Apparatus and method for setting electrical dosage

Abstract

Methods and apparatus (e.g., devices, systems, etc.) for applying a therapeutic dose of electrical energy from a nerve cuff on a nerve to modulate nerve function, including reducing pain, may include using a normalized therapeutic dose value (or range of values) that indicates a target therapeutic charge dose to be applied. These apparatus and methods may use the impedance value of the nerve at the nerve cuff and the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff, along with the target normalized therapeutic dose value, to determine parameters of the applied energy. In particular, the parameters may be parameters necessary to achieve a radiofrequency nerve block at the target normalized therapeutic dose value.

Description

[Technical Field]

[0001] Priority claims This application claims priority to U.S. Provisional Patent Application No. 63 / 417,646, filed October 19, 2022, and entitled "APPARATUSES AND METHODS FOR SETTING AN ELECTRICAL DOSE."

[0002] Incorporation by Reference All publications and patent applications mentioned in this specification are herein 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 technology]

[0003] Implantable neuromodulators (e.g., implantable neurostimulators, implantable nerve block devices) are increasingly being used to treat pain and other symptoms by applying electrical energy directly to one or more nerves, including nerve bundles, in many cases. Such electrical modulation may be used to excite or inhibit a nerve, or to both excite and inhibit it. In addition to treating pain, electrical modulation may also be applied to nerves to treat unwanted and / or uncoordinated generation of nerve impulses, which may otherwise be disruptive in some medical conditions. Implantable neuromodulators may be implanted on, around, or adjacent to a patient's nerve to deliver electrical energy.

[0004] Electrical modulation for treating a patient generally varies depending on the amount, duration, and intensity of the applied energy. For example, one non-limiting type of electrotherapy involves applying high-frequency alternating current (HFAC) to nerves, which has been shown to block neural 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 to be the amount that inhibits neural activity and produces a desired effect, such as pain relief. Inappropriate administration can be ineffective or, in some cases, can irritate the nerve. Unfortunately, determining an appropriate dose is generally quite difficult, especially when dealing with pain treatment, which can be somewhat subjective and vary greatly between individuals. Determining the appropriate dose for a patient is generally a time-consuming and complex process that requires patient-reported empirical information. As a result, the optimal dose for treating a patient can vary greatly between individuals and, in fact, can vary over time for the same patient. Therefore, it would be advantageous to provide methods and / or devices for simplifying and reliably setting patient doses. Described herein are methods and devices that can address these needs. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2020 / 041323 [Patent Document 2] U.S. Patent Application Publication No. 2021 / 0220642 [Patent Document 3] U.S. Patent No. 7,389,145 [Patent Document 4] U.S. Patent No. 8,060,208 [Patent Document 5] U.S. Patent No. 4,602,624 Summary of the Invention [Means for solving the problem]

[0006] The inventions described herein relate to the field of implantable neuromodulators, and in particular to the field of high-frequency nerve block. Such methods and devices may provide customized, patient-specific pulse profiles to refine electrical charge so that applied therapy produces significant therapeutic benefits. These methods and devices provide techniques that may address and prevent, for the first time, a patient's failure to respond to neuromodulation for blocking pain, including (but not limited to) phantom limb pain. Generally, these devices (e.g., systems, devices, etc., including software, firmware, and / or hardware) are configured to determine a pulse profile for a high-frequency (e.g., nerve block) signal to be applied to a nerve based on a normalized therapeutic dose value (either a specific value, a preset value, or a range of values). For example, the pulse profile for the high-frequency signal may be estimated by a method or device using a 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.

[0007] Generally, a normalized therapeutic dose value is a charge density value that can be delivered, e.g., equivalent to the charge density delivered by a bidirectional waveform (with 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) divided by the cross-sectional area of ​​the region of the nerve under the nerve cuff. This charge per phase can then be normalized as the dose delivered to the nerve (the "normalized dose") that blocks the conduction of pain signals to the central nervous system and brain. For example, a normalized dose value can be about 0.1 μC / phase / cm. 2 ~5μC / phase / cm 2 (For example, about 0.2 μC / phase / cm 2 ~5μC / phase / cm 2 , about 0.2μC / phase / cm 2 ~3.5μC / phase / cm 2 , about 0.3μC / phase / cm 2 ~5μC / phase / cm 2, about 0.4μC / phase / cm 2 ~5μC / phase / cm 2 , about 0.5μC / phase / cm 2 ~5μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~4.5μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~4μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~3.5μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~3μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~2.5μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~2μC / phase / cm 2 etc.).

[0008] For example, the present specification describes a system for applying a high-frequency nerve block, the system comprising: a nerve cuff having one or more electrodes, the nerve cuff 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; and 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 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.

[0009] Any of these apparatus (e.g., systems, devices, etc.) may include an input for either determining or receiving the cross-sectional area of ​​the region of the nerve under the nerve cuff (e.g., across the long axis of the nerve). The controller may be configured to receive data from the input. The cross-sectional area may be input once (e.g., at the time of implantation or shortly after implantation) or multiple times, for example, after healing has occurred after implantation and / or periodically after implantation (e.g., weekly, monthly, every three months, every six months, yearly, etc.).

[0010] Any of these systems may include a memory accessible by the controller, the memory configured to store a normalized therapeutic dose value and / or a cross-sectional area of ​​a region of a nerve at least partially surrounded by the nerve cuff. The pulse generator may be configured to generate a high-frequency signal having a frequency of 1 kHz or greater. The pulse generator may be configured to generate a high-frequency signal having a frequency of 1 kHz to 100 kHz.

[0011] In any of these devices, at least a portion of the device (e.g., implantable controller, pulse generator, memory, etc.) may be contained within a housing that is inserted into the body. For example, the device may include a housing that contains the controller, memory, and pulse generator. Thus, the controller may be configured to be implantable. As described in more detail herein, in some examples, a second controller (external controller) may also be included, and the second controller may be in communication with the pulse generator and the internal controller. In some examples, the calculation of the pulse profile may be performed internally using a controller contained within the housing. Alternatively, in some examples, the controller that determines the pulse profile is an external controller that communicates with the pulse generator and / or the internal controller, e.g., wirelessly (e.g., Wi-Fi, Bluetooth, etc., using a wireless subsystem). Thus, in any of these systems, the controller may be an external controller and may communicate wirelessly with an implant controller coupled to the pulse generator. In some examples, the controller may distribute functionality between the internal controller and the external controller. In some examples, the internal controller determines the pulse profile and simply transmits the pulse profile and / or impedance measurements, etc. to an external controller, memory, etc. for storage, transmission, and / or future analysis.

[0012] The device may receive and / or determine the cross-sectional area. For example, in any of these devices, the controller may be configured to calculate the cross-sectional area from an indication of the cross-sectional area received by the controller. The indication of the cross-sectional area may include one or more measures of diameter, circumference, etc. This indication may be provided by a medical professional (doctor, surgeon, nurse, technician, etc.) based on measurements made during implantation. Accordingly, these devices (e.g., systems) may include one or more inputs configured to receive an indication of the cross-sectional area of ​​a region of the nerve at least partially surrounded by the nerve cuff.

