CN110755148B - Pulsed electric field tumor ablation parameter optimization system - Google Patents

Pulsed electric field tumor ablation parameter optimization system Download PDF

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CN110755148B
CN110755148B CN201910890502.9A CN201910890502A CN110755148B CN 110755148 B CN110755148 B CN 110755148B CN 201910890502 A CN201910890502 A CN 201910890502A CN 110755148 B CN110755148 B CN 110755148B
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tissue
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electrode
parameters
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CN110755148A (en
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姚陈果
董守龙
赵亚军
余亮
郑爽
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Hangzhou Vena Anke Medical Technology Co Ltd
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
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Abstract

The invention discloses a pulsed electric field tumor ablation parameter optimization system which mainly comprises an image processing module, a physical parameter measuring module, a pulsed electrode parameter setting module, a pulse sequence forming module, a plurality of pulsed electrodes and a database; the image processing model acquires a biological tissue image of a user; the image processing model carries out optimization processing on the biological tissue image of the user to obtain a three-dimensional structure of the biological tissue. The pulse electrode parameter selection model processes the received physical parameters, calculates the pulse voltage, the pulse number, the pulse electrode position parameters and the depth of the pulse electrode inserted into the biological tissue of the user, and sends the parameters to the pulse sequence forming module; the pulsed electrode pulses biological tissue of a user. The system can realize complete ablation of tumor tissues, minimum damage to normal tissues and minimum thermal damage by setting optimal electrode arrangement and pulse parameters.

Description

Pulsed electric field tumor ablation parameter optimization system
Technical Field
The invention relates to the field of pulsed electric field application, in particular to a pulsed electric field tumor ablation parameter optimization system.
Background
The global cancer survival trend monitoring plan report (year 2000-: the 5-year survival rate of most cancer patients in China is lower than the average level in the world, the life quality is poor, and the cancer treatment situation is still not optimistic. The latest research finds that: in the process of tumor growth, after multiple division and proliferation, daughter cells of the tumor have obvious differences in the aspects of tumor growth speed, invasion capacity, drug sensitivity, prognosis and the like, show high tumor heterogeneity on average of patients, tissues, cells and molecules, and reduce and kill the curative effects of a plurality of traditional therapies. Currently, personalized precise medicine is the development direction of modern medicine, however, tumor heterogeneity seriously hinders the clinical realization of precise tumor therapy.
The pulsed electric field tumor therapy has the advantages of nonheat, rapidness, selectivity and the like, and becomes a research hotspot in the field of tumor therapy in recent years. From the viewpoint of bioelectromagnetism, the dielectric properties of cells or tissues are fundamental physical characteristics of organisms, and play an important role in the field of biomedical research. A large number of researches show that dielectric properties of tumors of the same type of different patients, tumors of different parts of the same patient and even different development stages of the same tumor tissue are obviously different, and electrical response effects (corresponding treatment effects) under the action of different pulse parameters have obvious difference. The current method for treating tumor by pulse electric field is to couple pulse electric field to act on biological dielectric medium and induce the transmembrane potential of inner and outer membranes of cell to change sharply, break the balance between inside and outside of cell, thus achieving the purpose of killing tumor cells. How to combine tumor tissue form and dielectric parameter specificity, determine the optimal electrode parameters and pulse parameters for realizing complete ablation of tumor tissues and protecting normal tissues as much as possible through simulation, construct an effective preoperative tumor ablation system for realizing accurate ablation of tumors, and is a key problem to be solved at present in pulsed electric field tumor therapy.
Disclosure of Invention
The present invention is directed to solving the problems of the prior art.
The technical scheme adopted for achieving the purpose of the invention is that the pulsed electric field tumor ablation parameter optimization system mainly comprises an image processing module, a physical parameter measuring module, a pulsed electrode parameter setting module, a pulse sequence forming module, a plurality of pulsed electrodes and a database.
