System and method for trans-spinal magnetic stimulation

Abstract

A system for quasi-resonant high-frequency trans-spinal magnetic stimulation for a region of a spine of a subject incudes a signal generator including a bulk capacitor bank (BCB), am H-Bridge in signal communication with the BCB, and a resonant capacitor bank (RCB) in signal communication with the H-bridge. The system further includes a controller in signal communication with the signal generator and configured to: 1) provide pulse sequence having a set of pulse sequence parameters to the signal generator including a pulse frequency configured to enable the RCB to operate in a quasi-resonance mode and 2) to control the H-bridge based on the pulse sequence, wherein the pulse sequence is configured to provide sequence-controlled zero current switching (SCZCS).

Description

MGH 2023-110-02Q&B 125141.04865SYSTEM AND METHOD FOR TRANS-SPINAL MAGNETIC STIMULATIONCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is based on, claims priority to, and incorporates herein by reference in its entirety U.S. Serial No. 63 / 688,805 fded August 29, 2024, and entitled “Trans-Spinal Magnetic Stimulation System for Sciatica."STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] This invention was made with government support under award number 5R01MH111875-04 awarded by the NIH-NIMH National Institute of Mental Health. The government has certain rights in the invention.FIELD

[0003] The present disclosure relates generally to trans-spinal magnetic stimulation (TSMS) and, more particularly, to systems and methods for quasi-resonant high-frequency TSMS.BACKGROUND

[0004] Spinal cord stimulation (SCS) is a state-of- the-art medical procedure used to treat chronic pain when other nonsurgical treatment options fail to provide sufficient relief. For example, chronic back pain after failed back surgery syndrome, complex regional pain syndrome, neuropathy, and certain other types of chronic pain that don't respond well to other treatments. SCS entails the surgical implantation of an electrical stimulator under the lower back skin that delivers small electrical pulses into the spinal cord via thin wires equipped with electrodes positioned at the tip. These pulses disrupt the transmission of pain signals to the brain, potentially altering or blocking nerve activity and thereby diminishing the perception of pain. The perceived effect may include a tingling sensation called paresthesia. Following years of research and technological advancements aimed at improving electrode design for more targeted stimulation, SCS has gained increased acceptance among healthcare providers and patients. In this context, the development of implantable pulse generators (IPGs), which facilitate personalized therapy by allowing adjustments to stimulation parameters such as frequency, amplitude, and pulseMGH 2023-110-02Q&B 125141.04865 width, has also drawn attention. This culminated in the approval of SCS as a treatment for intractable back and leg pain in 1989 by the U.S. Food and Drug Administration (FDA). As research and clinical experience expanded, the indications for SCS went beyond traditional pain conditions, encompassing complex regional pain syndrome, ischemic limb pain, neuropathic pain, and others. In 2015, the FDA also approved the use of high-frequency (HF) SCS at 10 kHz, involving the delivery of electrical pulses that are shorter in duration, lower in amplitude, and do not induce paresthesia. Besides the widely recognized benefits of SCS, the use of this surgical approach has also raised several concerns and issues over the years, primarily because it involves invasive procedures that may result in complications such as infection, lead migration, lead fracture, spinal fluid leakage, and hardware malfunction. Furthermore, the success rates of this treatment vary depending on the specific condition being addressed, individual patient factors and over time the efficacy of SCS may diminish, posing challenges for long-term management. Consequently, there is an urgent need for non-invasive and safer treatment alternatives for spinal cord conditions that are equally selective and effective as SCS.

[0005] Several ways have been explored for non-invasive SCS, including transcutaneous electrical stimulation (TES) and focused ultrasound (FU). TES would require less power but is limited by skin nociceptors’ activation and by current attenuation due to tissue impedance. Preliminary trials have been performed for relief of spasticity in patients with paraplegia, but it was made possible because these patients had a diminished pain perception. Moreover, it is difficult to achieve high levels of stimulation in the target regions of the spinal cord with high spatial resolution. Low-intensity focused ultrasound (LIFU) has been increasingly studied for neuromodulation because it offers several advantages, including spatial resolution and depth penetration. However, there are significant drawbacks, including the difficulty of penetrating the bone without causing substantial heating.SUMMARY

[0006] In accordance with an embodiment, a system for quasi-resonant high-frequency trans- spinal magnetic stimulation for a region of a spine of a subject includes a signal generator including a bulk capacitor bank (BCB), am H-Bridge in signal communication with the BCB, and a resonant capacitor bank (RCB) in signal communication with the H-bridge. The system further includes a controller in signal communication with the signal generator and configuredMGH 2023-110-02Q&B 125141.04865 to: 1) provide a pulse sequence having set of pulse sequence parameters to the signal generator including a pulse frequency configured to enable the RCB to operate in a quasi-resonance mode and 2) to control the H-bridge based on the pulse sequence, wherein the pulse sequence is configured to provide sequence-controlled zero current switching (SCZCS).

[0007] In accordance with another embodiment, a method for quasi-resonant high-frequency trans-spinal magnetic stimulation for a region of a spine of a subject includes receiving, using a signal generator, a pulse sequence having a set of pulse sequence parameters including a pulse frequency configured to enable a resonant capacitor bank (RCB) of the signal generator to operate in a quasi-resonance mode, applying, using the signal generator, a set of driving voltages to an H-bridge of the signal generator, generating, using the signal generator, high frequency current pulses by controlling the H-bridge based on the pulse sequence, wherein the pulse sequence is configured to provide sequence-controlled zero current switching (SCZCS), and applying, using the signal generator, the high frequency current pulses to a TSMS coil.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The present disclosure will hereafter be described with reference to the accompanying drawings, wherein like reference numerals denote like elements.

