Multimodal monomaterial phantom, and use

Abstract

The invention relates to a multimodal, monomaterial phantom comprising surrogates for different tissue types, wherein the phantom is formed from at least two surrogates, the surrogates are arranged separately so as to be in contact with one another in an anatomically appropriate manner, and the surrogates are designed and / or arranged to replicate the same and / or different tissue types, characterized in that the surrogates can be manufactured from the same material system, wherein the material system comprises a hydrogel, a diversity and / or an adaptability of the surrogates formed is produced or formed by way of varying formulations within the material system and by controlling the polymerization of the hydrogel in the cross-linking process, and the CT attenuation and shear wave velocity within the material system are adjustable independently of one another, wherein the surrogates formed are distinguishable from one another using non-invasive medical diagnostic and imaging methods comprising ultrasound imaging and x-ray CT, replicate the mechanical properties of real tissue as well as possible, are cuttable and are in malleable and shape-retaining form. The invention also relates to a use.

Description

[0001] MULTIMODAL, MONOMATERIAL PHANTOM AND USE

[0002] The invention relates to a multimodal, monomaterial phantom comprising surrogates for different tissue types, wherein the phantom is formed from at least two surrogates, the surrogates are arranged separately, anatomically correspondingly in contact with each other and the surrogates are formed and / or arranged to simulate the same and / or different tissue types.

[0003] Furthermore, the invention relates to a use of a multimodal, monomaterial phantom.

[0004] In particular, the subject matter of the invention and its use is a medical, multimodal, monomaterial phantom comprising surrogates for different tissue types. "Medical" within the meaning of the disclosure is to be interpreted in such a way that it is a phantom capable of simulating medical conditions.

[0005] Multimodal, within the meaning of this invention, is understood as being usable in a variety of ways. In particular, the phantom can be classified as being suitable for examination in multiple ways, particularly in a meaningful way. Furthermore, multimodality can refer to the various measurement methods that can be applied to it, for example, including surgical training. Monomaterial, within the meaning of this invention, is understood as being made from the same material system.

[0006] Today, phantoms are available for almost all aspects of the examination chain leading to surgery, including computed tomography (CT), ultrasound (US) imaging, and mechanical surgical technique.

[0007] Current phantoms are not multimodal, meaning they are tailored to only one of these techniques. They are not suitable for combining multiple techniques because they are tailored to only one important aspect.

[0008] Typically, phantoms mimic soft tissue by being made from elastomeric materials. Silicones are most commonly used for ultrasound phantoms, but they exhibit higher X-ray attenuation for CT scans than normal tissue. Silicones can be adjusted in their elasticity by altering their cross-linking. However, their CT attenuation depends on density and atomic mass and cannot reach the level of normal soft tissue in the body. Therefore, they cannot be used independently for both measurements. Secondly, these phantoms are not suitable for later surgical training, as they are difficult to cut and must be expensively manufactured elsewhere. Since the phantom is destroyed after the initial surgical training, the reusability of the silicone phantom for its originally intended purpose is limited.From both an economic and ecological perspective, these already destroyed models must be reused, which has a significant negative impact on surgical training. In this regard, such phantoms may even exhibit certain abnormalities, essentially diseases.

[0009] In particular, many difficult surgeries such as tumor resection of vital organs require precise, multimodal imaging to localize the affected tissue. Precise tumor localization and the identification of risks, such as proximity to an artery, are crucial for a positive surgical outcome. However, despite precise imaging, the surgeon's work is severely hampered by the lack of correspondence between the images and the real-world perspective. A tumor still looks like the surrounding tissue and is difficult to distinguish by simple visual inspection. This is especially true for laparoscopic, robotic-assisted surgery, where there is no haptic feedback. The problem is that surgeons typically only have one chance, which is time-critical in itself.Appropriate surgical preparation through training and trial tests prior to the procedure can facilitate the process and dramatically increase the chances of a positive surgical outcome. Phantoms are necessary for simulating the pathological details.

[0010] The state of the art provides numerous examples of so-called “tissue-mimicking materials” (TMM) that are used in medical phantoms.

[0011] For example, US Pat. No. 6,635,486 B2 presents a phantom material consisting of an open-cell polyurethane mesh, with the cells filled with vegetable oil and embedded in a gel matrix. Optionally, copper salts and glass beads can be added. The material is formed into simple geometric shapes in a box and serves as a test body for multimodal medical imaging. Among other things, ultrasound properties and magnetic resonance measurement data are replicated from living tissue. Furthermore, X-ray opacity and scattering are also adjustable. The described phantom is not intended for targeted destruction, but rather as a long-term stable test body. Accordingly, its production may be somewhat more expensive.

