Apparatus and method for setting electrical dose

Abstract

Methods and apparatus (e.g., devices, systems, etc.) for applying a therapeutic dose of electrical energy from a nerve sheath to a nerve to modulate neurological function, including mitigating pain, may include using a normalized therapeutic dose value (or range of values) indicative of a target therapeutic charge dose to be applied. The devices and methods may determine a parameter of the applied energy using an impedance value of the nerve at the nerve sheath and a cross-sectional area of a region of the nerve at least partially surrounded by the nerve sheath in combination with a target normalized therapeutic dose value (s). In particular, the parameter may be a parameter required to achieve high frequency nerve block at a target normalized therapeutic dose value (s).

Description

[0001] Claim for Priority

[0002] This patent application claims priority to U.S. Provisional Patent Application No. 63 / 417,646, filed on October 19, 2022, with the title "APPARATUSES AND METHODS FOR SETTING AN ELECTRICAL DOSE".

[0003] Incorporation by Reference

[0004] All publications and patent applications mentioned in this specification are hereby incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. Background Art

[0005] In many cases, implantable nerve modulators (e.g., implantable nerve stimulators, implantable nerve block devices) are increasingly used to treat pain and other indications by directly applying electrical energy to one or more nerves, including nerve bundles. This electrical modulation can be used to excite or inhibit the nerves, or both. In addition to treating pain, electrical modulation can be applied to nerves to treat unwanted and / or uncoordinated nerve impulse generation, which otherwise may be a disabling factor in some medical conditions. The implantable nerve modulator can be implanted on, around, or adjacent to one or more nerves of a patient to deliver electrical energy.

[0006] Electrical modulation for treating patients is typically sensitive to the amount, duration, and intensity of the applied energy. For example, a non-limiting type of electrotherapy is the application of high-frequency alternating current (HFAC) to a nerve that has been shown to block nerve activity, e.g., in the treatment of pain. An appropriate dose (e.g., the amount of electrical energy applied to a patient for effective treatment) can be understood as the amount that causes a desired effect, such as inhibiting nerve activity to relieve pain. An inappropriate dose may result in ineffectiveness or may stimulate the nerve. Unfortunately, determining an appropriate dose is generally very difficult, especially in the treatment of pain, which can be somewhat subjective and vary greatly among individuals. Typically, determining the appropriate dose for a patient is a time-consuming and complex process that requires experiential information reported by the patient. Thus, the optimal dose for treating a patient can vary widely among patients and even within the same patient over time. Accordingly, it would be beneficial to provide a method and / or device for simplifying and reliably setting a patient's dose. Methods and devices that can address these needs are described herein. Summary of the Invention

[0007] The invention described herein relates to the field of implantable neuromodulators and, in particular, to the field of high-frequency nerve blocks. These methods and devices can provide patient-specific customized pulse profiles to enhance the change in the significant therapeutic effects that the applied therapy will bring. These methods and devices provide for the first time a technique that can solve and prevent patients from being insensitive to neuromodulation for pain block, including (but not limited to) phantom limb pain. Generally speaking, these devices (e.g., systems, equipment, etc., including software, firmware, and / or hardware) and methods are configured to determine the pulse profile of the high-frequency (e.g., nerve block) signal to be applied to the nerve based on a normalized therapeutic dose value (or a specific preset value, or a range of values). For example, the pulse profile of the high-frequency signal can be estimated by the method or device using the target normalized therapeutic dose value, an estimate of the cross-sectional area of the region of the nerve under the nerve cuff, and the impedance of the tissue (e.g., nerve) in contact with the nerve cuff.

[0008] Generally speaking, the normalized therapeutic dose value is the charge density value that can be delivered, for example, equivalent to the charge density delivered by a biphasic waveform (with an associated pulse width and amplitude), where the charge density is equal to the current (e.g., in Coulombs / second or μC / second) multiplied by the pulse width (in seconds / phase) and then divided by the cross-sectional area of the region of the nerve under the nerve cuff. Thus, the charge per phase can be normalized to the dose delivered to the nerve that blocks the pain signal from being conducted to the central nervous system and the brain ("normalized dose"). For example, the normalized dose value can be between approximately 0.1 and 5 μC / phase / cm 2 (e.g., between approximately 0.2 and 5 μC / phase / cm 2 between, between approximately 0.2 and 3.5 μC / phase / cm 2 between, between approximately 0.3 and 5 μC / phase / cm 2 between, between approximately 0.4 and 5 μC / phase / cm 2 between, between approximately 0.5 and 5 μC / phase / cm 2 between, between approximately 0.1 and 4.5 μC / phase / cm 2 between, between approximately 0.1 and 4 μC / phase / cm 2 between, between approximately 0.1 and 3.5 μC / phase / cm 2 between, between approximately 0.1 and 3 μC / phase / cm 2 between, between approximately 0.1 and 2.5 μC / phase / cm 2 between, between approximately 0.1 and 2 μC / phase / cm 2 between, etc.).

[0009] For example, this document describes a system for applying high-frequency nerve block, the system including: a nerve cuff including one or more electrodes, wherein the nerve cuff is configured to at least partially surround a region of a nerve; a pulse generator configured to generate a high-frequency signal having a pulse profile; a controller configured to determine the pulse profile based on a normalized therapeutic dose value, a cross-sectional area of the region of the nerve at least partially surrounded by the nerve cuff, and an impedance measured from the one or more electrodes, wherein the controller is configured to drive the pulse generator to deliver the high-frequency signal having the pulse profile from the one or more electrodes.

[0010] Any one of these devices (e.g., systems, apparatuses, etc.) can include an input for determining or receiving the cross-sectional area of the region of the nerve under the nerve cuff (e.g., transverse to the nerve long axis). The controller can be configured to receive data from the input. The cross-sectional area can be entered once (e.g., at the time of implantation or shortly after implantation) or multiple times, e.g., after healing has occurred, after implantation and / or periodically thereafter (e.g., weekly, monthly, every 3 months, every 6 months, annually, etc.).

[0011] Any one of these systems can include a memory accessible by the controller, the memory being configured to store the normalized therapeutic dose value and / or the cross-sectional area of the region of the nerve at least partially surrounded by the nerve cuff. The pulse generator can be configured to generate a high-frequency signal having a frequency of 1 kHz or greater. The pulse generator can be configured to generate a high-frequency signal having a frequency between 1 kHz and 100 kHz.

[0012] In any of these devices, at least a portion of the device (e.g., an implantable controller, a pulse generator, a memory, etc.) can be enclosed within a housing to be inserted into the body. For example, the device can include a housing enclosing a controller, a memory, and a pulse generator. Thus, the controller can be configured to be implantable. As described in more detail herein, in some examples, a second controller (an external controller) can also be included, which can communicate with the pulse generator and the internal controller. In some examples, the controller enclosed within the housing can perform the calculation of the pulse profile internally. Alternatively, in some examples, the controller that determines the pulse profile can be external (e.g., an external controller), which communicates with the pulse generator and / or the internal controller, e.g., wirelessly (e.g., using Wi-Fi, Bluetooth, etc. of a wireless subsystem). Thus, in any of these systems, the controller can be external and can communicate wirelessly with an implant controller coupled to the pulse generator. In some examples, the (one or more) controllers can distribute functions between the internal controller and the external controller. In some examples, the internal controller determines the pulse profile and only sends the pulse profile and / or impedance measurements, etc. to the external controller, memory, etc. for storage, transmission, and / or future analysis.

[0013] The device can receive and / or determine the cross-sectional area. For example, in any of these devices, the controller can be configured to calculate the cross-sectional area based on an indicator of the cross-sectional area received by the controller. The indicator of the cross-sectional area can include measurements of one or more of diameter, perimeter, etc. The indicator can be provided by a medical professional (e.g., a doctor, a surgeon, a nurse, a technician, etc.) based on measurements taken during implantation (e.g., using a vascular loop). Thus, any of these devices (e.g., systems) can include one or more input terminals configured to receive an indicator of the cross-sectional area of a region of a nerve at least partially surrounded by a nerve cuff.

