Noninvasive evaluation device for inactivation rate of liver microwave ablation cells based on Young modulus

Abstract

The invention discloses a liver microwave ablation cell inactivation rate noninvasive evaluation device based on Young modulus, which is characterized in that a user terminal, a main control board, a microwave source and a microwave ablation needle are sequentially connected, and a linear shear wave elastic imaging diasonograph and an array ultrasonic probe are sequentially connected; liver minimally invasive microwave ablation can be carried out by utilizing the built liver microwave ablation cell inactivation rate non-invasive evaluation device. The method comprises the following steps: measuring Young moduli corresponding to different ablation areas in liver minimally invasive microwave ablation, and obtaining cell inactivation rates of the different ablation areas through cell activity flow experiments of the different ablation areas; fitting modeling is conducted on the average Young modulus and the average cell inactivation rate of the different ablation areas, and a cell inactivation rate-Young modulus model is obtained. Therefore, an effective cell inactivation rate and Young modulus relation model is established, the cell inactivation rate of the microwave ablation tissue is estimated through the Young modulus obtained in real time, the ablation effect is accurately evaluated, and real-time 2D evaluation of microwave ablation is achieved.

Description

Technical Field

[0001] The invention relates to the technical field of non-invasive assessment, and in particular to a non-invasive assessment device for liver microwave ablation cell inactivation rate based on Young's modulus. Background Art

[0002] The key to the efficacy of precise tumor ablation is how to monitor the ablation effect in real time. Real-time efficacy monitoring technology has always been the research focus of thermal ablation. At present, temperature is mainly used as a determining factor for tumor cell inactivation in clinical practice, which cannot correctly reflect the degree of ablation of tumor tissue. Temperature and measurement alone cannot obtain other relevant parameters of tumor tissue during ablation in real time, including protein coagulation degree, tissue hardness, enzyme activity, etc. How to associate the efficacy evaluation factors (physical parameters) that characterize the degree of protein coagulation and tissue hardness with tissue inactivation indicators (cell inactivation rate) is the key issue to be solved by microwave ablation.

[0003] The microwave ablation process of tumors is essentially a process of protein denaturation and gradual coagulation during the ablation process. During the coagulation process, the mechanical properties of tumor tissue (tissue hardness) will change dynamically with tissue dehydration and coagulation. Shear wave elastography (SWE) can measure tissue hardness (Young's modulus E) in real time and obtain 2D images of tissue hardness. The researchers used SWE to measure the changes in hardness of the lesions and surrounding liver parenchyma before and after tumor microwave ablation. The hardness after ablation was significantly higher than that before ablation. Young's modulus can more stably reflect the coagulation state of proteins during the ablation process. However, there is currently a lack of microwave ablation efficacy evaluation standards and evaluation models based on Young's modulus. How to use Young's modulus to complete accurate real-time efficacy evaluation of microwave ablation requires more detailed research.

[0004] Currently, there is no effective 2D evaluation model based on Young's modulus for the inactivation rate of cells during microwave ablation of the liver in vivo. Summary of the invention

[0005] The present invention provides a non-invasive assessment device for liver microwave ablation cell inactivation rate based on Young's modulus. A microwave ablation module and a shear wave elastic imaging module are used to perform microwave ablation and imaging, and an effective cell inactivation rate-Young's modulus model is established. The cell inactivation rate of microwave ablated tissue is estimated by Young's modulus, and the ablation effect is accurately evaluated.

[0006] The embodiment of the present invention provides a non-invasive evaluation device for liver microwave ablation cell inactivation rate based on Young's modulus, comprising: a microwave ablation module and a shear wave elastic imaging module;

[0007] The microwave ablation module includes a microwave source, a microwave ablation needle, a main control board and a user terminal;

[0008] The shear wave elastic imaging module includes a shear wave elastic imaging ultrasound diagnostic instrument and a linear array ultrasound probe;

[0009] The microwave ablation needle, the microwave source, the main control board and the user terminal are connected in sequence, and the linear array ultrasound probe is connected to the shear wave elastic imaging ultrasound diagnostic instrument.

