Reducing inductance using closed loop techniques when treating subject using alternating electric field

Abstract

A subject can be treated with an alternating electric field (e.g., a TT field) by applying the alternating electric field to a target area and measuring neurological or muscular activity resulting from the subject's body in response to the application of the alternating electric field. The treatment process is then modified based on the measured neurological or muscular activity to reduce or eliminate inductance. The neural or muscular activity may be, for example, neural activity measured based on an electrically evoked compound action potential (ECAP). In some embodiments, the modification is performed by adjusting the amplitude or frequency of the alternating electric field. In other embodiments, the modification is performed by applying an electrical signal to the subject's body, where the electrical signal is configured to reduce inductance.

Description

Technical Field

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 355,871, filed on June 27, 2022, the entire contents of which are incorporated herein by reference. Background Art

[0002] Tumor Treating Field (TT Field) therapy is a proven tumor treatment approach that uses alternating electric fields with frequencies between 50 kHz and 1 MHz (e.g., 150-200 kHz). In the system, the TT field is delivered to the patient via four transducer arrays 21-24, which are placed on the patient's skin near the tumor (e.g., Figure 1 As shown, for people with glioblastoma). The transducer arrays 21-24 are arranged in two pairs, and each transducer array is connected to an AC signal generator via a multi-wire cable. The AC signal generator (a) sends AC current for 1 second through the front / rear paired transducer arrays 21, 22, which induces an electric field having a first direction through the tumor; then (b) sends AC current for 1 second through the left / right paired arrays 23, 24, which induces an electric field having a second direction through the tumor; then steps (a) and (b) are repeated during treatment. Each transducer array 21-24 includes a plurality (e.g., between 9 and 20) of capacitively coupled electrode elements, each electrode element having a conductive substrate with a dielectric layer arranged thereon.

[0003] AC electric fields can also be used to treat medical conditions other than tumors. For example, as described in U.S. Pat. No. 10,967,167 (incorporated herein by reference in its entirety), AC electric fields can be used to increase the permeability of the blood-brain barrier (BBB), allowing, for example, chemotherapeutic drugs to reach the brain. Summary of the invention

[0004] One aspect of the present application relates to a first method of treating a target area of ​​a subject's body with an alternating electric field. The first method includes applying an alternating electric field to the target area during a treatment process; measuring nerve or muscle activity generated by the subject's body in response to the application of the alternating electric field; and modifying the treatment process based on the measured nerve or muscle activity. The frequency of the alternating electric field is between 50 kHz and 1 MHz.

[0005] In some instances of the first method, the nerve or muscle activity includes nerve activity and the nerve activity is measured using a passive array of ECAP electrodes. In some instances of the first method, the nerve or muscle activity includes muscle activity and the muscle activity is measured using electromyography. In some instances of the first method, the nerve or muscle activity includes muscle activity and the muscle activity is measured by mechanically sensing a muscle twitch.

[0006] In some instances of the first method, the modification includes adjusting the amplitude of the AC electric field applied to the target area based on the measured neural or muscle activity. In some instances of the first method, the modification includes reducing the amplitude of the AC electric field applied to the target area when the measured neural or muscle activity indicates that inductance is expected. In some instances of the first method, the modification includes increasing the amplitude of the AC electric field applied to the target area when the measured neural or muscle activity indicates that the amplitude can be increased without causing inductance. In some instances of the first method, the modification includes adjusting the frequency of the AC electric field applied to the target area based on the measured neural or muscle activity. In some instances of the first method, the modification includes increasing the frequency of the AC electric field applied to the target area when the measured neural or muscle activity indicates that inductance is expected.

[0007] In some instances of the first method, the modifying comprises applying an electrical signal to the subject's body during each of a plurality of time intervals during the treatment process. In these instances, the electrical signal is configured to reduce inductance when an alternating electric field is applied during the treatment process, and a determination of when to apply the electrical signal is based on measured nerve or muscle activity. Optionally, in these instances, the determination of when to apply the electrical signal is based on when the measured nerve or muscle activity indicates that inductance is expected. Optionally, in these instances, the electrical signal comprises a sequence of at least 10 pulses.