[0013] Alternatively, or additionally, the cross-sectional area indicator may be automatically determined by the device, e.g., based on the status of the nerve cuff. For example, the nerve cuff may include a sensor for directly detecting the indicator (e.g., measuring the distance between the two sides of the nerve cuff and thus approximating the diameter, estimating or measuring the constricted size and therefore the circumference of the nerve cuff's channel upon application to the nerve, etc.). The device may include a module (which may be part of the internal and / or external controller) that determines the cross-sectional area of ​​the region of the nerve at least partially contained by the nerve cuff from the indicator. The indicator and / or the cross-sectional area of ​​the region of the nerve may be stored in memory that may be accessible by or part of the controller. The memory may store the indicator and / or cross-sectional area of ​​the region of the nerve in a non-volatile manner, thereby retaining the values ​​even if power is lost. The device may back up the cross-sectional area of ​​the region of the nerve and / or the indicator values, including backing up to a remote (e.g., cloud) site.

[0014] The same memory or a different memory accessible by the controller may store normalized therapeutic dose values. As noted above, normalized therapeutic dose values ​​may be in the range of values ​​(e.g., about 0.1 μC / phase / cm 2 ~5μC / phase / cm 2 ) or a specific value within this range, e.g., 2 μC / phase / cm 2 Sometimes it is.

[0015] These devices and methods may be configured to allow the patient to trigger and / or set the duration and / or stop (e.g., immediately stop) the delivery of the radiofrequency signal. In some examples, the devices and methods may be configured to allow the user to select from one or more different dose values ​​(e.g., select from several different discrete normalized therapeutic dose values ​​or continuously varying normalized therapeutic dose values). In some examples, the device may include an external controller configured to instruct the controller to deliver the radiofrequency signal. The external controller may include one or more controls (buttons, dials, touchscreen inputs, etc.) that may select on / off (e.g., to deliver a dose, to turn a dose off) and optimally select an input (e.g., “high,” “medium,” “low,” etc.) that may be associated by the controller with a normalized therapeutic dose value. Optionally, the user may select a dose duration (e.g., 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, etc.) and / or schedule (calendar and / or time-of-day) the delivery of the dose. The external controller may be a dedicated device that communicates wirelessly with the implant and / or may include software and / or firmware that may run on a general-purpose device (e.g., a phone, a tablet, etc.).

[0016] As mentioned above, in general, a controller (internal and / or external controller) may calculate a pulse profile. The pulse profile may refer to one or more characteristics of a radiofrequency waveform emitted by a pulse generator for delivery by electrodes of a nerve cuff. The pulse profile may include one or more of pulse width, pulse amplitude, pulse frequency (pulse frequency within a specified radiofrequency domain), and pulse burst duration (e.g., treatment time). Any of these parameters may be fixed or set by the controller, while one or more of the other parameters may be variable / calculated. For example, in some examples, the pulse amplitude may be fixed. In some examples, the pulse amplitude may be variable. In some examples, the controller may calculate the pulse width.

[0017] In some examples, the devices described herein comprise an implant subsystem including a housing containing a pulse generator, controller, battery, etc., and a nerve cuff. The nerve cuff may be directly coupled to the housing (or more specifically to the electronics within the housing), or the nerve cuff may be coupled to the housing / electronics by an elongated, flexible lead, e.g., a lead that couples the pulse generator to the nerve cuff.

[0018] Any of these devices may include an impedance sensing subsystem configured to determine impedance measured from one or more electrodes. For example, the device may include, as part of an internal (e.g., implantable) controller, an impedance sensing circuit configured to detect impedance at one or more electrodes of the nerve cuff. The detected impedance (Z) may approximate real and / or complex impedance.

[0019] For example, described herein is a system for applying a high frequency nerve block, the system comprising: an implantable nerve cuff having one or more electrodes, the nerve cuff 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 that stores a normalized therapeutic dose value and an indication of a 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 therapeutic dose value, the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff, and 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.

[0020] Described herein are methods for setting and / or adjusting a dose of electrical energy to treat a patient using a normalized therapeutic dose. These methods may be used to set an initial pulse profile (e.g., parameters of the applied pulse energy, including the radiofrequency pulse energy used specifically for nerve blocks). These methods and devices may be used to adjust the pulse profile. For example, described herein is a method for applying a radiofrequency nerve block to treat pain, the method including: determining 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; estimating impedance values ​​from one or more of the electrodes; determining, in a controller, a pulse profile based on the normalized therapeutic dose value, the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff, and the impedance values; and applying a radiofrequency signal having the pulse profile to the nerve.

[0021] Any of these methods may include wrapping a nerve cuff at least partially around the nerve (or in some cases, wrapping the nerve cuff encircling the nerve). The nerve cuff may be implanted using a lead or leadless configuration, along with a pulse generator, internal (e.g., implantable) controller, power source, etc.

[0022] In any of these methods, the high frequency signal may have a frequency of about 1 kHz or greater. For example, the high frequency signal may have a frequency between 1 kHz and 100 kHz. The frequency may be set (e.g., predetermined) or adjustable.

[0023] As noted above, the normalized therapeutic dose value may be selected or predetermined from a range of values. For example, the normalized therapeutic dose value may be 0.1 μC / phase / cm 2 ~5μC / phase / cm 2 In some examples, the normalized therapeutic dose value may be about 0.5 μC / phase / cm 2 ~4μC / phase / cm2 The minimum normalized therapeutic dose value is approximately 0.1 μC / phase / cm 2 More than about 0.2μC / phase / cm 2 More than about 0.3μC / phase / cm 2 More than about 0.4μC / phase / cm 2 More than about 0.5μC / phase / cm 2 More than about 0.6μC / phase / cm 2 The maximum normalized therapeutic dose value is 1.4 μC / phase / cm 2 Below, approximately 1.5μC / phase / cm 2 Below, approximately 1.6μC / phase / cm 2 Below, approximately 1.7μC / phase / cm 2 Below, approximately 1.8μC / phase / cm 2 Below, approximately 1.9μC / phase / cm 2 Below, approximately 2.0μC / phase / cm 2 Below, approximately 2.1μC / phase / cm 2 Below, approximately 2.2μC / phase / cm 2 Below, approximately 2.3μC / phase / cm 2 Below, approximately 2.5μC / phase / cm 2 Below, about 3μC / phase / cm 2 Below, approximately 3.5μC / phase / cm 2 Below, about 4μC / phase / cm 2 Below, approximately 4.5μC / phase / cm 2 Below, about 5μC / phase / cm 2 Below, approximately 5.1μC / phase / cm 2 Below, about 5.5μC / phase / cm 2 It could be the following:

[0024] Any of these methods may include estimating the cross-sectional area of ​​a region of the nerve at least partially surrounded by the nerve cuff from an indicator of the cross-sectional area of ​​the region of the nerve contained or partially contained by the nerve cuff. In some examples, the method may include obtaining (e.g., measuring) an indicator of the cross-sectional area of ​​the region of the nerve contained or partially contained by the nerve cuff (e.g., nerve diameter, nerve circumference, etc.). Thus, in any of these methods, determining the indicator of the cross-sectional area of ​​the region of the nerve may include measuring the circumference or diameter of the region of the nerve that is or will be at least partially surrounded by the nerve cuff. The indicator may be measured directly and / or determined indirectly. Any of these methods may include storing either or both the cross-sectional area of ​​the region of the nerve contained or partially contained by the nerve cuff or the indicator of the cross-sectional area of ​​the region of the nerve contained or partially contained by the nerve cuff. This value may be stored in a memory accessible by the controller. The value of the cross-sectional area of ​​the region of the nerve contained or partially contained by the nerve cuff and / or the index of the cross-sectional area of ​​the region of the nerve contained or partially contained by the nerve cuff may be set once when the nerve cuff is surgically implanted, or may be updated periodically (e.g., as described above, particularly when the value or index is determined automatically).

