CN113593386A

CN113593386A - Multi-modal phantom model and preparation method and application thereof

Info

Publication number: CN113593386A
Application number: CN202110746556.5A
Authority: CN
Inventors: 黄光亮; 郭语清; 张晓儿; 谢晓华; 李蔓英; 庄博文; 谢晓燕
Original assignee: First Affiliated Hospital of Sun Yat Sen University
Current assignee: First Affiliated Hospital of Sun Yat Sen University
Priority date: 2021-07-01
Filing date: 2021-07-01
Publication date: 2021-11-02

Abstract

The invention discloses a multimodal phantom model and a preparation method and application thereof. The multimodal phantom model of the present invention includes a simulated tissue colloid and a simulated tumor pellet. The multimodal phantom model of the invention has excellent transparency, the model is always displayed stably, and has strong contrast; it can be applied to interventional operations under the guidance of ultrasound and CT at the same time, and can be used for simulation, teaching, training ultrasound or intervention under the guidance of CT. Needle placement and needle biopsy operations for ablation therapy have good display under ultrasound or CT scans, and can be used for accurate and quantitative assessment of multiple aspects and dimensions of ablation needles. Currently, it is the only ultrasound that can be used to guide ablation needles. CT multimodal phantom model.

Description

Multi-modal phantom model and preparation method and application thereof

Technical Field

The invention relates to the field of medicine, in particular to a multi-modal phantom model and a preparation method and application thereof.

Background

Percutaneous thermal tumor ablation therapies such as radio frequency ablation, microwave ablation, and laser ablation are minimally invasive therapies that are widely used to achieve efficient local tumor control, i.e., complete necrosis of the tumor without damaging adjacent critical structures and minimizing damage to surrounding normal tissue. The tumor thermal ablation treatment is that under the guidance of imaging technologies such as ultrasound and CT, an ablation needle is accurately positioned, punctured and placed in or around a tumor, so that an ideal ablation range is formed to completely cover the tumor and a safety boundary of 5mm around the tumor, and the in-situ complete inactivation of the tumor is realized. Due to the limited ablation range of each ablation needle, in order to achieve complete ablation of the tumor and meet the ablation safety margin, a mode of jointly placing a plurality of ablation needles is often required in clinical practical application. The process of accurately positioning, puncturing and placing the ablation needle inside or around the tumor is called needle distribution. At present, ultrasound is the most common image guidance mode for percutaneous tumor thermal ablation treatment, and has a plurality of significant advantages of simple and convenient operation, easy acquisition, no radiation, safety, real-time guidance and monitoring and the like.

The accurate needle arrangement in a three-dimensional space layer under the guidance of ultrasound is a key step for generating an ideal multiple-overlapping ablation area so as to completely ablate a tumor, and particularly when a larger tumor needs multiple overlapping ablations, the positioning puncture and inaccurate placement of an ablation needle in the tumor may cause insufficient ablation, cause multiple treatments or local treatment progress and recurrence, and seriously affect the curative effect of the treatments and the prognosis of a patient. It is noted, however, that conventional two-dimensional ultrasound guidance can only provide continuous two-dimensional sectional image information, in which case accurate and optimal needle placement is very difficult due to the three-dimensional structure of the tumor, especially when a large tumor requires multi-slice, multi-point needle placement in space. Furthermore, operators often reconstruct three-dimensional images in a self-perception to help guide needle placement, which is highly subjective and dependent on their own spatial reconstruction capabilities and operational experience. Thus, image-guided ablation therapy places great demands on the operating experience of the physician.

In conclusion, interventional therapy under ultrasound guidance puts higher requirements on the operation technology of an operator, and considerable operation experience is needed to better master the interventional operation technology under ultrasound guidance, and particularly, compared with the needle arrangement operation under ultrasound guidance, the needle arrangement operation of tumor ablation therapy under ultrasound guidance puts higher standard requirements on the operation technology and the three-dimensional space reconstruction capability of the operator. Currently, although there are a few ultrasound phantom models for teaching and training, including ultrasound-guided puncture models, there are limitations to this: 1. the existing models are biopsy models under ultrasonic guidance, and no phantom model which can be applied to needle distribution under ultrasonic guidance and CT guidance exists. 2. The existing models are all monomodal models, namely, the models can be only applied and observed under ultrasound. 3. The transparency of the existing model is still poor, an operator cannot clearly observe the relative position relationship between the puncture needle and a focus and the puncture path of the puncture needle, the understanding of the positioning, puncture and needle distribution principle under the guidance of ultrasound is relatively slow, and the model has certain delay in the culture aspect of an interventional beginner. 4. The display of the existing model under ultrasound, namely the contrast of the display under ultrasound between the simulated tissue colloid and the simulated tumor globule is not clear enough.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provide a multi-modal phantom model.

