WO2022218312A1 - 脉冲控制方法、装置及消融设备、系统、存储介质 - Google Patents

脉冲控制方法、装置及消融设备、系统、存储介质 Download PDF

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WO2022218312A1
WO2022218312A1 PCT/CN2022/086396 CN2022086396W WO2022218312A1 WO 2022218312 A1 WO2022218312 A1 WO 2022218312A1 CN 2022086396 W CN2022086396 W CN 2022086396W WO 2022218312 A1 WO2022218312 A1 WO 2022218312A1
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pulse
millisecond
nanosecond
pulse sequence
sequence
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PCT/CN2022/086396
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English (en)
French (fr)
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衷兴华
汪龙
杨克
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杭州维纳安可医疗科技有限责任公司
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Priority to US18/286,953 priority Critical patent/US20240189014A1/en
Publication of WO2022218312A1 publication Critical patent/WO2022218312A1/zh

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206Generators therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14Probes or electrodes therefor
    • A61B18/1477Needle-like probes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/05Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0502Skin piercing electrodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/327Applying electric currents by contact electrodes alternating or intermittent currents for enhancing the absorption properties of tissue, e.g. by electroporation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00017Electrical control of surgical instruments
    • A61B2017/00137Details of operation mode
    • A61B2017/00154Details of operation mode pulsed
    • A61B2017/00159Pulse shapes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
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    • A61B2017/00017Electrical control of surgical instruments
    • A61B2017/00137Details of operation mode
    • A61B2017/00154Details of operation mode pulsed
    • A61B2017/00181Means for setting or varying the pulse energy
    • A61B2017/00185Means for setting or varying the pulse height
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
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    • A61B2017/00017Electrical control of surgical instruments
    • A61B2017/00137Details of operation mode
    • A61B2017/00154Details of operation mode pulsed
    • A61B2017/00181Means for setting or varying the pulse energy
    • A61B2017/0019Means for setting or varying the pulse width
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61B2018/00571Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00577Ablation
    • AHUMAN NECESSITIES
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    • A61B2018/00571Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00613Irreversible electroporation
    • AHUMAN NECESSITIES
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    • A61B2018/00636Sensing and controlling the application of energy
    • A61B2018/00666Sensing and controlling the application of energy using a threshold value
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61B2018/00636Sensing and controlling the application of energy
    • A61B2018/00696Controlled or regulated parameters
    • A61B2018/00702Power or energy
    • AHUMAN NECESSITIES
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    • A61B2018/00636Sensing and controlling the application of energy
    • A61B2018/00696Controlled or regulated parameters
    • A61B2018/00732Frequency
    • AHUMAN NECESSITIES
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    • A61B2018/0091Handpieces of the surgical instrument or device
    • A61B2018/00916Handpieces of the surgical instrument or device with means for switching or controlling the main function of the instrument or device
    • A61B2018/00928Handpieces of the surgical instrument or device with means for switching or controlling the main function of the instrument or device by sending a signal to an external energy source
    • AHUMAN NECESSITIES
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    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14Probes or electrodes therefor
    • A61B2018/1405Electrodes having a specific shape
    • A61B2018/1425Needle

Definitions

  • the present application relates to the technical field of medical equipment, and in particular, the present application relates to a pulse control method, device, and ablation device, system, and storage medium.
  • Electroablation mainly uses the phenomenon of electroporation.
  • the ions inside and outside the cells move and accumulate on both sides of the outer membrane of the cell, causing a sharp change in the transmembrane potential, and the outer membrane of the cell undergoes electroporation, breaking the balance inside and outside the cell , and then achieve the purpose of ablation.
  • the existing electrical ablation schemes usually have the defects of small ablation scope, poor ablation effect, or easy to cause muscle contraction, poor patient experience, the need to use anesthetics, and high treatment costs.
  • the present application proposes a pulse control method, device, and ablation device, system, and storage medium, so as to solve at least one aspect of the above-mentioned technical problems existing in the prior art at least to a certain extent.
  • an embodiment of the present application provides a pulse control method, including:
  • the amplitude of the nanosecond pulse sequence is greater than the preset first threshold voltage, and the amplitude of the millisecond pulse sequence is less than the preset second threshold voltage.
  • an embodiment of the present application provides a pulse control device, including:
  • an electrical pulse control module configured to control the pulse generator to output a nanosecond pulse sequence, and to control the pulse generator to output a millisecond pulse sequence
  • the amplitude of the nanosecond pulse sequence is controlled to be greater than the preset first threshold voltage, and the amplitude of the millisecond pulse sequence is controlled to be less than the preset second threshold voltage.
  • an ablation device including:
  • the electrode needle is used to contact with the target object and output electrical pulses to the target object;
  • a pulse generator electrically connected to the electrode needles, for generating electrical pulses and conducting the electrical pulses to the electrode needles;
  • a controller connected in communication with the pulse generator, is configured to execute the pulse control method according to an embodiment of the first aspect of the present disclosure.
  • an embodiment of the present application provides an ablation system, including: the ablation device provided in the third aspect, and an upper computer;
  • the upper computer is connected in communication with the controller in the ablation device.
  • the embodiments of the present application provide a non-volatile computer-readable storage medium storing a computer program, and when the computer program is executed by a processor, the pulse control method according to the embodiment of the first aspect is implemented.
  • the beneficial technical effects brought about by the technical solutions provided in the embodiments of the present application include: cooperating with a nanosecond pulse sequence with an amplitude greater than a threshold voltage and a millisecond pulse sequence with an amplitude smaller than the threshold voltage, for example, the combination of a high voltage nanosecond pulse sequence and a low voltage millisecond pulse sequence
  • the synergistic effect can increase the effective ablation range, make the ablation more thorough, and can effectively reduce the amplitude of muscle contraction or reduce the probability of muscle contraction, which can improve the patient's sense of treatment experience, and can reduce the use of anesthetics, thereby effectively reducing treatment costs. , reduce side effects.
  • the high-voltage nanosecond pulse sequence can cause irreversible electroporation of cells close to the electrode needle, and then enter the apoptosis process, and reversible electroporation of cells farther away from the electrode needle;
  • the distant cells undergoing reversible electroporation undergo electrolysis (there are water and electrolytes in the cells. Under certain electrolysis conditions, the electrolytes will combine with the hydroxide ions produced by the electrolyzed water, so that the concentration of the electrolytes decreases, which will destroy the osmotic pressure of the cells. balance, acid-base balance, and water balance, etc., thereby destroying cell activity), so that cells far from the electrode needle can also enter the apoptosis process. Therefore, compared with the existing electrical ablation solution, the ablation treatment range obtained by the technical solution provided by the embodiments of the present application is larger and the ablation is more thorough.
  • the high-voltage nanosecond pulse sequence is beneficial to reduce the stress contraction of the muscle due to its parameter characteristics, while the low-voltage millisecond pulse sequence uses a lower voltage and will not cause the stress contraction of the muscle. Therefore, the technical solutions provided in the embodiments of the present application It can greatly relieve the phenomenon of muscle contraction in the patient during the treatment process, and improve the treatment experience of the patient.
  • FIG. 1 is a schematic frame diagram of the structure of an ablation device according to an embodiment of the present application.
  • FIG. 2 is a schematic frame diagram of the structure of another ablation device according to an embodiment of the present application.
  • FIG. 3 is a schematic framework diagram of the structure of an ablation system provided by an embodiment of the present application.
  • Example 4 is a schematic diagram of a pulse waveform of Example 1 generated by a pulse control method provided in an embodiment of the present application;
  • Example 5 is a schematic diagram of a pulse waveform of Example 2 generated by a pulse control method provided in an embodiment of the present application;
  • FIG. 6 is a schematic diagram of a pulse waveform of Example 3 generated by a pulse control method provided in an embodiment of the present application;
  • Example 7 is a schematic diagram of a pulse waveform of Example 4 generated by a pulse control method provided in an embodiment of the present application;
  • Example 8 is a schematic diagram of a pulse waveform of Example 5 generated by a pulse control method provided in an embodiment of the present application;
  • FIG. 9 is a schematic diagram of a pulse waveform of Example 6 generated by a pulse control method provided in an embodiment of the present application.
  • FIG. 10 is a schematic diagram of a pulse waveform of Example 7 generated by a pulse control method provided in an embodiment of the present application;
  • Example 11 is a schematic diagram of a pulse waveform of Example 8 generated by a pulse control method provided in an embodiment of the present application;
  • Example 12 is a schematic diagram of a pulse waveform of Example 9 generated by a pulse control method provided in an embodiment of the present application;
  • Example 13 is a schematic diagram of a pulse waveform of Example 10 generated by a pulse control method provided in an embodiment of the present application;
  • FIG. 14 is a schematic diagram of a pulse waveform of Example 11 generated by a pulse control method provided in an embodiment of the present application.
  • 110-ablation device 111-electrode needle; 112-pulse generator; 112a-first sub-generator; 112b-second sub-generator; 113-controller;
  • Threshold voltage refers to a critical voltage value used to define adjacent voltage intervals, such as a voltage value defining a high voltage interval and a low voltage interval, such as 144V (volts)-1000V.
  • microsecond pulses or nanosecond pulses can be used alone for treatment, and cells close to the electrode needle can undergo irreversible electroporation, and then enter apoptosis.
  • the cells far away from the electrode needle undergo reversible electroporation, and the cells undergoing reversible electroporation will survive later, so the expected ablation effect cannot be achieved. Therefore, the existing electrical ablation scheme has the defects of relatively small ablation range and incomplete ablation.
  • the pulse voltage needs to be increased, but the high-voltage pulse will cause the patient's muscle contraction during the treatment process, which will seriously affect the patient's treatment experience.
  • the use of anesthetics not only increases the cost of treatment, but also brings certain side effects to patients.
  • the pulse control method, device, and ablation device, system, and storage medium provided by the present application aim to solve the above technical problems in the prior art.
  • the embodiment of the present application provides an ablation device 110 , and a schematic structural diagram of the ablation device is shown in FIG. 1 , including but not limited to: an electrode needle 111 , a pulse generator 112 and a controller 113 .
  • the electrode needle 111 is used for contacting the target object and outputting electrical pulses to the target object.
  • the electrode needle can be used to penetrate into the target biological tissue and output electrical pulses to the target biological tissue.
  • the pulse generator 112 is electrically connected to the electrode needles 111 for generating and conducting electrical pulses to the electrode needles.
  • the controller 113 is connected in communication with the pulse generator 112, and the controller 113 is configured to execute any one of the pulse control methods provided by the embodiments of the present application.
  • the pulse control method will be described in detail below, so it is not repeated here.
  • the controller 113 can be used to control the pulse generator 112 to generate and output nanosecond pulse sequences and millisecond pulse sequences to the electrode needle 111 .
  • the electrode needle 111 can be used to apply nanosecond pulse sequences and millisecond pulse sequences to the target biological tissue.
  • the nanosecond pulse sequence with an amplitude greater than the threshold voltage may be a high-voltage nanosecond pulse sequence, and the millisecond pulse sequence with an amplitude smaller than the threshold voltage may be a low-voltage millisecond pulse sequence.
  • the high-voltage nanosecond pulse sequence can cause irreversible electroporation of cells close to the electrode needle 111, and then enter the apoptosis process, and make the cells farther from the electrode needle 111 undergo reversible electroporation.
  • the low-voltage millisecond pulse sequence can electrolyze the reversibly electroporated cells far away from the electrode needle 111 (there are water and electrolytes in the cells, and under certain electrolysis conditions, the electrolytes will combine with the hydroxide ions produced by the electrolyzed water, so that the electrolytes
  • the concentration of the electrode decreases, which will destroy the osmotic pressure balance, acid-base balance and water balance of the cells, thereby destroying the cell activity), so that cells farther away from the electrode needle 111 can also enter the apoptosis process. Therefore, compared with the existing electrical ablation solution, the ablation device 110 provided in this embodiment of the present application can achieve a wider range of ablation treatment, and the ablation can be more thorough.