[0009] FIG. 1 is a block diagram of an example trans-spinal magnetic stimulation (TSMS) system in accordance with an embodiment;

[0010] FIG. 2 is a schematic block diagram of a quasi-resonant high-frequency TSMS system in accordance with an embodiment;

[0011] FIGs. 3A and 3B are perspective views of a figure-8 TSMS coil in accordance with an embodiment;

[0012] FIG. 3C is a cross-sectional view of the figure-8 TSMS coil of FIG. 3A in accordance with an embodiment;

[0013] FIG. 4 is a circuit diagram of an H-bridge of a TSMS signal generator (or stimulator) in accordance with an embodiment;

[0014] FIGs. 5 A and 5B are circuit diagrams of the H-B ridge of FIG. 4 in a) an R-pull up and b) an R-pull down mode in accordance with an embodiment;

[0015] FIG. 6 shows a graph of an example output voltage and output current of the H-Bridge of FIG. 4 in accordance with an embodiment;MGH 2023-110-02Q&B 125141.04865

[0016] FIG. 7 illustrates a method for quasi-resonant high-frequency TSMS in accordance with an embodiment; and

[0017] FIG. 8 is a block diagram of an example computer system in accordance with an embodiment.DETAILED DESCRIPTION

[0018] Trans-spinal magnetic stimulation (TSMS) has been explored as a promising alternative solution for treatment of chronic pain. Unlike SCS, TSMS is non-invasive and targets specific regions of the spinal cord using the electromagnetic induction principle (Faraday’s law) to induce an electric field that is capable of firing neuronal tissue beneath the coil. Basically, a magnetic field is generated by a coil positioned externally on the patient’s back. This targeted stimulation can be used, for example, to modulate neural activity associated with chronic back and leg pain.

[0019] FIG. 1 is a block diagram of an example trans-spinal magnetic stimulation (TSMS) system in accordance with an embodiment. A TSMS system 100 may include an input 102, a controller 104, a signal generator 106 (e.g., a signal stimulator or driver) and an electromagnetic coil 108. The controller 104 is in communication with the signal generator 106 and is configured to direct the signal generator 106 to provide various signals to the electromagnetic coil 108. In some implementations, the controller 104 may be any general-purpose computing system or device, such as a personal computer, workstation, cellular phone, smartphone, laptop, tablet, or the like. As such, the controller 104 may include any suitable hardware and components designed or capable of carrying out a variety of processing and control tasks, including steps for optimizing and directing the signal generator 106 to provide various signals to the electromagnetic coil 108. For example, the controller 104 may include a programmable processor or combination of programmable processors, such as central processing units (CPUs), graphics processing units (GPUs), and the like. In some implementations, the controller 104 may be configured to execute instructions stored in a non-transitory computer readable-media. In this regard, the controller 104 may be any device or system designed to integrate a variety of software, hardware, capabilities and functionalities. Alternatively, and by way of particular configurations and programming, the controller 104 may be a special-purpose system or device. For instance, such special-purpose system or device may include one or more dedicated processing units or modules that may be configured (e.g., hardwired, or pre-programmed) to carry out steps, in accordance with aspects of the present disclosure. In some embodiments,MGH 2023-110-02Q&B 125141.04865 controller 104 can be a computer system such as computer system 800 described below with respect to FIG. 8.

[0020] The electromagnetic coil 108 is positioned proximate to and over the subject, for example, the spine (not shown) of a subject 112. In some embodiments, the electromagnetic coil 108 can include a figure-8 TSMS coil as described further below with respect to FIG. 3 below. The electromagnetic coil 108 may be insulated using known methods and materials. In some embodiments, the electromagnetic coil 108 may be positioned and held in place over the subject 112 by an operator or using a mechanical arm (not shown). The position of the coil 108 over the subject 112 is selected to target and stimulate a specific area of the spine. Accordingly, the electromagnetic coil 108 may be positioned over the region to be stimulated in the spine. Signal generator 106 can be configured to generate and deliver electrical signals (e.g., electric current or voltage signals) to the electromagnetic coil 108. In some embodiments, the signal generator 106 may be based on capacitor banks, power amplifiers, or H-bridge type designs. The electric current delivered from the signal generator 106 and flowing through the electromagnetic coil 108 generates a magnetic field 114. The magnetic field 114 (e.g., magnetic pulses) passes through the subject 112 and into the spine of the subject 112 and causes or induces electrical currents that stimulate nerve cells in the targeted region of the spine. Different coil types may be used for electromagnetic coil 108 to elicit different magnetic field patterns. The strength and distribution of the time-varying magnetic fields 114 may be dependent on both the geometry and the amount of current traveling through the electromagnetic coil 108. The induced electric field 114 may also be dependent on fixed variables unique to individual subjects such as the geometry and electrical properties of anatomies in and around the brain. The induced electric field may also be triggered by the user or by the controller 104 based on external data such as magnetic resonance imaging (MRI) data, or the like.

[0021] In some embodiments, the signals generated by the signal generator 106 and provided to the electromagnetic coil 108 may be in the form of a pulse sequence having a plurality of pulses. The power, amplitude, duration, shape, and frequency of the pulses may be selected to achieve a desired level of or depth of stimulation, as well as to optimize heat or magnetic forces induced in the electromagnetic coil 108. An operator may select the specific type and characteristics of the electric pulses to be generated by the signal generator 106 using an input (or user interface) 102MGH 2023-110-02Q&B 125141.04865 coupled to the controller 104. The input 102 can be, for example, a keyboard, a mouse, a touch screen, etc.