The database stores data of the image processing module, the physical parameter measuring module, the pulse electrode parameter setting module and the pulse sequence forming module.
The image processing model obtains a user biological tissue image. The image processing model carries out optimization processing on the biological tissue image of the user to obtain a three-dimensional structure of the biological tissue and determine the volume V of the tumor tissue in the three-dimensional structureTAnd a location.
Further, the biological tissue image of the user is a medical image such as a CT image, an MRI image, and an ultrasound image.
Further, the biological tissue includes tumor tissue and normal biological tissue. The normal biological tissue has a conduit system including tissue vessels.
The physical parameter measuring module measures physical parameters of the biopsy biological tissue and sends the physical parameters to the pulse electrode parameter setting module.
Preferably, the physical parameters mainly include tumor tissue dielectric parameters, normal biological tissue dielectric parameters, electrical conductivity, thermal conductivity, specific heat capacity, density, activation energy barrier and metabolic heat.
The pulse electrode parameter setting module stores a pulse electrode parameter selection model and a tissue ablation statistical model.
Further, the main steps for establishing the pulse electrode parameter selection model are as follows:
1) and carrying out binary coding on the parameters to be optimized.
2) And randomly generating an initial population of the parameters to be optimized. The parameter to be optimized is pulse voltage, pulse number, pulse electrode position parameter or depth of the pulse electrode inserted into the biological tissue of the user. The maximum number of iterations m is set.
3) A fitness function F is determined, namely:
Figure BDA0002208584720000021
in the formula, VTirreIs the irreversible electroporation volume of tumor tissue. VTTumor tissue volume. VHirreIs the irreversible electroporation volume of normal biological tissue. Fitness F>0. The k value is related to the importance degree of the target ablation tumor, and is larger near the important organs, blood vessels and other pipeline systems.
4) Calculating the fitness value F and the fitness average F of any individualmeanAnd determining the number a of times the individual is selected. The value of the selected number of times a is equal to the individual fitness value F and the fitness mean FmeanThe quotient of the divisions. Individual fitness value F and fitness mean FmeanThe remainder of the division is denoted y.
5) And sequentially arranging all remainders, and selecting individuals corresponding to the first j remainders.
6) And crossing the selected j individuals, and mainly comprising the following steps:
6.1) calculating the Cross probability value P for each individualcNamely:
Figure BDA0002208584720000031
in the formula, FmaxThe maximum fitness value of the individual in the population. Fmean1Is the maximum of the two individual fitness values to be crossed.
6.2) generating a random number g1. If the cross probability value Pc>g1Then cross, if the cross probability value Pc≤g1Then there is no crossover.
7) Performing mutation operation on the crossed j individuals, which mainly comprises the following steps:
7.1) calculating the variation probability value P of each individualmNamely:
Figure BDA0002208584720000032
7.2) generating a random number g2. If the probability value P is variedm>g2Then, mutation is performed, if the probability value P is mutatedm≤g2Then there is no variation.
8) Judging termination condition, namely inputting the individual into a tissue ablation statistical model, and if the cell survival rate S is 0, the biological tissue is damaged KTDMinimum sum of VTirre/VTAnd if not, returning to the step 3 and repeating the iteration.
And the tissue ablation statistical model judges the tissue cell ablation degree.
Further, the main steps for establishing the tissue ablation statistical model are as follows:
1) calculating the survival rate S of the tumor tissue cells, namely:
Figure BDA0002208584720000033
wherein S is cell survival rate. And E is a pulse voltage. Ec(n) is the corresponding electric field strength when 50% of the tumor tissue cells dieAnd (4) degree. A. thec(n) is the corresponding pulse amplitude at which 50% of the tumor tissue cells die.
Wherein 50% of the tumor tissue cells die corresponding to the electric field intensity Ec(n) and pulse amplitude A corresponding to 50% of tumor tissue cell deathc(n) are respectively as follows:
Figure BDA0002208584720000041
in the formula, E0Is the initial value of the pulse voltage. k1 is the electric field strength calculation coefficient. n is the number of pulses.