[0014] Alternatively or additionally, an indicator of the cross-sectional area can be automatically determined by the device, e.g., based on the condition of the nerve cuff. For example, the nerve cuff can include sensors to directly detect the indicator (e.g., measure the distance between opposite sides of the nerve cuff and thus approximate the diameter, estimate or measure the constricted size of the channel when the nerve cuff is applied to the nerve, and thus estimate its perimeter, etc.). The device can include a module (which can be part of an internal and / or external controller) for determining, based on the indicator, the cross-sectional area of the region of the nerve that is at least partially surrounded by the nerve cuff. The indicator and / or the cross-sectional area of the region of the nerve can be stored in a memory accessible by the controller or can be part of the controller. The memory can store the value of the indicator and / or the cross-sectional area of the region of the nerve in a non-volatile manner, so that the value is retained even if power is lost. The device can back up the value of the cross-sectional area of the region of the nerve and / or the indicator, including backing it up to a remote (e.g., cloud) site.

[0015] The same or a different memory accessible by the controller can store the normalized treatment dose value. As mentioned above, the normalized treatment dose value can be a range of values (e.g., between about 0.1 and 5 μC / phase / cm2) or a specific value within this range, e.g., 2 μC / phase / cm2.

[0016] These devices and methods can be configured such that the patient can trigger the delivery of the high-frequency signal and / or set the duration, and / or stop (e.g., immediately stop) the delivery of the high-frequency signal. In some examples, the devices and methods can be configured to enable the user to select between one or more different dose values (e.g., select between multiple different discrete or continuously varying normalized treatment dose values). In some examples, the device can include an external controller that is configured to signal the controller to deliver the high-frequency signal. The external controller can include one or more controls (buttons, dials, touchscreen inputs, etc.) that can select on / off (e.g., delivery dose, off dose), and optimally can select inputs (e.g., "high", "medium", "low", etc.) that can be associated by the controller with the normalized treatment dose. Optionally, the user can select the dose duration (e.g., 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, etc.) and / or can schedule the delivery of the dose (based on a calendar and / or time of day). The external controller can be a dedicated device that communicates wirelessly with the implant and / or can include software and / or firmware that can run on a general-purpose device (e.g., a phone, a tablet, etc.).

[0017] As mentioned above, generally, a controller (internal and / or external controller) can calculate a pulse profile. The pulse profile can refer to one or more characteristics of a high-frequency waveform emitted by a pulse generator and delivered by electrodes of a nerve cuff. The pulse profile can include one or more of the following: pulse width, pulse amplitude, pulse frequency (within a specified high-frequency range), and pulse burst duration (e.g., treatment time). Any one of these parameters can be fixed or set by the controller, while one or more of the other parameters can be changed / calculated. For example, in some examples, the pulse amplitude can be fixed. In some examples, the pulse amplitude can vary. In some examples, the (one or more) controller can calculate the pulse width.

[0018] In some examples, the devices described herein include an implant subsystem that includes a housing enclosing a pulse generator, a controller, a battery, etc., and a nerve cuff. The nerve cuff can be directly coupled to the housing (or more specifically, to electronics within the housing), or the nerve cuff can be coupled to the housing / electronics via an elongate flexible lead (e.g., a lead coupling the pulse generator to the nerve cuff).

[0019] Any one of these devices can include an impedance sensing subsystem configured to determine the impedance measured from one or more electrodes. For example, the device can include impedance sensing circuitry as part of an internal (e.g., implantable) controller, the impedance sensing circuitry being configured to detect the impedance at one or more electrodes of the nerve cuff. The detected impedance (Z) can approximate real impedance and / or complex impedance.

[0020] For example, systems for applying high-frequency nerve blocks are described herein that include: an implantable nerve cuff including one or more electrodes, wherein the nerve cuff is configured to at least partially surround a region of a nerve; a pulse generator configured to generate a high-frequency signal having a pulse profile; a memory storing a normalized treatment dose value and an indication of the cross-sectional area of the region of the nerve at least partially surrounded by the nerve cuff; and a controller configured to determine the pulse profile based on the normalized treatment dose value, the cross-sectional area of the region of the nerve at least partially surrounded by the nerve cuff, and the impedance measured from one or more electrodes, wherein the controller is configured to drive the pulse generator to deliver the high-frequency signal having the pulse profile from the one or more electrodes.

[0021] The present disclosure also describes methods of using normalized treatment dose settings and / or adjusting the dose of electrical energy to treat a patient. These methods can be used to set an initial pulse profile (e.g., parameters of the applied pulsatile energy, particularly including high-frequency pulsatile energy for nerve block). These methods and devices can also be used to adjust the pulse profile. For example, the present disclosure describes a method of applying high-frequency nerve block to treat pain, the method including: determining an index of the cross-sectional area of a region of a nerve at least partially surrounded by a nerve cuff having one or more electrodes; estimating an impedance value from one or more of the electrodes; in a controller, determining a pulse profile based on a normalized treatment dose value, the cross-sectional area of the region of the nerve at least partially surrounded by the nerve cuff, and the impedance value; and applying a high-frequency signal having the pulse profile to the nerve.

[0022] Any of these methods can include applying the nerve cuff at least partially around the nerve (or in some cases, applying the nerve cuff to surround the nerve). The nerve cuff can be implanted using a wired or wire-free configuration together with a pulse generator, an internal (e.g., implantable) controller, a power source, and the like.

[0023] In any of these methods, the high-frequency signal can have a frequency of about 1 kHz or greater. For example, the high-frequency signal can have a frequency between 1 kHz and 100 kHz. The frequency can be set (e.g., predetermined) or adjustable.

[0024] As mentioned above, the normalized treatment dose value can be selected from a range of values or pre-determined. For example, the normalized treatment dose value can be between about 0.1 and 5 μC / phase / cm 2 . In some examples, the normalized treatment dose value is between about 0.5 and 4 μC / phase / cm 2 . The minimum value of the normalized treatment dose value can be about 0.1 μC / phase / cm 2 or greater, about 0.2 μC / phase / cm 2 or greater, about 0.3 μC / phase / cm 2 or greater, about 0.4 μC / phase / cm 2 or greater, about 0.5 μC / phase / cm 2 or greater, about 0.6 μC / phase / cm 2 or greater, and so on. The maximum value of the normalized treatment dose value can be about 1.4 μC / phase / cm 2 or less, about 1.5 μC / phase / cm 2 or less, about 1.6 μC / phase / cm 2 or less, about 1.7 μC / phase / cm 2 or less, about 1.8 μC / phase / cm2 or less, approximately 1.9 μC / phase / cm 2 or less, approximately 2.0 μC / phase / cm 2 or less, approximately 2.1 μC / phase / cm 2 or less, approximately 2.2 μC / phase / cm 2 or less, approximately 2.3 μC / phase / cm 2 or less, approximately 2.5 μC / phase / cm 2 or less, approximately 3 μC / phase / cm 2 or less, approximately 3.5 μC / phase / cm 2 or less, approximately 4 μC / phase / cm 2 or less, approximately 4.5 μC / phase / cm2 or less, approximately 5 μC / phase / cm 2 or less, approximately 5.1 μC / phase / cm 2 or less, approximately 5.5 μC / phase / cm 2 or less, and so on.

[0025] Any of these methods can include estimating the cross-sectional area of a nerve at least partially surrounded by a nerve cuff based on an indicator of the cross-sectional area of the region of the nerve surrounded or partially surrounded by the nerve cuff. In some examples, the method can include obtaining (e.g., measuring) an indicator of the cross-sectional area of the region of the nerve surrounded or partially surrounded by the nerve cuff (e.g., nerve diameter, nerve perimeter, etc.). Thus, in any of these methods, determining an indicator of the cross-sectional area of the region of the nerve can include measuring the perimeter or diameter of the region of the nerve that is at least partially surrounded or will be at least partially surrounded by the nerve cuff. The indicator can be measured directly and / or determined indirectly. Any of these methods can include storing either or both of the cross-sectional area of the region of the nerve surrounded or partially surrounded by the nerve cuff or an indicator of the cross-sectional area of the region of the nerve surrounded or partially surrounded by the nerve cuff. This value can be stored in a memory accessible by a controller. The value of the cross-sectional area of the region of the nerve surrounded or partially surrounded by the nerve cuff and / or the indicator of the cross-sectional area of the region of the nerve surrounded or partially surrounded by the nerve cuff can be set once at the time of surgical implantation of the nerve cuff or can be updated periodically (e.g., particularly when it is automatically determined, as described above).