[0025] Any of these methods may include receiving a signal from a user to apply a radiofrequency signal having a pulse profile to a nerve and / or selecting a signal from a variety of possible applied signals (e.g., "high," "medium," "low," etc.) within a normalized therapeutic dose value range. The user may control turning the applied signal on / off (as needed) and / or schedule the application of the therapy (e.g., once or several times per day).

[0026] Any of these methods may include determining a pulse profile by determining one or more of pulse width, pulse amplitude, pulse frequency, and pulse burst duration. Applying the radiofrequency signal may include applying the radiofrequency signal for a treatment period. Any suitable treatment period may be used (e.g., a treatment period of 10 minutes or more, 15 minutes or more, 20 minutes or more, 25 minutes or more, 30 minutes or more, 35 minutes or more, etc.). The normalized treatment dose value may be estimated based on a standard treatment period (e.g., 30 minutes) and / or adjusted based on the treatment period.

[0027] For example, a method of applying a radiofrequency nerve block to treat pain may include wrapping a nerve cuff comprising one or more electrodes at least partially around a nerve of a patient, determining a measure of a cross-sectional area of ​​a region of the patient's nerve at least partially surrounded by the nerve cuff, estimating impedance values ​​from one or more of the electrodes, and, in a controller, controlling the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff to a value less than 0.1 μC / phase / cm. 2 ~5μC / phase / cm 2 determining a pulse profile based on a normalized therapeutic dose value of the nerve cuff, a cross-sectional area of ​​a region of the patient's nerve at least partially surrounded by the nerve cuff, and an impedance value; and applying a radiofrequency signal having the pulse profile to the patient's nerve.

[0028] The method (including, but not limited to, a method of applying a high frequency nerve block to treat pain) includes the steps of determining or receiving, in a controller of a nerve stimulator coupled to a nerve cuff having one or more electrodes at least partially around the patient's nerve, a cross-sectional area of ​​a region of the patient's nerve at least partially surrounded by the nerve cuff; determining impedance values ​​from one or more of the electrodes; and, in the controller, determining a cross-sectional area of ​​the region of the patient's nerve at least partially surrounded by the nerve cuff. 2 ~5μC / phase / cm 2determining a pulse profile based on a normalized therapeutic dose value of the nerve cuff, a cross-sectional area of ​​a region of the patient's nerve at least partially surrounded by the nerve cuff, and an impedance value; and applying a radiofrequency signal having the pulse profile to the patient's nerve.

[0029] All of the methods and devices described herein are contemplated herein in any combination and can be used to achieve the benefits described herein.

[0030] The features and advantages of the methods and apparatus described herein will be better understood by reference to the following detailed description and accompanying drawings that set forth illustrative embodiments. [Brief explanation of the drawings]

[0031] [Figure 1] Figure 1 shows the percentage of patient sessions with at least 30% pain reduction immediately after 30 minutes of treatment with a single nerve cuff as a function of normalized dose (in μC / phase / cm²) for all subjects in a clinical trial (QUEST RCT treated subjects, n=85). "Absolute" non-responders (e.g., 0% of sessions when doses were in the >=2 range) were included. However, these patients likely represent false positives during lidocaine screening. [Figure 2] FIG. 1 is a graph showing the percentage of patient sessions with at least 50% pain reduction 120 minutes after treatment with a single nerve cuff as a function of normalized dose (in μC / phase / cm) for treated subjects (n=85). [Figure 3A] FIG. 1 illustrates an example of a neuromodulation system (showing an implantable controller / waveform generator that may include a nerve cuff, leads, and a dose setting controller). [Figure 3B]3A is a diagram showing an example of the system of FIG. 3A implanted in a patient, also showing the dose setting controller and, in this example, an optional external controller that may be in communication with the implant. The optional external controller (also referred to herein as a patient controller or user controller) may include or be in communication with a dose selector that drives the application of energy by the implant. [Figure 3C] FIG. 1 is a schematic diagram of a system for treating pain in a patient using radiofrequency nerve block including a dose setting controller as described herein. [Figure 4] FIG. 1 is a schematic diagram illustrating an example of a system for treating pain in a patient including normalized titration. [Figure 5] 1 is a flow chart illustrating an example method of treating pain in a patient by delivering neuromodulation from an implant using a normalized dose as described herein. DETAILED DESCRIPTION OF THE INVENTION

[0032] Methods and apparatus (e.g., devices, systems, etc.) for applying therapeutic doses of electrical energy from a nerve cuff onto a nerve to modulate nerve function, including reducing pain, may include using a normalized therapeutic dose value (or range of values) that indicates a target therapeutic charge dose to be applied. These apparatus and methods may use the impedance value of the nerve at the nerve cuff and the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff, along with the target normalized therapeutic dose value, to determine parameters for the applied energy. In particular, the parameters may be parameters required to achieve a radiofrequency nerve block at the target normalized therapeutic dose value.

[0033] For example, any of the methods and devices described herein may include implanting a nerve cuff electrode in a patient in direct electrical contact with the nerve. The nerve cuff electrode may partially or completely surround the nerve. The nerve cuff electrode may be connected to a pulse generator (PG) configured to generate a bidirectional waveform with an amplitude controlled by voltage or current. The pulse generator may be configured to send and receive data from a processor (e.g., a computer) via a communications software protocol. In any of these devices, the pulse generator may be configured to receive a measured impedance (Z) at the nerve cuff electrode / neural interface, and the pulse generator may be configured to send an increase or decrease in voltage or current to the nerve cuff electrode / neural interface. Any of these devices may 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 cuff. In general, these devices may be configured to respond to the measured impedance (Z), changes in voltage or current, and the charge density delivered by the bidirectional waveform (having a pulse width related to the charge density) according to the following mathematical formula:

[0034]

number

[0035] The charge per phase can be normalized as the dose delivered to the nerve that blocks the conduction of pain signals to the central nervous system and brain (the "normalized dose"). As shown in Equation (1), the normalized dose is C / (phase*cm 2 ), or more often, microC / (phase*cm 2 ) units, e.g., μC / phase / cm 2 It can be in units of

[0036] As described in detail herein, by normalizing the dose to the cross-sectional area of ​​the region of the nerve encompassed by the nerve cuff, the response, similar to the dose of a drug, can be more predictable and more gradual, which can provide several advantages to both patients and caregivers, including the ability to more precisely treat a variety of different patients, prevent adaptation, reduce side effects, and prevent or limit desensitization.

[0037] Surprisingly, the methods and devices described herein can also provide electrical pain treatment similar to pharmaceutical pain relief, with increasing doses (e.g., below the threshold of intolerable side effects) resulting in increased levels of pain relief experienced by the patient. Generally, the methods and devices described herein provide treatments in which the charge density can be set for initial administration and controlled to increase or decrease to modulate pain relief. Pain relief can be measured by patient-reported outcomes (PROs).

[0038] For example, Figure 1 shows the results of a recent study using a nerve cuff device similar to that described herein. This study ("QUEST") enrolled lower-limb amputees with chronic, severe residual or phantom limb pain who achieved significant pain relief after a local nerve block injection (lidocaine injection). A single cuff electrode was placed around the sciatic nerve, or two cuffs (one on each nerve) were placed on the tibial and common peroneal nerves, e.g., above or below the knee. An implantable generator was used to apply a 5 kHz or 10 kHz sinusoidal waveform, applying up to 16 V or 20 mA at 30-minute intervals between each subject-initiated treatment session. Pain intensity was recorded before and after each session using a diary.