[0008] Another aspect of the present application relates to a first apparatus for treating a target area of ​​a subject's body with an alternating electric field. The first apparatus includes an AC voltage generator and a controller, the AC voltage generator having an AC output and at least one control input, the AC output operating at a frequency between 50 kHz and 1 MHz. The controller is configured to (a) receive a signal from at least one sensor that measures nerve or muscle activity generated by the subject's body in response to application of the alternating electric field, and (b) modify a treatment process based on the measured nerve or muscle activity.

[0009] In some embodiments of the first device, at least one sensor includes a set of ECAP electrodes, and the controller is configured to receive signals representing neural activity from the set of ECAP electrodes. In some embodiments of the first device, at least one sensor includes a set of electromyography electrodes, and the controller is configured to receive signals representing muscle activity from the set of electromyography electrodes. In some embodiments of the first device, at least one sensor includes an accelerometer, and the controller is configured to receive signals representing muscle activity from the accelerometer.

[0010] Some embodiments of the first device further include at least one first electrode element configured to be positioned on or within the body of the subject and at least one second electrode element configured to be positioned on or within the body of the subject. In these embodiments, the AC output is applied between the at least one first electrode element and the at least one second electrode element.

[0011] In some embodiments of the first device, the controller is programmed to send a signal to at least one control input causing the AC voltage generator to adjust the amplitude of the AC output based on the measured nerve or muscle activity. In some embodiments of the first device, the controller is programmed to send a signal to at least one control input causing the AC voltage generator to reduce the amplitude of the AC output when the measured nerve or muscle activity indicates that inductance is expected. In some embodiments of the first device, the controller is programmed to send a signal to at least one control input causing the AC voltage generator to increase the amplitude of the AC output when the measured nerve or muscle activity indicates that the amplitude can be increased without causing inductance. In some embodiments of the first device, the controller is programmed to send a signal to at least one control input causing the AC voltage generator to adjust the frequency of the AC output based on the measured nerve or muscle activity. In some embodiments of the first device, the controller is programmed to send a signal to at least one control input causing the AC voltage generator to reduce the frequency of the AC output when the measured nerve or muscle activity indicates that inductance is expected.

[0012] Some embodiments of the first apparatus further include a signal generator that generates an electrical signal configured to reduce inductance when the alternating electric field is applied to the subject's body. In these embodiments, the controller is programmed to activate the signal generator based on the measured nerve or muscle activity.

[0013] Some embodiments of the first apparatus further include a signal generator that generates an electrical signal configured to reduce inductance when an alternating electric field is applied to the subject's body. In these embodiments, the controller is programmed to activate the signal generator based on the measured nerve or muscle activity, and the decision to activate the signal generator is based on when the measured nerve or muscle activity indicates that inductance is expected. Optionally, in these embodiments, the electrical signal includes a sequence of at least 10 pulses.

[0014] Some embodiments of the first device further include: a signal generator that generates an electrical signal configured to reduce inductance when an alternating electric field is applied to the body of a subject; at least one first electrode element configured to be positioned on or in the body of the subject; at least one second electrode element configured to be positioned on or in the body of the subject; a third electrode element configured to be positioned on or in the body of the subject; and a fourth electrode element configured to be positioned on or in the body of the subject. In these embodiments, the controller is programmed to activate the signal generator based on the measured neural or muscle activity. The AC output is applied between the at least one first electrode element and the at least one second electrode element. The electrical signal is applied between the third electrode element and the fourth electrode element. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 Depicted is how the transducer array is positioned for treating glioblastoma using alternating electric fields.

[0016] Figure 2 An apparatus for treating a target area of ​​a subject's body with an alternating electric field that reduces or eliminates inductance is depicted.

[0017] Figure 3 A method of treating a target area of ​​a subject's body with an alternating electric field is described.

[0018] Figure 4 Another apparatus for treating a target area of ​​a subject's body with an alternating electric field that reduces or eliminates inductance is depicted.

[0019] Figure 5 Another method of treating a target area of ​​a subject's body with an alternating electric field is depicted.

[0020] Various embodiments are described in detail below with reference to the drawings, wherein like reference numerals represent like elements. DETAILED DESCRIPTION

[0021] When using AC electric field to treat subjects, higher amplitude is closely related to higher therapeutic efficacy. However, as the amplitude of the AC electric field increases, and / or as the frequency of the AC electric field decreases (e.g., to around 100kHz), some subjects experience inductive effects when the AC electric field switches direction. This inductance can be, for example, a sense of vibration, paresthesia and / or a sense of twitching or contraction of muscle fibers, or light flashes (phosphenes) in the eyes. These sensations may prevent some subjects from continuing to use AC electric fields for treatment. Inductance is believed to originate from the interaction between the AC electric field and nerve cells or fibers (i.e., neurons or axons) located near or adjacent to the transducer array.

