Systems and methods for hemodynamic monitoring based treatment

Abstract

A system for monitoring hemodynamic effectiveness includes a lead assembly including a lead body configured to deliver electrical stimulation or to deliver a fluid. The system includes at least one stimulation source including a drug pump or a pulse generator, a sensing device configured to detect a hemodynamic property of a body part, and a processor configured to determine hemodynamic effectiveness based on the detected hemodynamic property. Hemodynamic properties may include vasodilation, vasoconstriction, increased blood flow, decreased blood flow, or other hemodynamic changes. A method for providing treatment includes positioning a lead body adjacent to a blood vessel, obtaining a baseline hemodynamic property, administering stimulation, detecting an updated hemodynamic property, and determining hemodynamic effectiveness based on a change between the baseline and updated hemodynamic properties. A closed-loop treatment system adjusts treatment values based on measurements detected by the sensing device to cause stimulation to reach target values.

Description

Attorney Docket No.: 00333-0003-00304SYSTEMS AND METHODS FOR HEMODYNAMIC MONITORING BASED TREATMENTCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 761,631, filed February 21, 2025. This application is related to U.S. Provisional Patent Application 63 / 334,373, filed April 25, 2022, U.S. Provisional Patent Application 63 / 478,285, filed January 3, 2023, U.S. Non-Provisional Patent Application 18 / 855,883 filed October 10, 2024, and International Application PCT / US23 / 66133 filed April 24, 2023, the entire contents of each of which are incorporated herein by reference.FIELD

[0002] The present disclosure relates to multimodal stimulation systems for delivering chemical and / or electrical stimulation to a patient, and more particularly to devices, systems, and methods for pain management, hemodynamic monitoring (e.g., vasodilation, vasoconstriction, blood flow changes), and arteriovenous fistula (AVF) maturation.BACKGROUND

[0003] Peripheral nerve blocks may be used to mitigate intra-operative and postoperative pain. A nerve block involves the injection of a local anesthetic around a nerve that innervates the surgical site. A drawback of nerve blocks is that they mitigate surgical pain for only a limited amount of time.

[0004] Opioids are often prescribed to address post-operative pain beyond the effective window of anesthetic injection. However, opioids are notoriously addictive, often leading to a potential cascade of social and health problems, including death.

[0005] This section is provided herein is for the purpose of generally presenting the context of the disclosure. Unless otherwise indicated herein, the materials described in this section are not prior art to the claims in this application and are not admitted to be prior art, or suggestions of the prior art, by inclusion in this section.SUMMARYAttorney Docket No.: 00333-0003-00304

[0006] According to an aspect of the present disclosure, a system for monitoring hemodynamic effectiveness is provided. The system comprises a lead assembly including a lead body, wherein the lead body includes at least one stimulation delivery point. The system further comprises at least one stimulation source in communication with the lead assembly for providing a stimulation via the at least one stimulation delivery point. The system further comprises a sensing device comprising a sensor configured to detect a hemodynamic property of a body part. The system further comprises a processor configured to execute instructions to determine hemodynamic effectiveness based on the detected hemodynamic property at least one of before, during, or after the stimulation is delivered by the at least one stimulation source.

[0007] According to an aspect, the processor may be configured to calculate a perfusion index associated with tissue at the body part based on detection of a photoplethysmographic waveform using the sensor.

[0008] According to an aspect, the sensor may be a pulse oximeter sensor configured to emit light through skin and detect changes in light absorption caused by blood flow, wherein the pulse oximeter sensor may be configured to detect an alternating current signal corresponding to pulsatile blood flow and a direct current signal corresponding to non-pulsatile blood flow, and wherein the perfusion index may be determined based on a relationship between the alternating current signal and the direct current signal.

[0009] According to an aspect, the processor may be further configured to execute instructions to compare the detected hemodynamic property to a target hemodynamic property to detect capture, wherein capture may be detected when the detected hemodynamic property reaches or exceeds the target hemodynamic property.

[0010] According to an aspect, the at least one stimulation source may be at least one of a pulse generator, wherein the at least one stimulation delivery point includes one or more electrodes configured to deliver electrical stimulation; a drug pump, wherein the at least one stimulation delivery point includes one or more exit ports configured to deliver a fluid; or a thermal device, wherein the at least one stimulation delivery point includes a thermal element to change a temperature at the stimulation delivery point.

[0011] According to an aspect, the sensing device may be configured to detect at least one of a regional oximetry via oxygen saturation detection, a perfusion index, a near-infrared spectroscopy (NIRS) value, a blood flow rate, or a temperature at the body part.

[0012] According to an aspect, the processor may be further configured to execute instructions to determine a treatment value based on the detected hemodynamic property, wherein the treatment value comprises at least one of a dosage, a timing, a frequency, anAttorney Docket No.: 00333-0003-00304amplitude, a type, a polarity, a pulse width, or a rate related to the stimulation delivered by the at least one stimulation source, and to adjust the at least one stimulation source based on the treatment value.

[0013] According to an aspect, the treatment value may be determined based on at least one of a target oxygen level, a target perfusion index, a target NIRS value, a target temperature, or a target blood flow.

[0014] According to an aspect, the treatment value may be determined based on at least one of a target elasticity or dimensions of blood vessels.

[0015] According to another aspect of the present disclosure, a method for providing treatment based on monitoring hemodynamic properties is provided. The method comprises positioning a lead body adjacent to a nerve, wherein the lead body comprises at least one of one or more electrodes or one or more exit ports. The method further comprises obtaining, via a sensing device, a baseline hemodynamic property at a body part. The method further comprises administering at least one of chemical stimulation via the one or more exit ports or electrical stimulation via the one or more electrodes. The method further comprises detecting, via the sensing device, an updated hemodynamic property at the body part after administering the at least one of chemical stimulation or electrical stimulation. The method further comprises determining hemodynamic effectiveness based on a change between the baseline hemodynamic property and the updated hemodynamic property.

[0016] According to an aspect, the baseline hemodynamic property and the updated hemodynamic property may include a perfusion index, and wherein the perfusion index may reflect peripheral vasomotor tone at the body part.

[0017] According to an aspect, the method may further comprise, in response to determining that the change between the baseline hemodynamic property and the updated hemodynamic property reaches a target hemodynamic property, at least one of providing an indication that capture is confirmed or triggering an automated action comprising at least one of initiating subsequent electrical stimulation or initiating subsequent chemical stimulation.

[0018] According to an aspect, administering the at least one of chemical stimulation or electrical stimulation may be performed for at least one of lead placement capture confirmation, arteriovenous fistula maturation, critical limb ischemia treatment, Buerger's disease, Raynaud's disease treatment, spinal cord ischemia treatment, increase in blood vessel diameter, migraines, wound healing, or treatment of wound dehiscence.

[0019] According to an aspect, the method may further comprise adjusting at least one of a dosage, a timing, a frequency, an amplitude, a type, a pulse width, a polarity, or a rate ofAttorney Docket No.: 00333-0003-00304the at least one of chemical stimulation or electrical stimulation based on the determined hemodynamic effectiveness to reach at least one of a target oxygen level, a target perfusion index, a target NIRS value, a target temperature, or a target blood flow.

[0020] According to another aspect of the present disclosure, a closed-loop treatment system is provided. The closed-loop treatment system comprises a lead assembly comprising a lead body having one or more electrodes configured to deliver electrical stimulation and one or more exit ports configured to deliver a chemical stimulation. The closed-loop treatment system further comprises a drug pump in fluid communication with the one or more exit ports. The closed-loop treatment system further comprises a pulse generator in electrical communication with the one or more electrodes. The closed-loop treatment system further comprises a sensing device configured to detect at least one of oxygen levels, an NIRS value, a perfusion index, blood flow, or temperature at a treatment site. The closed-loop treatment system further comprises a processor configured to determine a treatment value based on measurements detected by the sensing device and to adjust the treatment value based on updated measurements detected by the sensing device to cause the at least one of the chemical stimulation or the electrical stimulation to reach at least one of a target oxygen level, a target NIRS value, a target perfusion index, a target temperature, or a target blood flow.

[0021] According to an aspect, the processor may be configured to execute a machine learning model trained to output the treatment value based on inputs comprising at least one of the measurements detected by the sensing device, an area of treatment, patient biometric values, patient demographics, or target values.

[0022] According to an aspect, the treatment value may comprise at least one of a dosage, a timing, a frequency, an amplitude, a pulse width, a type, a polarity or a rate related to at least one of the chemical stimulation delivered via the drug pump or the electrical stimulation delivered via the pulse generator, and wherein the treatment value may be adjusted to cause the at least one of the chemical stimulation or the electrical stimulation to reach at least one of the target oxygen level, the target NIRS value, the target perfusion index, the target temperature, or the target blood flow.

[0023] According to an aspect, the processor may be configured to output the treatment value such that stimulation is adjusted to prevent paresthesia by at least one of capping or reducing stimulation intensity, duration, or frequency levels.

[0024] According to an aspect, the sensing device may comprise a pulse oximeter sensor configured to determine the perfusion index based on a ratio of pulsatile blood flow to non-pulsatile blood flow.Attorney Docket No.: 00333-0003-00304

[0025] According to an aspect, the lead body may comprise at least one of a bioresorbable polymer or a biodegradable metal.BRIEF DESCRIPTION OF THE FIGURES

[0026] The accompanying drawings, which are incorporated into and constitute a part of this specification, illustrate various exemplary embodiments and, together with the description, serve to explain the principles of the disclosed embodiments. The drawings show different aspects of the present disclosure and, where appropriate, reference numerals illustrating like structures, components, materials, and / or elements in different figures are labeled similarly. It is understood that various combinations of the structures, components, and / or elements, other than those specifically shown, are contemplated and are within the scope of the present disclosure.

[0027] The drawings illustrate example embodiments of the present disclosure and, along with the description, serve to explain the principles of the disclosure. The drawings are only illustrative of certain embodiments and do not limit the disclosure or invention.

[0028] Figure 1 is a schematic illustration showing a portion of a multimodal system, according to an example embodiment of the present disclosure.

[0029] Figure 1A is a schematic illustration showing a drug pump, for use with the system of Figure 1, according to an example embodiment of the present disclosure.

[0030] Figure IB is a schematic illustration showing a pulse generator, for use with the system of Figure 1, according to an example embodiment of the present disclosure.

[0031] Figure 1C is a schematic illustration showing a combined drug pump and pulse generator, for use with the system of Figure 1, according to an example embodiment of the present disclosure.

[0032] Figure ID is a schematic illustration of another drug pump, according to an example embodiment of the present disclosure.

[0033] Figure IE is a schematic illustration of an internal view of the drug pump of Figure ID, according to an example embodiment of the present disclosure.

[0034] Figure IF is a flow diagram of operation of the drug pump of Figure ID, according to an example embodiment of the present disclosure.

[0035] Figure 2 is a schematic illustration showing a housing, an adhesive patch, and a connector, according to an example embodiment of the present disclosure.

[0036] Figure 2A is a schematic illustration showing another connector, according to an example embodiment of the present disclosure.Attorney Docket No.: 00333-0003-00304

[0037] Figure 2B is a schematic illustration showing another connector, according to an example embodiment of the present disclosure.

[0038] Figure 2C is a schematic illustration showing a top view of the housing and adhesive patch of Figure 2, according to an example embodiment of the present disclosure.

[0039] Figure 2D is a schematic illustration showing a bottom view of the housing and adhesive patch of Figure 2, according to an example embodiment of the present disclosure.

[0040] Figure 2E is a schematic illustration showing a side view of the housing and adhesive patch of Figure 2, according to an example embodiment of the present disclosure.

[0041] Figure 2F is a schematic illustration showing a cap, according to an example embodiment of the present disclosure.

[0042] Figure 2G is a schematic illustration showing another top view of the housing and adhesive patch of Figure 2, according to an example embodiment of the present disclosure.

[0043] Figure 2H is a schematic illustration of a drug pump, according to an example embodiment of the present disclosure.

[0044] Figure 21 is a schematic illustration of another housing, according to an example embodiment of the present disclosure.

[0045] Figure 2J is a schematic illustration of the interior of the housing of Figure 21, according to an example embodiment of the present disclosure.

[0046] Figure 2K is a schematic illustration of a bottom portion of the housing of Figure 21, according to an example embodiment of the present disclosure.

[0047] Figure 2L is a schematic illustration of a perspective view of the housing of Figure 21, according to an example embodiment of the present disclosure.

[0048] Figure 2M is a schematic illustration of a wearable pump, according to an example embodiment of the present disclosure.

[0049] Figure 2N is a schematic illustration of a back view of the wearable pump of Figure 2M, according to an example embodiment of the present disclosure.

[0050] Figure 20 is a schematic illustration of a wearable pump strap, according to an example embodiment of the present disclosure.

[0051] Figure 2P is a schematic illustration of the wearable pump of Figure 2M having a cover, according to an example embodiment of the present disclosure.

[0052] Figure 2Q is a schematic illustration of another wearable pump, according to an example embodiment of the present disclosure.

[0053] Figure 2R is a schematic illustration of a wearable pump attached to a user, according to an example embodiment of the present disclosure.Attorney Docket No.: 00333-0003-00304

[0054] Figure 2S is a schematic illustration of another wearable pump, according to an example embodiment of the present disclosure.

[0055] Figure 2T is a schematic illustration of the wearable pump of Figure 2S attached to a user, according to an example embodiment of the present disclosure.

[0056] Figure 2U is a schematic illustration of another wearable pump, according to an example embodiment of the present disclosure.

[0057] Figure 2V is a schematic illustration of the wearable pump of Figure 2U attached to a user, according to an example embodiment of the present disclosure.

[0058] Figure 2W is a schematic illustration of a needle guide system, according to an example embodiment of the present disclosure.

[0059] Figure 2X is another schematic illustration of the needle guide system of Figure 2W, according to an example embodiment of the present disclosure.

[0060] Figures 3 A-3F are schematic illustrations for positioning an infusion lead body substantially parallel to a nerve, according to an example embodiment of the present disclosure.

[0061] Figure 3G is a schematic illustration showing an infusion lead body inserted into a nerve sheath, according to an example embodiment of the present disclosure.

[0062] Figures 3H-3M are schematic illustrations for positioning an infusion lead body in a nerve sheath, according to an example embodiment of the present disclosure.

[0063] Figure 4A is a schematic illustration showing an implantable pulse generator (IPG), according to an example embodiment of the present disclosure.

[0064] Figure 4B is a schematic illustration showing a receiver (RX) module and a transmission (TX) module, according to an example embodiment of the present disclosure.

[0065] Figures 5A - 5C are schematic illustrations showing another multimodal system, according to an example embodiment of the present disclosure.

[0066] Figure 6 is a flowchart for bimodal, e.g., multimodal, stimulation, according to an example embodiment of the present disclosure.

[0067] Figure 7 is a flowchart for infusion lead body placement, according to an example embodiment of the present disclosure.

[0068] Figure 8A is a schematic illustration of an electronic placement detector, according to an example embodiment of the present disclosure.

[0069] Figure 8B is a schematic illustration of a visual placement detector, according to an example embodiment of the present disclosure.

[0070] Figure 9 is another schematic illustration of a multimodal system, according to an example embodiment of the present disclosure.Attorney Docket No.: 00333-0003-00304

[0071] Figure 10 is a flow diagram for training a machine learning model, according to an example embodiment of the present disclosure.

[0072] Figure 11 is a schematic example of a computing device, according to an example embodiment of the present disclosure.

[0073] Figures 12A-12B are images of sensing devices, according to an example embodiment of the present disclosure.

[0074] Figures 13A-13E are images of oxygen level outputs resulting from electrical and / or chemical stimulation, according to an example embodiment of the present disclosure.

[0075] Figure 14 depicts charts showing experimental hemodynamic measurements resulting from electrical and / or chemical stimulation, according to an example embodiment of the present disclosure.

[0076] Figure 15 is an image showing a clinical setting during a procedure involving vein dilation, according to an example embodiment of the present disclosure.

[0077] Figure 16 is a sequence diagram illustrating a closed-loop treatment process for monitoring hemodynamic effectiveness and adjusting treatment, according to an example embodiment of the present disclosure.

[0078] Figure 17 is a flowchart illustrating a method for providing treatment based on monitoring hemodynamic properties, according to an example embodiment of the present disclosure.

[0079] While embodiments of the disclosure are amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in some detail. It should be understood, however, that the intention is not to limit the disclosure to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.DETAILED DESCRIPTION

[0080] There are many embodiments described and illustrated herein. The described embodiments are neither limited to any single aspect nor implementation thereof, nor to any combinations and / or permutations of such aspects and / or implementations. Moreover, each of the aspects of the described embodiments, and / or implementations thereof, may be employed alone or in combination with one or more of the other aspects of the described embodiments and / or implementations thereof. For the sake of brevity, certain permutations and combinations are not discussed and / or illustrated separately herein. Notably, an embodiment orAttorney Docket No.: 00333-0003-00304implementation described herein as “exemplary” is not to be construed as preferred or advantageous, for example, over other embodiments or implementations; rather, it is intended reflect or indicate the embodiment(s) is / are “example” embodiment s).

[0081] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements, but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. The term “exemplary” is used in the sense of “example,” rather than “ideal.” In addition, the terms “first,” “second,” and the like, herein do not denote any order, quantity, or importance, but rather are used to distinguish an element or a structure from another. Moreover, the terms “a” and “an” herein do not denote a limitation of quantity, but rather denote the presence of one or more of the referenced items.

[0082] The term “distal end,” or any variation thereof, refers to the portion of a device farthest from an operator of the device during a procedure. Conversely, the term “proximal end,” or any variation thereof, refers to the portion of the device closest to the operator of the device. Further, any use of the terms “around,” “about,” “substantially,” and “approximately” generally mean + / - 10% of the indicated value(s).

[0083] A way to address post-operative pain is the use of a catheter and pump to deliver anesthetic over a prolonged period of time. However, the toxic nature of such anesthetics and / or the size and / or complexity of the catheters and pumps limits their standard use to several days post-operatively.

[0084] Peripheral nerve stimulation may be used to mitigate post-operative pain, but requires a separate procedure. The procedure involves inserting a lead with electrodes adjacent to the nerve that innervates the surgical site. A pulse generator is connected to the proximal end of the lead to deliver electrical stimulation to the nerve via the electrodes at the distal end of the lead. In a significant percentage of cases, nerve stimulation is not entirely effective at relieving post-operative pain. However, such cases are not identified until after the procedure is performed.

[0085] U.S. Patent No. 7,386,350 to Vilims describes a combination electrical and chemical stimulation lead for use in intervertebral discs to promote tissue regeneration and repair.

[0086] U.S Patent Application Publication 2021 / 0330977 to Sinha describes a similar combination catheter, but for use in providing pain control. The catheter includes a lumen for the delivery of an anesthetic to the target nerve in addition to electrodes for the delivery ofAttorney Docket No.: 00333-0003-00304electrical stimulation to the target nerve. To avoid interference between the anesthetic solution and the electrical stimulation, Sinha proposes that the exit port(s) be spaced apart from the electrodes. However, this may be problematic if the port(s) and electrodes are at different distances from the nerve, because proximity influences power requirements, stray effects, concentration and dilution rates at the nerve, and ultimately efficacy.

[0087] Other shortcomings of pain management systems in the prior art relate to practical challenges of self-administered pain management in the home setting, such as the use of an injection port requiring the patient to properly dose and inject anesthetic, the potential for migration of the stimulation electrodes, the potential for infection, etc. Further, the prior art does not address efficient conversion of post-operative (sub-chronic) pain management to chronic pain management, if needed.

[0088] Embodiments disclosed herein address an ongoing need to improve multimodal (chemical and electrical) pain management systems. For example, it is desirable to configure such systems and / or methods of use such that one mode of therapy does not compromise the other. It is also desirable to provide selective treatment (e.g., chemical and / or electrical stimulation) to provide motor pain management, sensory pain management, vasodilation, and / or arteriovenous fistula (AVF) maturation. A variable set of parameters, including current amplitude, frequency, pulse width, and polarity, may allow for intra or extra vascular neurostimulation to alter the elasticity or dimensions of blood vessels, including arteries and veins, so that fluid flow rate can be controllably manipulated. Neuromodulation parameter settings may potentially induce a local and systemic effect. The interaction between neuromodulation parameters, specific to patient and application, may provide an optimal scenario specific to the application. It is also desirable to configure such systems and / or methods such that they are suitable for use by patients in the home-setting and / or without attendance by medical staff. Further, it is desirable to configure such systems such that they may be converted to partially or fully implantable systems to address chronic pain management if the need arises. For implantable applications, a closed loop system may allow for longitudinal optimization of settings. The present disclosure offers a number of different embodiments to address these needs.

[0089] With reference to Figure 1, a portion of a multimodal pain management system consistent with some embodiments is shown schematically. The system may generally include an infusion lead assembly 100 configured for releasable connection to a drug pump 200 as shown in Figure 1 A, a pulse generator 300 as shown in Figure IB, or a combined drug pump and pulse generator 200 / 300 as shown in Figure 1C via a housing 140, a connector 150 andAttorney Docket No.: 00333-0003-00304associated infusion tube 210 and cable 310. The housing 140 may be secured to the epidermis via an adhesive patch 160 to mitigate migration. The top portion of the adhesive patch 160 may be attached (e.g., permanently) to the underside of the housing 140, and the bottom portion of the patch 160 may include an adhesive layer (e.g., suitable for approximately 10 - 14-day use under most living conditions) covered by a removable covering (e.g., removable wax paper) until ready for application to the epidermis.

[0090] The infusion lead assembly 100 may include a tubular infusion lead body 110 having a proximal end connected to the housing 140. The infusion lead body 110 may include an infusion lumen (not visible) extending therethrough providing fluid communication between exit ports 118 and the drug pump 200 via housing 140, connector 150, and infusion tube 210 (e.g., when connector 150 is connected to housing 140). The infusion lead body 110 may further include one or more distal electrodes 112 and one or more proximal electrodes 114 in electrical communication with the pulse generator 300 via wires (not visible) embedded in the wall of the infusion lead body 110, via internal wires (not shown) extending through the housing 140 and connector 150, and via cable 310. The internal wires embedded in the wall of the infusion lead body 110 may extend alongside at least a portion of the infusion lumen of infusion lead body 110.

[0091] When inserted through and / or adhered to the skin as shown, the infusion lead body 110 may have a suitable length to position the distal electrodes 112 and exit ports 118 adjacent a nerve that innervates a surgical site. With this arrangement, a drug (e.g., a fluid, an anesthetic solution, etc.) may be delivered from the drug pump 200 to the nerve via ports 118, and electrical stimulation may be delivered from the pulse generator 300 to the nerve via electrodes 112, to provide combined chemical and electrical nerve block effects. Exit ports 118 may be a single opening or a plurality of openings.