[0012] US Pat. No. 10,726,742 B2 discloses a 3D-printable metamaterial designed to establish an anisotropy of physical parameters, particularly the elastic modulus. For this purpose, a second, structured material is embedded into a first material, which is shaped like an organ. Each structure of the second material has a predetermined shape, so that the phantom can offer greater resistance to deformation along a predetermined direction, for example, than perpendicular to it. The printed materials here are printable elastic polymers.

[0013] US Pat. No. 10,755,600 B2 discloses a layered phantom material comprising two or more layers, essentially made of silicone rubber and oil. The purpose here is to model a patient surface into which a medical procedure is to be performed, such as a subcutaneous injection.

[0014] US 2021 / 0373108 A1 discloses a phantom material suitable for calibrating ultrasound and magnetic resonance imaging. Possible ingredients include sodium alginate as a gelling agent and coconut oil as a vegetable fat. Significant amounts of protein powder are also added to establish the dielectric properties for MRI compatibility.

[0015] From the work of Aoyagi, Minoru and Hiraguri, Tomomi, “Ultrasound Phantom Using Sodium Alginate as a Gelling Agent”, J Ultrasound Med 36, 11 , pp. 2345-2353, https: / / doi.org / 10.1002 / jum.14252, a phantom material made of sodium alginate is known whose degree of polymerization or cross-linking can be varied in order to adapt the speed of sound and ultrasound attenuation to tissue conditions. It is emphasized that the mechanical properties of the alginate correspond well to those of human tissue, so that soft tissue surrogates can be produced without expensive chemicals and without special equipment. However, it proves difficult to simulate actual anatomical structures with the proposed phantom. The phantom can be used to accurately replicate the ultrasound properties of human tissue.

[0016] US 2019 / 0 130 791 A1 discloses a method for evaluating the performance of a human or a robot performing a medical procedure using a phantom resembling a human or animal organ or tissue, and an evaluation instrument comprising such a phantom.

[0017] BOOTSMA, K., et al.: Materials Used as Tissue Phantoms in Medical Simulation. In: Springer Int. Publ., 2016 (Studies in mechanobiology, tissue engineering and biomaterials). pp. 1-48 discloses simulation technology that can be used to train the performance of various clinical procedures without endangering patients. There is a need for more realistic tissue-analog materials that take into account the biomechanical responses of tissue in different situations. An overview of the materials used in medical simulation is provided here. HERNÄNDEZ-GONZÄLEZ, AC, Tellez-Jurado, L, Rodriguez-Lorenzo, LM: Alginate hydrogels for bone tissue engineering, from injectables to bioprinting: A review. Carbohydrate polymers, 2020, 229th vol., pp. 1-22. doi: 10.1016 / j.carbpol.2019.115514 discloses injectable alginate hydrogels and alginate composites for applications in bone tissue regeneration and the properties of alginates that have made them useful for medical applications.

[0018] DABBAGH, A., et al.: Tissue-mimicking gel phantoms for thermal therapy studies. In: Ultrasonic imaging, 2014, 36th vol., no. 4, pp. 291–316. doi: 10.1177 / 01617346145263 reveals that the tissue-mimicking gel phantoms currently available for routine biomedical applications may not be suitable for high-temperature experiments or the calibration of thermal modalities, making the development and fabrication of custom thermal phantoms with tailored properties necessary for thermal therapy studies. Various materials and techniques that may be relevant for the fabrication of phantoms in the gel state are reviewed here.

[0019] MIRDAMADI, E., et al.: FRESH 3D bioprinting a full-size model of the human heart. In: ACS Biomaterials Science & Engineering, 2020, Vol. 6, No. 11, pp. 6453-6459. doi: 10.1021 / acsbiomaterials.0c01133. In: ACS Biomaterials Science & Engineering, 2020, Vol. 6, No. 11, pp. 6453-6459. doi: 10.1021 / acsbiomaterials.0c01133, the paper reveals that there are advances in embedded three-dimensional (3D) bioprinting that expand the design scope for the production of geometrically complex tissues using hydrogels whose mechanical properties are comparable to those of native tissues and tissues and organs in the human body. With FRESH-printed alginate, high print fidelity can be achieved on a cost-effective printer platform, and mechanically tunable and sewable models can also be produced.

[0020] AOYAGI, M.: Sodium alginate ultrasound phantom for medical education. In: Ultrasonic Imaging, 2021, Vol. 43, No. 5, pp. 253–261. doi: 10.1177 / 01617346211018643 discloses that ultrasound phantoms used for the training of medical students should not only mimic the ultrasound properties of human soft tissue, but should also be inexpensive and easy to manufacture. For this purpose, an ultrasound phantom made of calcium alginate hydrogel is proposed, with the addition of ethanol reducing speckle patterns.

[0021] DE 102016 217 316 B3 provides a training model that represents at least the external anatomical shape of the human or animal body. The training model is used for practicing minimally invasive percutaneous image-guided intervention techniques. The material and shape of the training model and its components are selected to be suitable for ultrasound, MRI, and CT examination, as well as for puncture and palpation.

