CN115192182A

CN115192182A - Irreversible electroporation therapy apparatus and bioimpedance measurement method

Info

Publication number: CN115192182A
Application number: CN202210815951.9A
Authority: CN
Inventors: 谭坚文; 李建勇; 徐黎; 夏舒河
Original assignee: Shenzhen Maiwei Medical Technology Co ltd
Current assignee: Shenzhen Maiwei Medical Technology Co ltd
Priority date: 2022-07-12
Filing date: 2022-07-12
Publication date: 2022-10-18

Abstract

The present application relates to an irreversible electroporation therapy apparatus and a bioimpedance measurement method. The irreversible electroporation treatment equipment comprises a high-voltage pulse module, a differential sampling module, a voltage processing module, a current sensing module, a high-frequency sampling module and a main control module. This application carries out the partial pressure through the voltage of the anodal output of difference sampling module to high-voltage pulse module and negative output, gather, can sample high-voltage pulse signal's voltage in real time when irreversible electroporation treatment equipment carries out high-voltage pulse and perforates, and through voltage processing module, current sensing module and high frequency sampling module finally obtain the digital feedback signal who corresponds with the impedance of target tissue, thereby need not additionally to export a pulse signal in high-voltage pulse signal's output gap, can acquire the impedance of target tissue in real time.

Description

Irreversible electroporation therapy apparatus and bioimpedance measurement method

Technical Field

The application belongs to the technical field of surgical medical equipment, and particularly relates to irreversible electroporation treatment equipment and a bioimpedance measurement method.

Background

At present, in irreversible electroporation therapy of tumors by using high-frequency high-voltage electric pulses, research on the action mechanism is not deep, and the therapeutic effect is closely related to the peak voltage, the pulse width, the pulse pause time, the pulse repetition frequency and the like of the high-voltage pulses. Besides, irreversible electroporation therapy lacks a means for evaluating the efficacy in real time to confirm the efficacy of the therapy in real time during the course of the therapy. Meanwhile, the real-time curative effect evaluation means can provide a basis for adjusting the high-voltage pulse parameters so as to realize personalized and optimized treatment.

The physiological function and pathological state of the living body can be reflected by the electrical impedance of the living body, namely the bioelectrical impedance. In recent years, the bioelectrical impedance technology is mostly applied to the fields of basic medicine, clinical diagnosis, human body composition analysis and the like. The method for measuring the bioelectrical impedance mainly comprises the following steps: a balanced bridge method, a double-electrode method and a four-ring electrode method. In recent years, technical methods for obtaining an electrical impedance spectrum of a measured object through time-frequency domain transformation of a time-domain impulse response have been applied in various fields.

At present, the measurement of the tissue electrical impedance spectrum representing the treatment process and the result in the irreversible electroporation treatment process is obtained by additionally applying a measurement signal, namely, a scanning signal in a frequency domain or a low-voltage pulse is applied, the measurement mode is implemented in the treatment interval of the irreversible electroporation, and real-time monitoring is difficult to realize. In addition, in the prior art, measurement signals need to be additionally added, so that the treatment time is increased, the system complexity is increased, and the popularization and the application of the technology are not facilitated.

Disclosure of Invention

The present application aims to provide an irreversible electroporation therapy apparatus and a bio-impedance measurement method, which aim to solve the problem that the conventional irreversible electroporation therapy apparatus cannot really acquire an impedance spectrum of a target tissue in real time.

A first aspect of embodiments of the present application provides an irreversible electroporation therapy apparatus, comprising: a high voltage pulse module configured to generate a corresponding high voltage pulse signal according to a pulse control signal and apply the high voltage pulse signal to a target tissue through a positive output terminal and a negative output terminal of the high voltage pulse module; a differential sampling module connected to a positive output terminal and a negative output terminal of the high-voltage pulse module, and configured to generate and output a first feedback voltage and a second feedback voltage according to voltage changes of the positive output terminal and the negative output terminal, respectively, when the high-voltage pulse module applies the high-voltage pulse signal to the target tissue; the voltage processing module is connected with the differential sampling module and is configured to generate and output a voltage feedback signal according to the first feedback voltage and the second feedback voltage; a current sensing module connected to the high voltage pulse module and configured to generate and output a current feedback signal according to a current of the positive output terminal or the negative output terminal when the high voltage pulse module applies the high voltage pulse signal to the target tissue; the high-frequency sampling module is respectively connected with the voltage processing module and the current sensing module and is configured to generate and output corresponding digital feedback signals according to the voltage feedback signals and the current feedback signals; and the main control module is respectively connected with the high-voltage pulse module and the high-frequency sampling module, is configured to generate and output the pulse control signal, and generates a bioelectrical impedance spectrum and adjusts the high-voltage pulse signal according to the received digital feedback signal.

In one embodiment, the differential sampling module includes a first sampling branch and a second sampling branch, the first sampling branch is connected between the positive output end and the voltage processing module, and the second sampling branch is connected between the negative output end and the voltage processing module; the first sampling branch is configured to generate the first feedback voltage, and the second sampling branch is configured to generate the second feedback voltage.

