Irreversible electroporation ablation effect evaluation method and equipment based on biological impedance analysis

Abstract

The invention provides an irreversible electroporation ablation effect evaluation method based on biological impedance analysis, and the method is characterized in that the method comprises the following steps: applying an electric signal to a to-be-ablated tissue; measuring a voltage across the subject tissue generated by the electrical signal; determining an impedance value across the subject tissue at a predetermined frequency based on the measured voltage; carrying out IRE ablation on the biological tissue, and repeating the previous steps to measure the impedance value of the tissue after ablation; and evaluating the irreversible electroporation ablation effect based on the impedance value across the tested tissue at the predetermined frequency and the impedance value of the tissue after ablation. The invention provides an irreversible electroporation ablation effect evaluation method for bioimpedance analysis. The method can evaluate the ablation effect of IRE and feed back IRE treatment.

Description

Technical Field

[0001] The present application relates to the technical field of surgical medical equipment, and in particular to a method and device for evaluating the effect of irreversible electroporation ablation based on bioimpedance analysis. Background Art

[0002] In recent years, the biological and medical effects of pulsed electric fields (PEF) have received widespread attention. High-intensity PEF can form nanoscale pores on the cell membrane, thereby changing the permeability of the cell membrane. When the parameters of PEF exceed a certain threshold, these pores will not reclose, resulting in irreversible electroporation (IRE), causing the cell to lose balance and eventually die. This technology has important applications in atrial fibrillation ablation, tumor treatment and other fields.

[0003] During the treatment process, evaluating the ablation effect of IRE is the key to ensuring the success of treatment. IRE induces cell death by destroying cell structures through electric fields, but this process does not cause specific clinical symptoms or imaging changes immediately after treatment. Therefore, there is a certain lag in the use of medical imaging methods such as ultrasound, computed tomography, magnetic resonance imaging, or histopathological examination to evaluate the ablation effect. However, timely evaluation of the treatment effect of IRE is crucial for most clinicians and to promote the application of IRE in clinical trials.

[0004] Therefore, a new method is urgently needed to evaluate the ablation effect immediately or in real time after IRE treatment. Summary of the invention

[0005] In order to overcome the defects of the above-mentioned related technologies, the present application provides a method and device for evaluating the ablation effect of irreversible electroporation based on bioimpedance analysis, which can evaluate the ablation effect of IRE and provide feedback on IRE treatment.

[0006] Based on one aspect of the present application, the present application provides a method for evaluating the effect of irreversible electroporation ablation based on bioimpedance analysis, comprising the following steps:

[0007] applying an electrical signal to the tissue to be ablated;

[0008] measuring a voltage across the tissue under test generated by the electrical signal;

[0009] determining an impedance value across the tissue under test at a predetermined frequency based on the measured voltage;

[0010] Performing IRE ablation on biological tissue, and repeating the above steps to measure the impedance value of the ablated tissue;

[0011] Based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the ablated tissue, the irreversible electroporation ablation effect is evaluated.

[0012] In some embodiments of the present application, the electrical signal is set to an electrical signal of a fixed frequency, and the determining of the impedance value across the test tissue at a predetermined frequency based on the measured voltage includes: using the impedance formula in Ohm's law: Z=V / I to calculate the impedance value across the test tissue at the fixed frequency, where Z is impedance, V is voltage, and I is current. The evaluating of the effect of irreversible electroporation ablation based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the ablated tissue includes: recording and analyzing the impedance value across the test tissue at the predetermined frequency and the impedance value of the ablated tissue; evaluating the effect of irreversible electroporation ablation based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the ablated tissue.

[0013] In some embodiments of the present application, the electrical signal is set to an alternating current signal of different frequencies, including low frequency and high frequency, to obtain impedance data of the full spectrum. The impedance value of the ablated tissue is characterized by the Cole-Cole model. The evaluation of the irreversible electroporation ablation effect based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the ablated tissue comprises: analyzing the impedance value across the test tissue at the predetermined frequency at different frequencies and the impedance value of the ablated tissue, evaluating the changes in membrane resistance, capacitance and tissue conductivity, and evaluating the tissue ablation effect based on the changes.

