Ultrasonic tissue-imitating phantom special for cardiovascular system and preparation method thereof

Abstract

The invention discloses a special ultrasonic tissue-imitating phantom for cardiovascular and a preparation method thereof. The special ultrasonic tissue-imitating phantom comprises a heart phantom and a blood-imitating fluid, the heart body model is prepared from the following raw materials in percentage by mass: 5 to 35 weight percent of polyvinyl alcohol, 2 to 5 weight percent of a first cross-linking agent, 10 to 12 weight percent of a water-soluble organic solvent, 1 to 3 weight percent of an initiator, 5 to 7 weight percent of a second cross-linking agent and the balance of water, the first cross-linking agent comprises one or more than two of carboxymethyl cellulose sodium, glucose, boric acid and adipic acid; the second cross-linking agent is an amide compound; the simulated blood fluid is prepared from the following components in percentage by mass: 20 to 40 weight percent of polyvinylpyrrolidone and the balance of solvent. The system and the method can be simultaneously suitable for photoacoustic / ultrasonic imaging modes.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and more specifically, to a cardiovascular-specific ultrasonic tissue-mimicking phantom and a preparation method thereof. Background Art

[0002] Photoacoustic imaging is a new type of non-invasive and non-ionizing biomedical imaging method developed in recent years. The basic principle of photoacoustic imaging is that when a pulsed laser is irradiated into biological tissue, the light absorption domain of the tissue will generate an ultrasonic signal. We call this ultrasonic signal generated by light excitation a photoacoustic signal. The photoacoustic signal generated by biological tissue carries the light absorption characteristic information of the tissue. By detecting the photoacoustic signal, the light absorption distribution image in the tissue can be reconstructed. Photoacoustic imaging combines the advantages of high selectivity in pure optical tissue imaging and deep penetration in pure ultrasonic tissue imaging, and can obtain high-resolution and high-contrast tissue images. In principle, it avoids the influence of light scattering, breaks through the "soft limit" (~1mm) of high-resolution optical imaging depth, and can achieve 50mm deep in vivo tissue imaging.

[0003] Ultrasonic tissue phantoms are similar to biological tissues in terms of ultrasonic properties and are mainly used for the correction, inspection, and in vitro learning and training of ultrasonic products. Cardiovascular-specific ultrasonic tissue phantoms include a heart phantom with ultrasonic properties similar to those of heart tissue and a blood flow channel located inside the phantom. A pump is used to make the simulated blood fluid flow in the blood flow channel to simulate the blood flow in the heart. However, existing heart phantom materials can only simulate pure ultrasonic imaging and are not suitable for photoacoustic imaging technology. Summary of the invention

[0004] The purpose of the present invention is to overcome the above-mentioned defects of the prior art and provide a cardiovascular-specific ultrasound tissue-mimicking phantom and a preparation method thereof, which can be applied to both photoacoustic and ultrasound imaging modes.

[0005] To achieve the above object, the technical solution of the present invention is as follows:

[0006] A cardiovascular-specific ultrasound tissue-mimicking phantom, comprising a heart phantom and a mimicking blood fluid;

[0007] The raw materials of the heart phantom include the following components in percentage by mass:

[0008] 5wt.% to 35wt.% of polyvinyl alcohol, 2wt.% to 5wt.% of a first crosslinking agent, 10wt.% to 12wt.% of a water-soluble organic solvent, 1wt.% to 3wt.% of an initiator, 5wt.% to 7wt.% of a second crosslinking agent, and the balance water;

[0009] The first cross-linking agent includes one or more of sodium hydroxymethyl cellulose, glucose, boric acid, and adipic acid;

[0010] The second cross-linking agent is an amide compound;

[0011] The blood-simulating fluid comprises the following components in percentage by mass:

[0012] 20wt.% to 40wt.% of polyvinyl pyrrolidone and the balance is solvent.

[0013] The present invention also discloses a method for preparing the above-mentioned cardiovascular ultrasound tissue-mimicking phantom, which comprises the following steps:

[0014] Dissolving polyvinyl alcohol in water and heating to obtain polyvinyl alcohol hydrogel;

[0015] adding a first cross-linking agent into the polyvinyl alcohol hydrogel and mixing them to obtain a first cross-linked product;

[0016] adding a second crosslinking agent and an initiator to the first crosslinked product to carry out a chemical crosslinking reaction to obtain a second crosslinked product;

[0017] performing ultrasonic homogenization on the second cross-linked product to obtain a homogeneous copolymer solution;

[0018] adding a water-soluble organic solvent to the homogeneous copolymer solution and mixing them to obtain a freezing liquid, pouring the freezing liquid into a mold for freezing, and then thawing after freezing, repeating freezing and thawing to obtain a heart phantom;

[0019] Polyvinyl pyrrolidone is dissolved in a solvent to obtain a blood-mimicking fluid.