In one embodiment, the first sampling branch includes a first broadband voltage dividing unit and a first single-ended amplifying unit; the first broadband voltage dividing unit is respectively connected with the anode output end and the first single-ended amplifying unit, the first single-ended amplifying unit is further connected with the voltage processing module, and the first single-ended amplifying unit is configured to generate the first feedback voltage according to a voltage obtained by voltage division of the first broadband voltage dividing unit.

In an embodiment, the second sampling branch includes a second broadband voltage dividing unit and a second single-ended amplifying unit; the second broadband voltage dividing unit is respectively connected with the anode output end and the second single-ended amplifying unit, the second single-ended amplifying unit is further connected with the voltage processing module, and the second single-ended amplifying unit is configured to generate the second feedback voltage according to the voltage obtained by voltage division of the second broadband voltage dividing unit.

In an embodiment, the first sampling branch further includes a first protection unit, the second sampling branch further includes a second protection unit, the first protection unit is connected between the first broadband voltage dividing unit and the first single-ended amplification unit, and the second protection unit is connected between the second broadband voltage dividing unit and the second single-ended amplification unit; the first and second protection units are configured to limit magnitudes of voltages transmitted to the first and second single-ended amplification units, respectively.

In one embodiment, the voltage processing module includes a differential amplifying unit and a third protection unit, which are connected to each other, the differential amplifying unit is further connected to the differential sampling module, the differential amplifying unit is configured to generate the voltage feedback signal according to the first feedback voltage and the second feedback voltage, the third protection unit is further connected to the high-frequency sampling module, and the third protection unit is configured to limit the amplitude of the voltage transmitted to the high-frequency sampling module.

In one embodiment, the current sensing module includes a coupling coil and a load unit, the coupling coil is sleeved on an output wire of the positive output end or the negative output end, an output end of the coupling coil is connected with the load unit, the load unit is further connected with the high-frequency sampling module, the coupling coil is configured to generate a corresponding induced current according to a current of the output wire, and the load unit is configured to generate and output the current feedback signal according to the induced current.

In one embodiment, the high-frequency sampling module comprises a filtering and shaping unit, a range selection unit, an AD conversion unit and a sampling processing unit which are connected in sequence, the filtering and shaping unit is respectively connected with the voltage processing module and the current sensing module, and the sampling processing unit is connected with the main control module and the range selection unit; the filtering and shaping unit is configured to convert the received voltage feedback signal and the received current feedback signal according to a set measuring range to obtain a corresponding analog signal, and the AD conversion unit is configured to sample the analog signal according to a preset frequency to obtain a digital signal; the sampling processing unit is configured to generate a corresponding digital feedback signal according to the digital signal output by the AD conversion unit and configure the range of the range selection unit according to the digital feedback signal.

A second aspect of the embodiments of the present application provides a bioimpedance measurement method applied to the irreversible electroporation therapy apparatus as described above, the bioimpedance measurement method including: under the condition that the high-voltage pulse module outputs a high-voltage pulse signal, acquiring the digital feedback signal provided by the high-frequency sampling module; wherein the digital feedback signal comprises a voltage digital signal and a current digital signal; performing wavelet denoising and filtering processing on the digital feedback signal to obtain a reconstructed signal; wherein the reconstructed signal comprises a voltage reconstructed signal corresponding to the voltage digital signal and a current reconstructed signal corresponding to the current digital signal; and carrying out fast Fourier transform on the reconstructed signal to obtain the bioelectrical impedance of the target tissue.

In an embodiment, the performing wavelet denoising and filtering processing on the digital feedback signal includes: performing discrete wavelet transform on the digital feedback signal to obtain wavelet coefficients C of each layer _j,k Wherein k is the wavelet coefficient order of the j-th layer of wavelet space; will be provided withEach of the wavelet coefficients C _j,k Substituting the threshold function to perform threshold function processing; the wavelet coefficient C after threshold value function processing _j,k And carrying out inverse discrete wavelet transform to obtain the reconstructed signal.

Compared with the prior art, the embodiment of the application has the advantages that: this application carries out partial pressure through the voltage of the anodal output of difference sampling module to high-voltage pulse module and negative pole output, gather, can sample high-voltage pulse signal's voltage in real time when irreversible electroporation treatment equipment carries out high-voltage pulse and perforates, and through voltage processing module, current sensing module and high frequency sampling module finally obtain the digital feedback signal that corresponds with the impedance of target tissue, thereby need not additionally to export a pulse signal in high-voltage pulse signal's output gap, this application can acquire the impedance of target tissue in real time, in order to be used for generating corresponding bioelectrical impedance spectrum.

Drawings

Fig. 1 is a schematic view of an irreversible electroporation therapy apparatus according to a first embodiment of the present application;

fig. 2 is a schematic diagram of a differential sampling module and a voltage processing module according to a first embodiment of the present disclosure;

fig. 3 is a schematic circuit diagram of a differential sampling module according to a first embodiment of the present application;

fig. 4 is a schematic diagram of a protection unit according to another embodiment of the present application;

fig. 5 is a schematic circuit diagram of a protection unit according to another embodiment of the present application;

fig. 6 is a circuit schematic diagram of a differential amplifying unit according to a first embodiment of the present application;

fig. 7 is a schematic structural diagram of a coupling coil according to a first embodiment of the present application;

fig. 8 is an equivalent circuit schematic diagram of a current sensing module according to a first embodiment of the present application;

fig. 9 is a schematic diagram of a high-frequency sampling module according to a first embodiment of the present application;

FIG. 10 is a flow chart of a bio-impedance measurement method provided in a second embodiment of the present application;

FIG. 11 is a detailed flowchart of step S20 in FIG. 10;

FIG. 12 is a schematic of a hard threshold function and a soft threshold function.