[0092] Drug pump 200, pulse generator 300, connector 150, housing 140, and / or one or more other components disclosed herein may include or be associated with (e.g., in communication with) a safety mechanism. The safety mechanism may be configured to prevent chemical and / or electrical stimulation from being administered to a user in excess of one or more threshold properties (e.g., prevent accidental stimulation). The safety mechanism may be implemented as a software component, hardware component, mechanical, and / or firmware component. The safety mechanism may prevent or mitigate accidental stimulation and may be configured to be overridden by a user (e.g., a patient or an administrator). The threshold property may be, for example, a threshold amount (e.g., approximately 2cc, approximately 5cc, approximately 30v, etc.), a threshold time (e.g., approximately 5 seconds,Attorney Docket No.: 00333-0003-00304approximately 20 seconds, etc.), a threshold frequency (e.g., within approximately 3 hours of a previous delivery, approximately once a day, etc.), and / or the like. For example, the safety mechanism may be a software or electronic component that tracks chemical and / or electrical properties (e.g., an amount, duration, time, etc.) of chemical and / or electrical stimulation. The safety mechanism may track one or more properties using one or more sensors, such as a volume sensor (e.g., configured to track an amount of drug), a clock, a counter, a signal sensor, and / or the like. The safety mechanism may electronically prevent chemical and / or electrical stimulation (e.g., for a determined or predetermined duration of time) by transmitting a signal to a component (e.g., drug pump 200, pulse generator 300, a physical blocking component, etc.). As another example, the safety mechanism may be or may be associated with a physical component (e.g., a ticker, a physical counter, a lock, a valve, switch, etc.) configured to detect a chemical and / or electrical stimulation property and / or to prevent chemical and / or electrical stimulation (e.g., for a determined or predetermined amount of time, in excess of a determined or predetermined amount, etc.). The physical component may block or otherwise restrict chemical and / or electrical stimulation in response to a signal or in response to determining a chemical and / or electrical stimulation property reaching or exceeding a threshold value.

[0093] The electrical stimulation may be provided in a unipolar mode or a bipolar mode. For example, one of the distal electrodes 112 may serve as a cathode while the other distal electrode 112 serves as an anode. Alternatively, both distal electrodes 112 may be electrically configured (e.g., shorted) to serve as a combined anode or cathode, and the proximal electrode 114 may serve as a cathode or anode, respectively. The proximal electrode 114 may serve as effective ground.

[0094] Infusion lead body 110 may further include or be attached to an anchor 113 or anchor 113 A. Anchor 113 and / or anchor 113 A may be shaped to or may include a material to secure infusion lead body 110 at a determined or predetermined location such that infusion lead body 110 remains proximate to and / or substantially parallel to a nerve. Anchor 113 and / or anchor 113 A may be a cuff or other attachment mechanism. Anchor 113 and / or anchor 113 A may prevent gross migration of infusion lead body 110 such that movement of lead body 110 is prevented or mitigated. Anchor 113 and / or anchor 113 A may be configured to have strain relief (e.g., via coiling of anchor 113 and / or anchor 113A) such that the strain relief prevents or mitigates movement and / or detachment of anchor 113, anchor 113A, and or infusion lead body 110. Anchor 113 and / or anchor 113A may be include bioresorbable or biodegradable material, as discussed herein. Anchor 113 of infusion lead body 110 may attach to tissue (e.g., tissue proximate to a nerve) via any applicable attachment technique such as, but not limitedAttorney Docket No.: 00333-0003-00304to, a force connection, a friction connection, an adhesive connection, or the like or a combination thereof. For example, anchor 113 may include a proximal end attached to infusion lead body 110 and a distal end having a hook shape or C-shape. The hook shaped or C-shaped distal end may be latched to tissue such that the tissue is positioned within the hook or C-shape of the distal end of anchor 113. The distal end of anchor 113 may be latched to the tissue by rotating infusion lead body 110 and / or infusion lead assembly 100 during insertion of infusion lead body 110 and / or infusion lead assembly 100, as discussed in reference to Figures 3A-3F. Anchor 113A may be positioned proximate to the housing 140 and may attach to tissue proximate to housing 140, to a patient’s skin (e.g., the underside of the patient’s skin), and / or to adhesive patch 160. Anchor 113A may include a magnetic or metallic component which may magnetically attract a corresponding magnetic or metallic component of housing 140. Infusion lead body 110 may include no anchors, may include anchor 113 or anchor 113 A, may include anchor 113 and anchor 113 A, and / or any other applicable mechanism to secure infusion lead body 110 such that infusion lead body 110 remains proximate to and / or substantially parallel to a given nerve. Infusion lead body 110 may be braided to prevent coiling.

[0095] Figure ID is a schematic illustration of another drug pump 180, according to an example embodiment of the present disclosure. Drug pump 180 may be a spring-loaded drug pump and may be activated by depressing an activation button 182. Activation of drug pump 180 may cause a fluid (e.g., drug) stored at drug pump 180 to expel via port 183. Activation of drug pump 180 by depressing activation button 182 may trigger transmission of the fluid via port 183 and through an internal lumen (e.g., internal lumen 154, as further discussed herein) and / or to a delivery site (e.g., proximate to a nerve). Drug pump 180 may include an inlet 184 configured to retrieve a fluid from an external container (not shown), as further discussed herein in reference to Figure IE and Figure IF.

[0096] Figure IE is a schematic illustration of an internal view of drug pump 180. As shown, drug pump 180 may include a spring system including one or more resilient members, e.g., springs 186. Depressing activation button 182 may result in depressing springs 186 causing springs 186 to transition to a first position (e.g., loaded position). Depressing activation button 182 may cause the activation button 182 to lock in the depressed position for a determined or predetermined amount of time, until released by a user, and / or until released based on a signal. For example, a safety mechanism, as discussed herein, may generate a signal to release activation button 182 after a threshold amount of time has expired. The threshold amount of time may be determined by a machine learning model and / or based on user treatment plan. The locking of activation button 182 may mitigate or prevent accidental delivery of aAttorney Docket No.: 00333-0003-00304drug in excess of an intended amount. After completion of a depressing action (e.g., releasing activation button 182, release of lock, signal from a safety mechanism, etc.), the loaded springs 186 expand from the first position to a second position (e.g., unloaded position). The change of springs 186 from the first position to the second position may cause the activation button 182 to expand to a first position (e.g., initial position) such that activation button 182 can be depressed a subsequent time, causing additional fluid to expel from port 183. Additionally, the change of springs 186 from the first position to the second position may cause a suction condition such that a suction pressure is applied via inlet 184. Inlet 184 may be connected to an external container that includes additional fluid (e.g., the same fluid expelled by drug pump 180 or a different fluid). The suction pressure may cause the additional fluid from the external container to be retrieved into drug pump 180, via inlet 184.

[0097] Drug pump 180 may include a valve system 190 (e.g., a dual valve system) that facilitates expelling fluid from drug pump 180, via port 183, upon depressing activation button 182. For example, a first valve component (not shown) of valve system 190 may be in an open position as fluid is expelled from drug pump 180, via port 183. The first valve component may transition to a closed position after the fluid is expelled and a second valve component (not shown) may transition from a closed position to an open position such that suction pressure is applied via inlet 184, as discussed herein. Accordingly, valve system 190 may facilitate expelling fluid via port 183 and may further facilitate retrieving additional fluid from an external container, via inlet 184. Valve system 190 and / or the second valve component may be configured such that no more than a determined or predetermined amount of fluid is retrieved from the external container. For example, valve system 190 and / or the second valve component may be configured such that only a determined or predetermined amount (e.g., approximately 2cc) of fluid is retrieved into drug pump 180, thereby preventing accidental delivery of a fluid in excess of the determined or predetermined amount of fluid.

[0098] Figure IF is a flow diagram illustrating example operation of drug pump 180. As shown at step 192, activation button 182 may be depressed from a first position to a second position, causing a fluid to be expelled from drug pump 180 to a device (e.g., connector 150), via port 183. Step 194 shows the activation button 182 in a second position, where springs 186 of Figure IE are in a first position (e.g., loaded position) and the fluid has been expelled via port 183. Springs 186 may transition from the first position to a second position (e.g., unloaded position), causing the activation button to return to the first position. The transition may cause application of the suction pressure discussed herein, resulting in additional fluid to be retrieved from an external container into drug pump 180, via inlet 184 of Figures ID and Figure IE.Attorney Docket No.: 00333-0003-00304

[0099] With reference to Figure 2, a more detailed top-view schematic of housing 140 and connector 150 are shown. Connector 150 may have a pair of tabs 151 that provide snap-fit interlock with corresponding indents 141 in housing 140. It will be understood that connector 150 may connect or attach to housing 140 in any applicable manner including, but not limited to, the snap-fit interlock show in Figure 2, via another snap-fit connection, via a force connection, via a fastener, or the like or a combination thereof. Connector 150 may detach from housing 140 via any applicable manner (e.g., a threshold amount of force, a release mechanism, a button or other input, etc.). Connector 150 may detach from housing 140 without dislocating and / or disturbing infusion lead body 110. Connector 150 may also include an insert molded hypodermic needle 152 in fluid communication, via an internal lumen 154, with infusion tube 210, as well as one or more metal pins 153 in electrical communication, via internal conductive traces 155, with cable 310. Similarly, housing 140 may include a hypodermic needle receptacle 142 and one or more pin receptacles 143, each with a corresponding gasket to form a fluid seal. Metal pins 153, internal conductive trances 155, pin receptacles 143, and / or conductive trances 145 may include electrical surfaces to transmit electrical signals across each respective component. The gaskets may be combined with one or more in-line filters to mitigate the ingress of bacteria. For example, an in-line filter may include or may be coated with antibacterial material or coating. A lumen 144 in the housing 140 provides fluid communication with the internal lumen of infusion lead body 110, and thus fluid communication with exit ports 118. Similarly, conductive traces 145 in housing 140 provide electrical communication with electrodes 112, 114. When connector 150 engages housing 140 (e.g., by sliding towards housing 140), the male fittings on the connector 150 functionally engage with the corresponding female fittings in the housing 140, thus functionally connecting the infusion lead body 110 to the drug pump 200 and / or pulse generator 300.

[0100] The housing 140 may further include a gasket 146 to provide a fluid seal around an insertion needle (described elsewhere herein) and subsequently close when the insertion needle is removed. The connector 150 may be configured for electrical stimulation only as shown in Figure 2A, or the connector 150 may be configured for chemical stimulation only as shown in Figure 2B. As shown in Figure 2A, according to an embodiment, connector 150 may be manufactured or adjusted to include internal conductive traces 155, one or more metal pins 153, and a pair of tabs 151 and / or any other applicable connecting elements. As shown in Figure 2B, according to an embodiment, connector 150 may be manufactured or adjusted to include insert molded hypodermic needle 152, internal lumen 154, and a pair of tabs 151 and / or any other applicable connecting elements. According to an embodiment, connector 150 may be aAttorney Docket No.: 00333-0003-00304replaceable component such that the connector 150 of Figure 2, connector 150 of Figure 2A, connector 150 of Figure 2B, and / or cap 150A of Figure 2F may be interchangeable and / or disposable. Alternatively, or in addition, connector 150 may be modular such that one or more components of connector 150 (e.g., one or more metal pins 153, internal conductive traces 155, insert molded hypodermic needle 152, or internal lumen 154) may be attached to or detached from connector 150.

[0101] Figures 2C - 2E schematically show housing 140 and a variant of adhesive patch 160 in more detail. Figure 2C is a top view, Figure 2D is a bottom view, and Figure 2E is a side view. In this embodiment, adhesive patch 160 may include an open space 162 surrounded by perimeter 164 having a thickness that is greater than the infusion lead body 110. With this arrangement, excess length of the infusion lead body 110 may be arranged (e.g., in a spiral fashion), for example, inside the open space 162. The upper portion of the open space 162 may comprise an adhesive surface to secure the infusion lead body 110 (e.g., in its spiral configuration), and the bottom portion of the perimeter 164 may comprise an adhesive surface to secure the assembly to the skin. This configuration allows the infusion lead body 110 with its associated electrodes 112 and exit ports 118 to be placed in the desired lengthwise position (e.g., parallel to a nerve) independent of the length of the infusion lead body 110 while mitigating migration thereof. Additionally, this configuration allows the release of the excess length of infusion lead body 110 if housing 140 is accidentally detached from a user’s skin. For example, if housing 140 is accidentally detached from a user’s skin, release of the excess length of infusion lead body 110 may mitigate or prevent the portion of infusion lead body 110 inside the user’s body from dislodging and / or or being pulled out.

[0102] According to an embodiment, excess length of the infusion lead body 110 may be cut or otherwise removed from a remaining portion of the infusion lead body 110 (e.g., the portion inserted into a patient’s body). An excess proximal portion of the infusion lead body 110 may be cut using any applicable technique such as by using a blade or sharp surface, a laser, a perforation, or the like, or a combination thereof. The remaining portion of infusion lead body 110 may be connected to housing 140. For example, lumen 144 of housing 140 may be connected to the internal lumen of the remaining portion of infusion lead body 110. Similarly, conductive traces 145 of housing 140 may be connected to the internal wire of infusion lead body 110. This configuration allows the infusion lead body 110 with its associated electrodes 112 and exit ports 118 to be placed in the desired lengthwise position (e.g., parallel to a nerve) independent of the original length of the infusion lead body 110, while mitigating migration thereof.Attorney Docket No.: 00333-0003-00304

[0103] Figure 2F schematically shows cap 150A. Cap 150A may connect to housing 140 when connector 150 is not connected to housing 140. Connector 150 may be detached when electrical stimulation or chemical stimulation is not required (e.g., during activity). Cap 150A may be connected to housing 140 to mitigate infection risk by preventing contaminants (e.g., bacteria) from entering hypodermic needle receptacle 142 and one or more pin receptacles 143.

[0104] Cap 150A may connect to housing 140 in any applicable manner that provides a full or partial seal between hypodermic needle receptacle 142 one or more pin receptacles 143 and the environment. Cap 150A may have a pair of tabs 151 A that provide snap-fit interlock with corresponding indents 141 in housing 140. Cap 150A may also include a lumen insert 152A shaped to fit in lumen 144 and trace inserts 153 A shaped to fit in conductive traces 145. Lumen insert 152A and / or trace inserts 153A may include an anti-microbial treatment (e.g., a coating, a finish, a material, etc.) which may further mitigate risk of infection. Accordingly, lumen insert 152A and trace inserts 153 A may be shaped to fit lumen 144 and conductive traces 145, respectively, such that the anti-microbial treatment can be applied to lumen 144 and conductive traces 145. Connecting cap 150Ato housing 140 may mitigate risk of exposure to contaminants and the anti-microbial treatment provide via cap 150A may treat the gaskets, filters, openings, inner space, and / or inner surfaces of lumen 144 and / or conductive traces 145 to remove contaminants therefrom. Cap 150A may be stored or positioned in an anti-microbial component when disconnected from housing 140, such that the cap 150A antimicrobial treatment is restored while cap 150A is disconnected from housing 140. Alternatively, or in addition, the anti-microbial treatment of cap 150A may be periodically replenished by application of the anti -microbial treatment onto cap 150A (e.g., onto lumen insert 152A and trace inserts 153 A). As discussed herein, a safety mechanism configured to facilitate chemical and / or electrical stimulation based on a threshold property may be included in or may be associated with one or more of connector 150, cap 150A, housing 140, and / or another component discussed herein.

[0105] Figure 2G is a schematic illustration showing a top view of housing 140 and adhesive patch 160. Housing 140 may include pressure button 280A and pressure button 280B. When activated (e.g., pressed), pressure buttons 280A and 280B may cause pressure rods 282A and 282B, respectively, to apply a pressure at or around gasket 146. The pressure at or around gasket 146 may be transferred to needle 50, as further discussed herein. The pressure may cause needle 50 to be held in place such that needle 50 is not able to advance or retract from its current position. The pressure may cause needle 50 and infusion lead body 110 to remainAttorney Docket No.: 00333-0003-00304approximately stationary relative to each other. Buttons 280A and 280B and pressure rods 282A and 282B may be operated using a single hand to prevent or mitigate movement of needle 50 relative to infusion lead body 110. It will be understood that although activating pressure buttons 280A and 280B is describe to apply a pressure, buttons 280A and 280B and / or pressure rods 282A and 282B may be configured to apply the pressure when buttons 280A and 280B are not activated and release the pressure when 280A and 280B are activated. According to this embodiment, one or more additional components such a lever, a hinge, a release, or the like may be used to covert an activation pressure (e.g., as applied to activate buttons 280A and 280B) to release the pressure applied by pressure rods 282 A and 282B.

[0106] Figure 2H is a schematic illustration of a drug pump 200A. Drug pump 200A may be the same as or similar to drug pump 200 as disclosed herein. Drug pump 200A may include a knob 290, one or more handles 292, and / or a drug container 294 housed at least partially within drug pump 200A. Drug container 294 may be configured to house an amount of one or more drugs (e.g., approximately 20cc per drug). Knob 290 may manually or automatically rotate such that each rotation may expel a predetermined amount of a drug stored at drug container 294 (e.g., approximately 5cc). Operation of knob 290 may be controlled by a safety mechanism, as discussed herein, where the safety mechanism is configured to prevent accidental and / or excess rotation of knob 290 (e.g., prevent an excess volume of drug, prevent frequent administration of a drug beyond a threshold amount, etc.). Although a rotatable knob 290 is shown, it will be understood that any applicable activation mechanism may be used to expel an amount of drug stored at drug container 294. For example, the activation mechanism may be a button, a slider, an electronic input receiver, a digital input receiver, and / or the like. Additionally, although a single drug container 294 is shown, it will be understood that multiple drug containers 294 storing the same or different drugs may be provided. In an embodiment where multiple drug containers are provided, an activation mechanism for each drug container of the multiple drug containers may be provided. Each such activation mechanism may be configured to expel all or a portion of the drug contained within a respective drug container based on a respective activation using a respective activation mechanism.

[0107] Knob 290 may be activated by rotating knob 290 by a given amount. The given amount may be predetermined amount. For example, one or more locks (not shown) may apply a counterforce to the rotation force of knob 290 such that rotation of knob 290 is temporarily terminated, after a partial rotation of knob 290, as a result of the counterforce. The one or more locks may prevent or mitigate accidental rotation of knob and, thereby prevent accidental administration of an excess amount of drug. A predetermined amount (e.g., approximately 5cc)Attorney Docket No.: 00333-0003-00304of drug contained in the drug container 294 may be expelled as result of the rotation of knob 290. Rotation of knob 290 may be reinitiated for a subsequent partial rotation, after the temporary termination, such that an additional amount of drug is expelled based on the subsequent partial rotation. Rotation of knob 290 may cause expelling of the drug contained in drug container 294 as a result of a pressure applied by rotation of knob 290, by an opening created as a result of the of rotation of knob 290, and / or the like.

[0108] Drug container 294 may be formed of any applicable material configured to contain the drug. Drug container 294 may be sealed such that the drug contained in drug container 294 is not expelled without activation of an activation mechanism, such as rotation of knob 290. Drug container 294 may be formed of any applicable material configured to contain a drug such as, but not limited to, polyvinyl chloride (PVC), plastic, glass, and / or the like. Drug container 294 may be a compartment, a bag, and / or the like. Drug container 294 may be configured to house a removable and / or replaceable drug holder (e.g., a replaceable bag) which may be replaced by a user (e.g., when all or most of the drug in a current drug holder is expelled). Drug container 294 and / or the drug holder may store an amount of one or more drugs corresponding to a given number of activations (e.g., approximately 4-6 activations).

[0109] According to an embodiment, an activation mechanism (e.g., knob 290) may be activated automatically based on an electronic signal generated by a controller (e.g., by an external controller as further discussed herein). The electronic signal may trigger a motor or other component configured to cause activation of the activation mechanism. The electronic signal may further indicate a degree of activation of the activation mechanism. For example, the degree of activation may cause an amount of corresponding activation (e.g., rotation). The amount of corresponding activation may result in a corresponding amount of drug expelled from drug container 294 such that a higher amount of activation may expel a higher amount of drug.

[0110] One or more handles 292 may protrude from drug pump 200 A and may be positioned against a user’s body part such that the base of drug pump 200A and / or one or more handles 292 provide stability when positioning drug pump 200 A against the user’s body part. Alternatively, or in addition, a strap (not shown) may be extended through the one or more handles 292. The strap may extend through the one or more handles 292 as well as a user’s body part (e.g., an ankle, a shoulder, an arm, a leg, etc.) such that drug pump 200A is secured to the user’s body part via the strap. As an example, the strap may be self-securing (e.g., a VelcroTM strap) such that a portion of the strap attaches to another portion of the strap.Attorney Docket No.: 00333-0003-00304

[0111] Figure 21 is a schematic illustration of another housing 140A, according to an example embodiment of the present disclosure. Housing 140A may be the same as, similar to, or different than housing 140, as discussed herein. Housing 140A may include a rear portion including an infusion tube port 210A and a cable port 310A. According to an implementation, housing 140A may connect (e.g., directly) to pulse generator 300 via cable 310 and / or connect (e.g., directly) to drug pump 200 via infusion tube port 210A. For example, infusion tube port 210A may be configured to receive and / or connect to infusion tube 210. Cable port 310A may be configured to receive and / or connect to cable 310. According to another implementation, housing 140A may connect to a connector (e.g., connector 150) For example, infusion tube port 210A may connect to insert molded hypodermic needle 152 of connector 150 and cable port 310A may connect to internal lumen 154 of connector 150.