[0022] The embodiments described below determine when inductance occurs or is about to occur based on measured nerve or muscle activity generated by the subject's body in response to application of an alternating electric field. The treatment process is then modified based on the measured nerve or muscle activity to improve inductance.

[0023] Some approaches to determining that inductance is occurring or about to occur are based on measured neural activity. During certain types of electrical stimulation of biological tissue, electrically evoked compound action potentials (ECAPs) represent approximately synchronized discharges of a population of electrically stimulated nerve fibers. After an electrical signal of sufficient energy is applied to activate the nerve fibers, fibers of different diameters and different locations are activated at approximately the same time (e.g., within a few milliseconds), and their action potentials (APs) propagate to the vicinity of the recording electrode at different speeds. In addition, different nerve fibers of different diameters have different activation thresholds and conduction velocities, transmitting different signals, such as sensory types of signals (vibration, temperature, hair movement, muscle contraction, joint position, etc.).

[0024] It turns out that ECAPs, which are related to inductance, can be measured using a set of electrodes positioned on a subject's skin. These electrodes detect the composite sum of individual APs that arrive at approximately the same time, which appears as a curve of given amplitude and duration.

[0025] Combine the following Figure 2-Figure 5 The described embodiments rely on using the ECAP signals received by such electrodes to detect or predict whether a subject may be experiencing inductance and / or approaching a threshold beyond which inductance is expected to occur, and modifying the course of treatment to improve inductance. One way to modify the course of treatment is to adjust the amplitude of the AC electric field to improve inductance. Another way to modify the course of treatment is to adjust the frequency of the AC electric field.

[0026] Yet another way to modify the course of treatment is to apply a signal designed to block the activation of fibers that produce inductance. For example, a signal that increases the threshold of the inductance signal conducting nerves allows a higher amplitude treatment signal to be applied without causing inductance. Blocking the propagation of the inductance signal before it reaches the brain will also allow the use of higher treatment amplitudes.

[0027] Combine the following Figure 2-Figure 5 The described embodiments use ECAP as feedback to modify the AC electric field, for example, to improve treatment efficacy or reduce adverse side effects, ie, "closing the loop" of the treatment procedure. The closed loop techniques described herein may also be referred to as adaptive control techniques or adaptive delivery techniques.

[0028] Figure 2An apparatus for treating a target area of ​​a subject's body with an alternating electric field that avoids or improves inductance by measuring neural activity using an ECAP and modifying the course of treatment based on the measured neural activity is depicted. Figure 2 Embodiments include an AC voltage generator 40 that generates an AC output having a frequency between 50 kHz and 1 MHz (e.g., 50-500 kHz, 75-300 kHz, or 150-250 kHz). The AC voltage generator 40 has at least one control input that can be used, for example, to control the output amplitude of the AC voltage generator 40. The frequency of the AC voltage generator 40 will depend on the type of treatment. For example, to treat a tumor using a TT field, the frequency can be between 150 and 200 kHz. Alternatively, to increase the permeability of the subject's blood-brain barrier, the frequency can be between 50 kHz and 200 kHz (e.g., 100 kHz).

[0029] exist Figure 2 In the example shown, a set of first electrode elements 45L is positioned on the left side of the target area on the subject's body (e.g., on shaved skin), and a set of second electrode elements 45R is positioned on the right side of the target area on the subject's body. In an alternative embodiment, the first set of electrode elements 45L and the second set of electrode elements 45R can be implanted in the subject's body (e.g., just below the skin) on the left and right sides of the target area, respectively. When the AC voltage generator 40 applies a voltage between the electrode elements 45L and the electrode elements 45R, an alternating electric field having field lines extending generally from right to left is induced through the target area. The frequency of the alternating electric field will match the frequency of the AC voltage generator 40. The electrode elements 45L / 45R can be capacitively coupled electrode elements or conductive electrode elements.

[0030] In addition to the electrode elements 45L / 45R for inducing an AC electric field in the target area, a separate group of electrodes 55 is provided to determine whether the subject may be experiencing induction or induction is about to occur. More specifically, a first group of ECAP electrodes 55 configured to pick up ECAP signals is positioned near a group of first electrodes 45L, and a second group of ECAP electrodes 55 configured to pick up ECAP signals is positioned near a group of second electrodes 45R. The first group of ECAP electrodes 55 and the second group of ECAP electrodes 55, respectively positioned on the left and right sides, can both be electrode passive arrays.