The above figures illustrate: 100. a high voltage pulse module; 200. a differential sampling module; 210. a first sampling branch; 211. a first broadband voltage dividing unit; 212. a first single-ended amplification unit; 220. a second sampling branch; 221. a second broadband voltage dividing unit; 222. a second single-ended amplification unit; 230. a first protection unit; 240. a second protection unit; 300. a voltage processing module; 310. a differential amplification unit; 320. a third protection unit; 400. a current sensing module; 410. a coupling coil; 420. a load unit; 500. a high-frequency sampling module; 510. a filter shaping unit; 520. a range selection unit; 530. an AD conversion unit; 540. a sampling processing unit; 550. an optical fiber transmission module; 600. a main control module; 700. an auxiliary power supply; 800. a target tissue; 900. and a man-machine interaction module.

Detailed Description

In order to make the technical problems, technical solutions and advantageous effects to be solved by the present application clearer, the present application is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of and not restrictive on the broad application.

It will be understood that when an element is referred to as being "secured to" or "disposed on" another element, it can be directly on the other element or be indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or be indirectly connected to the other element.

It will be understood that the terms "length," "width," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," and the like, refer to an orientation or positional relationship illustrated in the drawings for convenience in describing the present application and to simplify description, and do not indicate or imply that the referenced device or element must have a particular orientation, be constructed and operated in a particular orientation, and thus should not be construed as limiting the present application.

Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to 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 explicitly or implicitly include one or more of that feature. In the description of the present application, "a plurality" means two or more unless specifically limited otherwise.

Fig. 1 shows a schematic diagram of an irreversible electroporation therapy apparatus according to a first embodiment of the present application, and for convenience of illustration, only the portions related to this embodiment are shown, and the detailed description is as follows:

an irreversible electroporation therapy apparatus, comprising: the high-voltage pulse module 100, the differential sampling module 200, the voltage processing module 300, the current sensing module 400, the high-frequency sampling module 500 and the main control module 600.

The high-voltage pulse module 100 is configured to generate a corresponding high-voltage pulse signal according to the pulse control signal, and the positive output terminal V1 and the negative output terminal V2 of the high-voltage pulse module 100 apply the high-voltage pulse signal to the target tissue 800, specifically, the positive output terminal V1 and the negative output terminal V2 may apply the high-voltage pulse signal to the target tissue 800 through the corresponding positive electrode needle and the corresponding negative electrode needle, respectively, the target tissue 800 may be a biological tissue, the amplitude range of the high-voltage pulse signal is 0.5V to 5kV, and the pulse width is 0.5us to 200us. The differential sampling module 200 is connected to the positive output terminal V1 and the negative output terminal V2 of the high voltage pulse module 100, and the differential sampling module 200 is configured to generate and output a first feedback voltage and a second feedback voltage according to voltage changes of the positive output terminal V1 and the negative output terminal V2 of the high voltage pulse module 100, respectively, when the high voltage pulse module 100 applies a high voltage pulse signal to the target tissue 800. The voltage processing module 300 is connected to the differential sampling module 200, and the voltage processing module 300 is configured to generate and output a voltage feedback signal according to the first feedback voltage and the second feedback voltage. The current sensing module 400 is connected to the high voltage pulse module 100, and the current sensing module 400 is configured to generate and output a current feedback signal according to the current of the positive output terminal V1 or the negative output terminal V2 when the high voltage pulse module 100 applies the high voltage pulse signal to the target tissue 800. The high-frequency sampling module 500 is respectively connected to the voltage processing module 300 and the current sensing module 400, and the high-frequency sampling module 500 is configured to generate and output a corresponding digital feedback signal according to the voltage feedback signal and the current feedback signal. The main control module 600 is respectively connected to the high-voltage pulse module 100 and the high-frequency sampling module 500, and is configured to generate and output a pulse control signal, and generate a bioelectrical impedance according to the received digital feedback signal, so as to generate a corresponding bioelectrical impedance spectrum, and the main control module 600 may further adjust the high-voltage pulse signal according to the digital feedback signal. The main control module 600 may be an industrial personal computer, a single chip microcomputer or a microcontroller.

In this embodiment, the differential sampling module 200 divides and collects the voltages of the positive output terminal V1 and the negative output terminal V2 of the high voltage pulse module 100, so that a high voltage signal generated when the irreversible electroporation therapy apparatus performs high voltage pulse electroporation can be sampled in real time, and a digital feedback signal corresponding to the impedance of the target tissue 800 is finally obtained through the voltage processing module 300, the current sensing module 400 and the high frequency sampling module 500, so that a pulse signal does not need to be additionally output in an output interval of the high voltage pulse signal, the main control module 600 can obtain the impedance of the target tissue 800 in real time according to the digital feedback signal and adjust the high voltage pulse signal, and a corresponding bioelectrical impedance spectrum can be generated.