[0022] As mentioned, TSMS uses magnetic pulses to stimulate the spinal cord for potential therapeutic benefits. For example, a TSMS system can use electromagnetic pulses to non- invasively deliver a rapidly pulsed magnetic field that can depolarize neurons either in the central nervous system or in the peripheral nervous system. However, current systems are limited and typically cannot produce high frequency pulses (e.g., at or above 10 kHz). The present disclosure described systems and methods for quasi-resonant high-frequency TSMS for spinal cord magnetic neuromodulation. In some embodiments, the quasi-resonant high frequency TSMS system can be based on pulse width modulation (PWM) and can include a signal generator having a bulk capacitor bank (BCB), a an H-bridge formed using IGBT transistors, and a resonant capacitor bank (RCB) that are configured to generate high frequency current pulses that can be applied to a TSMS coil. A pulse sequence for the signal generator (or stimulator) can be configured to control the H-bridge to advantageously provide zero-current switching (e.g., sequence-controlled-zero current switching (SCZCS). The SCZCS enables transitions at zero current and can reduce or minimize switching losses. In addition, the RCB can advantageously be configured to operate in a quasi-resonance mode so that the capacitance of the RCB cancels the inductance of the TSMS coil. Accordingly, significantly lower voltage can be used on the BCB and the H-bridge than would otherwise be required to generate the high frequency pulses and the lower voltages can reduce the size and cost of these components and can enable the use of a high-inductance TSMS coil. The disclosed system and metho can drive TSMS coils at a lower voltage than traditional transcranial magnetic stimulators (TMS). In addition, the disclosed system and method can allow for operation frequencies well above that of current TMS systems (e.g., 2.5 kHz). In some embodiments, the signal generator (or stimulator, or driver) for the disclosed quasi-resonant high frequency TSMS system can work at high frequency such as, up to 100 kHz. The disclosed systems and methods can provide improved efficiency, minimal energy loss, and capacitor charge conservation.

[0023] FIG. 2 is a schematic block diagram of a quasi-resonant high-frequency TSMS system in accordance with an embodiment. The system can include an input 202, a controller 204, a signal generator (or signal stimulator or driver) 206, and a TSMS coil 208. In some embodiments, the quasi-resonant high frequency TSMS system can be used for non-invasive chronic painMGH 2023-110-02Q&B 125141.04865 management for a subject, for example, the system can be used to target specific regions of the spinal cord to treat and manage chronic back pain, chronic leg pain, sciatica, neuropathy, etc. The signal generator 206 can include a bulk capacitor bank (BCB) 210, an H-bridge 212, a resonant capacitor bank (RCB) 214, a power supply 216, and pulse commands 218. In FIG. 2, the system for quasi-resonant high-frequency TSMS is simplified to show some key components, however, implementation can involve additional components. For example, in some embodiments, the signal generator 206 can include additional components such as digital and analog input / output, a waveform generator, attenuators, etc. While FIG. 2 illustrates various components of the system for quasi-resonant high-frequency TSMS, other embodiments of the system can vary the arrangement, communication paths, and specific components of the system.

[0024] As discussed above with respect to FIG. 1, the controller 204 can be in communication with the signal generator (or stimulator) 206 to direct the signal generator 206 to provide various signals to the TSMS coil 208, for example, electric signals (e.g., electric current or voltage signals), to cause the TSMS coil 208 to generate a magnetic field. As mentioned above, the controller 204 can be a computing system such as, for example, computing system 800 discussed below with respect to FIG. 8. In some embodiments, the signals generated by the signal generator 206 and provided to the electromagnetic coil 108 may be in the form of a pulse sequence having a plurality of pulses. The power, amplitude, duration, shape, and frequency of the pulses may be selected to achieve a desired level of or depth of stimulation, as well as to optimize heat or magnetic forces induced in the electromagnetic coil 108. An operator may select a set of pulse sequence parameters including parameters of the electric pulses to be generated by the signal generator 206 using an input (or user interface) 202 coupled to the controller 204. As mentioned, the input 202 can be, for example, a keyboard, a mouse, a touch screen, etc. In some embodiments, the parameters of the pulse sequence (and the pulses to be generated by the signal generator) can include, for example, the pulse frequency (or pulse switching frequency), timing, waveform shape, voltage, etc.

[0025] The TSMS coil 208 is an electromagnetic coil and can be, for example, a figure 8 coil configured for use at high frequency (e.g., up to 100 kHz). In some embodiments, the figure-8 coil can be a low resistance, low inductance, high turn-count coil and optimized for selective stimulation and scalability. FIGs. 3A and 3B are perspective views of a figure-8 TSMS coil in accordance with an embodiment and FIG. 3C is a cross-sectional view of the figure-8 TSMS coilMGH 2023-110-02Q&B 125141.04865 of FIG. 3 A in accordance with an embodiment. The figure-8 coil 302 can be configured with a low resistance and smaller diameter to allow for more focal stimulation. In some embodiments, the coil 302 can be formed using ribbon copper strips with a rectangular cross section 320 (shown in FIG. 3C) which can result in an ultra-low resistance. The ribbon copper strips with rectangular cross-section 320 can be wrapped together to form two circular coils 304, 306, each with a number of turns. In FIG. 3A, the number of turns of one of the two circular coils is illustrated with arrow 308. In one example, each circular coil 304, 306 can have 14 turns. The rectangular cross-section 320 of the coil 302 can advantageously utilize all available space in each turn to deliver current, without any voids, which provides increased efficiency. By using ribbon wire for coil 302, a larger cross-sectional area of the coil 302 can advantageously be achieved by increasing the height, not the width of the coil 302. In addition, the design and structure of figure-8 coil 302 illustrated in FIGs. 3A-3C advantageously allows for high current and low heating (e.g., reduces or eliminates heating) during operation of the coil 302 for treatment of a subject using a TSMS system (e.g., the TSMS system illustrated in FIG. 2) without requiring a wider coil. A total diameter 310 of the coil 302 is the sum of the diameter of each circular coil 304, 306 in the figure-8 shape. In some embodiments, the two circular coils 304, 306 can be connected in series so that flowing current can be maximum at the center of the figure-8 shape. The figure-8 coil can be placed in a housing 312 for use with a subject (e.g., subject 112 shown in FIG. 1). For example, in some embodiments, the housing 312 for the figure-8 coil 302 can be formed using a three-dimensional (3D) printed mold and electrically and thermally insulated. In some embodiments, the coil 302 can have low resistance and allow for magnetic stimulation at elevated voltages and frequencies, while mitigating the risk of overheating. In one example, the figure-8 coil can be designed with a resistance of approximately 10 mO.