[0010] Optionally, in one embodiment of the present invention, the device further comprises:

[0011] The measurement module is used to measure the Young's modulus corresponding to different ablation areas in minimally invasive microwave ablation of the liver;

[0012] An acquisition module is used to obtain the cell inactivation rates of different ablation areas through flow cytometry experiments of cell activity in different ablation areas;

[0013] The evaluation module is used to fit and model the average Young's modulus and average cell inactivation rate of different ablation areas to obtain a cell inactivation rate-Young's modulus model.

[0014] Optionally, in one embodiment of the present invention, different ablation areas include: completely destroyed tissue, i.e., coagulation area, edge of completely destroyed tissue, i.e., periphery of coagulation area, congestion zone, i.e., transition zone, edge of congestion zone, i.e., periphery of transition zone and normal area.

[0015] Optionally, in one embodiment of the present invention, in the acquisition module, the cell activity flow cytometry experiment adopts the Annexin V-FITC / PI method to obtain the proportion of naked nucleus cells, living cells, necrotic or late apoptotic cells and early apoptotic cells in different ablation areas.

[0016] Optionally, in one embodiment of the present invention, normal cells, i.e., living cells, have an intact cell membrane, and the phosphatidylserine PS in the components of the cell membrane of living cells is located on the inner side of the cell membrane. When apoptosis occurs in the cell, the PS originally on the inner side of the cell membrane is turned inside out to the surface of the cell membrane. Therefore, Annexin V is used to detect early apoptotic cells; Annexin V-FITC single positive cells are early apoptotic cells, Annexin V-FITC and PI double positive cells are necrotic or late apoptotic cells, and PI single positive cells are naked nucleus cells.

[0017] Optionally, in one embodiment of the present invention, the cell inactivation rate is the sum of the proportion of necrotic or late apoptotic cells and the proportion of early apoptotic cells.

[0018] Optionally, in one embodiment of the present invention, in the evaluation module, the average cell inactivation rate is taken as the variable x and the average Young's modulus is taken as the dependent variable y, and the average Young's modulus and the average cell inactivation rate of different ablation areas are fitted to obtain a cell inactivation rate-Young's modulus model with the maximum goodness of fit.

[0019] The embodiment of the present invention provides a non-invasive assessment device for liver microwave ablation cell inactivation rate based on Young's modulus. The shear wave elastic imaging ultrasound diagnostic instrument is turned on, and the ultrasound probe is placed above the ablation site and perpendicular to the ablation needle. The center of the ultrasound probe coincides with the energy radiation point, and a 2D Young's modulus image of the ablation site is obtained. A cell inactivation rate-Young's modulus model is established, and the cell inactivation rate of the microwave ablated tissue can be estimated by the obtained Young's modulus, and the ablation effect can be accurately evaluated. The real-time 2D distribution of the cell inactivation rate can also be obtained, which is helpful for clinical real-time 2D non-invasive assessment of tissue thermal damage effects during microwave ablation.

[0020] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which:

[0022] Figure 1 A schematic diagram of a non-invasive evaluation device for liver microwave ablation cell inactivation rate based on Young's modulus according to an embodiment of the present invention;

[0023] Figure 2 A flow chart of a non-invasive evaluation method for liver microwave ablation cell inactivation rate based on Young's modulus according to an embodiment of the present invention;

[0024] Figure 3 This is a regional division diagram of a rabbit liver after ablation according to an embodiment of the present invention;

[0025] Figure 4 This is a distribution diagram of cell activity in five regions of a rabbit liver after in vivo ablation according to an embodiment of the present invention;

[0026] Figure 5 is a curve diagram of the Ψ-E correlation model of an embodiment of the present invention (0 <E≤55kPa);

[0027] Figure 6 4 is a curve diagram of the Ψ-E correlation model of an embodiment of the present invention. DETAILED DESCRIPTION

[0028] Embodiments of the present invention are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, and should not be construed as limiting the present invention.

[0029] Figure 1This is a schematic diagram of a non-invasive evaluation device for liver microwave ablation cell inactivation rate based on Young's modulus according to an embodiment of the present invention.

[0030] like Figure 1 As shown, a non-invasive assessment device for liver microwave ablation cell inactivation rate based on Young's modulus includes: a microwave ablation module and a shear wave elastic imaging module; the microwave ablation module includes a microwave source 1, a microwave ablation needle 2, a main control board 3 and a user terminal 4, and the shear wave elastic imaging module includes a shear wave elastic imaging ultrasound diagnostic instrument 5 and a linear array ultrasound probe 6; the microwave ablation needle 2, the microwave source 1, the main control board 3 and the user terminal 4 are connected in sequence, and the linear array ultrasound probe 6 is connected to the shear wave elastic imaging ultrasound diagnostic instrument 5.

