JP7543767B2 - Organ Models and Training Systems - Google Patents

Description

The present invention relates to an organ model and a training system.

The progress of three-dimensional modeling technology is remarkable, and various 3D printers such as fused deposition modeling, binder jetting, photolithography, powder sintering additive manufacturing, and material jetting are used in the manufacturing industry. In addition to the conventionally known metals and resins, various materials have been developed as materials for use in 3D printers. New applications for these various materials have also been proposed, and applications are expected not only in the industrial field but also in the medical and healthcare fields. Examples of applications of 3D printers in the medical field include, for example, the creation of implantable artificial bones using titanium, hydroxyapatite, PEEK, etc., and research into artificial organs by direct cell layering. Examples of applications of 3D printers in the healthcare field include, for example, applications to hearing aids and prosthetic limbs that need to reflect the unique shapes of each individual.

Another application of 3D printers in the medical field is the use of models that mimic the shape of actual organs or living organisms for the purpose of surgical training and simulation. The background to the expected application to such models is that medical equipment has been developed in recent years, and minimally invasive medical treatments that place less strain on patients, such as catheters, endoscopes, and robot assistance, are becoming mainstream, replacing the traditional medical treatments that involve large incisions and removal. Surgical operations using these medical equipment require very advanced technology and expertise, so the importance of surgical training using appropriate models is recognized from the perspective of preventing medical accidents. Furthermore, in difficult surgeries that are rarely performed, if a model that reproduces the details of the target area can be obtained in advance, it will be possible to perform detailed preoperative simulations.

Patent Document 1 discloses a method of forming a three-dimensional model of an organ or the like by irradiating a photocurable resin with laser light to form hardened layers that match each tomographic shape based on two-dimensional tomographic image data obtained by a tomographic shape measuring device such as a CT scanner, and then stacking these layers in sequence.

Patent Document 2 discloses a method for creating design data that indicates two or more of the organ's shape, hardness, density, and effective atomic number individually for each voxel based on a medical 3D image having multiple voxels that indicate the organs of a subject, and for creating a 3D object based on the design data.

However, it is difficult to create an organ model that accurately reproduces the distribution of physical properties in a living body.

The present invention relates to an organ model that is shaped based on biophysical property information indicating the biophysical properties obtained by MRE measurement of a living body, and has a distribution of strength properties corresponding to the distribution of the biophysical properties.

The present invention provides an organ model that accurately reproduces the distribution of physical properties in a living body.

FIG. 1 is a schematic diagram showing an example of a medical image dataset. FIG. 2 is a schematic diagram showing an example of medical 3D data. FIG. 3 is a schematic diagram showing an example of medical 3D data. FIG. 4 is a schematic diagram showing an example of regional medical 3D data acquired by dividing the medical 3D data into voxel regions. FIG. 5 is a schematic diagram showing an example of data in STL format acquired by converting regional medical 3D data into a surface model. FIG. 6 is a schematic diagram showing an example of data in FAV format acquired by converting regional medical 3D data into the FAV format. FIG. 7 is a schematic diagram showing an example of seven-level strength properties expressed by the arrangement patterns of the high-strength shaping composition and the low-strength shaping composition. FIG. 8 is a schematic diagram showing an example of a water-swellable layered clay mineral as a mineral, and a state in which the water-swellable layered clay mineral is dispersed in water. FIG. 9 is a schematic diagram showing an example of an organ model forming apparatus. FIG. 10 is a schematic diagram showing an example of an organ model peeled off from a support. FIG. 11 shows the results of compressive strength measurements for Samples 1 to 4. FIG. 12 shows the measurement results of the tensile test for Samples 5 to 8.

1. Organ Model In the present disclosure, an "organ model" refers to a three-dimensional object (also referred to as a "model") that mimics the shape and physical properties of at least a part of an organ. An organ is a functional organ that constitutes a living body, and includes not only internal organs but also all organs that constitute a living body, such as bones, skin, and blood vessels.

The material constituting the organ model is not particularly limited as long as it is a material capable of forming a three-dimensional object that mimics the shape and physical properties of at least a part of an organ. For example, it is preferable that the material satisfies the following three conditions:
・The material must be soft and the physical properties of the material must be controllable. ・The material must be self-supporting (capable of retaining its shape). ・The material must be capable of being modeled using a modeling device (also known as a 3D printer).

Examples of such materials include soft plastics containing polyurethane resin and silicone resin, and hydrogels containing polyvinyl alcohol, but hydrogels are preferred. In this disclosure, "hydrogel" refers to a structure in which water is contained in a three-dimensional network structure containing a polymer, and when such a three-dimensional network structure is a three-dimensional network structure formed by the composite of a polymer and a mineral, it is particularly called an "organic-inorganic composite hydrogel." Note that hydrogels contain water as a main component, and specifically, the water content is preferably 30.0% by mass or more, more preferably 40.0% by mass or more, and even more preferably 50.0% by mass or more, based on the total amount of the hydrogel.

The material constituting the organ model is formed from a modeling composition that is a precursor of the material. In this case, when the material constituting the organ model is a hydrogel, the hydrogel is formed from a hydrogel 3D modeling composition that is a precursor of the hydrogel. In this disclosure, the term "hydrogel 3D modeling composition" refers to a liquid composition that hardens to form a hydrogel when irradiated with active energy rays such as light or heat, and is particularly a liquid composition used to model a 3D object made of hydrogel. The hydrogel 3D modeling composition contains water and a polymerizable compound, and may contain minerals, organic solvents, and other components as necessary. Each component contained in the hydrogel 3D modeling composition will be described below.

(1) Water The hydrogel three-dimensional modeling composition contains water. The water is not particularly limited as long as it can be used as a solvent in general, and examples of water that can be used include pure water such as ion-exchanged water, ultrafiltered water, reverse osmosis water, and distilled water, and ultrapure water.
When the hydrogel 3D modeling composition is used to model an organ model, the water content is preferably 30.0% by mass or more and 90.0% by mass or less, and more preferably 40.0% by mass or more and 90.0% by mass or less, relative to the total amount of the hydrogel 3D modeling composition.
In addition, other components such as organic solvents may be dissolved or dispersed in the water depending on the purpose of imparting moisture retention, antibacterial properties, electrical conductivity, adjusting hardness, etc.

(2) Polymerizable Compound The hydrogel three-dimensional modeling composition contains a polymerizable compound, which is a compound having a polymerizable functional group. Examples of the polymerizable compound include monomers and oligomers. The polymerizable compound is polymerized by irradiation with active energy rays or heat to form at least a part of a polymer. That is, the polymer has a structural unit derived from the polymerizable compound. In addition, it is preferable that the polymer is crosslinked with a mineral to form a composite and form a three-dimensional network structure in the hydrogel. Here, it is preferable that the polymerizable compound is water-soluble. Water-soluble means that, for example, when 100 g of water at 30° C. and 1 g of monomer are mixed and stirred, 90% by mass or more of the monomer is dissolved.

The polymerizable compound is not particularly limited as long as it has a polymerizable functional group, but is preferably a compound having a photopolymerizable functional group. In this disclosure, the term "polymerizable functional group" refers to a functional group that undergoes a polymerization reaction when irradiated with active energy rays or when heat is added, and the term "photopolymerizable functional group" refers to a functional group that undergoes a polymerization reaction when irradiated with active energy rays. Examples of photopolymerizable functional groups include, but are not limited to, groups having an ethylenically unsaturated bond such as a (meth)acryloyl group, a vinyl group, or an allyl group, and cyclic ether groups such as an epoxy group. Specific examples of compounds containing a group having an ethylenically unsaturated bond include, for example, a compound having a (meth)acrylamide group, a (meth)acrylate compound, a compound having a (meth)acryloyl group, a compound having a vinyl group, and a compound having an allyl group.