  • the high-voltage nanosecond pulse sequence is beneficial to reduce the stress contraction of the muscle due to its parameter characteristics, while the low-voltage millisecond pulse sequence uses a lower voltage and will not cause the stress contraction of the muscle. Therefore, the ablation device provided in the embodiment of the present application 110 can effectively reduce the patient's muscle contraction amplitude, or reduce the probability of muscle contraction during the ablation process, or even avoid muscle contraction phenomenon, improve the patient's treatment experience, and can reduce or even eliminate the use of anesthetics, thereby effectively reducing treatment costs and side effects. .
  • the pulse generator 112 includes, but is not limited to, a first sub-generator 112 a and a second sub-generator 112 b.
  • the first sub-generator 112a is electrically connected to the electrode needle 111 and communicatively connected to the controller 113 for generating a nanosecond pulse sequence.
  • the second sub-generator 112b is electrically connected to the electrode needle 111 and communicatively connected to the controller 113 for generating a millisecond pulse sequence.
  • the pulse generator 112 adopts a structure including two sub-pulse generators, which can realize the independent generation of the nanosecond pulse sequence and the millisecond pulse sequence, which is beneficial to the circuit design of each sub-pulse generator. structure to achieve the corresponding pulse parameters.
  • the circuit structure of the first sub-generator 112a may be configured to generate a desired nanosecond pulse sequence
  • the circuit structure of the second sub-generator 112b may be configured to generate a desired millisecond pulse sequence.
  • the first sub-generator 112a and the second sub-generator 112b may be two pulse generating chips integrated on the same circuit board.
  • first sub-generator 112a and the second sub-generator 112b may be independent pulse generating units respectively located on different circuit boards.
  • the ablation device 110 may also include, but is not limited to, a memory.
  • the controller 113 is electrically connected to the memory, such as through a bus.
  • the controller 113 may be a CPU (Central Processing Unit, central processing unit), a general-purpose processor, a DSP (Digital Signal Processor, a data signal processor), an ASIC (Application Specific Integrated Circuit, an application-specific integrated circuit), an FPGA ( Field-Programmable Gate Array) or other programmable logic devices, transistor logic devices, hardware components, or any combination thereof. It may implement or execute the various exemplary logical blocks, modules and circuits described in connection with this disclosure.
  • the controller 113 can also be a combination that implements computing functions, such as a combination of one or more microprocessors, a combination of a DSP and a microprocessor, and the like.
  • the bus may include, but is not limited to, a path to communicate information between the aforementioned components.
  • the bus can be a PCI (Peripheral Component Interconnect, Peripheral Component Interconnect Standard) bus or an EISA (Extended Industry Standard Architecture, Extended Industry Standard Architecture) bus or the like.
  • the bus can be divided into address bus, data bus, control bus and so on.
  • the memory can be ROM (Read-Only Memory, read only memory) or other types of static storage devices that can store static information and instructions, RAM (random access memory, random access memory) or can store information and instructions.
  • ROM Read-Only Memory
  • RAM random access memory, random access memory
  • Other types of dynamic storage devices can also be EEPROM (Electrically Erasable Programmable Read Only Memory), CD-ROM (Compact Disc Read-Only Memory, read-only CD-ROM) or other CD-ROM storage,
  • Optical disc storage including but not limited to compact discs, laser discs, optical discs, digital versatile discs, Blu-ray discs, etc.
  • magnetic disk storage media or other magnetic storage devices or capable of carrying or storing desired programs in the form of instructions or data structures code and any other medium that can be accessed by a computer, without limitation.
  • the ablation device 110 may also include, but is not limited to, a monitoring unit.
  • the monitoring unit can be used to monitor the current and/or voltage parameters of the electrode needle 111 , and the controller 113 determines the working state of the electrode needle 111 through the current and/or voltage parameters of the electrode needle 111 obtained by the monitoring unit. For example, if the current current and/or current voltage parameters of the electrode needle 111 obtained by the monitoring unit are consistent with the current and/or voltage of the electrode needle 111 when it is no-load (no load is connected), it is considered that the electrode needle 111 has been charged with electricity. The pulse train output is completed.
  • the ablation device 110 may also include, but is not limited to, a transceiver.
  • Transceivers can be used for both reception and transmission of signals.
  • the transceiver can allow the controller 113 of the ablation device 110 to communicate wirelessly or by wire with other devices to exchange data, for example, when the controller 113 receives a user input stop ablation instruction or needle withdrawal instruction through the transceiver, the controller 113 is triggered to control pulses
  • the generator 112 starts to output the electrical pulse train or controls the pulse generator 112 to stop outputting the electrical pulse train.
  • the transceiver is not limited to one.
  • the ablation device 110 may also include, but is not limited to, an input unit.
  • the input unit may be used to receive input numerical, character, image and/or sound information, or generate key signal input related to user settings and function control of the controller 113 .
  • the input unit may include, but is not limited to, one or more of a touch screen, a physical keyboard, function keys (such as volume control keys, switch keys, etc.), trackballs, mice, joysticks, cameras, pickups, and the like.
  • the ablation device 110 may also include, but is not limited to, an output unit.
  • the output unit may be used to output or display the information processed by the controller 113 .
  • the output unit may include, but is not limited to, one or more of a display device, a speaker, a vibration device, and the like.
  • controller 113 of the ablation device 110 may be specially designed and manufactured for the required purpose, or may also include but not limited to known devices in general-purpose computers. These devices have computer programs stored in them that are selectively activated or reconfigured. Such a computer program may be stored in a device (e.g., computer) readable medium or in any type of medium suitable for storing electronic instructions and coupled to a bus, respectively.
  • a pulse control method which includes but is not limited to:
  • the pulse generator is controlled to output a nanosecond pulse sequence and the pulse generator is controlled to output a millisecond pulse sequence, and the pulses output by the pulse generator can be used to output a nanosecond pulse sequence and a millisecond pulse sequence to the target biological tissue.
  • the amplitude of the nanosecond pulse sequence is greater than the preset first threshold voltage, and the amplitude of the millisecond pulse sequence is less than the preset second threshold voltage.
  • the controller 113 in the ablation device 110 controls the pulse generator 112 to generate and output nanosecond pulse sequences and millisecond pulse sequences to the electrode needle 111, thereby enabling the electrode needle 111 to output nanosecond pulse sequences to the target biological tissue.
  • Second pulse train and millisecond pulse train controls the pulse generator 112 to generate and output nanosecond pulse sequences and millisecond pulse sequences to the electrode needle 111, thereby enabling the electrode needle 111 to output nanosecond pulse sequences to the target biological tissue.
  • the nanosecond pulse sequence with an amplitude greater than the preset first threshold voltage may be a high-voltage nanosecond pulse sequence
  • the millisecond pulse sequence with an amplitude smaller than the preset second threshold voltage may be a low-voltage millisecond pulse sequence
  • the pulse amplitude voltage of the nanosecond pulse sequence may be set between 5KV and 100KV, that is, the preset first threshold voltage may be between 5KV and 100KV.
  • the pulse amplitude voltage of the millisecond pulse train may be set between 5V and 100V, that is, the preset first threshold voltage may be between 5V and 100V.
  • outputting a nanosecond pulse sequence to a target biological tissue can induce irreversible electroporation of cells in a first region of the target biological tissue (usually corresponding to a region relatively close to the electrode needle), and induce the target biological tissue to undergo irreversible electroporation.
  • Reversible electroporation of cells occurs in a second region of the biological tissue (usually corresponding to a relatively distant region from the electrode needle).
  • the duration of the electroporation has a certain time window. Therefore, in order to utilize the duration of the reversible electroporation to achieve a therapeutic effect, in some embodiments, at least a part of the cells in the second region are reversibly electroporated. During the duration of the perforation, the millisecond pulse sequence is output to the target biological tissue to induce apoptosis in cells in the second region.
  • the electroporation phenomenon of the cell membrane during the duration of reversible electroporation can be used to make it easier for the electric field induced by the millisecond pulse to penetrate the cell membrane and act on the inside of the cells of the target biological tissue, and it is easier to realize the effect of the electric field such as cell electrolysis, thereby inducing the effect of the electric field. apoptosis.
  • the electric field induced by the millisecond pulse is also easier to act on the target biological tissue, and it is easier to realize electric field effects such as cell electrolysis, which is similar to that of cell electrolysis.
  • apoptosis can use the body's immune function to promote cell death.
  • Apoptotic cells will be recognized by the body as normal dead cells, and will be eliminated through phagocytosis to promote normal Tissue regeneration and repair, thus making it more conducive to restore the physiological function of the ablation area. Therefore, according to the method of the present disclosure, in the treatment of tumors and the like, a better therapeutic effect can be obtained compared with the single nanosecond pulse ablation or the single millisecond pulse ablation.
  • the millisecond pulse refers to a pulse with a pulse width of the order of milliseconds to distinguish it from a pulse with a pulse width of the order of nanoseconds, rather than limiting the pulse width to be several milliseconds.
  • the pulse width of the millisecond pulses may be between 1 millisecond and 1000 milliseconds.
  • the duration of reversible electroporation of the target biological tissue varies according to different target biological tissue morphology, different nanosecond pulse excitation, and different distances from the electrode needle.
  • Those skilled in the art can select corresponding pulse generation parameters according to the specific scene of the treatment under the teaching of the present disclosure, and these selected parameters will also fall within the protection scope of the present application.
  • the nanosecond pulse sequence and the millisecond pulse sequence are output alternately to the target biological tissue such that the end time of at least one of the nanosecond pulses coincides with the start of a subsequent adjacent millisecond pulse.
  • the time interval is set time, and the set time is not more than 1 second.
  • the interval time from the end of the nanosecond pulse to the beginning of the millisecond pulse may be negative, that is, it may be during the occurrence of the nanosecond pulse, and the millisecond pulse occurs simultaneously, so that the nanosecond pulse and the millisecond pulse simultaneously act on the target biological tissue .
  • the pulse control method provided in this embodiment can increase the effective ablation range, increase the effective ablation range, and increase the effective ablation range by cooperating with a nanosecond pulse sequence whose amplitude is greater than the preset first threshold voltage and a millisecond pulse sequence whose amplitude is less than the preset second threshold voltage. More thoroughly, it can also effectively reduce the amplitude of muscle contraction, or reduce the probability of muscle contraction, or even avoid muscle contraction, which can improve the patient's sense of treatment experience, and can reduce or even eliminate the use of anesthetics, thereby effectively reducing treatment costs and side effects.
  • the high-voltage nanosecond pulse sequence can cause irreversible electroporation of cells close to the electrode needle 111, and then enter the apoptosis process, and reversible electroporation of cells farther away from the electrode needle 111;
  • the cells with reversible electroporation at a distance from the needle 111 are electrolyzed (there are water and electrolytes in the cells, and under certain electrolysis conditions, the electrolytes will combine with the hydroxide ions produced by the electrolyzed water, so that the concentration of the electrolytes decreases, which will destroy the cells.
  • the ablation treatment range obtained by the technical solution provided by the embodiments of the present application is larger and the ablation is more thorough.
  • the high-voltage nanosecond pulse sequence is beneficial to reduce the stress contraction of the muscle due to its parameter characteristics, while the low-voltage millisecond pulse sequence uses a lower voltage and will not cause the stress contraction of the muscle. Therefore, the technical solutions provided in the embodiments of the present application It can greatly relieve or even no muscle contraction in the patient during the treatment process, and improve the treatment experience of the patient.
  • the embodiments of the present application provide another pulse control method, which includes but is not limited to:
  • the amplitude of the nanosecond pulse sequence is greater than the preset first threshold voltage, and the amplitude of the millisecond pulse sequence is less than the preset second threshold voltage.
  • the controller 113 in the ablation device 110 controls the pulse generator 112 to alternately generate and output nanosecond pulse sequences and millisecond pulse sequences to the electrode needles 111 , so that the electrode needles 111 alternately move toward the target biological tissue. Output nanosecond pulse trains and millisecond pulse trains.