[0031] When performing microwave ablation, the microwave ablation needle 2 is minimally invasively inserted into the rabbit liver 7 , and the linear array ultrasound probe 6 is placed on the upper part of the liver and attached to the skin surface above the rabbit liver 7 .

[0032] In an embodiment of the present invention, the device further comprises:

[0033] A measurement module is used to measure the Young's modulus corresponding to minimally invasive microwave ablation of the liver according to different ablation areas;

[0034] An acquisition module is used to obtain the cell inactivation rates of different ablation areas through flow cytometry experiments of cell activity in different ablation areas;

[0035] The evaluation module is used to fit and model the average Young's modulus and average cell inactivation rate of different ablation areas to obtain a cell inactivation rate-Young's modulus model.

[0036] Specifically, if Figure 2 As shown, minimally invasive microwave ablation of the liver was performed using the constructed liver microwave ablation cell inactivation rate non-invasive evaluation device, different ablation areas were marked, and the corresponding Young's modulus E was measured. Samples of the marked different ablation areas were sampled and cell activity flow cytometry experiments were performed separately to obtain the cell inactivation rate Ψ in different ablation areas. The experiment was repeated to obtain the average Young's modulus and average cell inactivation rate of different ablation areas, and the average Young's modulus and average cell inactivation rate of different areas were fitted and modeled to obtain the Ψ-E correlation model.

[0037] In an embodiment of the present invention, the cell activity flow cytometry experiment uses the Annexin V-FITC / PI method to obtain the proportions of naked nucleus cells, living cells, necrotic or late apoptotic cells, and early apoptotic cells in different ablation areas.

[0038] In an embodiment of the present invention, the cell inactivation rate Ψ refers to the sum of the proportion of late necrosis or apoptosis cells (upper right quadrant) and the proportion of early apoptosis cells (lower right quadrant). After a large number of rabbit liver in vivo ablation and cell activity experiments, it was found that the cell inactivation rate of completely damaged tissue (coagulation area) was 97.86%-98.8%, the cell inactivation rate of the edge of completely damaged tissue (outside of coagulation area) was 83.28%-90.1%, the cell inactivation rate of the congestion zone (transition area) was 64.1%-70.85%, the cell inactivation rate of the edge of the congestion zone (outside of the transition area) was 24.8%-41.52%, and the cell inactivation rate of normal tissue (normal area) was 2.2%-7.2%.

[0039] In an embodiment of the present invention, the average cell inactivation rate is used as a variable (x) and the average Young's modulus is used as a dependent variable (y). The average Young's modulus and the average cell inactivation rate of different regions are fitted to obtain the Ψ-E related model equation with the maximum goodness of fit. Since the Young's modulus of the coagulation region is greater than 55 kPa, there is no relatively definite upper limit. Therefore, the tissue Young's modulus and the inactivation rate are segmented modeled. The average Young's modulus of different regions other than the coagulation region and the corresponding average cell inactivation rate are modeled by polynomial fitting. The two have a linear positive correlation and have the highest goodness of fit (R ) on the first-order polynomial. 2 ), its R 2 Closest to 1, we can get the Ψ-E relationship model:

[0040] Ψ=aE+b;0 <E≤55kPa

[0041] Among them, a and b are constants.

[0042] The cell inactivation rate in the coagulation area is a constant value, and the constant c can be used as the average cell inactivation rate in the coagulation area. Therefore, the final Ψ-E relationship model is as follows:

[0043]

[0044] In an embodiment of the present invention, a rabbit weighing about 3 kg is selected as an experimental subject, a minimally invasive opening is made in the abdominal cavity of the animal to ensure that the liver can be seen, and then the ablation needle is horizontally inserted into the liver, and the ultrasound probe is placed above the ablation site, close to the skin, and perpendicular to the ablation needle. The ablation power is set to 10 W, and the ablation time is set to 240 s. The center of the ultrasound probe coincides with the energy radiation point to ensure that the obtained Young's modulus image is an image along the vertical direction of the needle track. The shear wave elastic imaging module is started at the same time as the ablation begins.