[0112] Figure 2J is a schematic illustration of the interior view of housing 140A, Figure 2K is a schematic illustration of a bottom portion of housing 140A, and Figure 2L is a schematic illustration of a perspective view of housing 140A. As shown in Figures 2J - 2L, housing 140A may include an interior infusion tube port 210B connected to and / or in fluid communication with infusion tube port 210A. Housing 140 A may include an interior cable port 310B connected to and / or in electrical communication with cable port 310A. Internal infusion tube port 210B may include a lumen (e.g., lumen 144) in fluid communication with infusion tube 210, internal lumen 154, and / or an infusion lead body 110A. Infusion lead body 110A may be the same as or similar to infusion lead body 110, as discussed herein. A wire or electrical traces (not shown) may be provided to connect internal cable port 310B with an internal wire of infusion lead body 110A (e.g., via interior infusion tube port 210B) to provide electrical communication between cable 310 and wires (not visible) embedded in a wall of the infusion lead body 110A, as discussed herein in reference to infusion lead body 110. A bottom surface of housing 140A, shown in Figure 2K, may be or include an adhesive (e.g., a foam backed adhesive) for securing housing 140 A to a surface such as user’ s skin. An interior portion of housing 140 A that includes the internal infusion tube port 210B and interior cable port 310B may be filled with an electrical isolation material (e.g., a potting material) to insulate the wires and / or electrical traces connecting internal cable port 310B with the internal wire of infusion lead body 110A. Infusion tube port 210A, internal infusion tube port 210B, cable port 310A, internal cable port 310B, and / or one or more components associated with housing 140A may include a safety mechanism as discussed herein, where the safety mechanism is configured to prevent accidental and / or excess output of chemical and / or electrical stimulation. As discussed, the safety mechanism may be facilitated using an electrical signal such that chemical and / or electrical stimulation isAttorney Docket No.: 00333-0003-00304controlled in response to the electrical signal. For example, electrical activity via internal cable port 31 OB may be suspended for a determined or predetermined period of time, based on a signal generated by a safety mechanism. As another example, internal infusion tube port 21 OB may include a valve component that is configured to close for a determined or predetermined amount of time after a chemical stimulation is provided via internal tube port 210B. A signal to initiate closer of the valve may be generated by the safety mechanisms and a signal to terminate closer of the valve may be generated by the safety mechanism or may be automatically generated, for example, based on a duration of time.

[0113] According to an implementation, one or more drugs may be stored within a strap which may be secured to a user’s body part. The strap may be elastic and / or malleable (e.g., may have a softness or give above a threshold amount of softness or give), may be selfsecuring, and / or may be securable to a user’s body part. The strap may be or may include a drug holder (e.g., an Intravenous (IV) bag approximately 2 inches by 6 inches in size) configured to expel one or more drugs. The drug holder may be connected to a one way check valve (e.g., forming a “T” shape) configured to expel a drug from the drug holder. For example, a syringe or prime bulb (e.g., having approximately 3cc of volume) may be in connection with the drug holder and configured to pull a drug from the drug holder through a tube in fluid communication with a user (e.g., through tubing 210) via the one way check valve. The drug holder as well as one or more of a tube, a valve, etc. may be embedded within or otherwise attached to the strap. Accordingly, the strap may configured to contain one or more drugs via a drug holder and the one or more drugs may be expelled to be received by a user from the strap. According to an implementation, the strap may include one or more drug holders which may hold a given amount of drug (e.g., approximately lOOcc to approximately 500cc).

[0114] According to an implementation, one or more drugs may be stored within a wearable pump secured to a user’s body (e.g., using a strap, using an adhesive, etc.). Figure 2M is a schematic illustration of a wearable pump 296A and Figure 2N is a back view of the wearable pump 296A, according to an example embodiment of the present disclosure. Wearable pump 296A may include drug holding component 296C shaped to store a drug (e.g., within a chamber), as shown in Figure 2M. Drug holding component 296C may include a fluid container to hold a drug and may further include a retrieval component (e.g., a plunger) to expel and / or retrieve the drug from drug holding component 296C or into drug holding component 296C. Although Figure 2M shows a retrieval component (e.g., plunger) that may be exposed past an upper surface of holding component 296C for ease of access, it will be understood that a retrieval component, some components, and / or all movable components of and / or associatedAttorney Docket No.: 00333-0003-00304with holding component 296C may be secured and / or inaccessible during an operational state and / or during a nonoperational state of a wearable pump such as wearable pump 296A. For example, as shown in Figures 2P, 2R, and 2U, as further discussed herein, a retrieval component and / or other movable component may not extend past the boundaries of the respective wearable pumps, mitigating unintentional contact with and / or accidental movement of such a component. Wearable pump 296A may be connected to one or more straps 296B, as shown in Figure 20. The one or more straps 296B may be configured to secure the wearable pump 296A to a user’s body part, as discussed herein. Wearable pump 296A may be connected to a connector (e.g., connector 150) and / or may be directly connected to housing 140A to provide the drug to an infusion lead body (e.g., infusion lead body 110, infusion lead body 110A, etc.).

[0115] Figure 2P is a schematic illustration of wearable pump 296A having cover 296D, according to an example embodiment of the present disclosure. Figure 2P shows the cover 296D in a closed position at 295A, shows cover 296D in an open position from a back view at 295B, and shows the cover 296D in the open position from a front view at 295C. Cover 296D may cover all or a portion of holding component 296C. For example, cover 296D may cover all or portion of holding component 296C such that a user may not accidentally touch, move, or otherwise unintentionally interact with holding component 296C. According to an implementation, cover 296D may be shaped to include a chamber (not shown) to store a drug. According to this implementation, when cover 296D is in the open position, the holding component 296C may retrieve a determined or predetermined amount of drug from cover 296D (e.g., from a chamber of cover 296D). For example, in operation, a drug may be expelled from holding component 296C while cover 296D is in a closed position. Cover 296D may be transitioned to the open position and an additional amount of drug may be retrieved from cover 296D (e.g., from a chamber of cover 296D) into holding component 296C (e.g., by activating a plunger component associated with holding component 296C, causing a suction pressure to transfer an amount of drug from a chamber of cover 296D into holding component 296C).

[0116] Figure 2Q is a schematic illustration of another wearable pump 297A, according to an example embodiment of the present disclosure. Wearable pump 297A may be similar to wearable pump 296 A. Wearable pump 297 A may be configured to receive one or more cartridges 297B containing one or more drugs therein. Cartridges 297B may be interchangeable such that a user may remove a first cartridge 297B from wearable pump 297A and may insert a second cartridge 297B into wearable pump 297A. As shown, one or more cartridges 297B may be stored within a storage component of wearable pump 297A. As also shown, cartridgesAttorney Docket No.: 00333-0003-00304297B may be inserted into and / or removed from wearable pump 297A while a cover 297D is in an open or closed position. According to an implementation, instead of cartridges 297B, a holding component 297C may be inserted into wearable pump 297A. Alternatively, or in addition, holding component 297C may be used to refill one or more cartridges 297B. Wearable pump 297A may include a cover 297D, which may be similar to cover 296D discussed herein in reference to Figure 2P.

[0117] Figure 2R is a schematic illustration of a wearable pump 297A attached to a user, according to an example embodiment of the present disclosure. As shown, wearable pump 297A may be attached to a user body part (e.g., a leg). Wearable pump 297A may be attached to the user body part via an adhesive material (not shown). Alternatively, wearable pump 297A may be attached to the user body part via a strap (e.g., strap 296B).

[0118] Figure 2S is a schematic illustration of another wearable pump 298 A, according to an example embodiment of the present disclosure. Wearable pump 298A may be similar to drug pump 200A discussed in reference to Figure 2H. Wearable pump 298A may include an activation mechanism such as a knob 298B which may be similar to knob 290 of Figure 2H. Figure 2T is a schematic illustration of wearable pump 298A attached to a user body part. Wearable pump 298A may be attached to the user body part via an adhesive material (not shown). Alternatively, wearable pump 298A may be attached to the user body part via a strap (e.g., strap 296B).

[0119] Figure 2U is a schematic illustration of another wearable pump 299A, according to an example embodiment of the present disclosure. Wearable pump 299A may be similar to wearable pump 296A and / or wearable pump 297A. Wearable pump 299A may be connected to an infusion tube 299B which may be similar to infusion tube 210, as discussed herein. Wearable pump 299A may include a cover 299C, which may be similar to cover 296D discussed herein in reference to Figure 2P. As shown in Figure 2V, infusion tube 299B may be removable from wearable pump 299A such that while wearable pump 299A is not in operation, infusion tube 29B may be removed from wearable pump 299A. As also shown in Figure 2V, wearable pump 299A may be attached to a user body part. Wearable pump 299A may be attached to the user body part via an adhesive material (not shown). Alternatively, wearable pump 299A may be attached to the user body part via a strap (e.g., strap 296B).

[0120] According to an implementation, infusion lead body 110 and / or infusion lead body 110A may be positioned to be substantially parallel to a nerve, thus spacing the two modes of stimuli along a length of the nerve where they do not interfere with each other. Methods for achieving this position are described with reference to Figures 3A-3F, as further discussedAttorney Docket No.: 00333-0003-00304herein. According to another implementation, infusion lead body 110 may be positioned within a nerve sheath of a nerve that innervates a surgical site. Methods for achieving this position are described with reference to Figures 3H-3M, as further discussed herein.

[0121] Figure 2W is a schematic illustration of a needle guide system 2003, according to an example embodiment of the present disclosure. Needle guide system 2003 may be used to position infusion lead body 2008 (e.g., similar to infusion lead body 110 and / or infusion lead body 110A) substantially parallel to a nerve, as described with reference to Figures 3A-3F and / or within a nerve sheath of a nerve as described with reference to Figures 3H-3M. Needle guide system 2003 may include a needle guide base 2002 that is connected to a needle guide 2006. Needle guide 2006 may be configured to receive an infusion lead body 2008 and needle 50A (e.g., similar to needle 50 discussed herein), as shown in Figure 2X. Needle guide base 2002 may be positioned over a user’s skin proximate to an insertion point where needle 50A is inserted into the user’s body. A needle guide cover 2004, as shown in Figure 2W and Figure 2X, may be positioned on needle guide 2006. Needle guide 2006 may be rotatable around a first axis (e.g., substantially parallel to the needle guide base 2002), such that rotation of needle guide 2006 around the first axis may change the angle of insertion at which needle 50A is inserted at the insertion point. For example, rotation of needle guide 2006 around the first axis may cause the angle of insertion to change from approximately 85 degrees to approximately 5 degrees. The angle of insertion may be adjustable while needle guide cover 2004 is not positioned on needle guide 2006. The angle of insertion may be locked when needle guide cover 2004 is positioned on needle guide 2006. Once the angle of insertion is locked when needle guide cover 2004 is positioned on needle guide 2006, the angle may not change as needle 50A and / or infusion lead body 2008 is inserted into the insertion point (e.g., due to unintended movement). Accordingly, a practitioner may lock an angle of insertion and, once locked, may implement the techniques disclosed herein in reference to Figures 3A-3F and / or Figures 3H-3M using one hand, without risk of the angle of insertion changing. The angle of insertion may be determined based on the intended position of the infusion lead body 2008 such that a first intended position may require a first angle (e.g., 35 degrees) and as a second intended position may require a second, different, angle (e.g., 45 degrees). The intended position may be based on, for example, a nerve site, a body area for treatment (e.g., shoulder area, leg area, ankle area, etc.).

[0122] One or more drugs, as disclosed herein, may cause a regional anesthesia block for a vein proximate to the point of delivery (e.g., proximate to exit ports 118) of the one or more drugs, resulting in pain relief. Alternatively, or in addition, the one or more drugs mayAttorney Docket No.: 00333-0003-00304cause vasodilation of the tissue, vein, and / or nerve (e.g., resulting in a vein diameter over approximately 3mm), which may result in AVF maturation. AVF maturation may correspond to the ability of an inflow artery and the vein to respond to increased blood flow that occurs upon anastomosis of the artery and vein. The duration of the AVF maturation may exceed the duration of the vasodilation, such that a determined or predetermined amount of drug may result in vasodilation for a first period of time, and may cause AVF maturation for a second period of time, where the second period of time is greater than the first period of time. The vasodilation and / or AVF maturation may provide clinical benefits such as for vein grafts, improved wound healing, reduced infection rate, and / or the like based at least on increased blood flow over a period of time. For example, expelling a drug over a period of approximately five days may catalyze healing by a certain amount. Accordingly, vasodilation and / or AVF maturation, as discussed herein, may be used for pain management benefits, may facilitating ease of insertion or vein selection during a procedure (e.g., vasodilation may provide larger veins and / or better vein selection for an improved acute result), may increase blood flow, and / or the like. According to an implementation, chemical stimulation via the one or more drugs may be used to treat chronic wound healing and / or chronic pain relief (e.g., for complex regional pain syndrome (CRPS), dry gangrene, etc.).

[0123] According to an embodiment, an amount, frequency, or duration of stimulation may be determined to cause a given amount of vasodilation and / or AVF maturation (e.g., any vasodilation and / or AVF maturation) without providing pain relief. For example, a first amount, frequency, and / or duration of chemical stimulation may result in vasodilation and / or AVF maturation whereas a second greater amount, frequency, and / or duration of chemical stimulation may result in pain relief in addition to vasodilation and / or AVF maturation.

[0124] As disclosed herein, one or more drugs may be provided via drug pump 200 / 200A. The one or more drugs may include, but are not limited to, any applicable anesthetic, ropivacaine, bupivacaine, markain, lidocaine, dextrose, etc. A drug may be selected based on the conductivity or lack of conductivity of the drug. The amount of drug expelled via drug pump 200 / 200A may depend on the target nerve, tissue surrounding the target nerve, type of drug, and / or the target chemical stimulation (e.g., anesthetic effect, vasodilation, AVF maturation, etc.). For example, when targeting the tibial nerve, approximately 5cc may be expelled (e.g., as a single dose, per hour, per predetermined period of time, per activation, etc.). As another example, when targeting a shoulder nerve, 5cc may be expelled per hour. According to an implementation, a first initial amount of drug may be expelled at a first time (e.g., a first activation) and a second amount of drug may be expelled at a second time subsequent time. AsAttorney Docket No.: 00333-0003-00304further disclosed herein, the one or more drugs may be expelled as a bolus and / or may be expelled based on pulsed dosing (e.g., 3-5cc per period of time such as per approximately 3-4 hours). The amount of drug and / or frequency of activation may result in a corresponding result (e.g., approximately 6-8 hours of pain relief, approximately 8-10 hours of pain relief, approximately 10-12 hours of pain relief, a duration and / or amount of vasodilation, a duration and / or time of AVF maturation, etc. or a combination thereof). The duration of time and / or frequency that the one or more drugs are expelled may be based on a corresponding amount of battery life for a battery powering drug pump 200 / 200A and or external controller, as further discussed herein.

[0125] According to an embodiment, chemical or electrical stimulation may be triggered, modified, and / or updated based on user input or may be triggered automatically. User input may be received via a user device (e.g., a mobile device, computer, wearable device, etc.) and / or via an input component associated with any device or component disclosed herein. For example, a user may provide user input via a button or interface associated with housing 140, drug pump 200, pulse generator 300, and / or the like or a combination thereof. Such user input may be an instruction to trigger, modify, or update chemical or electrical stimulation, may be feedback regarding existing chemical or electrical stimulation, may be a user pain indication (e.g., a pain score), and / or the like.

[0126] Chemical and / or electrical stimulation may be conditioned on user input. For example, to increase compliance for user entered data, chemical and / or electrical stimulation may be administered in response to a user input. According to this example, the chemical and / or electrical stimulation may be triggered based on any user input, so long as there is a user input. For example, one or more properties (e.g., amount, frequency, duration, etc.) of chemical and / or electrical stimulation, as discussed herein, may or may not be determined based on the user input. However, the chemical and / or electrical stimulation may be withheld until a user input is received. According to an implementation, chemical and / or electrical stimulation may be conditioned on a specific user input based on a specific treatment. For example, receipt of a pain score may be required before administering (e.g., automatically) a bolus drug delivery. As another example, updated pain scores may be required for administering continued drug delivery (e.g., basal delivery).

[0127] Automatic stimulation may be triggered based on an event, an algorithmic output, or a machine learning output. An event based trigger may be based on, for example, a pain indication provided by a user, based on a change in a detected impedance, and / or the like. For example, one or more impedance sensors may be in contact with a vein, nerve, or tissueAttorney Docket No.: 00333-0003-00304and may generate impedance signals. Upon determining an impedance greater than a threshold impedance, based on the impedance signals, an event based trigger may cause automatic stimulation (e.g., chemical and / or electric stimulation). An algorithmic output may be generated based on one or inputs (e.g., a user input indicating pain or a pain amount, detected impedance, etc.) such that an amount, frequency, and / or duration of chemical or electrical stimulation is triggered based on application of the inputs to an algorithm. Machine learning outputs are further discussed herein.

[0128] To avoid potential interference between the anesthetic solution and stimulation (either by dispersion of the electric field in the anesthetic solution or by blocking the Sodium-Potassium receptor on nerve cell or neuron), when the two modes of nerve block are administered simultaneously or in near-time, exit ports 118 and electrodes 112 may be spaced apart along the length of infusion lead body 110. However, to maintain the same or similar efficacy of the chemical and electrical stimuli, infusion lead body 110 may be positioned to be substantially parallel to the nerve as shown, thus spacing the two modes of stimuli along a length of the nerve where they do not interfere with each other. Methods for achieving this position are described with reference to Figures 3A - 3F. However, other techniques may be employed such as alternating the delivery of chemical and electrical stimuli on a temporal basis such that electrical stimulation is delivered after the anesthetic solution has been substantially dispersed. For example, electrical stimuli could be delivered during the day, and chemical stimuli could be delivered during the night. This may be advantageous because chemical stimuli may interfere with motor function, whereas electric stimuli may not interfere with motor function. This would allow a patient to have physical therapy during the day without having motor function compromised.

[0129] Figures 3A - 3F schematically illustrate example methods for positioning infusion lead body 110 substantially parallel to the nerve for the reasons stated above. The example methods of Figures 3 A - 3F may be implemented using the needle guide system 2003 of Figure 2W and Figure 2X. It will be understood that although ultrasonic guidance is generally discussed herein, any applicable guidance technique (e.g., using radar, optical devices, sensors, etc.) may be used instead of and / or in addition to ultrasonic guidance. Needle 50 may include a proximal hub and a distal end (e.g., a sharped point) and may have a length suitable for extending through the gasket 146 in the housing 140, through infusion lead body 110, with the distal end of needle 50 extending out the distal end of infusion lead body 110. Needle 50 is also substantially more rigid than infusion lead body 110, thereby maintaining a straight configuration until removed. The diameter of needle 50 may be selected to closelyAttorney Docket No.: 00333-0003-00304match the inside diameter of the infusion lead body 110 to allow free movement therebetween but avoid a substantial gap that may otherwise compromise insertion through the skin.

[0130] Ultrasonic guidance may be used to locate a nerve (N) and / or a peripheral vein (V) or artery, adjacent to which a peripheral nerve (N) resides. The infusion lead assembly 100 may be pre-loaded onto the needle 50 such that the needle 50 extends through gasket 146 in housing 140 and out the distal end of the infusion lead body 110. According to an embodiment, buttons 280 A and 280B may be activated or deactivated to pre-load infusion lead assembly 100 onto needle 50. Under continued ultrasound guidance, needle 50 and pre-loaded infusion lead assembly 100 may be inserted through the skin (S) as shown in Figure 3 A, until the distal tip of the needle 50 is adjacent the nerve (N). The hub of the needle 50 may be pushed toward the skin (S), without advancement of the needle 50, as shown in Figures 3B and 3C, to urge the assembly 100 into substantially parallel alignment with the nerve (N). This step involves displacing the nerve (N) and surrounding tissue in the opposite direction of the pushing force as opposed to cutting through tissue. With the infusion lead body 110 generally running parallel with the nerve, the needle 50 and infusion lead assembly 100 may be advanced under continued ultrasound guidance to avoid damage to the nerve (N) and avoid puncturing the vein (V) as shown in Figure 3D. According to an implementation, infusion lead body 110 may be advanced past the needle tip of needle 50 without substantial movement of needle 50. Accordingly, needle 50 may surround a proximate portion of the infusion lead body 110 while a distal portion of the infusion lead body 110 extends past the tip of needle 50. Once the infusion lead assembly 100 is fully advanced with the adhesive patch 160 engaging the skin (S), the paper backing of the adhesive patch 160 may be removed, and then the needle 50 may be removed from the infusion lead assembly 100 as shown in Figure 3E. According to an embodiment, buttons 280A and 280B may be activated or deactivated to remove needle 50 from infusion lead assembly 100. As the needle 50 is removed, the flexible nature of the infusion lead body 110 and the absence of the stiff needle 50 allows the nerve (N) and surrounding tissue to relax to its resting state, thereby resulting in a curved proximal portion of the infusion lead body 110, a relatively straight portion of the infusion lead body 110 running substantially parallel with the nerve (N), and the adhesive patch 160 securing the housing 140 to the skin directly over the insertion site to mitigate migration as shown in Figure 3F.

[0131] According to an embodiment, infusion lead body 110 may be positioned within a nerve sheath of a nerve that innervates a surgical site. A nerve sheath is a layer of myelin and / or connective tissue that surrounds and insulates nerve fibers. Figure 3G schematically shows infusion lead body 110 positioned to be substantially parallel to the nerve with a distalAttorney Docket No.: 00333-0003-00304portion of infusion lead body 110 positioned within a nerve sheath (sheath). When inserted through and / or adhered to the epidermis (skin) and inserted in the sheath, as shown, the infusion lead body 110 may have a suitable length to position the distal electrodes 112 and exit ports 118 adjacent a nerve that innervates a surgical site. With this arrangement, a drug (e.g., anesthetic solution) may be delivered from the drug pump 200 to the nerve via exit ports 118, and electrical stimulation may be delivered from the pulse generator 300 to the nerve via electrodes 112, to provide combined chemical and electrical nerve block effects. A cover (e.g., having a valve, a slit, etc.) may be positioned over exit ports 118 and may mitigate or prevent occlusion of exit ports 118. The cover may be a silicone cover or may include bioresorbable or biodegradable material. The cover may be on an external surface of exit ports 118 or an internal surface of exit ports 118 (e.g., internal to infusion lead body 110).