[0026] Any of these methods can include receiving a signal from a user to apply a high-frequency signal having a pulse profile to the nerve and / or selecting between various possible applied signals (e.g., "high", "medium", "low", etc.) within a normalized therapeutic dose value range. The user can control the on / off of the applied signal (as needed) and / or can schedule the application of the therapy (e.g., once or multiple times per day).

[0027] Any one of these methods can include determining a pulse profile by determining one or more of the following: pulse width, pulse amplitude, pulse frequency, and pulse train duration. Applying a high-frequency signal can include applying the high-frequency signal for a treatment duration. Any suitable treatment duration can be used (e.g., a treatment duration of 10 minutes or longer, 15 minutes or longer, 20 minutes or longer, 25 minutes or longer, 30 minutes or longer, 35 minutes or longer, etc.). The normalized treatment dose value can be estimated based on a standard treatment duration (e.g., 30 minutes), and / or can be adjusted based on the treatment duration.

[0028] For example, a method of applying high-frequency nerve block to treat pain, the method comprising: applying a nerve cuff that includes one or more electrodes at least partially surrounding a patient's nerve; determining an indicator of the cross-sectional area of the region of the patient's nerve at least partially surrounded by the nerve cuff; estimating an impedance value from one or more of the electrodes; in a controller, based on a normalized treatment dose value between 0.1 and 5 μC / phase / cm 2 and the cross-sectional area of the region of the patient's nerve at least partially surrounded by the nerve cuff and the impedance value, determining a pulse profile; and applying a high-frequency signal having the pulse profile to the patient's nerve.

[0029] A method (including but not limited to a method of applying high-frequency nerve block to treat pain) can include: determining or receiving in a controller of a nerve stimulator coupled to a nerve cuff an indicator of the cross-sectional area of the region of the patient's nerve at least partially surrounded by the nerve cuff, the nerve cuff including one or more electrodes at least partially surrounding the patient's nerve; determining an impedance value from one or more of the electrodes; in the controller, based on a normalized treatment dose value between 0.1 and 5 μC / phase / cm 2 and the cross-sectional area of the region of the patient's nerve at least partially surrounded by the nerve cuff and the impedance value, determining a pulse profile; and applying a high-frequency signal having the pulse profile to the patient's nerve.

[0030] All methods and devices described herein in any combination are contemplated herein and can be used to achieve the benefits described herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] A better understanding of the features and advantages of the methods and devices described herein will be obtained by reference to the following detailed description and the drawings that illustrate illustrative embodiments, in which:

[0032] Figure 1Shows the percentage of patient courses in which pain was immediately reduced by at least 30% after 30 minutes of treatment with a single nerve cuff for all subjects in a clinical trial (QUEST RCT treated subjects, n = 85) according to the normalized dose (in μC / phase / cm 2 as the unit). Includes "absolute" non-responders (e.g., when the dose equivalent range >= 2, the course is 0%), but these patients may show false positives in lidocaine screening.

[0033] Figure 2 Is a graph showing the percentage of patient courses in which pain was reduced by at least 50% after 120 minutes of treatment with a single nerve cuff for treated subjects (n = 85) according to the normalized dose (in μC / phase / cm 2 as the unit).

[0034] Figure 3A Shows an example of a neuromodulation system (shows a nerve cuff, a lead, and an implantable controller / waveform generator that may include a dose setting controller).

[0035] Figure 3B Shows an example of the Figure 3A system implanted in a patient, and also shows a dose setting controller that can communicate with the implant. In this example, an optional external controller. The optional external controller (also referred to herein as a patient controller or user controller) may include a dose selector that drives the application of energy to the implant or communicates with the dose selector.

[0036] Figure 3C Is a schematic diagram of a system for treating a patient's pain using high-frequency nerve block, the system including a dose setting controller as described herein.

[0037] Figure 4 Schematically illustrates an example of a system for treating a patient's pain, the system including a normalized dose setting.

[0038] Figure 5 Is a flowchart illustrating an example of a method for treating a patient's pain by delivering neuromodulation from an implant using a normalized dose as described herein. Detailed Description

[0039] Methods and devices (e.g., apparatuses, systems, etc.) for applying a therapeutic dose of electrical energy from a nerve cuff to a nerve to modulate nerve function (including pain relief) can include using a normalized therapeutic dose value (or range of values) indicative of the target therapeutic charge dose to be applied. These devices and methods can use the impedance value of the nerve at the nerve cuff and the cross-sectional area of the region of the nerve that is at least partially surrounded by the nerve cuff, in combination with the (one or more) target normalized therapeutic dose values, to determine the parameters for the energy to be applied. In particular, the parameters can be those required to achieve high-frequency nerve block at the (one or more) target normalized therapeutic dose values.

[0040] For example, any of the methods and devices described herein can include implanting a nerve cuff electrode into a patient in direct electrical contact with a nerve. The nerve cuff electrode can partially or completely surround the nerve. The nerve cuff electrode can be connected to a pulse generator (PG) configured to generate a bidirectional waveform, the amplitude of which is controlled by voltage or by current. The pulse generator can be configured to send and receive data to and from a processor (e.g., a computer) via a communication software protocol. In any of these devices, the pulse generator can be configured to receive the impedance (Z) measured at the nerve cuff electrode / nerve interface, and the pulse generator can be configured to send an increase or decrease in voltage or current to the nerve cuff electrode / nerve interface. Any of these devices can be configured to determine and / or store the nerve cross-sectional area of the region of the nerve surrounded (or at least partially surrounded) by the nerve cuff. Generally, these devices can be configured to, in response to the measured impedance (Z), change the charge density delivered by the bidirectional waveform (and its associated pulse width) according to the following equation:

[0041]

[0042] The charge per phase can be normalized to the dose delivered to the nerve that blocks the conduction of pain signals to the central nervous system and the brain (“normalized dose”). As shown in Equation (1), the unit of the normalized dose can be C / (phase*cm2), or more likely microC / (phase*cm2), e.g., μC / phase / cm2.

[0043] As described in detail herein, in a manner similar to drug dosing, by normalizing the dose to the cross-sectional area of the region of the nerve surrounded by the nerve cuff, the response can be more predictable and graded. This can provide numerous benefits to patients and caregivers, including the ability to more precisely treat a variety of different patients and prevent indications, reduce side effects, and prevent or limit desensitization.

[0044] Surprisingly, the methods and apparatuses described herein can also provide electrical therapy in a manner similar to how pharmaceutical pain relievers alleviate pain, where increasing the dose (e.g., below the threshold of intolerable side effects) also increases the degree of pain relief experienced by the patient. Generally, the methods and apparatuses described herein provide therapy where a charge density can be set for an initial dose and the charge density can be increased or decreased in a controlled manner to modulate pain relief. Pain relief can be measured by patient-reported outcomes (PROs).

[0045] For example, Figure 1 FIG. illustrates the results of a recent trial using a nerve cuff device similar to that described herein. In this trial (“QUEST”), lower limb amputee patients suffering from chronic and severe stump pain or phantom limb pain were recruited, who had significant pain relief after a local nerve block injection (e.g., lidocaine injection). A single cuff electrode was wrapped around the sciatic nerve, or two cuffs (one each) were wrapped around the tibial nerve and the common peroneal nerve, e.g., above or below the knee. During each subject-initiated therapy session, a sinusoidal waveform of 5 kHz or 10 kHz was applied using an implantable generator, and up to 16 V or 20 mA was applied at 30-minute intervals. A diary was used to record the pain intensity before and after each session.