[0022] Already commercially available phantoms include the PetVitalShop phantom, which was specifically developed for computed tomography and cannot be cut and used for surgical training. It is very expensive. CT phantoms from other companies have the same disadvantages and limitations.

[0023] The common training phantoms (e.g. from Erler-Zimmer) are usually phantoms for conducting basic training and these phantoms cannot be used for CT measurements.

[0024] With the HumanX surgical training phantom, the various organs or tissues can be cut into. However, they are differentiated or identified by color, and the structure is exposed to the surgeon, which is not the case in reality. The various organs cannot be identified by CT or other measurements.

[0025] The main problems with the state of the art are that current phantoms are not multimodal, meaning they are designed for only one technique—computed tomography (CT), ultrasound (US), or mechanical surgical technique. They are not suitable for combining multiple procedures because they are tailored to only one important aspect. Typically, phantoms mimic soft tissues using elastomeric materials. Silicones are most commonly used for ultrasound phantoms, but they exhibit higher X-ray attenuation for CT scans than normal tissue. Silicones can be adjusted in their elasticity by altering their cross-linking. However, their CT attenuation depends on density and atomic mass and cannot reach the level of normal soft tissue in the body. Therefore, they cannot be used independently for both measurements.Second, these phantoms are unsuitable for subsequent surgical training, as they are difficult to tailor and require expensive manufacturing elsewhere. Since the phantom is destroyed during initial surgical training, the reusability of the silicone phantom for its originally intended purpose is limited. However, from both an economic and environmental perspective, these already destroyed models must be reused, which has a significant negative impact on surgical training.

[0026] The present invention is based on the object of providing a phantom, particularly for the medical field, that is multimodally applicable and, at the same time, as simple and cost-effective to manufacture as possible. This object is achieved with a multimodal, monomaterial phantom according to the main claim.

[0027] A multimodal, monomaterial phantom has surrogates for different tissue types, whereby

[0028] - the phantom is formed from at least two surrogates;

[0029] - the surrogates are arranged separately, anatomically in contact with each other;

[0030] - the surrogates are designed and / or arranged to simulate the same and / or different tissue types; wherein the phantom and / or the surrogates consist of exactly one material system during or during manufacture, wherein the material system comprises a material composition of at least:

[0031] - Sodium alginate and

[0032] - Glucono-delta-lactone (GDL) or an acid-forming compound by hydrolysis or lactones and

[0033] - Calcium carbonate and

[0034] - Fat and

[0035] - water in the form of a hydrogel, and the material system is available in at least two different variations of the

[0036] Material system composition is formed within the phantom and / or surrogate.

[0037] A very inexpensive and easy-to-manufacture phantom can be created here.

[0038] In particular, a monomaterial system is provided here which nevertheless ensures adjustability, so that the requirements for a phantom are fully met here.

[0039] Also, no cavities form between the individual areas of the phantom, which can arise due to poor bonding with different materials. Glucono-delta-lactone (GDL), the acid-forming compound formed by hydrolysis, or the lactones are intended to retard the reaction of calcium carbonate. Calcium carbonate is itself insoluble in water and is decomposed by the acid formed by hydrolysis. The formation of the acid depends on the type of acid-forming compound. Lactones undergo acid hydrolysis and thus ring opening, which reforms the carboxylic acid. This can then attack the calcium carbonate, dissolve it, and thus provide the calcium ions necessary for cross-linking.

[0040] The composition of the materials used in the phantoms is crucial, as these substances naturally undergo transformation during the reaction. The phantoms are designed in such a way that the calcium carbonate ultimately reacts with GDL / lactones, so that these are essentially no longer present in this form.

[0041] Instead of calcium carbonate, one could therefore also speak of calcium ions.

[0042] The invention can also work with a different calcium source and a different acidity regulator, whereby the acidity regulator only needs to decompose over time and provide a sufficiently strong acid to dissolve the calcium source.

[0043] Calcium carbonate, for example, is particularly suitable because it allows the CO2 to escape from the phantom, leaving no unnecessary residue of the compound behind. The GDL forms gluconic acid through hydrolysis in water, which then reacts with the calcium carbonate to form water-soluble calcium gluconate, so that these two substances will no longer be present in the final phantom. The calcium ions react with the sodium alginate and displace the sodium ions, which then form sodium gluconate, which is also water-soluble.

[0044] A further preferred embodiment is provided by varying recipes and / or proportions within the material composition of the material system and by controlling the polymerization of the hydrogel in the crosslinking process, whereby

[0045] - a diversity and / or adaptability of the trained surrogates is brought about or developed;

[0046] - within the material system, the CT attenuation and the

[0047] Shear wave speed can be adjusted independently of each other; the surrogates formed

[0048] - can be distinguished from one another using non-invasive medical diagnostic and imaging techniques, including ultrasound imaging and X-ray CT;

[0049] - simulate the mechanical properties of real tissues as closely as possible; - are cuttable;

[0050] - are malleable and retain their shape.