(I) Monomer The monomer that can be used as the polymerizable compound is preferably a compound having one or more polymerizable functional groups such as an unsaturated carbon-carbon bond, and examples thereof include monofunctional monomers and polyfunctional monomers. Furthermore, examples of polyfunctional monomers include bifunctional monomers and trifunctional or higher functional monomers. These may be used alone or in combination of two or more.

(A) Monofunctional Monomer Examples of the monofunctional monomer include acrylamide, N-substituted acrylamide derivatives, N,N-disubstituted acrylamide derivatives, N-substituted methacrylamide derivatives, N,N-disubstituted methacrylamide derivatives, acrylic acid, 2-ethylhexyl (meth)acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, caprolactone-modified tetrahydrofurfuryl (meth)acrylate, 3-methoxybutyl (meth)acrylate, tetrahydrofurfuryl (meth)acrylate, lauryl (meth)acrylate, 2-phenoxyethyl (meth)acrylate, isodecyl (meth)acrylate, isooctyl (meth)acrylate, tridecyl (meth)acrylate, caprolactone (meth)acrylate, and ethoxylated nonylphenol (meth)acrylate. These may be used alone or in combination of two or more. Among these, acrylamide, N,N-dimethylacrylamide, N-isopropylacrylamide, acryloylmorpholine, hydroxyethylacrylamide, isobornyl (meth)acrylate, and the like are preferable.

The content of the monofunctional monomer is preferably 0.5% by mass or more and 30.0% by mass or less based on the total amount of the hydrogel three-dimensional modeling composition.

(B) Bifunctional Monomer Examples of the bifunctional monomer include tripropylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, polypropylene glycol di(meth)acrylate, neopentyl glycol hydroxypivalic acid ester di(meth)acrylate, hydroxypivalic acid neopentyl glycol ester di(meth)acrylate, 1,3-butanediol di(meth)acrylate, 1,4-butanediol di(meth)acrylate, and 1,6-hexanediol di(meth)acrylate. Examples of such acrylates include 1,9-nonanediol di(meth)acrylate, diethylene glycol di(meth)acrylate, neopentyl glycol di(meth)acrylate, tripropylene glycol di(meth)acrylate, caprolactone-modified hydroxypivalic acid neopentyl glycol ester di(meth)acrylate, propoxylated dipentyl glycol di(meth)acrylate, ethoxy-modified bisphenol A di(meth)acrylate, polyethylene glycol 200 di(meth)acrylate, and polyethylene glycol 400 di(meth)acrylate. These may be used alone or in combination of two or more.

(C) Trifunctional or higher monomers Examples of trifunctional or higher monomers include trimethylolpropane tri(meth)acrylate, pentaerythritol tri(meth)acrylate, dipentaerythritol hexa(meth)acrylate, triallyl isocyanurate, ε-caprolactone-modified dipentaerythritol tri(meth)acrylate, ε-caprolactone-modified dipentaerythritol tetra(meth)acrylate, ε-caprolactone-modified dipentaerythritol penta(meth)acrylate, ε-caprolactone-modified dipentaerythritol hexa(meth)acrylate, tris Examples of such compounds include (2-hydroxyethyl)isocyanurate tri(meth)acrylate, ethoxylated trimethylolpropane tri(meth)acrylate, propoxylated trimethylolpropane tri(meth)acrylate, propoxylated glyceryl tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, ditrimethylolpropane tetra(meth)acrylate, dipentaerythritol hydroxypenta(meth)acrylate, ethoxylated pentaerythritol tetra(meth)acrylate, penta(meth)acrylate ester, etc. These compounds may be used alone or in combination of two or more.

The content of the polyfunctional monomer is preferably 0.01% by mass or more and 10.0% by mass or less based on the total amount of the hydrogel three-dimensional modeling composition.

(II) Oligomer The oligomer is a low polymer of the above-mentioned monofunctional monomer or a low polymer having a reactive unsaturated bond group at the end. These may be used alone or in combination of two or more kinds.

(3) Mineral The hydrogel composition for three-dimensional modeling preferably contains a mineral. The mineral is not particularly limited as long as it is capable of bonding with the polymer formed from the polymerizable compound, and may be appropriately selected depending on the purpose. For example, layered clay minerals, particularly water-swellable layered clay minerals, may be mentioned.
The water-swellable layered clay mineral will be described with reference to FIG. 8. FIG. 8 is a schematic diagram showing an example of a water-swellable layered clay mineral as a mineral and a state in which the water-swellable layered clay mineral is dispersed in water. As shown in the upper diagram of FIG. 8, the water-swellable layered clay mineral exists in a single layer state, and exhibits a state in which two-dimensional disk-shaped crystals having unit lattices within the crystal are stacked. When the water-swellable layered clay mineral in the upper diagram of FIG. 8 is dispersed in water, each single layer separates to form a plurality of two-dimensional disk-shaped crystals, as shown in the lower diagram of FIG. 8.
The term "water-swellable" refers to the property of water molecules being inserted between the individual monolayers of the layered clay mineral and dispersing in water, as shown in Fig. 8. The shape of the monolayer of the water-swellable layered clay mineral is not limited to a disk shape, and may be other shapes.

Examples of water-swellable layered clay minerals include water-swellable smectite and water-swellable mica. More specifically, water-swellable hectorite, water-swellable montmorillonite, water-swellable saponite, water-swellable synthetic mica, and the like, each containing sodium as an interlayer ion, may be used. These may be used alone or in combination of two or more. Among these, water-swellable hectorite is preferred because it can produce a highly elastic hydrogel.
The water-swellable hectorite may be appropriately synthesized or may be a commercially available product. Examples of commercially available products include synthetic hectorite (Laponite XLG, manufactured by Rockwood), SWN (manufactured by Coop Chemical Ltd.), and fluorinated hectorite SWF (manufactured by Coop Chemical Ltd.). Among these, synthetic hectorite is preferred from the viewpoint of improving the elastic modulus of the hydrogel.

The mineral content is preferably 1.0% by mass or more and 40.0% by mass or less based on the total amount of the hydrogel 3D modeling composition.

(4) Organic Solvent The hydrogel three-dimensional modeling composition may contain an organic solvent, if necessary. The organic solvent is contained for the purpose of increasing the moisture retention of the hydrogel, for example.
Examples of the organic solvent include alkyl alcohols having 1 to 4 carbon atoms, amides, ketones, ketone alcohols, ethers, polyhydric alcohols, polyalkylene glycols, lower alcohol ethers of polyhydric alcohols, alkanolamines, N-methyl-2-pyrrolidone, etc. These may be used alone or in combination of two or more.
Among these, polyhydric alcohols are preferred from the viewpoint of moisturizing properties, and specifically, polyhydric alcohols such as ethylene glycol, propylene glycol, 1,2-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, diethylene glycol, triethylene glycol, 1,2,6-hexanetriol, thioglycol, hexylene glycol, and glycerin are preferably used.
The content of the organic solvent is preferably 10.0% by mass or more and 50.0% by mass or less based on the total amount of the hydrogel 3D modeling composition, in which case drying of the hydrogel 3D modeling composition can be suppressed, and dispersibility of the mineral in the hydrogel 3D modeling composition can be improved by setting the content to 50.0% by mass or less.

(5) Other Components The hydrogel three-dimensional modeling composition may contain other components as necessary.
The other components are not particularly limited and can be appropriately selected depending on the purpose. Examples of the other components include stabilizers, surface treatment agents, polymerization initiators, colorants, viscosity modifiers, adhesion promoters, antioxidants, antiaging agents, crosslinking agents, ultraviolet absorbers, plasticizers, preservatives, metal ions, fillers, metal fine particles, and dispersants.

(I) Stabilizer The stabilizer is contained in order to stably disperse the mineral and maintain the sol state of the hydrogel 3D modeling composition. In addition, when the hydrogel 3D modeling composition is used in a method of ejecting the composition as droplets, the stabilizer is contained in order to stabilize the properties of the composition as a liquid.
Stabilizers include, for example, high concentration phosphates, glycols, non-ionic surfactants, and the like.

