CN114014976B

CN114014976B - Tumor-bearing tissue model for US/CT (US/computed tomography) guided descending tumor puncture or thermal ablation training and preparation method thereof

Info

Publication number: CN114014976B
Application number: CN202111164314.1A
Authority: CN
Inventors: 周平; 钟新宇; 李家乐
Original assignee: Central South University; Third Xiangya Hospital of Central South University
Current assignee: Central South University; Third Xiangya Hospital of Central South University
Priority date: 2021-09-30
Filing date: 2021-09-30
Publication date: 2023-01-24
Anticipated expiration: 2041-09-30
Also published as: CN114014976A

Abstract

The invention discloses a tumor-bearing tissue model for US/CT (US/computed tomography) guided downlink tumor puncture or thermal ablation training, which comprises a normal tissue phantom and a tumor phantom embedded in the normal tissue phantom; the normal tissue phantom contains: acrylamide gel, temperature-sensitive ink and sodium chloride; the tumor phantom contains: acrylamide gel, temperature-sensitive ink, sodium chloride, US contrast agent and CT contrast agent; the acrylamide gel is formed by polymerization and crosslinking reaction of acrylamide and methylene bisacrylamide. The tumor-bearing tissue model can accurately position and evaluate the position and the size of a tumor, and carry out tumor puncture and thermal ablation training under the guidance of US/CT; the range of the coagulative necrotic area after thermal ablation can be simply and intuitively displayed in a color change mode, so that the tumor thermal ablation effect can be accurately evaluated. Also discloses a preparation method of the tumor-bearing tissue model, which has the advantages of simple operation, low cost, high reaction efficiency, easy process control and environmental protection.

Description

Tumor-bearing tissue model for US/CT (US/computed tomography) guided descending tumor puncture or thermal ablation training and preparation method thereof

Technical Field

The invention belongs to the field of medicine, particularly relates to the field of interventional therapy, and relates to a tumor-bearing tissue model for US/CT (US/computed tomography) guided downlink tumor puncture or thermal ablation training and a preparation method thereof.

Background

Image-guided thermal ablation therapy is widely used as an interventional therapy for clinically treating tumors in various parts of the human body, such as the liver, the breast, the thyroid and the like. The basic operation is to insert an ablation needle into the interior of a tumor under precise guidance of imaging (e.g., ultrasound, CT, etc.) and to cause a large amount of heat to be locally generated in the tumor tissue. The main principle is that when the temperature reaches about 60 ℃, the tumor cells can immediately generate coagulative necrosis, thereby achieving the purpose of killing the tumor cells.

In recent years, the image-guided thermal ablation technology is rapidly developed, is one of clinically recognized effective means for local treatment of tumors, and has the advantages of good curative effect, small wound, few complications and the like. However, thermal ablation techniques have significant dependence, both on new instrumentation and on the operating experience of the clinician. Therefore, in order to accelerate the young doctors to understand and master the thermal ablation technology, it is important to develop an artificial tumor-bearing tissue model for thermal ablation teaching and training.

The invention with publication number CN105427725A prepares a phantom model for ultrasonic single-mode image fusion assessment of tumor ablation range based on carrageenan, and the model can accurately assess tumor ablation range and can be used as a teaching and training model of tumor ablation technology. Unfortunately, the operation process is complicated because the gel-like model after ablation can be formed by absorbing the dissolved gel and the partially dissolved normal tissue gel in the surrounding in a short time and then injecting new gel for ablation. Publication numbers CN105374266A and CN105590531A both describe a phantom model for simulating tumor ultrasound contrast, which is beneficial to practice of tumor biopsy and tumor ablation treatment under ultrasound contrast scanning method and ultrasound guidance. Unfortunately, none of them gives an accurate way to assess the extent of tumor ablation. In conclusion, a few techniques for preparing the phantom model for the thermal ablation training exist, and optimization and improvement spaces exist. Therefore, there is a need for a new tumor-bearing tissue model that can be used for imaging-guided downlink tumor puncture and thermal ablation training.

Disclosure of Invention

The technical problem to be solved by the invention is to overcome the defects and shortcomings in the background technology, and provide a tumor-bearing tissue model for US/CT guided descending tumor puncture or thermal ablation training and a preparation method thereof, which can simply and intuitively display the range of the coagulative necrosis area after thermal ablation.