[0046] The dose in the QUEST trial was initially calibrated as per the prior art recommendations. For example, see PCT / US2019 / 047281, titled “APPARATUSES AND METHODS FOR ADJUSTING A THERAPEUTIC ELECTRICAL DOSE” (filed on Aug. 20, 2019), and the corresponding U.S. patent application No. 17 / 265,532. The initial calibration used patient feedback during an initial calibration period, thus requiring a technician to set the initial dose level and patient participation. In addition to other patient-specific data (including anatomy, age, and other relevant parameters), the selected and applied voltage and impedance were also determined. The results of the QUEST trial were analyzed as described herein. It became apparent that the pain relief effectiveness for different patients could be titrated based on the normalized dose only by analyzing the results of multiple patient groups (both responders and non-responders) at different apparent effectiveness levels (e.g., different percentages of pain relief at different time points), and only after adjusting the applied energy to a normalized dose that takes into account the nerve area at least partially encircled by the nerve cuff, as described herein.

[0047] For example, eighty-five (85) subjects in the QUEST trial were analyzed according to their charge density or “dose” based on the percentage of at least 30% pain relief after 30 minutes of current delivery in the PRO sessions of the eighty-five (85) subjects.Figure 1 Shows a positive linear correlation or “dose - response effect” for two different groups of subjects, where the electrical doses for the two groups of subjects are larger (between ∼0.75 and 1 and between ∼1.5 and 2). Two example (dashed) lines of linear regression for approximately responsive patients are shown in the figure. Subjects within the above - mentioned range achieve a 30% pain reduction immediately after a 30 - minute session in 70% or more of their sessions.

[0048] Figure 2 The data shown further confirm the drug “dose - response effect” of electricity delivered to the nerves. In this example, Figure 1 the outcome data reported by patients are represented as the percentage of sessions with at least a 50% pain reduction 120 minutes after an initial 30 - minute session. That is, these subjects received a single 30 - minute electrotherapy session, and then their pain was recorded immediately after the session ( Figure 1 ), and the pain was recorded again 120 minutes later ( Figure 2 ), thus showing the persistence of the effect.

[0049] Generally speaking, in a single session (e.g., 30 minutes), an electrical dose can provide at least a 30% immediate and moderately important pain reduction within the above - mentioned dose range ( Figure 1 ). Within the same dose range at 120 minutes ( Figure 2 ), the pain reduction improvement is now significant (at least 50%). The moderately important and significant improvements in pain reduction are highly clinically significant. A 10 - 20% reduction in pain intensity is considered a “minimally important” reduction in pain intensity, a ≥30% reduction corresponds to a “moderately important” improvement in pain intensity as perceived by the patient, and for people with acute and chronic pain, a reduction of approximately 50% or more can be considered a “significant” improvement in pain intensity. The percentage of pain reduction is generally considered a useful method for determining whether a patient has a meaningful improvement. The preliminary results also indicate that these dose - dependent reductions in pain intensity do not result in significant adverse effects such as disturbances in sleep, mood, and function, and thus are of great benefit to patients.

[0050] The data obtained and the invention of the electrical dose for pain conduction block can be used to create a baseline for the starting dose for a given patient. As mentioned above, it is currently usually required that a trained technician test the patient with the necessary calibration process devices shortly after or during the implantation process in order to set and adjust the treatment baseline. For example, the patient must gradually increase the voltage from 0 volts during a question - and - answer discussion with an experienced programmer, and the programmer slowly increases the voltage to the threshold that the patient can tolerate for 30 minutes. This time - consuming and labor - intensive invasive method is crucial for setting the initial treatment intensity and can be used to program the treatment.

[0051] In contrast, the methods and devices described herein can alternatively use the measurement of the cross-sectional diameter of the region of a nerve (e.g., sciatic nerve, tibial nerve, etc.) enclosed by a nerve cuff and the impedance of the nerve / cuff tissue interface to determine the treatment dose to control and set the treatment dose, and can set the treatment dose within a target range (e.g., between approximately 0.1 and 5 μC / phase / cm 2 between, between 0.2 and 5 μC / phase / cm 2 between, between 0.2 and 3.5 μC / phase / cm 2 between, between approximately 0.3 and 5 μC / phase / cm 2 between, between approximately 0.4 and 5 μC / phase / cm 2 between, etc., between approximately 0.5 and 5 μC / phase / cm 2 between, between approximately 0.1 and 4.5 μC / phase / cm 2 between, between approximately 0.1 and 4 μC / phase / cm 2 between, between approximately 0.1 and 3.5 μC / phase / cm 2 between, between approximately 0.1 and 3 μC / phase / cm 2 between, between approximately 0.1 and 2.5 μC / phase / cm 2 between, between approximately 0.1 and 2 μC / phase / cm 2 between, etc.). Thus, for a given patient with a cross-sectional area of a nerve portion enclosed by a nerve cuff, while monitoring the impedance of the nerve cuff (electrode) at the tissue (e.g., at the nerve), the dose can be set within the therapeutic dose by setting pulse parameters (e.g., pulse width, amplitude, etc.).

[0052] After knowing the nerve diameter of the patient and the nerve cuff / nerve impedance, a range of normalized doses can be set (e.g., using data such as the data shown in Figure 1 and Figure 2 ). This will allow the programmer to optimally position the voltage (and thus related to the electrical dose) within a narrow range known to produce moderate to significant pain relief improvement.

[0053] Thus, the devices and methods using therapeutic doses as described herein can provide a range of energies applied specific to a particular patient (based on the relationship between the impedance and cross-sectional area of the nerve at the nerve cuff) to provide effective treatment. The initial treatment parameters (e.g., the energy applied) can be set within the range of normalized therapeutic dose values.

[0054] Although Figure 1 and Figure 2The data in [study] are specific to patients with a single nerve cuff applied, but similar results have also been observed in patients using two nerve cuffs (e.g., applied simultaneously to the tibial nerve and the common peroneal nerve). Thus, the methods and devices described herein can be used for two (or more) nerve cuffs applied to the same patient. In some examples, the effects of the two nerve cuffs (including cross-sectional area) can be used in combination with the impedance of each nerve surrounded (or partially surrounded) by each nerve cuff along with the same (or in some examples, scaled or distributed) normalized treatment dose. For example, using the impedance and cross-sectional area of the region of a nerve that is at least partially surrounded by a nerve cuff, the same normalized treatment dose value can be used to determine the pulse profile applied to each nerve cuff. Alternatively, the normalized treatment dose can be distributed between the nerve cuffs based on, for example, the ratio of the cross-sectional area and / or impedance values of each nerve at each nerve cuff.

[0055] Device

[0056] The devices described herein generally include a controller that can determine the parameters of the energy applied (e.g., pulse profile) such that the applied energy is within a predetermined range (and / or reaches a specific value) of the normalized treatment dose value, and a nerve cuff that at least partially surrounds the nerve to which the energy is applied. For example, the device can generally include a nerve cuff having one or more electrodes (e.g., an array of electrodes), an implantable pulse generator configured to generate a high-frequency signal having a pulse profile, and a controller configured to determine the pulse profile based on the normalized treatment dose value (e.g., charge delivered). Thus, the controller can be configured to determine the pulse profile based on the normalized treatment dose value, the cross-sectional area of the region of the nerve that is at least partially surrounded by the nerve cuff, and the impedance measured from one or more electrodes, wherein the controller is configured to drive the pulse generator to deliver a high-frequency signal having the pulse profile from the one or more electrodes.

[0057] These devices (e.g., systems, devices, and software, including neuromodulators and neuromodulation systems) can be configured to treat a patient's pain and can include one or more subsystems or modules that can be hardware, software, and / or firmware for determining the energy applied for treatment (e.g., pulse profile) such that the delivered energy is within a target normalized treatment dose value range (and / or at a normalized treatment dose value).