  • Another pulse control method provided in this embodiment also uses a nanosecond pulse sequence whose amplitude is greater than a threshold voltage to cooperate with a millisecond pulse sequence whose amplitude is less than the threshold voltage, so that the effective ablation range can be increased, the ablation is more thorough, and the effective Reducing the amplitude of muscle contraction, or reducing the probability of muscle contraction, or even avoiding the phenomenon of muscle contraction, can improve the patient's sense of treatment experience, and can reduce or even eliminate the use of anesthetics, thereby effectively reducing treatment costs and side effects.
  • the nanosecond pulse sequence and the millisecond pulse sequence are alternately output to the target biological tissue, which is beneficial to control the length of the high-voltage nanosecond pulse sequence, that is, to control the impact of each high-voltage nanosecond pulse sequence on the target biological tissue.
  • the action time of the tissue reduces the stress contraction probability of the muscle; on the other hand, it is beneficial to realize the continuous progress of the overall pulse including the nanosecond pulse sequence and the millisecond pulse sequence, reduce the gap period, and improve the ablation efficiency.
  • the inventors of the present application provide the following nine optional implementations for alternately outputting nanosecond pulse sequences and millisecond pulse sequences:
  • the controller 113 in the ablation device 110 determines that the electrode needle 111 has output a nanosecond pulse in the nanosecond pulse sequence
  • the controller 113 controls the pulse generator 112 to generate and output the millisecond pulse to the electrode needle 111 .
  • One millisecond pulse in the pulse sequence so that the electrode needle 111 outputs one millisecond pulse in the millisecond pulse sequence to the target biological tissue.
  • each nanosecond pulse in the nanosecond pulse sequence is alternately generated and output with each millisecond pulse in the millisecond pulse sequence, and the high voltage nanosecond pulse is generated and output before, and the low voltage millisecond pulse is generated after Generate and output.
  • the controller 113 in the ablation device 110 determines that the electrode needle 111 has output a millisecond pulse in the millisecond pulse sequence
  • the controller 113 controls the pulse generator 112 to generate and output nanosecond pulses to the electrode needle 111 .
  • One nanosecond pulse in the sequence makes the electrode needle 111 output one nanosecond pulse in the nanosecond pulse sequence to the target biological tissue.
  • each nanosecond pulse in the nanosecond pulse sequence is alternately generated and output with each millisecond pulse in the millisecond pulse sequence, the low-voltage millisecond pulse is generated and output first, and the high-voltage nanosecond pulse is generated later and output.
  • the millisecond pulse sequence is output at least a portion of the millisecond pulse.
  • the controller 113 in the ablation device 110 determines that the electrode needle 111 has output at least a part of the nanosecond pulses in the nanosecond pulse sequence
  • the controller 113 controls the pulse generator 112 to generate and output the nanosecond pulses to the electrode needle 111 .
  • each nanosecond pulse subsequence in the nanosecond pulse sequence is alternately generated and output with each segment of the millisecond pulse subsequence in the millisecond pulse sequence, and the high voltage nanosecond pulse subsequence is generated and output before , the low-voltage millisecond pulse sub-sequence is generated and outputted later.
  • the nanosecond pulse sequence sequentially includes: nanosecond pulse No. 1, nanosecond pulse No. 2, nanosecond pulse No. 3, nanosecond pulse No. 4, nanosecond pulse No. 5, and nanosecond pulse No. 6.
  • the No. 1 nanosecond pulse and No. 2 nanosecond pulse form a No. 1 nanosecond pulse subsequence
  • No. 3 nanosecond pulse and No. 4 nanosecond pulse form a No. 2 nanosecond pulse subsequence
  • No. 5 nanosecond pulse and No. 6 nanosecond pulse subsequence The nanosecond pulses form a subsequence of nanosecond pulses No. 3.
  • the millisecond pulse sequence sequentially includes: millisecond pulse No. 1, millisecond pulse No. 2, millisecond pulse No. 3, millisecond pulse No. 4, millisecond pulse No. 5 and millisecond pulse No. 6.
  • the No. 1 millisecond pulse and No. 2 millisecond pulse form the No. 1 millisecond pulse subsequence
  • the No. 3 millisecond pulse and No. 4 millisecond pulse form the No. 2 millisecond pulse subsequence
  • the No. 5 millisecond pulse and No. 6 millisecond pulse form the No. 3 millisecond pulse subsequence.
  • the controller 113 in the ablation device 110 determines that the electrode needle 111 has output the No. 1 nanosecond pulse sub-sequence (including No. 1 nanosecond pulse and No. 2 nanosecond pulse), it controls the pulse generator 112 to generate and send the The electrode needle 111 outputs a No. 1 millisecond pulse subsequence (including No. 1 millisecond pulse and No. 2 millisecond pulse), and so on.
  • the controller 113 in the ablation device 110 determines that the electrode needle 111 has output at least a part of the millisecond pulses in the millisecond pulse sequence, it controls the pulse generator 112 to generate and output nanosecond pulses to the electrode needle 111 . At least a part of the nanosecond pulses in the pulse sequence, so that the electrode needle 111 outputs at least a part of the nanosecond pulses in the nanosecond pulse sequence to the target biological tissue.
  • each nanosecond pulse subsequence in the nanosecond pulse sequence is alternately generated and output with each millisecond pulse subsequence in the millisecond pulse sequence, the low-voltage millisecond pulse subsequence is generated and output first, the high-voltage Subsequences of nanosecond pulses are generated and output later.
  • the controller 113 in the ablation device 110 determines that the electrode needle 111 has output at least a part of the nanosecond pulses in the nanosecond pulse sequence
  • the controller 113 controls the pulse generator 112 to generate and output the nanosecond pulses to the electrode needle 111 .
  • One millisecond pulse in the millisecond pulse sequence so that the electrode needle 111 outputs one millisecond pulse in the millisecond pulse sequence to the target biological tissue.
  • each nanosecond pulse subsequence in the nanosecond pulse sequence is alternately generated and output with each millisecond pulse in the millisecond pulse sequence, and the high voltage nanosecond pulse subsequence is generated and output before, the low voltage Millisecond pulses are generated and output later.
  • the controller 113 in the ablation device 110 determines that the electrode needle 111 has output at least a part of the millisecond pulses in the millisecond pulse sequence, it controls the pulse generator 112 to generate and output nanosecond pulses to the electrode needle 111 .
  • One nanosecond pulse in the pulse sequence makes the electrode needle 111 output one nanosecond pulse in the nanosecond pulse sequence to the target biological tissue.
  • one nanosecond pulse in the nanosecond pulse sequence is alternately generated and output with each segment of the millisecond pulse subsequence in the millisecond pulse sequence, the low-voltage millisecond pulse subsequence is generated and output first, and the high-voltage nanosecond pulse Generate and output later.
  • the interval between at least one nanosecond pulse and the adjacent millisecond pulse is set time.
  • the controller 113 in the ablation device 110 controls the pulse generator 112 to generate and output one nanosecond pulse or a sub-sequence of nanosecond pulses in the nanosecond pulse sequence to the electrode needle 111, and pause. After the set time, the pulse generator 112 is then controlled to generate and output one millisecond pulse or a sub-sequence of millisecond pulses in the millisecond pulse sequence to the electrode needle 111 .
  • the controller 113 in the ablation device 110 controls the pulse generator 112 to generate and output a millisecond pulse or a sub-sequence of millisecond pulses in the millisecond pulse sequence to the electrode needle 111, and after a pause for a set time, The pulse generator 112 is then controlled to generate and output one nanosecond pulse or a sub-sequence of nanosecond pulses in the nanosecond pulse sequence to the electrode needle 111 .
  • the transition node between nanosecond pulses and millisecond pulses can be paused for a set time, which is beneficial to provide buffer time for cells at the target biological tissue and meet the needs of some treatment scenarios.
  • the set time is not less than 1 nanosecond and not more than 1 second.
  • the cells at the target biological tissue can continue the action inertia of a certain electric pulse, and at the same time, the probability that the cells at the target biological tissue completely lose the action of the electric pulse is reduced, so as to ensure the ablation effect.
  • the falling edge of at least one nanosecond pulse corresponds to the rising edge of the adjacent millisecond pulse.
  • the pulse generator 112 is controlled to generate and output one millisecond pulse or a sub-sequence of millisecond pulses in the millisecond pulse sequence to the electrode needle 111 .
  • the rising edge of at least one nanosecond pulse corresponds to the falling edge of an adjacent millisecond pulse.
  • the controller 113 in the ablation device 110 determines that the electrode needle 111 has output a millisecond pulse in the millisecond pulse sequence or the last millisecond pulse in a subsequence of millisecond pulses, it immediately controls the pulse generation.
  • the generator 112 generates and outputs one nanosecond pulse or a sub-sequence of nanosecond pulses in the nanosecond pulse sequence to the electrode needle 111 .
  • the inventors of the present application considered that the high-voltage nanosecond pulse sequence can cause irreversible electroporation of cells close to the electrode needle, and then enter the apoptosis process, and reversible electroporation of cells farther from the electrode needle, and reduce muscle stress. contraction.
  • the present application provides the following possible implementations for the relevant parameters or characteristics of the nanosecond pulse sequence:
  • the frequency of the nanosecond pulse sequence is not less than 0.1 Hz and not more than 10 Hz.
  • the nanosecond pulse sequence includes, but is not limited to, no less than 2 nanosecond pulses, and no more than 5000 nanosecond pulses.
  • the pulse width of at least one nanosecond pulse in the nanosecond pulse sequence is not less than 10 nanoseconds and not more than 1000 nanoseconds.
  • the amplitude of at least one nanosecond pulse in the nanosecond pulse sequence is not less than 5 kV and not more than 100 kV.
  • the nanosecond pulse sequence is a square wave pulse sequence.
  • the nanosecond pulse sequence is a bipolar pulse sequence.
  • the inventors of the present application consider that the low-voltage millisecond pulse sequence can electrolyze the reversibly electroporated cells far from the electrode needle, so that the cells far from the electrode needle can also enter the apoptosis process.
  • the present application provides the following possible implementations for the relevant parameters or characteristics of the nanosecond pulse sequence:
  • the frequency of the millisecond pulse sequence is not less than 0.1 Hz and not more than 10 Hz.
  • the millisecond pulse sequence includes, but is not limited to, no less than 2 millisecond pulses, and no more than 5000 millisecond pulses.
  • the pulse width of at least one millisecond pulse in the millisecond pulse sequence is not less than 1 millisecond and not more than 1000 milliseconds.
  • the amplitude of at least one millisecond pulse in the millisecond pulse sequence is not less than 5 volts and not more than 100 volts.
  • the millisecond pulse sequence is a square wave pulse sequence.
  • the millisecond pulse sequence is a bipolar pulse sequence.
  • a pulse control device provided by an embodiment of the present application includes, but is not limited to, an electrical pulse control module.
  • the electrical pulse control module is used to output nanosecond pulse sequence and millisecond pulse sequence to the target biological tissue.
  • the amplitude of the nanosecond pulse train is greater than the threshold voltage, and the amplitude of the millisecond pulse train is less than the threshold voltage.
  • the pulse control device can increase the effective ablation range, make the ablation more thorough, and effectively reduce the muscle contraction amplitude by using the nanosecond pulse sequence whose amplitude is greater than the threshold voltage to cooperate with the millisecond pulse sequence whose amplitude is less than the threshold voltage. , or reduce the probability of muscle contraction, or even avoid the phenomenon of muscle contraction, which can improve the patient's sense of treatment experience, and can reduce or even eliminate the use of anesthetics, thereby effectively reducing treatment costs and side effects.
  • the high-voltage nanosecond pulse sequence can cause irreversible electroporation of cells close to the electrode needle 111, and then enter the apoptosis process, and reversible electroporation of cells farther away from the electrode needle 111;
  • the cells with reversible electroporation at a distance from the needle 111 are electrolyzed (there are water and electrolytes in the cells, and under certain electrolysis conditions, the electrolytes will combine with the hydroxide ions produced by the electrolyzed water, so that the concentration of the electrolytes decreases, which will destroy the cells.