[0045] like Figure 3As shown, it is a regional division diagram of rabbit liver after ablation; the ablation area of ​​the in vivo liver can be subdivided into coagulation area (completely destroyed tissue), coagulation area (edge ​​of completely destroyed tissue), transition area (congestion zone), edge of transition area (edge ​​of congestion zone), and normal area (normal tissue). The method of the present invention can be used to measure the average value of Young's modulus of different areas.

[0046] like Figure 4 The figure shows the distribution of cell activity in five areas of rabbit liver after in vivo ablation; Annexin V-FITC / PI method cell activity flow cytometry experiment. Normal cells (living cells) have intact cell membranes. At this time, phosphatidylserine (PS) in the cell membrane components is located on the inner side of the cell membrane. When cells undergo apoptosis, PS originally on the inner side of the cell membrane turns outward to the surface of the cell membrane. Therefore, Annexin V, which has a high affinity with PS and is labeled with fluorescein, is used to detect early apoptotic cells. Annexin V-FITC (Fluorescein Isothiocyanate) single positive cells are early apoptotic cells, Annexin V-FITC and PI (Propidium Iodide) double positive cells are necrotic or late apoptotic cells, and PI single positive cells are naked nucleus cells. The results of the cell activity flow cytometry experiment are displayed in four quadrants, and the four quadrants correspond to cells of different activities: upper left quadrant: naked nucleus cells; lower left quadrant: live cells; upper right quadrant: necrotic or late apoptotic cells; lower right quadrant: early apoptotic cells. The proportion of the number of cells in each quadrant to the total number of cells in the four quadrants will be displayed as a percentage. According to this experiment, the cell inactivation rate in different ablation areas can be obtained. The cells in the upper right quadrant and the lower right quadrant can be counted as inactive (inactivated) cells, and the cell inactivation rate (Ψ) can be calculated. The cell inactivation rate in the normal area is 5.78%, the cell inactivation rate in the periphery of the transition area is 41.52%, the cell inactivation rate in the transition area is 67.85%, the cell inactivation rate in the periphery of the coagulation area is 90.1%, and the cell inactivation rate in the coagulation area is 98.8%.

[0047] After 20 groups of in vivo ablation and cell viability experiments on rabbit livers, it was found that the cell inactivation rate in the completely ablated tissue (coagulation area) was 97.86% - 98.8%, the cell inactivation rate at the edge of the completely ablated tissue (outside the coagulation area) was 83.28% - 90.1%, the cell inactivation rate in the hyperemic zone (transition area) was 64.1% - 70.85%, the cell inactivation rate at the edge of the hyperemic zone (edge of the transition area) was 24.8% - 41.52%, and the cell inactivation rate in the normal tissue (normal area) was 2.2% - 7.2%. Young's modulus measurements and cell inactivation rate calculations were performed on different regions of 20 groups of rabbit livers, and the average Young's modulus and average cell inactivation rate in different regions after in vivo ablation of rabbit livers were obtained, as shown in Table 1.

[0048] Table 1 Average Young's modulus and average cell inactivation rate in different regions after in vivo ablation of rabbit livers

[0049]

[0050] As Figure 5 shown, it is the curve graph of the Ψ-E related model of Embodiment Ψ-E of the present invention (0 < E ≤ 55 kPa); since the Young's modulus of the coagulation area > 55 kPa and there is no relatively definite upper limit, therefore, piecewise modeling is performed on the tissue Young's modulus and inactivation rate. Polynomial fitting modeling is performed on the average Young's modulus and the corresponding average cell inactivation rate in different regions except the coagulation area, and there is a linear positive correlation between the two, with the highest goodness of fit on the first-order polynomial (R 2 ), and its R 2 is closest to 1, and the obtained Ψ-E related model is as follows:

[0051] Ψ = (2.077E - 16.766)%; 0 < E ≤ 55 kPa

[0052] where, R 2 = 0.9977.