2) Calculating the tumor tissue ablation percentage KEPNamely:
KEP＝(1-S)·100。 (6)
3) determining the thermal damage of the biological tissue, namely:
Figure BDA0002208584720000042
wherein R is a general gas constant. Zeta is an index factor used to represent the effective collision frequency of the reacting molecules in the biological reaction. EaReflecting the activation energy barrier that the molecule needs to overcome.
4) Determining biological tissue damage, namely:
KTD＝100·(1-exp(-Ω(t)))。 (8)
in the formula, Ω (t) represents thermal damage to the biological tissue.
The pulse electrode parameter selection model processes the received physical parameters, calculates the pulse voltage, the pulse number, the pulse electrode position parameters and the depth of the pulse electrode inserted into the biological tissue of the user, and sends the parameters to the pulse sequence forming module.
And the pulse sequence forming module determines the position of the pulse electrode according to the optimized pulse electrode position parameter.
The pulse sequence forming module drives the pulse electrode to be inserted into the biological tissue of the user according to the optimized depth of the pulse electrode to be inserted into the biological tissue of the user.
And the pulse sequence forming module outputs pulse voltage to the pulse electrode according to the optimized pulse voltage.
Further, the plurality of pulse electrodes output pulse voltages in a cyclic single/multiple manner or a direct application manner.
And the pulse sequence forming module determines the number of output pulses of the pulse electrode according to the optimized number of pulses.
The pulsed electrode pulses biological tissue of a user.
The database stores an image processing module, a physical parameter measuring module, a pulse electrode parameter setting module and a pulse sequence forming module.
It is worth noting that whether tumor tissue can be effectively ablated is closely related to the electric field distribution within the tissue. When the electric field intensity of a certain area reaches or exceeds the ablation threshold field intensity, the tissue of the area can be effectively ablated. Researches show that under the action of a pulse electric field, the electrical parameters of biological tissues can be obviously changed, the tissue performance changes caused by different pulse amplitudes and pulse widths are different, and the changes present a nonlinear accumulation effect with the continuous application of pulses, so that the final electrical parameters of the tissues present a non-uniform distribution. Along with the dynamic change of the electrical parameters of the biological tissue, the electric field in the tissue can change correspondingly, so that the distribution of the electric field and the electrical parameters in the tissue presents a coupled change process, and finally, a dynamic balance is achieved. Therefore, the research on the electric field distribution in the tissue under the action of the pulse electric field can be closer to the actual condition only by considering the mutual coupling effect of the electric field distribution and the electrical characteristics of the tissue, and an important basis is laid for accurately determining the ablation region. Furthermore, the pulsed electrode arrangement is also a major factor affecting the electric field distribution within the tissue. Therefore, the final determination of the ablation range requires a comprehensive consideration of the tissue electrical parameter distribution, the treatment electrode arrangement, and the selection of pulse parameters.
The technical effect of the present invention is undoubted. The invention proposes a system with optimal electrode placement and pulse parameter configuration by mathematical optimization algorithm based on tumor location, size and electrical characteristic information. For tumors with specific forms and parameters and normal tissues around the tumors, the system can obtain optimal electrode arrangement and pulse parameter configuration, and can achieve the effects of complete tissue ablation, minimum damage to normal tissues and minimum thermal damage.
Therefore, the invention provides a new system which optimizes and controls the pulse parameters and the electrode parameters through a genetic algorithm according to the difference between the tumor cell morphology and the dielectric parameters of each patient, obtains the optimal treatment parameters meeting the clinical treatment requirements through simulation calculation, and enables the optimal treatment parameters to selectively and efficiently act on tumor tissues, thereby establishing a personalized treatment strategy and realizing accurate tumor ablation.