The invention also aims to provide a preparation method of the multi-modal phantom model.

Another object of the present invention is to provide an application of the above multi-modal phantom model.

The purpose of the invention is realized by the following technical scheme: a multi-modal phantom model comprises a simulated tissue colloid and a simulated tumor pellet.

The simulated tissue colloid comprises the following components: 2.5-3% (w/v) of citric acid, 2.6-3% (w/v) of sodium citrate, 7.6-8% (w/v) of acrylamide, 0.4-0.6% (w/v) of methylene bisacrylamide, 0.1-0.15% (w/v) of ascorbic acid, 0.1-0.2% (w/v) of ferrous sulfate, 1.5-3% (w/v) of hydrogen peroxide and the balance of water.

Preferably, the simulated tissue colloid comprises the following components: 2.49% (w/v) of citric acid, 2.66% (w/v) of sodium citrate, 7.6% (w/v) of acrylamide, 0.4% (w/v) of methylene bisacrylamide, 0.1% (w/v) of ascorbic acid, 0.2% (w/v) of ferrous sulfate, 3% (w/v) of hydrogen peroxide and the balance of water.

The simulated tumor pellet comprises the following components: 3-3.5% (w/v) of agarose, 0.5-1% (w/v) of dye, 2-2.5% (w/v) of gastrointestinal ultrasound developing aid, 1.5-3% (w/v) of iodine source and the balance of water.

Preferably, the dye is one of congo red, methyl blue or carbon black; more preferably congo red.

The dosage of the iodine source is calculated according to the mass of the iodine.

Preferably, the iodine source is iopromide.

The preparation method of the multi-modal phantom model comprises the following steps: the container is divided into an upper layer and a lower layer, and two layers of simulated tissue colloids and simulated tumor pellets positioned in the middle layer are sequentially paved from bottom to top.

Preferably, the multi-modal phantom model adjusts the thickness of the two layers of simulated tissue colloids and the height of the middle simulated tumor globule according to the puncture depth.

Preferably, the simulated tumor pellets are threaded with thin threads through the central aperture on both sides of the container, in such a way that the simulated tumor pellets are secured to the middle layer.

Preparing the simulated tissue colloid: weighing citric acid, sodium citrate, acrylamide, methylene bisacrylamide and ascorbic acid according to a ratio, mixing with water, immediately dissolving, standing, adding a hydrogen peroxide solution and a ferrous sulfate solution, uniformly mixing, and standing again to obtain a simulated tissue colloid;

preferably, the dissolution is performed by forming a clear, colorless and transparent solution, and the dissolution is performed by stirring.

Preferably, the concentration of the hydrogen peroxide solution is 3% (v/v).

Preferably, the ferrous sulfate solution has a concentration of 1% (w/v).

Preferably, the ferrous sulfate solution is ready to use.

Preferably, the time for standing and standing again is 20-30 min.

Preparing the simulated tumor globules: respectively dissolving agarose and the gastrointestinal ultrasonic development aid, mixing, adding a dye, an iodine source and the rest water, uniformly mixing, heating to boil, injecting into a mold, cooling and solidifying, and tightly wrapping the pellets by using a transparent preservative film to obtain the tumor-simulated pellets.

Preferably, the gastrointestinal ultrasound development aid is dissolved by boiling water.

Preferably, the injection mould is a drop injection mould using a syringe.

The multi-modal phantom model is applied to image-guided tumor positioning puncture and interventional diagnosis and treatment of multi-point needle arrangement.

Preferably, when the multi-modal phantom model is applied to positioning puncture, an iodine source is not added when the simulated tumor pellet is manufactured, and a preservative film is not required to wrap the pellet.

Preferably, the interventional diagnosis and treatment is an ablation needle.

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

1. the multi-mode phantom model has excellent transparency, the simulated tumor beads can be stably displayed, the surrounding simulated tissue colloid cannot be tinged, the model is stably displayed all the time, the contrast is strong, and the puncture needle access can be clearly displayed due to the transparent characteristic.