In this embodiment, as shown in fig. 2, the differential sampling module 200 includes a first sampling branch 210 and a second sampling branch 220, the first sampling branch 210 is connected between the positive output terminal V1 and the voltage processing module 300, and the second sampling branch 220 is connected between the negative output terminal V2 and the voltage processing module 300; the first sampling branch 210 is configured to generate a first feedback voltage and the second sampling branch 220 is configured to generate a second feedback voltage.

The differential sampling module 200 can perform differential sampling on the bipolar high-voltage pulse signal, and simultaneously sample the voltages of the positive output end V1 and the negative output end V2 through two independent sampling branches, so that mutual influence between the positive output end V1 and the negative output end V2 can be avoided, and a relatively accurate corresponding first feedback voltage and a relatively accurate corresponding second feedback voltage can be obtained.

In this embodiment, the first sampling branch 210 includes a first broadband voltage dividing unit 211 and a first single-ended amplifying unit 212; the first broadband voltage dividing unit 211 is respectively connected to the positive output terminal V1 and the first single-ended amplifying unit 212, the first single-ended amplifying unit 212 is further connected to the voltage processing module 300, and the first single-ended amplifying unit 212 is configured to generate a first feedback voltage according to a voltage divided by the first broadband voltage dividing unit 211. The second sampling branch 220 includes a second broadband voltage dividing unit 221 and a second single-ended amplifying unit 222; the second broadband voltage dividing unit 221 is connected to the positive output terminal V1 and the second single-ended amplifying unit 222, the second single-ended amplifying unit 222 is further connected to the voltage processing module 300, and the second single-ended amplifying unit 222 is configured to generate a second feedback voltage according to a voltage divided by the second broadband voltage dividing unit 221.

It should be noted that, because the voltage amplitude of the high-voltage pulse signal is too high, the first wideband voltage dividing unit 211 and the second wideband voltage dividing unit 221 are required to divide the voltage, and meanwhile, in order to obtain the voltage signals of the positive output terminal V1 and the negative output terminal V2 without distortion, the bandwidths of the first wideband voltage dividing unit 211 and the second wideband voltage dividing unit 221 are high, and both the high-frequency signal and the low-frequency signal can be transmitted to the first single-ended amplification unit 212 or the second single-ended amplification unit 222 through the first wideband voltage dividing unit 211 or the second wideband voltage dividing unit 221. The first single-ended amplification unit 212 and the second single-ended amplification unit 222 may amplify the divided voltages of the positive output terminal V1 and the negative output terminal V2 by a certain multiple, respectively, to obtain a first feedback voltage and a second feedback voltage. The amplification factors of the first single-ended amplification unit 212 and the second single-ended amplification unit 222 may be configured according to practical situations, and the present embodiment does not limit the same. In this embodiment, the first single-ended amplification unit 212 and the second single-ended amplification unit 222 can achieve a Gain-Bandwidth Product (GBWP) of 70MHz, and can obtain a slew rate of 200V/μ s and a low noise voltage of 6.3nV/√ Hz.

The first broadband voltage dividing unit 211 includes a first low-frequency impedance voltage dividing unit and a first high-frequency impedance voltage dividing unit, the first low-frequency impedance voltage dividing unit is connected to the positive output terminal V1 and the first single-ended amplifying unit 212, and the first high-frequency impedance voltage dividing unit is connected in parallel to the first low-frequency impedance voltage dividing unit. The second broadband voltage dividing unit 221 includes a second low-frequency impedance voltage dividing unit and a second high-frequency impedance voltage dividing unit, the second low-frequency impedance voltage dividing unit is connected to the positive output terminal V1 and the second single-ended amplification unit 222, and the second high-frequency impedance voltage dividing unit is connected in parallel to the second low-frequency impedance voltage dividing unit. The first low-frequency impedance voltage division unit is used for dividing the low-frequency signal of the positive output end V1, the second low-frequency impedance voltage division unit is used for dividing the low-frequency signal of the negative output end V2, the first high-frequency impedance voltage division unit is used for dividing the high-frequency signal of the positive output end V1, and the second high-frequency impedance voltage division unit is used for dividing the high-frequency signal of the negative output end V2. In this embodiment, even if the voltage amplitude of the high voltage pulse signal is 5kV, the maximum voltage obtained by the final voltage division still does not exceed 5V through the voltage division of the first broadband voltage dividing unit 211 and the second broadband voltage dividing unit 221, and meanwhile, the voltage variation condition of the positive output terminal V1 and the negative output terminal V2 can be maintained.

In an example, as shown in fig. 3, the first low-frequency impedance voltage-dividing unit includes a resistor R1, a resistor R2, a resistor R3, and a resistor R4 connected in series in sequence, where the resistor R1 is connected to the positive output terminal V1, and the resistor R4 is connected to the first single-ended amplifying unit 212. The first high-frequency impedance voltage division unit comprises a capacitor C1, a capacitor C2, a capacitor C3 and a capacitor C4 which are sequentially connected in series, wherein the capacitor C1, the capacitor C2, the capacitor C3 and the capacitor C4 are respectively in one-to-one correspondence with the resistor R1, the resistor R2, the resistor R3 and the resistor R4 and are connected in parallel. The resistor R1, the resistor R2, the resistor R3 and the resistor R4 are all high-frequency non-inductive resistors, and the capacitor C1, the capacitor C2, the capacitor C3 and the capacitor C4 are all capacitors with low equivalent inductance.