Drawings
FIG. 1 is a flow chart of a pulse electrode parameter selection model establishment;
FIG. 2 is a diagram of the outline of each part of the liver;
FIG. 3 is a three-dimensional model of the liver and its surroundings;
FIG. 4 is a tumor and electrode arrangement;
FIG. 5 is a tissue mesh generation;
FIG. 6 is a schematic diagram of a single application of a pulse;
FIG. 7 is a schematic diagram of multiple applications of pulses;
FIG. 8 shows the electric field distribution under the action of composite pulses;
FIG. 9 is a composite pulse irreversible electroporation tumor ablation scenario;
FIG. 10 is a graph showing temperature distribution under the effect of conventional pulsing and composite pulsing;
FIG. 11 illustrates the thermal injury of conventional pulse and composite pulse irreversible electroporation tumors;
FIG. 12 is an original CT slice;
FIG. 13 is a tumor and liver outline marker;
FIG. 14 is a tumor segmentation;
FIG. 15 is liver segmentation;
FIG. 16 is a polygon stage liver;
fig. 17 is a polygonal stage tumor image;
FIG. 18 is a graph of a slice of a liver;
FIG. 19 is a curved slice tumor map;
FIG. 20 is a three-dimensional liver map;
FIG. 21 is a three-dimensional tumor map;
FIG. 22 is a tumor model map;
FIG. 23 is a liver model diagram;
FIG. 24 is a diagram of tumor and liver models;
FIG. 25 is a model view of tumor and liver after placement of electrodes.
Detailed Description
The present invention is further illustrated by the following examples, but it should not be construed that the scope of the above-described subject matter is limited to the following examples. Various substitutions and alterations can be made without departing from the technical idea of the invention and the scope of the invention is covered by the present invention according to the common technical knowledge and the conventional means in the field.
Example 1:
referring to fig. 1 to 25, the pulsed electric field tumor ablation parameter optimization system mainly includes an image processing module, a physical parameter measuring module, a pulsed electrode parameter setting module, a pulse sequence forming module, a plurality of pulsed electrodes, and a database.
The database stores data of the image processing module, the physical parameter measuring module, the pulse electrode parameter setting module and the pulse sequence forming module.
The image processing model obtains a user biological tissue image. The image processing model carries out optimization processing on the biological tissue image of the user to obtain a three-dimensional structure of the biological tissue and determine the volume V of the tumor tissue in the three-dimensional structureTAnd a location.
Further, the user biological tissue image is a CT image or an MRI image.
Further, the biological tissue includes tumor tissue and normal biological tissue (including important conduit systems such as tissue blood vessels).
The physical parameter measuring module measures physical parameters of the biopsy biological tissue and sends the physical parameters to the pulse electrode parameter setting module.
Further, the physical parameter measuring module measures physical parameters of the tumor tissue of the user and normal biological tissue attached to the tumor tissue according to a small amount of biological tissue samples of the user, and sends the physical parameters to the pulse electrode parameter setting module.
Preferably, the physical parameters mainly include tumor tissue dielectric parameters, normal biological tissue dielectric parameters, electrical conductivity, thermal conductivity, specific heat capacity, density, activation energy barrier and metabolic heat.
The pulse electrode parameter setting module stores a pulse electrode parameter selection model and a tissue ablation statistical model.
Further, referring to fig. 1, the main steps of establishing the pulse electrode parameter selection model are as follows:
1) and carrying out five-bit binary coding on the parameter to be optimized, wherein the length of each individual chromosome is 5 Xn-bit binary number.
2) And randomly generating an initial population of the parameters to be optimized. The parameter to be optimized is pulse voltage, pulse number, pulse electrode position parameter or depth of the pulse electrode inserted into the biological tissue of the user. The maximum iteration number m is set to 50. The range of pulse voltage is 450V-3000V, the range of electrode spacing is 5 mm-20 mm, and the range of exposure length is 1 mm-30 mm.