[0058] These methods and devices can be used with any suitable neuromodulator. Figure 3AIllustrated is an example of an implantable neuromodulator that includes a nerve cuff 101 and leads 103 that couple the nerve cuff to a controller (e.g., waveform generator, control circuitry, power supply, communication circuitry, and / or antenna, etc.) within an implantable housing 105. For example, a system including a nerve cuff (such as the nerve cuff described herein) can be used to apply high-frequency nerve blocks to acutely treat a person's pain, whether acute or chronic (lasting more than 6 months), by blocking nerve conduction on action potentials. Acute treatment can refer to on-demand treatment that provides pain relief substantially immediately. The nerve cuff can be applied to medium-diameter and relatively large-diameter nerves, such as but not limited to the sciatic nerve. One therapy involves reversibly blocking peripheral nerves by applying high-frequency alternating current directly on the nerve trunk. Currents in the range of 1 kHz to 100 kHz (e.g., 5 kHz to 50 kHz) can be applied; this can be referred to as high-frequency modulation compared to currents less than 1 kHz applied in conventional electrical modulation. The efficacy of high-frequency alternating current therapy has been reported in acute non-human animal experiments (frogs, cats). U.S. Patent Nos. 7,389,145 and 8,060,208 generally describe such electrical modulation techniques.

[0059] The nerve cuff can encircle a particular section of a target peripheral nerve (e.g., sciatic nerve, tibial nerve, etc.). Using an implanted electrode connected to an electrical waveform generator, an electrical waveform can be applied at certain time intervals, e.g., 10 minutes (15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, etc.), which is sufficient to achieve immediate substantial pain relief for the patient, e.g., within 10 minutes, and extend the pain relief for several hours. The current can be determined as described herein such that the total energy (charge) delivered approximates (one or more) target normalized treatment dose values (including within the range of the normalized treatment dose values).

[0060] The application of 10 kHz alternating current generated by a custom generator via a custom implanted nerve electrode can significantly reduce pain in most treated patients. For example, an implantable electrode operably connected to an external or implanted waveform generator can be used. The electrode can be a helical cuff electrode similar to that described in U.S. Patent No. 4,602,624. The electrode can be implanted on the desired peripheral nerve trunk of a human mammalian near the pain source (e.g., neuroma) such that the cuff encircles the desired peripheral nerve where action potentials will be blocked. The inner diameter of the cuff can be in the range of approximately 4 mm to approximately 13 mm. The sciatic nerve is known to have a relatively large nerve trunk; the diameter of the proximal part of the sciatic nerve can vary between individuals. In one embodiment, the device and method are used on the sciatic nerve to treat limb pain in above-knee amputees. In one embodiment, the device and method are used on the tibial nerve to treat limb pain in below-knee amputees.

[0061] Figure 3B Illustrated is the use of a system that includes a cuff electrode applied to the sciatic nerve of an amputee patient. In this example, amputee 107 has had a nerve cuff 101 implanted around the sciatic nerve (nerve trunk) and is connected via a lead 103 to a controller that includes a pulse generator (also referred to herein as a waveform generator) within an implantable housing 105. For example, this process can be accomplished by first dissecting to expose the nerve during an opening procedure and then wrapping the nerve with a flexible (self-closing) cuff. During this process, the diameter and / or circumference of the nerve within the implanted cuff can be measured directly or indirectly. This value can be sent to the implanted controller and / or an external controller. Once implanted, the controller / waveform generator is placed in a pocket in the anterolateral abdominal wall, and a tunneling electrode cable can be positioned along the midaxillary line (including across the abdomen) to connect the controller / waveform generator to the nerve cuff electrode. The impedance of the nerve cuff can be determined (e.g., by the system) and the incision can be sutured. The incision for implanting the nerve cuff can be greater than about 1.5 inches (e.g., between 1.5 and 3 inches) such that sufficient visualization and access can be achieved. Once implanted and allowed to heal, the implanted nerve modulator can be set as described herein to provide a treatment dose (e.g., an optimized dose) as described herein.

[0062] Figure 3B The system shown also includes an external controller 131 (e.g., a patient controller) that includes one or more processors and can be configured to perform at least a portion of the methods described herein. The controller or a separate device coupled to the controller can include input terminals for user control. The controller can be software (such as an application software) running on a personal device (such as a smart phone, a tablet, etc.) and can include one or more user interfaces to allow a user to control the operation of the implant.

[0063] Figure 3CSchematically illustrates an example of system 300 (e.g., a system for applying high-frequency nerve block). The system includes an implant 251 with a nerve cuff, the nerve cuff including one or more electrodes. The nerve cuff is configured to at least partially surround a region of a nerve. The implant 251 further includes a pulse generator configured to generate a high-frequency signal having a pulse profile, and a controller configured to determine the pulse profile based on a range of normalized treatment dose values. The implant may be configured to communicate wirelessly with an external controller 231, which may include one or more user (e.g., patient, doctor, technician, etc.) controls 241, such as a touch screen, knob, button, etc. The external controller 231 may further include one or more outputs (e.g., LED, display, speaker, etc.). In some examples, the external controller is software running on a smartwatch, phone, tablet, etc. The implant and the external controller may communicate with each other 315 (e.g., via a wireless communication protocol and / or subsystem). Either or both of the implant and the external controller may also or alternatively communicate with a remote server 261, which may also receive inputs and provide outputs to the implant and / or the external controller.

[0064] As mentioned above, an implantable controller and / or an external controller can be used to determine a pulse profile based on the (one or more) normalized treatment dose values. The pulse profile can correspond to the delivered neuromodulation dose and can include various dose parameters for treating pain. Generally, a set of dose parameters can include dose duration (e.g., the time of delivering the dose, which can be the total duration or can be a part of the total duration, and the treatment time), dose frequency (e.g., treatment frequency; in high-frequency nerve block variants, the frequency can be greater than 1 kHz, such as between 1 - 100 kHz), and peak voltage (e.g., peak modulation voltage, such as between 0.1 V and 20 V, e.g., between 5 V and 15 V, etc.). In some variants, the dose parameters can include the treatment rise time to reach the peak modulation voltage and the peak modulation time maintained, during which the voltage remains at the peak modulation voltage (the dose duration can include the rise time and the peak modulation time). The dose parameters can also include the applied waveform parameters, e.g., pulsatile or repetitive (e.g., sine wave, square wave, sawtooth, biphasic, etc.) and the frequency of the applied waveform (e.g., high-frequency component). Other dose parameters can include the initial (e.g., starting) voltage, which can be, for example, zero, or can be an offset (e.g., voltage offset) voltage. In some variants, the treatment dose parameters can include pulse duration (in treatment variants including bursts / pulses), burst duration (in variants including bursts / pulses), pulse shape (e.g., square, triangular, sinusoidal, etc.), biphasic / monophasic (positive and / or negative), carrier frequency (in variants using a carrier frequency), DC offset level (in variants including a DC offset), current level (in variants modulating current), current limit (in variants limiting current), electrode number / position (in variants having more than one pair of electrodes), and so on.

[0065] Generally, the controller (either or both of the internal controller in implant 251 and / or external controller 231) can be configured to determine a pulse profile in order to determine the delivered treatment dose such that the treatment dose (delivered charge) is generally within the range of the normalized treatment dose value (or within the range of the (one or more) normalized treatment dose values).

[0066] Figure 4FIG. is an example of a neuromodulation system 270A configured to set a treatment dose based on a normalized treatment dose value as described above. The modules of the neuromodulation system 270A can include one or more modules (which may be referred to herein as subsystems or engines) and one or more data repositories (e.g., memories). The modules can include hardware, firmware, and / or software and can be part of a controller (e.g., a processor, a memory, circuitry, etc.). The modules (e.g., engines / subsystems) can be implemented as part of a controller having one or more processors, or one or more modules can be implemented as part of the same (or multiple) controllers. Thus, as used herein, a module (engine / subsystem) can include one or more processors or a portion thereof. A portion of one or more processors can include a portion of the hardware that is less than all of the hardware that includes any given one or more processors, such as a subset of registers, a portion of the processor dedicated to one or more threads of a multi-threaded processor, a time slice during which the processor is dedicated in whole or in part to execute a portion of the engine function, and so on. Thus, the first engine and the second engine can have one or more dedicated processors or the first engine and the second engine can share one or more processors with another or other engines. Depending on the implementation specific or other considerations, the engines can be centralized or their functions are distributed. Thus, the engines can include hardware, firmware, or software implemented in a computer-readable medium for execution by a processor. The processor uses the implemented data structures and methods to convert data into new data, such as described with reference to the figures herein.