  • the ablation treatment range obtained by the technical solution provided by the embodiments of the present application is larger and the ablation is more thorough.
  • the high-voltage nanosecond pulse sequence is beneficial to reduce the stress contraction of the muscle due to its parameter characteristics, while the low-voltage millisecond pulse sequence uses a lower voltage and will not cause the stress contraction of the muscle. Therefore, the technical solutions provided in the embodiments of the present application It can greatly relieve or even no muscle contraction in the patient during the treatment process, and improve the treatment experience of the patient.
  • the electrical pulse control module is configured to alternately output nanosecond pulse sequences and millisecond pulse sequences to the target biological tissue.
  • the electrical pulse control module is configured to output one millisecond pulse in the millisecond pulse sequence every time it is determined that one nanosecond pulse in the nanosecond pulse sequence has been output.
  • the electrical pulse control module is configured to output one nanosecond pulse in the nanosecond pulse sequence every time it is determined that one millisecond pulse in the millisecond pulse sequence has been output.
  • the electrical pulse control module is configured to output at least a part of the millisecond pulses in the millisecond pulse sequence every time it is determined that at least a part of the nanosecond pulses in the nanosecond pulse sequence has been output.
  • the electrical pulse control module is configured to output at least a part of nanosecond pulses in the nanosecond pulse sequence every time it is determined that at least a part of the millisecond pulses in the millisecond pulse sequence has been output.
  • the electrical pulse control module is configured to output one millisecond pulse in the millisecond pulse sequence every time it is determined that at least a part of the nanosecond pulses in the nanosecond pulse sequence has been output.
  • the electrical pulse control module is configured to output one nanosecond pulse in the nanosecond pulse sequence every time it is determined that at least a part of the millisecond pulses in the millisecond pulse sequence has been output.
  • the embodiments of the present application provide a computer-readable storage medium, where a computer program is stored on the computer-readable storage medium, and when the program is executed by a processor, any pulse provided by the embodiments of the present application is implemented. Control Method.
  • the embodiments of the present application provide a computer-readable storage medium suitable for various optional implementations of any of the above pulse control methods. It is not repeated here.
  • the computer-readable storage medium provided in this embodiment may be any available medium that can be accessed by an electronic device, including volatile and nonvolatile media, removable media or non-removable media.
  • Computer-readable storage media include but are not limited to any type of disk (including floppy disk, hard disk, optical disk, CD-ROM, and magneto-optical disk), ROM, RAM, EPROM (Erasable Programmable Read-Only Memory, Erasable Programmable Read-Only Memory) memory), EEPROM (Electrically Erasable Programmable Read Only Memory, Electrically Erasable Programmable Read Only Memory), flash memory, magnetic card or optical card. That is, a computer-readable storage medium includes any medium that stores or transmits information in a form that can be read by a device (eg, a computer).
  • an embodiment of the present application provides an ablation system 100 , a schematic diagram of which is shown in FIG. 3 , including but not limited to: any of the ablation devices 110 provided in the foregoing embodiments, and an upper computer 120.
  • the upper computer 120 is connected in communication with the controller 113 in the ablation device 110 .
  • the host computer 120 can implement program update or data backup of the ablation device 110 , and can also implement remote control of the ablation device 110 , which can facilitate the function expansion of the ablation device 110 .
  • the host computer 120 communicates with the controller 113 in the ablation device 110 through WIFI (Wireless Fidelity, wireless fidelity, also known as mobile hotspot).
  • WIFI Wireless Fidelity, wireless fidelity, also known as mobile hotspot.
  • the host computer 120 is communicatively connected with the controller 113 in the ablation device 110 through the cloud.
  • the experimental subjects are New Zealand white rabbits (female, 6 months old, body weight 2.5kg ⁇ 0.2kg). rearing.
  • Each experimental example and comparative example adopts the ablation equipment 110 independently developed by the company, including the electrode needle 111 , the pulse generator 112 and the controller 113 .
  • the pulse generator 112 of the ablation device 110 can output pulse parameters ranging from 10 ns to 100 ms, with an adjustable amplitude of 0 to 200 kV and a frequency of 0.1 to 1 kHz.
  • the electrode needles are processed by medical stainless steel by themselves. The diameter of the electrode needles is 1mm, the exposed length is 8mm, and the electrode spacing is uniformly fixed at 10mm by using a self-made spacer.
  • Experimental example 1 adopts the synergistic effect of a high-voltage nanosecond pulse sequence and a low-voltage millisecond pulse sequence. Please refer to Table 1 for relevant data.