In order to solve the technical problems, the technical scheme provided by the invention is as follows:

a tumor-bearing tissue model for US/CT guided downlink tumor puncture or thermal ablation training belongs to a gel phantom, in particular to a phantom based on acrylamide gel; the tumor-bearing tissue model comprises the following parts: a tumor phantom (tumor glue) for simulating a tumor, and a normal tissue phantom (normal tissue glue) for simulating surrounding normal tissue, the tumor phantom being embedded in the normal tissue phantom;

the normal tissue phantom contains: acrylamide gel, temperature-sensitive ink and sodium chloride;

the tumor phantom contains: acrylamide gel, temperature-sensitive ink, sodium chloride, US contrast agents and CT contrast agents.

The tumor-bearing tissue phantom is preferably composed of acrylamide gel, temperature-sensitive ink 3-7% v/v and sodium chloride 9 mg/mL; the tumor phantom consists of acrylamide gel, temperature-sensitive ink with the weight percent of 3-7 v/v, sodium chloride with the weight percent of 9mg/mL, US contrast agent with the weight percent of 8-32mg/mL and CT contrast agent with the weight percent of 15-45 mg/mL. The acrylamide gel is a main body part forming the tumor-bearing tissue model, the sodium chloride endows the tumor-bearing tissue model with conductivity similar to that of human tissues, and the temperature-sensitive ink endows the tumor-bearing tissue model with temperature-sensitive characteristics.

Preferably, the acrylamide gel is a gel with a net-shaped three-dimensional structure formed by dissolving acrylamide and methylene acrylamide in a mass ratio of 19; in the normal tissue phantom or the tumor phantom, the total concentration of acrylamide and methylene bisacrylamide is 50-120mg/mL. At this mass ratio and concentration, the acrylamide gel formed has an elasticity and texture similar to those of biological soft tissue. More preferably, the polymerizer is Ammonium Persulfate (APS) and the catalyst is TEMED (tetramethylethylenediamine), wherein methylene bisacrylamide acts as a crosslinking agent, the more methylene bisacrylamide (crosslinker), the smaller the pores of the gel.

Preferably, the temperature-sensitive ink is water-soluble temperature-sensitive ink changing color (from colorless to peach-red) at the temperature of more than or equal to 60 ℃, and more preferably the water-soluble temperature-sensitive ink changing color at the temperature of 60 ℃. By adding 9mg/mL of sodium chloride and 60 ℃ temperature-sensitive ink, the acrylamide gel has electrical and thermal characteristics more similar to those of human soft tissues.

Compared with the low melting point (50-70 ℃) of carrageenan adopted by a conventional body membrane, the acrylamide gel provided by the invention can obviously resist high temperature and can maintain stability at the high temperature of 120 ℃, which is undoubtedly a great advantage in the field of thermal therapy; in addition, the simulated thermal ablation range of the carrageenan is the melting point range (50-70 ℃), while the polyacrylamide gel in the invention utilizes 60 ℃ temperature-sensitive ink, so the simulated thermal ablation range is more accurate.

Preferably, the CT contrast agent is iohexol, and can enhance the CT value of a tumor phantom on CT imaging; the US contrast agent is Plantain seed husk powder, and can improve the echo signal intensity of a tumor phantom in US imaging.

The normal tissue phantom portion exhibits hypoechoic and low density under US/CT imaging, while the tumor phantom portion exhibits hyperechoic and high density under US/CT imaging due to the addition of US/CT contrast agents, so the size and location of the tumor in the tumor-bearing tissue model can be accurately assessed and located by either the US diagnostic or CT imager. Because the echo signal and the CT value of the puncture needle or the ablation needle are higher than those of tumor-bearing tissues, the position of the puncture needle or the ablation needle in the tumor-bearing tissue model can be clearly positioned through US/CT imaging. Meanwhile, the tumor-bearing tissue model can generate obvious color change when the ablation temperature reaches above 60 ℃, so that the tumor-bearing tissue model can be used for evaluating the range of a thermal ablation focus.