2. The multi-mode phantom model can be simultaneously applied to interventional operation under the guidance of ultrasound and CT, can be used for needle arrangement operation and puncture biopsy operation of interventional ablation treatment under the guidance of simulation, teaching, training ultrasound or CT, has good display under ultrasound or CT scanning, can be used for multi-aspect multi-dimensional accurate quantitative evaluation of ablation needle arrangement, and is the only ultrasound-CT multi-mode phantom model which can be applied to guide ablation needle arrangement at present.

3. The multi-modal phantom model has the advantages of easily available preparation raw materials, simple preparation method, repeated manufacture and repeated use.

Drawings

FIG. 1 is a simulated tumor pellet tightly wrapped with a transparent plastic wrap in a multi-modal phantom model.

FIG. 2 is a comparison of the appearance of a multi-modal phantom model and a prior phantom model; where A and B are existing phantom models and C and D are multi-modal phantom models.

FIG. 3 is an appearance view of a multi-modal phantom model and a schematic representation of the display under ultrasound after lancing; wherein, A is an appearance diagram, and B is a display schematic diagram of the model after puncture under ultrasound.

FIG. 4 is a comparison of a schematic representation of a multi-modal phantom model and a prior art phantom model under ultrasound; where A and B are existing phantom models and C and D are multi-modal phantom models.

FIG. 5 is a diagram showing a comparison of a puncture specimen taken out when the multi-modal phantom model and a conventional phantom model are used for a puncture biopsy; wherein A is the existing phantom model and B is the multi-modal phantom model.

Fig. 6 is a comparison graph of simulated tumor pellets wrapped tightly with transparent plastic wrap (left) and simulated tumor pellets unwrapped with transparent plastic wrap (right) shown under CT.

FIG. 7 is an effect diagram of a multi-modal phantom model for needle placement; wherein, A is a schematic diagram of the multi-modal phantom model, B is a schematic diagram of the multi-modal phantom model after needle arrangement under the guidance of ultrasound, and C, D, E, F is a schematic diagram of multiple angles of the multi-modal phantom model after needle arrangement after CT scanning three-dimensional reconstruction.

FIG. 8 is a schematic diagram of a multi-modal phantom model applied to precision metrology analysis, scientific research and teaching.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

The first step is that the container is divided into an upper layer and a lower layer according to the height and the puncture depth of the multi-mode imitation model to be prepared, and then small holes are punched on two sides of the layering position of the container box. The second step is to prepare the lower layer of simulated tissue colloid in advance according to the actual volume of the lower layer, and the layer of simulated tissue colloid does not contain small balls. The third step is to use a thin line to penetrate the simulated tumor globule, and then fix the simulated tumor globule on the middle layer of the container box through the small holes at the two sides of the container box. And fourthly, preparing the simulated tissue colloid on the upper layer according to the actual volume of the upper layer, taking out the thin wire which is threaded on the simulated tumor pellet for fixing after the simulated tissue colloid is solidified, and obtaining the multi-modal phantom model.

Preparation of the above simulated tissue colloid

Material reagent: citric acid, sodium citrate, acrylamide, methylene bisacrylamide, ascorbic acid, 1% (m/v) ferrous sulfate solution, and 3% (v/v) hydrogen peroxide solution.

The material ratio is as follows: 24.9g of citric acid, 26.6g of sodium citrate, 76g of acrylamide, 4g of methylene bisacrylamide, 1g of ascorbic acid, 2mL of 1% ferrous sulfate solution and 10mL of 3% hydrogen peroxide solution are added to each liter of water.

The manufacturing process comprises the following steps: weighing citric acid, sodium citrate, acrylamide, methylene bisacrylamide and ascorbic acid reagent according to the material proportion, adding a proper amount of clear water, fully and uniformly mixing, and then rapidly stirring and dissolving. After the solution is fully dissolved (the solution is clear, colorless and transparent), pouring 3 percent hydrogen peroxide solution and the prepared 1 percent ferrous sulfate solution, fully and uniformly stirring, and standing for 20-30 minutes to form colorless and homogeneous simulated tissue colloid. In the process, the solution needs to be fully stirred and dissolved into clear, colorless and transparent solution, and the ferrous sulfate solution is easy to oxidize and deteriorate, so that ferrous sulfate powder needs to be immediately prepared and then quickly added.

Preparation of the above tumor-simulating pellet

Material reagent: agarose, congo red, gastrointestinal ultrasonic developing aid and a mould.

The material ratio is as follows: 3g of agarose powder, 0.8g of Congo red, 2g of gastrointestinal ultrasound developing aid and 5mL of iopromide injection are added into 0.1L of water.