(II) Surface Treatment Agent Examples of the surface treatment agent include polyester resins, polyvinyl acetate resins, silicone resins, coumarone resins, fatty acid esters, glycerides, and waxes.

(III) Polymerization initiator Examples of the polymerization initiator include a thermal polymerization initiator, a photopolymerization initiator, etc. Among these, from the viewpoint of storage stability, a photopolymerization initiator that generates a radical or a cation by irradiation with an active energy ray is preferred.
As the photopolymerization initiator, any substance that generates radicals when irradiated with light (particularly ultraviolet light having a wavelength of 220 nm or more and 400 nm or less) can be used.
The thermal polymerization initiator is not particularly limited and can be appropriately selected depending on the purpose. Examples of the thermal polymerization initiator include azo-based initiators, peroxide initiators, persulfate initiators, and redox (oxidation-reduction) initiators.

(6) Physical properties of the hydrogel three-dimensional modeling composition The viscosity of the hydrogel three-dimensional modeling composition at 25 ° C. is preferably 3.0 mPa · s or more and 20.0 mPa · s or less, more preferably 6.0 mPa · s or more and 12.0 mPa · s or less. By having a viscosity of 3.0 mPa · s or more and 20.0 mPa · s or less, it can be suitably applied to droplet ejection in a 3D printer (particularly a material jetting method). The viscosity can be measured using, for example, a rotational viscometer (VISCOMATE VM-150III, manufactured by Toki Sangyo Co., Ltd.).

The surface tension of the hydrogel 3D modeling composition is preferably 20 mN/m or more and 45 mN/m or less, and more preferably 25 mN/m or more and 34 mN/m or less. If the surface tension is 20 mN/m or more, the ejection stability can be improved, and if it is 45 mN/m or less, it becomes easier to fill the hydrogel 3D modeling composition into an ejection nozzle for modeling. The surface tension can be measured, for example, using a surface tensiometer (automatic contact angle meter DM-701, manufactured by Kyowa Interface Science Co., Ltd.).

2. Method for Forming an Organ Model The organ model of the present invention is formed based on biological property information indicating biological properties obtained by MRE measurement of a living body. By forming the organ model in this manner, the organ model of the present invention has a distribution of intensity properties corresponding to the distribution of the biological properties. Hereinafter, a method for forming the organ model of the present invention based on the biological property information will be described.

The modeling method is not particularly limited as long as it is possible to model an organ model having a distribution of strength properties corresponding to the distribution of biological properties, and examples of the method include a modeling method using a 3D printer. In addition, the modeling method using a 3D printer preferably has a modeling step of modeling an organ model using a 3D printer based on medical 3D data of a living body. When performing such a modeling method having a modeling step, as necessary, a step performed before the modeling step may include an acquisition step of acquiring medical 3D data of a living body, and a generation step of generating modeling 3D data based on the medical 3D data. Furthermore, when performing such a modeling method having a modeling step, as necessary, a step performed after the modeling step may include an evaluation step of evaluating the accuracy of the modeled organ model. Hereinafter, as an example of a method for modeling an organ model, a case having an acquisition step, a generation step, a modeling step, and an evaluation step will be described.
In the present disclosure, the term "living body" refers to at least a part of a human or non-human organism, and the number of subjects may be one or more. Note that at least a part of a human or non-human organism refers to, for example, a predetermined region in a living body, such as the chest, or a predetermined organ in a living body.
In addition, in the present disclosure, "printing an organ model using a 3D printer based on medical 3D data of a living organism" is not limited to the direct use of medical 3D data, such as inputting the medical 3D data into a 3D printer to print an organ model, but also refers to the indirect use of medical 3D data, such as inputting 3D data for printing generated based on the medical 3D data into a 3D printer to print an organ model.

(1) Acquisition Step The modeling method preferably includes an acquisition step of acquiring medical 3D data of a living body. In the present disclosure, "medical 3D data" refers to data created based on at least medical image data acquired by photographing a living body with a medical imaging device and biological properties acquired by MRE measurement of the living body. That is, the acquisition step of acquiring medical 3D data of a living body includes an imaging step of acquiring medical image data by photographing the living body with a medical imaging device, a measurement step of acquiring biological properties by MRE measurement of the living body, and a creation step of creating medical 3D data based on the medical image data and the biological properties.

(I) Photographing Process The photographing process is a process of acquiring medical image data by photographing a living body with a medical imaging device. The medical imaging device is also called a modality, and is a device that scans a living body as a subject to acquire medical image data. Examples of the medical imaging device include a CT (Computed Tomography) device, an MRI (Magnetic Resonance Imaging) device, and an ultrasonic diagnostic device. Among these, it is preferable to use an MRI device from the viewpoint of also performing MRE measurement in the measurement process described later. The medical imaging device performs slice tomography to photograph a cross section of the living body multiple times. As a result, as shown in FIG. 1, multiple medical image data, which are images showing the cross sections of the living body, can be acquired. Each of these multiple medical image data (also called a "medical image data set") is preferably an image in the DICOM format, which is an international standard for medical image exchange. In addition, the medical image data includes image density information indicating the image density acquired by the medical imaging device. The image density is, for example, a CT value (X-ray transmittance) when a CT device is used as the medical imaging device, an MRI signal value when an MRI device is used, and reflection intensity when an ultrasound diagnostic device is used.

(II) Measuring step The measuring step is a step of acquiring biological properties by MRE measurement of a biological body. MRE measurement refers to measurement by a method of magnetic resonance elastography (MRE). This method is a non-invasive method of measuring the viscoelastic distribution inside a biological body by generating shear waves inside the biological body using a vibration device and taking an image with an MRI device. That is, the biological property acquired by MRE measurement of a biological body is preferably viscoelasticity. In addition to the method of performing MRE measurement, a method of performing measurement by ultrasonic elastography can be mentioned as a method of acquiring viscoelasticity of a biological body. In this regard, while the information obtained by measurement by ultrasonic elastography is one-dimensional, the information obtained by MRE measurement is two-dimensional, and 3D data can be easily generated, so that MRE measurement is preferable. In addition, when the measurement target is an organ such as the heart or blood vessels that itself undergoes periodic motion, a method of measuring the amount of deformation of the organ accompanying this motion and estimating the biophysical properties from the measured values based on a mechanical model or the like can also be mentioned. However, the biophysical properties obtained by this method are merely estimated values, and are inferior to MRE measurement in terms of accurate information acquisition of the living body. In addition, this method can be used only when the measurement target is an organ that undergoes periodic motion such as the heart or blood vessels, so MRE measurement is preferable in that organs that do not undergo periodic motion or organs for which it is difficult to measure the amount of deformation accompanying periodic motion can also be used as measurement targets. In addition, MRE measurement is often included in the system as an optional function of the MRI device, and is also preferable in that the imaging process and the measurement process can be performed by the same MRI device. In addition to this, the imaging process by the MRI device and the measurement process by the MRI device can be performed almost simultaneously. It is preferable in that the burden on the subject such as a patient can be reduced by performing them almost simultaneously, and that the time of acquiring medical image data and the time of acquiring biophysical properties are almost simultaneous, thereby obtaining accurate information on the living body. In particular, the latter point is an important point considering that the subject of imaging and measurement is a living body that is prone to change over time in terms of shape, physical properties, etc. Note that "almost simultaneously" refers to a case where the imaging process and the measurement process overlap at least partially, or where both the imaging process and the measurement process can be performed by using an MRI device once. In addition, MRE measurement is preferable in that it can be performed on a living body, and therefore the physical properties of the organ in the living body can be obtained in a state where blood pressure is applied.

(III) Creation Process The creation process is a process of creating medical 3D data based on the medical image data acquired in the imaging process and the biological properties acquired in the measurement process. The medical 3D data is information including a plurality of voxels created based on the medical image data, image density information indicating the image density in the medical image data assigned to each voxel, and biological property information indicating the biological properties assigned to each voxel. In other words, the medical 3D data is information in which the voxels, the image density information, and the biological property information are associated with each other.