[0026] Returning to FIG. 2, as mentioned, the signal generator (or stimulator) 206 can be configured to generate and deliver electrical signals or pulses, for example, current pulses, to the TSMS coil 208. The BCB 210 can be used along with the power supply 216 to provide a power source for the signal generator 206. In some embodiments, the power supply 216 is a high- voltage capacitor charging power supply. The BCB 210 can include a capacitor bank of a plurality of capacitors configured to allow for high-voltage storage. In some embodiments, the capacitance of the BCB 210 can depend on the voltage over the duration of a pulse and can beMGH 2023-110-02Q&B 125141.04865 selected based on a desired voltage drop over a duration of a maximum current pulse. The BCB 210 can be used to supply high peak power demands during each stimulation pulse generated by the signal generator 206. In some embodiments, during operation, the BCB 210 can be charged slowly by the power supply 216. The BCB 210 can be configured to discharge quickly during a pulse by sourcing an extremely high instantaneous current (e.g., up to 5 kA) to the TSMS coil 208 (e.g., via the H-bridge 212 and RCB 214). In some embodiments, the BCB may include a voltage divider (not shown) to scale down the output of the BCB 210 and allow for monitoring the BCB voltage for safety. The BCB may be implemented on a printed circuit board (PCB). For safety, in some embodiments, the PCB may also include a “fast discharge” circuit which can discharge the stored energy in the capacitors into an array of special resistors to reduce the voltage to a safe level (e.g., in less than 10 seconds). In some embodiments, the BCB is not configured to be part of the resonant circuit of the signal generator 206 does not determine the pulse shape or width of the pulses generated by the signal generator 206. The capacitance of the BCB can be configured to be large enough to supply the necessary energy during a current pulse, while keeping the H-B ridge 212 relatively stable.

[0027] The resonant circuit of the signal generator 206 can include the H-bridge 212 and the RCB 214. The RCB 214 can include a plurality of high-voltage series capacitors. In some embodiments, the RCB 214 include a plurality of pairs of high-voltage series capacitors. In some embodiments, the RCB 214 can be divided into two sections wired in series and each section can be connected to one side of the TSMS coil 208. Each pair of series capacitors can contribute to the total resonant capacitance of the RCB 210. In some embodiments, the RCB 210 can be scalable to allow additional capacitor pairs to be added to adjust the available capacitance as needed. In some embodiments, the number of capacitors included in the RCB 210 can be based on the inductance of the TSMS coil and the desired operating frequency, which can depend on the application of the TSMS system. The RCB 210 can optionally be pre-charged by the high- voltage power supply 216 used for the BCB 210, which can allow for faster ramp-up to the steady-state output current amplitude.

[0028] The RCB 214 is advantageously configured to operate in a quasi-resonance mode so that the inductance of the TSMS coil 208 is canceled by the capacitance of the RCB 214. The TSMS coil 208 and the signal generator 206 can be configured to operate at a pulse frequency, fs, close to the natural frequency, f0, of the equivalent series RLC circuit formed by the TSMS coilMGH 2023-110-02Q&B 125141.04865208 (including both a resistance and an inductance) and the RCB 214. The resonance of the series RLC circuit occurs when the inductive and capacitive reactance (i.e., the RCB 214) are equal in magnitude but cancel each other because their phase is shifted by 180 degrees. If f0is the operating frequency, L is the total coil inductance, and C is the RCB 214 capacitance, then:

[0029] As for the component’s reactance, by increasing the frequency, the inductive reactance will increase, while the capacitive reactance will decrease according to the definition:

[0030] In the series configuration, at f0, XL, and Xccancel each other out and the impedance will depend only on the value of the resistance of the TSMS coil 208, therefore in this condition the current in the circuit will be maximal. Instead, for fs< f0,XL« Xcand the circuit is capacitive, while for fs> f0, XL» Xcand the circuit is inductive. In some embodiments, the pulse switching frequency (or pulse frequency,^) can be selected (e.g., as a pulse sequence parameter provided by controller 204) to be a predetermined amount above (or greater than) the resonant frequency (m0= 1 / VZC) to maintain the inductive behavior of the load (i.e., quasi-resonance mode). In other words, to ensure the system operates in inductive mode, in some embodiments, the pulse frequency, fs, can be selected to be a predetermine amount greater than the frequency, f0(or resonant frequency). For example, the pulse frequency can be selected to be slightly above the resonant frequency). The cancellation of the TSMS coil’s 208 inductance with the series resonant circuit (e.g., formed by the TSMS coil 208 and the RCB 214) allows the use of significantly lower voltages on the BCB 210 and H-bridge 212 than would otherwise be required. This can advantageously reduce the size and cost of the BCB 210 and H-bridge 212 components and enable the use of a high-inductance, high turn-count TSMS coil 208. In one example, operating in the quasi-resonance mode can enable extremely high current pulses (e.g., up to 10 kA peak) at 10 kHz (fs) with 600 V in the BCB 210.

[0031] The signal generator 206 also include an H-bridge 212 which can be configured to control the voltage across the TSMS coil 208 by switching the BCB 210 voltage through the RCB 214 which generates current pulses with desired widths and timings (e.g., pulse widths andMGH 2023-110-02 Q&B 125141.04865 timing provided by the controller 204 to the signal generator 206 in a set of pulse sequence parameters). FIG. 4 is a circuit diagram of an H-bridge of a TSMS signal generator (or stimulator) in accordance with an embodiment. The H-bridge 402 can be configured as a full bridge that includes a plurality of switching blocks that each include an Insulted-Gate Bipolar Transistor (IGBT) 404, 406, 408, 410 and a free-wheeling diode 412, 414, 416, 418, respectively. In some embodiments, the H-bridge 402 can be separated into two half-bridges (e.g., on two different PCBs). In some embodiments, the PCB for each half-bridge can include one or more local decoupling capacitors to stabilize collector voltages. To safeguard the IGBTs 404, 406, 408, 410 against reverse currents induced by the inductive load, the free-wheeling diodes 412, 414, 416, 418 can be configured to clamp the output to the positive and negative rails and to allow for dissipation of the energy stored in the inductor. If the IGBTs 404, 406, 408, 410 are suddenly switched off, the free-wheeling diodes 412, 414, 416, 418 can offer a path for the reverse current coming from the TSMS coil 208 to prevent negative voltages across the IGBTs 404, 406, 408, 410 and subsequent damage. Gate drivers 420, 422 can be used to facilitate the control of the IGBTs 404, 406, 408, 410. In some embodiments, a pulse command 218 (shown in FIG. 2) can set each gate driver 420, 422 output high or low and can provide the driving voltages for each IGBT 404, 406, 408, 410. In some embodiments, each gate driver 420, 422 can be configured to provide a fault output signal to controller 204 that can report the status of the gate driver 420, 422. As mentioned above, the TSMS coil 208 and RCB 214 can be configured to operate in inductive-mode which can provide the benefit of soft turn OFF for the IGBT 404, 406, 408, 410 tail currents, thus preventing reverse-recovery currents in the freewheeling diodes 412, 414, 416, 418.