[0051] Furthermore, the material system may contain dyes and / or anti-mould agents.

[0052] In particular and particularly preferably, the material system composition has variations in the range of (weight-%)

[0053] - 0.1 to 20 percent sodium alginate

[0054] - 0.01 to 20 percent calcium carbonate

[0055] - 0.01 to 20 percent glucono-delta-lactone (GDL)

[0056] - 0.1 to 50 percent fat

[0057] - 0 to 10 percent surfactant

[0058] - 0 to 5 percent anti-mold agent

[0059] - 0 to 5 percent dye and

[0060] - Water, total 100%.

[0061] The medical phantoms presented here can mimic various aspects of medical procedures such as computed tomography (CT) and ultrasound (US), as well as surgical interventions. Unlike current state-of-the-art phantoms, the phantoms presented here are not limited to a specific imaging modality or procedure, making them versatile, as the CT, US, and mechanical properties of the existing material system can be adjusted independently of each other.

[0062] In contrast to the phantoms known in the prior art, which are usually made of synthetic polymers that are expensive and difficult to manufacture both in terms of material and production, and are also harmful to the environment, a simple and high-performance material system with independently adjustable CT, US and mechanical properties is disclosed here.

[0063] The system disclosed herein is particularly advantageous for surgical practice because the materials are inexpensive and the phantoms are easy to manufacture, making realistic and versatile phantoms available to everyone to improve patient care.

[0064] In particular, an environmentally friendly hydrogel composite made of sodium alginate and vegetable fat was developed for the production of multipurpose medical phantoms. Independent adjustment of CT, US, and mechanical properties works reliably, and the properties can be precisely determined by the respective formulation and variation of the individual components of the material system and their composition.

[0065] Another possible configuration is: a multimodal, monomaterial phantom has surrogates for different tissue types, whereby

[0066] - the phantom is formed from at least two surrogates;

[0067] - the surrogates are arranged separately, anatomically in contact with each other;

[0068] - the surrogates are designed and / or arranged to simulate the same and / or different tissue types; characterized in that

[0069] - the surrogates can be produced from the same material system, whereby the

[0070] Material system comprises a hydrogel;

[0071] - by varying formulations within the material system and by controlling the polymerization of the hydrogel in the cross-linking process

[0072] - a diversity and / or adaptability of the trained surrogates is brought about or developed;

[0073] - within the material system, the CT attenuation and the

[0074] Shear wave speed can be adjusted independently of each other; the surrogates formed

[0075] - can be distinguished from one another using non-invasive medical diagnostic and imaging techniques, including ultrasound imaging and X-ray CT;

[0076] - simulate the mechanical properties of real tissues as closely as possible;

[0077] - can be cut;

[0078] - are malleable and retain their shape.

[0079] It should be noted at this point that the diversity and / or adaptability is to be understood in the sense of the properties according to the invention, whereby, for example, equipping the material with higher cell compatibility properties would not be seen in the sense of the invention.

[0080] In particular, the material system may contain sodium alginate.

[0081] The material system may also contain fat and / or vegetable fat.

[0082] The material system can comprise the components sodium alginate, fat, calcium carbonate, water, and glucono-delta-lactone (GDL). Preferably, the material system can comprise 0.1 to 20 percent sodium alginate and 0.1 to 50 percent fat.

[0083] Furthermore, the material system may contain dyes and / or anti-mould agents.

[0084] In a preferred embodiment, the material system may comprise 0.1 to 20 percent sodium alginate, 0.01 to 20 percent calcium carbonate, 0.01 to 20 percent glucono-delta-lactone (GDL), 0.1 to 50 percent fat, 0 to 10 percent surfactant, 0 to 5 percent anti-mold agent, 0 to 5 percent dye, and water.

[0085] In addition, the material system is preferably easily disposable or can be disposed of as normal organic waste. Furthermore, the material system can be vegan and / or food-safe.

[0086] The multimodal, monomaterial phantom can be used in particular in the surgical and / or radiological training and / or further education of specialist personnel, in the preparation of surgical procedures and in the development and / or calibration of devices for robot-assisted surgery.

[0087] In a preferred embodiment, the multimodal, monomaterial phantom can be used to model individual organs and / or tissues, organ arrangements and / or tissue arrangements, organ arrangements and / or tissue arrangements including defined pathologies and / or phantom bodies comprising organ arrangements and tissue arrangements.

[0088] The phantom according to the invention is usable for surgical procedures, which means that the phantom will be damaged and eventually destroyed during use. The phantom is composed of separate and anatomically arranged soft tissue surrogates. These surrogates are cuttable and replicate the mechanical properties and radiopacity of real tissue as closely as possible.