A method for creating medical 3D data will be specifically described.
First, medical 3D data corresponding to 3D image processing is created from medical image data acquired in the imaging process by a medical imaging device or an image processing device related to the medical imaging device (also referred to as "medical imaging device, etc."). Medical 3D data is a collection of voxels including at least one minimum unit such as a cube as shown in FIG. 2, and various information can be associated with each voxel. Next, the medical imaging device, etc. associates image density information indicating image density in the medical image data acquired in the imaging process with each voxel. Furthermore, the medical imaging device, etc. associates biological property information indicating biological properties acquired in the measurement process with each voxel. As a result, medical 3D data, which is information in which voxels, image density information, and biological property information are associated, can be created as shown in FIG. 3. The medical 3D data can be segmented into voxel regions using image density information. Voxel region segmentation refers to classifying and segmenting voxels with similar image densities. This enables shape recognition, structure division, tissue analysis, and 3D image analysis of the internal structure of a living body based on the medical 3D data, and allows medical 3D data of a target organ part to be obtained from the medical 3D data of the living body. In the present invention, medical 3D data in a partial region obtained by dividing the medical 3D data into voxel regions as shown in Figure 4 is called medical 3D data by region. Note that medical 3D data by region is considered to be one concept included in medical 3D data.

(2) Generation Step The modeling method preferably includes a generation step of generating 3D modeling data based on the medical 3D data. In this disclosure, "3D modeling data" refers to data generated based on the medical 3D data and input to a 3D printer. The 3D modeling data may be composed of one piece of data or may be composed of multiple pieces of data. Below, two specific examples of a method for generating 3D modeling data will be described, but the present method is not limited to these.

(I) Generation of 3D Modeling Data Including Data in STL Format A case will be described where 3D modeling data including data in STL (Standard Triangulated Language) format is generated based on medical 3D data.
In this case, as shown in Fig. 5, surface model conversion is performed on the regional medical 3D data obtained by dividing the medical 3D data into voxel regions, and data in the STL format corresponding to the regional medical 3D data is created. Since the STL format data is surface data, the biological property information assigned to each voxel of the regional medical 3D data is lost by performing surface model conversion. Therefore, apart from the surface model conversion, biological property information for 3D printing is created from the regional medical 3D data, including position information indicating the position of the voxel and biological property information assigned to each position information. The biological property information assigned to each position information is biological property information associated with the voxel located at the position indicated by the position information. That is, the 3D data for printing in this description includes data in the STL format and biological property information for 3D printing.

(II) Generation of 3D Modeling Data Including Data in FAV Format A case will be described where 3D modeling data including data in the FAV (Fabricatable Voxel) format is generated based on medical 3D data.
In this case, as shown in Fig. 6, the medical 3D data is divided into voxel regions, and the medical 3D data by region is obtained by performing FAV format conversion to generate FAV format data corresponding to the medical 3D data by region. Note that the FAV format data is defined as voxel data, not as surface data as in the STL format data. This allows the medical 3D data, which is voxel data to which image density information, biological property information, etc. are added, to be converted to FAV format data with the image density information, biological property information, etc. added. In other words, this is preferable in that it can omit a separate data processing process for necessary information such as biological property information, as in the case of conversion to STL format data.

(3) Modeling process The modeling method includes a modeling process of modeling an organ model using a 3D printer based on the medical 3D data of a living body. As described above, in the present disclosure, "modeling an organ model using a 3D printer based on the medical 3D data of a living body" is not limited to a case where the medical 3D data is directly used, such as inputting the medical 3D data to a 3D printer to model an organ model, but also represents a case where the medical 3D data is indirectly used, such as inputting modeling 3D data generated based on the medical 3D data to a 3D printer to model an organ model. Hereinafter, the modeling process will be described using as an example a case where modeling 3D data generated based on the medical 3D data is input to a 3D printer to model an organ model.

First, a case will be described in which 3D modeling data including the above-mentioned STL format data is input to a 3D printer. In this case, the 3D modeling data includes STL format data and biological property information for 3D modeling. These data may be input simultaneously or separately.
The 3D printer converts the input data in the STL format into a 2D image data set for printing. The 2D image data set for printing is a data set including a plurality of 2D image data for printing, and the 2D image data for printing is two-dimensional slice data obtained by slicing the data in the STL format in accordance with the resolution of the 3D printer in the Z-axis direction. Next, the 3D printer imparts strength property information indicating the strength property in each region of the 2D image data for printing based on the input biological property information for 3D printing. Based on the 2D image data for printing and the strength property information in each region of the 2D image data for printing, the 3D printer repeats the process of discharging a plurality of types of modeling compositions in a predetermined amount into each predetermined region and curing them, thereby forming an organ model having a distribution of strength properties corresponding to the distribution of biological properties. Here, in the present disclosure, the "strength property" represents the property of the organ model formed by the 3D printer, and specifically, represents viscoelasticity since it is a property corresponding to the biological property.

Next, a case where 3D modeling data including the above-mentioned FAV format data is input to a 3D printer will be described.
The 3D printer converts the input data in the FAV format into a 2D image data set for printing, which is slice data similar to the above. However, each 2D image data set for printing included in the 2D image data set for printing is provided with strength property information indicating the strength property in each region based on the biological property information included in the FAV format data. Based on this 2D image data for printing and the strength property information in each region of the 2D image data for printing, the 3D printer repeats the process of discharging a plurality of types of modeling compositions in a predetermined amount into each predetermined region and curing them, thereby forming an organ model having a distribution of strength properties corresponding to the distribution of biological properties.

The 3D printer used in the modeling process can be, for example, a printer that can control the strength properties of the organ model to be modeled for each part by discharging multiple types of modeling compositions in predetermined amounts onto each predetermined area. Specific examples include material jetting type (MJ type) 3D printers that discharge modeling compositions using an inkjet head.

As described above, as a method for using a 3D printer to make the strength properties correspond to the biological properties, a method using a 3D printer capable of expressing the strength properties by gradation can be given. Hereinafter, an example of this method will be described.
First, a high-strength molding composition capable of molding a three-dimensional object having high strength physical properties and a low-strength molding composition capable of molding a three-dimensional object having low strength physical properties are prepared. At least one type of each of these molding compositions is used, but multiple types of each may be used. In this case, it is preferable that the strength property of the organ model molded with the high-strength molding composition is equal to or greater than the maximum value of the biological property in a living body, and it is preferable that the strength property of the organ model molded with the low-strength molding composition is equal to or less than the minimum value of the biological property in a living body.
Next, the strength properties of the organ model are controlled by a pattern of the modeling composition arranged to fill a certain grid area. For example, as shown in FIG. 7, when an expression with seven gradations of strength properties is required, a combination pattern in which a grid with a minimum unit of six sections is filled with a high-strength modeling composition and a low-strength modeling composition enables the expression of seven gradations of strength. By increasing the number of sections of the unit grid, various gradation expressions are possible. By arranging in the XY plane, the planar intensity distribution can be set, and by arranging in the Z direction, the vertical intensity distribution can be set, thereby forming an organ model having a distribution of strength properties corresponding to the distribution of biological properties. That is, in the present disclosure, the "distribution of strength properties corresponding to the distribution of biological properties" is not limited to the case where the strength properties in the distribution are the same as the biological properties at the corresponding position, but also includes the case where the strength properties realized by the gradation expression are approximate to the biological properties at the corresponding position. An example of the case where the strength properties (synonymous with the model properties described later) are within 5% of the biological properties. In addition, in the present disclosure, "gradation" refers to an arrangement pattern formed by respectively arranging multiple types of molding compositions, as described above, in which the strength properties of the cured product differ for each arrangement pattern.
In addition, since this method can be expressed as voxels, it is efficient to make it compatible with a voxel format such as FAV. Also, the number of droplets of the modeling composition filling the unit section may be any number.
Furthermore, by understanding the intensity properties in the gradations that can be expressed by a 3D printer in advance using MRE measurements, it is possible to more accurately create organ models having a distribution of intensity properties that corresponds to the distribution of biological properties.