[0014] In some embodiments of the present application, the Cole-Cole model is set as:

[0015] (1) ,

[0016] (2) ,

[0017] (3) ,

[0018] (4) ,

[0019] (5) ,

[0020] in, and are the impedance at zero frequency and infinite frequency respectively, is the impedance of the extracellular fluid, is the impedance of the intracellular fluid, is the capacitance component of the cell membrane, is the complex impedance of the model, is the impedance of the cell membrane, is the angular frequency, is the time constant, is the characteristic frequency of the dispersion, represents the frequency dependence, the angle is the phase shift of the impedance.

[0021] In some embodiments of the present application, the electrical signal is set to an alternating current signal of a high-low frequency mixing, and the mixing has consistency. The evaluating the irreversible electroporation ablation effect based on the impedance value across the test tissue and the impedance value of the ablated tissue at the predetermined frequency includes: using a mixing algorithm to process the measured impedance value across the test tissue and the impedance value of the ablated tissue at the predetermined frequency, extracting comprehensive information about the electrical characteristics of the tissue, and evaluating the tissue ablation effect based on the comprehensive information.

[0022] According to another aspect of the present application, the present application provides a device for evaluating ablation effect based on a multi-frequency bioimpedance method, comprising:

[0023] High voltage pulse generator, impedance detection equipment, transfer switch, biological tissue;

[0024] The high-voltage pulse generating device is provided with electrodes HC and LC for outputting high-voltage pulse electrical signals. The electrodes HC and LC simultaneously serve as excitation current release electrodes of the impedance detection device. The electrode HC is at a high level, and the electrode LC is at a low level. The opening and closing of the electrodes HC and LC are switched by the transfer switch.

[0025] The impedance detection device is provided with an analysis and calculation module for collecting and calculating the impedance information of biological tissue; a current-voltage conversion module for stimulating current output; a voltage acquisition module for filtering and amplifying the acquired voltage signal; and impedance detection electrodes for collecting voltage across biological tissue. The impedance detection device can quickly perform frequency scanning and transmit the calculation results to a computer. The device is also provided with a Cole-Cole model algorithm for calculating the impedance value of the tissue after ablation.

[0026] In some embodiments of the present application, the high-voltage pulse generating device can generate positive and negative pulse signals with a variety of adjustable parameters, including adjustable pulse voltage of 0-3000V, adjustable pulse width of 500ns to 100μs, adjustable delay between pulses of 10-5000μs, adjustable pulse trains and pulse logarithms, the rise time and fall time of the device are both 50ns, and the delay time between pulse trains is 0.5 seconds.

[0027] In some embodiments of the present application, the analysis and calculation module is connected to the current-voltage conversion module and the voltage acquisition module, and is used to receive the biological detection voltage signal amplified and filtered from the voltage acquisition module, and convert the output excitation voltage into current through the current-voltage conversion module;

[0028] The current-to-voltage conversion module is used to convert the voltage into a sinusoidal current with a peak value of 200 μA, and reduce the offset voltage in the circuit through a negative feedback circuit;

[0029] The excitation current is injected into the biological tissue through the HC electrode, and the current signal flowing through the biological tissue is collected by the LC electrode; the HV electrode and the LV electrode of the impedance detection electrode are used to collect voltage signals to the voltage collection module, and after filtering out high-frequency and low-frequency interference, the voltage signal is transmitted to the analysis and calculation module for impedance calculation.

[0030] Compared with the prior art, the advantages of this application are:

[0031] The present application utilizes bioimpedance to evaluate IRE therapy, thus avoiding the lag of medical imaging methods such as ultrasound or histopathological evaluation. Furthermore, based on the evaluation of the ablation effect, the pulse generating device can be subjected to negative feedback control of the applied ablation dose, and the treatment endpoint can be accurately determined, thereby avoiding excessive or insufficient treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The above and other features and advantages of the present application will become more apparent by describing in detail example embodiments thereof with reference to the attached drawings.