[0039] First, the dose in the QUEST study was calibrated as proposed in the art. See, for example, U.S. Patent Application Publication No. 2019 / 0129999 entitled "APPARATUSES AND METHODS FOR ADJUSTING A THERAPEUTIC ELECTRICAL DOSE" (filed August 20, 2019) and corresponding U.S. Patent Application Publication No. 2019 / 0129999). Initial calibration required a technician to set the initial dose and involved the patient, using patient feedback during an initial calibration period. The selected and applied voltage and impedance were determined along with other patient-specific data, including body structure, age, and other relevant parameters. The results of the QUEST study were analyzed as described herein. Only by analyzing the results of multiple patient groups (including both responders and non-responders) at different apparent efficacy levels (e.g., various percentages of pain relief at different time points) did it become clear that only after adjusting the applied energy to a normalized dose that targets the region of the nerve at least partially surrounded by the nerve cuff could pain relief efficacy across different patients be titrated based on the normalized dose as described herein.

[0040] For example, 85 subjects from the QUEST study were analyzed based on the percentage of PRO sessions in which subjects achieved at least 30% pain relief after 30 minutes of electricity delivery as a function of the subject's charge density, or "dose." Figure 1 shows a positive linear dependence, or "dose-response effect," in two separate groups of subjects receiving larger electrical doses (approximately 0.75-1 and approximately 1.5-2). Two example (dashed) lines are shown approximating the linear recurrence of responding patients. Subjects in these ranges experienced 30% pain relief immediately following the 30-minute session in over 70% of their sessions.

[0041] The pharmacological "dose-response effect" of nerve-delivered electricity is further supported by the data shown in Figure 2. In this example, patient-reported outcome data are presented as the percentage of sessions in which pain was reduced by at least 50% 120 minutes after the initial 30-minute session in Figure 1. That is, these subjects received a single 30-minute dose of electricity, and then their pain was recorded immediately after the session (Figure 1) and then again 120 minutes later (Figure 2), and these recordings show a sustained effect.

[0042] Generally, a single electrical dose in a single session (e.g., 30 minutes) can produce an immediate, moderately effective pain reduction of at least 30% in the dose range noted above (Figure 1). At 120 minutes in the same dose range (Figure 2), the improvement in pain reduction becomes substantial (at least 50%). Moderately effective and substantial improvements in pain reduction are highly clinically significant. A 10% to 20% reduction in pain intensity is considered a "minimally effective" pain intensity reduction, a reduction of 30% or less corresponds to what patients consider a "moderately effective" improvement in pain intensity, and a reduction of approximately 50% or more can be considered a "substantial" improvement in pain intensity for individuals with acute and chronic pain. Percent pain reduction is generally considered a useful tool for determining whether meaningful improvements have been achieved in patients. Preliminary results also indicate that such dose-dependent pain intensity reduction does not result in significant adverse effects, such as sleep disturbance, mood disturbance, and functional impairment, thus providing significant benefit to patients.

[0043] The resulting data, and the invention of electrical doses for pain conduction block, can be used to create a baseline for a given patient's starting dose. As noted above, currently, patients must be tested immediately after or during the implantation process, during a required calibration process by a skilled technician, to set and adjust the treatment baseline. For example, the patient must receive gradually increasing voltages starting from 0 V while being questioned by a knowledgeable programmer. The programmer slowly increases the voltage to a threshold the patient can tolerate for 30 minutes. This time- and resource-intensive method is necessary to set the initial treatment intensity and can be used to program the treatment.

[0044] In contrast, the methods and devices described herein may instead control and set the therapeutic dose using a measure of the cross-sectional area of ​​the region of the nerve contained by the nerve cuff (e.g., sciatic, tibia, etc.) and the impedance of the nerve / cuff tissue interface region to determine the therapeutic dose, and to achieve a therapeutic dose within a target range (e.g., approximately 0.1 μC / phase / cm 2 ~5μC / phase / cm 2 , 0.2μC / phase / cm 2 ~5μC / phase / cm 2 , 0.2μC / phase / cm 2 ~3.5μC / phase / cm 2 , about 0.3μC / phase / cm 2 ~5μC / phase / cm 2 , about 0.4μC / phase / cm 2 ~5μC / phase / cm 2 etc., approximately 0.5 μC / phase / cm 2 ~5μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~4.5μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~4μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~3.5μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~3μC / phase / cm 2 , about 0.1μC / phase / cm 2~2.5μC / phase / cm 2 , about 0.1μC / phase / cm 2 ~2μC / phase / cm 2 Thus, for a given patient with a cross-sectional area of ​​the portion of the nerve contained by the nerve cuff, the dose can be set within the therapeutic dose by setting the pulsation parameters (e.g., pulse width, amplitude, etc.) while monitoring the impedance of the nerve cuff (electrode) at the tissue (e.g., at the nerve).

[0045] Knowing the patient's nerve diameter and nerve cuff / nerve impedance (e.g., using data such as that shown in Figures 1 and 2) allows the programmer to optimally position the voltage (and associated electrical dose) within a narrow range known to be reasonably effective in substantially improving pain relief.

[0046] Thus, the devices and methods using therapeutic doses described herein can provide a range of applied energies specific to a particular patient (based on the relationship between impedance and cross-sectional area of ​​the nerve in the nerve cuff) to result in effective treatment. Initial treatment parameters (e.g., applied energy) can be set within a normalized therapeutic dose value range.

[0047] While the data in Figures 1 and 2 are specific to a patient with a single cuff, similar results are seen in patients in which two cuffs are used (e.g., wrapped around both the tibial and common peroneal nerves). Accordingly, the methods and devices described herein can be used with two (or more) nerve cuffs wrapped around the same patient. In some instances, a combination of the effects of both nerve cuffs, including the cross-sectional area and impedance of each nerve surrounded (or partially surrounded) by each nerve cuff, can be used with the same (or in some instances, scaled or distributed) normalized therapeutic dose. For example, the same normalized therapeutic dose value can be used, and the impedance and cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff can be used to determine the pulse profile applied at each of the nerve cuffs. Alternatively, the normalized therapeutic dose can be distributed between the nerve cuffs based, for example, on the ratio of the cross-sectional area and / or impedance values ​​of each nerve in the various nerve cuffs.

[0048] Device The devices described herein generally include a controller that can determine parameters of the applied energy (e.g., a pulse profile) so that the applied energy falls within a predetermined range of normalized therapeutic dose values ​​(and / or targets a particular normalized therapeutic dose value), as well as a nerve cuff for at least partially surrounding the nerve to which the energy is applied. For example, the device may generally include a nerve cuff having one or more electrodes (e.g., an array of electrodes), an implantable pulse generator configured to generate a radiofrequency signal having a pulse profile, and a controller configured to determine the pulse profile based on the normalized therapeutic dose value (e.g., the charge to be delivered). Thus, the controller may be configured to determine the pulse profile based on the normalized therapeutic dose value, a cross-sectional area of ​​a region of the nerve at least partially surrounded by the nerve cuff, and impedance measured from one or more electrodes, and the controller is configured to drive the pulse generator to deliver a radiofrequency signal having the pulse profile from the one or more electrodes.