Based on a general inventive concept, the present invention also provides a method for preparing a tumor-bearing tissue model, comprising the steps of:

(1) Preparing a tumor phantom: dissolving acrylamide and methylene acrylamide powder in water to prepare an acrylamide-methylene acrylamide solution, adding sodium chloride, a CT contrast agent, temperature sensing ink and a US contrast agent, uniformly stirring, then adding a polymerization agent and a catalyst to obtain a mixed solution A, and introducing the mixed solution A into a mold before the mixed solution A is completely gelatinized to form a tumor phantom;

(2) Preparing a mixed solution B of a normal tissue phantom: dissolving acrylamide and methylene acrylamide powder in water to prepare an acrylamide-methylene acrylamide solution, adding sodium chloride and temperature-sensitive ink, uniformly stirring, and then adding a polymerizing agent and a catalyst to obtain a mixed solution B;

(3) Embedding the tumor phantom obtained in the step (1) in the mixed solution B before the mixed solution B is completely gelatinized to form a normal tissue phantom, and obtaining the tumor-bearing tissue model after the mixed solution B is completely gelatinized to form a normal tissue phantom.

In the above preparation method, it is preferable that the mixed solution a contains: acrylamide 47.5-114mg/mL, methylene acrylamide 2.5-6mg/mL, temperature sensitive ink 3-7% v/v, sodium chloride 9mg/mL, polymerization agent 1-2mg/mL, catalyst 0.1-0.2% v/v, US contrast agent 8-32mg/mL, CT contrast agent 15-45mg/mL, and ultrapure water;

the mixed solution B contains: acrylamide 47.5-114mg/mL, methylene acrylamide 2.5-6mg/mL, temperature sensitive ink 3-7% v/v, sodium chloride 9mg/mL, polymerizer 1-2mg/mL, catalyst 0.1-0.2% v/v, and ultrapure water.

More preferably, the mixed solution a contains: acrylamide 66.5mg/mL, methylene acrylamide 3.5mg/mL, temperature sensitive ink 5% v/v, sodium chloride 9mg/mL, polymerization agent 1.4mg/mL, catalyst 0.14% v/v, US contrast agent 30mg/mL, CT contrast agent 16mg/mL, and ultrapure water;

the mixed solution B contains: acrylamide 66.5mg/mL, methylene acrylamide 3.5mg/mL, temperature sensitive ink 5% v/v, sodium chloride 9mg/mL, polymerizer 1.4mg/mL, catalyst 0.14% v/v, and ultrapure water.

Preferably, the polymerization agent is ammonium persulfate which is used as a polymerization initiator and can initiate the polymerization reaction of acrylamide and methylene acrylamide to help the conversion of the acrylamide solution to acrylamide gel; the catalyst is TEMED (tetramethylethylenediamine) which can accelerate the polymerization reaction. The combination of the two can promote the acrylamide solution to begin to crosslink into a three-dimensional network gel structure.

Preferably, the mixed solution A and the mixed solution B are gelatinized at the temperature of 4-10 ℃.

Compared with the prior art, the invention has the beneficial effects that:

1. the tumor-bearing tissue model can accurately position and evaluate the position and the size of a tumor in the model by an US/CT imaging means, and carry out tumor puncture and thermal ablation training under the guidance of US/CT; moreover, the model can simply and intuitively display the range of the coagulative necrotic area after thermal ablation in a color change mode, thereby being helpful for accurately evaluating the tumor thermal ablation effect.

2. The tumor-bearing tissue model takes acrylamide-methylene acryloyl gel as a main structure and has elasticity and texture similar to those of biological soft tissues; the added NaCl and the temperature-sensitive ink have electrical and thermal characteristics similar to those of human soft tissues.

3. The preparation method disclosed by the invention is simple to operate, low in cost, high in reaction efficiency, easy to control in preparation process and environment-friendly.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.

FIG. 1 is a schematic view of the process for preparing a tumor-bearing tissue model according to the present invention.

FIG. 2 is a photograph of US and CT imaging of a tumor-bearing tissue model of the present invention; a is an appearance diagram of a tumor-bearing tissue model; b is a CT image of a normal tissue phantom part; c is a CT image of the tumor phantom part; d is an US image (linear array probe) of the tumor-bearing tissue model: wherein the spherical part is a tumor phantom, and the surrounding part is a normal tissue phantom; e is US diagram of tumor-bearing tissue model (convex probe): the spherical part is a tumor phantom, and the surrounding part is a normal tissue phantom.

FIG. 3 is CT measurements of a tumor-bearing tissue model of the present invention.

FIG. 4 is a diagram of the location of a puncture or ablation needle in a tumor-bearing tissue model located by US/CT imaging; (A and B are US-guided tumor punctures; C and D are CT-guided tumor punctures).