[0132] Methods for achieving this position are described with reference to Figures 3H - 3M. The example methods of Figures 3H - 3M may be implemented using the needle guide system 2003 of Figure 2W and Figure 2X. Aspects of this method are similar to those described in Figures 3 A-3F. Ultrasonic guidance may be used to locate a nerve, a nerve sheath, and / or a peripheral vein or artery, adjacent to which a peripheral nerve resides. The infusion lead assembly 100 may be pre-loaded onto the needle 50 such that the needle 50 extends through gasket 146 (not shown) in housing 140 and out the distal end of the infusion lead body 110. According to an embodiment, buttons 280A and 280B may be activated or deactivated to preload infusion lead assembly 100 onto needle 50. Under continued ultrasound guidance, needle 50 and pre-loaded infusion lead assembly 100 may be inserted through the skin as shown in Figure 3H, until the distal tip of the needle 50 punctures the sheath, as shown. As shown in Figure 31, the distal end of infusion lead body 110 may also breach the sheath through the opening created by the tip of needle 50 puncturing the sheath. The hub of the needle 50 may be pushed toward the skin, without substantial advancement of the needle 50, as shown in Figures 31 and 3 J, to urge the assembly 100 into substantially parallel alignment with the nerve while the distal tip of needle 50 and the distal end of infusion lead body 110 is between the sheath and the nerve. This step involves displacing the nerve and surrounding material (e.g., tissue, sheath material, etc.) in the opposite direction of the pushing force. As shown in Figures 3L3L, the hub of needle 50 may be pulled away from infusion lead body 110 while infusion lead body 110 is pushed further into the sheath. Accordingly, the distal end of infusion lead body 110 may be inserted into the sheath without needle 50 being inserted into the sheath, mitigating the risk of needle 50 puncturing or damaging the vein or nerve. According to an embodiment, buttons 280A and 280B may be activated or deactivated to pull needle 50 awayAttorney Docket No.: 00333-0003-00304from infusion lead body 110. With the distal end of infusion lead body 110 positioned between the sheath and the nerve, and infusion lead body 110 generally running parallel with the nerve, infusion lead assembly 100 may be advanced under continued ultrasound guidance to avoid damage to the nerve and avoid puncturing the vein as shown in Figure 3K. Once the infusion lead assembly 100 is fully advanced with the adhesive patch 160 engaging the skin, the paper backing of the adhesive patch 160 may be removed, and then the needle 50 may be fully removed from the infusion lead assembly 100 as shown in Figure 3L. As the needle 50 is removed, the flexible nature of the infusion lead body 110 and the absence of the stiff needle 50 allows the nerve, nerve sheath, and surrounding tissue to relax to its resting state, thereby resulting in a curved proximal portion of the infusion lead body 110, a relatively straight portion of the infusion lead body 110 running substantially parallel with the nerve. As shown in Figure 3M, electrodes 112 and exit ports 118 may be positioned within the sheath such that a drug (e.g., anesthetic solution) may be delivered from the drug pump 200 to the nerve via ports 118 within the sheath, and electrical stimulation may be delivered from the pulse generator 300 to the nerve via electrodes 112 within the sheath, to provide combined chemical and electrical nerve block effects. Adhesive patch 160 may secure the housing 140 to the skin directly over the insertion site to mitigate migration, as shown in Figure 3M.

[0133] According to an embodiment, the sheath may be punctured or otherwise cut prior to inserting needle 50 and pre-loaded infusion lead assembly 100 through the skin and sheath, as shown in Figure 3H. The sheath may be punctured or otherwise cut using any applicable technique such as a cutting device used to puncture or cut the sheath under ultrasound guidance. Accordingly, needle 50 and pre-loaded infusion lead assembly 100 may be inserted through the skin and the pre-punctured or pre-cut sheath, instead of the distal tip of needle puncturing the sheath in Figure 3H.

[0134] According to an embodiment, electrodes 112 and exit ports 118 may be positioned proximate to each other such that both electrodes 112 and exit ports 118 are positioned inside the sheath, as shown in Figures 3M. According to this embodiment, the amount of fluid (e.g., drug) delivered via exit ports 118 may be less than if exit ports 118 are positioned external to the sheath. Additionally, according to this embodiment, the size of exit ports 118 may be smaller than the size if exit ports 118 are positioned external to the sheath.

[0135] According to an embodiment, the distal end of infusion lead body 110 may be positioned such that electrodes 112 are positioned inside the sheath while exit ports 118 remain outside the sheath. According to this embodiment, infusion lead body 110 may still be positioned substantially parallel to the nerve, as disclosed herein. Electrical stimulation may beAttomey Docket No.: 00333-0003-00304delivered from the pulse generator 300 to the nerve via electrodes 112 within the sheath, while a drug delivered from the drug pump 200 to the nerve is delivered outside the sheath.

[0136] For sub-chronic (e.g., for less than approximately 60 days) and / or chronic pain management (e.g., for approximately 60 days or more), all or a portion of the infusion lead assembly 100, the drug pump 200 and the pulse generator 300 may be implanted under the skin. For example, an implantable pulse generator (IPG) 400 implanted under the skin may replace the housing 140 as shown in Figure 4A. Alternatively, a combination of a receiver (RX) module 500 implanted under the skin and a wirelessly linked to a transmission (TX) module 550 (connected to an external pulse generator (EPG)) may replace the housing 140 as shown in Figure 4B. A safety mechanism, as discussed herein, may be included in or associated with RX module 500 and / or TX module 550. The safety mechanism may be configured to prevent accidental and / or excess chemical and / or electrical stimulation in accordance with the techniques disclosed herein. For example, a safety mechanism may generate a signal to prevent electrical stimulation for a determined or predetermined period of time, in response to administration of electrical stimulation. After the determined or predetermined period of time, RX module 500, TX module 550, and / or the safety mechanism may generate a release signal allowing additional electrical stimulation. To facilitate the injection of an anesthetic drug via a needle 60 (e.g., hypodermic needle), a subcutaneous injection port 70 including a sealed gasket and lumen may be incorporated into IPG 400 or the RX module 500. In the embodiment of Figure 4B, the RX module 500 may include a receiver antenna (e.g., coil) and / or any applicable inductive component to wirelessly receive a stimulation signal from the external pulse generator 300 wirelessly (e.g., RF or inductive) such that the stimulation signal is generated by the external pulse generator 300. Alternatively, the RX module 500 may include a stimulation circuit and a receiver antenna (e.g., coil) to receive power from the TX module 550 via a wireless link (e.g., RF or inductive) such that the stimulation signal is generated by the RX module 500.

[0137] In embodiments described herein, the components that are placed subcutaneously (excluding IPG 400 due to the battery contained therein) may comprise a bioresorbable or biodegradable polymer (e.g., infusion lead body 110) and / or a bioresorbable or biodegradable metal (e.g., electrodes 112, RX module 500, etc.). Such polymers and metals are described by Choi et al. in the article entitled “Fully implantable and bioresorbable cardiac pacemakers without leads or batteries”, Nature Biotechnology (2021), the entire disclosure of which is incorporated herein by reference. Other examples of biodegradable polymers include Polyglycolide or poly(glycolic acid) (PGA), poly(L-lactic acid) (PLLA), poly(3-Attorney Docket No.: 00333-0003-00304hydroxybutyrate) (PHB), Polycaprolactone (PCL), or the like, or a combination thereof. Electrodes 112 and / or electrodes 114 may be may be wirelessly powered and may be controlled from outside a patient’s body, as disclosed herein. Electrodes 112 and / or electrodes 114 may deliver electrical signals at up to approximately 30V-60V. An electrical signal delivered via electrodes 112 and / or electrodes 114 may be a pulse train with a given pulse width, frequency (e.g., approximately 50kHz-40kHz), and amplitude (e.g., approximately 0-15Vpp). According to an embodiment, a patient may adjust the amplitude and / or frequency via patient input provided via external pulse generator 300 and / or an external controller. For example, a patient may input an amplitude and / or frequency or may select an amplitude and / or frequency from two or more pre-programmed amplitudes and / or frequencies.

[0138] Table 1 shows example electrical parameters that may be output or applied by one or more electrical components disclosed herein such as electrical pulse generator 300, IPG 400, RX module 500, TX module 550, electrodes 112, and / or electrodes 114.Attorney Docket No.: 00333-0003-00304

[0139] Bioresorbable and / or biodegradable materials may conduct energy until a threshold amount of degradation occurs, after which point the energy conduction may be limited or reduced below a threshold (e.g., a usability threshold). Biodegradable material may degrade in tiers. For example, a first tier may be a first number of days (e.g., 5-12 days), where energy conduction (e.g., via an electrode) is reduced to a first conduction tier. The biodegradable material may degrade to one or more second tiers (e.g., 12-20 days, 12-40 days, 40-60 days, etc.), when the energy conduction is reduced to one or more second condition tiers and / or to no conduction. Non-biodegradable material may be used to insert and / or place the biodegradable material.

[0140] Degradation of biodegradable material may be accelerated or decelerated based on one or more of material and / or material amount selected for the biodegradable material,Attorney Docket No.: 00333-0003-00304application of a degradation catalyst (e.g., amount or type of catalyst), an area of placement of biodegradable material within body, and / or the like. A receiver antenna (e.g., an antenna of RX module 500) may receive a wireless transmission at a determined or predetermined frequency range. If wireless transmission is received at the determined or predetermined frequency range, then energy may be generated at the electrode (e.g., based on the receiver antenna resonating).

[0141] The distance between the transmission coil and the receiving antenna may be determined based on length of time the biodegradable material is within a body (e.g., a longer length of time may require a shorter distance).

[0142] A control device (e.g., a mobile device, an external device, etc.) may be used to control an external device (e.g., TX module 550) that may be positioned on or near a user’s skin (e.g., via a patch), via wired or wireless connection. The control device may cause a transmission coil to output a wireless pacing signal. The control device may determine properties of the wireless pacing signal based on one or more of: the location of the electrode, user attribute (e.g., level of pain, level of medication consumed (e.g., opioid), type of medication consumed, type of stimulation (e.g., neuro-stimulation), duration of time from past stimulation and / or drug consumption, pattern of past stimulation and / or drug consumption, or the like).

[0143] For example, a biodegradable electrode may be inserted into a patient’s body and may provide electrical current to a portion of the patient’s nervous system (e.g., spinal cord). The patient may undergo a procedure and may input a pain level. The control device may determine a pacing signal to be output by a wireless pacing device such that the electrode resonates to stimulate an area of the spinal cord to reduce the pain sensed by the user. Such stimulation may be used as a substitute for or to complement medication (e.g. pain medication).

[0144] With reference to Figures 5A - 5C, an alternative multimodal pain management system is shown schematically. In this embodiment, the alternative system includes a module 170 connected to an infusion lead body 110 (as described previously). Module 170 may include a housing 172, a fluid line connector 174 (e.g., touhy borst) and a female electrical receptacle 176, optionally sealed with a removable silicone rubber plug, for example. The fluid line connector 174 may include an in-line filter to mitigate the ingress of bacteria and / or pathogens, and may include a sealed diaphragm. The fluid line connector 174 may be removably attached to a drug pump 200 via tubing 210 to provide fluid communication from the drug pump 200 to the nerve (N) via infusion lead body 110 as described previously. Similarly, and the female electrical receptacle 176 may be removably connected to a male jack 178 and cable 310 for electrical connection to an external pulse generator 300 to provide electrical communicationAttorney Docket No.: 00333-0003-00304from pulse generator 300 to the nerve via infusion lead body 110 and associated electrodes as described previously. The module 170 and infusion lead body 110 may be covered by an adhesive patch attached to the skin (S) to secure the system in place. The alternative multimodal pain management system of Figures 5A-5C may be inserted adjacent to a nerve in accordance with the techniques described in reference to Figures 3 A-3M.

[0145] The drug pump 200 may be an electromechanical pump (e.g., motor-controlled piston in chamber) or a mechanical pump (e.g., spring or manually operated syringe type or bulb), for example. As shown in Figure 5B, the drug pump 200 may have a simple user interface that allows only a prescribed amount of drug (e.g., anesthetic) to be administered by the patient, thus allowing the drug to be delivered in controlled-volume discrete boluses, such as three boluses of approximately 5cc-10cc each, one or more boluses for transmission of 50cc-100cc per day, etc., for example. Each bolus may be activated by the user pressing a button 220, for example, to administer the drug as needed (e.g., in response to perceived pain). The other buttons may be locked-out for a period of time to prevent the delivery of multiple boluses simultaneously. The external pulse generator 300 may also have a simplified user interface that allows the patient to select from a limited number of prescribed pulse regimens (e.g., prescribed frequency and amplitude) using up / down, select and start buttons 320 and display screen 330.

[0146] Drug pump 200 may allow a periodic basal delivery of a prescribed amount of drug (e.g., anesthetic) to be administered throughout a period of time (e.g., a day, a night, on a continuous basis, etc.). The basal delivery may be activated by a user via a drug pump 200 interface or an external controller, as further discussed herein. The basal delivery may be implemented based on one or more pre-programmed basal delivery settings that may be input by a user or may be stored at drug pump 200 or an external controller. The basal delivery settings may be adjustable by a user or via a signal received at drug pump 200 or an external controller. Drug pump 200 may allow a bolus dose delivery based on patient activation. A patient may provide patient input to activate a bolus dose delivery via drug pump 200 and / or via an external controller. For example, drug pump 200 may be programmed to provide basal doses at a constant or variable levels. Additionally, the patient may provide patient input to trigger a bolus dose delivery, which may be greater in amount than the basal doses.

[0147] According to an embodiment, drug pump 200 and / or external pulse generator 300 may communicate with an external controller (e.g., a mobile device, a stand-alone device, etc.). Such communication may be wired or wireless. According to this embodiment, drug pump 200 may not include buttons 220 or may include a subset of the buttons 220. Similarly, external pulse generator 300 may not include buttons 320 or may include a subset of buttonsAttorney Docket No.: 00333-0003-00304320. The external controller may include an interface (e.g., a graphical interface, a physical interface, etc.) that provides selectable components (e.g., buttons, icons, etc.). Selection of such selectable components may cause one or more signals to be transmitted by the external controller. The signals may be received at a receiver in communication drug pump 200 and / or external pulse generator 300. The one or more signals may cause drug pump 200 and / or external pulse generator 300 to perform the actions disclosed herein (e.g., activating drug pump 200 and / or pulse generator 300, causing drug pump 200 to output a determined or predetermined amount of fluid, causing pulse generator 300 to output an electrical signal, etc.). For example, the external controller may have a simple user interface that allows only a prescribed amount of drug (e.g., anesthetic) to be administered by the patient based on the user selecting a corresponding selectable component.

[0148] The external controller may include code, a script, and / or the like which may cause an external controller processor to generate the one or more signals. The one or more signals may be generated based on user input selecting one or more selectable components (e.g., via buttons, icons, etc.) and / or based on programmed instructions. For example, the external controller may be a mobile device having component (e.g., a transmitter) to wirelessly transmit the one or more signals (e.g., via Bluetooth, infra-red, WiFi, a local area network, a wide area network, etc.). An application or interface may be accessed using the mobile device (e.g., a web application, a mobile application, etc.) and the application may receive user inputs (e.g., an input to activate drug pump 200 and / or external pulse generator 300, an input to modify a drug dosage or frequency, an input to trigger electrical activity, etc.) via one or more selectable components of the application. The application may cause the mobile device to transmit the one or more signals based on a selected selectable component. The transmitted signal may be received by drug pump 200 and / or external pulse generator 300 and may cause drug pump 200 and / or external pulse generator 300 to perform an action.

[0149] The external controller may be programmable such that the one or more signals are generated based on pre-programmed settings. Such settings may automatically cause the external controller to transmit the one or more signals based on a trigger. The trigger may be a time, a duration of time, a sensor input, an external signal, or the like or a combination thereof.

[0150] According to an implementation, machine learning outputs of a machine learning model may control chemical and / or electrical stimulation. The machine learning model may be trained based on historical or simulated inputs and corresponding historical and / or simulated chemical and / or electrical stimulation. The inputs may include, but are not limited to, treatment properties (e.g., type of procedure, type or severity of injury or condition,Attorney Docket No.: 00333-0003-00304etc.), user properties (e.g., user demographics, user weight, user biological properties, user pain thresholds, etc.), pain relief, vasodilation (e.g., amount vasodilation), AVF maturation (e.g., amount of AVF maturation), impedance, etc. The machine learning model may be trained by modifying one or more weights, layers, synapsis, nodes, or the like of the machine model, based on a machine learning algorithm, as further disclosed herein.

[0151] The trained machine learning model may receive current inputs associated with a user and may generate one or more outputs based on the same. For example, the machine learning model may receive treatment properties, user properties, pain relief properties, current or expected vasodilation information, current or expected AVF maturation information, and / or impedance values. The current inputs may be provided based on user input and / or one or more sensors configured to detect a respective current input. Based on the current inputs, the machine learning model may output a chemical or electrical stimulation properties such as chemical or electrical stimulation amount, frequency, and / or duration. The output may be based on a target time (e.g., target termination of electrical and / or chemical stimulation), a trend (e.g., reduction of electrical and / or chemical stimulation over time), and / or target electrical and / or chemical stimulation. The algorithmic and / or machine learning outputs discussed herein may facilitate a closed-loop system such that electrical and / or chemical stimulation and related properties (e.g., frequency, amount, duration, etc.) are automatically determined based on algorithmic and / or machine learning outputs. For example, electrical and / or chemical stimulation may be output based on an algorithmic and / or machine learning output schema which may be adjusted based on user input (e.g., pain scores). Electrical and / or chemical stimulation may be adjusted in accordance with the algorithmic and / or machine learning output schema based on trend analysis to, for example, wean the electrical and / or chemical stimulation over time (e.g., based on a user’s response to such stimulation). The weaning may include reducing electrical and / or chemical stimulation without the user experiencing an adverse effect such as an increase in pain. The chemical or electrical stimulation properties may be provided to the external controller and external controller may be configured to trigger pump 200 / 200A and / or pulse generator 300 based on the chemical or electrical stimulation properties. The machine learning model may be configured to provide updated chemical or electrical stimulation properties based on updated current inputs.

[0152] Figure 6 is a flowchart 600 for multimodal electrical and chemical stimulation in accordance with the embodiments disclosed herein. At step 602, an electrical signal may be received at a connector (e.g., connector 150). The electrical signal may be received form a pulse generator (e.g., pulse generator 300) and may be generated at the pulse generator basedAttorney Docket No.: 00333-0003-00304on a user input, a pre-programmed setting, etc. At step 604, the electrical signal or one or more signals generated based on the electrical signal may be transmitted through an electrical path via connector conductive trace, a connector metal pin, a housing pin receptacle (e.g., of housing 140) a housing conductive trace (e.g., of housing 140), and / or an infusion lead body internal wire (e.g., of infusion lead body 110) to an internal lead body distal electrode (e.g., distal electrode 112).

[0153] At step 606, a fluid may be received at the connector. The fluid may be received from a pump (e.g., pump 200) and may be a drug or other chemical or fluid. The fluid may be received based on a user input, a pre-programmed setting, etc. At step 608, the fluid may flow through a fluid path via a connector internal lumen, a connector needle, a housing needle receptacle (e.g., of housing 140), a housing lumen (e.g., of housing 140), and / or an infusion lead body infusion lumen (e.g., of infusion lead body 110) to an infusion lead body exit port (e.g., exit ports 118).

[0154] The techniques described in flowchart 600 may be used to provide both electrical stimulation and chemical stimulation to a user. The electrical signal transmitted through the distal electrode at step 604 may provide electrical stimulation based on one or more electrical signal properties (e.g., frequency, amplitude, change in frequency or amplitude, phase, duration, etc.). The fluid transmitted through the exit port at step 608 may provide chemical stimulation based on chemical properties of the transmitted fluid.

[0155] Figure 7 is a flowchart 700 for infusion lead body placement in accordance with embodiments disclosed herein. At step 702, an infusion lead assembly (e.g., infusion lead assembly 100) may be loaded onto a needle (e.g., needle 50). The needle may include a needle tip at a first end and a needle hub at a second end opposite the first end. The infusion lead assembly may be loaded onto the needle by traversing the needle tip through a gasket (e.g., gasket 146) or other opening at an infusion lead assembly housing (e.g., housing 140). The needle tip may advance through an infusion lead body (e.g., infusion lead body 110) of the infusion lead assembly through a distal end of the infusion lead body.

[0156] At 704, as shown in Figure 3 A, the infusion lead assembly loaded onto the needle may be inserted through a user’s skin. The needle may puncture the user’s skin and the infusion lead assembly loaded onto the needle may advance through the opening created by the needle puncturing the user’s skin. At step 706, as shown in Figures 3A-3C, a force may be applied (e.g., at the needle hub and / or the proximal portion of the infusion lead assembly) to position the needle hub towards the user’s skin. The force at step 706 may be applied until theAttorney Docket No.: 00333-0003-00304infusion lead assembly loaded onto the needle is substantially parallel to a nerve, as shown in Figure 3C.

[0157] At step 708, as shown in Figure 3D, a force may be applied to the needle hub to advance the infusion lead assembly loaded onto the needle further inside the user’s body. The force applied at step 708 may be applied such that the infusion lead assembly loaded onto the needle is advanced further inside the user’s body while the infusion lead assembly loaded onto the needle remains substantially parallel to the vein. At step 710, as shown in Figure 3E, the needle may be removed (e.g., unloaded) from the infusion lead assembly. The needle may be removed by pulling or otherwise extracting the needle away from the infusion lead assembly such that the needle trip traverses the infusion lead assembly and exists via the proximal end of the infusion lead assembly. As shown in Figure 3F, an infusion lead body (e.g., infusion lead body 110) of the infusion lead assembly may remain inside the user’s body after the needle is removed from the infusion lead assembly. The infusion lead body may remain substantially parallel to the user’s vein. The steps described in Figures 3A-Figure 3F may be performed using a single hand. For example, at step 702, the infusion lead assembly loaded onto the needle may be inserted through a user’ s skin using a single hand. As another example, the force applied at step 708 may be applied by a single hand. Accordingly, he infusion assembly and / or needle may include gripping material and / or contours such that the steps described in Figures 3A-Figure 3F may be performed using a single hand.

[0158] Figure 8A is a schematic illustration of an electronic placement detector 802. Electronic placement detector 802 may be attached to placement connector 806 via a wire 804. Placement connector 806 may include one or more conductive traces. The conductive traces in placement connector 806 may connect with conductive traces 145 in housing 140 to provide electrical communication between electronic placement detector 802 and electrodes 112, 114. During insertion of infusion lead body 110 (e.g., as described in Figures 3A-3M) and / or after placement of infusion lead body 110 inside a patient’s body, electronic placement detector 802 may be connected to housing 140 via wire 804 and placement connector 806.

[0159] Electronic placement detector 802 may generate low voltage electronic signals that are transmitted to electrodes 112 and / or electrodes 114 via an electrical path created by the electronic placement detector 802, wire 804, placement connector 806, conductive traces 145 in housing 140, and infusion lead body 110 internal wire. A patient and / or medical provider may trigger electronic placement detector 802 to generate low voltage electronic signals such that they are output via electrodes 112 and / or electrodes 114. Placement of infusion lead body 110 proximate to the nerve may be confirmed based on the patient reporting a sensation inAttorney Docket No.: 00333-0003-00304response to the low voltage electronic signals. Alternatively, or in addition, the low voltage electronic signals may trigger a motor response and placement of infusion lead body 110 proximate to the nerve may be confirmed based on the observed motor response.

[0160] Figure 8B is a schematic illustration of a visual placement detector 808. Visual placement detector 808 may be attached to placement connector 806 via a fluid channel 810. As shown in Figure 8B, visual placement detector 808 may be connected to infusion lead body 110 at the same time as electronic placement detector 802 is connected to infusion lead body 110. Alternatively, either visual placement detector 808 or electronic placement detector 802 may be connected to insertion of infusion lead body 110 at a given time. Placement connector 806 may include a fluid channel. The fluid channel in placement connector 806 may connect with lumen 144 in housing 140 to provide fluid communication between visual placement detector 808 and exit ports 118. During insertion of infusion lead body 110 (e.g., as described in Figures 3A-3M) and / or after placement of infusion lead body 110 inside a patient’s body, visual placement detector 808 may be connected to housing 140 via fluid channel 810 and placement connector 806.