[0049] These apparatuses (e.g., systems, devices, and software, including neuromodulators and neuromodulation systems) may be configured to treat a patient's pain and may include one or more subsystems or modules. The one or more subsystems or modules may be hardware, software, and / or firmware for determining the energy (pulse profile) to be applied for therapy such that the delivered energy is within (and / or at) a target normalized therapeutic dose value.

[0050] These methods and devices may be used with a suitable neuromodulator. Figure 3A shows an example of an implantable neuromodulator including a nerve cuff 101 and electrical leads 103 connecting the nerve cuff to a controller (e.g., a waveform generator, control circuitry, power source, communication circuitry, and / or antenna, etc.) within an implantable housing 105. A system including a nerve cuff as described herein may be used to apply high-frequency nerve blocks to acutely treat pain, either acute pain or chronic pain (for periods greater than six months) in humans, for example, by blocking nerve conduction over action potentials. Acute treatment may refer to on-demand treatment with a substantially immediate pain-relieving effect. A nerve cuff may be wrapped around a nerve of a moderate to relatively large diameter, such as, but not limited to, the sciatic nerve. One therapy involves reversibly blocking a peripheral nerve by applying high-frequency alternating current directly to the nerve trunk. Currents in the range of 1 kHz to 100 kHz (e.g., 5 kHz to 50 kHz) can be applied, which may be referred to as high-frequency modulation, compared with currents below 1 kHz applied in conventional electrical modulation. The efficacy of high-frequency alternating current therapy has been reported in acute non-human animal studies (frogs, cats). Patent Documents 3 and 4 provide a general description of this electrical modulation technique.

[0051] The nerve cuff may surround a specific segment of a targeted peripheral nerve, e.g., the sciatic nerve, tibial nerve, etc. Using implantable electrodes connected to an electrical waveform generator, electrode waveforms may be applied at intervals of time sufficient to produce substantially immediate patient pain relief, e.g., 10 minutes (15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, etc.), to produce patient pain relief within 10 minutes for an extended period of pain relief up to several hours. The current is determined as described herein so that the total energy (charge) delivered approximates (including is within) the targeted normalized therapeutic dose.

[0052] A 10 kHz alternating current generated by a custom generator via a custom implantable nerve electrode can significantly reduce pain in the majority of treated patients. For example, an implantable electrode operably connected to an external or implantable waveform generator can be used. The electrode can be a helical cuff electrode similar to the electrode described in Patent Document 5. The electrode can be implanted on the desired nerve trunk proximal to a pain source (e.g., a neuroma) in a mammal, whereby the cuff surrounds the desired peripheral nerve where action potentials are to be blocked. The inner diameter of the cuff can range from about 4 mm to about 13 mm. The sciatic nerve is known to have a relatively large nerve trunk, and the diameter of the proximal portion of the sciatic nerve can vary between individuals. In one embodiment, the device and method were used on the sciatic nerve to treat lower limb pain in patients with above-knee amputees. In one embodiment, the device and method were used on the tibial nerve to treat lower limb pain in patients with below-knee amputees.

[0053] FIG. 3B illustrates the use of a system including a cuff electrode wrapped around the sciatic nerve of an amputee. In this example, a nerve cuff 101 is implanted around the sciatic nerve (nerve trunk) of an amputee 107, who is connected via leads 103 to a controller including a pulse generator (also called a waveform generator) in an implantable housing 105. This procedure may be performed, for example, by first making an incision to expose the nerve in an open procedure and then enveloping the nerve with a flexible (self-closing) cuff. During the procedure, the diameter and / or circumference of the nerve where the cuff is implanted may be measured directly or indirectly. This value may be sent to an implanted controller and / or an external controller. After the controller / waveform generator is implanted, it may be placed in a pouch in the anterolateral abdominal wall, and a tunneled electrode cable may be positioned along the mid-axillary line (including across the abdomen) to connect the controller / waveform generator to the nerve cuff electrode. The impedance of the nerve cuff may be determined (e.g., by the system), and the incision may be closed. The incision for implanting the nerve cuff may be larger than about 1.5 inches (e.g., 1.5 inches to 3 inches), thereby allowing for adequate visualization and access. After implanting the neuromodulator and allowing for healing, the implanted neuromodulator may be configured as described herein to provide a therapeutic dose (e.g., an optimized dose) as described herein.

[0054] 3B also includes an external controller 131 (e.g., a patient controller), which may include one or more processors and be configured to implement at least some of the methods described herein. The controller, or a separate device coupled to the controller, may include user-controlled inputs. The controller may be software (e.g., application software) running on a personal device such as a smartphone, tablet, etc., and may include one or more interfaces to allow a user to control the operation of the implant.

[0055] FIG. 3C schematically illustrates an example of a system 300 (e.g., a system for applying a radiofrequency nerve block). The system includes an implant 251 having a nerve cuff with one or more electrodes. The nerve cuff is configured to at least partially surround a region of a nerve. The implant 251 also includes a pulse generator configured to generate a radiofrequency signal having a pulse profile and a controller configured to determine the pulse profile based on a normalized therapeutic dose value range. The implant may be configured to wirelessly communicate with an external controller 231, which may include one or more user (e.g., patient, physician, technician, etc.) controls 241, such as a touchscreen, knobs, buttons, etc. The external controller 231 may also include one or more outputs (e.g., LEDs, displays, speakers, etc.). In some examples, the external controller is software running on a smartphone, phone, tablet, etc. The implant and external controller may communicate with each other 315 (e.g., via wireless communication protocols and / or subsystems). Either or both of the implant and the external controller may additionally or alternatively be in communication with a remote server 261, which may receive input and provide output to the implant and / or the external controller.

[0056] As described above, an implantable controller and / or an external controller may be used to determine a pulse profile from the normalized therapeutic dose value. The pulse profile may correspond to the neuromodulation dose to be delivered and may include various dose parameters for treating pain. Generally, the set of dose parameters may include a dose duration (e.g., the time over which the dose is delivered, which may be the total duration or a portion of the total duration, and the treatment time), a dose frequency (e.g., the treatment frequency; in high-frequency nerve block variations, the frequency may be higher than 1 kHz, such as 1 kHz to 100 kHz), and a peak voltage (e.g., a peak modulation voltage of 0.1 V to 20 V, e.g., 5 V to 15 V). In some variations, the dose parameters may include a treatment signal rise time to reach the peak modulation voltage and a sustained peak modulation time during which the voltage is maintained at the peak modulation voltage (the dose duration may include both the signal rise time and the peak modulation time). Dose parameters may also include applied waveform parameters, e.g., pulsatile or repetitive waveform (sine, square, sawtooth, biphasic, etc.), and frequency of the applied waveform (e.g., high frequency component). Other dose parameters may include initial (e.g., starting) voltage, which may be, for example, zero or an offset (e.g., voltage offset) voltage. In some variations, treatment dose parameters may include pulse duration (treatment variations including bursting / pulsing), burst duration (treatment variations including bursting / pulsing), pulse shape (e.g., square, triangular, sinusoidal, etc.), biphasic / monophasic (positive and / or negative), carrier frequency (variations using a carrier frequency), DC offset level (variations including a DC offset), current level (variations that modulate the current), current limit (variations that limit the current), electrode number / position (variations having multiple pairs of electrodes), etc.

[0057] In general, a controller (either or both of the internal controller within implant 251 and / or the external controller 231) can be configured to determine a pulse profile to determine the therapeutic dose to be delivered so that the therapeutic dose (charge delivered) is approximately within a normalized therapeutic dose value (or within a normalized therapeutic dose value range).