[0020] Implementing the embodiments of the present invention will have the following beneficial effects:

[0021] In the embodiment of the present invention, the strength of polyvinyl alcohol can be enhanced by the first cross-linking agent. The first cross-linking agent is also a thickener, a dispersant and a stabilizer, which can enhance the viscosity, strength, dispersibility and stability of polyvinyl alcohol, reduce ionic polyvinyl alcohol, and improve the dispersion uniformity of polyvinyl alcohol, so as to facilitate the later acquisition of a homogeneous porous three-dimensional network structure; then, the second cross-linking agent is chemically grafted and copolymerized with polyvinyl alcohol and the first cross-linking agent to form a three-dimensional network copolymer structure, and the amide compound can enhance the crystallinity, transparency and mechanical strength of the copolymer by chemical grafting; by adding a water-soluble organic solvent to the freezing liquid, the water-soluble organic solvent can be soluble in water, and can have good compatibility and binding with organic impurities such as polyvinyl alcohol with a lower alcoholysis degree that are not involved in the three-dimensional network copolymer structure, and can be replaced by water in the freeze-thaw cycle, thereby further improving the transmittance of the phantom, and also further improving the homogeneity of the phantom. The present invention can obtain a high-transmittance phantom through the combined effect of chemical grafting of the second cross-linking agent and removal of organic impurities by a water-soluble organic solvent during a freeze-thaw cycle, thereby being able to apply a photoacoustic / ultrasound dual-modality imaging technique.

[0022] The polyvinyl pyrrolidone solution of the embodiment of the present invention is a non-Newtonian fluid. Polyvinyl pyrrolidone can reflect ultrasound to form an ultrasonic signal, and the polyvinyl pyrrolidone solution will not precipitate. At the same time, polyvinyl pyrrolidone is also light-transmissive and can be used for both photoacoustic and ultrasonic detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] in:

[0025] Figure 1 It is a schematic structural diagram of a single blood vessel model according to a specific embodiment of the present invention.

[0026] Figure 2 It is a schematic structural diagram of a single blood vessel model according to another specific embodiment of the present invention.

[0027] Figure 3 It is a schematic structural diagram of a coronary vessel model according to a specific embodiment of the present invention.

[0028] Figure 4 It is a structural schematic diagram of the opening and closing of the mitral valve model structure according to a specific embodiment of the present invention.

[0029] Figure 5It is a structural schematic diagram of a bi-atrial ventricle model according to a specific embodiment of the present invention.

[0030] Figure 6 This is a transparency photograph of the tissue-mimicking phantom material prepared in Example 1 on a black substrate.

[0031] Figure 7 This is a transparency photograph of the tissue-mimicking phantom material prepared in Comparative Example 1 on a black substrate.

[0032] Figure 8 This is a transparency photograph of the tissue-mimicking phantom material prepared in Comparative Example 2 on a black substrate.

[0033] Fig. 9 This is a transparency photograph of the tissue-mimicking phantom material prepared in Comparative Example 3 on a black substrate.

[0034] Fig.10 This is a transparency photograph of the tissue-mimicking phantom material prepared in Comparative Example 4 on a black substrate.

[0035] Fig.11 This is a transparency photograph of the tissue-mimicking phantom material prepared in Comparative Example 5 on a black substrate.

[0036] Fig.12 This is a photograph of the blood-simulating fluid of Example 6 when it is poured.

[0037] Fig.13 This is a photograph of the blood-simulating fluid of Example 6 showing a siphon effect.

[0038] Fig.14 This is a photograph of the blood-simulated fluid ultrasound imaging of Example 6.

[0039] Fig.15 1 is a comparison of the acoustic attenuation coefficient curves of the blood-simulating fluid of Example 6 and human blood. DETAILED DESCRIPTION

[0040] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0041] The invention discloses a special ultrasonic tissue-mimicking phantom for cardiovascular system, comprising a heart phantom, a mimicking blood fluid and a blood pumping device. The blood pumping device drives the mimicking blood fluid to flow in the heart phantom.

[0042] The cardiovascular ultrasound tissue phantom of the present invention includes two imaging modes, B mode and C mode. The B mode is mainly used to correct and test the main performance of B-type ultrasound (lateral and longitudinal resolution of the ultrasound system and probe, penetration depth, sound beam divergence angle, image grayscale, etc.), and the C mode is mainly used for intracardiac color Doppler blood flow imaging test, which can assist in simulating the flow condition of blood flow in the heart cavity.

[0043] The structure of the heart phantom of the present invention includes a heart phantom and one or more of a single blood vessel model, a coronary blood vessel model structure, a mitral valve model structure, a tricuspid valve model structure, a uni-atrial ventricle model structure, and a bi-atrial ventricle model structure located inside the heart phantom. In a preferred embodiment, the structure of the heart phantom includes a heart phantom and a single blood vessel model, a coronary blood vessel model structure, a mitral valve model structure, a tricuspid valve model structure, a uni-atrial ventricle model structure, and a bi-atrial ventricle model structure located inside the heart phantom.

[0044] The single blood vessel model can be used to simulate the flow of blood fluid in a single blood vessel. The blood vessel diameter of the single blood vessel model is 2.5 mm to 3.3 mm. In a specific embodiment, two single blood vessel models are included. The blood vessel inclination angle of one single blood vessel model relative to the acoustic window surface is 30° to 45°. Figure 1 As shown in FIG. 1 , the blood vessel inclination angle of another single blood vessel model relative to the acoustic window surface is 0°, as shown in FIG. Figure 2 As shown, it is convenient to observe the blood flow in a single blood vessel model at different angles. In this specific embodiment, the acoustic window surface refers to the surface to which the ultrasonic transducer is attached.

[0045] refer to Figure 3 In a specific embodiment, the coronary vessel model structure includes a main vessel and branch vessels extending from the main vessel, and the vessel diameter is 1 mm to 5 mm. The coronary vessel model structure is used to simulate the flow of blood fluid in the coronary vessel.