[0053] As Figure 6 shown, it is the curve graph of the Ψ-E related model of Embodiment of the present invention; combining the Young's modulus and average cell inactivation rate of the coagulation area, the established Ψ-E related model is as follows:

[0054]

[0055] The non-invasive evaluation device for liver microwave ablation cell inactivation rate based on Young's modulus of the embodiment of the present invention connects the user terminal, the main control board, the microwave source and the microwave ablation needle in sequence, and the linear shear wave elastic imaging ultrasound diagnostic instrument and the array ultrasound probe in sequence. The constructed non-invasive evaluation device for liver microwave ablation cell inactivation rate can be used to perform minimally invasive microwave ablation of the liver. By measuring the Young's modulus corresponding to different ablation areas in minimally invasive microwave ablation of the liver, the cell inactivation rates of different ablation areas are obtained through flow cytometry experiments of cell activity in different ablation areas; the average Young's modulus and the average cell inactivation rate of different ablation areas are fitted and modeled to obtain a cell inactivation rate-Young's modulus model. Thus, an effective relationship model between cell inactivation rate and Young's modulus is established. The cell inactivation rate of microwave ablated tissue is estimated by the real-time acquired Young's modulus, the ablation effect is accurately evaluated, and real-time 2D evaluation of microwave ablation is achieved.

[0056] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or N embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0057] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In the description of the present invention, the meaning of "N" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0058] Any process or method description in a flowchart or otherwise described herein may be understood to represent a module, fragment or portion of code comprising one or N executable instructions for implementing the steps of a custom logical function or process, and the scope of the preferred embodiments of the present invention includes alternative implementations in which functions may not be performed in the order shown or discussed, including performing functions in a substantially simultaneous manner or in reverse order depending on the functions involved, which should be understood by technicians in the technical field to which the embodiments of the present invention belong.

Claims

1. A non-invasive evaluation device for liver microwave ablation cell inactivation rate based on Young's modulus, characterized in that: include: Microwave ablation module and shear wave elastography module; The microwave ablation module includes a microwave source, a microwave ablation needle, a main control board and a user terminal; The shear wave elastic imaging module includes a shear wave elastic imaging ultrasound diagnostic instrument and a linear array ultrasound probe; The microwave ablation needle, the microwave source, the main control board and the user terminal are connected in sequence, and the linear array ultrasound probe is connected to the shear wave elastic imaging ultrasound diagnostic instrument.

2. The device according to claim 1, characterized in that The device also includes: The measurement module is used to measure the Young's modulus corresponding to different ablation areas in minimally invasive microwave ablation of the liver; An acquisition module is used to obtain the cell inactivation rates of different ablation areas through flow cytometry experiments of cell activity in different ablation areas; The evaluation module is used to fit and model the average Young's modulus and average cell inactivation rate of different ablation areas to obtain a cell inactivation rate-Young's modulus model.

3. The device according to claim 2, characterized in that Different ablation areas include: completely destroyed tissue, namely the coagulation area, the edge of completely destroyed tissue, namely the periphery of the coagulation area, the congestion zone, namely the transition zone, the edge of the congestion zone, namely the periphery of the transition zone, and the normal area.

4. The device according to claim 2, characterized in that In the acquisition module, the cell activity flow cytometry experiment uses the Annexin V-FITC / PI method to obtain the proportions of naked nucleus cells, living cells, necrotic or late apoptotic cells and early apoptotic cells in different ablation areas.

5. The device according to claim 4, characterized in that Normal cells, i.e. living cells, have intact cell membranes. Among the components of the cell membrane of living cells, phosphatidylserine PS is located on the inner side of the cell membrane. When cells undergo apoptosis, the PS originally on the inner side of the cell membrane turns outside to the surface of the cell membrane. Therefore, Annexin V is used to detect early apoptotic cells; Annexin V-FITC single positive cells are early apoptotic cells, Annexin V-FITC and PI double positive cells are necrotic or late apoptotic cells, and PI single positive cells are naked nucleus cells.

6. The device according to claim 2, characterized in that The cell inactivation rate is the sum of the proportion of necrotic or late apoptotic cells and the proportion of early apoptotic cells.

7. The device according to claim 2, characterized in that In the evaluation module, the average cell inactivation rate is taken as the variable x and the average Young's modulus is taken as the dependent variable y. The average Young's modulus and the average cell inactivation rate in different ablation regions are fitted to obtain a cell inactivation rate-Young's modulus model with the maximum goodness of fit.

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