[0161] Visual placement detector 808 may include a chamber or may be connected to a chamber that includes a detection medium. The detection medium may be any applicable fluid (e.g., saline solution) or gas (e.g., air) that may be inserted into a patient’s body via exit ports 118. Visual placement detector 808 may provide the detection medium to exit ports 118 via a fluid path created by the visual placement detector 808, fluid channel 810, placement connector 806, lumen 144 in housing 140, and infusion lead body 110 infusion lumen. A patient and / or medical provider may trigger visual placement detector 808 to provide the detection medium via exit ports 118. Placement of infusion lead body 110 proximate to the nerve may be confirmed based on visual confirmation (e.g., via ultrasound) detection medium location as it exits exit ports 118 and comparing the detection medium location to the location of a given nerve.

[0162] Figure 9 is another schematic illustration of a multimodal system. The system may generally include an infusion lead assembly 100 configured for releasable connection to a drug pump 200 (shown in Figure 1A), a pulse generator 300 (shown in Figure IB), or a combined drug pump and pulse generator 200 / 300 (shown in Figure 1C) via a housing 140, a connector 150 and associated infusion tube and cable. The housing 140 may be secured to the epidermis via an adhesive patch 160 to mitigate migration. The top portion of the adhesive patch 160 may be attached (e.g., permanently) to the underside of the housing 140, and the bottom portion of the patch 160 may include an adhesive layer (e.g., suitable for approximatelyAttorney Docket No.: 00333-0003-0030410 - 14-day use under normal living conditions) covered by a removable covering (e.g., removable wax paper) until ready for application to the epidermis.

[0163] The infusion lead assembly 100 may include a tubular infusion lead body 110 having a proximal end connected to the housing 140. The infusion lead body 110 may include an infusion lumen (not visible) extending therethrough providing fluid communication between exit ports 118 (as shown in Figure 1 A) and the drug pump 200 via housing 140, connector 150, and infusion tube (e.g., when connector 150 is connected to housing 140). The infusion lead body 110 may further include one or more distal electrodes 112 (as shown in Figure 1 A) and one or more proximal electrodes 114 (as shown in Figure 1 A) in electrical communication with the pulse generator 300 via wires (not visible) embedded in the wall of the infusion lead body 110, via internal wires (not shown) extending through the housing 140 and connector 150, and via the cable. The internal wires embedded in the wall of the infusion lead body 110 may extend alongside at least a portion of the infusion lumen of infusion lead body 110.

[0164] According to implementations of the disclosed subject matter, techniques, devices, and systems disclosed herein may be used to provide selective treatment (e.g., chemical and / or electrical stimulation) to provide motor pain management, sensory pain management, hemodynamic changes (e.g., vasodilation, vasoconstriction, increased or decreased blood flow), and / or arteriovenous fistula (AVF) maturation. As discussed herein, chemical and / or electrical stimulation may be provided via a regional block (e.g., at a shoulder, knee, spinal area, neural area, or other applicable body part). For example, electrical and / or chemical stimulation may be provided, and the resulting hemodynamic response may be measured minutes, hours, days, and / or weeks after the stimulation. Chemical and / or electrical stimulation may be provided one time (e.g., after a procedure) or may be provided multiple times such as on an ongoing basis (e.g., via a pump that provides ongoing chemical dilation treatment, via electrical peripheral stimulation for a period of time, or the like or a combination thereof). The resulting hemodynamic response may be measured after each stimulation or after one or more stimulations.

[0165] According to an implementation, hemodynamic properties (e.g., vasodilation, vasoconstriction, blood flow changes) may be detected by calculating a perfusion index (PI) associated with treatment site tissue, blood vessels, veins, and / or nerves treated based on the electrical and / or chemical stimulation discussed herein. The PI may be calculated, for example, by a sensor and / or device that detects a photoplethysmographic waveform and reflects peripheral vasomotor tone. The PI value may reflect the strength of blood flow (e.g., perfusion) at the sensor site (e.g., the site used for pulse oximetry). According to an implementation, theAttorney Docket No.: 00333-0003-00304PI value may be calculated by using the ratio of pulsatile (arterial) blood flow to non-pulsatile (static) blood flow in peripheral tissues.

[0166] The PI value may be calculated as a pulse oximeter measurement by using a pulse oximeter sensor that emits light (e.g., red light, infrared light, and / or near red light or near infrared light) through the skin. The pulse oximeter sensor may detect changes in light absorption caused by blood flow. For example, the pulse oximeter sensor may detect an alternating current (AC) signal that corresponds to the pulsatile blood flow (e.g., arterial blood influenced by heartbeats). The pulse oximeter sensor may also detect a direct current (DC) signal that corresponds to the non-pulsatile blood flow (e.g., venous and tissue background). A PI value may be determined based on a relationship between the AC and DC values.

[0167] According to implementations disclosed herein, hemodynamic effectiveness (e.g., vasodilation effectiveness, vasoconstriction effectiveness, blood flow changes) resulting from the chemical and / or electrical stimulation may be detected using an oxygen sensing device. For example, techniques, devices, and / or systems provided in U.S. Patent Numbers 8,560,035, 8,670,812, and / or 8,718,736, each of which are incorporated herein by reference, may be used to detect oxygen levels (e.g., to detect hemodynamic effectiveness resulting from the chemical and / or electrical stimulation). An oxygen sensing device may be used to detect regional oximetry (e.g., via oxygen saturation detection).

[0168] A sensing device may include one or more sensors configured to detect hemodynamic properties of a body part (e.g., NIRS, PI Index, flow, temperature, 02 saturation and / or 02 consumption associated with tissue, tissue, blood vessels, veins, and / or nerves). Hemodynamic properties may indicate vasodilation, vasoconstriction, increased blood flow, decreased blood flow, or other hemodynamic changes. One or more sensing devices (e.g., an oxygen sensing device, NIRS sensing device, PI sensing device, flow sensing device, temperature sensing device, etc.) may be placed on body parts (e.g., one or more extremities) prior to, during, and / or after a treatment (e.g., electrical and / or chemical stimulation).

[0169] For example, in relation to lower leg treatment, a first sensing device may be placed on a patient's calf and / or a second sensing device may be placed on a patient's foot, as shown in image 1200 of Figure 12A and image 1202 of Figure 12B. As another example, in relation to an upper extremity treatment, a first sensing device may be placed on a patient's upper arm and / or a second sensing device may be placed on a patient's forearm. The first and / or second sensing devices may be placed on the respective body parts prior to the treatment and may detect a baseline measurement of hemodynamic properties (e.g., 02 saturation, 02 consumption of the underlying tissue, NIRS, PI Index, flow, temperature, etc.). The first and / orAttorney Docket No.: 00333-0003-00304second sensing devices may output measurements during and post administration of the treatment.

[0170] Figures 13 A-13E show experiment results based on performing electrical and / or chemical stimulation treatment techniques disclosed herein. Specifically, Figures 13A-13E show oxygen levels corresponding to vasodilation effectiveness resulting from the electrical and / or chemical stimulation disclosed herein. The oxygen levels and changes from a baseline measurement are obtained using one or more oxygen sensing devices, as disclosed herein. Image 1300 of Figure 13 A shows a 32% increase in oxygen levels via oxygen sensing device(s) placed at a patient’s calf and a 26% increase in oxygen levels via oxygen sensing device(s) placed at a patient’s foot. Image 1302 of Figure 13B shows a 30% increase in oxygen levels post treatment at a first location, and 21% increase in oxygen levels post treatment at a second location. Image 1304 of Fig. 13C shows a 16% increase in oxygen levels post treatment at a first location, a 54% increase in oxygen levels post treatment at a second location, a 13% decrease in oxygen levels post treatment at a third location, and 22% increase in oxygen levels post treatment at a fourth location. Image 1306 of Fig. 13D shows a 2% decrease in oxygen levels post treatment at a first location, a 46% increase in oxygen levels post treatment at a second location, a 7% decrease in oxygen levels post treatment at a third location, and 23% increase in oxygen levels post treatment at a fourth location. Image 1308 of Fig. 13E shows a 2% increase in oxygen levels post treatment at a first location, a 46% increase in oxygen levels post treatment at a second location, a 10% decrease in oxygen levels post treatment at a third location, and 20% increase in oxygen levels post treatment at a fourth location. Observation time for one or more of the experiments for which results are provided in Figures 13A-E was approximately 30 minutes, such that the oxygen levels were detected for the duration of approximately 30 minutes and / or at the end of the approximately 30 minutes. In certain instances, the baseline oxygen levels indicated a high oxygen saturation. In these instances, the change or increase in oxygen levels was still significant (e.g., approximately 5% or more).

[0171] With reference to Figures 13A-13E, oxygen level outputs resulting from electrical and / or chemical stimulation are shown. As shown in image 1300 of Figure 13 A, a monitoring device display shows oxygen measurements at multiple locations. Chart 1312A shows trend data over time for a first measurement location, with first location oxygen level 1312B displaying a current value of 58 and first location oxygen change 1312C showing a 32% increase from baseline. Chart 1314A shows corresponding measurements for a second location, with second location oxygen level 1314B displaying a current value of 72 and second location oxygen change 1314C showing a 26% increase from baseline. These measurementsAttorney Docket No.: 00333-0003-00304demonstrate acute increases in tissue oxygen following a popliteal nerve block. As shown in image 1302 of Figure 13B, chart 1316A displays first location oxygen level 1316B of 57 with first location oxygen change 1316C of 30%, while chart 1317A displays second location oxygen level 1317B of 69 with second location oxygen change 1317C of 21%. As shown in image 1304 of Figure 13C, multiple sensor channels display varying oxygen levels and percentage changes, including first location oxygen level 1318A of 51 with first location oxygen change 1318B of 16%, second location oxygen level 1320A of 86 with second location oxygen change 1320B of 54%, third location oxygen level 1322A of 59 with third location oxygen change 1322B of 13%, and fourth location oxygen level 1324A of 73 with fourth location oxygen change 1324B of 22%. As shown in image 1306 of Figure 13D, first location oxygen level 1326A displays 43 with first location oxygen change 1326B of 2%, second location oxygen level 1328 A displays 82 with second location oxygen change 1328B of 46%, third location oxygen level 1330A displays 63 with third location oxygen change 1330B of 7%, and fourth location oxygen level 1332A displays 74 with fourth location oxygen change 1332B of 23%. As shown in image 1308 of Figure 13E, first location oxygen level 1334A displays 45 with first location oxygen change 1334B of 2%, second location oxygen level 1336A displays 82 with second location oxygen change 1336B of 46%, third location oxygen level 1338 A displays 61 with third location oxygen change 1338B of 10%, and fourth location oxygen level 1340A displays 72 with fourth location oxygen change 1340B of 20%. These figures demonstrate the monitoring of oxygen levels at multiple body locations post treatment with varying degrees of change from baseline measurements at different sensor positions.

[0172] According to a set of experiments, visualized in charts 1400 of Figure 14, the following parameters were used for testing:• Arteriovenous (AV) fistula treatments:o IRB 1 : Standard of Care (SOC) block in shoulder■ Monitored vessel dilation and pulse index in hours and days post AV fistula o IRB2: SOC block in shoulder■ Patient continued chemical stimulation with pump (at home, post procedure) (pain / 3 days)o IRB3: SOC block in shoulderAttorney Docket No.: 00333-0003-00304■ Patient continued electrical stimulation via peripheral stimulation (pain / 1 week) • Charts 1400 of Figure 14 show medial values: Four from IRB1, two from IRB2• Charts 1400 show percent change from baseline• IIRB(1,2,3) shows intervention• CIRB(1,2,3) show control / contralateral

[0173] With reference to Figure 14, charts 1400 show experimental hemodynamic properties or hemodynamic measurements resulting from electrical and / or chemical stimulation over time. Vein diameter chart 1402A displays vein diameter percentage changes over time points including Pre, Post, Hour 0, Hour 2, Day 7, and Day 50 for intervention groups (IRB1, IRB2) and control groups (CIRB1, CIRB2). Arterial diameter chart 1402B shows arterial diameter percentage changes over the same time points. Perfusion index chart 1402C displays perfusion index percentage changes, demonstrating significant increases following intervention. Vein velocity chart 1402D shows vein velocity percentage changes, and artery velocity chart 1402E displays artery velocity percentage changes. The data demonstrates that peripheral nerve blocks lead to increased artery and vein diameters of approximately 30-50% and increased perfusion index of approximately 2-5x.

[0174] With reference to Figure 15, image 1500 shows a clinical setting during a procedure involving vein dilation 1502. The image demonstrates the practical application of the sensing and monitoring technology in a medical setting, where multiple monitoring electrodes with colored leads are attached to the exposed tissue area. This setup is consistent with clinical studies where peripheral nerve stimulation is being evaluated to observe hemodynamic changes including vessel dilation and perfusion index measurements.

[0175] According to an experimental peripheral nerve stimulation for pain in brachial plexus, a perfusion index of approximately 0.9 to approximately 4.4 was observed resulting from the stimulation. According to experiments, drug stimulation in a brachial plexus caused hemodynamic changes (e.g., vasodilation) and pain impact improvements. Additional benefits included increased vein size, increased flow with fistula, and improved native vein selection and maturation. According to experiments, stimulation (e.g., electrical and / or chemical) caused hemodynamic changes as indicated by measuring the corresponding effects downstream. Low levels of stimulation were shown to cause significant hemodynamic responses.Attorney Docket No.: 00333-0003-00304

[0176] According to an embodiment, a treatment property may be determined and / or adjusted based on a sensed measurement, providing a closed loop system for providing electrical and / or chemical stimulation which is adjusted based on sensed measurements. The closed loop diagnostic may include any measurement to assess change, including NIRS values, oxygen values, perfusion index, blood flow, and / or temperature. For example, one or more treatment values such as dosage, timing, frequency, amplitude, type, pulse width, polarity, rate and / or the like related to electrical and / or chemical stimulation may be determined and / or adjusted based on a sensed or received PI index, blood flow levels, and / or oxygen levels. According to an embodiment, a determination to stop treatment may be based on a sensed measurement (e.g., if the sensed measurement exceeds or is below a sensed measurement threshold). The received PI index, blood flow levels, and / or oxygen levels may be detected with devices disclosed herein. For example, an oxygen sensing device may be used to determine baseline oxygen levels at a patient's body part prior to an electrical and / or chemical stimulation. The oxygen sensing device may provide updated oxygen levels during and / or after administration of the electrical and / or chemical stimulation.

[0177] A sensed measurement sensed during and / or after a treatment may be used to determine a treatment value or to modify a treatment value. For example, a sensed measurement sensed while administering a chemical and / or electrical stimulation may be provided to a processor having a program, code, algorithm, machine learning model, and / or the like configured to output a treatment value or updated treatment value. The processor may output a treatment value or updated treatment value based on the sensed measurement and / or based on other factors such as area of treatment, patient biometric values, patient demographics, target values (e.g., target hemodynamic response, target oxygen levels, target PI index, target temperature, target blood flow, target elasticity or dimensions of blood vessels, etc.). The treatment value may be output such that a given treatment is updated to prevent paresthesia (e.g., by capping or reducing stimulation intensity, duration, and / or frequency levels). A machine learning model may be trained to output a treatment value or updated treatment value based on inputs such as the sensed measurement, area of treatment, patient biometric values, patient demographics, target values (e.g., target hemodynamic response, target oxygen levels, target PI index, etc.). The machine learning model may be trained using historical or simulated measurement values, areas of treatment, patient biometric values, patient demographics, target values (e.g., target hemodynamic response, target oxygen levels, target PI index, etc.).

[0178] Accordingly, techniques disclosed herein provide a closed loop system for providing electrical and / or chemical stimulation, which is adjusted based on sensedAttorney Docket No.: 00333-0003-00304measurements. For example, treatment values associated with chemical stimulation (e.g., ropivacaine, bupivacaine, or the like) or electrical stimulation are adjusted based on sensed or determined PI indices, blood flow values, and / or oxygen values. In addition to PI indices, blood flow values, and / or oxygen values, it will be understood that the size (e.g., diameter) changes in a vein, blood vessel, nerve, etc. may be measured and may be used as a sensed measurement as discussed herein. According to embodiments, electrical stimulation alone may be used to prevent affecting motor nerves. Such electrical stimulation may be refined (e.g., treatment values adjusted) based on feedback from the closed loop system (e.g., via PI index, blood flow, and / or oxygen values). Additionally, stimulation may need to cycle as nerves may adjust back to normal flow with continuous stimulation. The cycling of stimulation may maintain the desired hemodynamic response over extended treatment periods. Drug-based approaches may cause hemodynamic changes (e.g., vasodilation) but may affect motor nerves and may not be quickly reversible or capable of fine adjustment. Stimulation-based approaches may avoid motor nerve effects and may potentially allow for dialing in a desired oxygen level or cycling the stimulation to maintain effectiveness.

[0179] The techniques disclosed herein may be applied for one or more indications such as, but not limited to, acute (e.g., intra-procedure) indications, extended therapy indications, arteriovenous fistula maturation, critical limb ischemia, Buerger's disease, Raynaud's disease, spinal cord ischemia on aortic procedures, wound healing, treatment of wound dehiscence, migraines, lead placement capture confirmation, increased blood vessel diameter, and / or the like. The techniques provided herein may be implemented in limb salvage / wound healing and / or diabetic patients with microvascular disease, Buerger's disease, etc. The techniques provided herein may be implemented in patients with Raynaud's disease (e.g., who have vasospasm of microcirculation and / or digital arteries in cold exposure). For arteriovenous fistula maturation, the stimulation device may be placed preoperatively a few days prior to surgery for increasing vessel size, or intra-procedurally during the fistula creation procedure.

[0180] According to embodiments, techniques, devices, and systems disclosed herein may be used to provide selective treatment (e.g., chemical and / or electrical stimulation) to provide motor pain management, sensory pain management, hemodynamic changes (e.g., vasodilation, vasoconstriction, blood flow modulation), and / or arteriovenous fistula (AVF) maturation. A variable set of parameters, including current amplitude, frequency, pulse width, and polarity, may allow for intra or extra vascular neurostimulation to alter the elasticity or dimensions of blood vessels, including arteries and veins, so that fluid flow rate can beAttorney Docket No.: 00333-0003-00304controllably manipulated. Neuromodulation parameter settings may potentially induce a local and systemic effect. The interaction between neuromodulation parameters, specific to patient and application, may provide an optimal scenario specific to the application. For applications such as, but not limited to, implantable applications, a closed loop system may allow for longitudinal optimization of settings. Data analytics may be used to determine optimal settings relevant to patient demographics that can be used for a broader patient population.

[0181] According to embodiments, hemodynamic properties (e.g., vasodilation, vasoconstriction, blood flow changes) may be detected by calculating a perfusion index (PI) associated with treatment site tissue, blood vessels, veins, and / or nerves treated based on the electrical and / or chemical stimulation. The PI may be calculated by a sensor and / or device that detects a photoplethysmographic waveform. The PI reflects peripheral vasomotor tone at a sensor site. According to embodiments, a pulse oximeter sensor may be configured to emit light through skin and detect changes in light absorption caused by blood flow. The pulse oximeter sensor may be configured to detect an alternating current (AC) signal corresponding to pulsatile blood flow and a direct current (DC) signal corresponding to non-pulsatile blood flow. The perfusion index may be determined based on a relationship between the AC signal and the DC signal, such as a ratio of pulsatile blood flow to non-pulsatile blood flow.

[0182] Clinical observations have demonstrated PI increases of approximately 2-5x following peripheral nerve blocks, with values ranging from approximately 0.6 to 4.4 with stimulation. Peripheral nerve blocks have been shown to lead to increased artery and vein diameters of approximately 30-50% and increased PI of approximately 2-5x. The PI may be calculated based on a detected photoplethysmographic waveform. The photoplethysmographic waveform may be detected by a sensor such as a pulse oximeter. The pulse oximeter may emit light through the skin and detect changes in light absorption caused by blood flow. The detected changes may include an AC signal corresponding to pulsatile arterial blood flow and a DC signal corresponding to non-pulsatile components including venous blood, bone, and tissue. The PI may be calculated as a ratio or other mathematical relationship between the AC and DC components, providing a non-invasive measure of peripheral perfusion that correlates with hemodynamic effectiveness.

[0183] According to embodiments, hemodynamic effectiveness resulting from the chemical and / or electrical stimulation may be detected using a sensing device (e.g., a hemodynamic sensing device). The sensing device may include one or more sensors configured to detect a hemodynamic property of a body part. The hemodynamic property may include oxygen properties such as 02 saturation and / or 02 consumption associated with tissue,Attorney Docket No.: 00333-0003-00304blood vessels, veins, and / or nerves. The sensing device may be an oxygen sensing device configured to measure regional tissue oxygen (rSO2) levels. The oxygen sensing device may utilize near-infrared spectroscopy (NIRS) technology to measure regional oxygen saturation in tissue, providing continuous, non-invasive assessment of tissue perfusion and oxygenation changes that occur in response to therapeutic interventions such as peripheral nerve blocks or neurostimulation. According to certain implementations, the sensing device may be configured to detect at least one of regional oximetry via oxygen saturation detection, a perfusion index, a NIRS value, a blood flow rate, or a temperature at the body part.

[0184] With reference to Figures 12A-12B, sensing devices may be positioned on a patient's body part to detect hemodynamic properties. As shown in image 1200 of Figure 12A, sensing devices may be positioned on a patient's lower leg at foot location 1210 and calf location 1212. As shown in image 1202 of Figure 12B, a sensing device may be positioned at foot location 1214. As an example, the sensors may be placed on the extremity that is planned to receive a nerve block or neurostimulation therapy. The single and / or dual sensor placement may allow for baseline measurements of oxygen saturation and oxygen consumption at multiple tissue locations, enabling real-time observation of hemodynamic changes following therapeutic intervention. On the lower leg, sensors may be placed on the calf and foot. On the upper extremity, sensors may be placed on the upper arm and forearm. Prior to the block or stimulation, a baseline measurement of 02 saturation and 02 consumption of the tissue may be obtained. The block or stimulation may then be administered and changes may be observed in real-time. Within seconds, minutes, hours, or days, changes of 02 consumption of the tissue may be observed.