[0046] refer to Figure 4 In a specific embodiment, the mitral valve model structure includes a first cavity and a mitral valve structure located inside the first cavity; the mitral valve structure is composed of two cusp valve structures.

[0047] The tricuspid valve model has a similar structure Figure 4 The mitral valve structure includes a second cavity and a tricuspid valve structure located in the second cavity; the tricuspid valve structure is composed of three cusp valve structures. The mitral valve model structure and the tricuspid valve model structure are used to simulate the opening and closing movements of the mitral valve and the tricuspid valve when the heart pumps blood.

[0048] refer to Figure 5In a specific embodiment, the bi-atrial ventricle model includes a fourth cavity, a left atrium, a left ventricle, a right atrium and a right ventricle located inside the fourth cavity, two mitral valve structures disposed between the right atrium and the right ventricle, and two tricuspid valve structures disposed between the left atrium and the left ventricle. The two mitral valve structures are used for blood intake and bleeding, respectively, and the two tricuspid valve structures are also used for blood intake and bleeding, respectively. The bi-atrial ventricle model can be used to simulate the heart contraction when the heart pumps blood and the opening and closing movements of the mitral valve and tricuspid valve in the left and right atrium ventricles when the heart contracts, and can simulate the blood pumping of a real heart.

[0049] In a specific embodiment, the single atrium-ventricle model structure includes a third cavity, a single atrium and a single ventricle located in the third cavity, and two mitral valve structures or two tricuspid valve structures arranged between the single atrium and the single ventricle. The single atrium-ventricle model structure can refer to Figure 5 Half of the structure shown. The single atrium-ventricle model structure can be used to simulate the contraction of the heart as it pumps blood and the opening and closing of the mitral or tricuspid valve during contraction.

[0050] In the above embodiments, the cusp structure is triangular or conical, the tip of the triangle or cone is the opening end, and the other end opposite to the tip is the end fixedly connected to the cavity.

[0051] The heart phantom of the present invention can be used to simulate endoscopic ultrasound / photoacoustic imaging tests such as intracardiac ultrasound (ICE), intravascular ultrasound (IVUS), transesophageal ultrasound (TEE), and extracorporeal ultrasound (TTE), and can be reused.

[0052] The existing heart phantom only includes a single blood vessel model, which can only simply simulate the blood flow of a single blood vessel artery and vein, and cannot simulate the heart pumping blood and the closure of the heart valve.

[0053] The raw materials of the heart phantom of the present invention include the following components in percentage by mass:

[0054] 5wt.% to 35wt.% of polyvinyl alcohol, 2wt.% to 5wt.% of a first cross-linking agent, 10wt.% to 12wt.% of a water-soluble organic solvent, 1wt.% to 3wt.% of an initiator, 5wt.% to 7wt.% of a second cross-linking agent and the remainder water; wherein the first cross-linking agent comprises one or more of sodium hydroxymethyl cellulose, glucose, boric acid and adipic acid; and the second cross-linking agent is an amide compound.

[0055] In the embodiment of the present invention, the strength of polyvinyl alcohol can be enhanced by the first cross-linking agent. The first cross-linking agent is also a thickener, a dispersant and a stabilizer, which can enhance the viscosity, strength, dispersibility and stability of polyvinyl alcohol, reduce ionic polyvinyl alcohol, and improve the dispersion uniformity of polyvinyl alcohol, so as to facilitate the later acquisition of a homogeneous porous three-dimensional network structure; then, the second cross-linking agent is chemically grafted and copolymerized with polyvinyl alcohol and the first cross-linking agent to form a three-dimensional network copolymer structure, and the amide compound can enhance the crystallinity, transparency and mechanical strength of the copolymer by chemical grafting; by adding a water-soluble organic solvent to the freezing liquid, the water-soluble organic solvent can be soluble in water, and can have good compatibility and binding with organic impurities such as polyvinyl alcohol with a lower alcoholysis degree that are not involved in the three-dimensional network copolymer structure, and can be replaced by water in the freeze-thaw cycle, thereby further improving the transmittance of the phantom, and also further improving the homogeneity of the phantom.

[0056] The present invention can obtain a high-transmittance phantom through the combined effect of chemical grafting of the second cross-linking agent and removal of organic impurities by a water-soluble organic solvent during a freeze-thaw cycle, thereby being able to apply a photoacoustic / ultrasound dual-modality imaging technique.

[0057] The acoustic impedance of the photoacoustic / ultrasonic dual-mode tissue-mimicking phantom material of the present invention is 1.5 MRayls, the sound velocity is close to 1540 m / s of human soft tissue, and the sound attenuation is close to 0.5 dB / MHz.cm, which is close to the ultrasonic characteristics of human heart tissue. It can be used in endoscopic ultrasound systems such as intracardiac ultrasound (ICE) and transesophageal ultrasound (TEE) or photoacoustic systems for blood flow simulation and function calibration.

[0058] In a specific embodiment, the amide compound is preferably an amide compound containing a carbon-carbon double bond. Specifically, the amide compound may include one or more of acrylamide and N,N-methylenebisacrylamide.

[0059] In a specific embodiment, the polyvinyl alcohol includes one or more of PVA1699, PVA1799, and PVA2699.