3) A fitness function F is determined, namely:
Figure BDA0002208584720000071
in the formula, VTirreIs the irreversible electroporation volume of tumor tissue. VTTumor tissue volume. VHirreIs the irreversible electroporation volume of normal biological tissue. Fitness F>0. The k value is an empirical value, the size of the k value is related to the importance degree of the target ablation tumor, and the k value is larger near the important organs, blood vessels and other conduit systems and ranges from 0.1 to 0.5.
4) Calculating the fitness value F and the fitness average F of any individualmeanAnd determining the number a of times the individual is selected. The value of the selected number of times a is equal to the individual fitness value F and the fitness mean FmeanThe quotient of the divisions.Individual fitness value F and fitness mean FmeanThe remainder of the division is denoted y.
5) And sequentially arranging all remainders, and selecting individuals corresponding to the first j remainders. j is 26.
6) And crossing the selected j individuals, and mainly comprising the following steps:
6.1) calculating the Cross probability value P for each individualcNamely:
Figure BDA0002208584720000081
in the formula, FmaxThe maximum fitness value of the individual in the population. Fmean1Is the maximum of the two individual fitness values to be crossed.
6.2) generating a random number g1. If the cross probability value Pc>g1Then cross, if the cross probability value Pc≤g1Then there is no crossover.
7) Performing mutation operation on the crossed j individuals, which mainly comprises the following steps:
7.1) calculating the variation probability value P of each individualmNamely:
Figure BDA0002208584720000082
7.2) generating a random number g2. If the probability value P is variedm>g2Then, mutation is performed, if the probability value P is mutatedm≤g2Then there is no variation.
8) Judging termination condition, namely inputting the individual into a tissue ablation statistical model, and if the cell survival rate S is 0, the biological tissue is damaged KTDMinimum sum of VTirre/VTAnd if not, returning to the step 3 and repeating the iteration.
And the tissue ablation statistical model judges the tissue cell ablation degree.
Further, the main steps for establishing the tissue ablation statistical model are as follows:
1) calculating the survival rate S of the tumor tissue cells, namely:
Figure BDA0002208584720000083
wherein S is cell survival rate. And E is a pulse voltage. Ec(n) is the electric field strength corresponding to 50% of the tumor tissue cells dead. A. thec(n) is the corresponding pulse amplitude at which 50% of the tumor tissue cells die.
Wherein 50% of the tumor tissue cells die corresponding to the electric field intensity Ec(n) and pulse amplitude A corresponding to 50% of tumor tissue cell deathc(n) are respectively as follows:
Figure BDA0002208584720000091
in the formula, E0Is the initial value of the pulse voltage. k1 is the electric field strength calculation coefficient. n is the number of pulses.
2) Calculating the tumor tissue ablation percentage KEPNamely:
KEP＝(1-S)·100。 (6)
3) determining the thermal damage of the biological tissue, namely:
Figure BDA0002208584720000092
wherein R is a general gas constant, and R is 8.314J mol-1K-1. Zeta is an index factor used to represent the effective collision frequency of the reacting molecules in the biological reaction. EaReflecting the activation energy barrier that the molecule needs to overcome.
4) Determining biological tissue damage, namely:
KTD＝100·(1-exp(-Ω(t)))。 (8)
in the formula, Ω (t) represents thermal damage to the biological tissue.
The pulse electrode parameter selection model processes the received physical parameters, calculates the pulse voltage, the pulse number, the pulse electrode position parameters and the depth of the pulse electrode inserted into the biological tissue of the user, and sends the parameters to the pulse sequence forming module. Simultaneously, the parameters of the pulse electrode enable the effective electric field of the electrode to cover the whole tumor area.
And the pulse sequence forming module determines the position of the pulse electrode according to the optimized pulse electrode position parameter.
The pulse sequence forming module drives the pulse electrode to be inserted into the biological tissue of the user according to the optimized depth of the pulse electrode to be inserted into the biological tissue of the user.
And the pulse sequence forming module outputs pulse voltage to the pulse electrode according to the optimized pulse voltage.