(4) Evaluation step The modeling method may include an evaluation step of evaluating the accuracy of the modeled organ model. The evaluation step is a step of evaluating the accuracy of the modeled organ model based on biological property information indicating biological properties acquired by MRE measurement of a living body in the acquisition step and model property information indicating model properties acquired by MRE measurement of the organ model modeled in the modeling step. This step may be executed by a person or an information processing device such as a personal computer.

First, a method for evaluating the accuracy of an organ model created based on biological physical property information and model physical property information will be described.
Methods for evaluating the accuracy of an organ model include, for example, a method for evaluating the accuracy by determining whether the distribution of biological properties and the distribution of model properties show approximately identical distributions, and a method for evaluating the accuracy by determining whether corresponding parts of a living organism and an organ model have approximately identical biological properties and model properties.

Examples of the corresponding parts of the living body and the organ model include parts in the living body and parts in the organ model that have almost the same coordinates when the coordinates are assigned to the living body and the organ model according to the same standard, parts having a specific structure in the living body (such as a tumor part) and parts in the organ model that imitate the part having the specific structure in the living body (such as a tumor part), and the latter is preferable. In the latter case, for example, 10 positions are selected for each of the parts having a specific structure in the living body and the parts in the organ model that imitate the part having the specific structure in the living body, the average of the living body properties and the average of the model properties at each part are calculated, and the accuracy of the organ model is evaluated based on these averages.
An example of a criterion for determining whether the corresponding parts of a living body and an organ model have substantially the same biological properties and model properties is that the difference between the model properties and the biological properties at the corresponding parts is within 5%. The difference is not limited to within 5% and can be appropriately selected depending on the degree of accuracy required, and may be within 50%, within 40%, within 30%, within 20%, within 10%, etc., but it is preferable that the difference is small from the viewpoint of evaluating high accuracy. An organ model with a difference of within 5% can be realized by performing the imaging process by the MRI device and the measurement process by the MRI device almost simultaneously. As described above, this is because the time of acquiring medical image data and the time of acquiring biological properties are almost simultaneous, and accurate information on the living body can be obtained. Note that, "almost simultaneously" refers to a case where at least a part of the time of the imaging process and the time of the measurement process overlap, or a case where both the imaging process and the measurement process can be performed by using the MRI device once.

As described above, in order to compare the biophysical information and the model physical information at corresponding sites of the living body and the organ model, it is preferable to also have information indicating the position in the living body where the biophysical properties were measured and information indicating the position in the organ model where the model physical properties were measured. Therefore, when evaluating the accuracy of the organ model, it is preferable to use medical 3D data, which is information in which voxels, image density information, and biophysical information are associated, and model 3D data, which is information in which voxels, image density information, and model physical property information are associated, and compare the biophysical information and the model physical property information contained in these data. This is because voxels correspond to the information indicating the above-mentioned position. Note that the model 3D data is data obtained in the same manner as the medical 3D data, and represents data created based on at least model image data obtained by photographing the organ model with a medical imaging device and model physical properties obtained by MRE measurement of the organ model.

This evaluation process uses model properties obtained by subjecting the organ model to MRE measurement. This means that it is preferable that the material constituting the organ model contains water, which is suitable for MRE measurement using hydrogen nuclei as a signal source, as one of the main components. In other words, it is preferable that the material constituting the organ model contains the above-mentioned hydrogel.

3. Method for modeling an organ model using a 3D printer As an example of a method for modeling an organ model using a 3D printer (hereinafter also referred to as a "modeling device"), a method for modeling an organ model using the above-mentioned hydrogel three-dimensional modeling composition with a material jetting type 3D printer will be described.

The method for modeling an organ model by the material jetting method includes a liquid film forming step of applying droplets of a hydrogel composition for three-dimensional modeling to form a liquid film, and a curing step of curing the liquid film of the hydrogel composition for three-dimensional modeling, and is characterized in that the liquid film forming step and the curing step are repeated in sequence. Note that the method for modeling an organ model may include a support modeling step of modeling a support that supports the organ model, and other steps, as necessary.
The organ modeling device using the material jetting method has a storage means for storing a hydrogel composition for 3D modeling, a liquid film forming means for applying droplets of the stored hydrogel composition for 3D modeling to form a liquid film, and a hardening means for hardening the liquid film of the hydrogel composition for 3D modeling, and is characterized in that the liquid film formation by the liquid film forming means and the hardening by the hardening means are sequentially repeated.

First, the material jetting method will be described with reference to Figures 9 and 10. Figure 9 is a schematic diagram showing an example of an organ model forming apparatus. Figure 10 is a schematic diagram showing an example of an organ model peeled off from a support. The organ model forming apparatus 10 of the material jetting method shown in Figure 9 uses a head unit in which inkjet heads are arranged, and sprays the hydrogel three-dimensional modeling composition contained in a hydrogel three-dimensional modeling composition storage container from the hydrogel three-dimensional modeling composition jetting head unit 11 and the support modeling composition contained in a support modeling composition storage container from the support modeling composition jetting head unit 12 toward the modeling body support substrate 14, and stacks the hydrogel three-dimensional modeling composition and the support modeling composition while hardening them with the adjacent ultraviolet irradiator 13. Here, the support modeling composition represents a liquid composition that is hardened by irradiation with active energy rays such as light or heat to form a support that supports the organ model, and examples of such compositions include acrylic materials. The modeling device 10 may also have a smoothing member 16 that smoothes the sprayed hydrogel three-dimensional modeling composition.

The modeling device 10 stacks layers while lowering the stage 15 according to the number of layers to maintain a constant gap between the hydrogel 3D modeling composition jetting head unit 11, the support modeling composition jetting head unit 12, and the ultraviolet irradiator 13 and the organ model (hydrogel) 17 and support (support material) 18.

The ultraviolet irradiator 13 in the modeling device 10 is used when moving in either direction of arrow A or B, and the heat generated by ultraviolet irradiation smoothes the layered surface, resulting in improved dimensional stability of the organ model 17.

After modeling is completed in the modeling device 10, the organ model 17 and the support 18 can be pulled horizontally as shown in Figure 10, and the support 18 can be peeled off as a single unit, allowing the organ model 17 to be easily removed.

(1) Liquid film forming process In the liquid film forming process, the method of applying the hydrogel three-dimensional modeling composition is not particularly limited as long as it is a method that can apply droplets to the target position with appropriate accuracy, and can be appropriately selected depending on the purpose, and a known droplet ejection method can be used. Specific examples of the droplet ejection method include a dispenser method, a spray method, and an inkjet method, and the inkjet method is preferable.

The volume of the droplets of the hydrogel 3D modeling composition is, for example, preferably 2 pL or more and 60 pL or less, and more preferably 15 pL or more and 30 pL or less. If the volume of the droplets is 2 pL or more, the ejection stability can be improved, and if it is 60 pL or less, it becomes easier to fill the hydrogel 3D modeling composition into an ejection nozzle for modeling, etc.

(2) Curing Step In the curing step, the liquid film of the hydrogel three-dimensional modeling composition can be cured by, for example, an ultraviolet (UV) irradiation lamp, an electron beam, etc. Examples of the type of ultraviolet (UV) irradiation lamp include a high-pressure mercury lamp, an ultra-high-pressure mercury lamp, a metal halide lamp, etc.
As a curing means for the hydrogel three-dimensional modeling composition, a UV-LED (Ultra Violet-Light Emitting Diode) is preferably used. The emission wavelength of the LED is not particularly limited, and generally includes 365 nm, 375 nm, 385 nm, 395 nm, 405 nm, etc., but in consideration of the effect of color on the modeled object, it is more advantageous to emit light with a short wavelength so that the absorption of the initiator is increased. In addition, compared with commonly used ultraviolet irradiation lamps (high pressure mercury lamps, ultra-high pressure mercury lamps, metal halide lamps), electron beams, etc., UV-LEDs generate less heat energy during curing, and the thermal damage to the hydrogel is reduced. In particular, since the hydrogel modeled by the hydrogel three-dimensional modeling composition is used in a state containing water, this effect is remarkable.