[0031] The signals from these ECAP electrodes 55 (which may be, for example, on the order of 0.2-2 mV) are received by the ECAP measurement system 50, which measures the ECAP on the left and right sides of the subject's body based on the signals from the ECAP electrodes 55 positioned on the left and right sides, respectively. The ECAP measurement system 50 processes these signals (e.g., using an amplifier and an analog-to-digital converter) and forwards the resulting data to the controller 30. In this way, the ECAP generated by each side of the subject's body in response to the application of the alternating electric field is measured.

[0032] Because the ECAP associated with inductance is measured using the ECAP electrodes 55 and the ECAP measurement system 50, and these measurements are reported to the controller 30, the controller 30 is able to determine whether the subject may be experiencing inductance and / or approaching a threshold beyond which inductance is expected. The controller 30 can then modify the treatment process based on the measured ECAP. The modification based on the measured ECAP can be, for example, adjusting the amplitude or frequency of the AC electric field applied to the target area based on the measured ECAP.

[0033] Figure 3 An example of a method for treating a target area of ​​a subject's body with an alternating electric field is depicted, wherein the controller 30 modifies the treatment process based on the measured ECAP. In S20, an alternating electric field is applied to the target area during the treatment process (e.g., when the AC voltage generator 40 applies an AC output to the electrodes 45L / 45R). In S30, the electrically induced compound action potential (ECAP) generated by the subject's body in response to the application of the alternating electric field in S20 is measured. The measurement is implemented using the ECAP electrode 55 and the ECAP measurement system 50 described above, and the measurement results are reported to the controller 30. In S40, the controller 30 determines whether inductance is expected based on the measured ECAP. If inductance is expected, the method continues at S45, wherein the controller 30 sends commands to the control input of the AC voltage generator 40, which cause the AC voltage generator 40 to reduce its output amplitude. The reduction in amplitude will improve the inductance.

[0034] If no inductance is expected, the method proceeds to S50, where the controller 30 determines whether the amplitude can be increased without causing inductance based on the measured ECAP. If the result is yes, the method continues at S55, where the controller 30 issues a command to the AC voltage generator 40, causing the AC voltage generator to increase its output amplitude (provided that this does not cause any of the electrodes 45 to overheat). This increase in amplitude will improve the efficacy of the alternating electric field treatment without causing discomfort to the subject. If the result in S50 is no, the method continues at S56. Figure 3 method to restart.

[0035] In many anatomical locations, it is preferred to use an electric field whose orientation alternates between different directions. In these locations, additional sets of electrode elements 45 ( Figure 2 The AC voltage generator 40 is preferably configured to alternate between: (a) applying a voltage between the left electrode element 45L and the right electrode element 45R and (b) applying a voltage between the front electrode element and the rear electrode element. The AC voltage generator 40 can switch between these two states every 1 second or at different intervals (e.g., between 50ms and 10s). Therefore, the orientation of the electric field in these embodiments will alternate back and forth between the left / right and front / back directions.

[0036] In these embodiments where additional groups of electrode elements 45 are positioned on other sides of the target area, corresponding additional groups of ECAP electrodes 55 should be positioned near the additional electrode elements 45 to determine whether the subject may be experiencing inductance or an inductance is about to occur. The controller 30 processes the signals from these additional groups of ECAP electrodes 55 as described above for the left and right groups of ECAP electrodes 55 (e.g., by reducing the voltage amplitude applied to the additional groups of electrode elements 45 when inductance is expected at those electrode elements 45).

[0037] Adjust the output amplitude of the AC voltage generator 40 (as described above in conjunction with Figure 2-Figure 3 The above-described method is not the only way to avoid or improve inductance. On the contrary, because lower frequencies generally cause more inductance than higher frequencies, another way to avoid or improve inductance is that whenever the controller 30 determines that inductance is occurring or is about to occur, the controller 30 sends a command to the AC voltage generator 40 to increase the frequency of the AC electric field.