Preferably, the pulse sequence forming module is an all-solid-state pulse circuit composed of devices such as a semiconductor switch, a capacitor, an inductor, a lead and a diode.
Preferably, the pulse sequence forming module is a pulse generator.
Further, the pulse electrodes output pulse voltages in a cyclic single or multiple manner.
And the pulse sequence forming module determines the number of output pulses of the pulse electrode according to the optimized number of pulses.
The pulsed electrode pulses biological tissue of a user.
The database stores an image processing module, a physical parameter measuring module, a pulse electrode parameter setting module and a pulse sequence forming module.
Example 2:
the pulsed electric field tumor ablation parameter optimization system has the main module as described in embodiment 1, and further the user biological tissue image is an electronic Computed Tomography (CT) image or an Magnetic Resonance Imaging (MRI) image.
The CT image or MRI image may be processed by image segmentation, etc. to obtain three-dimensional spatial structures of normal biological tissue, tumor, and various parts of artery, as shown in fig. 2 to 4, respectively. After the three-dimensional space structure is obtained, mesh generation and finite element calculation can be performed on the three-dimensional space structure, as shown in fig. 5.
Among them, the standard DICOM (digital Imaging and communications in medicine) format is selected for CT pictures. The pictures in the format contain relevant information during CT scanning, such as scanning intervals, pixel sizes of the pictures and the like, and are beneficial to the identification and processing of image processing software.
Example 4:
the main modules of the pulsed electric field tumor ablation parameter optimization system are the same as those in embodiment 1, and further, the biological tissue comprises tumor tissue and normal biological tissue. The biological tissue is liver.
Example 5:
the main modules of the pulsed electric field tumor ablation parameter optimization system are the same as those in embodiment 1, and preferably, the physical parameters mainly comprise tumor tissue dielectric parameters, normal biological tissue dielectric parameters, electrical conductivity, thermal conductivity, specific heat capacity, density, activation energy barrier and metabolic heat.
The physical parameters are shown in table 1:
table 1 physical parameters of each part
Figure BDA0002208584720000111
Example 6:
the main modules of the system are the same as those of embodiment 1, and further, 4 pulse electrodes respectively output pulse voltages in a circulating single or multiple mode, namely the pulse voltages are circularly applied in a mode of electrode 1-electrode 2, electrode 2-electrode 3, electrode 3-electrode 4 and electrode 4-electrode 1. A single application, i.e. the next pair of pulse actions is performed after each pair of electrode actions will optimize the resulting pulses are applied, as shown in fig. 6; and (3) multiple times of application, namely, each pair of electrodes is applied with a part of optimized number of pulses, and after cyclic application, part of pulses are continuously applied until all pulses are applied, as shown in fig. 7.
Example 7:
the main modules of the pulsed electric field tumor ablation parameter optimization system are the same as those in embodiment 1, and furthermore, the acquired CT slices are imported by using Mimics software. And the Mimics software determines the sequence of the images according to the information in the CT images so as to correctly generate the required images. After the picture is imported, the software segments images of liver tumors and livers in each CT slice by setting corresponding pixel threshold ranges, processes the segmented images through a 3D modeling function to respectively obtain three-dimensional models of the liver tumors and the livers, and outputs the three-dimensional models in an stl format. And establishing a solid geometric model. The three-dimensional model output by the Mimics software is a surface network model, the model cannot be subjected to solid modeling, and the model also has some defects, such as holes and unsmooth surfaces, and therefore the model needs to be further processed. The model output by the Mimics can be optimized by using Geomagic Studio software, some defects in the model can be repaired, and a solid model of tumor and normal tissues can be generated. The Geomagic processed image is output in stp format. The stp format three-dimensional image can be imported into the finite element analysis software COMSOL for numerical modeling.
Example 8:
an experiment for verifying the pulsed electric field tumor ablation parameter optimization system of embodiments 1 to 7 mainly comprises the following steps:
1) and determining the electric field distribution of the electrodes when the electrodes of the pulsed electric field tumor ablation parameter optimization system output pulsed voltage.