  • Experimental example 2 adopts the synergistic effect of a high-voltage nanosecond pulse sequence and a low-voltage millisecond pulse sequence. Please refer to Table 2 for relevant data.
  • Experimental example 3 adopts the synergistic effect of a high-voltage nanosecond pulse sequence and a low-voltage millisecond pulse sequence. Please refer to Table 3 for relevant data.
  • Comparative example 1 uses a high-voltage microsecond pulse sequence, see Table 4 for relevant data.
  • the effective ablation range can be increased, the ablation can be more thorough, and the amplitude of muscle contraction can be effectively reduced, or the probability of muscle contraction can be reduced , and even avoid muscle contraction, which can improve the patient's sense of treatment experience, and can reduce or even eliminate the use of anesthetics, thereby effectively reducing treatment costs and side effects.
  • the nanosecond pulse sequence and the millisecond pulse sequence are alternately output to the target biological tissue, which is beneficial to control the length of the high-voltage nanosecond pulse sequence, that is, to control the action time of each high-voltage nanosecond pulse sequence on the target biological tissue. , reducing the stress contraction probability of the muscle; on the other hand, it is beneficial to realize the continuous progress of the whole pulse including nanosecond pulse sequence and millisecond pulse sequence, reduce the gap period, and improve the ablation efficiency.
  • the transition node between nanosecond pulses and millisecond pulses can pause for a set time, which is beneficial to provide buffer time for cells at the target biological tissue and meet the needs of some treatment scenarios.
  • first and second are only used for descriptive purposes, and should not be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as “first” or “second” may expressly or implicitly include one or more of that feature. In the description of this application, unless stated otherwise, "plurality" means two or more.
  • the terms “installed”, “connected” and “connected” should be understood in a broad sense, for example, it may be a fixed connection or a detachable connection Connection, or integral connection; it can be directly connected, or indirectly connected through an intermediate medium, and it can be the internal communication of two elements.
  • installed should be understood in a broad sense, for example, it may be a fixed connection or a detachable connection Connection, or integral connection; it can be directly connected, or indirectly connected through an intermediate medium, and it can be the internal communication of two elements.

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Abstract

一种脉冲控制方法、装置及消融设备(110)、系统(100)、存储介质,其中,脉冲控制方法包括:控制脉冲发生器(112)输出纳秒脉冲序列和毫秒脉冲序列;纳秒脉冲序列的幅值大于预设的第一阈值电压,毫秒脉冲序列的幅值小于预设的第二阈值电压。通过幅值大于阈值电压的纳秒脉冲序列协同幅值小于阈值电压的毫秒脉冲序列作用,能够增大有效的消融范围、消融更彻底,还能有效减少肌肉收缩幅度、或降低肌肉收缩的概率,可以提高患者的治疗体验感,并且可以减少甚至无需麻醉剂的使用,从而有效降低治疗成本、减少副作用。

Description

脉冲控制方法、装置及消融设备、系统、存储介质 技术领域
本申请涉及医疗器材技术领域,具体而言,本申请涉及一种脉冲控制方法、装置及消融设备、系统、存储介质。
背景技术
电消融主要利用电穿孔现象,通过对病灶细胞发送电场脉冲,使细胞内外的离子运动并聚集在细胞外膜两侧,引起跨膜电位的急剧变化,细胞外膜发生电穿孔,打破细胞内外平衡,进而达到消融目的。
但现有的电消融方案通常存在消融范围小、消融效果差,或易引发肌肉收缩、患者体验感差,需配合麻醉剂使用、治疗成本高等缺陷。
发明内容
本申请针对现有方式的缺点,提出一种脉冲控制方法、装置及消融设备、系统、存储介质,用以至少在一定程度上解决现有技术存在的上述技术问题中的至少一个方面。
第一个方面,本申请实施例提供了一种脉冲控制方法,包括:
控制脉冲发生器输出纳秒脉冲序列,以及
和控制脉冲发生器输出毫秒脉冲序列;
其中,纳秒脉冲序列的幅值大于预设的第一阈值电压,毫秒脉冲序列的幅值小于预设的第二阈值电压。
第二个方面,本申请实施例提供了一种脉冲控制装置,包括:
电脉冲控制模块,被配置为控制脉冲发生器输出纳秒脉冲序列,以及控制脉冲发生器输出毫秒脉冲序列;
并且,控制纳秒脉冲序列的幅值大于预设的第一阈值电压,控制毫秒 脉冲序列的幅值小于预设的第二阈值电压。
第三个方面,本申请实施例提供了一种消融设备,包括:
电极针,用于与目标物体接触并向目标物体输出电脉冲;
脉冲发生器,与电极针电连接,用于生成电脉冲并将电脉冲传导到电极针;
控制器,与脉冲发生器通信连接,控制器被配置为用于执行根据本公开第一个方面实施例的脉冲控制方法。
第四个方面,本申请实施例提供一种消融系统,包括:如第三个方面提供的消融设备,和上位机;
上位机与消融设备中的控制器通信连接。
第五个方面,本申请实施例提供一种非易失性计算机可读存储介质,存储有计算机程序,计算机程序被处理器执行时实现根据第一个方面实施例的脉冲控制方法。
本申请实施例提供的技术方案带来的有益技术效果包括:通过幅值大于阈值电压的纳秒脉冲序列协同幅值小于阈值电压的毫秒脉冲序列,例如高压纳秒脉冲序列与低压毫秒脉冲序列的协同作用,能够增大有效的消融范围、消融更彻底,还能有效减少肌肉收缩幅度、或降低肌肉收缩的概率,可以提高患者的治疗体验感,并且可以减少麻醉剂的使用,从而有效降低治疗成本、减少副作用。
具体地,高压纳秒脉冲序列可以使靠近电极针的细胞发生不可逆电穿孔、进而进入凋亡程序,并使距离电极针较远的细胞发生可逆电穿孔;低压毫秒脉冲序列可以对距离电极针较远的发生可逆电穿孔的细胞进行电解(细胞内存在水和电解质,在一定电解条件下,电解质会与电解水产生的氢氧根离子结合,从而电解质的浓度降低,这样会破坏细胞的渗透压平衡、酸碱平衡以及水平衡等,进而破坏细胞活性),使得距离电极针较远的细胞也可以进入凋亡程序。因此,与现有的电消融方案相比,本申请实施例提供的技术方案所获得的消融治疗范围更大、消融更加彻底。
并且,高压纳秒脉冲序列因其参数特性利于降低肌肉的应激收缩,而低压毫秒脉冲序列所使用的电压较低,也不会引发肌肉的应激收缩,因此 本申请实施例提供的技术方案能够实现患者在治疗过程中极大缓解肌肉收缩的现象,提高患者的治疗体验。
本申请附加的方面和优点将在下面的描述中部分给出,这些将从下面的描述中变得明显,或通过本申请的实践了解到。
附图说明
本申请上述的和/或附加的方面和优点从下面结合附图对实施例的描述中将变得明显和容易理解,其中:
图1为本申请实施例提供的一种消融设备的结构的框架示意图;
图2为本申请实施例提供的另一种消融设备的结构的框架示意图;
图3为本申请实施例提供的一种消融系统的结构的框架示意图;
图4为本申请实施例提供的一种脉冲控制方法产生的示例一的脉冲波形示意图;
图5为本申请实施例提供的一种脉冲控制方法产生的示例二的脉冲波形示意图;
图6为本申请实施例提供的一种脉冲控制方法产生的示例三的脉冲波形示意图;
图7为本申请实施例提供的一种脉冲控制方法产生的示例四的脉冲波形示意图;
图8为本申请实施例提供的一种脉冲控制方法产生的示例五的脉冲波形示意图;
图9为本申请实施例提供的一种脉冲控制方法产生的示例六的脉冲波形示意图;
图10为本申请实施例提供的一种脉冲控制方法产生的示例七的脉冲波形示意图;
图11为本申请实施例提供的一种脉冲控制方法产生的示例八的脉冲波形示意图;
图12为本申请实施例提供的一种脉冲控制方法产生的示例九的脉冲波形示意图;
图13为本申请实施例提供的一种脉冲控制方法产生的示例十的脉冲波形示意图;
图14为本申请实施例提供的一种脉冲控制方法产生的示例十一的脉冲波形示意图。
100-消融系统;
110-消融设备;111-电极针;112-脉冲发生器;112a-第一子发生器;112b-第二子发生器;113-控制器;
120-上位机;
1-纳秒脉冲;2-毫秒脉冲;
10-纳秒脉冲子序列;20-毫秒脉冲子序列。
具体实施方式
下面详细描述本申请,本申请的实施例的示例在附图中示出,其中自始至终相同或类似的标号表示相同或类似的部件或具有相同或类似功能的部件。此外,如果已知技术的详细描述对于示出的本申请的特征是不必要的,则将其省略。下面通过参考附图描述的实施例是示例性的,仅用于解释本申请,而不能解释为对本申请的限制。
本技术领域技术人员可以理解,除非另外定义,这里使用的所有术语(包括技术术语和科学术语),具有与本申请所属领域中的普通技术人员的一般理解相同的意义。还应该理解的是,诸如通用字典中定义的那些术语,应该被理解为具有与现有技术的上下文中的意义一致的意义,并且除非像这里一样被特定定义,否则不会用理想化或过于正式的含义来解释。
本技术领域技术人员可以理解,除非特意声明,这里使用的单数形式“一”、“一个”、“所述”和“该”也可包括复数形式。应该进一步理解的是,本申请的说明书中使用的措辞“包括”是指存在所述特征、整数、步骤、操作、元件和/或组件,但是并不排除存在或添加一个或多个其他特征、整数、步骤、操作、元件、组件和/或它们的组。应该理解,当我 们称元件被“连接”或“耦接”到另一元件时,它可以直接连接或耦接到其他元件,或者也可以存在中间元件。此外,这里使用的“连接”或“耦接”可以包括无线连接或无线耦接。这里使用的措辞“和/或”包括一个或更多个相关联的列出项的全部或任一单元和全部组合。