[0038] Figure 4-Figure 5 Another approach to treating a target area of ​​a subject's body with an alternating electric field is depicted, avoiding or improving inductance by measuring neural activity using an ECAP. Notably, these embodiments avoid or improve inductance by applying additional electrical signals to the subject's body. These additional electrical signals are configured to reduce the subject's sensation when the alternating electric field is applied during the treatment process.

[0039] As noted above, the inductance is believed to originate from the interaction between the AC electric field and the neural cells or fibers (i.e., neurons or axons) located near or adjacent to the transducer array. Without being bound by this theory, it is believed that Figure 4-Figure 5The additional electrical signal applied in the embodiments reduces the subject's sensation by increasing the action potential threshold of the relevant nerve cells or otherwise blocking their activation, such as by interfering with the operation of ion channel gates or by exerting similar effects on axonal regions near the point of AP generation to hinder AP propagation.

[0040] The electrical signal that reduces the subject's sensation may include a sequence of at least 10 pulses. In some embodiments, each such electrical signal may include a sequence of at least 12 pulses, at least 15 pulses, or at least 20 pulses, because experiments have shown that different nerve fibers respond to different blocking signal designs. For example, it has been shown that the activation threshold of the median nerve and the sural nerve increases significantly in response to a sequence of 10 or more pulses, but not in response to a single pulse. In some embodiments, each electrical signal may include a sequence of 10 to 15 pulses or a sequence of 10 to 20 pulses. In some embodiments, each of these pulses has a width of at least 100 μs. In some embodiments, each of these pulses has a width of at least 150 μs, 200 μs, 250 μs, 300 μs, or 400 μs. In some embodiments, each of these pulses has a width of 100 μs to 500 μs, 100 μs to 250 μs, or 100 μs to 200 μs. In some embodiments, each of these pulses has a width of at least 20 ms, 50 ms, or 100 ms. In some embodiments, each of these pulses has a width of 20-50 ms, 50-100 ms, or 100-200 ms.

[0041] In some embodiments, the sequence of pulses lasts at least 100 ms. In some embodiments, the sequence of pulses lasts at least 150 ms, 200 ms, 250 ms, 300 ms, or 400 ms. In some embodiments, the sequence of pulses lasts from 100 ms to 500 ms, from 100 ms to 250 ms, or from 100 ms to 200 ms. In some embodiments, the pulses are configured to provide a charge balancing waveform.

[0042] It has been demonstrated that when the applied block sequence lasts for a few hundred milliseconds, the threshold increase for the median and sural nerves lasts longer, and for some block protocols, the threshold increase can last for several minutes or even tens of minutes. Longer time periods of threshold increase are desirable because the block signal does not need to be applied as frequently, thereby simplifying treatment and reducing energy requirements.

[0043] The electrical signal that reduces the subject's sense can also have a frequency between 4kHz and 30kHz. Optionally, the electrical signal can have a frequency between 0.1 and 30Hz (e.g., 0.1-1Hz or 1-10Hz). In certain embodiments, the electrical signal has a frequency between 1Hz and 2Hz. In certain embodiments, the electrical signal has an amplitude of 0.5-10mA. In certain embodiments, the amplitude is 0.5 to 1mA, 1 to 2mA or 2 to 10mA. In certain embodiments, the electrical signal has a duration between 1 and 60s. In certain embodiments, the electrical signal has a duration less than 10s (e.g., between 1 and 10s, between 1 and 2s, between 2 and 5s or between 5 and 10s).

[0044] The electrical signal that reduces the subject's sensation may also have a frequency between 0.25 and 10 Hz (e.g., between 0.5 and 5 Hz, or between 1 and 2 Hz). In these embodiments, the electrical signal may optionally be offset from zero amplitude. In these embodiments, each of the electrical signals may have a duration between 100 ms and 30 s, between 200 ms and 20 s, between 500 ms and 20 s, or between 500 ms and 10 s.

[0045] The electrical signal that reduces the subject's sensation may be below the threshold of the nerve fibers that produce the unwanted sensation, or it may be above the threshold. In some embodiments, the electrical signal is initially applied below the threshold of the nerve fibers that produce the unwanted sensation, and after the initial electrical signal causes the action potential threshold of the relevant nerve cells to increase, their amplitude subsequently increases to above the threshold. The applied electrical signal may be below the threshold of the 7-15 μm Aβ nerve fibers that produce at least one of vibration and paresthesia, or it may be above the threshold. In some embodiments, the electrical signal is initially applied below the threshold of the 7-15 μm Aβ nerve fibers that produce at least one of vibration and paresthesia, and after the initial electrical signal has caused the action potential threshold of the relevant nerve cells to increase, its amplitude subsequently increases to above its original threshold. The electrical signal is preferably always below the threshold of the nerve fibers that produce at least one of muscle twitches and contractions.