[0060] The initiator is used to initiate a crosslinking reaction between the polyvinyl alcohol, the first crosslinking agent and the second crosslinking agent to generate a three-dimensional network polymer. The initiator can be any initiator that initiates a crosslinking reaction. In a specific embodiment, the initiator includes one or more of ammonium persulfate, undecane diammonium, and diethylenetriamine.

[0061] The water-soluble organic solvent is soluble in water and has high binding and compatibility with polyvinyl alcohol with low alcoholysis degree and other organic impurities that are not involved in forming a three-dimensional network structure. It can be replaced by water during the freeze-thaw cycle, thereby further improving the light transmittance of the phantom and the homogeneity of the phantom. In a specific embodiment, the water-soluble organic solvent includes one or more of dimethyl sulfoxide, ethylene glycol, ethylenediamine, dimethylformamide and glycerol.

[0062] In a specific embodiment, the raw material of the heart phantom further includes a first defoamer with a mass percentage of 1% to 5%, and the first defoamer is used to eliminate fine bubbles and maintain the stability of the system. Specifically, the defoamer can include one or more of emulsified silicone oil, high carbon alcohol fatty acid ester, polydimethylsiloxane, and polyoxypropylene glycerol ether.

[0063] In a specific embodiment, the raw material of the heart phantom further includes 1% to 3% by weight of a pH buffer solution, the pH value of the pH buffer solution ranges from 6.5 to 8.0, and the pH buffer solution is used to adjust the acid-base balance.

[0064] In a specific embodiment, the pH buffer includes one or more of PBS buffer, boric acid buffer, and potassium hydrogen phthalate buffer.

[0065] In a specific embodiment, the raw material of the heart phantom further includes 0.1% to 0.5% by mass of a toner. Preferably, the toner includes a water-soluble dye.

[0066] The blood-simulating fluid of the present invention comprises the following components in percentage by mass:

[0067] 20wt.% to 40wt.% of polyvinyl pyrrolidone and the balance is solvent.

[0068] In the above embodiment, the polyvinyl pyrrolidone solution is a non-Newtonian fluid. The polyvinyl pyrrolidone can reflect ultrasound to form an ultrasonic signal, and the polyvinyl pyrrolidone solution will not precipitate. At the same time, the polyvinyl pyrrolidone is also light-transmissive and can be used for both photoacoustic and ultrasonic detection.

[0069] In the above technical solution, the solvent is a solvent that can dissolve polyvinyl pyrrolidone, which can be a polar solvent or an organic solvent. By adjusting the content of polyvinyl pyrrolidone and selecting a suitable solvent, the viscosity, density, sound velocity and sound attenuation of the blood-like fluid can be adjusted to be similar to those of blood, so as to obtain the ability to

[0070] In a specific embodiment, the solvent includes one or more of water, glucose, physiological saline, etc. Aqueous solution is preferred, which has the advantages of low cost, non-toxicity, good biocompatibility, etc.

[0071] In a specific embodiment, the average molecular weight of polyvinyl pyrrolidone is 8000-1200000. Specifically, it can include one or more of PVP K15 (average molecular weight 8000-12000), PVP K17 (average molecular weight 10000-16000), PVP K25 (average molecular weight 30000-40000), PVP K30 (average molecular weight 45000-58000), PVP K60 (average molecular weight 270000-400000), and PVP K90 (average molecular weight 1000000-1300000).

[0072] Preferably, the average molecular weight of polyvinyl pyrrolidone is 30,000 to 58,000, and specifically, PVP K25 and / or PVP K30 are preferred.

[0073] In a specific embodiment, the blood-simulating fluid further includes 3 wt.% to 5 wt.% of a thickener, and the thickener is mainly used to adjust the viscosity of the fluid.

[0074] Specifically, in a specific embodiment, the thickener may include one or more of sodium hydroxymethyl cellulose, hydroxyethyl methacrylate, and sodium alginate.

[0075] In a specific embodiment, the blood-simulating fluid also includes 0.1 wt.% to 0.5 wt.% of a second defoaming agent, which is mainly used to eliminate tiny bubbles generated by the peristaltic pump driving the liquid circulation, maintain the stability of the fluid system, and avoid affecting the ultrasound image.

[0076] Specifically, in a specific embodiment, the second defoaming agent may include one or more of emulsified silicone oil and dimethylsiloxane polymer.

[0077] In a specific embodiment, the blood-simulating fluid further includes 0.1% to 0.5% of a dye, which can be dyed into a corresponding color as required. The dye is preferably soluble in a solvent to avoid precipitation.

[0078] The present invention also discloses a method for preparing the above-mentioned cardiovascular ultrasound tissue-mimicking phantom, which comprises the following steps:

[0079] 1) Dissolving polyvinyl alcohol in water and heating to obtain polyvinyl alcohol hydrogel.

[0080] In a specific embodiment, a vessel containing polyvinyl alcohol and water is placed in a water bath of an ultrasonic cleaner for heating. The water bath heating temperature is preferably 80°C to 100°C. The vessel is heated for 10min to 20min. The vessel is taken out and a magnetic stirrer is placed in the vessel for stirring. The water bath heating and stirring are repeated until a homogeneous, transparent polyvinyl alcohol hydrogel without flocculent precipitation is formed.

[0081] When the raw materials further include a toner, the toner may be added into the polyvinyl alcohol hydrogel for mixing before step 2).