[0058] FIG. 4 illustrates an example of a neuromodulation system 270A configured to set a therapeutic dose based on the normalized therapeutic dose values ​​described above. The modules of the neuromodulation system 270A may include one or more modules (sometimes referred to herein as subsystems or engines) and one or more data stores (e.g., memories). The modules may include hardware, firmware, and / or software and may be part of a control device (e.g., processor, memory, circuitry, etc.). A module (e.g., an engine / subsystem) may be implemented as part of a controller having one or more processors, or one or more modules may be implemented as part of the same (or multiple) controllers. Thus, as used herein, a module (engine / subsystem) may include one or more processors or portions thereof. A portion of one or more processors may include some portion of less than all of the hardware comprising any given processor(s), such as a subset of registers, a portion of a processor dedicated to one or more threads of a multithreaded processor, or a time slice in which all or a portion of a processor is dedicated to performing some of the engine's functions. Thus, the first engine and the second engine may have one or more dedicated processors, or the first engine and the second engine may share one or more processors with one or more other engines. Depending on implementation-specific or other requirements, the engines may be centralized, or their functions may be distributed. Thus, the engines may include hardware, firmware, or software embodied in a computer-readable medium for execution by a processor. The processor transforms data into new data using the implemented data structures and methods, as described herein with reference to the figures.

[0059] The engines described herein, or engines capable of implementing the systems and devices described herein, can be local engines or cloud-based engines. As used herein, a cloud-based engine is an engine that can execute applications and / or functions using a cloud-based computing system. All or part of the applications and / or functions can be distributed across multiple computing devices and need not be limited to only one computing device. In some embodiments, the cloud-based engine can execute functions and / or modules that end users access via a web browser or container application without installing the functions and / or modules locally on the end user's computing device.

[0060] As used herein, memory may be equivalently referred to as a data store and is intended to include one or more repositories having any applicable organization of data, including tables, comma-separated values ​​(CSV) files, traditional databases (e.g., SQL), or other applicable known or convenient organizational formats. A data store may be implemented, for example, as physical computer-readable media on a special-purpose machine, firmware, hardware, a combination thereof, or software embodied in an applicable known or convenient device or system. A database may be a data store or part of a data store. Data store-related components, such as a database interface, may be considered "part" of the data store, part of some other system component, or a combination thereof. However, the physical location and other characteristics of data store-related components are not important to understanding the techniques described herein.

[0061] A data store can include a data structure. As used herein, a data structure refers to a specific way of storing and organizing data in a computer, thereby allowing it to be used efficiently within a given context. Data structures are generally based on a computer's ability to fetch and store data anywhere in memory, where the data is specified by an address, i.e., 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 using arithmetic, while other data structures are based on storing the address of the data item within the structure itself. Many data structures use both principles, sometimes combining them in trivial ways. Implementing a data structure typically involves writing a set of procedures to create and manipulate instances of the structure. The data store described herein is a cloud-based data store. A cloud-based data store is a data store that is compatible with cloud-based computing systems and engines.

[0062] Neuromodulator system 270A may include computer-readable media, an implantable neuromodulator 271, one or more pulse generators 278, and one or more data stores (memories) for holding normalized therapeutic dose values ​​or ranges of values, e.g., a normalized therapeutic dose value data store 282. The same or a different data store 280 may be used to hold either or both an indicator of the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff (e.g., nerve circumference, nerve diameter, etc.) and / or the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff. The system may include an input / output engine 276 for inputting the indicator of the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff and / or the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff. The input / output engine may include or involve wireless communication with the controller. In some examples, the system includes an area estimation engine 274 for estimating the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff from the indicators. In some examples, the cross-section estimation engine may be configured to receive input from a nerve cuff indicative of the cross-sectional area of ​​a region of the nerve at least partially surrounded by the nerve cuff. The system may also include an impedance sensing engine 277 for determining the impedance morphology of the electrode / tissue interface from the nerve cuff.

[0063] The systems described herein may also include a pulse profile generation engine 272 configured to determine a pulse profile based on the normalized therapeutic dose value (range), the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff (or equivalently, an indication of the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff), and the impedance (from the impedance sensing engine). Accordingly, the pulse profile engine may output one or more parameters for setting a pulse waveform to the pulse generator 278 to deliver a radio frequency signal having the pulse profile from one or more electrodes of the nerve cuff of the implantable neuromodulator 271.

[0064] The implantable neuromodulator may be implanted in a patient (as shown in FIG. 3B) and may communicate with other components of the system. The input / output engine 276 also allows the patient to adjust the dose, including switching between different normalized therapeutic dose value ranges, as described above. In some variations, the pulse profile engine may be integrated with or part of the patient controller, or may communicate with an external controller to allow selection of different normalized therapeutic dose values.

[0065] In practice, the neuromodulation system may set an initial dose, e.g., a starting dose, for the patient based on the normalized therapeutic dose value. In some instances, subsequent doses may then be based on this initial dose. Alternatively, or additionally, subsequent doses may be recalculated because impedance may change and / or the target normalized therapeutic dose value may change. For example, a user may increase or decrease the desired intensity, and the intensity may be adjusted by selecting more or less charge within the range of acceptable normalized therapeutic dose values.

[0066] method FIG. 5 illustrates an example of a method for treating a patient, including using a normalized therapeutic dose value (or range of normalized therapeutic dose values) to set a therapeutic dose and determine parameters for applying therapy. Optionally, in some examples, a nerve cuff may be implanted at least partially on a target nerve (e.g., sciatic nerve, tibial nerve, etc.) 501. The nerve cuff may completely or partially wrap around a portion of the nerve. A measure of cross-sectional area, such as the diameter and / or circumference of the region of the nerve contained (or partially contained) by the nerve cuff, may then be estimated, providing the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff 503. The cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff may be determined automatically and / or manually. For example, a clinician may measure or approximate the circumference or diameter of the nerve when wrapping the nerve cuff and input this measure so that the system can calculate the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff. Alternatively, the clinician may calculate and input the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff. In some examples, the device may automatically estimate the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff.

[0067] In any of these methods, the impedance of one or more electrodes on the tissue may be determined from one or more electrodes on the nerve cuff 505. In some examples, the impedance is checked as part of the implantation process to wrap the nerve cuff around the nerve and confirm good contact with the nerve. Optionally, the impedance may be detected as part of the implant (e.g., as part of the neuromodulation system, such as as part of the impedance sensing engine).

[0068] The method may include setting or determining a target normalized therapeutic dose 507 (or range of doses). For example, the method may include using a normalized therapeutic dose or receiving a user-selected normalized therapeutic dose (e.g., from an external controller). The selected or determined normalized therapeutic dose may then be used to determine 509 parameter values ​​for applying energy (e.g., charge) to a nerve having a measured cross-sectional area when the impedance matches the determined impedance. Some of the parameters (e.g., amplitude, frequency, burst duration, etc.) may be preset, while other parameters (e.g., pulse width) may be value-determined to determine what the parameter values ​​should be to achieve a target normalized therapeutic dose within an allowed range of the normalized therapeutic dose. Any of the stimulation parameters may be varied, with the remaining parameters being fixed to preset values.