[0185] The body part may be, for example, a calf, a foot, an upper arm, a shoulder, a spinal area, a neural area, or a forearm. As used herein, the term "spinal area" may refer to a region of the body proximate to the spinal column where spinal cord tissue, paraspinal muscles, and associated neural structures are located. A spinal area may include, for example, paraspinal regions at cervical, thoracic, or lumbar levels, and may be a location at which sensing devices may be placed to monitor regional tissue oxygen saturation for applications such as spinal cord ischemia detection during aortic procedures. As used herein, the term "neural area" may refer to a region of the body where neural structures are located. A neural area may include, for example, areas where nerves, nerve plexuses, ganglia, or nerve bundles are present. In some aspects, a neural area may include the brachial plexus region, the femoral nerve region, the sciatic nerve region, a paravertebral region, or other anatomical locations where nerves suitable for stimulation or monitoring may be present. A neural area may be a location at which aAttorney Docket No.: 00333-0003-00304sensing device may be placed to detect hemodynamic properties or other physiological parameters associated with neural activity or neural stimulation.

[0186] According to embodiments, the sensing device may be configured to detect a baseline measurement of the detected hemodynamic property prior to delivery of stimulation by the at least one stimulation source and to detect an updated hemodynamic property during or after delivery of the stimulation. The baseline measurement establishes a reference point for subsequent comparison. For example, changes of approximately 5 points or approximately 10 points in oxygen saturation may be considered clinically relevant. The change in the upper extremity may be less dramatic when starting at high saturation levels, but may still be significant (e.g., approximately 5%) because of the high starting point.

[0187] The techniques provided herein may be implemented in the treatment of patients at risk for spinal cord ischemia following cardiac / vascular aortic procedures. Spinal cord ischemia may result from reduced arterial flow during and after these aortic surgeries. For such patients, techniques disclosed herein may be implemented by stimulating the paraspinal nerves, which may provide local vasodilation to the spine to mitigate or prevent paralysis. Improved oxygen delivery to the spine may be achieved through such stimulation. A product implementation may include adding stimulation electrodes to a lumbar drainage shunt catheter, which may be used for patients experiencing spinal cord ischemia. There are a number of ways to monitor / assess for improved arterial flow to the extremity or spine. An oxygen sensing device, as disclosed herein, may be used to obtain sensed measurements. Alternatively, or in addition, other techniques may be used (e.g., those related to sympathectomy, such as for critical limb ischemia, lumbar sympathectomies, etc.) to implement the techniques disclosed herein or to obtain sensed measurements.

[0188] Spinal cord ischemia is one of the complications that can occur after open and endovascular thoracoabdominal aortic repair. This occurs despite various perioperative approaches, including distal aortic perfusion, hybrid procedures with extra anatomical bypasses, motor-evoked potential, and cerebrospinal fluid drainage. The inability to recognize spinal ischemia in a timely manner remains a devastating complication after thoracoabdominal aortic repair. Novel technologies are designed for continuous monitoring to detect early changes that signal the development of spinal cord ischemia. Techniques disclosed herein may be used to monitor and / or treat postoperative spinal cord ischemia. Spinal cord ischemia monitoring by stimulating paraspinal nerves may be implemented in accordance with the techniques disclosed herein by using motor and sensory evoked potentials intraoperativelyAttorney Docket No.: 00333-0003-00304and / or via near-infrared spectroscopy (NIRS). NIRS and other hemodynamic measurements may be used as a diagnostic to assess lead placement and nerve capture.

[0189] Techniques have been studied as potentially useful monitoring tools that could provide simple and effective monitoring of the spinal cord. These include near-infrared spectroscopy, contrast-enhanced ultrasound, magnetic resonance imaging, fiber optic monitoring of the spinal cord, and cerebrospinal fluid biomarkers. According to embodiments, the techniques disclosed herein may be applied for embolization procedures. Benefits may include improved targeting, precision of delivery, embolic material retention, dynamic flow control for optimized material delivery specific to agent, reduced non-targeted tissue embolization, improved dwell time, improved occlusion time, improved anatomic access, and individual patient optimization. A stimulating microcatheter may be used to increase arterial flow and delivery of more and deeper embolization particles.

[0190] According to embodiments, the techniques disclosed herein may be applied for increased arterial diameter applications. A stimulation electrode may be placed on a guide sheath or other interventional devices (e.g., thrombectomy devices) to dilate distal vessels for improved crossability. For radial artery access, stimulation may be applied in the brachial plexus extra-vascularly, or a stimulation wire / catheter may be advanced up the arm artery prior to sheath insertion to relax and dilate the vessel. Use of techniques to monitor for postoperative spinal cord ischemia remains limited. Techniques disclosed herein may be used to monitor and / or treat postoperative spinal cord ischemia.

[0191] Certain indications may require or benefit from one or both electrical and chemical stimulation. The duration of a treatment (e.g., chemical and / or electrical stimulation) and whether the treatment is administered one-time, multiple times, and / or on an ongoing basis may be determined based on the indication (e.g., ailment, disease, etc.), the type of treatment, type of medication, type of electrical stimulation, intensity or dosage of treatment, frequency of treatment, and / or the like. For example, chemical and / or electrical stimulation may be provided for minutes, hours, days, weeks, and / or months. According to embodiments, the processor may be configured to output the treatment value such that stimulation is adjusted to prevent paresthesia by at least one of capping or reducing stimulation intensity, duration, or frequency levels. Stimulation levels that avoid paresthesia may be desired for certain applications.

[0192] With reference to Figure 16, process 1600 illustrates a closed-loop treatment process involving sensing device 1602, drug pump and / or pulse generator 1604, body part 1606, and processor 1608. The process 1600 demonstrates the sequence of interactions betweenAttorney Docket No.: 00333-0003-00304these components to achieve closed-loop monitoring and treatment adjustment based on detected hemodynamic properties. The sensing device 1602 may include one or more sensors configured to detect hemodynamic properties such as oxygen saturation, oxygen consumption, perfusion index, NIRS values, blood flow, or temperature. The drug pump and / or pulse generator 1604 may be configured to deliver chemical stimulation via a drug pump through one or more exit ports of an infusion lead body, electrical stimulation via a pulse generator through one or more electrodes of the infusion lead body, or both chemical and electrical stimulation. The body part 1606 may comprise at least one of a calf, a foot, an upper arm, a shoulder, a spinal area, or a forearm. The processor 1608 may be configured to determine hemodynamic effectiveness and treatment values based on sensed measurements and target values.

[0193] The process 1600 begins with sensing device 1602 performing step 1610 to sense body part 1606. The sensing may involve activating one or more sensors configured to detect hemodynamic properties. At step 1612, sensing device 1602 receives a hemodynamic property from body part 1606. The hemodynamic property represents a baseline measurement of the physiological state of the body part prior to stimulation. At step 1614, sensing device 1602 provides the hemodynamic property to processor 1608. The communication between sensing device 1602 and processor 1608 may occur via wired or wireless communication pathways.

[0194] Drug pump and / or pulse generator 1604 performs step 1616 to provide stimulation to body part 1606. The stimulation may comprise chemical stimulation delivered via a drug pump through one or more exit ports of an infusion lead body, electrical stimulation delivered via a pulse generator through one or more electrodes of the infusion lead body, or both chemical and electrical stimulation. Following stimulation delivery, sensing device 1602 performs step 1618 to sense body part 1606 again. This post-stimulation sensing captures the physiological response to the delivered stimulation. At step 1620, sensing device 1602 receives an updated hemodynamic property from body part 1606. The updated hemodynamic property reflects changes in the physiological state resulting from the stimulation. At step 1622, sensing device 1602 provides the updated hemodynamic property to processor 1608.

[0195] Processor 1608 performs step 1624 to determine hemodynamic effectiveness by comparing the baseline and updated hemodynamic properties. The determination of hemodynamic effectiveness may involve calculating a percentage change, an absolute change, or other mathematical relationship between the baseline and updated measurements. Processor 1608 performs step 1626 to determine a treatment value based on the hemodynamicAttorney Docket No.: 00333-0003-00304effectiveness and target values. The target values may include a target oxygen level, a target perfusion index, a target NIRS value, a target temperature, a target blood flow, or a target elasticity or dimensions of blood vessels. The treatment value may be determined by comparing the current hemodynamic effectiveness to the target values and calculating adjustments needed to reach the target values.

[0196] At step 1628, processor 1608 provides the treatment value to drug pump and / or pulse generator 1604. The treatment value may specify adjustments to at least one of dosage, timing, frequency, amplitude, pulse width, polarity, type, or rate of the stimulation. Drug pump and / or pulse generator 1604 performs step 1630 to configure the drug pump and / or pulse generator based on the treatment value. The configuration may involve adjusting internal settings, parameters, or operational modes to implement the treatment value. At step 1632, drug pump and / or pulse generator 1604 provides stimulation based on the treatment value to body part 1606. The adjusted stimulation is delivered according to the new treatment parameters determined by the closed-loop feedback process.

[0197] According to embodiments, the process 1600 may operate in a continuous monitoring mode where the sequence of steps repeats iteratively to provide ongoing adjustment of stimulation parameters based on real-time feedback. In another embodiment, the process 1600 may operate in a single adjustment mode where stimulation is adjusted once based on initial baseline and post-stimulation measurements. In some embodiments, only chemical stimulation may be adjusted while electrical stimulation remains constant. In other embodiments, only electrical stimulation may be adjusted while chemical stimulation remains constant. In further embodiments, both chemical and electrical stimulation may be adjusted simultaneously or sequentially based on the detected hemodynamic properties. The process 1600 may incorporate a machine learning model for determining treatment values based on inputs including sensed measurements, area of treatment, patient biometric values, patient demographics, and target values.

[0198] According to embodiments, the sensing device 1602 may comprise various sensor types including near-infrared spectroscopy (NIRS) sensors, pulse oximeters, transcutaneous oxygen monitors (tcpO2), laser Doppler flowmeters, photoplethysmography (PPG) sensors, thermistors or thermocouples for temperature sensing, ultrasound doppler probes for blood flow velocity measurement, or combinations thereof. The sensing device 1602 may be a skin-adhered patch sensor, a clip-on sensor, a probe-based sensor, or an implantable sensor. In some embodiments, the sensing device 1602 may comprise multiple sensorsAttorney Docket No.: 00333-0003-00304positioned at different anatomical locations to provide comparative measurements between treatment and control sites.

[0199] According to embodiments, the drug pump component of drug pump and / or pulse generator 1604 may comprise various pump types including peristaltic pumps, syringe pumps, elastomeric pumps, spring-loaded pumps, piezoelectric pumps, or osmotic pumps. The drug pump may be configured to deliver various agents including local anesthetics (e.g., ropivacaine, bupivacaine, lidocaine), vasodilators, anti-inflammatory agents, or combinations thereof. The drug pump may be an external wearable pump, a patient-controlled analgesia (PCA) pump, or an implantable pump. Delivery rates may be continuous, bolus, patient-controlled, or programmatically controlled based on sensed measurements.

[0200] According to embodiments, the pulse generator component of drug pump and / or pulse generator 1604 may comprise various stimulation configurations including monopolar stimulation, bipolar stimulation, or multipolar stimulation. Stimulation waveforms may include constant current, constant voltage, charge-balanced biphasic pulses, or asymmetric waveforms. Frequency ranges may span from low frequency (e.g., approximately 1-10 Hz) to high frequency (e.g., approximately 1-10 kHz) depending on the target neural structures and desired physiological response. Amplitude ranges may span from sub-threshold levels for sensing to supra-threshold levels for therapeutic effect. The pulse generator may be an external device, a partially implantable device with external controller, or a fully implantable pulse generator (IPG).

[0201] According to embodiments, the body part 1606 may comprise various anatomical regions depending on the clinical indication. For lower extremity applications, the body part 1606 may include the foot, ankle, calf, knee, or thigh. For upper extremity applications, the body part 1606 may include the hand, wrist, forearm, elbow, upper arm, or shoulder. For spinal applications, the body part 1606 may include paraspinal regions at cervical, thoracic, or lumbar levels. For vascular access applications, the body part 1606 may include regions adjacent to target vessels such as the radial artery, brachial artery, femoral artery, or jugular vein.

[0202] According to embodiments, the processor 1608 may comprise various computing architectures including microcontrollers, digital signal processors (DSPs), field-programmable gate arrays (FPGAs), application-specific integrated circuits (ASICs), or general-purpose processors. The processor 1608 may be integrated within the drug pump and / or pulse generator 1604, integrated within the sensing device 1602, or provided as a separate computing device such as a smartphone, tablet, laptop, or dedicated controller. TheAttorney Docket No.: 00333-0003-00304processor 1608 may execute various algorithms including proportional-integral-derivative (PID) control algorithms, fuzzy logic controllers, model predictive control algorithms, or machine learning models including neural networks, decision trees, or reinforcement learning agents.

[0203] According to embodiments, at step 1610, the sensing device 1602 (e.g., a hemodynamic sensing device) may sense the body part 1606 using various modalities. NIRS sensing may involve emitting near-infrared light at wavelengths between approximately 700-900 nm and detecting reflected or transmitted light to determine tissue oxygen saturation. Pulse oximetry may involve emitting red and infrared light and calculating oxygen saturation based on differential absorption. Transcutaneous oxygen monitoring may involve heating a skin region and measuring oxygen diffusion through the skin. Laser Doppler flowmetry may involve emitting coherent light and detecting frequency shifts caused by moving red blood cells. Temperature sensing may involve measuring skin surface temperature or subcutaneous temperature using thermistors, thermocouples, or infrared sensors.

[0204] According to embodiments, the hemodynamic property received at step 1612 and provided at step 1614 may comprise various physiological parameters. Oxygen-related parameters may include regional oxygen saturation (rSO2), tissue oxygen tension (PtO2), oxygen consumption rate, or arterial-venous oxygen difference. Perfusion-related parameters may include perfusion index (PI), pulsatility index, resistive index, or blood flow velocity. Vascular parameters may include vessel diameter, vessel wall compliance, or vascular resistance. Temperature parameters may include absolute temperature, temperature gradient, or rate of temperature change. The hemodynamic property may be provided as raw sensor data, processed values, trend data, or derived indices.

[0205] According to embodiments, the processor may be configured to calculate a perfusion index associated with a treatment site tissue of the body part based on detection of a photoplethysmographic waveform using the sensor. For example, the sensor may detect a photoplethysmographic waveform and may transmit signals corresponding to the detected waveform to the processor. The processor may receive an alternating current signal corresponding to pulsatile blood flow and a direct current signal corresponding to non-pulsatile blood flow from the sensor, and the processor may calculate the perfusion index based on a relationship between the alternating current signal and the direct current signal. In some embodiments, the processor may calculate the perfusion index as a ratio of the pulsatile component to the non-pulsatile component of the detected photoplethysmographic waveform. The calculated perfusion index may reflect peripheral vasomotor tone at the body part and mayAttorney Docket No.: 00333-0003-00304be used by the processor to determine hemodynamic effectiveness and treatment values as disclosed herein.

[0206] According to embodiments, at step 1616, the stimulation provided to body part 1606 may comprise various modalities. Chemical stimulation may involve bolus injection, continuous infusion, or intermittent dosing of pharmacological agents. Electrical stimulation may involve continuous stimulation, burst stimulation, cycling stimulation, or demand-based stimulation triggered by sensed conditions. Combined chemical and electrical stimulation may be delivered simultaneously, sequentially, or in alternating patterns. The stimulation may target various neural structures including peripheral nerves, nerve plexuses, sympathetic ganglia, dorsal root ganglia, or spinal cord segments.

[0207] According to embodiments, at step 1624, the processor 1608 may determine hemodynamic effectiveness using various analytical approaches. Simple comparison may involve calculating percentage change or absolute change between baseline and updated measurements. Statistical analysis may involve determining whether observed changes exceed measurement noise or natural variability. Trend analysis may involve evaluating the rate of change, time to peak effect, or duration of effect. Multi-parameter analysis may involve combining multiple hemodynamic properties into a composite effectiveness score. Machine learning analysis may involve classifying the response as adequate, inadequate, or excessive based on trained models.

[0208] According to embodiments, at step 1626, the processor 1608 may determine treatment values using various control strategies. Open-loop control may involve selecting treatment values from predefined lookup tables based on patient characteristics and clinical indication. Closed-loop control may involve continuously adjusting treatment values based on real-time or near real-time feedback (e.g., within seconds or minutes) from sensed measurements. Adaptive control may involve modifying control parameters over time based on observed patient responses. Predictive control may involve anticipating future states and proactively adjusting treatment values. The treatment value may specify absolute parameter values, incremental adjustments, or percentage modifications to current settings.

[0209] According to embodiments, at steps 1628-1632, the treatment value may be communicated via wired connection, wireless connection (e.g., Bluetooth, WiFi, proprietary RF), or optical connection. The drug pump and / or pulse generator 1604 may implement the treatment value immediately, gradually over a transition period, or at a scheduled future time. Safety limits may be applied to ensure treatment values remain within predefined safe ranges.Attorney Docket No.: 00333-0003-00304Confirmation feedback may be provided to the processor 1608 indicating successful configuration and delivery.

[0210] With reference to Figure 17, method 1700 illustrates steps for providing treatment based on monitoring hemodynamic properties. The method 1700 provides a systematic approach to positioning an infusion lead body, obtaining baseline measurements, administering stimulation, detecting post-stimulation oxygen levels, determining hemodynamic effectiveness, and adjusting stimulation parameters. At step 1702, an infusion lead body is positioned adjacent to a nerve, wherein the infusion lead body comprises one or more electrodes and one or more exit ports. The positioning may be performed using ultrasound guidance or other imaging modalities to ensure proper placement relative to the target nerve.

[0211] At step 1704, a baseline hemodynamic property is obtained via a sensing device. The baseline measurement may be obtained by placing the sensing device on an extremity such as a calf, foot, upper arm, shoulder, spinal area, or forearm, and allowing sufficient time for stable readings. At step 1706, chemical and / or electrical stimulation is administered via the one or more exit ports or the one or more electrodes. The stimulation may be delivered according to initial parameters including dosage, timing, frequency, amplitude, pulse width, and polarity. At step 1708, the hemodynamic property at the body part are detected poststimulation via the oxygen sensing device. The detection may occur within minutes of stimulation delivery to capture acute changes in the hemodynamic property (e.g., changes in tissue oxygenation).

[0212] At step 1710, hemodynamic effectiveness is determined based on the change between the baseline measurement and the detected hemodynamic property. For example, the determination may involve calculating a percentage change or absolute change in oxygen saturation. At step 1712, stimulation parameters are adjusted based on the determined effectiveness to reach at least one of a target hemodynamic property such as a target oxygen level, a target perfusion index, a target NIRS value, a target temperature, or a target blood flow. The adjustment may involve modifying at least one of dosage, timing, frequency, amplitude, type, pulse width, polarity, or rate of the chemical and / or electrical stimulation.

[0213] According to embodiments, at step 1702, the infusion lead body may be positioned using various guidance modalities including ultrasound guidance, fluoroscopic guidance, CT guidance, MRI guidance, or anatomical landmark-based approaches. The positioning may be performed percutaneously using needle-based insertion techniques, or surgically using open or minimally invasive approaches. The infusion lead body may be positioned adjacent to various target nerves including sciatic nerve, femoral nerve, brachialAttorney Docket No.: 00333-0003-00304plexus nerves, intercostal nerves, paravertebral nerves, or sympathetic chain ganglia. Positioning confirmation may be achieved using electrical stimulation to elicit motor or sensory responses, impedance measurements, or imaging verification.

[0214] According to embodiments, at step 1704, the baseline oxygen measurement may be obtained using various protocols. Single-point measurement may involve obtaining a single stable reading prior to stimulation. Multi-point measurement may involve obtaining readings at multiple anatomical locations for comparative analysis. Time-averaged measurement may involve averaging readings over a defined time period to reduce variability. The baseline measurement may be obtained with the patient at rest, during standardized activity, or under controlled environmental conditions (e.g., controlled room temperature for Raynaud's disease applications).

[0215] According to embodiments, at step 1706, the chemical and / or electrical stimulation may be administered according to various protocols. For chemical stimulation, bolus administration may involve rapid injection of a defined volume, while infusion administration may involve continuous delivery at a defined rate. For electrical stimulation, parameter selection may be based on published protocols, patient-specific titration, or adaptive algorithms. Stimulation may be administered unilaterally to the treatment side only, or bilaterally for comparative assessment. The duration of stimulation administration may range from seconds for acute testing to hours, days, or weeks for therapeutic applications.

[0216] According to embodiments, at step 1708, the oxygen levels may be detected at various time points post-stimulation. Immediate detection may occur within seconds to minutes to capture acute responses. Delayed detection may occur at hours or days post-stimulation to capture sustained effects. Continuous monitoring may involve ongoing detection throughout the treatment period. The detection may be performed at the same anatomical location as baseline measurement, at multiple locations, or at locations distal to the stimulation site to assess downstream effects.

[0217] According to embodiments, at step 1710, the hemodynamic effectiveness may be determined using various criteria. Threshold-based criteria may classify effectiveness as adequate if oxygen change exceeds a predefined threshold (e.g., 10% increase, 10-point absolute increase). Goal-based criteria may classify effectiveness based on whether target oxygen levels are achieved. Comparative criteria may classify effectiveness based on comparison to contralateral control measurements or historical patient data. Time-based criteria may consider not only the magnitude of change but also the onset time and duration of effect.Attorney Docket No.: 00333-0003-00304

[0218] According to embodiments, at step 1712, the stimulation parameters may be adjusted using various strategies. Incremental adjustment may involve small stepwise changes to individual parameters. Proportional adjustment may involve scaling parameters based on the magnitude of deviation from target values. Multi-parameter adjustment may involve simultaneous modification of multiple parameters according to predefined relationships. For chemical stimulation, adjustments may include modifying drug concentration, infusion rate, bolus volume, or dosing interval. For electrical stimulation, adjustments may include modifying amplitude, pulse width, frequency, duty cycle, electrode configuration, or stimulation pattern. The adjustment may be performed manually by a clinician, semi-automatically with clinician approval, or fully automatically by the closed-loop system.

[0219] According to embodiments, for arteriovenous fistula maturation applications, the system may be configured to maximize vein dilation and blood flow velocity to promote fistula development. The sensing device may be positioned to monitor the target vein diameter and flow characteristics. Target values may include vein diameter greater than approximately 6 mm and blood flow greater than approximately 600 mL / min. Treatment duration may span days to weeks, with the system cycling stimulation to maintain effectiveness while preventing neural adaptation. The infusion lead body may be positioned adjacent to brachial plexus nerves for upper extremity fistulas or fem oral / sciatic nerves for lower extremity fistulas.