Figure 5 is a graph comparing tumor-bearing tissue models of the present invention heated to 60 c (above) and unheated (below).

FIG. 6 is a diagram of tumor thermal ablation operation and ablation effect under the guidance of row US/CT imaging for the tumor-bearing tissue model of the present invention.

Detailed Description

In order to facilitate an understanding of the invention, reference will now be made in detail to the present preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings, and the scope of the invention is not limited to the following specific embodiments.

Unless otherwise defined, all terms of art used hereinafter have the same meaning as commonly understood by one of ordinary skill in the art. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention.

Unless otherwise specifically stated, various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or can be prepared by existing methods.

Example (b):

a tumor-bearing tissue model for US/CT guided downlink tumor puncture or thermal ablation training consisting of two parts: one part is a tumor glue (tumor phantom) used to mimic a tumor, and the other part is a normal tissue glue (normal tissue phantom) used to mimic surrounding normal tissue.

The preparation method comprises the following steps (the flow is schematically shown in figure 1):

step 1: preparation of tumor phantom

Taking 400mL as an example, 26.6g of acrylamide and 1.4g of methylenebisacrylamide were weighed in a mass ratio of 19 according to 1 and completely dissolved in 380mL of ultrapure water to obtain an acrylamide-methyleneacrylamide solution (7% w/v). Adding 3.6g NaCl (0.9% w/v) while stirring with an electric stirrer at constant speed and stirring uniformly; adding 12g iohexol (30 mg/mL or 3% w/v) and stirring well; slowly adding 20mL of temperature-sensitive ink (5% v/v) dropwise until the mixed solution is uniformly stirred; adding 6.4g of powdered carposine (16 mg/mL or 1.6% w/v) to the mixture and stirring well; rapidly adding 0.56g of polymerizing agent-ammonium persulfate (0.14% w/v) and 0.56mL of catalyst-TEMED (0.14% v/v) and stirring well. And finally, pouring a proper amount of mixed solution into a plurality of spherical molds with the diameter of about 3cm, placing the molds in a refrigerator at 4 ℃ to wait for gelling, and obtaining a tumor phantom after gelling.

Step 2: preparation of Normal tissue phantom (not completely gelled)

In a 400mL system as an example, 26.6g of acrylamide and 1.4g of methylenebisacrylamide were weighed out in a mass ratio of 19 and completely dissolved in 380mL of ultrapure water to obtain an acrylamide-methyleneacrylamide solution (7% w/v). Adding 3.6g NaCl (0.9% w/v) and stirring well under constant stirring with an electric stirrer; slowly adding 20mL of temperature-sensitive ink (5% v/v) dropwise until the mixed solution is uniformly stirred; rapidly adding 0.56g of polymerizing agent-ammonium persulfate (0.14% w/v) and 0.56mL of catalyst-TEMED (0.14% v/v) and stirring well, pouring the mixture into a cubic mold.

The temperature-sensitive ink adopted in the

steps

1 and 2 is water-soluble temperature-sensitive ink changing color at 60 ℃.

And step 3: and (3) suspending the tumor phantom prepared in the step (1) in the center of the mixed solution obtained in the step (2) through a thin line fine needle, so that the tumor phantom is embedded in a normal tissue phantom.

And 4, step 4: and (3) after the mixed solution obtained in the step (2) forms relatively stable gel, pulling out the fine line and the fine needle, putting the tumor-bearing tissue model into a refrigerator at 4 ℃ until complete gelatinization is achieved, and finishing the tumor-bearing tissue model.

To further demonstrate the utility of the tumor-bearing tissue model of the present invention, the following tests were performed:

1. the tumor-bearing tissue model prepared in the embodiment is detected and three-dimensionally reconstructed by using an US diagnostic apparatus and a CT imaging apparatus.

As shown in fig. 2, the normal tissue phantom portion exhibits hypoechoic and low density under US/CT imaging, while the tumor phantom portion exhibits hyperechoic and high density under US/CT imaging due to the addition of US/CT contrast agent, the hyperechoic tumor phantom contrasts sharply with the surrounding hypoechoic normal tissue phantom. Therefore, the size and location of the tumor in the tumor-bearing tissue model can be accurately assessed and located by the US diagnostic or CT imager.