[0082] 2) Adding a first cross-linking agent into the polyvinyl alcohol hydrogel and mixing the mixture to obtain a first cross-linked product.

[0083] In this process, the hydroxyl groups of polyvinyl alcohol and the hydroxyl groups of the first cross-linking agent are cross-linked through intermolecular hydrogen bonds. The first cross-linking agent is also a thickener, dispersant and stabilizer, which can enhance the viscosity, dispersibility and stability of polyvinyl alcohol, reduce ionic polyvinyl alcohol, improve the dispersion uniformity of polyvinyl alcohol, and facilitate the later acquisition of a homogeneous porous three-dimensional network structure.

[0084] When the raw materials further include a first defoaming agent, in step 2), the first defoaming agent and the first cross-linking agent can be added together into the polyvinyl alcohol hydrogel for mixing.

[0085] 3) Adding a second crosslinking agent and an initiator to the first crosslinked product to carry out a chemical crosslinking reaction to obtain a second crosslinked product.

[0086] In this process, the second crosslinking agents are chemically grafted with each other, and the second crosslinking agents are respectively grafted with polyvinyl alcohol and the first crosslinking agent to form a three-dimensional network copolymer. The second crosslinking agent can enhance the crystallinity, transparency and mechanical strength of the copolymer.

[0087] The initiator may be any initiator that initiates a crosslinking reaction. Preferably, the initiator is a photoinitiator. Specifically, the initiator includes one or more of ammonium persulfate, ammonium persulfate, undecanediammonium, and diethylenetriamine.

[0088] In a specific embodiment, the process of the chemical cross-linking reaction is: using ultraviolet light with a wavelength of 350nm to 400nm and a power of 30W to 50W to excite the initiator and perform chemical graft copolymerization.

[0089] 4) Ultrasonic homogenization is performed on the second cross-linked product to obtain a homogeneous copolymer solution.

[0090] The main function of ultrasonic homogenization is to make the three-dimensional network structure evenly and stably dispersed, and to improve the overall homogeneity and transparency of the phantom material.

[0091] In a specific embodiment, the ultrasonic homogenization process is: first use 40KHz~50KHz, 40W~60W ultrasonic sonication for 40min~80min, and then use 60KHz~100KHz, 40W~60W ultrasonic sonication for 40min~80min, so that the entire solution system is completely dissolved and the three-dimensional network structure is evenly and stably dispersed.

[0092] Preferably, in this process, a pH buffer is also added to the second cross-linked product to maintain the acid-base balance of the system, to prevent the reaction of the polyvinyl alcohol that is not fully alcoholyzed, and to maintain the stabilizer of the hydroxyl group.

[0093] 5) adding an organic solvent to the homogeneous copolymer solution and mixing to obtain a freezing liquid, pouring the freezing liquid into a mold for freezing, and then thawing after the freezing is completed, cyclically freezing and thawing to obtain a photoacoustic / ultrasound dual-modality tissue-mimicking phantom material.

[0094] In this process, the organic solvent has good compatibility and binding properties with polyvinyl alcohol with a lower degree of alcoholysis. In the subsequent freeze-thaw cycle, the organic solvent and the polyvinyl alcohol with a lower degree of alcoholysis combined with the organic solvent can also be replaced together with water, which not only increases the porosity and further improves the transmittance of the phantom, but also further improves the homogeneity of the phantom.

[0095] In a specific embodiment, the freezing temperature is -25°C to -15°C, the freezing time is 6h to 10h, the thawing temperature is room temperature (20°C to 30°C), the thawing time is 4h to 6h, and the number of freeze-thaw cycles is 2-3 times.

[0096] The final cross-linking of the phantom material of the present invention occurs during the temperature change process. Repeated freezing-thawing processes will form a three-dimensional network cross-linked structure. The temperature change has a gradient and time. Generally, the freezing temperature is -25°C to -15°C, and the freezing time is 6h to 10h; the thawing is carried out at room temperature (20°C to 30°C), and the thawing time is 4h to 6h.

[0097] 6) Dissolve polyvinyl pyrrolidone in a solvent to obtain a blood-mimicking fluid.

[0098] When the blood-simulating fluid also includes a thickener, a second defoamer and a dye, all the components can be added to the solvent together for dissolution, or added one by one in steps for dissolution. Of course, the dissolution process can also be accelerated by methods such as ultrasound, agitator, heating, etc.

[0099] In a specific embodiment, the acoustic impedance of the heart phantom is 1.5 MRayls to 1.6 MRayls, the speed of sound is 1540 m / s to 1570 m / s, the acoustic attenuation is 0.45 dB / MHz.cm to 0.55 dB / MHz.cm, and the light transmittance is 80% to 100%. The viscosity of the blood-simulating fluid is 3 cP to 5 cP, the speed of sound is 1570 m / s to 1600 m / s, the acoustic attenuation is less than 0.1 dB / cm / MHz, and the density is 1 g / cc to 1.1 g / cc.

[0100] The following are specific embodiments.

[0101] Example 1

[0102] A raw material of a heart phantom includes the following components in percentage by mass:

[0103] 5% PVA1699, 2% sodium hydroxymethylcellulose, 10% dimethyl sulfoxide, 1% ammonium persulfate, 5% acrylamide, 1% emulsified silicone oil, 1% PBS buffer and the balance water.