Specifically, the first single-ended amplification unit 212 and the second single-ended amplification unit 222 are both in-phase amplifier circuits. In an example, as shown in fig. 3, the first single-ended amplification unit 212 includes a first operational amplifier U1, a first feedback resistor R9, and a second feedback resistor R10, a non-inverting input terminal of the first operational amplifier U1 is connected to the first wideband voltage division unit 211, an output terminal of the first operational amplifier U1 is connected to the voltage processing module 300, a first end of the first feedback resistor R9 is connected to an output terminal of the first operational amplifier U1, a second end of the first feedback resistor R9 is connected to an inverting input terminal of the first operational amplifier U1, a first end of the second feedback resistor R10 is connected to an inverting input terminal of the first operational amplifier U1, and a second end of the second feedback resistor R10 is connected to ground. The second single-ended amplifying unit 222 includes a second operational amplifier U2, a third feedback resistor R11, and a fourth feedback resistor R12, a positive phase input terminal of the second operational amplifier U2 is connected to the second broadband voltage dividing unit 221, an output terminal of the second operational amplifier U2 is connected to the voltage processing module 300, a first end of the third feedback resistor R11 is connected to an output terminal of the second operational amplifier U2, a second end of the third feedback resistor R11 is connected to an inverting input terminal of the second operational amplifier U2, a first end of the fourth feedback resistor R12 is connected to an inverting input terminal of the second operational amplifier U2, and a second end of the fourth feedback resistor R12 is connected to ground.

In another embodiment, as shown in fig. 4, the first sampling branch 210 further includes a first protection unit 230, the second sampling branch 220 further includes a second protection unit 240, the first protection unit 230 is connected between the first broadband voltage dividing unit 211 and the first single-ended amplification unit 212, and the second protection unit 240 is connected between the second broadband voltage dividing unit 221 and the second single-ended amplification unit 222. The first and

second protection units

230 and 240 are configured to limit the magnitude of the voltage transmitted to the first and second single-ended

amplification units

212 and 222, respectively. In this embodiment, the first protection unit 230 and the second protection unit 240 have the same circuit structure.

In an example, as shown in fig. 5, the first protection unit 230 includes a voltage dividing resistor R17 and a breakdown diode VT1, a first end of the voltage dividing resistor R17 is connected to the first broadband voltage dividing unit 211, a second end of the voltage dividing resistor R17 is connected to the first single-ended amplification unit 212, a negative electrode of the breakdown diode VT1 is connected to a second end of the voltage dividing resistor R17, and a positive electrode of the breakdown diode VT1 is connected to the ground. When the amplitude of the voltage output by the first broadband voltage dividing unit 211 is too high and is greater than the breakdown voltage of the breakdown diode VT1, the breakdown diode VT1 is broken down, so that the second end of the voltage dividing resistor R17 is grounded to release the voltage.

In this embodiment, the voltage processing module 300 includes a differential amplifying unit 310, the differential amplifying unit 310 is respectively connected to the differential sampling module 200 and the high-frequency sampling module 500, and the differential amplifying unit 310 is configured to generate a voltage feedback signal according to the first feedback voltage and the second feedback voltage.

It should be noted that the differential amplifying unit 310 may be a differential amplifying circuit, and may amplify a voltage difference between the first feedback voltage and the second feedback voltage by a certain multiple, so as to generate a corresponding voltage feedback signal.

In one example, as shown in fig. 6, the differential amplifying unit 310 includes a third operational amplifier U3 and a fifth feedback resistor R15, wherein a non-inverting input terminal of the third operational amplifier U3 is connected to the first single-ended amplifying unit 212, an inverting input terminal of the third operational amplifier U3 is connected to the second single-ended amplifying unit 222, a first terminal of the fifth feedback resistor R15 is connected to an output terminal of the third operational amplifier U3, and a second terminal of the fifth feedback resistor R15 is connected to an inverting input terminal of the third operational amplifier U3.

In another embodiment, as shown in fig. 4 and 5, the voltage processing module 300 further includes a third protection unit 320, where the third protection unit 320 is connected between the differential amplification unit 310 and the high-frequency sampling module 500; the third protection unit 320 is configured to limit the magnitude of the voltage transmitted to the high frequency sampling module 500. The third protection unit 320 is used for clipping the voltage feedback signal. The first protection unit 230, the second protection unit 240, and the third protection unit 320 have the same structure.

In this embodiment, as shown in fig. 7 and fig. 8, the current sensing module 400 includes a coupling coil 410 and a load unit 420, the coupling coil 410 is sleeved on an output wire of the positive output end V1 or the negative output end V2, an output end of the coupling coil 410 is connected to the load unit 420, the load unit 420 is further connected to the high-frequency sampling module 500, the coupling coil 410 is configured to generate a corresponding induced current according to a current of the output wire, and the load unit 420 is configured to generate and output a current feedback signal according to the induced current. The load unit 420 may be a load resistor R16.