The method for forming an organ model includes a liquid film forming step of applying droplets of a hydrogel 3D modeling composition to form a liquid film, and a curing step of curing the liquid film of the hydrogel 3D modeling composition, and the liquid film forming step and the curing step are repeated in sequence. At this time, the number of repetitions is not particularly limited and can be appropriately selected depending on the size, shape, etc. of the organ model to be formed. In addition, the average thickness per layer after curing is preferably 10 μm or more and 50 μm or less. By having an average thickness of 10 μm or more and 50 μm or less, it is possible to form the model with high precision and with little peeling.

(3) Support Modeling Process The support modeling composition used in the support modeling process is a liquid composition that hardens when irradiated with active energy rays such as light or heat, and models a support that supports an organ model. The composition of the support modeling composition is different from that of the hydrogel three-dimensional modeling composition. Specifically, it preferably contains a hardening material and a polymerization initiator, and does not contain water or minerals. The hardening material is a compound that hardens by polymerization reaction when irradiated with active energy rays (ultraviolet rays, electron beams, etc.), heated, etc., and examples of such materials include active energy ray-curable compounds and thermosetting compounds. Among these, materials that are liquid at room temperature are preferred.
The support forming composition is applied to a position different from that of the hydrogel 3D modeling composition. This means that the support forming composition and the hydrogel 3D modeling composition do not overlap each other, and the support forming composition and the hydrogel 3D modeling composition may be adjacent to each other.
The method for applying the support modeling composition can be the same as the method for applying the hydrogel three-dimensional modeling composition.

(4) Other steps Examples of other steps include a step of smoothing the liquid film, a peeling step, a polishing step of the model, and a cleaning step of the model. However, it is preferable to include a step of smoothing the liquid film. This is because the liquid film formed in the liquid film forming step does not necessarily have the target film thickness (layer thickness) at all positions. For example, when forming a liquid film using an inkjet method, there are cases where non-ejection or steps between dots occur, making it difficult to form a highly accurate organ model. To address these issues, methods such as mechanically smoothing (leveling) the liquid film after it is formed, mechanically scraping off the thin hydrogel film obtained by hardening the liquid film, detecting the smoothness and adjusting the amount of film formation at the dot level when laminating the next layer, etc. are possible. Note that the hardness of the hydrogel, which is the material that constitutes the organ model, is relatively soft, so a method of mechanically leveling the liquid film is preferable as a method of smoothing. Examples of mechanically smoothing methods include a method of leveling with a blade-shaped member or a roller-shaped member.

(5) Method for modeling an organ model having parts with different strength properties Next, as a more specific explanation of the method for modeling an organ model, an example of a method for modeling an organ model having parts with different strength properties will be described. In the following explanation, a detailed explanation will be given using an example in which two types of hydrogel 3D modeling compositions with different compositions are used, but the present invention is not limited to this example. Those skilled in the art will easily understand other examples (e.g., an example in which three or more types of hydrogel 3D modeling compositions are used) from this explanation.

The method for forming an organ model having areas with different strength properties includes a liquid film formation process in which a liquid film having multiple regions with different compositions is formed by applying droplets of multiple hydrogel three-dimensional modeling compositions with different compositions, and a hardening process in which the liquid film is hardened, and is characterized in that the liquid film formation process and the hardening process are repeated sequentially.
The above modeling method uses an organ modeling device that includes a container means for containing a plurality of hydrogel compositions for 3D modeling each having a different composition, a liquid film forming means for forming a liquid film having a plurality of regions of different composition by applying droplets of each of the contained hydrogel compositions for 3D modeling each having a different composition, and a hardening means for hardening the liquid film, and is characterized in that liquid film formation by the liquid film forming means and hardening by the hardening means are repeated in sequence.
Specifically, a first hydrogel 3D modeling composition and a second hydrogel 3D modeling composition having a different composition from the first hydrogel 3D modeling composition are used, and the positions and amounts of droplets of each hydrogel 3D modeling composition are controlled to form a liquid film having multiple regions with different compositions. The first hydrogel 3D modeling composition is an example of the high-strength modeling composition, and the second hydrogel 3D modeling composition is an example of the low-strength modeling composition. Next, the liquid film is hardened to form a one-layer cured film having the above-mentioned regions continuously. Then, the liquid film is formed and cured by sequentially repeating the formation and curing of the liquid film to stack the cured films, and an organ model having multiple parts with different strength properties is formed. The multiple parts with different strength properties in the organ model may be present due to the difference in strength properties within one layer of the cured film, or may be present due to the difference in strength properties between the cured films.

4. Uses of Organ Models (1) General-purpose or Individual Use The uses of organ models can be broadly divided into two categories: organ models for individual use and organ models for general-purpose use.

Organ models for individual applications include, for example, organ models used in the medical field for informed consent, preoperative simulation, and surgical training. In this case, the organ model has the shape and physical properties of the organ, including the affected area, of the individual patient. In addition, it is preferable that the organ model in this case is shaped based on the data of the individual patient, and is a model that reproduces the affected area.

The method for forming an organ model for an individual application includes a forming step of forming an organ model for an individual application using a 3D printer based on individual medical 3D data, which is medical 3D data of one living organism. When performing such a forming method including a forming step, as necessary, a step performed before the forming step may include an acquisition step of acquiring individual medical 3D data, and a generation step of generating individual forming 3D data, which is forming 3D data, based on the individual medical 3D data. Furthermore, when performing such a forming method including a forming step, as necessary, a step performed after the forming step may include an evaluation step of evaluating the accuracy of the formed organ model.
In addition, the acquisition process includes an imaging process of acquiring individual medical image data, which is medical image data, by photographing a single living organism using a medical imaging device, a measurement process of acquiring individual biological properties, which are biological properties, by performing MRE measurement on a single living organism, and a creation process of creating individual medical 3D data based on the individual medical image data and the individual biological properties.
In addition, the evaluation process is a process of evaluating the accuracy of the formed organ model based on individual biological property information indicating the individual biological properties acquired in the acquisition process and model property information indicating the model properties acquired by performing MRE measurement on the organ model formed in the modeling process.

Organ models for general-purpose use are, for example, organ models used for performance confirmation in medical device development, calibration, training, structural confirmation in educational settings, etc. In this case, the organ model has the average shape and physical properties of the target organ. In addition, it is preferable that the organ model in this case is modeled mainly based on data from healthy individuals, and is a model in which the data from one or multiple individuals is averaged.

The method for forming an organ model for general-purpose use includes a forming step of forming an organ model for general-purpose use using a 3D printer based on average medical 3D data obtained by averaging individual medical 3D data, which is medical 3D data for each of a plurality of living organisms. When performing the forming method having such a forming step, as necessary, a step performed before the forming step may include an acquisition step of acquiring a plurality of individual medical 3D data and averaging the acquired plurality of individual medical 3D data to obtain average medical 3D data, and a generation step of generating average printing 3D data, which is printing 3D data, based on the average medical 3D data. Furthermore, when performing the forming method having such a forming step, as necessary, a step performed after the forming step may include an evaluation step of evaluating the accuracy of the formed organ model.
The acquisition step includes an imaging step of acquiring a plurality of individual medical image data by imaging a plurality of living bodies using a medical imaging device, a measurement step of acquiring a plurality of individual biological properties by MRE measurement of a plurality of living bodies, a creation step of creating a plurality of individual medical 3D data based on the individual medical image data and the individual biological properties for each living body, and an averaging step of averaging the plurality of individual medical 3D data to obtain average medical 3D data. The average medical 3D data includes average voxels, average image density information, and average biological property information obtained by averaging the individual voxels, individual image density information, and individual biological property information included in the plurality of individual medical 3D data. The averaging method can be any known method.
In addition, the evaluation process is a process of evaluating the accuracy of the formed organ model based on average biological property information indicating the average biological properties acquired in the acquisition process and model property information indicating the model properties acquired by performing MRE measurement of the organ model formed in the formation process.