[0104] The preparation method of the heart phantom includes the following steps:

[0105] 1) Place the PVA1699 particles in a 500 mL plastic container, place the entire plastic container in an ultrasonic cleaning machine for water bath heating and turn on the ultrasonic wave, the water temperature is 100°C, and keep warm for 15 minutes.

[0106] 2) Take out the container, put in the stirring bar of the magnetic stirrer, and mix the PVA solution; repeat steps 1) and 2) until the mixed solution is transparent without flocculent precipitation. The overall stirring process takes about 1h to 1.5h.

[0107] 3) adding sodium hydroxymethyl cellulose and emulsified silicone oil to the PVA hydrogel prepared in step 2), stirring until the solution becomes clear, to obtain a first cross-linked product.

[0108] 4) Add acrylamide and ammonium persulfate, irradiate with 350-400 nm UV light at a power of 40 W for 10 minutes to obtain a second cross-linked product.

[0109] 5) Add PBS buffer, heat to 80°C, first sonicate with 45KHz, 50W ultrasound for 60 minutes, then change to 80KHz, 50W ultrasound for 60 minutes to obtain a homogeneous copolymer solution.

[0110] 6) Add dimethyl sulfoxide, stir and remove bubbles to obtain a frozen liquid, pour the frozen liquid into a mold for freezing, the freezing temperature is -20°C, freeze for 8 hours, and then thaw naturally at 25°C for 4 hours, freeze and thaw for 3 times to obtain the heart phantom of the present invention.

[0111] Example 2

[0112] The difference between Example 2 and Example 1 is that the contents of the components are different, and the preparation process and parameters are exactly the same.

[0113] Specifically, a raw material of a heart phantom includes the following components in percentage by mass:

[0114] 35% PVA1699, 5% sodium hydroxymethylcellulose, 12% dimethyl sulfoxide, 3% ammonium persulfate, 7% acrylamide, 5% emulsified silicone oil, 3% PBS buffer and the balance water.

[0115] Example 3

[0116] The difference between Example 3 and Example 1 is that the components are different, but the preparation process and parameters are exactly the same.

[0117] Specifically, a raw material of a heart phantom includes the following components in percentage by mass:

[0118] 5% PVA2699, 2% glucose, 10% glycerol, 1% ammonium persulfate, 5% acrylamide, 1% emulsified silicone oil, 1% PBS buffer and the balance water.

[0119] Comparative Example 1

[0120] The difference between Comparative Example 1 and Example 1 is that the raw material components do not include acrylamide.

[0121] Comparative Example 2

[0122] The difference between Comparative Example 2 and Example 1 is that the components of the raw materials do not include dimethyl sulfoxide.

[0123] Comparative Example 3

[0124] The difference between Comparative Example 3 and Example 1 is that the raw material components do not include acrylamide and dimethyl sulfoxide.

[0125] Comparative Example 4

[0126] The difference between Comparative Example 4 and Example 1 is that the components of the raw materials do not include sodium hydroxymethyl cellulose.

[0127] Comparative Example 5

[0128] The only difference between Comparative Example 5 and Example 1 is that the preparation method does not include the step of ultrasonic homogenization.

[0129] Test Example 1

[0130] The acoustic performance indicators of the heart phantoms prepared in Examples 1 to 3 and Comparative Examples 1 to 5 were tested respectively, and the sound velocity was tested by the transmission method. The specific testing process was as follows: 1) Two Olympus commercial transducers were used, and the transducers were placed in a sound-absorbing water tank; 2) The transmitter was a DPR300PR pulse transmitter-receiver, and the distance between the two transducers was adjusted using the penetration mode, and the transducers were in a one-transmit-one-receive mode; 3) The delay time displayed on the oscilloscope was checked, and this time was recorded as T0; 4) The prepared phantom material of a certain thickness was placed between the two transducers to ensure that the transducer was facing the phantom material; 5) The thickness d and T1 of the phantom material were recorded; 6) The formula d / C was used to calculate the delay time displayed on the oscilloscope, and the delay time was recorded as T0; 7) The phantom material of a certain thickness was placed between the two transducers to ensure that the transducer was facing the phantom material; 8) The thickness d and T1 of the phantom material were recorded; 9) The thickness d and T1 of the phantom material were recorded; 10) The thickness d and T1 of the phantom material were recorded; 11) The thickness d and T1 of the phantom material were recorded; 12) The thickness d and T1 of the phantom material were recorded; 13) The thickness d and T1 of the phantom material were recorded; 14) The thickness d and T1 of the phantom material were recorded; 15) The thickness d and T1 of the phantom material were recorded; 16) The thickness d and T1 of the phantom material were recorded; 17) The thickness d and T1 of the phantom material were recorded; 18) The thickness d and T1 of the phantom material were recorded; 19 water -d / C phantom =T0-T1, where C water is the speed of sound in water at room temperature of 25℃, which can be obtained by referring to relevant data, Cphantom is the sound velocity of the phantom material; T0 and T1 are both values ​​that can be directly obtained on an oscilloscope. The acoustic properties of the tissue-mimicking phantom material obtained based on the above test process are shown in Table 1.

[0131] Table 1: Acoustic performance indicators of tissue-mimicking phantom materials

[0132]

[0133] From Table 1, it can be seen that the acoustic attenuation index of the heart phantoms prepared in Examples 1 to 3 of the present invention meets the standard, which is less than 0.5 dB / MHz.cm, close to human heart tissue. However, the acoustic attenuation index of the phantom materials prepared in Comparative Examples 1 to 5 does not meet the standard.