Specifically, the coupling coil 410 may be a self-integrating rogowski coil, two output ends of the coupling coil 410 are respectively connected to two ends of the load unit 420, two ends of the load unit 420 are both connected to the high-frequency sampling module 500, and when an induced current flows through the load unit 420, the high-frequency sampling module 500 may detect a voltage (a current feedback signal) at two ends of the load unit 420 to obtain the current feedback signal.

In this embodiment, as shown in fig. 9, the high-frequency sampling module 500 includes a filter shaping unit 510, a range selection unit 520, an AD conversion unit 530, and a sampling processing unit 540, which are connected in sequence, where the filter shaping unit 510 is connected to the voltage processing module 300 and the current sensing module 400, respectively, and the sampling processing unit 540 is connected to the main control module 600 and the range selection unit 520; the sampling processing unit 540 is configured to generate a corresponding digital feedback signal according to the digital signal output by the AD conversion unit 530 and configure the range of the range selection unit 520 according to the digital feedback signal.

The filter shaping unit 510 is configured to filter and shape the current feedback signal to obtain a current feedback signal with small distortion. Range selecting section 520 converts the current feedback signal according to the set range and outputs an analog signal corresponding to the input range of AD converting section 530. The AD conversion unit 530 is configured to sample the analog signal according to a preset frequency for converting the analog signal to a digital signal. The sampling processing unit 540 is configured to obtain a corresponding digital feedback signal according to the digital signal, and configure the range set by the range selecting unit 520 according to the digital feedback signal, so as to further improve the accuracy. The sampling Processing unit 540 may be a Field Programmable Gate Array (FPGA) or a Digital Signal Processing (DSP) unit.

The digital feedback signal includes a voltage digital signal and a current digital signal, the voltage digital signal corresponds to a voltage value between the positive output terminal V1 and the negative output terminal V2 (i.e., between two ends of the target tissue 800), and the current digital signal corresponds to a current value flowing through the positive output terminal V1 or the negative output terminal V2 (i.e., through the target tissue 800). The main control module 600 can obtain the impedance of the target tissue 800 according to the voltage digital signal and the current digital signal, thereby generating a corresponding bioelectrical impedance spectrum.

In this embodiment, the high-frequency sampling module 500 is further wrapped with a shielding housing for shielding an external electromagnetic signal.

In this embodiment, as shown in fig. 9, the high-frequency sampling module 500 further includes an optical fiber transmission module 550 connected to the sampling processing unit 540, and the optical fiber transmission module 550 is used for being connected to the main control module 600 in a communication manner, that is, the sampling processing unit 540 is connected to the main control module 600 in a communication manner through the optical fiber transmission module 550.

In this embodiment, as shown in fig. 1, the power supply system further includes an auxiliary power supply 700, the auxiliary power supply 700 is respectively connected to the voltage processing module 300, the high-frequency sampling module 500, and the main control module 600, and the auxiliary power supply 700 is configured to generate a multi-stage working voltage and can supply power to the voltage processing module 300, the high-frequency sampling module 500, and the main control module 600.

In this embodiment, as shown in fig. 1, the system further includes a human-computer interaction module 900, and the human-computer interaction module 900 is connected to the main control module 600. The human-computer interaction module 900 may be a touch screen, a physical button, or the like, and is configured to enter relevant parameters into the main control module 600 and display the irreversible electroporation therapy apparatus of the main control module 600 and the obtained electrical impedance spectrum of the target tissue 800.

Fig. 10 shows a flowchart of a bio-impedance measurement method provided in the second embodiment of the present application, and for convenience of description, only the parts related to the present embodiment are shown, and detailed descriptions are as follows:

in this embodiment, the bioimpedance measurement method may be applied to the irreversible electroporation therapy apparatus according to any one of the above-described embodiments.

As shown in fig. 10, the bio-impedance measuring method specifically includes steps S10 to S30:

and S10, acquiring a digital feedback signal provided by the high-frequency sampling module 500 under the condition that the high-voltage pulse module 100 outputs a high-voltage pulse signal. The digital feedback signal includes a voltage digital signal and a current digital signal, the voltage digital signal corresponds to a voltage value between the positive output terminal V1 and the negative output terminal V2 (i.e., between two ends of the target tissue 800), and the current digital signal corresponds to a current value flowing through the positive output terminal V1 or the negative output terminal V2 (i.e., flowing through the target tissue 800).

And S20, performing wavelet denoising and filtering processing on the digital feedback signal to obtain a reconstructed signal. Wherein the reconstruction signal comprises a voltage reconstruction signal corresponding to the voltage digital signal and a current reconstruction signal corresponding to the current digital signal.

And S30, performing fast Fourier transform on the reconstructed signal to obtain the bioelectrical impedance of the target tissue 800.

By the biological impedance measuring method, the influence of the overhigh voltage of the high-voltage pulse signal can be avoided, and the real-time biological electrical impedance Z (omega) is obtained.

Specifically, the formula of the fast fourier transform is:

where F { u (t) } is a voltage reconstruction signal, and F { i (t) } is a current reconstruction signal.