[0046] Figure 4 Another device for treating a target area of ​​a subject's body with an alternating electric field is depicted, the device relying on an ECAP to reduce or eliminate inductance. Figure 4 The embodiment includes an AC voltage generator 40, which is similar to the above combined Figure 2 The frequency of the AC voltage generator 40 will depend on the type of treatment, as described above in conjunction with Figure 2 As described.

[0047] Figure 4 The embodiment includes a set of first electrode elements 45L and a set of second electrode elements 45R, which are used to induce an alternating electric field in the target area and are similar to the above combined Figure 2 The electrode elements described are numbered accordingly. Figure 4 The embodiment has multiple sets of ECAP electrodes 55, which are similar to the above combined Figure 2 The signals from these ECAP electrodes 55 are received and processed by the ECAP measurement system 50, and the resulting data is forwarded to the controller 30 (e.g., as described above in conjunction with Figure 2 described).

[0048] Because the ECAP associated with inductance is measured using the ECAP electrodes 55 and the ECAP measurement system 50, and these measurements are reported to the controller 30, the controller 30 is able to determine whether the subject may be experiencing inductance and / or approaching a threshold above which inductance is expected. The controller 30 can then modify the course of treatment based on the measured ECAP.

[0049] exist Figure 4 In an embodiment of the present invention, during each of a plurality of time intervals during the treatment process, the treatment process is modified by applying an electrical signal to the subject's body via another set of electrode elements 65 using a signal generator 60. The electrical signal generated by the signal generator 60 is configured to reduce inductance when applying an alternating electric field to the subject's body during the treatment process (e.g., as described above).

[0050] exist Figure 4 In the example shown, the electrode elements 65 are arranged in pairs and are positioned adjacent to and on opposite sides of the corresponding set of electrode elements 45L / 45R. As a result, when an electrical signal is applied between the electrode elements 65, the electrical signal will pass through the skin areas below the electrode elements 45L / 45R. The electrical signal will interact with the nerve fibers in these areas, and this interaction will reduce the inductance during the period when the electrode elements 45L / 45R are active. Note that as used herein, adjacent means nearby; and the word "adjacent" does not require a relationship of contact or abutment.

[0051] The controller 30 decides when the signal generator 60 should apply the electrical signal to the electrode element 65 based on the measured ECAP, and implements the decision by sending appropriate commands to the signal generator 60. For example, the decision when to apply the electrical signal may be based on when the measured ECAP (which is measured using the ECAP electrode 55 and the ECAP system 50) indicates that inductance is expected.

[0052] Figure 5An example of a method of treating a target area of ​​a subject's body with an alternating electric field is depicted, wherein Figure 4 The controller 30 modifies the treatment process based on the measured ECAP. In S120, an AC electric field is applied to the target area during the treatment process (e.g., when the AC voltage generator 40 applies an AC output to the electrodes 45L / 45R). In S130, the ECAP generated by the subject's body in response to the AC electric field applied in S120 is measured. The measurement is implemented using the ECAP electrodes 55 and the ECAP measurement system 50 described above, and the measurement results are reported to the controller 30. In S140, the controller 30 determines whether inductance is expected based on the measured ECAP. If inductance is expected, the method continues at S160, where the controller 30 sends commands to the control input of the signal generator 60, which cause the signal generator 60 to generate an electrical signal configured to reduce the inductance (e.g., as described above). If no inductance is expected in S140, then the signal generator 60 is controlled to generate an electrical signal configured to reduce the inductance (e.g., as described above). Figure 5 method to restart.

[0053] As above combined Figure 3 As described, it is preferred to use an additional set of electrode elements 45 ( Figure 4 In these cases, each set of electrode elements 45 preferably has its own associated set of ECAP electrodes 55 and its own associated set of electrodes 65, which operate similarly to Figure 4 The corresponding electrodes 55 / 65 depicted in and described above.

[0054] exist Figure 4 In the example shown, electrode element 65 is adjacent to and distinct from electrode element 45. However, in alternative embodiments, a single physical electrode element may be used as more than one of these electrode elements 45, 65 at the same time (e.g., by combining the two signals using superposition and applying the superimposed signal to the single electrode element), or a single physical electrode element may be used as more than one of these electrode elements 45, 65 at different times (e.g., using time division multiplexing).