[0134] Test Example 2

[0135] The heart phantoms prepared in Example 1 and Comparative Examples 1 to 5 were placed on a black substrate, and then light was irradiated from above the heart phantoms. The transparency photographs thereof are shown in FIG. Figure 6 to Figure 11 The transmittance range is shown in Table 1. Figure 1 It can be seen that the phantom material prepared in Example 1 has a black base under light, has a transmittance of more than 80%, and the phantom material is uniform, and the opaque polymer particles are small and uniformly dispersed. Comparative Example 1 does not include acrylamide, has a transmittance of <80%, and the phantom material is uneven. Comparative Example 2 does not include dimethyl sulfoxide, and has poor transmittance. Comparative Example 3 does not include acrylamide and dimethyl sulfoxide, and has poor transmittance. Comparative Example 4 does not include sodium hydroxymethyl cellulose, and it can be seen that there are obvious opaque agglomerates of uneven size in the phantom, which affects the transmittance. Comparative Example 5 does not perform ultrasonic homogenization, and it can be seen that there are also obvious opaque agglomerates of uneven size in the phantom, which affects the transmittance.

[0136] Example 4

[0137] A blood-mimicking fluid comprising the following components in percentage by mass:

[0138] 20wt.% PVP K30 and the balance water solvent.

[0139] Example 5

[0140] A blood-mimicking fluid comprising the following components in percentage by mass:

[0141] 40wt.% PVP K30 and the balance water solvent.

[0142] Example 6

[0143] A blood-mimicking fluid comprising the following components in percentage by mass:

[0144] 20wt.% PVP K30, 3wt.% CMC (sodium hydroxymethylcellulose), 0.3wt.% emulsified silicone oil and the balance water solvent.

[0145] Example 7

[0146] A blood-mimicking fluid comprising the following components in percentage by mass:

[0147] 20wt.% PVP K30, 3wt.% hydroxyethyl methacrylate, 0.3wt.% emulsified silicone oil and the balance water solvent.

[0148] Example 8

[0149] A blood-mimicking fluid comprising the following components in percentage by mass:

[0150] 20wt.% PVP K30, 3wt.% CMC (sodium hydroxymethylcellulose), 0.3wt.% emulsified silicone oil and the balance physiological saline solvent.

[0151] Comparative Example 6

[0152] The Doppler Fluid Model 769DF blood-simulating fluid produced by CIRS Company was used as a comparative example.

[0153] Test Example 3

[0154] The blood-simulating fluid of Example 6 is configured as follows: Fig.12 When it is poured outward as shown, it can be observed that the falling fluid is a whole, unseparated liquid column, which means that the fluid has a certain viscosity and is deformable, which are the characteristics of a non-Newtonian fluid.

[0155] Take the syringe and draw the blood-like fluid in the measuring cup. Fig.13 As shown, it can be observed that: when the syringe tip leaves the measuring cup, the fluid in the measuring cup can still be sucked into the syringe, producing a siphon effect, which is a characteristic of non-Newtonian fluid. At the same time, it can also be observed that the diameter of the fluid outside the tip is larger than the diameter of the tip, which is also a characteristic of non-Newtonian fluid.

[0156] Test Example 4

[0157] The imaging of the blood-like fluid of Example 6 under the action of color Doppler ultrasound is as follows: Fig.14 shown.

[0158] Test Example 5

[0159] Fig.15 The acoustic attenuation coefficient curves of the simulated blood fluid of Example 6 and real blood are compared. Fig.15It can be seen that the acoustic attenuation coefficient of the blood-simulating fluid of the present invention is very close to that of real blood.

[0160] Test Example 6

[0161] The acoustic properties of Examples 4 to 8 and Comparative Example 6 are shown in Table 2.

[0162] Table 2: Acoustic characteristic parameters of blood-simulated fluid

[0163]

[0164] The standard refers to the requirements of IEC61685:2001BMF SPECIFICATION for the characteristics of blood-like fluids

[0165] It can be seen from Table 2 that the blood-simulating fluids of Examples 4 to 8 of the present invention can simulate human blood more realistically than the comparative example 6.

[0166] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A cardiovascular ultrasound tissue phantom, characterized in that: Includes heart phantom and blood-mimicking fluid; The raw materials of the heart phantom include the following components in percentage by mass: 5wt.% to 35wt.% of polyvinyl alcohol, 2wt.% to 5wt.% of a first crosslinking agent, 10wt.% to 12wt.% of a water-soluble organic solvent, 1wt.% to 3wt.% of an initiator, 5wt.% to 7wt.% of a second crosslinking agent, and the balance water; The first cross-linking agent includes one or more of sodium hydroxymethyl cellulose, glucose, boric acid, and adipic acid; The second cross-linking agent is an amide compound; The blood-simulating fluid comprises the following components in percentage by mass: 20wt.% to 40wt.% of polyvinyl pyrrolidone and the balance is solvent.