[0220] According to embodiments, continuous stimulation may result in neural adaptation where nerves adjust back toward baseline hemodynamic states over time. To maintain the desired hemodynamic response and prevent or mitigate neural adaptation, the system may be configured to cycle stimulation on and off rather than delivering continuous stimulation. Various cycling parameters may be configured including on-time duration, off-time duration, duty cycle, and cycling frequency. For example, stimulation may be delivered for a period of, for example, under approximately a minute (e.g., under approximately 60 seconds, under approximately 30 seconds, under approximately 10 seconds, etc.), under approximately 5 minutes, approximately 5 to 30 minutes followed by an off period of approximately 5 to 60 minutes, or stimulation may be delivered according to a duty cycle of approximately 25% to 75%. The processor may be configured to automatically adjust cycling parameters based on detected hemodynamic properties. For example, if the processor detects that hemodynamic effectiveness is decreasing during a stimulation on period, the processor may initiate an off period to allow neural recovery. Similarly, if the processor detects that hemodynamic properties have returned toward baseline during an off period, the processor may initiate a subsequent on period. Cycling may be particularly relevant for longer-termAttorney Docket No.: 00333-0003-00304applications, such as arteriovenous fistula maturation, where treatment spans days to weeks, as the cycling approach may help maintain therapeutic effectiveness throughout the extended treatment duration while preventing or mitigating neural fatigue or adaptation.

[0221] According to embodiments, for spinal cord ischemia monitoring and treatment applications, the system may be configured to maintain adequate oxygen delivery to spinal cord tissue during and after aortic procedures. The sensing device may include NIRS sensors positioned over paraspinal regions at multiple spinal levels. Target values may include maintaining rSO2 within approximately 20% of baseline values. The infusion lead body may be positioned adjacent to paraspinal nerves or integrated with a lumbar drainage catheter. Stimulation may be initiated prophylactically prior to aortic clamping or reactively in response to detected ischemia.

[0222] According to embodiments, the infusion lead body may be integrated with a lumbar drainage catheter that includes one or more stimulation electrodes. The lumbar drainage catheter with stimulation electrodes may be used as a bail-out intervention for patients experiencing spinal cord ischemia during or after aortic procedures. Alternatively, the catheter may be placed preemptively prior to aortic procedures to reduce the occurrence of spinal cord ischemia. The stimulation electrodes may be positioned at a lumbar level such as L4-L5, adjacent to nerve roots in the paraspinal region. The stimulation may be configured to increase blood flow and oxygen delivery to spinal cord tissue. In some embodiments, target improvements may include approximately 10% or greater improvement in regional oxygen saturation. The lumbar drainage catheter with stimulation electrodes may be connected to a pulse generator configured to deliver electrical stimulation according to parameters determined by the closed-loop system based on sensed vasodilation properties.

[0223] At step 1704, a baseline vasodilation property is obtained via a sensing device (e.g., a vasodilation sensing device). The baseline vasodilation property may include at least one of oxygen levels, NIRS values, perfusion index, blood flow, or temperature. The baseline measurement may be obtained by placing the sensing device on an extremity such as a calf, foot, upper arm, shoulder, spinal area, or forearm, and allowing sufficient time for stable readings. At step 1706, chemical and / or electrical stimulation is administered via the one or more exit ports or the one or more electrodes. The stimulation may be delivered according to initial parameters including dosage, timing, frequency, amplitude, pulse width, and polarity. At step 1708, vasodilation properties at the body part are detected post-stimulation via the sensing device. The vasodilation properties may include at least one of oxygen levels, NIRSAttorney Docket No.: 00333-0003-00304values, perfusion index, blood flow, or temperature. The detection may occur within minutes of stimulation delivery to capture acute changes in tissue perfusion and oxygenation.

[0224] According to embodiments, (e.g., for Raynaud's disease applications or other applications), the system may be configured to prevent or reverse vasospastic episodes affecting digital arteries. The sensing device may include temperature sensors and pulse oximeters positioned on affected digits. Target values may include maintaining digital temperature above threshold levels and oxygen saturation above approximately 95%. The system may operate in a demand mode, initiating stimulation in response to detected vasospastic episodes or environmental triggers such as cold exposure. The infusion lead body may be positioned adjacent to digital nerves or more proximally at the brachial plexus level.

[0225] According to embodiments, the closed-loop system may operate in various modes including: (a) continuous sensing with continuous stimulation adjustment, (b) continuous sensing with iterative stimulation adjustment, (c) iterative sensing with continuous stimulation adjustment, or (d) iterative sensing with iterative stimulation adjustment. The frequency of sensing and / or stimulation updates may be configurable based on the clinical application, patient response characteristics, or treatment phase. For acute applications, more frequent sensing and updates may be used. For chronic applications, less frequent sensing and updates may be sufficient.

[0226] According to embodiments, the system may include multiple sensing devices positioned at different anatomical locations to enable multi-channel monitoring. For example, as shown in Figures 12A-12B and 13C-13E, multiple sensors may be positioned at different locations such as the foot (foot location 1210, foot location 1214), calf (calf location 1212), or other body parts. Each sensing device may independently detect hemodynamic properties at its respective location, providing simultaneous measurements from multiple anatomical sites. The multiple sensing devices may be connected to a common monitoring device or processor, or may communicate wirelessly with a central processor.

[0227] According to embodiments, the processor may be configured to determine treatment values based on multiple inputs from the multiple sensing devices. The multiple inputs may include hemodynamic properties detected at different anatomical locations, such as oxygen levels, perfusion index, NIRS values, blood flow, or temperature at each location. The processor may aggregate, compare, or otherwise analyze the multiple inputs to determine an overall treatment effectiveness or to identify differential responses at different locations.

[0228] According to embodiments, the processor may use various methods to aggregate multiple inputs including averaging values across multiple locations, weighting values basedAttorney Docket No.: 00333-0003-00304on clinical significance of each location, identifying minimum or maximum values across locations, calculating differences or ratios between locations (e.g., treatment site vs. control site, proximal vs. distal), or applying machine learning models trained on multi-channel input data.

[0229] According to embodiments, multi-channel monitoring may enable identification of differential responses at different anatomical locations. For example, a treatment site may show a 46% increase in oxygen saturation while a control site shows only a 2% change, as illustrated in Figures 13D-13E. The processor may compare responses between treatment and control sites to isolate treatment effects from systemic changes. The processor may also compare proximal and distal measurements to assess the extent of hemodynamic response propagation.

[0230] According to embodiments, the processor may adjust treatment values based on the multi-channel data. For example, if distal measurements show inadequate response while proximal measurements show adequate response, the processor may increase stimulation intensity or duration to extend the hemodynamic effect distally. If all channels show adequate response, the processor may maintain or reduce stimulation to conserve resources. If some channels show excessive response while others show inadequate response, the processor may adjust stimulation parameters to achieve more uniform hemodynamic response across the treatment region.

[0231] According to embodiments, the system may be configured with channelspecific target values. For example, a target oxygen level of 70% may be set for a foot location while a target of 60% may be set for a calf location. The processor may independently evaluate each channel against its respective target and determine treatment adjustments to achieve all channel-specific targets.

[0232] According to embodiments, the system may transition between continuous and iterative modes based on detected conditions. For example, the system may switch to more frequent sensing when hemodynamic properties approach threshold values or target values. The system may also increase sensing frequency in response to rapid changes in hemodynamic properties or decrease sensing frequency when hemodynamic properties are stable. This adaptive approach may optimize battery life for implantable applications while maintaining therapeutic effectiveness.

[0233] According to embodiments, the closed-loop system may be implemented using implantable components for chronic or sub-chronic applications. The sensing device may be an implantable sensing device configured to be positioned beneath the skin for long-termAttorney Docket No.: 00333-0003-00304monitoring of hemodynamic properties. In some embodiments, the closed-loop system may include an implantable infusion lead assembly and an implantable sensing device. In some embodiments, the drug pump and / or pulse generator may also be implanted. The implantable sensing device may enable longitudinal optimization of stimulation settings over extended treatment periods, such as weeks, months, or years. The implantable sensing device may communicate wirelessly with external components such as an external controller, programmer, or monitoring device. In some embodiments, the implantable sensing device may communicate with other implanted components such as an implantable pulse generator or implantable drug pump via wired or wireless communication pathways. The implantable configuration may be suitable for applications requiring ongoing treatment and monitoring, such as chronic pain management, arteriovenous fistula maturation, or spinal cord ischemia prevention.

[0234] According to embodiments, chemical stimulation may involve various pharmacological agents. Local anesthetics such as ropivacaine (0.2-0.5%), bupivacaine (0.25-0.5%), or lidocaine (1-2%) may provide sympathetic blockade and vasodilation. Vasodilators such as papaverine, nitroglycerin, or calcium channel blockers may directly relax vascular smooth muscle. Alpha-adrenergic antagonists such as phentolamine may block sympathetic vasoconstriction. Combinations of agents may provide synergistic effects. Drug selection may be based on desired onset time, duration of effect, and side effect profile.

[0235] According to embodiments, electrical stimulation parameters may be selected based on target neural structures and desired effects. Low-frequency stimulation (1-10 Hz) may preferentially activate large-diameter sensory fibers. Medium-frequency stimulation (10-100 Hz) may provide conventional neurostimulation effects. High-frequency stimulation (1-10 kHz) may provide paresthesia-free analgesia. Burst stimulation patterns may provide enhanced efficacy for certain applications. Amplitude may range from sub-perception levels (0.1-1 mA) to supra-perception levels (1-10 mA) depending on electrode proximity to target nerves and desired effect intensity.

[0236] According to embodiments, the treatment value may be adjusted according to a pyramid therapy pattern in which one or more stimulation parameters are incrementally increased to a peak value and then incrementally decreased. The pyramid therapy pattern may be applied to any of the treatment value parameters including dosage, timing, frequency, amplitude, type, polarity, pulse width, or rate. For example, an amplitude pyramid therapy pattern may comprise a sequence of stimulation settings such as: a first setting of approximately 2 mA at 5 Hz with a pulse width of 500 microseconds; a second setting of approximately 3 mA at 5 Hz with a pulse width of 500 microseconds; a third setting of approximately 4 mA at 5 HzAttorney Docket No.: 00333-0003-00304with a pulse width of 500 microseconds; a fourth setting of approximately 3 mA at 5 Hz with a pulse width of 500 microseconds; and a fifth setting of approximately 2 mA at 5 Hz with a pulse width of 500 microseconds. In this example, the amplitude increases from 2 mA to 4 mA and then decreases back to 2 mA while frequency and pulse width remain constant. In other embodiments, the pyramid therapy pattern may be applied to frequency, where frequency is incrementally increased to a peak frequency and then incrementally decreased while amplitude and pulse width remain constant. In further embodiments, the pyramid therapy pattern may be applied to pulse width, dosage for chemical stimulation, or other treatment value parameters. The pyramid therapy pattern may be configured to optimize therapeutic effectiveness while minimizing adverse effects such as neural adaptation or paresthesia. The processor may be configured to automatically implement the pyramid therapy pattern based on sensed hemodynamic properties, or the pyramid therapy pattern may be pre-programmed based on clinical protocols.

[0237] According to embodiments, in addition to or as an alternative to chemical stimulation and / or electrical stimulation, thermal stimulation may be used to manipulate nerves and affect hemodynamic properties. Thermal stimulation may involve the application of heat or cold to target neural structures to induce vasodilation, vasoconstriction, or other hemodynamic changes. For example, localized heating of tissue adjacent to a nerve may cause vasodilation and increased blood flow, while localized cooling may cause vasoconstriction and decreased blood flow. The thermal stimulation may be delivered via a thermal element integrated with an infusion lead body, a separate thermal probe positioned adjacent to a nerve, or an external thermal device. The thermal element may include a resistive heating element, a device capable of both heating and cooling, a radiofrequency energy source, or other thermal energy delivery mechanisms. Temperature parameters such as target temperature, heating or cooling rate, duration of thermal application, and cycling patterns may be adjusted based on sensed hemodynamic properties to achieve target hemodynamic responses. In some embodiments, thermal stimulation may be used alone to induce hemodynamic changes. In other embodiments, thermal stimulation may be combined with chemical stimulation, electrical stimulation, or both to provide multimodal therapy. The closed-loop system disclosed herein may be configured to monitor hemodynamic properties and adjust thermal stimulation parameters to reach target oxygen levels, target perfusion index, target blood flow, or other target hemodynamic values. The processor may be configured to determine treatment values for thermal stimulation based on sensed hemodynamic properties, and may adjust the thermal stimulation in combination with or as an alternative to chemical or electrical stimulation.Attorney Docket No.: 00333-0003-00304

[0238] According to embodiments, the term "type" as used herein with respect to a treatment value may refer to one or more of the following aspects of stimulation. In some embodiments, type may refer to the modality of stimulation, including chemical stimulation delivered via a drug pump, electrical stimulation delivered via a pulse generator, or combined chemical and electrical stimulation delivered via both a drug pump and a pulse generator. In some embodiments, type may refer to the temporal pattern of stimulation delivery, including continuous stimulation where stimulation is delivered without interruption, cycling or intermittent stimulation where stimulation is delivered in alternating on and off periods, burst stimulation where stimulation is delivered in discrete bursts, or demand-based stimulation where stimulation is triggered in response to sensed conditions. In some embodiments, type may refer to the category of electrical stimulation based on frequency range, including low-frequency stimulation (e.g., approximately 1-10 Hz), medium-frequency stimulation (e.g., approximately 10-100 Hz), or high-frequency stimulation (e.g., approximately 1-10 kHz). The processor may be configured to adjust the type of stimulation based on detected hemodynamic properties, target values, or other treatment parameters to achieve desired therapeutic outcomes.

[0239] According to embodiments, the physiological rationale for cycling or intermittent stimulation patterns may relate to neural adaptation phenomena. In some cases, continuous stimulation may result in neural adaptation where the stimulated nerves adjust their response over time, potentially causing blood flow and other hemodynamic parameters to return toward baseline levels despite ongoing stimulation. To address this neural adaptation, the system may be configured to deliver stimulation in cycling or intermittent patterns rather than continuous stimulation. The cycling parameters, including on-time duration, off-time duration, and duty cycle, may be configured based on sensed vasodilation properties to maintain therapeutic effectiveness throughout the treatment period. In some embodiments, the closed-loop system may detect when vasodilation effectiveness decreases during a stimulation period, which may indicate the onset of neural adaptation, and may automatically adjust stimulation patterns in response. For example, the processor may be configured to initiate an off period when detected vasodilation properties begin to decline, allowing neural recovery before resuming stimulation. The processor may also be configured to monitor the rate of decline in vasodilation effectiveness and adjust cycling parameters accordingly, such as shortening on-time durations or lengthening off-time durations when more rapid adaptation is detected. This adaptive cycling approach may help maintain the desired hemodynamicAttorney Docket No.: 00333-0003-00304response over extended treatment durations by preventing or mitigating the effects of neural adaptation.

[0240] According to embodiments, the physiological rationale for cycling or intermittent stimulation patterns may relate to neural adaptation phenomena. In some cases, continuous stimulation may result in neural adaptation where the stimulated nerves adjust their response over time, potentially causing blood flow and other hemodynamic parameters to return toward baseline levels despite ongoing stimulation. To address this neural adaptation, the system may be configured to deliver stimulation in cycling or intermittent patterns rather than continuous stimulation. The cycling parameters, including on-time duration, off-time duration, and duty cycle, may be configured based on sensed hemodynamic properties to maintain therapeutic effectiveness throughout the treatment period. In some embodiments, the closed-loop system may detect when hemodynamic effectiveness decreases during a stimulation period, which may indicate the onset of neural adaptation, and may automatically adjust stimulation patterns in response. For example, the processor may be configured to initiate an off period when detected hemodynamic properties begin to decline, allowing neural recovery before resuming stimulation. The processor may also be configured to monitor the rate of decline in hemodynamic effectiveness and adjust cycling parameters accordingly, such as shortening on-time durations or lengthening off-time durations when more rapid adaptation is detected. This adaptive cycling approach may help maintain the desired hemodynamic response over extended treatment durations by preventing or mitigating the effects of neural adaptation.

[0241] According to embodiments, the stimulation may provide improved targeting during embolization procedures. By modulating blood flow through vasodilation or vasoconstriction of specific vessels, the stimulation may direct embolic material toward target vessels while reducing flow to non-target vessels. The improved targeting may result in more precise delivery of embolic material to the intended treatment site.

[0242] According to embodiments, the stimulation may provide precision of delivery of embolic material. The controlled modulation of blood flow may enable more accurate placement of embolic agents at the desired location within the vasculature. The precision of delivery may be enhanced by real-time monitoring of vasodilation properties and adjustment of stimulation parameters to achieve optimal flow conditions for embolic material delivery.

[0243] According to embodiments, the stimulation may improve embolic material retention at the target site. By modulating blood flow velocity and vessel diameter, the stimulation may create hemodynamic conditions that promote retention of embolic material atAttorney Docket No.: 00333-0003-00304the intended occlusion site. The improved retention may reduce the risk of embolic material migration to unintended locations.

[0244] According to embodiments, the stimulation may provide dynamic flow control for optimized material delivery specific to the embolic agent being used. Different embolic agents (e.g., particles, coils, liquid embolics, microspheres) may have different optimal flow conditions for delivery and retention. The stimulation parameters may be adjusted based on the specific embolic agent to optimize delivery conditions. For example, slower flow rates may be preferred for liquid embolics to allow adequate polymerization time, while faster flow rates may be preferred for particle delivery to achieve deeper penetration.

[0245] According to embodiments, the stimulation may reduce non-targeted tissue embolization. By precisely controlling blood flow patterns, the stimulation may minimize the risk of embolic material reaching non-target tissues. The reduction in non-targeted embolization may decrease the risk of complications such as ischemia to healthy tissue.

[0246] According to embodiments, the stimulation may provide improved dwell time of embolic material at the target site. Dwell time refers to the duration that embolic material remains in contact with the target vessel before being carried downstream by blood flow. By reducing blood flow velocity through vasodilation, the stimulation may increase dwell time, allowing embolic material to more effectively occlude the target vessel.

[0247] According to embodiments, the stimulation may provide improved occlusion time. Occlusion time refers to the time required to achieve complete vessel occlusion. By optimizing hemodynamic conditions, the stimulation may reduce the time required to achieve effective occlusion, potentially reducing procedure duration and radiation exposure.

[0248] According to embodiments, the stimulation may provide improved anatomic access during embolization procedures. By dilating vessels upstream of the target site, the stimulation may facilitate navigation of catheters and delivery devices to the target location. The improved access may enable treatment of lesions that would otherwise be difficult to reach due to vessel tortuosity or small vessel diameter.

[0249] According to embodiments, the stimulation may enable individual patient optimization during embolization procedures. The closed-loop monitoring and adjustment of stimulation parameters based on real-time vasodilation property measurements may enable customization of the procedure to each patient's unique vascular anatomy and hemodynamic characteristics. The individual patient optimization may improve procedural outcomes and reduce complications.Attorney Docket No.: 00333-0003-00304

[0250] According to embodiments, a stimulating microcatheter may be used for embolization procedures. The stimulating microcatheter may include one or more electrodes configured to deliver electrical stimulation to increase arterial flow and enable delivery of more and deeper embolization particles. The stimulating microcatheter may be used for various embolization procedures including transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and genicular artery embolization (GAE) for treatment of osteoarthritis.

[0251] According to embodiments, one or more stimulation electrodes may be integrated with a guide sheath or other interventional devices to provide electrical stimulation during interventional procedures. The stimulation electrodes may be positioned on an outer surface, an inner surface, or embedded within a wall of the guide sheath. In some embodiments, the stimulation electrodes may be integrated with thrombectomy devices, aspiration catheters, stent delivery systems, balloon catheters, or other interventional devices configured for navigation through the vasculature. The electrical stimulation delivered via the integrated electrodes may dilate distal vessels to improve crossability of the interventional device, increase arterial flow to enhance procedural outcomes, or provide vasodilation to facilitate device navigation through tortuous or small-diameter vessels. The stimulation electrodes integrated with the guide sheath or interventional device may be connected to a pulse generator via conductive traces or wires extending along or within the device. In some embodiments, the stimulation parameters including amplitude, frequency, pulse width, and polarity may be adjusted based on sensed vasodilation properties to optimize vessel dilation during the procedure.

[0252] According to embodiments, for radial artery access procedures, electrical stimulation may be applied to relax and dilate the radial artery prior to or during sheath insertion. In some embodiments, stimulation may be applied extravascularly in the brachial plexus region to induce vasodilation of the radial artery and associated vessels of the upper extremity. The extravascular stimulation may be delivered via an infusion lead body positioned adjacent to brachial plexus nerves, where the electrical stimulation causes sympathetic blockade and resultant vasodilation of downstream vessels including the radial artery. In other embodiments, a stimulation wire or stimulation catheter may be advanced intravascularly up the arm artery prior to sheath insertion. The stimulation wire or catheter may include one or more electrodes configured to deliver electrical stimulation to relax and dilate the vessel from within the arterial lumen. The intravascular stimulation may be delivered as the stimulation wire or catheter is advanced, providing progressive vasodilation along the arterial pathway. InAttorney Docket No.: 00333-0003-00304some embodiments, the stimulation may be delivered for a period of time prior to sheath insertion to allow adequate vessel relaxation, or the stimulation may be delivered concurrently with sheath advancement. The vasodilation induced by the stimulation may reduce the risk of radial artery spasm, improve sheath insertion success rates, and reduce patient discomfort during radial artery access procedures. In some embodiments, a sensing device may be used to monitor vasodilation properties during the radial artery access procedure, and stimulation parameters may be adjusted based on the sensed properties to achieve a target level of vessel dilation.

[0253] According to embodiments, the stimulation may be delivered using intravascular or extra- vascular approaches. In intra-vascular approaches, a stimulation lead, catheter, or other device may be positioned within a blood vessel such as an artery or vein, and electrical stimulation may be delivered from within the vessel lumen to affect the vessel wall or surrounding neural structures. In extra-vascular approaches, a stimulation lead may be positioned outside of blood vessels, adjacent to nerves that innervate the target vasculature, such that electrical stimulation of the nerves causes downstream hemodynamic effects in the vessels innervated by those nerves. For example, extra-vascular stimulation of brachial plexus nerves may cause vasodilation in downstream vessels of the upper extremity. The choice between intra-vascular and extra- vascular approaches may depend on the clinical application, target anatomy, desired hemodynamic effect, and procedural considerations. In some embodiments, intra-vascular and extra- vascular stimulation may be combined to achieve enhanced hemodynamic effects.