[0032] While FIG. 4 illustrates various components of the H-bridge 402, other embodiments of the H-bridge 402 can vary the arrangement, communication paths, and specific components of the system. In some embodiments, the H-bridge 402 can include fewer, additional, or different components in different configurations than illustrates in FIG. 4. For example. In some embodiments, the H-bridge can include additional IGBTs and free-wheeling diodes.

[0033] Returning to FIG. 2, a pulse sequence (e.g., as provided and controlled by controller 204 shown in FIG. 2) for the signal generator (or stimulator) 206 can be configured to control the H- bridge 212 to advantageously provide zero-current switching (e.g., sequence-controlled-zero current switching (SCZCS). Advantageously, the SCZCS can be implemented by the controllerMGH 2023-110-02 Q&B 125141.04865(e.g., software) via the pulse sequence and does not require additional components in the signa generator 206. FIGs. 5 A and 5B are circuit diagrams of the H-Bridge of FIG. 4 in a) an R-pull up and b) an R-pull down mode in accordance with an embodiment. In FIGs. 5A and 5B, four switching blocks are shown, namely, a first switching block 504, a second switching block 506, a third switching block 508, and a fourth switching block 510. As illustrated in FIGs. 5 A and 5B and discussed above with respect to FIG. 4, each switching block 540, 506, 508, 510 can include and IGBT and a free-wheeling diode (e.g., IGBT 404, 406, 408, 410 and free-wheeling diode 412, 414, 416, 418, respectively). As mentioned, components of the signal generator 206 (shown in FIG, 2) may be operated at a predetermined amount above the natural or resonant frequency, f0, to operate in the inductive mode (e.g., a quasi-resonance mode) rather than in the capacitive mode (i.e., operation below the resonant frequency). If operated in a capacitive mode, the output current of the H-bridge 212 will reverse before the high-side IGBT (e.g., the IGBT in the first switching block 504 or the third switching block 508) turns OFF, hence the current will be shifted from the IGBT to its anti-parallel diode, which then experiences reverse recovery as soon as the opposite (low-side) IGBT (e.g., the IGBT in the second switching block 406 or the fourth switching block 510) turns ON. On the contrary, in the inductive mode, the high-side IGBT (e.g., the IGBT in the first switching block 504 or the third switching block 508) turns OFF before the current reverses, so the current flows on the opposite anti- parallel diode, which will softly turn OFF as its corresponding low-side IGBT (e.g., the IGBT in the second switching block 406 or the fourth switching block 510) starts to conduct. In addition to operating in quasi- resonance mode, the pulse sequence (e.g., one or more parameters of the pulse sequence) can be configured to provide zero-current switching for the H-bridge 212. In some embodiments, to prevent the reverse-recovery of the free-wheeling diodes, which risks damaging the IGBTs with high currents, the pulse sequence (and pulse design) should be configured to ensure: 1) the output current of the H-bridge 212 crosses zero while the output voltage of the H-bridge 212 is in a positive or negative period and 2) switching transitions occur when an IGBT is conducting rather than when a diode is conducting. For example, when the high-side IGBT (e.g., the IGBT in the first switching block 504 or the third switching block 508) turns OFF, the low-side freewheeling diode begins to conduct. If the output current crosses zero while the low-side IGBT (e.g., the IGBT in the second switching block 406 or the fourth switching block 510) is ON, the low- side diode will undergo a soft turn OFF, and the low-side IGBT will then take over conduction,MGH 2023-110-02 Q&B 125141.04865 thus protecting the IGBTs. Conversely, if the output current does not cross zero while the low- side IGBT (e g., the IGBT in the second switching block 406 or the fourth switching block 510) is conducting, it will continue to flow through the low-side diode as it will be seen as negative for the low-side IGBT, preventing the transition to the low-side IGBT. Subsequently, when the high- side IGBT (e.g., the IGBT in the first switching block 504 or the third switching block 508) turns ON again, it will induce reverse- recovery in the still -conducting low-side diode, potentially causing issues.

[0034] FIG. 6 shows a graph of an example output voltage 602 and output current 604 of the H- bridge of FIG. 4 in accordance with an embodiment. In some embodiments, the first pulse 606 can be configured to have half the pulse width of the subsequent pulses 608, 610. The initial pulse 606 can ramp the output current up to its peak value ( / pfe). The pulses 608, 610 that can have twice the width of the first pulse will then decrease the output current 604 by 2Ipk. This can ensure that the output current 604 is centered around zero when the next IGBT begins conducting. FIG. 6 also illustrates the output current 604 having zero crossings 612, 614 when the output voltage 602 is in a positive 610 or negative 608 period.

[0035] Returning to FIGs. 5A and 5B, being connected in series, the current flowing through the H-bridge (e.g., H-bridge 212, 402) and RCB (e.g., RCB 214) circuit (illustrates in FIG. 5A as an R-pull up circuit diagram 502 and in FIG. 5B as an R-pull down circuit diagram 512) will be the same for the TSMS coil and the capacitors of the RCB, i.e., i(t) = IR= IL= Ic, while the total voltage will be the sum of the voltages across them, i.e., V (t) = VR+ VL+ VC(Kirchhoffs law). If T is the pulse period, from 0 to T / 2 (by using a R pull-up 502), the IGBT QI (switching block 504) and Q4 (switching block 510) are turned ON and the voltage in the circuit will be given by V=2Vs. Sincesubstituting in the Kirchhoff s voltage law and differentiating, the following differential equation can be obtained:The general solution of this differential equation is:Where, A3and 212are determined by the boundary conditions and the natural frequencies b±and b2are defined as follows:MGH 2023-110-02 Q&B 125141.04865Equation (3) can be rewritten as a function of a>0and a (neper frequency or attenuation) as follows:R where a — — indicates the rate at which the current dies after each pulse is sent.