The manufacturing process comprises the following steps: weighing agarose powder, stirring and dissolving with appropriate amount of water, and stirring and dissolving the gastrointestinal ultrasonic development aid with appropriate amount of boiling water. Mixing the agarose solution and the gastrointestinal ultrasonic development aid solution, and adding Congo red, iopromide injection (Youyi 300 iopromide injection, the concentration of iodine is 300g/mL) and water. The components are fully stirred and uniformly mixed, then are put into a microwave oven to be heated to be boiled, then are taken out, are dripped into a mould by using a proper injector empty cylinder, and then are kept stand or put into a refrigerator to be cooled and solidified, and then can be taken out. Finally, the small balls are tightly wrapped by transparent preservative films (figure 1).

The multi-modal phantom prepared in example 1 and a prior phantom (CN105448169A, a biopsy phantom for interventional ultrasound) are shown in fig. 2. It can be seen that the existing phantom model does not have obvious transparent characteristic, the whole appearance is milky turbid, the internal structure of the model cannot be observed by naked eyes, and the specific conditions such as the positions of the simulated tumor globule and the puncture needle in the model cannot be observed by naked eyes. The multi-modal phantom model prepared by the embodiment has excellent transparency, the whole appearance is a homogeneous transparent sample, the condition in the model can be observed by naked eyes, the simulated tumor globules can be stably displayed, the surrounding simulated tissue colloids cannot be stained, and the meat-eye contrast of the simulated tissue colloids and the simulated tumor globules is clear. Moreover, the puncture, distribution, arrangement and other conditions of the interventional therapy needle in the model and the simulated therapy ball can be clearly observed by naked eyes, the corresponding model has good display effect under ultrasound, the condition of the puncture path can be clearly displayed (figure 3), and the practical value is very high.

The multi-modal phantom model prepared in the embodiment 1 can be simultaneously applied to interventional operation under ultrasound and CT guidance, can be used for simulating, teaching, training interventional puncture biopsy and ablation needle distribution operation under ultrasound or CT guidance, has good display under ultrasound or CT scanning, and can be used for multi-aspect quantitative evaluation such as evaluation of ablation needle distribution. As is evident from fig. 4, a limitation of the prior phantom model is that the contrast effect is not good enough and the background echo is too heavy under ultrasound. The multi-modal phantom model has good display effect under ultrasound and has small contrast and clear interference. Has good application value for the training of the intervention operation.

Fig. 5 shows that the multi-modal phantom model and the conventional phantom model are used for the puncture specimen taken out during the puncture biopsy, the conventional phantom model can only be applied to the puncture biopsy operation, and the simulated tissue colloid and the simulated tumor globule are prepared by the same material and method and are distinguished by dyeing only. The length of the specimen is obtained by measuring the length of the red portion. In the multi-modal phantom model, the simulated tissue colloid and the simulated tumor globule are respectively prepared from different experimental materials and experimental methods, the corresponding textures of the simulated tissue colloid and the simulated tumor globule are different, when the model is used for puncture biopsy, the length of a puncture specimen taken out from a biopsy needle groove is only a dyed molded simulated tumor globule component (namely agar strips) with a hard and tough texture, the simulated tissue colloid is in a homogeneous transparent shape, the texture of the simulated tumor globule is softer than that of the simulated tumor globule, and the simulated tissue colloid is not shaped in the biopsy needle groove. That is to say, when the multi-modal model is used for the needle biopsy, because the simulated tissue colloid and the simulated tumor bead are different in material and preparation method, and the textures of the simulated tissue colloid and the simulated tumor bead are different, the multi-modal model has strong and good contrast and is more accurate when applied to a needle specimen taken out by the needle biopsy.

Fig. 6 is a comparison graph of simulated tumor pellets wrapped tightly with transparent plastic wrap (left) and simulated tumor pellets unwrapped with transparent plastic wrap (right) shown under CT. The inventor finds that in the process of preparing the multi-modal phantom model by coagulation forming, the iodine in the simulated tumor globule can permeate into the surrounding simulated tissue colloid, thereby influencing the CT imaging effect. The inventor uses the transparent preservative film to wrap the small ball tightly through practice, so that the inventor can see obviously that after the preservative film is wrapped, the practical boundary and the size of the small ball can be displayed well under different window width and window positions, the boundary is clear with the surrounding simulated tissue colloid, and further the position relation of the puncture needle can be displayed well.