[0089] Furthermore, they can be produced relatively quickly and inexpensively and, after their final use, should be able to be disposed of as much as possible like ordinary organic waste (e.g. slaughterhouse waste).

[0090] Sodium alginate-based surrogates can be diversified into a wide range of soft tissues by adding fats and controlling the polymerization during the cross-linking process. This allows not only individual organs but also more complex organ arrangements, including specific pathologies—especially tumors—to be modeled from the same material system. This not only simplifies the overall manufacturing process of a phantom, but also approximates real anatomy and allows for later disposal of the remains largely without dissection.

[0091] Thus, the phantom according to the invention makes it possible to provide phantom bodies in which only the bones are still made of 3D-printed plastic, and these can also be replaced by the phantom material depending on the phantom material.

[0092] Of great importance for the use of multimodal, monomaterial phantoms is that they generate realistic measurement values ​​during treatment with non-invasive medical diagnostic and imaging procedures, particularly in ultrasound diagnostics and X-ray CT imaging. These techniques are also expected to be used in robot-assisted surgery in the future, and new devices for this purpose must initially be tested and calibrated on phantoms – at least during development. Special phantoms, such as the phantom according to the invention, are advantageous in this regard. Pathologies that are designed for the robot to detect, for example, cancerous tumors or tissue pockets with hemorrhages, are particularly useful.

[0093] For this reason, the traditional measurements of X-ray attenuation (measured in Hounsfield Units, HU) and shear wave velocity (SWV, in m / s) are particularly important, with the latter being a measure of tissue elasticity. These values ​​can be varied independently of each other within physiologically reasonable intervals through the material formulation.

[0094] In contacting surrogates, even weak contrasts (HU ± 2, SWV ± 0.2 m / s) can be established at the interface, making the interface just detectable with imaging. Stronger contrasts can be generated without difficulty.

[0095] The multimodal, monomaterial phantom provides a material system that allows the independent adjustment of mechanical properties and CT attenuation.

[0096] A material system can preferably consist of 0.1-20% sodium alginate, 0.01-20% CaCO3, 0.01-20% glucono-delta-lactone (GDL), 0.1-50% (e.g., vegetable / coconut) fat, 0-10% surfactant, 0-5% anti-mold agent, 0-5% dye, and water. Stiffness can be adjusted, for example, through varying cross-linking within the material system, which does not lead to a change in CT contrast. The addition of fat can reduce CT contrast and does not lead to an irreversible change in stiffness.

[0097] By appropriately combining the cross-linking density of the hydrogel (e.g., sodium alginate) and the concentration ratio between the hydrogel and a fat component, the CT contrast and mechanical properties can be tailored to the desired values.

[0098] In addition to CT contrast and mechanical properties, shear wave elastography has become a rapidly developing ultrasound imaging technique for pre- and intra-operative lesion identification. Therefore, the shear wave velocity within the developed composite system is also taken into account. This velocity is directly linked to the shear elastic modulus and tissue density.

[0099] The material system is moldable and true to shape, allowing it to be used to create organ-like shapes and / or body parts, for example. Several versions of the material system with different compositions are molded into a phantom body (i.e., a dummy), which can then be used for CT and surgical training. The phantom body replicates physiological and pathological features useful for teaching surgery and CT measurements.

[0100] The multimodal, monomaterial phantom provides the most realistic training conditions possible. For example, a CT image can be measured. A tumor located in the phantom can be identified based on the different CT attenuation. Using the CT image, the surgeon can thus be trained to locate the tumor's position and remove it correctly.

[0101] The components of the developed material system, for example, using a combination of sodium alginate and fat as base materials, are food-safe, degradable, and environmentally friendly. More importantly, the components are inexpensive and easily obtainable, even for developing countries. The material system is simple and easy to manufacture as required.

[0102] For these reasons mentioned above, the provision of the multimodal, monomaterial phantom can ultimately lead to better patient care.

[0103] The invention is described below with reference to the enclosed figures in the figure description, which are intended to explain the invention and are not necessarily to be considered limiting:

[0104] They show:

[0105] Fig. 1 shows a tabular representation of exemplary recipe compositions for producing a phantom according to the invention comprising alginate and fat; Fig. 2 shows a graphic representation of the test results regarding elastic modulus and Hounsfield scale for phantom material produced according to two exemplary recipes 1 and 2 with a composition according to Fig. 1;

[0106] Fig. 3 is a graphical representation of the test results concerning elastic modulus and shear wave velocity for phantom material produced according to the exemplary recipes 1 and 2 with a composition according to Fig. 1;

[0107] Fig. 4 a graphical representation of the test results concerning elastic modulus and Hounsfield scale for phantom material produced according to two exemplary recipes 2 and 3 with a composition according to Fig. 1 ;

[0108] Fig. 5 is a graphical representation of the test results concerning Hounsfield scale and shear wave velocity for phantom material produced according to the exemplary recipes 2 and 3 with a composition according to Fig. 1 ;