[0033] Figure 1 The flowchart of the irreversible electroporation ablation effect evaluation method based on bioimpedance analysis of the present application is shown.

[0034] Figure 2 A schematic flow chart of a method for evaluating the effect of irreversible electroporation ablation based on bioimpedance analysis according to one embodiment of the present application is shown.

[0035] Figure 3 A schematic diagram of the Cole-Cole model of the present application is shown.

[0036] Figure 4 The Nyquist diagram of the absolute values ​​of the real and imaginary parts of the impedance of the present application is shown.

[0037] Figure 5 The relationship between the number of applied pulse groups and the normalized values ​​of Re and Ri of the present application is shown.

[0038] Figure 6 The relationship between the number of applied pulse groups and the normalized value of Cm in the present application is shown.

[0039] Figure 7 A schematic diagram of the structure of a device for evaluating ablation effects based on a multi-frequency bioimpedance method of the present application is shown.

[0040] Figure 8 A schematic structural diagram of the impedance detection device of the present application is shown. DETAILED DESCRIPTION

[0041] Example embodiments will now be described more fully with reference to the accompanying drawings. However, example embodiments can be implemented in a variety of forms and should not be construed as limited to the examples set forth herein; rather, these embodiments are provided so that this application will be more comprehensive and complete and fully convey the concepts of the example embodiments to those skilled in the art. The described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0042] In addition, the accompanying drawings are only schematic illustrations of the present application and are not necessarily drawn to scale. The same reference numerals in the figures represent the same or similar parts, and thus their repeated description will be omitted. Some of the block diagrams shown in the accompanying drawings are functional entities and do not necessarily correspond to physically or logically independent entities. These functional entities can be implemented in software form, or implemented in one or more hardware modules or integrated circuits, or implemented in different networks and / or processor devices and / or microcontroller devices.

[0043] The flowcharts shown in the accompanying drawings are only exemplary and do not necessarily include all the steps. For example, some steps may be decomposed, while some steps may be combined or partially combined. Therefore, the actual execution order may be changed according to the actual situation.

[0044] Figure 1 The flowchart of the irreversible electroporation ablation effect evaluation method based on bioimpedance analysis provided by the present application is shown. The irreversible electroporation ablation effect evaluation method based on bioimpedance analysis provided by the present application comprises the following steps S1 to S:

[0045] Step S1: Applying an electrical signal to the tissue to be ablated.

[0046] Step S2: Measure the voltage across the test tissue generated by the electrical signal.

[0047] Step S3: Determine the impedance value across the test tissue at a predetermined frequency based on the measured voltage.

[0048] Step S4: Perform IRE ablation on the biological tissue, and repeat the above steps to measure the impedance value of the tissue after ablation.

[0049] Step S5: Evaluate the irreversible electroporation ablation effect based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the ablated tissue.

[0050] In some embodiments of the present application, the electrical signal is set to be an electrical signal with a fixed frequency.

[0051] In some embodiments of the present application, determining the impedance value across the test tissue at a predetermined frequency based on the measured voltage includes: using the impedance formula in Ohm's law: Z=V / I to calculate the impedance value across the test tissue at the fixed frequency, where Z is impedance, V is voltage, and I is current.

[0052] In some embodiments of the present application, the evaluation of the irreversible electroporation ablation effect based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation includes: recording and analyzing the impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation; evaluating the irreversible electroporation ablation effect based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation.

[0053] In some embodiments of the present application, the electrical signal is set to an alternating current signal of different frequencies, including low frequency and high frequency, to obtain impedance data of the full spectrum.

[0054] In some embodiments of the present application, the impedance value of the tissue after ablation is characterized by using the Cole-Cole model.