In this embodiment, the high voltage pulse module 100, the differential sampling module 200, the voltage processing module 300, the current sensing module 400, and the high frequency sampling module 500 may be used to implement step S10, and the main control module 600 may be used to implement step S20 and step S30.

As shown in fig. 11, step S20 specifically includes steps S21 to S23:

s21, discrete wavelet transform is carried out on the digital feedback signal to obtain wavelet coefficients C of each layer _j,k . And k is the wavelet coefficient order of the j-th layer of wavelet space.

S22, dividing each wavelet coefficient C _j,k Substituting into the threshold function to perform threshold function processing.

S23, wavelet coefficient C processed by threshold function _j,k And performing inverse discrete wavelet transform to obtain a reconstructed signal.

Specifically, in step S22, the global threshold λ or the scale-dependent threshold λ needs to be calculated first _j . The global threshold λ is calculated by the formula:

wherein n is the global signal length; scale dependent threshold lambda _j The calculation formula of (2) is as follows:

in the formula, n _j For wavelet coefficient length, coefficient σ, at each scale _j Can be determined empirically and can also be determined by the following equation: sigma _j ＝MAD(|C _j,k |,0≤k≤2 ^j-1 -1)/q, where MAD () means taking the median value of the numerical values in parentheses, | C _j,k |,0≤k≤2 ^j-1 -1) is the median value in the wavelet coefficient sequence, and the coefficient q can be empirically selected from 0.4 to 1, and further, the q value can be selected from 0.6 to 0.8. The global threshold λ adopted in this embodiment specifically adopts whether the global threshold λ or the scale-dependent threshold λ _j Can be determined according to actual requirements.

In step S22, the threshold function includes a hard threshold function and a soft threshold function, and the schematic diagrams of the hard threshold function and the soft threshold function are shown in fig. 12, where the hard threshold function only retains wavelet coefficients whose absolute values are greater than the global threshold λ, and the retained wavelet coefficients are the same as the original coefficients, while the smaller wavelet coefficients are set to zero, and the hard threshold function specifically is:

the soft threshold function also takes zero for wavelet coefficient values with absolute values smaller than the global threshold lambda, and the wavelet coefficient values with absolute values larger than the global threshold lambda are shrunk by lambda, wherein the soft threshold function specifically comprises the following steps:

when a hard threshold function is used in step S22, the discontinuity of the threshold function at the global threshold λ may cause a large variance, which may cause additional oscillation of the reconstructed signal and may not have the same smoothness as the original signal, i.e., a reconstructed signal closer to the waveform of the digital feedback signal may be obtained after performing step S23. When the soft threshold function is used in step S22, the soft threshold function will generally make the denoised signal smoother, but some features of the signal will also be lost, which affects the approximation degree of the reconstructed signal and the original signal, that is, a smoother reconstructed signal than the waveform of the digital feedback signal can be obtained after step S23 is performed. Wherein, the discrete wavelet inverse transformation formula is as follows: f (t) = ∑ Σ _j,k c _j,k ψ _j,k (t) in the formula,. Phi. _j,k (t) is each wavelet coefficient C _j,k A corresponding scaling function.

It should be understood that, the sequence numbers of the steps in the foregoing embodiments do not imply an execution sequence, and the execution sequence of each process should be determined by functions and internal logic of the process, and should not constitute any limitation to the implementation process of the embodiments of the present application.

It should be clear to those skilled in the art that, for convenience and simplicity of description, the foregoing division of the functional units and modules is only used for illustration, and in practical applications, the above function distribution may be performed by different functional units and modules as needed, that is, the internal structure of the apparatus may be divided into different functional units or modules to perform all or part of the above described functions. Each functional unit and module in the embodiments may be integrated in one processing unit, or each unit may exist alone physically, or two or more units are integrated in one unit, and the integrated unit may be implemented in a form of hardware, or in a form of software functional unit. In addition, specific names of the functional units and modules are only for convenience of distinguishing from each other, and are not used for limiting the protection scope of the present application. The specific working processes of the units and modules in the system may refer to the corresponding processes in the foregoing method embodiments, and are not described herein again.

In the above embodiments, the description of each embodiment has its own emphasis, and reference may be made to the related description of other embodiments for parts that are not described or recited in any embodiment.

The above-mentioned embodiments are only used to illustrate the technical solutions of the present application, and not to limit the same; although the present application has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; such modifications and substitutions do not substantially depart from the spirit and scope of the embodiments of the present application and are intended to be included within the scope of the present application.

Claims

1. An irreversible electroporation therapy apparatus, comprising:

a high voltage pulse module configured to generate a corresponding high voltage pulse signal according to a pulse control signal and apply the high voltage pulse signal to a target tissue through a positive electrode output end and a negative electrode output end of the high voltage pulse module;

a differential sampling module connected to a positive output terminal and a negative output terminal of the high-voltage pulse module, and configured to generate and output a first feedback voltage and a second feedback voltage according to voltage changes of the positive output terminal and the negative output terminal, respectively, when the high-voltage pulse module applies the high-voltage pulse signal to the target tissue;

the voltage processing module is connected with the differential sampling module and is configured to generate and output a voltage feedback signal according to the first feedback voltage and the second feedback voltage;

a current sensing module connected to the high voltage pulse module and configured to generate and output a current feedback signal according to a current of the positive output terminal or the negative output terminal when the high voltage pulse module applies the high voltage pulse signal to the target tissue;

the high-frequency sampling module is respectively connected with the voltage processing module and the current sensing module and is configured to generate and output corresponding digital feedback signals according to the voltage feedback signals and the current feedback signals;

and the main control module is respectively connected with the high-voltage pulse module and the high-frequency sampling module, is configured to generate and output the pulse control signal, and generates a bioelectrical impedance spectrum and adjusts the high-voltage pulse signal according to the received digital feedback signal.