[0067] The engines described herein or the engines through which the systems and devices described herein can be implemented can be local or cloud-based engines. As used herein, a cloud-based engine is an engine that can use a cloud-based computing system to run applications and / or functions. All or part of the applications and / or functions can be distributed across multiple computing devices and need not be limited to one computing device. In some embodiments, the cloud-based engine can execute functions and / or modules that an end user accesses through a web browser or a container application without locally installing those functions and / or modules on the end user's computing device.

[0068] As used herein, a memory, which may equivalently be referred to as a data repository, is intended to include one or more repositories having any suitable data organization, including tables, comma-separated value (CSV) files, traditional databases (e.g., SQL), or other suitable known or convenient organizational formats. The data repository may be implemented, for example, as software in a physical computer-readable medium implemented on a dedicated machine, in firmware, in hardware, in a combination thereof, or in a suitable known or convenient device or system. A database may be a data repository or part of a data repository. Components associated with the data repository (such as, a database interface) may be considered as "part" of the data repository, part of some other system components, or a combination thereof, but the physical location and other characteristics of the components associated with the data repository are not important for understanding the techniques described herein.

[0069] The data repository may include a data structure. As used herein, a data structure is associated with a particular way of storing and organizing data in a computer such that it can be used efficiently in a given context. Data structures are generally based on the ability of a computer to fetch and store data at arbitrary locations in its memory, which is specified by an address, which is a bit string that can itself be stored in memory and manipulated by a program. Thus, some data structures are based on calculating the address of a data item with arithmetic operations; while other data structures are based on storing the address of a data item within the structure itself. Many data structures use both principles, sometimes combined in a non-trivial way. Implementing a data structure generally requires writing a set of procedures that create and manipulate instances of the structure. The data repositories described herein may be cloud-based data repositories. A cloud-based data repository is a data repository that is compatible with cloud-based computing systems and engines.

[0070] The neuromodulator system 270A may include a computer-readable medium, an implantable neuromodulator 271, and one or more pulse generators 278, and one or more data repositories (e.g., memories) (e.g., the normalized treatment dose value data repository 282) for holding one or more ranges of normalized treatment dose values or values. The same data repository or different data repositories 280 may be used to hold metrics of the cross-sectional area of a nerve at least partially surrounded by a nerve cuff (e.g., nerve perimeter, nerve diameter, etc.) and / or metrics of the cross-sectional area of a nerve at least partially surrounded by a nerve cuff. The system may include an input / output engine 276 for entering metrics of the cross-sectional area of a nerve at least partially surrounded by a nerve cuff and / or the cross-sectional area of a nerve at least partially surrounded by a nerve cuff. The input / output engine may include or may involve wireless communication with a controller. In some examples, the system includes a cross-sectional area estimation engine 274 for estimating the cross-sectional area of a nerve at least partially surrounded by a nerve cuff based on the metrics. In some examples, this cross-sectional area estimation engine may be configured to receive an input from the nerve cuff that indicates the cross-sectional area of a nerve at least partially surrounded by a nerve cuff. The system may also include an impedance sensing engine 277 to determine the form of impedance from the electrode / tissue interface of the nerve cuff.

[0071] The system described herein may also include a pulse profile generation engine 272 configured to determine a pulse profile based on the normalized treatment dose value(s) (range), the cross-sectional area of a nerve at least partially surrounded by a nerve cuff (or, equivalently, the metrics from the cross-sectional area of a nerve at least partially surrounded by a nerve cuff), and the impedance (from the impedance sensing engine). Thus, the pulse profile engine may output to the pulse generator 278 one or more parameters for setting the pulse waveform(s) to drive the pulse generator 278 to deliver a high-frequency signal with the pulse profile from one or more electrodes of the nerve cuff of the implantable neuromodulator 271.

[0072] The implantable neuromodulator may be implanted in a patient (as shown in Figure 3B ), and may communicate with other components of the system. The input / output engine 276 may also allow the patient to adjust the dose, including switching to different ranges of normalized treatment dose values as described above. In some variations, the pulse profile engine is integrated into or is part of the patient controller, or may communicate with an external controller to allow selection of different normalized treatment dose values.

[0073] In practice, a neuromodulation system can set an initial (e.g., starting) dose for a patient based on the (one or more) normalized therapy dose values as described above. Thereafter, in some examples, subsequent doses can be based on this initial dose. Alternatively or additionally, since impedance can change and / or the target normalized therapy dose value can change, subsequent doses can be recalculated. For example, a user can increase or decrease the desired intensity, which can be adjusted by selecting more or fewer charges within the acceptable range of normalized therapy dose values.

[0074] Method

[0075] Figure 5 Illustrated is an example of a method for treating a patient that includes setting a therapy dose using a normalized therapy dose value (or range of normalized therapy dose values) to determine parameters for applying a therapy. Optionally, in some examples, a nerve cuff can be at least partially implanted over a target nerve (e.g., sciatic nerve, tibial nerve, etc.) 501. The nerve cuff can completely or partially encircle a portion of the nerve. Then, an indicator of the cross-sectional area of the nerve encircled (or partially encircled) by the nerve cuff can be estimated, providing the cross-sectional area 503 of the region of the nerve that is at least partially surrounded by the nerve cuff. The cross-sectional area of the region of the nerve that is at least partially surrounded by the nerve cuff can be determined automatically and / or manually. For example, a clinician can measure or approximate the circumference or diameter of the nerve when applying the nerve cuff and can enter this indicator so that the system can calculate the cross-sectional area of the region of the nerve that is at least partially surrounded by the nerve cuff. Alternatively, the clinician can calculate and enter the cross-sectional area of the region of the nerve that is at least partially surrounded by the nerve cuff. In some examples, the device can automatically estimate the cross-sectional area of the region of the nerve that is at least partially surrounded by the nerve cuff.

[0076] In any of these methods, the impedance of one or more electrodes on the tissue can be determined based on one or more electrodes on the nerve cuff 505. In some examples, the impedance is checked as part of the implantation process for applying the nerve cuff to the nerve to ensure good contact with the nerve. Optionally, the impedance can be detected as part of the implant (e.g., part of a neuromodulation system, such as part of an impedance sensing engine).

[0077] The method can include selecting or determining a target normalized treatment dose (or range of doses) 507. For example, the method can include using a predetermined normalized treatment dose or receiving a user-selected normalized treatment dose (e.g., from an external controller). Then, the selected or determined normalized treatment dose can be used to solve for the parameters 509 for applying energy (e.g., charge) to a nerve having a measured cross-sectional area when the impedance is as determined. Some of these parameters (e.g., amplitude, frequency, burst duration, etc.) can be preset, while other parameters (e.g., pulse width) can be solved for to determine what their values should be in order to achieve the target normalized treatment dose within the allowable range of the normalized treatment dose. Any of the stimulation parameters can be varied while the remaining parameters are fixed at their preset values.

[0078] As Figure 5 shown, once the treatment parameters have been determined based on the target normalized treatment dose, impedance, and cross-sectional area of the nerve under the nerve cuff, energy can be applied via the nerve cuff to treat the patient 511. Thereafter, for example, after a sufficient "off" time has elapsed, and / or as the patient decides, in an on-demand system, the process can be repeated, optionally starting from the step of determining impedance 505 or determining the target normalized treatment dose 507, or by the step of solving for one or more of the pulse parameters 509. In some cases, the same pulse parameters can be used according to a timed or repeating schedule (or according to the needs from the patient).

[0079] In any of the methods and devices described herein, the pulse parameters (and the normalized dose) can refer to volume rather than cross-sectional area. For example, the controller can use the volume of the region of the nerve under the electrode rather than the cross-sectional area to determine the pulse profile. For example, the controller can determine the pulse profile based on the normalized treatment dose value, the volume of the region of the nerve at least partially enclosed by the nerve cuff, and the impedance measured from one or more electrodes. The volume can be determined by multiplying the cross-sectional area of the nerve (as described above) by the length of the nerve covered by the nerve cuff, or in some variations, by the length of the nerve within the nerve cuff that is in contact with the electrode. Thus, any of these methods and devices can refer to charge per volume rather than charge per cross-sectional area (e.g., cm 3 rather than cm 2 ).