[0069] 5, after determining treatment parameters from the target normalized therapeutic dose, the impedance and cross-sectional area of ​​the nerve under the nerve cuff, energy may be applied through the nerve cuff to treat the patient 511. Thereafter, for example, after sufficient "off" time and / or as determined by the patient in an on-demand system, the process may optionally be repeated from step 505 of determining impedance, or step 507 of determining the target normalized therapeutic dose, or by determining values ​​for one or more pulse parameters 509. In some cases, the same pulse parameters may be used (or as desired by the patient) in a timed or repeating schedule.

[0070] In any of the methods and devices described herein, the pulse parameters (and normalized dose) may refer to volume rather than cross-sectional area. For example, the volume of the region of the nerve under the electrodes, rather than cross-sectional area, may be used by the controller to determine the pulse profile. For example, the controller may determine the pulse profile based on the normalized therapeutic dose value, the volume of the region of the nerve at least partially surrounded by the nerve cuff, and the impedance measured from one or more electrodes. The volume may 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, the length of the nerve contacting the electrodes within the nerve cuff. Thus, any of these methods and devices may refer to charge per volume (e.g., cm) rather than charge per cross-sectional area. 2 Not cm 3 ).

[0071] It should be understood that the methods and devices described herein generally refer to the cross-sectional area of ​​the nerve beneath the electrode's target, and not to the cross-sectional area of ​​the electrode. The cross-sectional area of ​​the electrode used to express the current density (or charge density, as the case may be), which may refer to the electrochemical properties of a unit surface area of ​​the electrode, is not the same as the cross-sectional length (or volume) of the nerve at least partially surrounded by the nerve cuff described herein. Thus, the use of the nerve's cross-sectional area is not equivalent to the more conventional use of the electrode's cross-sectional area, which is traditionally used to estimate the electrode's charge density.

[0072] In any of the devices (or methods of using the devices) described herein, the device may include one or more inputs for manually inputting the cross-sectional area (or in some examples, volume) of the region of the nerve under the cuff. Alternatively, or additionally, the device may automatically estimate or determine the cross-sectional area (or volume) of the region of the nerve under the cuff, e.g., the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff.

[0073] The controllers described herein may include memory (e.g., storing the above-mentioned software / programs for determining and / or controlling the application of applied pulse parameters). The controller may include or be coupled to a pulse generator; in some examples, the pulse generator may include the controller; and / or the two may be collectively referred to as a pulse generator (PG) or implantable pulse generator (IPG) in fully implanted variations.

[0074] It should be appreciated that all combinations of the above concepts and additional concepts discussed in detail below (provided such concepts are not mutually inconsistent) are contemplated as part of the inventive subject matter disclosed herein and may be used to achieve the advantages described herein.

[0075] The process parameters and sequence of steps described and / or illustrated herein are given by way of example only and can be modified as desired. For example, although the steps illustrated and / or described herein may be shown or discussed in a particular order, these steps do not necessarily have to be performed in the order illustrated or discussed. 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 those disclosed.

[0076] Any of the methods (including user interfaces) described herein may be implemented as software, hardware, or firmware and may 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 smartphone, etc.), which instructions, when executed by the processor, cause the processor to perform any of the following steps: displaying, communicating with a user, analyzing, modifying parameters (including timing, frequency, intensity, etc.), determining, alerting, etc. For example, any of the methods described herein may be performed, at least in part, by an apparatus including one or more processors having a memory storing a non-transitory computer-readable storage medium that stores a set of instructions for the processes of the method.

[0077] While various embodiments have been described and / or illustrated in the context of a fully functional computing system, one or more of these exemplary embodiments may be distributed as program products in various forms, regardless of the particular type of computer-readable medium used to actually perform the distribution. The embodiments disclosed herein may also be implemented using software modules that perform particular tasks. These software modules may include script, batch, or other executable files that may be stored on a computer-readable storage medium or within a computing system. In some embodiments, these software modules may configure a computing system to implement one or more of the exemplary embodiments disclosed herein.

[0078] As described herein, the computing devices and systems described and / or illustrated herein broadly represent any type or form of computing device or system capable of executing computer-readable instructions, such as those included within the modules described herein. In their most basic configuration, these computing devices may each comprise at least one memory device and at least one physical processor.

[0079] 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, a memory device may store, load, and / or maintain one or more of the modules described herein. Examples of memory devices include, without limitation, 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 these, or other suitable storage memories.

[0080] Furthermore, 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 devices described above. Examples of physical processors include, without limitation, a microprocessor, a microcontroller, a central processing unit (CPU), a field programmable gate array (FPGA) implementing a software processor, an application specific integrated circuit (ASIC), portions of one or more of these, variations or combinations of one or more of these, or any other suitable physical processor.

[0081] The method steps described and / or illustrated herein, although illustrated as separate elements, may represent portions of a single application. Further, in some embodiments, one or more of these steps may represent or correspond to one or more software applications or programs that, when executed by a computing device, may cause the computing device to perform one or more tasks, such as method steps.

[0082] Further, one or more of the devices described herein may transform data, physical devices, and / or representations of physical devices from one data, device, and / or representation 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 portion of a physical computing device from one form of computing device to another by executing on, storing data on, and / or otherwise interacting with the computing device.

[0083] The term "computer-readable medium," as used herein, generally refers to any form of device, carrier wave, or medium capable of storing or carrying computer-readable instructions. Examples of computer-readable media include, without limitation, transmission 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 distribution systems.

[0084] Those skilled in the art will recognize that any process or method disclosed herein can be modified in numerous ways. The process parameters and sequence of steps described and / or illustrated herein are given by way of example only and can be changed as desired. For example, although the steps illustrated and / or described herein may be shown or discussed in a particular order, these steps do not necessarily have to be performed in the order shown or discussed.

[0085] The various exemplary methods described and / or illustrated herein may omit one or more of the steps described or illustrated herein, or may include additional steps in addition to those disclosed. Furthermore, the steps of any method disclosed herein may be combined with any one or more steps of any other method disclosed herein.

[0086] The processors described herein may be configured to perform one or more steps of any of the methods disclosed herein. Alternatively, or in combination, the processor may be configured to combine one or more steps of one or more of the methods disclosed herein.

[0087] When a feature or element is referred to herein as being on another feature or element, the feature or element can be directly on the other feature or element, or intervening features and / or elements may be present. In contrast, when a feature or element is referred to as being directly on another feature or element, there are no intervening features or elements present. When a feature or element is referred to as being "connected," "attached," or "coupled" to another feature or element, it is understood that the feature or element can be directly "connected," "attached," or "coupled" to the other feature or element, or there may be intervening features or elements 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, there are no intervening features or elements present. Although described or illustrated with respect to one embodiment, the features and elements so described or illustrated may be applicable to other embodiments. Those skilled in the art will also appreciate that a reference to a structure or feature being disposed "adjacent" another feature may have portions that overlap or underlie the adjacent feature.

[0088] 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," "an," and "the" are intended to include the plural unless the context clearly dictates otherwise. It will be further understood that the terms "comprises" and / or "comprising," as used herein, specify the presence of stated features, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ."

[0089] Spatially relative terms such as "below," "below," "bottom," "top," and the like may be used herein for ease of description to describe the relationship of one element or feature to another element or feature as shown in the figures. It will be understood that spatially relative terms are intended to encompass different orientations of the device during use or operation in addition to the orientation shown. For example, if the device in the figures were inverted, elements described as "below" or "below" other elements or features would be oriented "above" the other elements or features. Thus, the exemplary term "below" can encompass both an orientation of above and below. The device may be oriented in other ways (rotated 90 degrees or to other orientations), and the spatially relative descriptors used herein may be interpreted accordingly. Similarly, terms such as "upward," "downward," "vertical," "horizontal," and the like are used herein for descriptive purposes only, unless expressly indicated otherwise.