[0055] In some embodiments of the present application, the Cole-Cole model is set as follows: Figure 3-Figure 4 As shown:

[0056] (1) ,

[0057] (2) ,

[0058] (3) ,

[0059] (4) ,

[0060] (5) ,

[0061] in, and are the impedance at zero frequency and infinite frequency respectively, is the impedance of the extracellular fluid, is the impedance of the intracellular fluid, is the capacitance component of the cell membrane, is the complex impedance of the model, is the impedance of the cell membrane, f is the direction of frequency increase, is the time constant, is the characteristic frequency of the dispersion, represents the frequency dependence, the angle is the phase shift of impedance. Ri represents the impedance of intracellular fluid, which is determined by the total amount of fluid inside the cell. The volume of intracellular fluid can also be characterized.

[0062] Specifically, by fitting the multi-frequency bioimpedance using the Cole-Cole model and nonlinear least squares method, we can obtain , , and The optimal solution of Figure 3 ,like Figure 3 As shown, the real part R and negative imaginary part of impedance at different frequencies are shown. The arrow indicates the direction of increasing frequency. , endpoint and Represent the impedance at zero frequency and infinite frequency, characteristic frequency Mark at the vertex of the semicircle, angle reflects the phase shift of the impedance, It is the capacitance component of the cell membrane. By fitting the Cole-Cole model of multi-frequency bioimpedance, the changes in the capacitance of the extracellular fluid, intracellular fluid and cell membrane can be revealed.

[0063] Furthermore, the bioimpedance of tissues is mainly determined by the ion concentration and the overall fluid composition of the tissue. High electric field strength causes the lipid bilayer of the cell membrane to rupture, forming stable nanoscale pores, and the degree of perforation increases with the increase of the electric field strength. These pores allow more ions and small molecules to freely pass through the cell membrane, resulting in a change in the balance of electrolytes inside and outside the cell. As electrolytes leak from the cell into the extracellular fluid, the ion concentration of the extracellular fluid increases and the ion concentration of the intracellular fluid decreases, thereby reducing the impedance Re of the extracellular fluid and increasing the impedance Ri of the intracellular fluid. At the same time, PEF causes the tight junctions between cells to be destroyed and increases the gap between cells, which allows more ions to flow and further reduces Re. Because the degree of reduction in Re is much greater than the degree of increase in Ri, the total impedance in the ablation area shows a downward trend. In addition, the formation of pores on the cell membrane increases the effective surface area of ​​the cell membrane, that is, the contact area between the insulating medium (cell membrane) and the electrode plate (intracellular / extracellular fluid) in each cell is increased, and the plate area A of the equivalent capacitor increases accordingly, and the equivalent capacitance increases. In addition, the formation of pores allows water molecules and ions inside and outside the membrane to penetrate into the phospholipid bilayer structure. This infiltration increases the overall dielectric constant ε of the membrane, further increasing the equivalent capacitance.

[0064] Further, Figure 5 The relationship between the number of applied pulse groups and the normalized values ​​of Re and Ri in the present application is shown. Figure 6The figure shows the relationship between the number of applied pulse groups and the normalized value of Cm in the present application. The figure further shows the functional relationship between the normalized values ​​of Re, Ri, and Cm and the number of applied pulse groups. Figure 5-Figure 6 It can be seen that with the increase of the number of pulse groups, the equivalent resistance Re of the cell membrane gradually decreases, almost linearly changing ( ) After treatment, it decreased by 92% compared with before treatment. The equivalent resistance Ri in the cell membrane gradually increased, almost linearly ( ), after treatment, it increased by 41% compared with before treatment. The cell membrane capacitance Cm increased rapidly, and after treatment, it increased by 563% compared with before treatment. It should be noted that when the pulse is continuously applied, the cell membrane will theoretically be completely lysed. At this time, the cell membrane capacitance Cm will theoretically decrease to near zero, and the internal and external resistances Ri and Re of the cell membrane will theoretically tend to be the same.

[0065] In some embodiments of the present application, the step of evaluating the irreversible electroporation ablation effect based on the impedance value across the test tissue and the impedance value of the ablated tissue at the predetermined frequency includes:

[0066] The impedance values ​​across the test tissue at the predetermined frequency at different frequencies and the impedance values ​​of the ablated tissue are analyzed to evaluate the changes in membrane resistance, capacitance and tissue conductivity, and the tissue ablation effect is evaluated based on the changes.