[0109] Fig. 6 is a graphical representation of the test results concerning elastic modulus and shear wave velocity for phantom material produced according to two exemplary recipes 1 and 4 with a composition according to Fig. 1 ;

[0110] Fig. 7 is a graphical representation of the test results concerning elastic modulus and shear wave velocity for phantom material produced according to two exemplary recipes 1 and 4 with a composition according to Fig. 1 ;

[0111] Fig. 8 is a graphical representation of the test results concerning elastic modulus, Hounsfield scale and shear wave velocity for phantom material prepared according to the exemplary recipes 1 to 8 with a composition according to Fig. 1;

[0112] Fig. 9 is a graphical representation of the test results concerning elastic modulus and / or Hounsfield scale and / or shear wave velocity for phantom material prepared according to the exemplary recipes 9 to 14 with a composition according to Fig. 1;

[0113] Fig. 10 is an exemplary representation of an embodiment of a phantom body prepared for final shaping;

[0114] Fig. 11 is an exemplary representation of an embodiment of a finally formed phantom body with a positive kidney tumor;

[0115] Fig. 12 shows an exemplary representation of the embodiment of the finally formed phantom body with a positive kidney tumor according to Fig. 11 during the performance of CT measurements; Fig. 13 shows an exemplary CT image of the embodiment of the finally formed phantom body with a positive kidney tumor according to Fig. 11;

[0116] Fig. 14 is an exemplary ultrasound image of the embodiment of the finally formed phantom body with a positive kidney tumor according to Fig. 11;

[0117] Fig. 15 is an exemplary representation of the embodiment of the finally formed phantom body with a positive kidney tumor according to Fig. 11 when used in robot-assisted surgery;

[0118] Fig. 16 a graphical representation of test results concerning the Hounsfield scale for an exemplary phantom material prepared with varying composition of alginate, fat and calcium carbonate and

[0119] Fig. 17 is a graphical representation of test results concerning the elastic modulus for an exemplary phantom material prepared with varying compositions of alginate, fat and calcium carbonate.

[0120] Figure 1 shows 14 possible, exemplary recipe compositions for producing an exemplary embodiment of a phantom according to the invention containing water, alginate, calcium carbonate, GDL, surfactant, and fat. In the table, the individual cells indicate the mass in grams and the weight percentage. The mass and weight percentage of individual components vary in the different recipes.

[0121] Figure 2 compares the elastic modulus and the Hounsfield scale of formulation variants 1 and 2 according to Figure 1. The main difference between the two formulation variants is that more fat is used in formulation variant 2. While there are no significant differences in the elastic modulus, the results of the Hounsfield scale are clearly different.

[0122] Fig. 3 shows a comparison of elastic modulus and shear wave velocity of formulation variants 1 and 2 according to Fig. 1. While there are no significant differences in elastic modulus, the result of the shear wave velocity is clearly different.

[0123] Furthermore, Figure 4 compares the elastic modulus and the Hounsfield scale of formulation variants 2 and 3 according to Figure 1. The main difference between the two formulation variants is that formulation variant 3 uses more alginate, calcium carbonate, and GDL, and less fat and surfactants, compared to variant 2. While there are no significant differences in the Hounsfield scale, the elastic modulus results are clearly different.

[0124] In Fig. 5, the Hounsfield scale and shear wave velocity of formulation variants 2 and 3 are compared according to Fig. 1. While there are no significant differences in the Hounsfield scale, the result of the shear wave velocity is clearly different.

[0125] Figure 6 shows a comparison of elastic modulus and shear wave velocity of formulation variants 1 and 4 according to Figure 1. The main difference between the two formulation variants is that formulation variant 4 uses more calcium carbonate and GDL and less fat and surfactant than variant 1. While there are no significant differences in shear wave velocity, the elastic modulus results are clearly different.

[0126] In addition, Figure 7 compares the Hounsfield scale and the shear wave velocity of formulation variants 1 and 4 according to Figure 1. While there are no significant differences in the shear wave velocity, the result of the Hounsfield scale is clearly different.

[0127] If the results of the measurements on elastic modulus, Hounsfield scale and shear wave velocity of the formulation variants 1 to 4 are compared, the following results:

[0128] For recipe variations 1 and 2, significantly different results for the Hounsfield scale or the shear wave velocity are obtained at constant elastic modulus.

[0129] For recipe variations 2 and 3, significantly different results for the elastic modulus or shear wave velocity are obtained at a constant Hounsfield scale. For recipe variations 1 and 4, significantly different results for the elastic modulus or the Hounsfield scale are obtained at a constant shear wave velocity.

[0130] It is thus possible to adjust the later mechanical properties of the phantom according to the invention by varying the formulations of the material system. In this embodiment, a material system based on alginate and fat is used as an example.