2. The irreversible electroporation therapy apparatus of claim 1, wherein the differential sampling module comprises a first sampling branch and a second sampling branch, the first sampling branch connected between the positive output terminal and the voltage processing module, the second sampling branch connected between the negative output terminal and the voltage processing module; the first sampling branch is configured to generate the first feedback voltage, and the second sampling branch is configured to generate the second feedback voltage.

3. The irreversible electroporation therapy apparatus of claim 2, wherein the first sampling arm comprises a first broadband voltage dividing unit and a first single-ended amplification unit; the first broadband voltage dividing unit is respectively connected with the anode output end and the first single-ended amplifying unit, the first single-ended amplifying unit is further connected with the voltage processing module, and the first single-ended amplifying unit is configured to generate the first feedback voltage according to a voltage obtained by voltage division of the first broadband voltage dividing unit.

4. The irreversible electroporation therapy apparatus of claim 3, wherein the second sampling branch comprises a second broadband voltage dividing unit and a second single-ended amplification unit; the second broadband voltage dividing unit is respectively connected with the anode output end and the second single-ended amplifying unit, the second single-ended amplifying unit is further connected with the voltage processing module, and the second single-ended amplifying unit is configured to generate the second feedback voltage according to the voltage divided by the second broadband voltage dividing unit.

5. The irreversible electroporation therapy apparatus of claim 4, wherein the first sampling branch further comprises a first protection unit, the second sampling branch further comprises a second protection unit, the first protection unit is connected between the first broadband voltage dividing unit and the first single-ended amplification unit, and the second protection unit is connected between the second broadband voltage dividing unit and the second single-ended amplification unit;

the first and second protection units are configured to limit magnitudes of voltages transmitted to the first and second single-ended amplification units, respectively.

6. The irreversible electroporation therapy apparatus of claim 1, wherein the voltage processing module comprises a differential amplification unit and a third protection unit coupled to each other, the differential amplification unit further coupled to the differential sampling module, the differential amplification unit configured to generate the voltage feedback signal based on the first feedback voltage and the second feedback voltage, the third protection unit further coupled to the high frequency sampling module, the third protection unit configured to limit an amplitude of a voltage transmitted to the high frequency sampling module.

7. The irreversible electroporation therapy apparatus according to any one of claims 1 to 6, wherein the current sensing module comprises a coupling coil and a load unit, the coupling coil is sleeved on the output lead of the positive output end or the negative output end, the output end of the coupling coil is connected with the load unit, the load unit is further connected with the high frequency sampling module, the coupling coil is configured to generate a corresponding induced current according to the current of the output lead, and the load unit is configured to generate and output the current feedback signal according to the induced current.

8. The irreversible electroporation therapy apparatus according to any one of claims 1 to 6, wherein the high frequency sampling module comprises a filter shaping unit, a range selection unit, an AD conversion unit and a sampling processing unit which are connected in sequence, the filter shaping unit is respectively connected with the voltage processing module and the current sensing module, and the sampling processing unit is connected with the main control module and the range selection unit; the filtering and shaping unit is configured to convert the received voltage feedback signal and the received current feedback signal according to a set measuring range to obtain a corresponding analog signal, and the AD conversion unit is configured to sample the analog signal according to a preset frequency to obtain a digital signal; the sampling processing unit is configured to generate a corresponding digital feedback signal according to the digital signal output by the AD conversion unit and configure the range of the range selection unit according to the digital feedback signal.

9. A bioimpedance measurement method applied to the irreversible electroporation therapy apparatus according to any one of claims 1 to 8, the bioimpedance measurement method comprising:

under the condition that the high-voltage pulse module outputs a high-voltage pulse signal, acquiring the digital feedback signal provided by the high-frequency sampling module; wherein the digital feedback signal comprises a voltage digital signal and a current digital signal;

performing wavelet denoising and filtering processing on the digital feedback signal to obtain a reconstructed signal; wherein the reconstructed signal comprises a voltage reconstructed signal corresponding to the voltage digital signal and a current reconstructed signal corresponding to the current digital signal;

and carrying out fast Fourier transform on the reconstructed signal to obtain the bioelectrical impedance of the target tissue.

10. The method of bio-impedance measurement according to claim 9, wherein the wavelet de-noising and filtering the digital feedback signal comprises:

performing discrete wavelet transform on the digital feedback signal to obtain small signals of each layerWave coefficient C _j,k Wherein k is the wavelet coefficient order of the jth layer of wavelet space;

each wavelet coefficient C is obtained _j,k Substituting the threshold function to perform threshold function processing;

the wavelet coefficient C after threshold value function processing _j,k And carrying out inverse discrete wavelet transform to obtain the reconstructed signal.