(2) Training Use The organ model is preferably used for surgery training. Since the organ model of the present invention reproduces the shape and physical properties of a living body, it is useful for manual training alone. However, for training of the entire surgery (training for understanding the procedure, approaching the affected area, etc.), it is preferable to use a training system having the organ model of the present invention and a housing that incorporates the organ model. There is no particular limitation on the housing, but its form and shape can be appropriately selected depending on the training purpose. For example, for endoscopic training, it is preferable that the organ model is not visible from the outside, so the housing is made of a material that does not have or reduces the visibility of the built-in organ, and the organ model is placed inside it. In this case, it is preferable that the shape of the housing is a structure that mimics a living body (such as the structure and skeleton of the human body), as this is effective. Such housings are commercially available in a variety of shapes, from simple ones such as laparoscopic training boxes to ones with complex shapes with ribs and the like arranged inside, and they may be used appropriately.

(3) Use as a human organ model When the shaped object is used as a human organ model, the water content in the material such as hydrogel forming the shaped object is preferably 70% by mass or more and 85% by mass or less with respect to the total amount of the organ model. By having a water content of 70% by mass or more and 85% by mass or less, the human organ model can have a water content equivalent to that of an actual human organ that is the subject of the human organ model, and can be used preferably. Specifically, the water content is preferably about 80% by mass for a human heart model, about 83% by mass for a human kidney model, and about 75% by mass for a human brain or intestine model. Therefore, the water content in the organ model is more preferably 75% by mass or more and 83% by mass or less with respect to the total amount of the organ model.

The following describes examples of the present invention, but the present invention is not limited to these examples.

<Preparation of Hydrogel 3D Modeling Composition 1>
First, degassing was performed on ion-exchanged water under reduced pressure for 30 minutes to prepare pure water, and 67.0 parts by mass of synthetic hectorite (Laponite RD, manufactured by BYK Corporation), which is a water-swellable clay mineral, was gradually added to 580.0 parts by mass of this pure water while stirring, and further stirred to prepare a mixed liquid. Next, 5.0 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was added to the mixed liquid as a dispersant for synthetic hectorite to obtain a dispersion liquid.
Next, 262.0 parts by mass of dimethylacrylamide (DMAA, manufactured by Tokyo Chemical Industry Co., Ltd.) from which polymerization inhibitors had been removed by passing through an activated alumina column was added as a monomer to the obtained dispersion. In addition, 2.4 parts by mass of N,N'-methylenebisacrylamide (MBAA, manufactured by Tokyo Chemical Industry Co., Ltd.) and 8.0 parts by mass of polyethylene glycol diacrylate (A-400, manufactured by Shin-Nakamura Chemical Co., Ltd.) were added as crosslinking agents. Furthermore, 300.0 parts by mass of glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) were added as a drying inhibitor and mixed.
Next, 6.7 parts by mass of N,N,N',N'-tetramethylethylenediamine (TEMED, manufactured by Tokyo Chemical Industry Co., Ltd.) was added as a polymerization accelerator, and 5.3 parts by mass of Emulgen LS-106 (manufactured by Kao Corporation) was added as a surfactant and mixed.
Next, while cooling in an ice bath, 12.3 parts by mass of a 4% by mass solution of a photopolymerization initiator (Irgacure 184, manufactured by BASF) in methanol was added, stirred and mixed, and then degassed under reduced pressure for 20 minutes. Then, filtration was performed to remove impurities, and a homogeneous hydrogel 3D modeling composition 1 was obtained.

<Preparation of Hydrogel 3D Modeling Composition 2>
First, degassing of ion-exchanged water under reduced pressure for 30 minutes was performed to prepare pure water, and 67.0 parts by mass of synthetic hectorite (Laponite RD, manufactured by BYK Corporation), which is a water-swellable clay mineral, was gradually added to 580.0 parts by mass of this pure water while stirring, and further stirring was performed to prepare a mixed liquid. Next, 5.0 parts by mass of etidronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was added to the mixed liquid as a dispersant for synthetic hectorite to obtain a dispersion liquid.
Next, 262.0 parts by mass of dimethylacrylamide (DMAA, manufactured by Tokyo Chemical Industry Co., Ltd.) from which polymerization inhibitors had been removed by passing through an activated alumina column was added as a monomer to the obtained dispersion. In addition, 0.6 parts by mass of N,N'-methylenebisacrylamide (MBAA, manufactured by Tokyo Chemical Industry Co., Ltd.) and 2.0 parts by mass of polyethylene glycol diacrylate (A-400, manufactured by Shin-Nakamura Chemical Co., Ltd.) were added as crosslinking agents. Furthermore, 300.0 parts by mass of glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) were added as a drying inhibitor and mixed.
Next, 6.7 parts by mass of N,N,N',N'-tetramethylethylenediamine (TEMED, manufactured by Tokyo Chemical Industry Co., Ltd.) was added as a polymerization accelerator, and 5.3 parts by mass of Emulgen LS-106 (manufactured by Kao Corporation) was added as a surfactant and mixed.
Next, while cooling in an ice bath, 12.3 parts by mass of a 4% by mass solution of a photopolymerization initiator (Irgacure 184, manufactured by BASF) in methanol was added, stirred and mixed, and then degassed under reduced pressure for 20 minutes. Then, filtration was performed to remove impurities, and a homogeneous hydrogel 3D modeling composition 2 was obtained.

[Evaluation of Young's Modulus]
First, hydrogel samples 1 to 4 were prepared using hydrogel 3D modeling composition 1 and hydrogel 3D modeling composition 2. Specifically, a container measuring 31 mm x 31 mm (10 mm thick) was prepared, and the inside was filled with a mixture of hydrogel 3D modeling composition 1 and hydrogel 3D modeling composition 2 in the mass ratio shown in Table 1 below, and cured using an ultraviolet irradiator (USHIO INC., SPOT CURE SP5-250DB) to prepare samples 1 to 4. The irradiation conditions were wavelength: 365 nm, and cumulative exposure: 350 mJ/ ^cm2 .
Next, the compressive strength of each sample was measured. The compressive strength was measured using an Autograph AG-1 (manufactured by Shimadzu Corporation) with a load cell of 1 MPa. The results are shown in Figure 11. The Young's modulus was calculated from the slope of the graph in Figure 11 and is shown in Table 1 below.
As shown in FIG. 11 and Table 1, the physical property (Young's modulus) of the hydrogel can be controlled by the mass ratio of the hydrogel 3D modeling composition 1 and the hydrogel 3D modeling composition 2.

[Evaluation of Viscoelasticity]
First, hydrogel samples 5 to 8 were prepared using hydrogel 3D modeling composition 1 and hydrogel 3D modeling composition 2. Specifically, a container shaped like a dumbbell No. 3 (JIS K 7139) was prepared, and the inside was filled with a mixture of hydrogel 3D modeling composition 1 and hydrogel 3D modeling composition 2 in the mass ratio shown in Table 2 below, and cured using an ultraviolet irradiator (USHIO INC., SPOT CURE SP5-250DB) to prepare samples 5 to 8. The irradiation conditions were wavelength: 365 nm, and cumulative exposure: 350 mJ/ ^cm2 .
Next, a tensile test was carried out on each sample. The tensile test was carried out using an Autograph AG-1 (manufactured by Shimadzu Corporation) and the stress was measured with a force gauge. The results are shown in FIG.
As shown in FIG. 12, the physical properties (viscoelasticity) of the hydrogel can be controlled by the mass ratio of the hydrogel 3D modeling composition 1 and the hydrogel 3D modeling composition 2.