[0131] Fig. 8 shows the results for elastic modulus, Hounsfield scale, and shear wave velocity for recipe variations 1 to 8. The figure shows that these properties can be independently adjusted by varying the recipe of the material system.

[0132] The results from Fig. 8 are summarized below:

[0133] For the recipe variations 1 and 5, 2 and 4, 2 and 5, 3 and 6, 2 and 8, 4 and 6, significantly different results are obtained for the elastic modulus, the Hounsfield scale and the shear wave velocity.

[0134] For recipe variations 1 and 2, 1 and 6, 1 and 7, 2 and 6, and 2 and 7, significantly different results are obtained for the Hounsfield scale and shear wave velocity. The elastic modulus shows no significant differences. For recipe variations 2 and 3, and 5 and 8, significantly different results are obtained for the elastic modulus and shear wave velocity. The Hounsfield scale shows no significant differences.

[0135] For recipe variations 1 and 3, 1 and 4, 1 and 8, 3 and 4, and 5 and 6, significantly different results are obtained for the elastic modulus and the Hounsfield scale. The shear wave velocity shows no significant differences.

[0136] Recipe variations 4 and 5 yield significantly different results for the shear wave velocity. The elastic modulus and the Hounsfield scale show no significant differences.

[0137] Recipe variations 6 and 7 yield significantly different results for the Hounsfield scale. The elastic modulus and shear wave velocity show no significant differences.

[0138] Recipe variations 4 and 8 yield significantly different results for the elastic modulus. The Hounsfield scale and shear wave velocity show no significant differences.

[0139] Fig. 9 shows in bar charts the elastic modulus of recipe variations 9 and 10 according to Fig. 1, the Hounsfield scale of recipe variations 11 and 12 according to Fig. 1 and the shear wave velocity of recipe variations 13 and 14 according to Fig. 1.

[0140] The figure shows how significant differences in the values ​​for the individual properties can be achieved by varying the recipe while maintaining the same material system.

[0141] The main difference between formulation variants 9 and 10 is that formulation variant 10 uses significantly more fat than variant 9. The amounts of calcium carbonate, GDL, and surfactant are also increased.

[0142] The main difference between recipe variants 11 and 12, however, is that in recipe variant 12 more calcium carbonate is used and the proportions of GDL, surfactant and, in particular, fat are reduced.

[0143] Neither fat nor surfactants are used in formulation variants 13 and 14. The main difference is that in variant 14, the calcium carbonate and GDL content are higher than in formulation variant 13.

[0144] With the multimodal, monomaterial phantom according to the invention, it is thus possible to produce surrogates for different tissue types by adjusting the physical and mechanical properties of the phantom, whereby each individual organ, tissue and anatomical landmark can be produced with the same material system.

[0145] Figure 10 shows a phantom body prepared for final molding, made from a material system based on alginate, calcium carbonate, and fat. The skeleton shown is a commercially available skeleton made of PVC plastic. Replacing the skeleton with one based on the material system used is also possible by utilizing a high calcium carbonate content in the material system. The vessel-like constructs, the kidney-like constructs, and the round sphere are individually tailored, CT-adapted, and mechanically tuned surrogates.

[0146] Fig. 11 shows a fully formed phantom body. The phantom body shows a positive kidney tumor and is prepared for CT scanning.

[0147] Fig. 12 shows the phantom body from Fig. 11 during a CT measurement.

[0148] In addition, Fig. 13 shows the CT image of the prepared phantom body from Figs. 11 and 12. The phantom tumor is designed to have a higher CT contrast, as would be the case with a real tumor.

[0149] Furthermore, Fig. 14 presents an ultrasound image of part of the phantom body from Figs. 11 and 12.

[0150] Figure 15 shows a phantom body with a positive kidney tumor during robot-assisted surgery.

[0151] Figure 16 shows a bar chart showing the Hounsfield scale for various formulation variants of a material system based on alginate and fat. Unless explicitly stated, the weight ratio of calcium, or more specifically calcium carbonate, to GDL is always 1 to 3.56. Additionally, values ​​on the Hounsfield scale for real tissue (tendon, skin, muscle, kidney, and adipose tissue) are given. These values ​​are taken from the literature.

[0152] Fig. 17 shows a bar chart plotting the elastic modulus for various formulation variants of a material system based on alginate and fat. Unless explicitly stated, the weight ratio of calcium, or in particular calcium carbonate, and GDL is always 1 to 3.56. Additionally, values ​​for the elastic modulus for real tissue (tendon, intestine, muscle, kidney) are given. These values ​​are taken from the literature. To produce a phantom with organs and, for example, a tumor in various CT attenuations and with the correct mechanical properties, a desired material variation can be selected, in particular, from the exemplary variations listed in Fig. 16 and Fig. 17.

[0153] Since the components of the exemplary material system used in the illustrations are inexpensive, food-safe, biodegradable, and easily available even in developing countries, they offer several advantages that make their use attractive. The exemplary material system is simple and easy to manufacture as required and can be easily disposed of after surgical training.