Whether the tissue can be effectively ablated or not is mainly determined by the electric field intensity at the corresponding position, and in order to observe the electric field distribution near the electrode in the tissue, a section is selected for reflecting the electric field distribution in a simulation mode. Fig. 8 shows the distribution of the electric field inside the tissue under the action of the pulsed electric field, and it can be seen that the high field intensity is mainly concentrated near the electrodes, and the peripheral electric field is rapidly attenuated, so that the distribution is beneficial to limiting the treatment area in the target area, and the ablation shape is controlled by optimizing the electrode arrangement and the pulse parameters.
2) Regional contrast analysis with 90% ablation probability:
when the statistical model is used for describing the tissue ablation condition, under the same pulse parameter effect, the tissue ablation volume obtained according to different death probabilities is also different. In the research, for unified comparative analysis, a region with 90% ablation probability is selected for comparative analysis.
Under the action of the composite pulse, under the conditions of different pulse train numbers and pulse voltages, the tumor ablation caused by irreversible electroporation is shown in fig. 9. With the increasing intensity of the pulse electric field and the number of pulse trains, the ablation degree of the irreversible electroporation of the tissue and the ablation probability of the irreversible electroporation of the tissue are increased gradually, so that the ablation area caused by the electric field is increased gradually. Due to the irregular shape of tumor tissues, the pulsed electric field inevitably causes slight damage to a small part of normal tissues around the tumor in the ablation process.
The tissue thermal damage condition is related to the temperature distribution in the tissue and the temperature duration, and the temperature rise in the tissue is closely related to the pulse electric field intensity and the number of pulse trains. FIG. 10 shows the temperature distribution of a section of the tissue interior. It can be seen that the temperature rise is mainly concentrated in a small range near the electrode in the tumor, and has no influence on surrounding normal tissues and blood vessels.
Likewise, thermal damage is also a statistical concept, and thus the volume of thermal damage resulting from selecting different probabilities of thermal damage is also different. Also, in order to compare the thermal damage degree uniformly, the region with 90% thermal damage degree is selected for comparative analysis of different pulse parameters. The joule heat caused by the composite pulses with different electric field intensities and different numbers of pulse trains is different, the higher the pulse electric field amplitude is, the more the pulse trains are, the more the naturally generated joule heat is, the more the thermal damage of the tissue caused by the joule heat is increased, and the thermal damage of the tissue near the electrode is as shown in fig. 11. Unlike tissue ablation by electric field-induced irreversible electroporation, the area of thermal injury, although increasing with increasing pulse parameters, is primarily confined to a small portion of the tumor tissue near the electrodes, leaving no damage to normal tissue. The volume of thermal damage is much smaller than the volume of tissue ablation caused by irreversible electroporation for the same pulse parameters.
In summary, for a tumor and its surrounding normal tissue with a specific morphology and parameters, the system can achieve complete ablation of tumor tissue, minimal damage to normal tissue, and minimal thermal damage by setting optimal electrode arrangement and pulse parameters.