As shown in fig. 3, the CT value of the Tumor phantom (Tumor) is significantly higher than that of the Normal tissue phantom (Normal tissue), indicating that the Tumor phantom in the Tumor-bearing tissue model can be clearly located by three-dimensional reconstruction.

2. The tumor position and size are accurately positioned and evaluated by using an imaging means (US/CT imaging), and then a puncture needle is accurately inserted into the tumor under the guidance of the US/CT imaging; and then starting a microwave therapeutic apparatus for treatment (adopting an MTC-3 microwave therapeutic apparatus, wherein the ablation frequency is 2450MHz, the output power is 5-100W, and the ablation needle is a 16g cold circulation type single-machine ablation needle), cutting the tumor-bearing tissue model along the long axis direction of the ablation needle after the ablation procedure is finished, observing the color change of the model, and evaluating the ablation effect.

As shown in figure 4, the echo signals and CT values of the puncture needle or the ablation needle are higher than those of tumor-bearing tissues and are in sharp contrast with those of a tumor phantom and a surrounding normal tissue phantom, so that the position of the puncture needle or the ablation needle in the tumor-bearing tissue model can be clearly positioned through US/CT imaging. Fig. 4B shows tumor puncture training under US imaging guidance, and fig. 4C-4D show tumor puncture training under CT imaging guidance.

As shown in fig. 5, the model sample heated to 60 ℃ is on the top (red color), and the unheated phantom sample is on the bottom (color of gel itself), which shows that the tumor-bearing tissue model can generate obvious color change when the ablation temperature reaches above 60 ℃, and therefore can be used for evaluating the range of thermal ablation focus.

As shown in fig. 6, the spherical part is a tumor phantom, the surrounding is a normal tissue phantom, the red part is an ablated region, the non-red part is an non-ablated region, the obvious color difference exists between the ablated region and the non-ablated region, and a clear boundary exists between the tumor and the liver, which indicates that the tumor-bearing tissue model can intuitively display the thermal ablation effect through color change.

Claims

1. A tumor-bearing tissue model for US/CT guided downlink tumor puncture or thermal ablation training, comprising a normal tissue phantom, and a tumor phantom embedded in the normal tissue phantom;

the normal tissue phantom consists of acrylamide gel, temperature sensitive ink 3-7%;

the tumor phantom consists of acrylamide gel, temperature-sensitive ink with the weight percent of 3-7 v/v, sodium chloride with the weight percent of 9mg/mL, US contrast agent with the weight percent of 8-32mg/mL and CT contrast agent with the weight percent of 15-45 mg/mL;

the acrylamide gel is formed by dissolving acrylamide and methylene acrylamide in a mass ratio of 19 in water and performing polymerization crosslinking reaction under the action of ammonium persulfate and TEMED, wherein the acrylamide gel has a net-shaped three-dimensional structure; in the normal tissue phantom or the tumor phantom, the total concentration of acrylamide and methylene bisacrylamide is 50-120mg/mL;

the temperature-sensitive ink is water-soluble temperature-sensitive ink changing color at the temperature of more than or equal to 60 ℃;

the CT contrast agent is iohexol, and the US contrast agent is plantain seed shell powder.

2. A method of preparing the tumor-bearing tissue model of claim 1, comprising the steps of:

(3) Embedding the tumor body model obtained in the step (1) into the mixed solution B before the mixed solution B is completely gelatinized to form a normal tissue body model, and obtaining the tumor-bearing tissue model after the mixed solution B is completely gelatinized to form the normal tissue body model.

3. The method according to claim 2, wherein the mixed solution a contains: acrylamide 47.5-114mg/mL, methylene acrylamide 2.5-6mg/mL, temperature sensitive ink 3-7% v/v, sodium chloride 9mg/mL, polymerizer 1-2mg/mL, catalyst 0.1-0.2% v/v, US contrast agent 8-32mg/mL, CT contrast agent 15-45mg/mL, and ultrapure water;

4. The production method according to claim 3, wherein the mixed solution A contains: acrylamide 66.5mg/mL, methylene acrylamide 3.5mg/mL, temperature sensitive ink 5%;

5. The method of any one of claims 2-4, wherein the polymerizer is ammonium persulfate and the catalyst is TEMED.

6. The preparation method according to any one of claims 2 to 4, wherein the mixed solution A and the mixed solution B are gelled at 4 to 10 ℃.