首先对本申请涉及的几个名词进行介绍和解释:
阈值电压:指用于界定相邻电压区间的临界电压值,例如界定高压区间和低压区间的电压值,例如144V(伏特)-1000V。
本申请的发明人进行研究发现,在现有的采用电脉冲治疗肿瘤的方案中,可以单独采用微秒脉冲或者纳秒脉冲来进行治疗,靠近电极针的细胞可以发生不可逆电穿孔、进而进入凋亡程序,但远离电极针的细胞发生的是可逆电穿孔,发生可逆电穿孔的细胞后期还会存活,因此无法达到预期的消融效果。故现有的电消融方案存在消融范围比较小、且消融不彻底的缺陷。
若想达到预期的治疗效果,需提高脉冲电压,但是高压脉冲在治疗过程中会引发患者的肌肉应激收缩,严重影响患者的治疗体验感,以至于治疗中往往需要配合麻醉剂来缓解肌肉收缩,麻醉剂的使用,不仅会增加治疗成本,还会对患者带来一定的副作用。
本申请提供的脉冲控制方法、装置及消融设备、系统、存储介质,旨在解决现有技术的如上技术问题。
下面以具体地实施例对本申请的技术方案以及本申请的技术方案如何解决上述技术问题进行详细说明。
本申请实施例提供了一种消融设备110,该消融设备的结构示意图如图1所示,包括但不限于:电极针111,脉冲发生器112和控制器113。
电极针111用于与目标物体接触并向所述目标物体输出电脉冲,例如电极针可用于伸入目标生物组织并向目标生物组织输出电脉冲。
脉冲发生器112与电极针111电连接,用于生成电脉冲并将所述电脉冲传导到所述电极针。
控制器113与脉冲发生器112通信连接,控制器113被配置为用于执行本申请实施例提供的任一种的脉冲控制方法,该脉冲控制方法将在下文 详细说明,故在此不赘述。
在本实施例中,控制器113可用于控制脉冲发生器112生成并向电极针111输出纳秒脉冲序列和毫秒脉冲序列。电极针111可用于将纳秒脉冲序列和毫秒脉冲序列作用于目标生物组织。
其中,幅值大于阈值电压的纳秒脉冲序列可以是高压纳秒脉冲序列,幅值小于阈值电压的毫秒脉冲序列可以是低压毫秒脉冲序列。
高压纳秒脉冲序列可以使靠近电极针111的细胞发生不可逆电穿孔、进而进入凋亡程序,并使距离电极针111较远的细胞发生可逆电穿孔。低压毫秒脉冲序列可以对距离电极针111较远的发生可逆电穿孔的细胞进行电解(细胞内存在水和电解质,在一定电解条件下,电解质会与电解水产生的氢氧根离子结合,从而电解质的浓度降低,这样会破坏细胞的渗透压平衡、酸碱平衡以及水平衡等,进而破坏细胞活性),使得距离电极针111较远的细胞也可以进入凋亡程序。因此,与现有的电消融方案相比,本申请实施例提供的消融设备110可以实现更大范围的消融治疗,消融可以更加彻底。
并且,高压纳秒脉冲序列因其参数特性利于降低肌肉的应激收缩,而低压毫秒脉冲序列所使用的电压较低,也不会引发肌肉的应激收缩,因此本申请实施例提供的消融设备110能够在消融过程中有效减少患者的肌肉收缩幅度、或降低肌肉收缩的概率,甚至避免肌肉收缩现象,提高患者的治疗体验,并且可以减少甚至无需麻醉剂的使用,从而有效降低治疗成本、减少副作用。
在一些可能的实施方式中,如图2所示,脉冲发生器112包括但不限于:第一子发生器112a和第二子发生器112b。
第一子发生器112a与电极针111电连接、且与控制器113通信连接,用于生成纳秒脉冲序列。
第二子发生器112b与电极针111电连接、且与控制器113通信连接,用于生成毫秒脉冲序列。
在本实施例中,脉冲发生器112采用包括两个子脉冲发生器的结构, 可实现纳秒脉冲序列与毫秒脉冲序列的独立发生,有利于各子脉冲发生器的电路设计,例如通过电路的物理结构来实现相应的脉冲参数。例如,第一子发生器112a的电路结构配置成能够生成所需的纳秒脉冲序列即可,第二子发生器112b的电路结构配置成能够生成所需的毫秒脉冲序列即可。
可选地,第一子发生器112a与第二子发生器112b可以是集成于同一块电路板的两个脉冲发生芯片。
可选地,第一子发生器112a与第二子发生器112b可以是分别位于不同电路板的独立脉冲发生单元。
在一些可能的实施方式中,消融设备110还可以包括但不限于:存储器。其中,控制器113和存储器相电连接,如通过总线相连。可选地,控制器113可以是CPU(Central Processing Unit,中央处理器),通用处理器,DSP(Digital Signal Processor,数据信号处理器),ASIC(Application Specific Integrated Circuit,专用集成电路),FPGA(Field-Programmable Gate Array,现场可编程门阵列)或者其他可编程逻辑器件、晶体管逻辑器件、硬件部件或者其任意组合。其可以实现或执行结合本申请公开内容所描述的各种示例性的逻辑方框,模块和电路。控制器113也可以是实现计算功能的组合,例如包含一个或多个微处理器组合,DSP和微处理器的组合等。
可选地,总线可包括但不限于一通路,在上述组件之间传送信息。总线可以是PCI(Peripheral Component Interconnect,外设部件互连标准)总线或EISA(Extended Industry Standard Architecture,扩展工业标准结构)总线等。总线可以分为地址总线、数据总线、控制总线等。
可选地,存储器可以是ROM(Read-Only Memory,只读存储器)或可存储静态信息和指令的其他类型的静态存储设备,RAM(random access memory,随机存取存储器)或者可存储信息和指令的其他类型的动态存储设备,也可以是EEPROM(Electrically Erasable Programmable Read Only Memory,电可擦可编程只读存储器)、CD-ROM(Compact Disc Read-Only Memory,只读光盘)或其他光盘存储、光碟存储(包括但不限于压缩光 碟、激光碟、光碟、数字通用光碟、蓝光光碟等)、磁盘存储介质或者其他磁存储设备、或者能够用于携带或存储具有指令或数据结构形式的期望的程序代码并能够由计算机存取的任何其他介质,但不限于此。
在一些可能的实施方式中,消融设备110还可以包括但不限于监测单元。监测单元可用于监测电极针111的电流和/或电压参数,控制器113通过监测单元获得的电极针111的电流和/或电压参数,来确定电极针111的工作状态。例如,若监测单元获得的电极针111的当前电流和/或当前电压参数,与电极针111在空载(未连接负载)时的电流和/或电压相符,则认为电极针111当前已将电脉冲序列输出完毕。
在一些可能的实施方式中,消融设备110还可以包括但不限于收发器。收发器可用于信号的接收和发送。收发器可以允许消融设备110的控制器113与其他设备进行无线或有线通信以交换数据,例如控制器113通过收发器接收到用户输入的停止消融指令或退针指令时,触发控制器113控制脉冲发生器112启动输出电脉冲序列或控制脉冲发生器112停止输出电脉冲序列。需要说明的是,实际应用中收发器不限于一个。
在一些可能的实施方式中,消融设备110还可以包括但不限于输入单元。输入单元可用于接收输入的数字、字符、图像和/或声音信息,或者产生与控制器113的用户设置以及功能控制有关的键信号输入。输入单元可以包括但不限于触摸屏、物理键盘、功能键(比如音量控制按键、开关按键等)、轨迹球、鼠标、操作杆、拍摄装置、拾音器等中的一种或多种。
在一些可能的实施方式中,消融设备110还可以包括但不限于输出单元。输出单元可用于输出或展示经过控制器113处理的信息。输出单元可以包括但不限于显示装置、扬声器、振动装置等中的一种或多种。
本技术领域技术人员可以理解,本申请实施例提供的消融设备110的控制器113可以为所需的目的而专门设计和制造,或者也可以包括但不限于通用计算机中的已知设备。这些设备具有存储在其内的计算机程序,这些计算机程序选择性地激活或重构。这样的计算机程序可以被存储在设备(例如,计算机)可读介质中或者存储在适于存储电子指令并分别耦联到 总线的任何类型的介质中。
基于同一发明构思,本申请实施例提供了一种脉冲控制方法,该方法包括但不限于:
控制脉冲发生器输出纳秒脉冲序列以及控制脉冲发生器输出毫秒脉冲序列,脉冲发生器输出的脉冲可以用于向目标生物组织输出纳秒脉冲序列和毫秒脉冲序列。纳秒脉冲序列的幅值大于预设的第一阈值电压,毫秒脉冲序列的幅值小于预设的第二阈值电压。
可选地,由前述实施例提供的消融设备110中的控制器113控制脉冲发生器112生成并向电极针111输出纳秒脉冲序列和毫秒脉冲序列,进而使得电极针111向目标生物组织输出纳秒脉冲序列和毫秒脉冲序列。
在本实施例中,幅值大于预设的第一阈值电压的纳秒脉冲序列可以是高压纳秒脉冲序列,幅值小于预设的第二阈值电压的毫秒脉冲序列可以是低压毫秒脉冲序列。
在一些实施例中,纳秒脉冲序列的脉冲幅值电压可以设置在5KV到100KV之间,即预设的第一阈值电压可以是5KV到100KV之间。毫秒脉冲序列的脉冲幅值电压可以设置在5V到100V之间,即预设的第一阈值电压可以是5V到100V之间。
在一些实施例中,向目标生物组织输出纳秒脉冲序列,可以诱导所述目标生物组织的第一区域(通常对应距离电极针相对较近的区域)出现细胞不可逆电穿孔,和诱导所述目标生物组织的第二区域(通常对应距离电极针相对较远的区域)出现细胞可逆电穿孔。
由于细胞膜发生可逆电穿孔时,电穿孔的存续是有一定时间窗口的,因此,为了利用可逆电穿孔存续期间实现治疗效果,在一些实施例中,在所述第二区域中至少一部分细胞可逆电穿孔存续期间,向所述目标生物组织输出所述毫秒脉冲序列,以诱导所述第二区域中的细胞启动细胞凋亡。
如此,可以利用可逆电穿孔存续期间,细胞膜的电穿孔现象,使得毫秒脉冲诱发的电场更容易穿透细胞膜而作用于目标生物组织的细胞内部,更易于实现细胞电解等电场引发的效应,从而诱发细胞凋亡。
应理解的是,显然,对于存在不可逆电穿孔的第一区域,由于细胞膜 电穿孔的存在,毫秒脉冲的诱发的电场也同样更容易作用于目标生物组织,更易于实现细胞电解等电场效应,与不可逆电穿孔本身对细胞的作用一起,在纳秒脉冲和毫秒脉冲的共同作用下诱导所述第一区域中的细胞凋亡。
由于细胞凋亡(apoptosis)与坏死(necrosis)不同,凋亡可以利用人体的免疫功能促成细胞死亡,凋亡的细胞将被人体识别为正常死亡的细胞,并通过细胞吞噬作用被清除,促进正常组织的再生与修复,从而使得更有利于恢复消融区域的生理功能。因此,根据本公开的方法,可以在肿瘤等的治疗中,相对于单独的纳秒脉冲消融,或者是单独的毫秒脉冲消融,获得更好的治疗效果。
要说明的是,在本公开中,所述毫秒脉冲表示脉宽为毫秒数量级的脉冲,以与脉宽为纳秒数量级的脉冲相区别,而不是限定了脉宽一定是几毫秒。例如,在一些实施例中,毫秒脉冲的脉宽可以在1毫秒到1000毫秒之间。
应理解的是,根据不同的目标生物组织形态和不同的纳秒脉冲激励,以及距离电极针的距离不同,目标生物组织发生可逆电穿孔的持续时间也有所不同。本领域技术人员可以在本公开的教导下,根据治疗的具体场景来选择对应的脉冲发生参数,这些选择的参数同样将落入本申请的保护范围。
在本公开的一些实施例中,向目标生物组织交替输出所述纳秒脉冲序列和所述毫秒脉冲序列,使至少一个所述纳秒脉冲的结束时间与随后相邻的所述毫秒脉冲的开始时间之间间隔设定时间,且所述设定时间不大于1秒。
在一些实施例中,纳秒脉冲结束到毫秒脉冲开始的间隔时间可以为负,即,可以是纳秒脉冲的发生期间,同时发生毫秒脉冲,使纳秒脉冲与毫秒脉冲同时作用于目标生物组织。
本实施例提供的脉冲控制方法,通过幅值大于预设的第一阈值电压的纳秒脉冲序列协同幅值小于预设的第二阈值电压的毫秒脉冲序列,能够增大有效的消融范围、消融更彻底,还能有效减少肌肉收缩幅度、或降低肌肉收缩的概率,甚至避免肌肉收缩现象,可以提高患者的治疗体验感,并 且可以减少甚至无需麻醉剂的使用,从而有效降低治疗成本、减少副作用。
具体地,高压纳秒脉冲序列可以使靠近电极针111的细胞发生不可逆电穿孔、进而进入凋亡程序,并使距离电极针111较远的细胞发生可逆电穿孔;低压毫秒脉冲序列可以对距离电极针111较远的发生可逆电穿孔的细胞进行电解(细胞内存在水和电解质,在一定电解条件下,电解质会与电解水产生的氢氧根离子结合,从而电解质的浓度降低,这样会破坏细胞的渗透压平衡、酸碱平衡以及水平衡等,进而破坏细胞活性),使得距离电极针111较远的细胞也可以进入凋亡程序。因此,与现有的电消融方案相比,本申请实施例提供的技术方案所获得的消融治疗范围更大、消融更加彻底。
并且,高压纳秒脉冲序列因其参数特性利于降低肌肉的应激收缩,而低压毫秒脉冲序列所使用的电压较低,也不会引发肌肉的应激收缩,因此本申请实施例提供的技术方案能够实现患者在治疗过程中极大缓解甚至不会出现肌肉收缩的现象,提高患者的治疗体验。
基于同一发明构思,本申请实施例提供了另一种脉冲控制方法,该方法包括但不限于:
向目标生物组织交替输出纳秒脉冲序列和毫秒脉冲序列。纳秒脉冲序列的幅值大于预设的第一阈值电压,毫秒脉冲序列的幅值小于预设的第二阈值电压。
可选地,由前述实施例提供的消融设备110中的控制器113控制脉冲发生器112交替生成并向电极针111输出纳秒脉冲序列和毫秒脉冲序列,进而使得电极针111向目标生物组织交替输出纳秒脉冲序列和毫秒脉冲序列。