[0254] According to embodiments, a stimulation lead may be positioned in the shoulder or brachial plexus region to induce hemodynamic changes in the upper extremity for various acute procedure applications. For arteriovenous fistula (AVF) creation or maturation, stimulation of brachial plexus nerves may cause vein dilation, increasing vein diameter and improving conditions for fistula creation and subsequent maturation. For renal artery access procedures, stimulation of brachial plexus nerves may cause artery dilation, facilitating catheter insertion and navigation for renal interventions. These applications may be acute procedures where stimulation is delivered during or immediately surrounding the interventional procedure to optimize vascular access and procedural outcomes. The sensing device may monitor hemodynamic properties such as vessel diameter, blood flow velocity, or perfusion index during the procedure to confirm adequate hemodynamic response and guide stimulation parameter adjustment.Attorney Docket No.: 00333-0003-00304

[0255] According to embodiments, the systems and methods disclosed herein may be applied to acute procedures, chronic treatments, or both. Acute procedure applications may include intra-operative stimulation during vascular access procedures, embolization procedures, or surgical interventions where hemodynamic modulation is desired for a limited duration during and immediately surrounding the procedure. Chronic treatment applications may include ongoing stimulation over days, weeks, or months for applications such as wound healing, AVF maturation, or management of conditions such as critical limb ischemia, Buerger's disease, or Raynaud's disease. The closed-loop system may be configured differently for acute versus chronic applications. For acute applications, the system may prioritize rapid response and real-time adjustment of stimulation parameters. For chronic applications, the system may incorporate cycling patterns to prevent neural adaptation, longitudinal optimization of stimulation settings, and remote monitoring capabilities.

[0256] According to embodiments, the hemodynamic property sensing may be used to detect or confirm capture. Capture may refer to the successful activation of target neural structures by the electrical and / or chemical stimulation, contact between a component (e.g., an electrode) and a target blood vesicle, contact between a drug and a target blood vesicle, and / or the like that may result in a measurable physiological response. The detection of capture may be used to confirm proper lead placement, verify that stimulation parameters are effective, and / or trigger subsequent actions.

[0257] According to embodiments, a change in a hemodynamic property may be compared to a target hemodynamic property to detect or confirm capture. The target hemodynamic property may include at least one of a target oxygen level, a target perfusion index, a target NIRS value, a target temperature, or a target blood flow. If the detected hemodynamic property reaches or exceeds the target hemodynamic property, then capture may be confirmed. For example, if a target oxygen level increase of 10% is set and the detected oxygen level increases by 12% following stimulation, capture may be confirmed.

[0258] According to embodiments, when capture is confirmed, an indication may be provided to a user or clinician. The indication may include a visual indication (e.g., a light, an icon on a display, a change in display appearance), an audible indication (e.g., a tone, a beep, a voice announcement), a tactile indication (e.g., a vibration), or a combination thereof. The indication may be provided via the monitoring device, the pulse generator, the drug pump, a separate user interface device, or a mobile device such as a smartphone or tablet.

[0259] According to embodiments, when capture is confirmed, an automated action may be triggered. The automated action may include initiating subsequent electricalAttorney Docket No.: 00333-0003-00304stimulation, initiating subsequent chemical stimulation, adjusting stimulation parameters, transitioning from a capture confirmation mode to a therapy delivery mode, recording capture confirmation data, or transmitting capture confirmation data to a remote system. For example, upon confirming capture, the system may automatically transition from low-level test stimulation to therapeutic-level stimulation.

[0260] According to embodiments, capture detection may be used for lead placement confirmation. During initial positioning of the infusion lead body adjacent to a nerve, test stimulation may be delivered and the vasodilation property response may be monitored. If the vasodilation property response reaches the target vasodilation property, the lead placement may be confirmed as correct. If the vasodilation property response does not reach the target, the lead may be repositioned and the test repeated until capture is confirmed. This approach may reduce the need for other lead placement confirmation techniques such as motor response testing or imaging verification.

[0261] According to embodiments, hemodynamic property sensing using NIRS, pulse oximetry, or other sensing modalities may be used to optimize lead placement during spinal cord stimulation (SCS) trialing or other neurostimulation procedures. In these applications, the lead body may be a standard stimulation lead comprising one or more electrodes without infusion capability. During SCS trialing, a clinician may position the lead body adjacent to target neural structures such as the spinal cord or dorsal root ganglia. The sensing device may detect hemodynamic properties such as regional oxygen saturation (rSO2) or perfusion index at one or more body locations during test stimulation. The detected hemodynamic response may be correlated with stimulation efficacy, such that an improved hemodynamic response (e.g., increased oxygen levels, increased perfusion index) at a given lead position may indicate improved stimulation efficacy for pain management at that position. The clinician may adjust the lead position and repeat test stimulation while monitoring the hemodynamic response to identify an optimal lead placement that maximizes the hemodynamic response. Once an optimal position is identified based on the hemodynamic response, the lead placement may be confirmed and the lead may be secured for ongoing therapy. This approach may provide an objective, quantitative measure for optimizing lead placement during SCS trialing, complementing or replacing subjective patient feedback regarding paresthesia coverage or pain relief. The hemodynamic-based lead placement optimization may be particularly useful in patients who are unable to provide reliable feedback, such as patients under anesthesia or patients with communication difficulties.Attorney Docket No.: 00333-0003-00304

[0262] According to embodiments, the hemodynamic property sensing may be used to detect hemodynamic deterioration. Deterioration may be indicated by a decrease in oxygen levels, a decrease in perfusion index, a decrease in blood flow, a decrease in NIRS values, or a decrease in temperature at the body part. The processor may compare current hemodynamic property measurements to baseline measurements, previous measurements, or target values to determine whether deterioration is occurring.

[0263] According to embodiments, if the sensed hemodynamic property indicates hemodynamic deterioration, an automated action may be triggered. The automated action may include stopping electrical stimulation, stopping chemical stimulation, stopping both electrical and chemical stimulation, reducing stimulation intensity, modifying stimulation parameters, or alerting a clinician. For example, electrical and / or chemical stimulation may be stopped for a period of time until the deterioration subsides or reverses.

[0264] According to embodiments, the system may be configured to pause stimulation in response to detected deterioration and resume stimulation when the deterioration subsides or reverses. The pause duration may be a predetermined time period, or may be dynamically determined based on the rate of recovery. The system may monitor hemodynamic properties during the pause period and automatically resume stimulation when the hemodynamic properties return to acceptable levels or stabilize.

[0265] According to embodiments, the system may be configured with deterioration thresholds that trigger automated actions. For example, a deterioration threshold may be set such that if oxygen saturation decreases by more than 5% from baseline, or if perfusion index decreases by more than 20% from a peak value, stimulation is automatically paused. The deterioration thresholds may be configurable based on the clinical application, patient characteristics, or clinician preferences.

[0266] According to embodiments, the deterioration detection and automated response may serve as a safety mechanism to prevent adverse effects from overstimulation or inappropriate stimulation. By automatically pausing stimulation when deterioration is detected, the system may prevent tissue damage, nerve fatigue, or other complications that could result from continued stimulation during adverse conditions.

[0267] With reference to Figure 16, deterioration detection may be incorporated into process 1600. At step 1624, when processor 1608 determines hemodynamic effectiveness, the processor 1608 may also determine whether the hemodynamic property indicates deterioration by comparing the updated hemodynamic property to the baseline hemodynamic property or to previous measurements. If deterioration is detected, processor 1608 may provide a treatmentAttorney Docket No.: 00333-0003-00304value at step 1628 that causes drug pump and / or pulse generator 1604 to stop or reduce stimulation at step 1630. The process 1600 may continue to monitor hemodynamic properties via steps 1618-1622 during the pause period, and processor 1608 may provide an updated treatment value to resume stimulation when deterioration subsides.

[0268] With reference to Figure 17, deterioration detection may be incorporated into method 1700. At step 1710, when hemodynamic effectiveness is determined based on the change between the baseline measurement and the detected hemodynamic property, the method may include determining whether the change indicates deterioration. If deterioration is detected, step 1712 may include adjusting stimulation parameters to stop or reduce stimulation until the deterioration subsides or reverses. The method may then return to step 1708 to continue monitoring hemodynamic properties during the pause period.

[0269] With reference to Figure 16, capture detection may be incorporated into process 1600. At step 1624, when processor 1608 determines hemodynamic effectiveness, the processor 1608 may compare the detected hemodynamic property to a target hemodynamic property to determine whether capture has been achieved. If capture is confirmed, processor 1608 may provide an indication to a user and / or trigger an automated action at step 1628 by providing a treatment value that initiates therapeutic stimulation.

[0270] With reference to Figure 17, capture detection may be incorporated into method 1700. At step 1710, when hemodynamic effectiveness is determined based on the change between the baseline measurement and the detected hemodynamic property, the method may include comparing the change to a target change to determine whether capture has been achieved. If capture is confirmed, the method may include providing an indication to a user and / or triggering an automated action such as proceeding to step 1712 to adjust stimulation parameters for therapeutic delivery.

[0271] As discussed, one or more implementations disclosed herein may be applied by using a machine learning model. A machine learning model as disclosed herein may be trained using the systems, components, techniques, or the like associated with Figures 1-17 disclosed herein. The machine learning model may be trained to output treatment values based on inputs comprising at least one of measurements detected by a sensing device, an area of treatment, patient biometric values, patient demographics, or target values. Data analytics may be used to determine optimal settings relevant to patient demographics that can be used for a broader patient population. As shown in flow diagram 1010 of Figure 10, training data 1012 may include one or more of stage inputs 1014 and known outcomes 1018 related to a machine learning model to be trained. The stage inputs 1014 may be from any applicable sourceAttorney Docket No.: 00333-0003-00304including a component or set shown in Figures 1-17. The known outcomes 1018 may be included for machine learning models generated based on supervised or semi-supervised training. An unsupervised machine learning model might not be trained using known outcomes 1018. Known outcomes 1018 may include known or desired outputs for future inputs similar to or in the same category as stage inputs 1014 that do not have corresponding known outputs.

[0272] The training data 1012 and a training algorithm 1020 may be provided to a training component 1030 that may apply the training data 1012 to the training algorithm 1020 to generate a trained machine learning model 1050. According to an implementation, the training component 1030 may be provided comparison results 1016 that compare a previous output of the corresponding machine learning model to apply the previous result to re-train the machine learning model. The comparison results 1016 may be used by the training component 1030 to update the corresponding machine learning model. The training algorithm 1020 may utilize machine learning networks and / or models including, but not limited to a deep learning network such as Deep Neural Networks (DNN), Convolutional Neural Networks (CNN), Fully Convolutional Networks (FCN) and Recurrent Neural Networks (RCN), probabilistic models such as Bayesian Networks and Graphical Models, and / or discriminative models such as Decision Forests and maximum margin methods, or the like. The output of the flow diagram 1010 may be a trained machine learning model 1050.

[0273] In general, any process or operation discussed in this disclosure that is understood to be computer-implementable, such as those discussed in reference to Figures 1-10, may be performed by one or more processors of a computer system. A process or process step performed by one or more processors may also be referred to as an operation. The one or more processors may be configured to perform such processes by having access to instructions (e.g., software or computer-readable code) that, when executed by the one or more processors, cause the one or more processors to perform the processes. The instructions may be stored in a memory of the computer system. A processor may be a central processing unit (CPU), a graphics processing unit (GPU), or any suitable types of processing unit.

[0274] According to implementations disclosed herein, means for collecting, storing, and / or transmitting drug delivery data may be implemented using one or more processors of a computer system, as discussed herein. Drug delivery data may include any data described herein including, but not limited to, data described in reference to Figures 1-10, data associated with one or more of bolus amounts, bolus times, basal doses, basal times, chemical stimulation properties (e.g., time, amount, frequency, etc.), electrical stimulation properties (e.g., time, amount, frequency, etc.), and / or the like or a combination thereof. Such means may includeAttorney Docket No.: 00333-0003-00304collecting, storing, and / or transmitting drug delivery data via wired or wireless communication and may include collecting, storing, and / or transmitting such data including servers, databases, memory, cloud components, and / or components disclosed in reference to Figure 11, further discussed herein.

[0275] A computer system, such as a system or device implementing a process or operation in the examples above, may include one or more computing devices, such as one or more of the systems or devices disclosed in or disclosed in relation to Figures 1-10. One or more processors of a computer system may be included in a single computing device or distributed among a plurality of computing devices. A memory of the computer system may include the respective memory of each computing device of the plurality of computing devices.

[0276] Figure 11 is a simplified functional block diagram of a computer 1100 that may be configured as a device for executing the systems and / or techniques of Figures 1-10, according to exemplary embodiments of the present disclosure. For example, the computer 1100 may be configured as a system according to exemplary embodiments of this disclosure. In various embodiments, any of the systems herein may be a computer 1100 including, for example, a data communication interface 1120 for packet data communication. The computer 1100 also may include a central processing unit (“CPU”) 1102, in the form of one or more processors, for executing program instructions. The computer 1100 may include an internal communication bus 1108, and a storage unit 1106 (such as ROM, HDD, SDD, etc.) that may store data on a computer readable medium 1122, although the computer 1100 may receive programming and data via network communications. The computer 1100 may also have a memory 1104 (such as RAM) storing instructions 1124 for executing techniques presented herein, although the instructions 1124 may be stored temporarily or permanently within other modules of computer 1100 (e.g., processor 1102 and / or computer readable medium 1122). The computer 1100 also may include input and output ports 1112 and / or a display 1110 to connect with input and output devices such as keyboards, mice, touchscreens, monitors, displays, etc. The various system functions may be implemented in a distributed fashion on a number of similar platforms, to distribute the processing load. Alternatively, the systems may be implemented by appropriate programming of one computer hardware platform.

[0277] Program aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of executable code and / or associated data that is carried on or embodied in a type of machine-readable medium. “Storage” type media include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, whichAttorney Docket No.: 00333-0003-00304may provide non-transitory storage at any time for the software programming. All or portions of the software may at times be communicated through the Internet or various other telecommunication networks 1190. Such communications, for example, may enable loading of the software from one computer or processor into another, for example, from a management server or host computer of the mobile communication network into the computer platform of a server and / or from a server to the mobile device. Thus, another type of media that may bear the software elements includes optical, electrical and electromagnetic waves, such as used across physical interfaces between local devices, through wired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links, or the like, also may be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

[0278] While the disclosed methods, devices, and systems are described with exemplary reference to transmitting data, it should be appreciated that the disclosed embodiments may be applicable to any environment, such as a desktop or laptop computer, an automobile entertainment system, a home entertainment system, etc. Also, the disclosed embodiments may be applicable to any type of Internet protocol.

[0279] It should be appreciated that in the above description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the Detailed Description are hereby expressly incorporated into this Detailed Description, with each claim standing on its own as a separate embodiment of this invention.

[0280] Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those skilled in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.Attorney Docket No.: 00333-0003-00304

[0281] Thus, while certain embodiments have been described, those skilled in the art will recognize that other and further modifications may be made thereto without departing from the spirit of the invention, and it is intended to claim all such changes and modifications as falling within the scope of the invention. For example, functionality may be added or deleted from the block diagrams and operations may be interchanged among functional blocks. Steps may be added or deleted to methods described within the scope of the present invention.

[0282] The above disclosed subject matter is to be considered illustrative, and not restrictive, and the appended claims are intended to cover all such modifications, enhancements, and other implementations, which fall within the true spirit and scope of the present disclosure. Thus, to the maximum extent allowed by law, the scope of the present disclosure is to be determined by the broadest permissible interpretation of the following claims and their equivalents, and shall not be restricted or limited by the foregoing detailed description. While various implementations of the disclosure have been described, it will be apparent to those of ordinary skill in the art that many more implementations are possible within the scope of the disclosure. Accordingly, the disclosure is not to be restricted except in light of the attached claims and their equivalents.

Claims

Attorney Docket No.: 00333-0003-00304CLAIMSWhat is claimed is:

1. A system for monitoring hemodynamic effectiveness, the system comprising: a lead assembly including a lead body, wherein the lead body includes at least one stimulation delivery point;at least one stimulation source in communication with the lead assembly for providing a stimulation via the at least one stimulation delivery point;a sensing device comprising a sensor configured to detect a hemodynamic property of a body part; anda processor configured to execute instructions to determine hemodynamic effectiveness based on the detected hemodynamic property at least one of before, during, or after the stimulation is delivered by the at least one stimulation source.

2. The system of claim 1, wherein the processor is configured to calculate a perfusion index associated with tissue at the body part based on detection of a photoplethysmographic waveform using the sensor.

3. The system of claim 2, wherein the sensor is a pulse oximeter sensor configured to emit light through skin and detect changes in light absorption caused by blood flow, wherein the pulse oximeter sensor is configured to detect an alternating current signal corresponding to pulsatile blood flow and a direct current signal corresponding to non-pulsatile blood flow, and wherein the perfusion index is determined based on a relationship between the alternating current signal and the direct current signal.

4. The system of claim 1, wherein the processor is further configured to execute instructions to compare the detected hemodynamic property to a target hemodynamic property to detect capture, wherein capture is detected when the detected hemodynamic property reaches or exceeds the target hemodynamic property.

5. The system of claim 1, wherein the at least one stimulation source is at least one of: a pulse generator, wherein the at least one stimulation delivery point includes one or more electrodes configured to deliver electrical stimulation;Attorney Docket No.: 00333-0003-00304a drug pump, wherein the at least one stimulation delivery point includes one or more exit ports configured to deliver a fluid; ora thermal device, wherein the at least one stimulation delivery point includes a thermal element to change a temperature at the stimulation delivery point.

6. The system of claim 1, wherein the sensing device is configured to detect at least one of a regional oximetry via oxygen saturation detection, a perfusion index, a near-infrared spectroscopy (NIRS) value, a blood flow rate, or a temperature at the body part.

7. The system of claim 1, wherein the processor is further configured execute instructions to:determine a treatment value based on the detected hemodynamic property, wherein the treatment value comprises at least one of a dosage, a timing, a frequency, an amplitude, a type, a polarity, a pulse width, or a rate related to the stimulation delivered by the at least one stimulation source; andadjust the at least one stimulation source based on the treatment value.

8. The system of claim 1, wherein the processor is further configured execute instructions to:determine a treatment value based on the detected hemodynamic property, wherein the treatment value comprises at least one of a dosage, a timing, a frequency, an amplitude, a type, a polarity, a pulse width, or a rate related to the stimulation delivered by the at least one stimulation source, and wherein the treatment value is determined based on at least one of a target oxygen level, a target perfusion index, a target NIRS value, a target temperature, or a target blood flow; andadjust the at least one stimulation source based on the treatment value.

9. The system of claim 1, wherein the processor is further configured execute instructions to:determine a treatment value based on the detected hemodynamic property, wherein the treatment value comprises at least one of a dosage, a timing, a frequency, an amplitude, a type, a polarity, a pulse width, or a rate related to the stimulation delivered by the at least oneAttorney Docket No.: 00333-0003-00304stimulation source, and wherein the treatment value is determined based on at least one of a target elasticity or dimensions of blood vessels; andadjust the at least one stimulation source based on the treatment value.

10. A method for providing treatment based on monitoring hemodynamic properties, the method comprising:positioning a lead body adjacent to a nerve, wherein the lead body comprises at least one of one or more electrodes or one or more exit ports;obtaining, via a sensing device, a baseline hemodynamic property at a body part; administering at least one of chemical stimulation via the one or more exit ports or electrical stimulation via the one or more electrodes;detecting, via the sensing device, an updated hemodynamic property at the body part after administering the at least one of chemical stimulation or electrical stimulation; and determining hemodynamic effectiveness based on a change between the baseline hemodynamic property and the updated hemodynamic property.

11. The method of claim 10, wherein the baseline hemodynamic property and the updated hemodynamic property include a perfusion index, and wherein the perfusion index reflects peripheral vasomotor tone at the body part.

12. The method of claim 10, further comprising, in response to determining that the change between the baseline hemodynamic property and the updated hemodynamic property reaches a target hemodynamic property, at least one of providing an indication that capture is confirmed or triggering an automated action comprising at least one of initiating subsequent electrical stimulation or initiating subsequent chemical stimulation.

13. The method of claim 10, wherein administering the at least one of chemical stimulation or electrical stimulation is performed for at least one of lead placement capture confirmation, arteriovenous fistula maturation, critical limb ischemia treatment, Buerger's disease, Raynaud's disease treatment, spinal cord ischemia treatment, increase in blood vessel diameter, migraines, wound healing, or treatment of wound dehiscence.

14. The method of claim 10, further comprising adjusting at least one of a dosage, a timing, a frequency, an amplitude, a type, a pulse width, a polarity, or a rate of the at least oneAttorney Docket No.: 00333-0003-00304of chemical stimulation or electrical stimulation based on the determined hemodynamic effectiveness to reach at least one of a target oxygen level, a target perfusion index, a target NIRS value, a target temperature, or a target blood flow.

15. A closed-loop treatment system comprising:a lead assembly comprising a lead body having one or more electrodes configured to deliver electrical stimulation and one or more exit ports configured to deliver a chemical stimulation;a drug pump in fluid communication with the one or more exit ports;a pulse generator in electrical communication with the one or more electrodes;a sensing device configured to detect at least one of oxygen levels, an NIRS value, a perfusion index, blood flow, or temperature at a treatment site; anda processor configured to determine a treatment value based on measurements detected by the sensing device and to adjust the treatment value based on updated measurements detected by the sensing device to cause the at least one of the chemical stimulation or the electrical stimulation to reach at least one of a target oxygen level, a target NIRS value, a target perfusion index, a target temperature, or a target blood flow.

16. The closed-loop treatment system of claim 15, wherein the processor is configured to execute a machine learning model trained to output the treatment value based on inputs comprising at least one of the measurements detected by the sensing device, an area of treatment, patient biometric values, patient demographics, or target values.

17. The closed-loop treatment system of claim 15, wherein the treatment value comprises at least one of a dosage, a timing, a frequency, an amplitude, a pulse width, a type, a polarity or a rate related to at least one of the chemical stimulation delivered via the drug pump or the electrical stimulation delivered via the pulse generator, and wherein the treatment value is adjusted to cause the at least one of the chemical stimulation or the electrical stimulation to reach at least one of the target oxygen level, the target NIRS value, the target perfusion index, the target temperature, or the target blood flow.

18. The closed-loop treatment system of claim 15, wherein the processor is configured to output the treatment value such that stimulation is adjusted to prevent paresthesia by at least one of capping or reducing stimulation intensity, duration, or frequency levels.Attorney Docket No.: 00333-0003-0030419. The closed-loop treatment system of claim 15, wherein the sensing device comprises a pulse oximeter sensor configured to determine the perfusion index based on a ratio of pulsatile blood flow to non-pulsatile blood flow.

20. The closed-loop treatment system of claim 15, wherein the lead body comprises at least one of a bioresorbable polymer or a biodegradable metal.

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