2. The cardiovascular ultrasound tissue-mimicking phantom according to claim 1, characterized in that: Include at least one of the following technical features: a. The initiator comprises one or more than two of ammonium persulfate, undecane diammonium and diethylenetriamine; b. The amide compound includes one or more of acrylamide and N,N-methylenebisacrylamide; c. The polyvinyl alcohol includes one or more of PVA1699, PVA1799 and PVA2699; d. The water-soluble organic solvent comprises one or more of dimethyl sulfoxide, ethylene glycol, ethylenediamine, dimethylformamide and glycerol; e. The average molecular weight of the polyvinyl pyrrolidone is 8000 to 1300000; f. The solvent includes one or more of water, glucose and physiological saline; g. The raw materials of the heart phantom further include 1 wt.% to 5 wt.% of a first defoaming agent and / or 0.1 wt.% to 0.5 wt.% of a toner; h The blood-simulating fluid further comprises 3 wt.% to 5 wt.% of a thickener and / or 0.1 wt.% to 0.5 wt.% of a second defoaming agent.

3. The cardiovascular ultrasound tissue phantom according to claim 2, characterized in that: The first defoaming agent includes one or more of emulsified silicone oil, higher alcohol fatty acid ester, polydimethylsiloxane, and polyoxypropylene glycerol ether; The thickener includes one or more of sodium hydroxymethyl cellulose, hydroxyethyl methacrylate, and sodium alginate; The second defoaming agent includes one or more of emulsified silicone oil and dimethylsiloxane polymer; The polyvinyl pyrrolidone includes one or more of PVP K15, PVP K17, PVP K25, PVP K30, PVP K60 and PVP K90.

4. The cardiovascular ultrasound tissue-mimicking phantom according to any one of claims 1 to 3, characterized in that: The structure of the heart phantom includes a heart phantom and one or more of a single blood vessel model, a coronary vessel model structure, a mitral valve model structure, a tricuspid valve model structure, a single atrium-ventricle model structure, and a double atrium-ventricle model structure located inside the heart phantom.

5. The cardiovascular ultrasound tissue-mimicking phantom according to claim 4, characterized in that: The coronary vessel model structure includes a main vessel and branch vessels extending from the main vessel; The mitral valve model structure includes a first cavity and a mitral valve structure located inside the first cavity; The tricuspid valve model structure includes a second cavity and a tricuspid valve structure located in the second cavity; The single atrium-ventricle model structure includes a third cavity, a single atrium and a single ventricle located inside the third cavity, and two mitral valve structures or two tricuspid valve structures arranged between the single atrium and the single ventricle; The bi-atrial ventricle model includes a fourth cavity, a left atrium, a left ventricle, a right atrium and a right ventricle located inside the fourth cavity, two mitral valve structures arranged between the right atrium and the right ventricle, and two tricuspid valve structures arranged between the left atrium and the left ventricle.

6. The cardiovascular ultrasound tissue phantom according to claim 4, characterized in that: Also included is a blood pumping device.

7. The cardiovascular ultrasound tissue phantom according to claim 1, characterized in that: The acoustic impedance of the heart phantom is 1.5 MRayls to 1.6 MRayls; The speed of sound of the heart phantom is 1540m / s to 1570m / s; The acoustic attenuation of the heart phantom is 0.45dB / MHz.cm to 0.55dB / MHz.cm; The light transmittance of the heart phantom is 80% to 100%; The viscosity of the blood-simulating fluid is 3 cP to 5 cP; The sound velocity of the blood-simulating fluid is 1570m / s to 1600m / s; The acoustic attenuation of the blood-simulating fluid is less than 0.1 dB / cm / MHz; The density of the blood-simulating fluid is 1 g / cc to 1.1 g / cc.

8. A method for preparing a cardiovascular ultrasound tissue-mimicking phantom as claimed in any one of claims 1 to 7, characterized in that: The process includes: Dissolving polyvinyl alcohol in water and heating to obtain polyvinyl alcohol hydrogel; adding a first cross-linking agent into the polyvinyl alcohol hydrogel and mixing them to obtain a first cross-linked product; adding a second crosslinking agent and an initiator to the first crosslinked product to carry out a chemical crosslinking reaction to obtain a second crosslinked product; performing ultrasonic homogenization on the second cross-linked product to obtain a homogeneous copolymer solution; adding a water-soluble organic solvent to the homogeneous copolymer solution and mixing them to obtain a freezing liquid, pouring the freezing liquid into a mold for freezing, and then thawing after freezing, repeating freezing and thawing to obtain a heart phantom; Polyvinyl pyrrolidone is dissolved in a solvent to obtain a blood-mimicking fluid.

9. The method for preparing a cardiovascular ultrasound tissue-mimicking phantom according to claim 8, characterized in that: The process of the chemical cross-linking reaction is: irradiating the initiator with ultraviolet light having a wavelength of 350nm to 400nm and a power of 30W to 50W; The ultrasonic homogenization process is: firstly use 40KHz to 50KHz, 40W to 60W ultrasonic sonication for 40min to 80min, and then use 60KHz to 100KHz, 40W to 60W ultrasonic sonication for 40min to 80min; The freezing temperature is -25°C to -15°C, the freezing time is 6h to 10h, the thawing temperature is 20°C to 30°C, the thawing time is 4h to 6h, and the freezing and thawing cycles are 2-3 times.

10. The method for preparing a cardiovascular ultrasound tissue-mimicking phantom according to claim 8 or 9, characterized in that: During the ultrasonic homogenization process, a pH buffer solution is also added to the second cross-linked product, and the pH value of the pH buffer solution is in the range of 6.5 to 8.0.

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