本实施例提供的另一种脉冲控制方法,也是通过幅值大于阈值电压的纳秒脉冲序列协同幅值小于阈值电压的毫秒脉冲序列,能够增大有效的消融范围、消融更彻底,还能有效减少肌肉收缩幅度、或降低肌肉收缩的概率,甚至避免肌肉收缩现象,可以提高患者的治疗体验感,并且可以减少甚至无需麻醉剂的使用,从而有效降低治疗成本、减少副作用。
在本实施例中,纳秒脉冲序列和毫秒脉冲序列是交替着向目标生物组织输出的,这样一方面有利于控制高压纳秒脉冲序列的长度,即控制每一段高压纳秒脉冲序列对目标生物组织的作用时间,降低肌肉的应激收缩概率;另一方面有利于实现包括纳秒脉冲序列和毫秒脉冲序列的整体脉冲的持续进行,减少空档期,提高消融效率。
基于上述实施例,本申请的发明人提供以下九种交替输出纳秒脉冲序列和毫秒脉冲序列的可选实施方式:
在第一种实施方式中,如图4和图8所示,每确定已输出纳秒脉冲序列中的一个纳秒脉冲,则输出毫秒脉冲序列中的一个毫秒脉冲。
可选地,由前述实施例提供的消融设备110中的控制器113每确定电极针111已输出纳秒脉冲序列中的一个纳秒脉冲,则控制脉冲发生器112生成并向电极针111输出毫秒脉冲序列中的一个毫秒脉冲,进而使得电极针111向目标生物组织输出毫秒脉冲序列中的一个毫秒脉冲。
在本实施例中,纳秒脉冲序列中的每一个纳秒脉冲,与毫秒脉冲序列中的每一个毫秒脉冲依次交替生成并输出,且高压纳秒脉冲在前生成并输出,低压毫秒脉冲在后生成及输出。
在第二种实施方式中,每确定已输出毫秒脉冲序列中的一个毫秒脉冲,则输出纳秒脉冲序列中的一个纳秒脉冲。
可选地,由前述实施例提供的消融设备110中的控制器113每确定电极针111已输出毫秒脉冲序列中的一个毫秒脉冲,则控制脉冲发生器112生成并向电极针111输出纳秒脉冲序列中的一个纳秒脉冲,进而使得电极针111向目标生物组织输出纳秒脉冲序列中的一个纳秒脉冲。
在本实施例中,纳秒脉冲序列中的每一个纳秒脉冲,与毫秒脉冲序列中的每一个毫秒脉冲依次交替生成并输出,低压毫秒脉冲在前生成并输出,高压纳秒脉冲在后生成及输出。
在第三种实施方式中,如图5、图7、图9、图11、图13和图14所示,每确定已输出纳秒脉冲序列中的至少一部分纳秒脉冲,则输出毫秒脉冲序列中至少一部分毫秒脉冲。
可选地,由前述实施例提供的消融设备110中的控制器113每确定电极针111已输出纳秒脉冲序列中的至少一部分纳秒脉冲,则控制脉冲发生器112生成并向电极针111输出毫秒脉冲序列中的至少一部分毫秒脉冲,进而使得电极针111向目标生物组织输出毫秒脉冲序列中的至少一部分毫秒脉冲。
在本实施例中,纳秒脉冲序列中的每段纳秒脉冲子序列,与毫秒脉冲序列中的每段毫秒脉冲子序列依次交替生成并输出,且高压纳秒脉冲子序列在前生成并输出,低压毫秒脉冲子序列在后生成及输出。
例如,纳秒脉冲序列依次包括:1号纳秒脉冲、2号纳秒脉冲、3号纳秒脉冲、4号纳秒脉冲、5号纳秒脉冲和6号纳秒脉冲。其中,1号纳秒脉冲和2号纳秒脉冲组成1号纳秒脉冲子序列,3号纳秒脉冲和4号纳秒脉冲组成2号纳秒脉冲子序列,5号纳秒脉冲和6号纳秒脉冲组成3号纳秒脉冲子序列。
毫秒脉冲序列依次包括:1号毫秒脉冲、2号毫秒脉冲、3号毫秒脉冲、4号毫秒脉冲、5号毫秒脉冲和6号毫秒脉冲。其中,1号毫秒脉冲和2号毫秒脉冲组成1号毫秒脉冲子序列,3号毫秒脉冲和4号毫秒脉冲组成2号毫秒脉冲子序列,5号毫秒脉冲和6号毫秒脉冲组成3号毫秒脉冲子序列。
前述实施例提供的消融设备110中的控制器113确定电极针111已输出1号纳秒脉冲子序列(包括1号纳秒脉冲和2号纳秒脉冲)后,控制脉冲发生器112生成并向电极针111输出1号毫秒脉冲子序列(包括1号毫秒脉冲和2号毫秒脉冲),以此类推。
在第四种实施方式中,每确定已输出毫秒脉冲序列中至少一部分毫秒脉冲,则输出纳秒脉冲序列中的至少一部分纳秒脉冲。
可选地,由前述实施例提供的消融设备110中的控制器113每确定电极针111已输出毫秒脉冲序列中的至少一部分毫秒脉冲,则控制脉冲发生器112生成并向电极针111输出纳秒脉冲序列中的至少一部分纳秒脉冲,进而使得电极针111向目标生物组织输出纳秒脉冲序列中的至少一部分 纳秒脉冲。
在本实施例中,纳秒脉冲序列中的每段纳秒脉冲子序列,与毫秒脉冲序列中的每段毫秒脉冲子序列依次交替生成并输出,低压毫秒脉冲子序列在前生成并输出,高压纳秒脉冲子序列在后生成及输出。
在第五种实施方式中,如图10所示,每确定已输出纳秒脉冲序列中的至少一部分纳秒脉冲,则输出毫秒脉冲序列中的一个毫秒脉冲。
可选地,由前述实施例提供的消融设备110中的控制器113每确定电极针111已输出纳秒脉冲序列中的至少一部分纳秒脉冲,则控制脉冲发生器112生成并向电极针111输出毫秒脉冲序列中的一个毫秒脉冲,进而使得电极针111向目标生物组织输出毫秒脉冲序列中的一个毫秒脉冲。
在本实施例中,纳秒脉冲序列中的每段纳秒脉冲子序列,与毫秒脉冲序列中的每一个毫秒脉冲依次交替生成并输出,且高压纳秒脉冲子序列在前生成并输出,低压毫秒脉冲在后生成及输出。
在第六种实施方式中,如图12所示,每确定已输出毫秒脉冲序列中的至少一部分毫秒脉冲,则输出纳秒脉冲序列中的一个纳秒脉冲。
可选地,由前述实施例提供的消融设备110中的控制器113每确定电极针111已输出毫秒脉冲序列中的至少一部分毫秒脉冲,则控制脉冲发生器112生成并向电极针111输出纳秒脉冲序列中的一个纳秒脉冲,进而使得电极针111向目标生物组织输出纳秒脉冲序列中的一个纳秒脉冲。
在本实施例中,纳秒脉冲序列中的一个纳秒脉冲,与毫秒脉冲序列中的每段毫秒脉冲子序列依次交替生成并输出,低压毫秒脉冲子序列在前生成并输出,高压纳秒脉冲在后生成及输出。
在第七种实施方式中,如图4和图5所示,至少一个纳秒脉冲与相邻的毫秒脉冲之间间隔设定时间。
可选地,由前述实施例提供的消融设备110中的控制器113控制脉冲发生器112生成并向电极针111输出纳秒脉冲序列中的一个纳秒脉冲或一段纳秒脉冲子序列,并停顿设定时间后,再控制脉冲发生器112生成并向电极针111输出毫秒脉冲序列中的一个毫秒脉冲或一段毫秒脉冲子序列。
或者,由前述实施例提供的消融设备110中的控制器113控制脉冲发生器112生成并向电极针111输出毫秒脉冲序列中的一个毫秒脉冲或一段毫秒脉冲子序列,并停顿设定时间后,再控制脉冲发生器112生成并向电极针111输出纳秒脉冲序列中的一个纳秒脉冲或一段纳秒脉冲子序列。
在本实施例中,纳秒脉冲与毫秒脉冲之间的转换节点处可以停顿设定时间,这样有利于为目标生物组织处的细胞提供缓冲时间,满足一些治疗场景的需求。
可选地,设定时间不小于1纳秒,且不大于1秒。这样有利于目标生物组织处的细胞能够延续一定的电脉冲的作用惯性,同时降低目标生物组织处的细胞完全失去电脉冲作用的概率,保证消融效果。
在第八种实施方式中,如图6所示,至少一个纳秒脉冲的下降沿与相邻的毫秒脉冲的上升沿对应。
可选地,由前述实施例提供的消融设备110中的控制器113每确定电极针111已输出纳秒脉冲序列中的一个纳秒脉冲或一段纳秒脉冲子序列中的最后一个纳秒脉冲,立刻控制脉冲发生器112生成并向电极针111输出毫秒脉冲序列中的一个毫秒脉冲或一段毫秒脉冲子序列。
在本实施例中,相邻的纳秒脉冲与毫秒脉冲之间是没有停顿间隔的无缝转换,这样有利于为目标生物组织处的细胞提供连续的电脉冲作用,有利于缩短治疗时间,提高电脉冲的作用强度。
在第九种实施方式中,至少一个纳秒脉冲的上升沿与相邻的毫秒脉冲的下降沿对应。
可选地,由前述实施例提供的消融设备110中的控制器113每确定电极针111已输出毫秒脉冲序列中的一个毫秒脉冲或一段毫秒脉冲子序列中的最后一个毫秒脉冲,立刻控制脉冲发生器112生成并向电极针111输出纳秒脉冲序列中的一个纳秒脉冲或一段纳秒脉冲子序列。
需要说明的是,纳秒脉冲序列和毫秒脉冲序列的交替输出形式并不局限于以上各实施例提供的实现方式。
本申请的发明人考虑到,高压纳秒脉冲序列可以使靠近电极针的细胞 发生不可逆电穿孔、进而进入凋亡程序,并使距离电极针较远的细胞发生可逆电穿孔,以及降低肌肉的应激收缩。为此,本申请为纳秒脉冲序列的相关参数或特征提供如下几种可能的实现方式:
可选地,纳秒脉冲序列的频率不小于0.1赫兹,且不大于10赫兹。
可选地,纳秒脉冲序列包括但不限于不少于2个纳秒脉冲,且不大于5000个纳秒脉冲。
可选地,纳秒脉冲序列中至少一个纳秒脉冲的脉宽不小于10纳秒,且不大于1000纳秒。
可选地,纳秒脉冲序列中至少一个纳秒脉冲的幅值不小于5千伏,且不大于100千伏。
可选地,纳秒脉冲序列为方波脉冲序列。
可选地,如图7-图14所示,纳秒脉冲序列为双极性脉冲序列。
本申请的发明人考虑到,低压毫秒脉冲序列可以对距离电极针较远的发生可逆电穿孔的细胞进行电解,使得距离电极针较远的细胞也可以进入凋亡程序。为此,本申请为纳秒脉冲序列的相关参数或特征提供如下几种可能的实现方式:
可选地,毫秒脉冲序列的频率不小于0.1赫兹,且不大于10赫兹。
可选地,毫秒脉冲序列包括但不限于不少于2个毫秒脉冲,且不大于5000个毫秒脉冲。
可选地,毫秒脉冲序列中至少一个毫秒脉冲的脉宽不小于1毫秒,且不大于1000毫秒。
可选地,毫秒脉冲序列中至少一个毫秒脉冲的幅值不小于5伏,且不大于100伏。
可选地,毫秒脉冲序列为方波脉冲序列。
可选地,如图7-图14所示,毫秒脉冲序列为双极性脉冲序列。
基于同一发明构思,本申请实施例提供的一种脉冲控制装置,包括但不限于:电脉冲控制模块。
电脉冲控制模块用于向目标生物组织输出纳秒脉冲序列和毫秒脉冲 序列。纳秒脉冲序列的幅值大于阈值电压,毫秒脉冲序列的幅值小于阈值电压。
在本实施例中,脉冲控制装置通过幅值大于阈值电压的纳秒脉冲序列协同幅值小于阈值电压的毫秒脉冲序列,能够增大有效的消融范围、消融更彻底,还能有效减少肌肉收缩幅度、或降低肌肉收缩的概率,甚至避免肌肉收缩现象,可以提高患者的治疗体验感,并且可以减少甚至无需麻醉剂的使用,从而有效降低治疗成本、减少副作用。
具体地,高压纳秒脉冲序列可以使靠近电极针111的细胞发生不可逆电穿孔、进而进入凋亡程序,并使距离电极针111较远的细胞发生可逆电穿孔;低压毫秒脉冲序列可以对距离电极针111较远的发生可逆电穿孔的细胞进行电解(细胞内存在水和电解质,在一定电解条件下,电解质会与电解水产生的氢氧根离子结合,从而电解质的浓度降低,这样会破坏细胞的渗透压平衡、酸碱平衡以及水平衡等,进而破坏细胞活性),使得距离电极针111较远的细胞也可以进入凋亡程序。因此,与现有的电消融方案相比,本申请实施例提供的技术方案所获得的消融治疗范围更大、消融更加彻底。
并且,高压纳秒脉冲序列因其参数特性利于降低肌肉的应激收缩,而低压毫秒脉冲序列所使用的电压较低,也不会引发肌肉的应激收缩,因此本申请实施例提供的技术方案能够实现患者在治疗过程中极大缓解甚至不会出现肌肉收缩的现象,提高患者的治疗体验。
在一些可能的实施方式中,电脉冲控制模块用于向目标生物组织交替输出纳秒脉冲序列和毫秒脉冲序列。
可选地,电脉冲控制模块用于每确定已输出纳秒脉冲序列中的一个纳秒脉冲,则输出毫秒脉冲序列中的一个毫秒脉冲。
可选地,电脉冲控制模块用于每确定已输出毫秒脉冲序列中的一个毫秒脉冲,则输出纳秒脉冲序列中的一个纳秒脉冲。
可选地,电脉冲控制模块用于每确定已输出纳秒脉冲序列中的至少一部分纳秒脉冲,则输出毫秒脉冲序列中至少一部分毫秒脉冲。
可选地,电脉冲控制模块用于每确定已输出毫秒脉冲序列中至少一部 分毫秒脉冲,则输出纳秒脉冲序列中的至少一部分纳秒脉冲。
可选地,电脉冲控制模块用于每确定已输出纳秒脉冲序列中的至少一部分纳秒脉冲,则输出毫秒脉冲序列中的一个毫秒脉冲。
可选地,电脉冲控制模块用于每确定已输出毫秒脉冲序列中的至少一部分毫秒脉冲,则输出纳秒脉冲序列中的一个纳秒脉冲。
基于同一的发明构思,本申请实施例提供了一种计算机可读存储介质,该计算机可读存储介质上存储有计算机程序,该程序被处理器执行时实现本申请实施例所提供的任一脉冲控制方法。
本申请实施例提供了一种计算机可读存储介质适用于上述任一脉冲控制方法的各种可选实施方式。在此不再赘述。
本技术领域技术人员可以理解,本实施例提供的计算机可读存储介质可以是任何能够被电子设备访问的可用介质,包括易失性介质和非易失性介质、可移动介质或不可移动介质。计算机可读存储介质包括但不限于任何类型的盘(包括软盘、硬盘、光盘、CD-ROM、和磁光盘)、ROM、RAM、EPROM(Erasable Programmable Read-Only Memory,可擦写可编程只读存储器)、EEPROM(Electrically Erasable Programmable Read Only Memory,电可擦可编程只读存储器)、闪存、磁性卡片或光线卡片。也就是,计算机可读存储介质包括由设备(例如,计算机)以能够读的形式存储或传输信息的任何介质。
基于同一发明构思,本申请实施例提供了一种消融系统100,该系统的框架示意图如图3所示,包括但不限于:如前述各实施例提供的任一种消融设备110,和上位机120。上位机120与消融设备110中的控制器113通信连接。
在本实施例中,上位机120可以实现对消融设备110的程序更新或数据备份,也可以实现对消融设备110的远程控制,进而可以利于消融设备110的功能扩展。
可选地,上位机120通过WIFI(Wireless Fidelity,无线保真,又称行动热点)与消融设备110中的控制器113通信连接。