<Acquisition of medical 3D data 1>
Using an MRI device capable of MRE measurement, medical 3D data 1 including the liver portion of a patient suffering from fatty liver was obtained. The medical 3D data 1 was created based on medical image data obtained by photographing the patient with the MRI device and biological properties obtained by MRE measurement of the patient. Specifically, the medical 3D data 1 included a plurality of voxels created based on the medical image data, image density information indicating the image density (MRI signal value) in the medical image data assigned to each voxel, and biological property information indicating the biological property (viscoelasticity) assigned to each voxel.
In addition, the biological properties (viscoelasticity) of the liver parts obtained by MRE measurement were within the range between the viscoelasticity of the cured product of Hydrogel 3D modeling composition 1 and the viscoelasticity of the cured product of Hydrogel 3D modeling composition 2 in all parts.

<Generation of 3D modeling data 1>
The medical 3D data 1 was divided into voxel regions to obtain regional medical 3D data 1 showing the liver. Next, the regional medical 3D data 1 was converted into an FAV format to generate 3D data for printing 1 in the FAV format.

<Example of liver model 1>
The hydrogel three-dimensional modeling composition 1 and the hydrogel three-dimensional modeling composition 2 were each placed in a 3D printer that uses a material jetting method and can express gradations of strength properties as shown in Fig. 9, and were filled into the inkjet head of the 3D printer. Next, the 3D modeling data 1 was input into the 3D printer, and a liver model 1 having a distribution of strength properties corresponding to the distribution of biological properties was modeled based on the 3D modeling data 1. Specifically, each modeling composition was sprayed from the inkjet head, and the formation of a liquid film and hardening were sequentially repeated to model the model.

<Acquisition of model 3D data 1>
An MRI device capable of MRE measurement was used to obtain model 3D data 1 of a liver model 1. The model 3D data 1 was created based on model image data obtained by photographing the liver model 1 with the MRI device and model properties obtained by MRE measurement of the liver model 1. Specifically, the model 3D data 1 included a plurality of voxels created based on the model image data, image density information indicating image density (MRI signal value) in the model image data assigned to each voxel, and model property information indicating model properties (viscoelasticity) assigned to each voxel.

[Accuracy evaluation of liver model 1]
Based on the biophysical property information included in the liver portion of the acquired medical 3D data 1 and the model physical property information included in the model 3D data 1 of the liver model 1, the accuracy of the liver portion of the liver model 1 was evaluated. Specifically, the difference in the model physical properties of the liver portion and the corresponding portion of the liver model 1 (average of 10 points in each portion) with respect to the biophysical properties was calculated to be 3%.

<Acquisition of medical 3D data 2'>
Using an MRI device capable of MRE measurement, medical 3D data 2 including liver parts of three healthy subjects was obtained. The medical 3D data 2 was created based on medical image data obtained by photographing the healthy subjects with the MRI device and biological properties obtained by MRE measurement of the healthy subjects. Specifically, the medical 3D data 2 included a plurality of voxels created based on the medical image data, image density information indicating image density (MRI signal value) in the medical image data assigned to each voxel, and biological property information indicating biological properties (viscoelasticity) assigned to each voxel.
Next, the medical 3D data 2 of the three healthy subjects was averaged to create medical 3D data 2' for an average healthy subject.
Furthermore, the biological properties (viscoelasticity) in the medical 3D data 2' of an average healthy individual were within the range of the viscoelasticity of the cured product of Hydrogel 3D modeling composition 1 and the viscoelasticity of the cured product of Hydrogel 3D modeling composition 2 at all parts of the body.

<Generation of 3D Modeling Data 2'>
The medical 3D data 2' of an average healthy subject was divided into voxel regions to obtain regional medical 3D data 2' showing the liver. Next, the regional medical 3D data 2' was converted into an FAV format to generate 3D data for printing 2' in the FAV format.

<Example of liver model 2'>
The hydrogel three-dimensional modeling composition 1 and the hydrogel three-dimensional modeling composition 2 were respectively accommodated in a 3D printer that uses a material jetting method and can express gradations of strength properties as shown in Fig. 9, and were filled into the inkjet head of the 3D printer. Next, 3D modeling data 2' was input to the 3D printer, and a liver model 2' having a distribution of strength properties corresponding to the distribution of biological properties was modeled based on the 3D modeling data 2'. Specifically, each modeling composition was sprayed from the inkjet head, and the liquid film formation and hardening were sequentially repeated to model the model.

<Acquisition of model 3D data 2'>
Using an MRI device capable of MRE measurement, model 3D data 2' of a liver model 2' was obtained. The model 3D data 2' was created based on model image data acquired by photographing the liver model 2' with an MRI device and model properties acquired by MRE measurement of the liver model 2'. Specifically, the model 3D data 2' included a plurality of voxels created based on the model image data, image density information indicating image density (MRI signal value) in the model image data assigned to each voxel, and model property information indicating model properties (viscoelasticity) assigned to each voxel.

[Accuracy evaluation of liver model 2']
Based on the biophysical property information contained in the liver portion of the medical 3D data 2' created by averaging and the model physical property information contained in the model 3D data 2' of the liver model 2', the accuracy of the averaged liver portion of the liver model 2' was evaluated. Specifically, the difference in the model physical properties of the averaged liver portion and the corresponding portion of the liver model 2' (average of 10 points in each portion) with respect to the biophysical properties was calculated to be 4%.

[Texture evaluation by a doctor of liver model 1 and liver model 2′]
Five doctors palpated the liver model 1 and the liver model 2' and compared the texture with that of an actual liver. As a result, they concluded that both liver models had a very high reproducibility.

<Preparation of training system>
A case was made that imitated the shape of the abdomen of the human body, including structures such as ribs, and a liver model 1 and structures imitating other organs were placed inside the case to create a training system 1. A training system 2' was also created by using a liver model 2' instead of the liver model 1. Holes were also made in some of these cases to allow the insertion of a laparoscope, a tube, etc., and instruments capable of endoscopic surgery were set in the case.
Next, three doctors performed the same operation as for taking tissue pieces of the liver using a biopsy tube on the liver model 1 and liver model 2' of these training systems, and evaluated the tactile sensations of the liver model 1 and liver model 2'. As a result, they felt a clear difference between the liver model 1 and liver model 2', and concluded that the tactile sensations were close to the real one.

REFERENCE SIGNS LIST 10 Modeling device 11 Hydrogel three-dimensional modeling composition jetting head unit 12 Support body modeling composition jetting head unit 13 Ultraviolet irradiator 14 Modeling body support substrate 15 Stage 16 Smoothing member 17 Organ model (hydrogel)
18 Support (support material)

Japanese Patent Application Publication No. 5-11689 JP 2019-153180 A

Claims (8)

An organ model which is shaped based on biological property information indicating biological properties obtained by MRE measurement of a living body, and has a distribution of strength properties corresponding to the distribution of the biological properties,
The organ model contains a hydrogel as a material constituting the organ model,
The difference between the model properties obtained by MRE measurement of the organ model and the biological properties is within 5%.
An organ model characterized by: A model is formed based on medical 3D data including the biological property information,
The organ model according to claim 1 , wherein the medical 3D data is created based on medical image data acquired by photographing the living body with a medical image photographing device and on the physical properties of the living body. The organ model according to claim 2, wherein the medical 3D data includes a plurality of voxels created based on the medical image data, image density information indicating image density in the medical image data assigned to each voxel, and the biological property information assigned to each voxel. The organ model according to any one of claims 1 to 3, wherein the biological property information is individual biological property information indicating individual biological properties obtained by MRE measurement of a single living organism. The organ model according to any one of claims 1 to 3, wherein the biophysical property information is average biophysical property information indicating an average biophysical property obtained by averaging multiple individual biophysical properties obtained by performing MRE measurement on multiple living organisms. The organ model according to claim 1 , wherein the hydrogel contains water, a polymer, and a mineral. A training system comprising: an organ model according to any one of claims 1 to 6 ; and a housing that houses the organ model. The training system according to claim 7 , wherein the housing is a replica that mimics at least a part of the structure of the living body.