[0080] It should be recognized that the methods and devices described herein generally refer to the cross-sectional area of the underlying nerve targeted by the electrode, rather than the cross-sectional area of the electrode itself. The cross-sectional area of the electrode used when describing current density (or in some cases charge density), which can refer to the electrochemical properties per unit surface area of the electrode, is not the same as the cross-sectional length (or volume) of the nerve that is at least partially surrounded by the nerve cuff. Thus, the use of the cross-sectional area of the nerve is not equivalent to the use of the cross-sectional area of a more traditional electrode, which is typically used when estimating the charge density of the electrode.

[0081] In any of the devices (or methods of using them) described herein, the device can include one or more input terminals for manually entering the cross-sectional area (or in some examples the volume) of the area of the nerve under the nerve cuff. Alternatively or additionally, the device can also automatically estimate or determine the cross-sectional area (or volume) of the area of the nerve under the nerve cuff, e.g., the cross-sectional area of the area of the nerve that is at least partially surrounded by the nerve cuff.

[0082] The controller described herein can include a memory (e.g., storing the software / program for determining the pulse parameters to be applied and / or controlling the application as described above). The controller can include a pulse generator or can be coupled to a pulse generator; in some examples, in a fully implanted variant, the pulse generator can include the controller and / or both can be collectively referred to as a pulse generator (PG) or an implantable pulse generator (IPG).

[0083] It should be recognized that all combinations of the foregoing concepts and additional concepts discussed in more detail below (so long as such concepts are not mutually inconsistent) are considered part of the inventive subject matter disclosed herein and can be used to achieve the benefits described herein.

[0084] The order of the process parameters and steps described and / or illustrated herein is given only as an example and can vary as desired. For example, although the steps described and / or illustrated herein can be shown or discussed in a particular order, these steps do not necessarily need to be performed in the order shown or discussed. The various example methods described and / or illustrated herein can also omit one or more of the steps described or illustrated herein or include additional steps other than the disclosed steps.

[0085] Any method (including user interfaces) described herein can be implemented as software, hardware, or firmware and can be described as a non-transitory computer-readable storage medium storing a set of instructions executable by a processor (e.g., a computer, a tablet, a smart phone, etc.), which when executed by the processor cause the processor to control the execution of any steps, including but not limited to: displaying, communicating with the user, analyzing, modifying parameters (including timing, frequency, intensity, etc.), determining, alerting, etc. For example, any one of the methods described herein can be at least partially executed by a device including one or more processors, the device having a memory storing a non-transitory computer-readable storage medium, the memory storing a set of instructions for the (one or more) processes of the method.

[0086] Although various embodiments have been described and / or illustrated herein in the context of a fully functional computing system, one or more of these example embodiments may be distributed in various forms as a program product, regardless of the particular type of computer-readable medium used for actual execution of the distribution. The embodiments disclosed herein may also be implemented using software modules that perform specific tasks. These software modules may include scripts, batch files, or other executable files that may be stored on a computer-readable storage medium or in a computing system. In some embodiments, these software modules may configure the computing system to perform one or more of the example embodiments disclosed herein.

[0087] As described herein, the computing devices and systems described and / or illustrated herein generally represent any type or form of computing device or system capable of executing computer-readable instructions (such as the instructions included in the modules described herein). In its most basic configuration, these (one or more) computing devices may each include at least one memory device and at least one physical processor.

[0088] As used herein, the term "memory" or "memory device" generally refers to any type or form of volatile or non-volatile storage device or medium capable of storing data and / or computer-readable instructions. In one example, the memory device may store, load, and / or maintain one or more of the modules described herein. Examples of memory devices include but are not limited to random access memory (RAM), read-only memory (ROM), flash memory, hard disk drive (HDD), solid state drive (SSD), optical disk drive, cache, variations or combinations of one or more of the foregoing, or any other suitable storage memory.

[0089] In addition, as used herein, the term "processor" or "physical processor" generally refers to any type or form of hardware-implemented processing unit capable of interpreting and / or executing computer-readable instructions. In one example, a physical processor may access and / or modify one or more modules stored in the memory device described above. Examples of physical processors include, but are not limited to, microprocessors, microcontrollers, central processing units (CPUs), field-programmable gate arrays (FPGAs) implementing soft-core processors, application-specific integrated circuits (ASICs), portions of one or more of the foregoing, variations or combinations of one or more of the foregoing, or any other suitable physical processor.

[0090] Although the method steps described and / or illustrated herein are shown as separate elements, they may represent parts of a single application. Additionally, in some embodiments, one or more of these steps may correspond to or represent one or more software applications or programs, which, when executed by a computing device, may cause the computing device to perform one or more tasks, such as the method steps.

[0091] In addition, one or more of the devices described herein may transform data, physical devices, and / or representations of physical devices from one form to another. Additionally or alternatively, one or more of the modules described herein may transform a processor, volatile memory, non-volatile memory, and / or any other part of a physical computing device from one form of computing device to another by executing on the computing device, storing data on the computing device, and / or otherwise interacting with the computing device.

[0092] As used herein, the term "computer-readable medium" generally refers to any form of device, carrier, or medium capable of storing or carrying computer-readable instructions. Examples of computer-readable media include, but are not limited to, transmission-type media (such as carrier waves) and non-transitory media (such as magnetic storage media (e.g., hard disk drives, tape drives, and floppy disks), optical storage media (e.g., compact discs (CDs), digital video discs (DVDs), and Blu-ray discs), electronic storage media (e.g., solid-state drives and flash media), and other distribution systems.

[0093] Those of ordinary skill in the art will recognize that any process or method disclosed herein can be modified in a variety of ways. The order of process parameters and steps described and / or illustrated herein is given only as an example and can be varied as required. For example, although the steps illustrated and / or described herein may be shown or discussed in a particular order, these steps do not necessarily need to be performed in the order shown or discussed.

[0094] The various exemplary methods described and / or illustrated herein may also omit one or more of the steps described or illustrated herein, or include additional steps in addition to the disclosed steps. Additionally, the steps of any method disclosed herein may be combined with one or more steps of any other method disclosed herein.

[0095] A processor as described herein may be configured to perform one or more of the steps of any method disclosed herein. Alternatively or in combination, the processor may be configured to combine one or more of the steps of one or more of the methods disclosed herein.

[0096] When a feature or element is referred to herein as being "on" another feature or element, it may be directly on the other feature or element, or intervening features and / or elements may also be present. In contrast, when a feature or element is referred to as being "directly on" another feature or element, no intervening features or elements are present. It will also be understood that when a feature or element is referred to as being "connected", "attached" or "coupled" to another feature or element, it may be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being "directly connected", "directly attached" or "directly coupled" to another feature or element, no intervening features or elements are present. Although described or illustrated with respect to one embodiment, the features and elements so described or illustrated may be applied to other embodiments. Those skilled in the art will also recognize that a structure or feature referred to as being "adjacent" to another feature may have portions that overlap or are beneath the adjacent feature.

[0097] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms "a" and "the" are also intended to include the plural forms, unless the context clearly indicates otherwise. It will be further understood that when used in this specification, the term "comprises" specifies the presence of the stated features, steps, operations, elements, and / or components, but does not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof. As used herein, the term "and /

[0098] or" includes any and all combinations of one or more of the associated listed items and may be abbreviated to " / ".

[0099] For ease of description, spatial relative terms, such as "below", "beneath", "lower", "above", "upper", etc., may be used herein to describe the relationship of one element or feature to another (or multiple) element or feature as shown in the figures. It will be understood that the spatial relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is inverted, an element described as "below" or "beneath" another element or feature will be oriented "above" the other element or feature. Thus, the exemplary term "below" can include both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or other orientations), and the spatial relative descriptors used herein may be interpreted accordingly. Similarly, unless specifically stated otherwise, the terms "upward", "downward", "vertical", "horizontal", etc. are used herein for purposes of explanation only.