[0055] Combination of the above Figure 2-Figure 5 The described embodiments rely on a passive array of ECAP electrodes to measure neural activity, based on the theory that neural activity can be used to determine that inductance is occurring or about to occur. However, a variety of alternative approaches can be used instead of the above ECAP-based techniques to determine that inductance is occurring or about to occur.

[0056] An example of an alternative approach uses electromyographic signals to measure muscle activity, based on the theory that muscle activity (e.g., twitching) can indicate that inductance is occurring. In these embodiments, an electromyographic (EMG) signal is obtained using a set of EMG electrodes, preprocessed by an EMG system, and forwarded to a controller (similar to the controller 30 described above, but programmed to interpret EMG signals instead of ECAP signals). Another example of an alternative approach is to use a mechanical sensor (e.g., accelerometer) to measure muscle activity, based on the theory that muscle activity (e.g., twitching) can indicate that inductance is occurring. In these embodiments, a mechanical sensor is used to capture vibration or acceleration signals, preprocessed by an appropriate front end, and forwarded to a controller (similar to the controller 30 described above, but programmed to interpret mechanical events instead of ECAP signals). Other approaches based on measuring nerve or muscle activity can also be used.

[0057] Combined with the above Figure 2 and Figure 4 In the described embodiment, the AC voltage generator 40 generates an AC output with a frequency between 50kHz and 1MHz. When the output signal from the AC voltage generator 40 drives the electrode elements 45L, 45R, an AC electric field with a frequency between 50kHz and 1MHz will be applied to the target area. However, this is not the only way to apply an AC electric field with a frequency between 50kHz and 1MHz to the target area. Instead, alternative approaches to applying a 50kHz-1 MHz AC electric field to the target area can be used.

[0058] One example of such an alternative approach relies on the concept of amplitude modulation (AM). More specifically, when a carrier signal of frequency f1 is AM modulated by a tone signal of frequency f2, the output of the modulator will include frequency components at f1, f1+f2, and f1-f2 (i.e., the original carrier, the sum, and the difference). Thus, if a 10 MHz carrier is AM modulated by a 9.8 MHz tone signal, the output of the modulator will include frequency components at 200 kHz, 10 MHz, and 19.8 MHz. Thus, if the output of the AM modulator is used to drive electrode elements 45L, 45R, the 200 kHz component present in the output of the AM modulator will induce an AC electric field having a frequency of 200 kHz (and additional frequency components in the MHz range) in the target area.

[0059] In this AM modulation-based embodiment, the frequency of the AC electric field applied to the target area can be increased by increasing the carrier frequency or by decreasing the tone frequency based on the measured neural or muscle activity; alternatively, the frequency of the AC electric field applied to the target area can be decreased by decreasing the carrier frequency or by increasing the tone frequency based on the measured neural or muscle activity.

[0060] Although the present invention has been disclosed with reference to certain embodiments, various modifications, changes and variations of the described embodiments are possible without departing from the field and scope of the invention as defined in the appended claims. Therefore, it is intended that the present invention is not limited to the described embodiments, but has the full scope defined by the language of the appended claims and their equivalents.

Claims

1. A method of treating a target area of ​​a subject's body with an alternating electric field, the method comprising: applying an alternating electric field to the target area during the treatment process, wherein the alternating electric field has a frequency between 50 kHz and 1 MHz; measuring neural or muscular activity resulting from said subject's body in response to said application of said alternating electric field; and The course of treatment is modified based on the measured nerve or muscle activity.

2. The method of claim 1, wherein the nerve or muscle activity comprises nerve activity, and wherein the nerve activity is measured using a passive array of ECAP electrodes.

3. The method of claim 1, wherein the neural or muscle activity comprises muscle activity, and wherein the muscle activity is measured using electromyography.

4. The method of claim 1, wherein the neural or muscle activity comprises muscle activity, and wherein the muscle activity is measured by mechanically sensing a muscle twitch.

5. The method of claim 1, wherein the modifying comprises adjusting an amplitude of the alternating electric field applied to the target area based on the measured nerve or muscle activity.

6. The method of claim 1, wherein the modifying comprises reducing the amplitude of the alternating electric field applied to the target area when the measured nerve or muscle activity indicates that inductance is expected.