可选地,上位机120通过云端与消融设备110中的控制器113通信连 接。
下面举例几组实验例与对比例,对本申请各实施例中高压纳秒脉冲序列与低压毫秒脉冲序列的协同作用的效果进行论证。
以下各实验例与对比例,实验对象均采用新西兰大白兔(雌性,6月龄,体重2.5kg±0.2kg),新西兰大白兔由重庆医科大学动物实验中心提供,在清洁恒温动物饲养实验室进行饲养。
各实验例与对比例均采用本公司自主研发的消融设备110,包括电极针111、脉冲发生器112和控制器113。消融设备110的脉冲发生器112可以输出的脉冲参数为10ns-100ms,幅值0-200kV可调,频率0.1-1kHz。其中电极针由医用不锈钢自行加工完成,电极针直径均为1mm,裸露长度8mm,电极间距统一采用自制的间隔器固定为10mm。
实验例1采用高压纳秒脉冲序列与低压毫秒脉冲序列的协同作用,相关数据请参见表1。
表1
Figure PCTCN2022086396-appb-000001
实验例2采用高压纳秒脉冲序列与低压毫秒脉冲序列的协同作用,相关数据请参见表2。
表2
Figure PCTCN2022086396-appb-000002
Figure PCTCN2022086396-appb-000003
实验例3采用高压纳秒脉冲序列与低压毫秒脉冲序列的协同作用,相关数据请参见表3。
表3
Figure PCTCN2022086396-appb-000004
对比例1采用高压微秒脉冲序列,相关数据请参见表4。
表4
对比例1 微秒脉冲
脉宽 100us(微秒)
幅值 1.5kV
个数 100
电极针间距 10mm
肌肉收缩表现 肌肉收缩强烈,收缩力度4g(克)
消融面积 110mm 2
消融区域的长宽尺寸 最大长度17mm,最大宽度11.2mm
由实验例1-3以及对比例1的相关数据可见,采用高压纳秒脉冲序列与低压毫秒脉冲序列的协同作用,能够增大有效的消融范围、消融更彻底,还能有效抑制肌肉收缩。
应用本申请实施例,至少能够实现如下有益效果:
1、通过幅值大于阈值电压的纳秒脉冲序列协同幅值小于阈值电压的毫秒脉冲序列,能够增大有效的消融范围、消融更彻底,还能有效减少肌肉收缩幅度、或降低肌肉收缩的概率,甚至避免肌肉收缩现象,可以提高患者的治疗体验感,并且可以减少甚至无需麻醉剂的使用,从而有效降低治疗成本、减少副作用。
2、纳秒脉冲序列和毫秒脉冲序列是交替着向目标生物组织输出的,这样一方面有利于控制高压纳秒脉冲序列的长度,即控制每一段高压纳秒脉冲序列对目标生物组织的作用时间,降低肌肉的应激收缩概率;另一方面有利于实现包括纳秒脉冲序列和毫秒脉冲序列的整体脉冲的持续进行,减少空档期,提高消融效率。
3、纳秒脉冲与毫秒脉冲之间的转换节点处可以停顿设定时间,这样有利于为目标生物组织处的细胞提供缓冲时间,满足一些治疗场景的需求。
4、相邻的纳秒脉冲与毫秒脉冲之间是没有停顿间隔的无缝转换,这样有利于为目标生物组织处的细胞提供连续的电脉冲作用,有利于缩短治疗时间,提高电脉冲的作用强度。
本技术领域技术人员可以理解,本申请中已经讨论过的各种操作、方法、流程中的步骤、措施、方案可以被交替、更改、组合或删除。进一步地,具有本申请中已经讨论过的各种操作、方法、流程中的其他步骤、措施、方案也可以被交替、更改、重排、分解、组合或删除。进一步地,现有技术中的具有与本申请中公开的各种操作、方法、流程中的步骤、措施、方案也可以被交替、更改、重排、分解、组合或删除。
在本申请的描述中,需要理解的是,术语“中心”、“上”、“下”、“前”、“后”、“左”、“右”、“竖直”、“水平”、“顶”、“底”、 “内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系,仅是为了便于描述本申请和简化描述,而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作,因此不能理解为对本申请的限制。
术语“第一”、“第二”仅用于描述目的,而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量。由此,限定有“第一”、“第二”的特征可以明示或者隐含地包括一个或者更多个该特征。在本申请的描述中,除非另有说明,“多个”的含义是两个或两个以上。
在本申请的描述中,需要说明的是,除非另有明确的规定和限定,术语“安装”、“相连”、“连接”应做广义理解,例如,可以是固定连接,也可以是可拆卸连接,或一体地连接;可以是直接相连,也可以通过中间媒介间接相连,可以是两个元件内部的连通。对于本领域的普通技术人员而言,可以具体情况理解上述术语在本申请中的具体含义。
在本说明书的描述中,具体特征、结构、材料或者特点可以在任何的一个或多个实施例或示例中以合适的方式结合。
应该理解的是,虽然附图的流程图中的各个步骤按照箭头的指示依次显示,但是这些步骤并不是必然按照箭头指示的顺序依次执行。除非本文中有明确的说明,这些步骤的执行并没有严格的顺序限制,其可以以其他的顺序执行。而且,附图的流程图中的至少一部分步骤可以包括多个子步骤或者多个阶段,这些子步骤或者阶段并不必然是在同一时刻执行完成,而是可以在不同的时刻执行,其执行顺序也不必然是依次进行,而是可以与其他步骤或者其他步骤的子步骤或者阶段的至少一部分轮流或者交替地执行。
以上所述仅是本申请的部分实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本申请原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本申请的保护范围。

Claims (22)

  1. 一种脉冲控制方法,其特征在于,包括:
    控制脉冲发生器输出纳秒脉冲序列,以及
    控制脉冲发生器输出毫秒脉冲序列;
    其中,所述纳秒脉冲序列的幅值大于预设的第一阈值电压,所述毫秒脉冲序列的幅值小于预设的第二阈值电压。
  2. 根据权利要求1所述的脉冲控制方法,其特征在于,所述控制脉冲发生器输出纳秒脉冲序列以及控制脉冲发生器输出毫秒脉冲序列,包括:
    交替输出所述纳秒脉冲序列和所述毫秒脉冲序列。
  3. 根据权利要求2所述的脉冲控制方法,其特征在于,所述交替输出所述纳秒脉冲序列和所述毫秒脉冲序列,包括:
    每确定已输出所述纳秒脉冲序列中的一个纳秒脉冲,则输出所述毫秒脉冲序列中的一个毫秒脉冲;和/或
    每确定已输出所述毫秒脉冲序列中的一个毫秒脉冲,则输出所述纳秒脉冲序列中的一个纳秒脉冲。
  4. 根据权利要求2所述的脉冲控制方法,其特征在于,所述交替输出所述纳秒脉冲序列和所述毫秒脉冲序列,包括:
    每确定已输出所述纳秒脉冲序列中的至少一部分纳秒脉冲,则输出所述毫秒脉冲序列中至少一部分毫秒脉冲;和/或
    每确定已输出所述毫秒脉冲序列中至少一部分毫秒脉冲,则输出所述纳秒脉冲序列中的至少一部分纳秒脉冲。
  5. 根据权利要求2所述的脉冲控制方法,其特征在于,所述交替输出所述纳秒脉冲序列和所述毫秒脉冲序列,包括:
    每确定已输出所述纳秒脉冲序列中的至少一部分纳秒脉冲,则输出所述毫秒脉冲序列中的一个毫秒脉冲;和/或
    每确定已输出所述毫秒脉冲序列中的至少一部分毫秒脉冲,则输出所述纳秒脉冲序列中的一个纳秒脉冲。
  6. 根据权利要求3-5中任一项所述的脉冲控制方法,其特征在于,至少一个所述纳秒脉冲与相邻的所述毫秒脉冲之间间隔设定时间。
  7. 根据权利要求6所述的脉冲控制方法,其特征在于,所述设定时间不小于1纳秒,且不大于1秒。
  8. 根据权利要求3-5中任一项所述的脉冲控制方法,其特征在于,至少一个所述纳秒脉冲的下降沿与相邻的所述毫秒脉冲的上升沿对应;和/或,
    至少一个所述纳秒脉冲的上升沿与相邻的所述毫秒脉冲的下降沿对应。
  9. 根据权利要求1-5中任一项所述的脉冲控制方法,其特征在于,至少一个所述纳秒脉冲的结束时间与随后相邻的所述毫秒脉冲的开始时间之间间隔设定时间,且所述设定时间不大于1秒。
  10. 根据权利要求1-5中任一项所述的脉冲控制方法,其特征在于,所述纳秒脉冲序列具备以下特征中的一项或一项以上:
    所述纳秒脉冲序列的频率不小于0.1赫兹,且不大于10赫兹;
    所述纳秒脉冲序列包括不少于2个纳秒脉冲,且不大于5000个纳秒脉冲;
    所述纳秒脉冲序列中至少一个纳秒脉冲的脉宽不小于10纳秒,且不大于1000纳秒;
    所述纳秒脉冲序列中至少一个纳秒脉冲的幅值不小于5千伏,且不大于100千伏;
    所述纳秒脉冲序列为方波脉冲序列;
    所述纳秒脉冲序列为双极性脉冲序列。
  11. 根据权利要求1-5中任一项所述的脉冲控制方法,其特征在于,所述毫秒脉冲序列具备以下特征中的一项或一项以上:
    所述毫秒脉冲序列的频率不小于0.1赫兹,且不大于10赫兹;
    所述毫秒脉冲序列包括不少于2个毫秒脉冲,且不大于5000个毫秒脉冲;
    所述毫秒脉冲序列中至少一个毫秒脉冲的脉宽不小于1毫秒,且不大于1000毫秒;
    所述毫秒脉冲序列中至少一个毫秒脉冲的幅值不小于5伏,且不大于100伏;
    所述毫秒脉冲序列为方波脉冲序列;
    所述毫秒脉冲序列为双极性脉冲序列。
  12. 一种脉冲控制装置,其特征在于,包括:
    电脉冲控制模块,被配置为控制脉冲发生器输出纳秒脉冲序列,以及控制脉冲发生器输出毫秒脉冲序列;
    并且,控制所述纳秒脉冲序列的幅值大于预设的第一阈值电压,控制所述毫秒脉冲序列的幅值小于预设的第二阈值电压。
  13. 一种消融设备,其特征在于,包括:
    电极针,用于与目标物体接触并向所述目标物体输出电脉冲;
    脉冲发生器,与所述电极针电连接,用于生成电脉冲并将所述电脉冲传导到所述电极针;
    控制器,与所述脉冲发生器通信连接,所述控制器被配置为用于执行 如权利要求1-11中任一项所述的脉冲控制方法。
  14. 根据权利要求13所述的消融设备,其特征在于,所述脉冲发生器包括:
    第一子发生器,与所述电极针电连接、且与所述控制器通信连接,用于生成所述纳秒脉冲序列;和
    第二子发生器,与所述电极针电连接、且与所述控制器通信连接,用于生成所述毫秒脉冲序列。
  15. 一种消融系统,其特征在于,包括:如权利要求13或14所述的消融设备,和上位机;
    所述上位机与所述消融设备中的控制器通信连接。
  16. 一种非易失性计算机可读存储介质,其特征在于,存储有计算机程序,所述计算机程序被处理器执行时实现如权利要求1-11中任一项所述的脉冲控制方法。
  17. 一种脉冲控制方法,其特征在于,包括:
    向目标生物组织输出纳秒脉冲序列,以及
    向目标生物组织输出毫秒脉冲序列;
    其中,所述纳秒脉冲序列的幅值大于预设的第一阈值电压,所述毫秒脉冲序列的幅值小于预设的第二阈值电压。
  18. 根据权利要求17所述的方法,其特征在于,
    所述向目标生物组织输出纳秒脉冲序列,以及向目标生物组织输出毫秒脉冲序列,包括:
    向目标生物组织输出纳秒脉冲序列,以诱导所述目标生物组织的第一区域出现细胞不可逆电穿孔,和诱导所述目标生物组织的第二区域出现细胞可逆电穿孔;以及
    在所述第二区域中至少一部分细胞可逆电穿孔存续期间,向所述目标生物组织输出所述毫秒脉冲序列,以诱导所述第二区域中的细胞启动细胞凋亡。
  19. 根据权利要求17或18所述的方法,其特征在于,所述向目标生物组织输出纳秒脉冲序列,以及向目标生物组织输出毫秒脉冲序列包括:
    向目标生物组织交替输出所述纳秒脉冲序列和所述毫秒脉冲序列。
  20. 根据权利要求19所述的方法,其特征在于,所述向目标生物组织交替输出所述纳秒脉冲序列和所述毫秒脉冲序列,包括:
    至少一个所述纳秒脉冲的结束时间与随后相邻的所述毫秒脉冲的开始时间之间间隔设定时间,且所述设定时间不大于1秒。
  21. 根据权利要求17或18所述的脉冲控制方法,其特征在于,所述纳秒脉冲序列具备以下特征中的一项或一项以上:
    所述纳秒脉冲序列的频率不小于0.1赫兹,且不大于10赫兹;
    所述纳秒脉冲序列包括不少于2个纳秒脉冲,且不大于5000个纳秒脉冲;
    所述纳秒脉冲序列中至少一个纳秒脉冲的脉宽不小于10纳秒,且不大于1000纳秒;
    所述纳秒脉冲序列中至少一个纳秒脉冲的幅值不小于5千伏,且不大于100千伏;
    所述纳秒脉冲序列为方波脉冲序列;
    所述纳秒脉冲序列为双极性脉冲序列。
  22. 根据权利要求17或18所述的脉冲控制方法,其特征在于,所述毫秒脉冲序列具备以下特征中的一项或一项以上:
    所述毫秒脉冲序列的频率不小于0.1赫兹,且不大于10赫兹;
    所述毫秒脉冲序列包括不少于2个毫秒脉冲,且不大于5000个毫秒 脉冲;
    所述毫秒脉冲序列中至少一个毫秒脉冲的脉宽不小于1毫秒,且不大于1000毫秒;
    所述毫秒脉冲序列中至少一个毫秒脉冲的幅值不小于5伏,且不大于100伏;
    所述毫秒脉冲序列为方波脉冲序列;
    所述毫秒脉冲序列为双极性脉冲序列。
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