[0036] In particular, the damping factor ( ) of the system is given by:(where Q is the quality factor of the circuit) and determines the type of response. At f0the current pulse (i.e., the output current pulse of the H-bridge 212, 402) is characterized by the quality factor Q of the circuit (e.g., circuit 502 or 512 shown in FIGs. 5A and 5B) that is the ratio between the power stored and power dissipated in the circuit reactance and resistance in one radian of oscillation. A higher Q indicates that energy is dissipated at a lower rate and the oscillations decrease more slowly. Similarly, if (" > 1, the system response is underdamped, while if < 1, the system is overdamped. To obtain very large induced electric fields in the subject, given that the E-fields must penetrate quite deep in the tissues to reach the spinal cord and its nuclei, in some embodiments an underdamped system can be used, that allows for a higher current peak, therefore, in some embodiments R, L, and C can be selected so that a 0. In this condition, eq. (4) becomes:where — = 60 kA (determined by the boundary conditions) and a)d

[0037] From T / 2 to T, Q1 / Q4 (switching blocks 504, 510) are switched OFF and Q2 / Q3 (switching blocks 506, 508) are ON, so the V = — 2VS. At this point, there can be an overlap ofT two pulses with opposite signs, one started at t=0 and the other started at t=T / 2, and for - < t <T, the current on the TSMS coil will be given by:T where G = t + -. To maximize the current in the TSMS coil, the two terms in eq. (8) must have the same sign, or the first pulse must have a negative peak when the second has aMGH 2023-110-02 Q&B 125141.0486537r T’X 7T 7T peak. This occurs when a>dt = — and a>d( t + - ) = 5- or T = — = Td. In other words, the2 \ 2 / 2IGBT switching period can ideally match the damped resonance period. Similar expressions to 71eq. (8) for the can be derived. For t = —and large values of n, ea« 1, hence the current cannot grow further, meaning that after a certain IGBT switching, the peak-to-peak current can settle. In some embodiments, two cycles may be used to reach the peak-to-peak maximum current in the coil.

[0038] The circuit can be powered by a high voltage DC power supply (e.g., power supply 216 shown in FIG. 2) of amplitude 2 Vs, which can be allowed to flow to the load LC for a given period T / 2 by controlling the bases of the various IGBT by turning them ON / OFF. Consequently, the load LC intermittently connects to the DC power supply, generating a stream of pulses (i.e., DC chopping). The pulse sequence provided by the controller 204 (shown in FIG. 2) can determine the driving voltages (SvS2,S3, and S4in FIGs. 5A, and 5B), which allows the control of both the ON-time and OFF-time of each of the IGBT transistors in the four switching blocks 504, 506, 508, 510.

[0039] Referring to FIG. 1, in one example, the TSMS coil (e.g., TSMS coil 208 shown in FIG. 2) and the driving components (e.g., H-bridge 212 and RCB 214 shown in FIG. 2) can operate in a resonant mode that allows the generation of approximately 10 kA peak-to-peak currents amplitude and of about 4 kV peak-to-peak voltages on the TSMS coil, that is over 3 times lower than the voltage that would be normally needed to generate such high current pulses with other conventional stimulation systems. The RCB 214 can also act as a bandpass filter to generate a sinusoidal current waveform from the voltage waveform (e.g., the square voltage waveform 602 shown in FIG. 6) created by the H-bridge 212 and the sinusoidal current waveform can be applied to the TSMS coil 208. The BCB 210 can store all the energy necessary to produce the desired HF- TSMS pulse train. Since the BCB 210 capacitors can only store a limited amount of charge, the Vs voltage can decrease as the charges in the BCB 210 are depleted, thus reducing the peak current in the TSMS coil 208. The charge left in the BCB 210 and the voltage drop during discharge of the BCB 210 can be given by:_ t_ _ t_Q = CVoe~Rc and Fs= Voe~Rc Eq. 10MGH 2023-110-02 Q&B 125141.04865

[0040] In some embodiments, the controller 206 can be configured to manage and monitor the TSMS coil 208 and the components of the signal generator 206. In some embodiment, the controller 206 can provide a digital pulse to the signal generator 206 to enable a pulse timer at the start of each current pulse burst generated by the signal generator 206. In some embodiments, the system of FIG. 2 can also include temperature sensors positioned proximate to the transistors of the H-bridge 212 and the TSMS coil 208 to measure the temperature and provide the temperature measurements to the controller 206. The controller 206 can be configured to monitor the temperature of the transistors of the H-bridge 212 and the TSMS coil 208. For example, the controller 206 may be configured to automatically switch the signal generator 306 off if the temperature of the transistors or the TSMS coil reaches a predetermined threshold. In some embodiments, the temperature sensor can be, for example, thermocouples placed in the center of the ISMS coil.

[0041] In some embodiments, the quasi -resonant high frequency TSMS system can include various types of protection circuitry (not shown) configured to prevent faults that may compromise system integrity or cause hardware damage. In one example, discharge resistors can be connected to each high-voltage capacitor in both the BCB 210 and the RCB 214 so that in the case of a failure of the fast-discharge circuit, the system will still self-discharge to safe voltage levels over a longer time period. In some embodiments, the controller 204 can be \configured to enforce a predetermined pulse time limit, for example, 2 ms and the gate drivers of the H-bridge 212 can be automatically disabled after this time. This can prevent a software error from leaving the H-bridge 212 permanently turned on and producing an excessive current pulse. In yet another example, a predetermined peak current limit can be set for each IGBT in the H-bridge 212. In another example, a minimum dead time, between turning off one H-bridge 212 leg and turning on an adjacent H-bridge 212 leg, can be enforced by the controller 204 to prevent damaging shoot-through currents. In another example, each IGBT gate driver (e.g., gates drivers 420, 422 shown in FIG. 4) can include a de-saturation detector, which can generate a fault if its H-bridge 212 leg has not achieved sufficiently low voltage in a short time after turn on. This can avoid damage to the system in the case of a shorted output or failed IGBT.