[0067] In some embodiments of the present application, the electrical signal is set to an alternating current signal of high and low frequency mixing, and the mixing is consistent.

[0068] In some embodiments of the present application, the evaluation of the irreversible electroporation ablation effect based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation includes: using a mixing algorithm to process the measured impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation, extracting comprehensive information about the electrical properties of the tissue, and evaluating the tissue ablation effect based on the comprehensive information.

[0069] In one possible embodiment of the present application, Figure 2 As shown,

[0070] The irreversible electroporation ablation effect evaluation method based on bioimpedance analysis of the present application specifically includes steps S10 to S90:

[0071] As shown in step S10, before the irreversible electroporation treatment, an alternating current at a predetermined frequency is applied to the tissue to be tested using an impedance detection device;

[0072] As shown in step S20, an impedance detection device is used to measure the trans-tissue voltage generated by the alternating current, and a multi-electrode configuration is required to measure the trans-tissue voltage;

[0073] As shown in step S30, the impedance of the biological tissue at a predetermined frequency is calculated by applying a current and measuring the voltage;

[0074] As shown in steps S40-S60, steps S20 and S30 are repeated according to the number of predetermined frequencies. In this embodiment, after comprehensively considering the measurement time and accuracy, 54 points in a logarithmic distribution within the frequency range of 500 Hz to 100 kHz are selected as the frequencies for multi-frequency bioimpedance measurement;

[0075] As shown in step S70, irreversible electroporation treatment is performed on the tissue to be tested, and the impedance of the tissue changes during the process;

[0076] As shown in step S80, another round of bioimpedance measurement is performed on the treated tissue;

[0077] As shown in step S90, the Ri, Re and Cm before and after treatment are calculated based on the cole-cole model fitting, and the ablation effect of IRE is judged by comparison, and this is used as feedback to the IRE ablation step S70. If the target ablation range is reached, the treatment is terminated, and if the treatment range is not reached, the treatment is continued.

[0078] Through the above-mentioned irreversible electroporation treatment method, the Cole-Cole model parameters: intracellular fluid impedance, extracellular fluid impedance and equivalent membrane capacitance can be used to monitor the IRE ablation degree in real time to obtain real-time bioelectrical impedance. Based on the evaluation of the ablation effect, the ablation dose applied by the pulse generator can be feedback-controlled to accurately determine the treatment endpoint, thereby avoiding excessive or insufficient treatment.

[0079] According to another aspect of the present application, the present application provides a device for evaluating ablation effect based on a multi-frequency bioimpedance method, comprising:

[0080] High voltage pulse generating device 1, impedance detection device 2, transfer switch 3, biological tissue 4;

[0081] The high-voltage pulse generating device 1 is provided with electrodes HC and LC for outputting high-voltage pulse electrical signals. The electrodes HC and LC simultaneously serve as excitation current release electrodes of the impedance detection device 2. The electrode HC is at a high level, and the electrode LC is at a low level. The opening and closing of the electrodes HC and LC are switched by the transfer switch 3. As can be understood by those skilled in the art, the electrode HC represents a high level, and the electrode LC represents a low level. In the high-voltage pulse generating device 1, the pulse signal is sent by the electrode HC and received by the electrode LC. In the impedance detection device, the excitation current is output by the electrode HC and received by the electrode LC.

[0082] The impedance detection device 2 is provided with an analysis and calculation module 100 for collecting and calculating the impedance information of the biological tissue 4; a current-voltage conversion module 200 for stimulating current output; a voltage acquisition module 300 for voltage signal acquisition; an impedance detection electrode 600 for impedance amplitude and phase calculation; the impedance detection device 2 can quickly perform frequency sweeping and transmit the calculation results to a computer; the device is also provided with a Cole-Cole model element for characterizing the impedance value of the tissue after ablation. Specifically, the impedance detection device 2 includes an analysis and calculation module 100, a current-voltage conversion module 200, a voltage acquisition module 300 and an impedance detection electrode 600. It can perform integrated operations of stimulating current output, voltage signal acquisition, impedance amplitude and phase calculation, can quickly perform frequency sweeping and impedance information acquisition and calculation, and transmit the calculation results to a computer. The impedance detection device 2 can accurately detect the impedance of 0-10kΩ, the impedance modulus detection error is less than 5%, the phase value detection error is less than 15%, and the Cole-Cole model element extraction value error is less than 6%.