[0090] The terms "first" and "second" may be used herein to describe various features / elements (including steps), but these features / elements should not be limited by these terms unless the context clearly dictates otherwise. These terms may be used to distinguish one feature / element from another. Thus, a first feature / element described below could be referred to as a second feature / element, and similarly, a second feature / element described below could be referred to as a first feature / element, without departing from the teachings of the present invention.

[0091] In general, any apparatus and methods described herein should be understood to be inclusive, although all or a subset of the components and / or steps may alternatively be exclusive and may be expressed as "consisting of" various components, steps, sub-components, or sub-steps, or alternatively as "consisting essentially of" steps, sub-components, or sub-steps.

[0092] All numbers used in this specification and claims, including those used in the examples, unless otherwise expressly indicated, may be read as if they were preceded by the words "about" or "approximately," even if the words do not explicitly appear. The terms "about" or "approximately" may be used in describing magnitudes and / or locations to indicate that the stated value and / or location is within a reasonably expected range of values ​​and / or locations. For example, a numerical value may have a value that is ±0.1% of the stated value (or range of values), ±1% of the stated value (or range of values), ±2% of the stated value (or range of values), ±5% of the stated value (or range of values), ±10% of the stated value (or range of values), etc. Any numerical value given herein should also be understood to include about or approximately that value, unless the context clearly indicates otherwise. For example, if the value "10" is disclosed, "about 10" is also disclosed. Any numerical range described herein is intended to include all subranges subsumed therein. When a value is disclosed, "less than or equal to" that value, "greater than or equal to" that value, and possible ranges between values ​​are also disclosed, as would be appropriately understood by one of ordinary skill in the art. For example, if a value "X" is disclosed, "less than or equal to X" and "greater than or equal to X" (e.g., X is a numeric value) are also disclosed. It is to be understood that throughout this application, data is provided in several different formats, and this data represents endpoints and starting points, and ranges for any combination of the data points. For example, if a specific data point "10" and a specific data point "15" are disclosed, it is to be understood that greater than 10 and 15, greater than or equal to 10 and 15, less than 10 and 15, less than or equal to 10 and 15, equal to 10 and 15, and between 10 and 15 are considered to be disclosed. It is also to be understood that each number between two specific numbers is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0093] While various exemplary embodiments have been described above, any of several modifications may be made to the various embodiments without departing from the scope of the invention as set forth in the claims. For example, in alternative embodiments, the order in which various described method steps are performed may often be changed, and in other alternative embodiments, one or more method steps may be skipped entirely. Optional features of the various device and system embodiments may be included in some embodiments but not in other embodiments. Therefore, the above description is primarily for illustrative purposes and should not be construed as limiting the scope of the invention as set forth in the claims.

[0094] The examples and illustrations contained herein show, by way of example, and not limitation, specific embodiments in which the subject matter may be practiced. As noted above, other embodiments may be utilized and derived, whereby structural and logical substitutions and changes may be made without departing from the scope of the present disclosure. Such embodiments of the present subject matter may be individually or collectively referred to by the term "invention" merely for convenience of description, and without any intention to intentionally limit the scope of this application to a single invention or inventive concept when, in fact, multiple inventions or inventive concepts are disclosed. Thus, although specific embodiments have been shown and described herein, any configuration calculated to achieve the same purpose may be substituted for the specific embodiments shown. The present disclosure is intended to cover all adaptations or variations of the various embodiments. Combinations of the above-described embodiments with other embodiments not specifically described herein will become apparent to those skilled in the art upon reviewing the above description. [Explanation of symbols]

[0095] 101 Nerve Cuff 103 Conductor 105 Housing 107 Amputee 131 Controller 231 Controller 241 Control Device 251 Implants 261 Remote Server 270A Neuromodulation System 271 Neuromodulators 272 Pulse Profile Generation Engine 274 Cross-section Estimation Engine 276 Input / Output Engine 277 Impedance Sensing Engine 278 Pulse Generator 280 data stores 282 Datastore 300 System 501 Target Nerve

Claims

1. 1. A system for applying a radiofrequency nerve block, comprising: a nerve cuff comprising one or more electrodes configured to at least partially surround a region of a nerve; a pulse generator configured to generate a radio frequency signal having a pulse profile; and 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 impedance measured from the one or more electrodes, wherein the controller is configured to drive the pulse generator to deliver the radiofrequency signal having the pulse profile from the one or more electrodes.

2. 10. The system of claim 1, further comprising a memory accessible by the controller, the memory 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.

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

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

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

7. 10. The system of claim 1, wherein the controller is an external controller that communicates wirelessly 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 from an indication of the cross-sectional area received by the controller.

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

10. The normalized therapeutic dose value is 0.1 μC / phase / cm ２ ~5μC / phase / cm ２ The system of claim 1 , wherein:

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

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

13. The system of claim 1 , further comprising a lead 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. 1. A system for applying a radiofrequency nerve block, comprising: an implantable nerve cuff comprising one or more electrodes, the nerve cuff configured to at least partially surround a region of a nerve; a pulse generator configured to generate a radio frequency signal having a pulse profile; a memory that stores a normalized therapeutic dose value and an indication of a cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff; a controller configured to determine the pulse profile based on the normalized therapeutic dose value, the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff, and impedance measured from the one or more electrodes, wherein the controller is configured to drive the pulse generator to deliver the radiofrequency signal having the pulse profile from the one or more electrodes.

16. 1. A method of administering a radiofrequency nerve block to treat pain, 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 impedance values ​​from one or more of the electrodes; determining, in a controller, a pulse profile based on a normalized therapeutic dose value, the cross-sectional area of ​​the region of the nerve at least partially surrounded by the nerve cuff, and the impedance value; applying a radio frequency signal having the pulse profile to the nerve; A method comprising:

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

18. 17. The method of claim 16, wherein the high frequency signal has a frequency of about 1 kHz or greater.

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

20. The normalized therapeutic dose value is 0.1 μC / phase / cm ２ ~5μC / phase / cm ２ 17. The method of claim 16, wherein:

21. The normalized therapeutic dose value is 0.5 μC / phase / cm ２ ~4μC / phase / cm ２ 17. The method of claim 16, wherein:

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

23. 17. The method of claim 16, wherein determining the indicator of the cross-sectional area of ​​the region of the nerve comprises measuring a circumference or diameter of the region of the nerve that is at least partially surrounded by the nerve cuff or that will be at least partially surrounded by the nerve cuff.

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

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

26. 17. The method of claim 16, wherein applying the radiofrequency signal comprises applying the radiofrequency signal for a treatment period greater than 10 minutes.

27. 1. A method of administering a radiofrequency nerve block to treat pain, comprising: determining or receiving, at a controller of a nerve stimulation device coupled to a nerve cuff comprising one or more electrodes at least partially around a nerve of the patient, a cross-sectional area of ​​a region of the nerve of the patient at least partially surrounded by the nerve cuff; determining impedance values ​​from one or more of the electrodes; In the controller, 0.1 μC / phase / cm ２ ~5μC / phase / cm ２ determining a pulse profile based on the normalized therapeutic dose value of the pulse profile, the cross-sectional area of ​​the region of the patient's nerve at least partially surrounded by the nerve cuff, and the impedance value; applying a radio frequency signal having the pulse profile to a nerve of the patient; A method comprising:

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