[0042] FIG. 7 illustrates a method for quasi-resonant high-frequency TSMS in accordance with an embodiment. The process illustrated in FIG. 7 is described as being carried out by the system in FIG. 2-5B, however, in some examples, the process of FIG. 7 may be implemented by anotherMGH 2023-110-02 Q&B 125141.04865 system. Although the blocks of the process are illustrated in a particular order, in some embodiments, one or more blocks may be executed in a different order than illustrated in FIG. 7 or may be bypassed. One or more aspects of the methods may be performed by a processing system including at least one electronic processor, where the at least one electronic processor may be or include a processor as described herein. One or more aspects of the methods may be performed using a signal generator (or signal stimulator) in communication with the processing system.

[0043] At block 702, a set of pulse sequence parameters that include a pulse frequency configured for a quasi-resonance mode can be received, for example, a signal generator 206 can receive the set of pulse sequence parameters from a controller 204. In some embodiments, the set of pulse sequence parameters can also include, for example, timing, waveform shape, voltage, etc. As mentioned, the pulse frequency can be selected to be greater than the resonance frequency of the circuit (e.g., an equivalent RLC circuit) formed by an RCB 214 in the signal generator 206 and the TSMS coil 108 so that the circuit operates in an inductive mode and quasi- resonance mode. In the quasi-resonance mode, the inductance of the TSMS coil 208 and the capacitance of the RCB 214 cancel each other out (e.g., as a series LC circuit) to leave a purely resistive circuit. In some embodiments, operation in the quasi-resonance mode allows the use of significantly lower voltages on the BCB 210 and H-bridge 212 than would otherwise be required. This can advantageously reduce the size and cost of the BCB 210 and H-bridge 212 components and enable the use of a high-inductance, high turn-count TSMS coil 208 without the need for excessively high driving currents. In addition, operating in quasi-resonant mode advantageously removes the need for a rectifying network (e.g., a snubber) in the signal generator 206 altogether. In some embodiments, the reduced DC voltage requirements on the BCB 210 can also offer advantages for safety of the TSMS system.

[0044] At block 704, a set of driving voltages (e.g., S1,S2,S3, and S4shown in FIGs. 4, 5A, and 5B) can be applied using, for example, pulse commands 218, to an H-bridge 212 based on the set of pulse sequence parameters. As mentioned, the H-bridge 212 can include a plurality of switching blocks that each include an IGBT 404, 406, 408, 410. In some embodiments, the driving voltages (SltS2, S3, and S4) can be determined by the pulse sequence (e g., the set of pulse sequence parameters) which can allow control of the on time and off time of the IGBTs.MGH 2023-110-02 Q&B 125141.04865

[0045] At block 706, a set of high frequency current pulses with sequence-controlled zero current switching (SCZCS) can be generated using the H-bridge 212 of the signal generator 206. As mentioned, the H-bridge 212 can be configured to control a voltage across a TSMS coil 208 by switching a BCB 210 voltage through an RCB 214 which generates current pulses with desired widths and timings (e.g., pulse widths and timing in the set of pulse sequence parameters received at block 702). As mentioned, the pulse sequence (e.g., the set of pulse sequence parameters) provided by the controller 206 can be configured to control the H-bridge 212 so that the transitions of the IGBTs 404, 406, 408, 410 in the H-bridge 212, 402 (e.g., when the H- bridge transitions from an R-pull up mode to an R-pull down mode (or vice versa) illustrated in FIGs. 5A and 5B) transition at the zero current crossings of the output current generated by the H-bridge 212 and the switching transitions occur when an IGBT 404, 406, 408, 410 is conducting rather than when a diode 412, 414, 416, 418 is conducting. For example, the IGBT driving voltages or switching commands (S1,S2,S3, and S4) can be synchronized with the output current’s zero crossing timing. Accordingly, SCZCS can ensure that the IGBTs 404, 406, 408, 410 turn on only when the output current is near zero which can facilitate reduced switching losses. In addition, the H-bridge can be controlled so that the output current of the H-bridge 212 crosses zero while the output voltage of the H-bridge 212 is in a positive of negative period (e.g., as illustrated in FIG. 6). In some embodiments, the current pulses (and voltages) generated using the H-bridge 212 can be filtered using the RCB 214 to generate sinusoidal current waveform pulses.

[0046] At block 708, the set of high frequency current pulses can be applied to a TSMS coil 208. As mentioned, the set of high frequency current pulses can cause the TSMS coil 208 to generate a magnetic field which can be applied to a subject, for example, to target specific regions of the spinal cord to treat and manage chronic back pain, chronic leg pain, sciatica, neuropathy, etc. Advantageously, the quasi-resonant high frequency TSMS system operated with SCZCS can be used to drive high inductance coils at higher frequencies (e.g., up to 100 kHz).

[0047] FIG. 8 is a block diagram of an example computer system in accordance with an embodiment. Computer system 800 may be used to implement the systems and methods described herein. In some embodiments, the computer system 800 may be a workstation, a notebook computer, a tablet device, a mobile device, a multimedia device, a network server, a mainframe, one or more controllers, one or more microcontrollers, or any other general-purposeMGH 2023-110-02 Q&B 125141.04865 or application-specific computing device. The computer system 800 may operate autonomously or semi -autonomously, or may read executable software instructions from the memory or storage device 816 or a computer-readable medium (e.g., a hard drive, a CD-ROM, flash memory, etc.), or may receive instructions via the input device 820 from a user, or any other source logically connected to a computer or device, such as another networked computer or server. Thus, in some embodiments, the computer system 800 can also include any suitable device for reading computer-readable storage media.