[0083] Specifically, the device for evaluating the ablation effect based on the multi-frequency bioimpedance method includes a high-voltage pulse generator 1 and an impedance detection device 2, as well as a transfer switch 3 and biological tissue 4. The electrodes HC and LC serve as both pulse output electrodes of the high-voltage pulse generator 1 and excitation current release electrodes of the impedance detection device 2, and their functions are switched by the switch. This structure can ensure that the impedance changes of the same area are measured before and after treatment. During the treatment, the impedance detection device 2 is disconnected to avoid damage to the device due to high voltage.

[0084] In some embodiments of the present application, the high-voltage pulse generating device 1 can generate positive and negative pulse signals with multiple adjustable parameters, including adjustable pulse voltage of 0-3000V, adjustable pulse width of 500ns to 100μs, adjustable delay between pulses of 10-5000μs, adjustable pulse train and pulse logarithm, the rise time and fall time of the device are both 50ns, and the delay time between pulse trains is 0.5 seconds. Specifically, the high-voltage pulse generating device 1 is structurally configured to generate positive and negative pulse signals with multiple adjustable parameters, including adjustable pulse voltage of 0-3000V, adjustable pulse width of 500ns to 100μs, adjustable delay between pulses of 10-5000μs, and adjustable pulse train and pulse logarithm. The rise time and fall time of the device are both 50ns, and the delay time between pulse trains is 0.5 seconds.

[0085] In some embodiments of the present application, the analysis and calculation module 100 is connected to the current-voltage conversion module 200 and the voltage acquisition module 300, and is used to receive the biological detection voltage signal after amplification and filtering from the voltage acquisition module 300, and convert the output excitation voltage into current through the current-voltage conversion module 200; the current-voltage conversion module 200 is used to convert the voltage into a sinusoidal current with a peak value of 200 μA, and reduce the offset voltage in the circuit through a negative feedback circuit;

[0086] The excitation current is injected into the biological tissue 4 through the HC electrode, and the current signal flowing through the biological tissue 4 is collected by the LC electrode; the HV electrode and the LV electrode of the impedance detection electrode 600 are used to collect voltage signals to the voltage collection module 300, and after filtering out high-frequency and low-frequency interference, the voltage signal is transmitted to the analysis and calculation module 100 and impedance calculation is performed.

[0087] Specifically, the analysis and calculation module 100 is connected to the current-voltage conversion module 200 and the voltage acquisition module 300, receives the biological detection voltage signal amplified and filtered from the voltage acquisition module 300, and converts the output excitation voltage into current through the current-voltage conversion module 200, and accurately controls the output current intensity to improve safety. The current-voltage conversion module 200 converts the voltage into a sinusoidal current with a peak-to-peak value of 200μA, and uses a negative feedback circuit to reduce the offset voltage in the circuit. The excitation current is injected into the biological tissue 4 through the HC electrode, and the current signal flowing through the tissue is collected by the LC electrode. The impedance detection electrode 600HV and LV electrodes collect voltage signals to the voltage acquisition module 300, and after filtering out high-frequency and low-frequency interference, the voltage signal is transmitted to the analysis and calculation module 100 and impedance calculation is performed. The impedance detection device 2 can accurately detect the impedance of 0-10kΩ, the impedance modulus detection error is less than 5%, the phase value detection error is less than 15%, and the Cole-Cole model component extraction value error is less than 6%.