Claims (5)

1. Pulsed electric field tumour ablation parameter optimization system which characterized in that: the system mainly comprises a database, an image processing module, a physical parameter measuring module, a pulse electrode parameter setting module, a pulse sequence forming module and a plurality of pulse electrodes;
the database stores data of the image processing module, the physical parameter measuring module, the pulse electrode parameter setting module and the pulse sequence forming module;
the image processing model acquires a biological tissue image; the image processing model processes the biological tissue image to obtain a three-dimensional structure of the biological tissue and determines the volume of the tumor tissue in the three-dimensional structureV T And a location;
the physical parameter measuring module measures physical parameters of the biopsy biological tissue and sends the physical parameters to the pulse electrode parameter setting module;
the pulse electrode parameter setting module stores a pulse electrode parameter selection model and a tissue ablation statistical model;
the main steps for establishing the pulse electrode parameter selection model are as follows:
1) binary coding is carried out on the parameters to be optimized;
2) randomly generating an initial population of parameters to be optimized; the parameters to be optimized are pulse voltage, pulse number, pulse electrode position parameters or the depth of the pulse electrode inserted into the biological tissue; setting the maximum iteration numberm；
3) Determining fitness functionFNamely:
Figure DEST_PATH_IMAGE002
； （1）
in the formula (I), the compound is shown in the specification,V Tirre is the irreversible electroporation volume of the tumor tissue;V T tumor tissue volume;V Hirre is the irreversible electroporation volume of normal biological tissue; degree of adaptabilityF>0; k is an empirical value；
4) Calculating an arbitrary individual fitness valueFAnd fitness averageF mean And determining the number of times the individual is selecteda(ii) a Number of times of selectionaIs equal to the individual fitness valueFAnd fitness averageF mean The quotient of the division; individual fitness valueFAnd fitness averageF mean The remainder of the division is notedy；
5) All remainders are arranged in sequence and selected to be frontjIndividuals corresponding to the number of remainders;
6) for selectedjThe individuals are crossed, and the main steps are as follows:
6.1) calculating the Cross probability value of each individualP c Namely:
Figure DEST_PATH_IMAGE004
； （2）
in the formula (I), the compound is shown in the specification,F max the maximum fitness value of the individuals in the population;F max1the maximum value of the fitness values of the two individuals to be crossed is obtained;
6.2) generating a random number g1(ii) a If cross probability valueP c >g 1Then cross, if cross probability valueP c ≤g1If so, no crossing is performed;
7) after crossingjThe individual carries out mutation operation, and the main steps are as follows:
7.1) calculating the variation probability value of each individualP m Namely:
Figure DEST_PATH_IMAGE006
； （3）
7.2) generating a random number g2(ii) a If the probability value of variationP m >g 2Then, mutation is performed, if the probability value is variedP m ≤g2If so, the change is not changed;
8) judging termination condition, namely inputting the individual into a tissue ablation statistical model, judging cell survival rate S =0 and biological tissue damageK TD Is minimum andV Tirre /V T =1, if the condition is met, outputting the individual numerical value as the numerical value of the parameter to be optimized, and if the condition is not met, returning to the step 3), and repeating iteration;
the pulse electrode parameter selection model processes the received physical parameters, calculates the optimized pulse voltage, the pulse number, the pulse electrode position parameters and the depth of the pulse electrode inserted into the biological tissue, and sends the parameters to the pulse sequence forming module;
the tissue ablation statistical model judges the tissue cell ablation degree;
the pulse sequence forming module determines the position of the pulse electrode according to the optimized pulse electrode position parameter;
the pulse sequence forming module drives the pulse electrode to be inserted into the biological tissue according to the optimized depth of the pulse electrode to be inserted into the biological tissue;
the pulse sequence forming module outputs pulse voltage to the pulse electrode according to the optimized pulse voltage;
the pulse sequence forming module determines the number of pulse output by the pulse electrode according to the optimized number of pulses;
the pulse electrode applies a pulse electric field to the biological tissue to realize tissue ablation.
2. The pulsed electric field tumor ablation parameter optimization system of claim 1, wherein: the physical parameters mainly comprise tumor tissue dielectric parameters, normal biological tissue dielectric parameters, electrical conductivity, thermal conductivity, specific heat capacity, density, activation energy barrier and metabolic heat.
3. The pulsed electric field tumor ablation parameter optimization system of claim 1, wherein: the biological tissue image is a CT image, an ultrasonic image or an MRI image.
4. The pulsed electric field tumor ablation parameter optimization system of claim 1, wherein: the biological tissues comprise tumor tissues and normal biological tissues; the normal biological tissue has a conduit system including tissue vessels.
5. The pulsed electric field tumor ablation parameter optimization system of claim 1, wherein: the pulse electrodes output pulse voltages in a cyclic single or multiple manner.
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