7. The method of claim 1, wherein the modifying comprises increasing the amplitude of the alternating electric field applied to the target area when the measured nerve or muscle activity indicates that the amplitude can be increased without causing inductance.

8. The method of claim 1, wherein the modifying comprises adjusting a frequency of the alternating electric field applied to the target area based on the measured nerve or muscle activity.

9. The method of claim 1, wherein the modifying comprises increasing the frequency of the alternating electric field applied to the target area when the measured nerve or muscle activity indicates that inductance is expected.

10. The method of claim 1, wherein the modifying comprises applying an electrical signal to the subject's body during each of a plurality of time intervals during the treatment process, wherein the electrical signal is configured to reduce inductance when the alternating electric field is applied during the treatment procedure, and Wherein the decision of when to apply the electrical signal is based on the measured nerve or muscle activity.

11. The method of claim 10, wherein the decision when to apply the electrical signal is based on when the measured nerve or muscle activity indicates that inductance is expected.

12. The method of claim 11, wherein the electrical signal comprises a sequence of at least 10 pulses.

13. An apparatus for treating a target area of ​​a subject's body with an alternating electric field, the apparatus comprising: an AC voltage generator having an AC output and at least one control input, the AC output operating at a frequency between 50 kHz and 1 MHz; as well as A controller configured to (a) receive a signal from at least one sensor that measures neural or muscle activity resulting from the subject's body responding to the application of the alternating electric field, and (b) modify a treatment procedure based on the measured neural or muscle activity.

14. The apparatus of claim 13, wherein the at least one sensor comprises a set of ECAP electrodes, and wherein the controller is configured to receive signals indicative of neural activity from the set of ECAP electrodes.

15. The apparatus of claim 13, wherein the at least one sensor comprises a set of electromyographic electrodes, and wherein the controller is configured to receive signals indicative of muscle activity from the set of electromyographic electrodes.

16. The device according to claim 13, wherein: The at least one sensor comprises an accelerometer, and wherein the controller is configured to receive a signal from the accelerometer indicative of muscle activity.

17. The apparatus of claim 13, further comprising at least one first electrode element configured for positioning on or in the subject's body and at least one second electrode element configured for positioning on or in the subject's body, wherein the AC output is applied between the at least one first electrode element and the at least one second electrode element.

18. The apparatus of claim 13, wherein the controller is programmed to send a signal to the at least one control input causing the AC voltage generator to adjust the amplitude of the AC output based on the measured nerve or muscle activity.

19. The apparatus of claim 13, wherein the controller is programmed to send a signal to the at least one control input causing the AC voltage generator to reduce the amplitude of the AC output when the measured nerve or muscle activity indicates that inductance is expected.

20. The apparatus of claim 13, wherein the controller is programmed to send a signal to the at least one control input causing the AC voltage generator to increase the amplitude of the AC output when the measured nerve or muscle activity indicates that the amplitude can be increased without inducing inductance.

21. The apparatus of claim 13, wherein the controller is programmed to send a signal to the at least one control input causing the AC voltage generator to adjust the frequency of the AC output based on the measured nerve or muscle activity.

22. The apparatus of claim 13, wherein the controller is programmed to send a signal to the at least one control input causing the AC voltage generator to reduce the frequency of the AC output when the measured nerve or muscle activity indicates that inductance is expected.

23. The apparatus of claim 13, further comprising a signal generator that generates an electrical signal configured to reduce inductance when the alternating electric field is applied to the subject's body, Wherein the controller is programmed to activate the signal generator based on the measured nerve or muscle activity.

24. The apparatus of claim 23, wherein the decision to activate the signal generator is based on when the measured nerve or muscle activity indicates that inductance is expected.

25. The apparatus of claim 24, wherein the electrical signal comprises a sequence of at least 10 pulses.

26. The apparatus of claim 23, further comprising: at least one first electrode element and at least one second electrode element, the at least one first electrode element being configured for positioning on or in the body of the subject, the at least one second electrode element being configured for positioning on or in the body of the subject, wherein the AC output is applied between the at least one first electrode element and the at least one second electrode element; as well as A third electrode element and a fourth electrode element, the third electrode element being configured for positioning on or in the subject's body, the fourth electrode element being configured for positioning on or in the subject's body, wherein the electrical signal is applied between the third electrode element and the fourth electrode element.

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