[0088] Furthermore, the analysis and calculation module 100 outputs an excitation voltage signal, which is converted into a current by the current-voltage conversion module 200 and output to the biological tissue 4. At the same time, the voltage across the biological tissue 4 is collected by the voltage acquisition module 300, and then the voltage is sent back to the analysis and calculation module 100. The DSP integrated inside the AD5933 chip of the analysis and calculation module 100 will calculate the input and output signals, and after DFT processing, it will return a real data word and an imaginary data word stored in the register. In order to convert this value into an actual impedance value and phase value, a gain coefficient and an initial phase are required. Taking resistance as an example, if Figure 4As shown, first, an external known resistor 400 is connected, the impedance amplitude at this time is calculated to calculate the gain coefficient, and the phase at this time, that is, the initial phase, is calculated; then the known resistor 400 is replaced with the resistor to be measured 500, and the actual impedance modulus value and phase value are calculated using the gain coefficient and initial phase obtained in the previous step.

[0089] In the method for evaluating the effect of irreversible electroporation ablation based on bioimpedance analysis provided in the present application, 1) by applying a single-frequency electrical signal to evaluate the effect of IRE ablation using bioimpedance technology, the resistance change of the tissue can be monitored in real time to reflect the tissue damage during the irreversible electroporation process; it is very sensitive to the change of tissue resistance and can detect small changes in bioimpedance in time, thereby evaluating the effect of IRE treatment; by measuring the change in resistance, the degree of electroporation in the treatment area can be quantitatively analyzed, which helps to optimize the treatment parameters. 2) The advantages of evaluating the effect of IRE ablation using bioimpedance technology by applying multi-frequency electrical signals are: using electrical signals of different frequencies helps to distinguish the contribution of resistance and capacitance, identify the conductivity and capacitance changes of the membrane, and thus more accurately evaluate the ablation effect caused by irreversible electroporation; it can provide impedance spectra at different frequencies, identify the sensitivity of different frequencies to tissues, reveal more complex tissue electrical properties, and provide a more comprehensive and in-depth perspective for the effect evaluation of IRE, which helps to optimize the treatment process and improve the treatment effect. 3) The bioimpedance technology is used to evaluate the IRE ablation effect by applying mixed-frequency electrical signals. The measurement and detection time is short, and the bioimpedance information at different frequencies at the same time can be obtained, and the changes in bioimpedance can be detected in time.

[0090] In summary, the use of bioimpedance to evaluate IRE treatment avoids the lag of medical imaging methods such as ultrasound or histopathological evaluation. And based on the evaluation of the ablation effect, the pulse generator is controlled by negative feedback of the applied ablation dose, which can accurately determine the treatment endpoint, thereby avoiding excessive or insufficient treatment.

[0091] The above are only a number of specific implementations of the obstacle recognition method based on multi-sensor fusion of the present application. Each implementation can be implemented independently or in combination, and the present application is not limited to this. Furthermore, the flowchart of the present application is only illustrative, and the execution order between the steps is not limited to this. The splitting, merging, order exchange, and other synchronous or asynchronous execution methods of the steps are all within the scope of protection of the present application.

[0092] Those skilled in the art will readily appreciate other embodiments of the present application after considering the specification and practicing the invention disclosed herein. The present application is intended to cover any modification, use or adaptation of the present application, which follows the general principles of the present application and includes common knowledge or customary techniques in the art that are not disclosed in the present application. The specification and examples are intended to be exemplary only, and the true scope and spirit of the present application are indicated by the appended claims.

Claims

1. A method for evaluating the effect of irreversible electroporation ablation based on bioimpedance analysis, characterized in that: The steps include: applying an electrical signal to the tissue to be ablated; measuring a voltage across the tissue under test generated by the electrical signal; determining an impedance value across the tissue under test at a predetermined frequency based on the measured voltage; Performing IRE ablation on biological tissue, and repeating the above steps to measure the impedance value of the ablated tissue; Based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the ablated tissue, the irreversible electroporation ablation effect is evaluated.

2. The evaluation method according to claim 1, characterized in that: The electrical signal is set to be an electrical signal of fixed frequency; Determining the impedance value across the test tissue at a predetermined frequency based on the measured voltage includes: calculating the impedance value across the test tissue at the fixed frequency using the impedance formula in Ohm's law: Z=V / I, where Z is impedance, V is voltage, and I is current; The method of evaluating the effect of irreversible electroporation ablation based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation includes: recording and analyzing the impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation; evaluating the effect of irreversible electroporation ablation based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation.