[0048] Data, such as data acquired with an imaging system (e.g., a magnetic resonance imaging (MRI) system) may be provided to the computer system 800 from a data storage device 816, and these data are received in a processing unit 802. In some embodiment, the processing unit 802 includes one or more processors. For example, the processing unit 802 may include one or more of a digital signal processor (DSP) 804, a microprocessor unit (MPU) 806, and a graphics processing unit (GPU) 808. The processing unit 802 also includes a data acquisition unit 810 that is configured to electronically receive data to be processed. The DSP 804, MPU 806, GPU 808, and data acquisition unit 810 are all coupled to a communication bus 812. The communication bus 812 may be, for example, a group of wires, or a hardware used for switching data between the peripherals or between any components in the processing unit 802.

[0049] The processing unit 802 may also include a communication port 814 in electronic communication with other devices, which may include a storage device 816, a display 818, and one or more input devices 820. Examples of an input device 820 include, but are not limited to, a keyboard, a mouse, and a touch screen through which a user can provide an input. The storage device 816 may be configured to store data, which may include data such as, for example, pulse sequence parameters, values of generated voltages and current, etc. whether these data are provided to, or processed by, the processing unit 802. The display 818 may be used to display images and other information, such as magnetic resonance images, patient health data, and so on.

[0050] The processing unit 802 can also be in electronic communication with a network 822 to transmit and receive data and other information. The communication port 814 can also be coupled to the processing unit 802 through a switched central resource, for example the communication bus 812. The processing unit can also include temporary storage 824 and a display controller 826. The temporary storage 824 is configured to store temporary information. For example, the temporary storage 824 can be a random access memory.MGH 2023-110-02 Q&B 125141.04865

[0051] Computer-executable instructions for quasi-resonant high-frequency trans-spinal magnetic stimulation (TSMS) according to the above-described methods may be stored on a form of computer readable media. Computer readable media includes volatile and nonvolatile, removable, and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data. Computer readable media includes, but is not limited to, random access memory (RAM), read-only memory (ROM), electrically erasable programmable ROM (EEPROM), flash memory or other memory technology, compact disk ROM (CD-ROM), digital volatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, cloud storage, USB drive, or any other medium which can be used to store the desired instructions and which may be accessed by a system (e.g., a computer), including by internet or other computer network form of access.

[0052] The present technology has been described in terms of one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.

Claims

MGH 2023-110-02 Q&B 125141.04865CLAIMS1. A system for quasi-resonant high-frequency trans-spinal magnetic stimulation for a region of a spine of a subject, the system comprising: a signal generator comprising a bulk capacitor bank (BCB), an H-Bridge in signal communication with the BCB, and a resonant capacitor bank (RCB) in signal communication with the H-bridge; and a controller in signal communication with the signal generator and configured to: 1) provide a pulse sequence having a set of pulse sequence parameters to the signal generator including a pulse frequency configured to enable the RCB to operate in a quasi-resonance mode and 2) to control the H-bridge based on the pulse sequence, wherein the pulse sequence is configured to provide sequence-controlled zero current switching (SCZCS).

2. The system according to claim 1, further comprising a trans-spinal magnetic stimulation (TSMS) coil in signal communication with the signal generator.

3. The system according to claim 2, wherein the TSMS coil is configured as a low resistance figure-8 coil formed from ribbon copper.

4. The system according to claim 3, wherein the ribbon copper has a rectangular crosssection.

5. The system according to claim 1, wherein the BCB includes a plurality of capacitors configured to store high voltage and wherein the BCB is configured to dissipate the stored high voltage to the H-bridge.

6. The system according to claim 1, wherein the H-bridge comprises a plurality of Insulted- Gate Bipolar Transistors (IGBTs).

7. The system according to claim 1, wherein the RCB includes a plurality of high -voltage series capacitors.MGH 2023-110-02 Q&B 125141.048658. The system according to claim 2, wherein the RCB has a capacitance and the TSMS coil has an inductance and wherein in the quasi-resonance mode the inductance of the TSMS coil is canceled by the capacitance of the RCB.

9. The system according to claim 2, wherein the pulse frequency is selected to be a predetermined amount greater than a resonant frequency of a circuit formed by the RCB and the TSMS coil.

10. The system according to claim 2, wherein the H-bridge generates an output current in the quasi-resonance mode and the output current in the quasi-resonance mode is provided to the RCB.

11. The system according to claim 10, wherein the RCB provides the output current in the quasi-resonance mode to the TSMS coil.

12. A method for quasi-resonant high-frequency trans-spinal magnetic stimulation (TSMS) for a region of a spine of a subject, the method comprising: receiving, using a signal generator, pulse sequence having a set of pulse sequence parameters including a pulse frequency configured to enable a resonant capacitor bank (RCB) of the signal generator to operate in a quasi-resonance mode; applying, using the signal generator, a set of driving voltages to an H-bridge of the signal generator; generating, using the signal generator, high frequency current pulses by controlling the H-bridge based on the pulse sequence, wherein the pulse sequence is configured to provide sequence-controlled zero current switching (SCZCS); and applying, using the signal generator, the high frequency current pulses to a TSMS coil.

13. The method according to claim 12, wherein the TSMS coil is configured as a low resistance figure-8 coil formed from ribbon copper.MGH 2023-110-02 Q&B 125141.0486514. The method according to claim 13, wherein the ribbon copper has a rectangular crosssection.

15. The method according to claim 12, wherein the H-bridge comprises a plurality of Insulted-Gate Bipolar Transistors (IGBTs).

16. The method according to claim 12, wherein the RCB includes a plurality of high -voltage series capacitors.

17. The method according to claim 12, wherein the RCB has a capacitance and the TSMS coil has an inductance and wherein in the quasi -resonance mode the inductance of the TSMS coil is canceled by the capacitance of the RCB.

18. The method according to claim 12, wherein the pulse frequency is selected to be a predetermined amount greater than a resonant frequency of a circuit formed by the RCB and the TSMS coil .

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