[0100] Although the terms "first" and "second" may be used herein to describe various features / elements (including steps), these features / elements should not be limited by these terms unless the context otherwise indicates. These terms may be used to distinguish one feature / element from another. Thus, without departing from the teachings of the present invention, a first feature / element discussed below may be referred to as a second feature / element, and similarly, a second feature / element discussed below may be referred to as a first feature / element.

[0101] In general, any apparatus and method described herein should be understood to be inclusive, but all or subsets of components and / or steps may alternatively be exclusive and may be expressed as "consisting of" or alternatively "consisting essentially of" various components, steps, sub-components or sub-steps.

[0102] As used herein in the specification and claims, including as used in the examples, and unless otherwise expressly specified, all numbers may be read as if prefaced by the word "about" or "approximately", even if the term does not expressly appear. When describing magnitudes and / or positions, the phrase "about" or "approximately" may be used to indicate that the described value and / or position is within a reasonable expectation range of the value and / or position. For example, a numerical value may have a value of + / −0.1% of the stated value (or range of values), a value of + / −1% of the stated value (or range of values), a value of + / −2% of the stated value (or range of values), a value of + / −5% of the stated value (or range of values), a value of + / −10% of the stated value (or range of values), etc. Any numerical value given herein should be understood to include about or approximately that value unless the context otherwise indicates. For example, if the disclosed value is "10", then "about 10" is also disclosed.

[0103] Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It should also be understood that, as would be appreciated by a person skilled in the art, when a value is disclosed as "less than or equal to" that value, "greater than or equal to that value" and the possible ranges between the values are also disclosed. For example, if the value "X" is disclosed, then "less than or equal to X" and "greater than or equal to X" are also disclosed (e.g., where X is a numerical value). It should also be understood that throughout the application, data is provided in several different formats, and that this data represents ranges of endpoints and starting points and any combination of data points. For example, if a particular data point "10" and a particular data point "15" are disclosed, then it should be understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed and between 10 and 15. It should also be understood that each unit between two particular units is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0104] Although the various illustrative embodiments have been described above, various changes among the several variations may be made without departing from the scope of the invention as described in the claims. For example, in alternative embodiments, the order of performing the various method steps described may often be changed, and in other alternative embodiments, one or more method steps may be entirely skipped. Optional features of the various device and system embodiments may be included in some embodiments and not included in other embodiments. Accordingly, the foregoing description has been provided primarily for exemplary purposes and should not be construed as limiting the scope of the invention as set forth in the claims.

[0105] The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived therefrom, such that structural and logical substitutions and changes may be made without departing from the scope of the disclosure. For convenience only, the term "invention" may be used herein, either alone or in combination, to refer to these embodiments of the subject matter of the invention, without intending to voluntarily limit the scope of this application to any single invention or inventive concept in the event that in fact more than one is disclosed. Accordingly, while specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. The disclosure is intended to cover any and all modifications or variations of the various embodiments. After reading the foregoing description, combinations of the above embodiments and other embodiments not specifically described herein will be apparent to those skilled in the art.

Claims

1. A system for applying high-frequency nerve block, the system comprising: A nerve cuff including one or more electrodes, wherein the nerve cuff is configured to at least partially surround a region of a nerve; A pulse generator configured to generate a high-frequency signal having a pulse profile; A controller configured to determine the pulse profile based on a normalized treatment dose value, a cross-sectional area of a region of the nerve at least partially surrounded by the nerve cuff, and an impedance measured from the one or more electrodes, wherein the controller is configured to drive the pulse generator to deliver the high-frequency signal having the pulse profile from the one or more electrodes.

2. The system of claim 1, further comprising a memory accessible by the controller, the memory being configured to store the normalized treatment dose value and / or the cross-sectional area of the region of the nerve at least partially surrounded by the nerve cuff.

3. The system of claim 1, wherein the pulse generator is configured to generate a high-frequency signal having a frequency of 1 kHz or greater.

4. The system of claim 1, wherein the pulse generator is configured to generate a high-frequency signal having a frequency between 1 kHz and 100 kHz.

5. The system of claim 1, further comprising a housing enclosing the controller, the memory, and the pulse generator.

6. The system of claim 1, wherein the controller is implantable.

7. The system of claim 1, wherein the controller is external and wirelessly communicates with an implant controller coupled to the pulse generator.

8. The system of claim 1, wherein the controller is configured to calculate the cross-sectional area based on an indicator of the cross-sectional area received by the controller.

9. The system of claim 1, further comprising an input configured to receive an indicator of the cross-sectional area of the region of the nerve at least partially surrounded by the nerve cuff.

10. The system according to claim 1, wherein the normalized treatment dose value is between 0.1 and 5 μC / phase / cm 2 inclusive.

11. The system of claim 1, further comprising an external controller configured to signal the controller to deliver the high-frequency signal.

12. The system of claim 1, wherein the pulse profile includes one or more of: pulse width, pulse amplitude, pulse frequency, and pulse burst duration.

13. The system of claim 1, further comprising a wire coupling the pulse generator to the nerve cuff.

14. The system of claim 1, further comprising an impedance sensing subsystem configured to determine the impedance measured from the one or more electrodes.

15. A system for applying high-frequency nerve block, the system comprising: An implantable nerve cuff including one or more electrodes, wherein the nerve cuff is configured to at least partially surround a region of a nerve; A pulse generator configured to generate a high-frequency signal having a pulse profile; A memory storing a normalized treatment dose value and an indicator of the cross-sectional area of the region of the nerve at least partially surrounded by the nerve cuff; A controller configured to determine a pulse profile based on a normalized therapeutic dose value, a cross-sectional area of a region of a nerve at least partially surrounded by a nerve cuff, and an impedance measured from the one or more electrodes, wherein the controller is configured to drive a pulse generator to deliver a high-frequency signal having the pulse profile from the one or more electrodes.

16. A method of applying high-frequency nerve block to treat pain, the method comprising: Determining or receiving an indication of a cross-sectional area of a region of a nerve at least partially surrounded by a nerve cuff having one or more electrodes; Determining an impedance value from one or more of the electrodes; In a controller, determining a pulse profile based on a normalized therapeutic dose value, a cross-sectional area of a region of a nerve at least partially surrounded by a nerve cuff, and the impedance value; And Applying a high-frequency signal having the pulse profile to the nerve.

17. The method of claim 16, further comprising applying the nerve cuff at least partially around the nerve.

18. The method of claim 16, wherein the high-frequency signal has a frequency of 1 kHz or higher.

19. The method of claim 16, wherein the high-frequency signal has a frequency between 1 kHz and 100 kHz.

20. The method of claim 16, wherein the normalized therapeutic dose value is between 0.1 and 5 μC / phase / cm2.

21. The method of claim 16, wherein the normalized therapeutic dose value is between 0.5 and 4 μC / phase / cm2.

22. The method of claim 16, further comprising estimating the cross-sectional area of the region based on the indication of the cross-sectional area of the region of the nerve at least partially surrounded by the nerve cuff.

23. The method of claim 16, wherein determining the indication of the cross-sectional area of the region of the nerve comprises measuring a perimeter or diameter of the region of the nerve at least partially surrounded or to be at least partially surrounded by the nerve cuff.

24. The method of claim 16, further comprising receiving a signal from a user to apply the high-frequency signal having the pulse profile to the nerve.

25. The method of claim 16, wherein determining the pulse profile comprises determining one or more of: pulse width, pulse amplitude, pulse frequency, and pulse burst duration.

26. The method of claim 16, wherein applying the high-frequency signal comprises applying the high-frequency signal for a treatment duration greater than 10 minutes.

27. A method of applying high-frequency nerve block to treat pain, the method comprising: In a controller of a nerve stimulator coupled to a nerve cuff, determining or receiving a cross-sectional area of a region of a patient's nerve at least partially surrounded by the nerve cuff, the nerve cuff comprising one or more electrodes at least partially surrounding the patient's nerve; Determining an impedance value from one or more of the electrodes; In the controller, a pulse profile is determined based on a normalized therapeutic dose value between 0.1 and 5 μC / phase / cm, a cross-sectional area of a region of a nerve of a patient that is at least partially surrounded by a nerve cuff, and an impedance value; 2 ​ And Applying a high-frequency signal having the pulse profile to the patient's nerve.

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