3. The evaluation method according to claim 1, characterized in that: The electrical signal is set to an alternating current signal of different frequencies, including low frequency and high frequency, to obtain impedance data of the full spectrum; the impedance value of the tissue after ablation is characterized by a Cole-Cole model; The method of evaluating the irreversible electroporation ablation effect based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the ablated tissue includes: analyzing the impedance value across the test tissue at the predetermined frequency and the impedance value of the ablated tissue at different frequencies, evaluating the changes in membrane resistance, capacitance and tissue conductivity, and evaluating the tissue ablation effect based on the changes.

4. The evaluation method according to claim 3, characterized in that: The Cole-Cole model is set up as: (1) ， (2) ， (3) ， (4) ， (5) ， in, and are the impedance at zero frequency and infinite frequency respectively, is the impedance of the extracellular fluid, is the impedance of the intracellular fluid, is the capacitance component of the cell membrane, is the complex impedance of the model, is the impedance of the cell membrane, is the angular frequency, is the time constant, is the characteristic frequency of the dispersion, represents the frequency dependence, the angle is the phase shift of the impedance.

5. The evaluation method according to claim 1, characterized in that: The electrical signal is set to be an alternating current signal of high and low frequency mixing, and the mixing is consistent; The method of evaluating the irreversible electroporation ablation effect based on the impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation includes: using a mixing algorithm to process the measured impedance value across the test tissue at the predetermined frequency and the impedance value of the tissue after ablation, extracting comprehensive information about the electrical properties of the tissue, and evaluating the tissue ablation effect based on the comprehensive information.

6. A device for evaluating ablation effect based on a multi-frequency bioimpedance method, characterized in that: include: High voltage pulse generator, impedance detection equipment, transfer switch, biological tissue; The high-voltage pulse generating device is provided with electrodes HC and LC for outputting high-voltage pulse electrical signals. The electrodes HC and LC simultaneously serve as excitation current release electrodes of the impedance detection device. The electrode HC is at a high level, and the electrode LC is at a low level. The opening and closing of the electrodes HC and LC are switched by the transfer switch. The impedance detection device is provided with an analysis and calculation module for collecting and calculating the impedance information of biological tissues; A current-voltage conversion module, used for stimulating current output; A voltage acquisition module, used for filtering and amplifying the collected voltage signal; The impedance detection electrode is used to collect the voltage across the biological tissue; the impedance detection device can quickly scan the frequency and transmit the calculation results to the computer.

7. The device according to claim 6, characterized in that The high-voltage pulse generating device can generate positive and negative pulse signals with multiple adjustable parameters, including pulse voltage adjustable from 0 to 3000V, pulse width adjustable from 500ns to 100μs, delay between pulses adjustable from 10 to 5000μs, pulse train and pulse logarithm adjustable, the rise time and fall time of the device are both 50ns, and the delay time between pulse trains is 0.5 seconds; The device is also provided with a Cole-Cole model element for characterizing the impedance value of the tissue after ablation.

8. The device according to claim 6, characterized in that The analysis and calculation module is connected to the current-voltage conversion module and the voltage acquisition module, and is used to receive the biological detection voltage signal after amplification and filtering from the voltage acquisition module, and convert the output excitation voltage into current through the current-voltage conversion module; The current-to-voltage conversion module is used to convert the voltage into a sinusoidal current with a peak value of 200 μA, and reduce the offset voltage in the circuit through a negative feedback circuit; The excitation current is injected into the biological tissue through the HC electrode, and the current signal flowing through the biological tissue is collected by the LC electrode; the HV electrode and the LV electrode of the impedance detection electrode are used to collect voltage signals to the voltage collection module, and after filtering out high-frequency and low-frequency interference, the voltage signal is transmitted to the analysis and calculation module for impedance calculation.

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