FIG. 7 is an effect diagram of a multi-modal phantom model for needle placement. The multi-mode phantom model not only shows well under ultrasound and can be applied to interventional operation under ultrasound guidance, but also has good display under CT, and the needle arrangement operation can be carried out by CT three-dimensional reconstruction for multi-angle analysis and observation on a spatial layer, thereby having very good practical value.

FIG. 8 is a schematic diagram of a multi-modal phantom model applied to precision metrology analysis, scientific research and teaching. The multi-modal phantom model can also be used for quantifying various indexes such as the distance between needles, the angle between needles, the area and the like in the needle distribution operation, and has very good application value and application prospect for accurate evaluation of operation, scientific research and teaching and the like.

While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention.

Claims

1. a multimodal phantom model, is characterized in that, comprises simulating tissue colloid and simulating tumor pellet;

The simulated tissue colloid includes the following components: citric acid 2.5%-3% (w/v), sodium citrate 2.6%-3% (w/v), acrylamide 7.6%-8% (w/v), Methylene bisacrylamide 0.4%-0.6% (w/v), ascorbic acid 0.1%-0.15% (w/v), ferrous sulfate 0.1%-0.2% (w/v), hydrogen peroxide 1.5%-3% ( w/v), water balance;

The simulated tumor pellet includes the following components: agarose 3%-3.5% (w/v), dye 0.5%-1% (w/v), gastrointestinal ultrasound aid 2%-2.5% (w/v) v), iodine source 1.5%-3% (w/v), water balance.

2. The multimodal phantom model according to claim 1, wherein the simulated tissue colloid comprises the following components: citric acid 2.49% (w/v), sodium citrate 2.66% (w/v), Acrylamide 7.6% (w/v), methylenebisacrylamide 0.4% (w/v), ascorbic acid 0.1% (w/v), ferrous sulfate 0.2% (w/v), hydrogen peroxide 3% (w/v) v), water balance.

3. according to the described multimodal phantom model of claim 2, it is characterized in that,

Described dyestuff is a kind of in Congo red, methyl blue or carbon black;

The iodine source is iopromide.

4. the preparation method of the multimodal phantom model described in any one of claims 1-3, is characterized in that, comprises the following steps: container is divided into upper and lower two layers, from bottom to top, spread into two layers of simulated tissue colloid and A simulated tumor pellet in the middle layer;

The preparation of the simulated tissue colloid: citric acid, sodium citrate, acrylamide, methylenebisacrylamide, and ascorbic acid are weighed according to the proportions, mixed with water and immediately dissolved, left standing, and added with hydrogen peroxide solution and ferrous sulfate solution, mix well, and let stand again to obtain simulated tissue colloid;

The preparation of the simulated tumor pellets: dissolve the agarose and the gastrointestinal ultrasound aid separately, mix, add dye, iodine source and remaining water, mix well, heat to boiling, inject into a mold, cool and solidify, and keep fresh with transparent The membrane tightly wraps the pellet, resulting in a simulated tumor pellet.

5. the preparation method of the multimodal phantom model according to claim 4, is characterized in that,

The multimodal phantom model adjusts the thickness of the two layers of simulated tissue colloid and the height of the middle simulated tumor pellet according to its height and puncture depth;

The simulated tumor pellets are threaded through thin wires tied to the middle holes on both sides of the container, so as to fix the simulated tumor pellets in the middle layer.

6. the preparation method of the multimodal phantom model according to claim 4, is characterized in that,

The concentration of the hydrogen peroxide solution is 3% by volume;

The concentration of the ferrous sulfate solution is 1% by mass and volume;

The time of standing and standing again is 20-30 min.

7. the preparation method of the multimodal phantom model according to claim 4, is characterized in that,

Described dissolving performance is to form clear colorless and transparent solution, adopts stirring mode to dissolve;

The ferrous sulfate solution is ready to use.

8. the preparation method of the multimodal phantom model according to claim 4, is characterized in that,

The gastrointestinal ultrasound aid is dissolved in boiling water;

The injection mold is drop-injected into the mold using a syringe.

9. The multimodal phantom model according to any one of claims 1-3 is applied to image-guided tumor localization puncture and interventional diagnosis and treatment of multi-point needle placement.

10 . The application according to claim 9 , wherein, when the multimodal phantom model is used for positioning and puncturing, no iodine source is added when making simulated tumor pellets, and there is no need to wrap the pellets with plastic wrap. 11 .