6. The system of any of claims 1 through 5, wherein the processing circuitry is configured to select the one or more stimulation parameters by at least selecting a stimulation electrode combination and a sensing electrode combination from the array of electrodes disposed within the blood vessel.

7. The system of any of claims 1 through 6, wherein the processing circuitry is configured to select the one or more stimulation parameters by at least identifying the one or more stimulation parameters defining stimulation that elicits an ECAP signal with a high amplitude ECAP characteristic value relative to other ECAP signals and a low amplitude physiological signal characteristic value relative to other physiological signals.

8. The system of any of claims 1 through 7, wherein to select the one or more stimulation parameters based on at least one ECAP characteristic value of the plurality of ECAP signals and at least one physiological signal characteristic value of the plurality of physiological signals, the processing circuitry is configured to at least: apply a first weight value to each ECAP characteristic value; and apply a second weight value to each physiological signal characteristic value, wherein the first weight value is larger than the second weight value.

9. The system of any of claims 1 through 8, wherein the processing circuitry is configured to: determine, for a plurality of potential pulse widths (PW) and a predefined current amplitude range, a corresponding plurality of growth curves; determine, based on the plurality of growth curves, a neural threshold;select, based on the neural threshold, a therapeutic dose, wherein the therapeutic dose comprises a PW of the plurality of potential PWs and a current amplitude range within the predefined current amplitude range; control therapy delivery circuitry of the system to deliver the therapeutic dose via at least one electrode of the array of electrodes disposed within the blood vessel; determine one or more physiological responses to the therapeutic dose based on one or more physiological signals sensed in response to delivery of the therapeutic dose; and adjust, based on the one or more physiological responses, the therapeutic dose to an adjusted therapeutic dose.

10. The system of claim 9, wherein the plurality of physiological signals comprises one or more of: an electroencephalogram (EEG) signal; a local field potential (LFP) signal; an electrocardiogram (ECG) signal; an EMG signal; a heart rate (HR) signal; a blood pressure (BP) signal; a signal indicative of cytokine activity; or a signal indicative of neurotransmitter activity.

11. The system of any of claims 1 through 10, wherein the array of electrodes is disposed on a stent.

12. The system of any of claims 1 through 11, wherein the processing circuitry is further configured to: determine an ECAP signal corresponding to the selected one or more stimulation parameters does not meet a signal quality criterion; and responsive to the ECAP signal not meeting the signal quality criterion, determine to output an instruction to reposition the array of electrodes.

13. The system of claim 12, wherein the signal quality criterion comprises a signal to noise ratio (SNR).

14. A non-transitory computer-readable medium comprising instructions that, when executed, cause the processing circuitry to perform the functions of any of claims 1 through 13.

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