[0154] Further example:

[0155] The following is a description of an exemplary production of a phantom according to the invention using a concrete production example in the form of recipe 1 according to Fig. 1 for the production of a phantom comprising sodium alginate and fat:

[0156] - 2 g of sodium alginate salt are mixed into 48 g of water at room temperature, hereinafter referred to as Premix 1. For homogeneous mixing, this process takes up to 24 hours, depending on the sodium alginate concentration.

[0157] - 0.2 g of CaCO3 microparticles are mixed into 24.8 g of water. This process takes only a few seconds to obtain a homogeneous dispersion (Premix 2). Additional dyes or anti-mold agents can be added during this step if necessary.

[0158] - Premix 2 is added to Premix 1 and stirred until the dispersion is homogeneous (Premix 3). This process takes a few minutes, depending on the sodium alginate concentration.

[0159] - 1.25 g of the surfactant decyl glucoside were added to premix 3 and stirred until completely mixed, which is referred to as premix 4.

[0160] - 23.75 g of melted coconut fat are added to premix 4 and stirred vigorously until homogeneous (premix 5).

[0161] - Premix 5 is degassed in a vacuum chamber to remove air bubbles. This process takes a few minutes.

[0162] - Add 0.71 g of glucono-delta-lactone (GDL) to 24.29 g of water and stir until completely dissolved (Premix 6). This process takes only a few seconds.

[0163] Immediately after preparing Premix 6, Premix 6 is poured into the degassed Premix 5 to obtain the final mixture and stirred gently to eliminate air bubbles. The final mixture can be degassed for a short time to remove any remaining air bubbles. The maximum available degassing time depends on the concentration of sodium alginate, CaCO3, and GDL.

[0164] The final product / mixture is poured and formed into the desired shape.

[0165] It is possible to swap, combine or carry out the above-mentioned production steps simultaneously.

[0166] The production of organs, tissue and anatomical landmarks of the phantom according to the invention can be carried out by molding, 3D printing or other manufacturing processes.

[0167] The manufactured phantom bodies can be used in particular both in the training of prospective surgeons and radiologists and for practicing a usually difficult procedure, whereby a practice run can lead to a significant improvement in the surgical outcome.

[0168] The multimodal, monomaterial phantom is particularly interesting for manufacturers of phantom bodies, companies that produce soft materials, or providers of assistance systems for robotic surgery such as Intuitive or Distal Motion.

[0169] To create a lifelike phantom body, real CT images of pathological and healthy bodies are preferred. The Hounsfield scale is used to determine the X-ray properties of a material and can be measured and determined at any location on a patient's body. CT images can be used to create a digital file of individual organs or anatomical landmarks. Mechanical properties can be obtained from the literature, allowing a fully customized phantom to be created from a material system.

[0170] Depending on the physiological and anatomical characteristics and the required level of detail, a phantom can be manufactured in different ways.

[0171] The process that allows for the most detail is 3D printing with a bioprinter such as Cellink's Bio X, which can combine three different materials.

[0172] In another process, the internal channels can be manufactured separately by casting, molding, or printing and then integrated into a larger mold, for example, to incorporate blood vessels into a harder matrix material. If an entire phantom body is required, the individual components such as bones, organs, blood vessels, etc., are manufactured separately and then incorporated into a larger mold.

[0173] The multimodal, monomaterial phantom is characterized by a wide variability in the reproduction of human soft tissue, whereby a largely arbitrary gradation of the measurable radiopacity and elasticity values ​​can be achieved by varying the formulations and controlling the cross-linking process.

[0174] This makes it possible to produce even complex anatomical tissue arrangements as phantoms from a single material system, thereby reducing manufacturing costs and subsequent disposal costs.

[0175] Due to the multimodal quality of the phantom, the field of computer surgery is considered a particular target market.

[0176] In addition, converting real CT images of a patient into a phantom can lead to patient-specific phantoms for the preparation of a difficult procedure, thus opening up a new market opportunity.

Claims

CLAIMS Multimodal, monomaterial phantom comprising surrogates for different Tissue types, where - the phantom is formed from at least two surrogates; - the surrogates are arranged separately, anatomically in contact with each other; - the surrogates are designed and / or arranged to simulate the same and / or different tissue types; characterized in that the phantom and / or the surrogates consist of exactly one material system during or during manufacture, wherein the material system has a material composition of at least: - Sodium alginate and - Glucono-delta-lactone (GDL) or an acid-forming compound by hydrolysis or lactones and - Calcium carbonate and - Fat and - water in the form of a hydrogel, and the material system is formed in at least two different variations of the material system composition within the phantom and / or surrogates. Phantom according to claim 1, characterized in that by varying recipes and / or proportions within the material composition of the material system and by controlling the polymerization of the hydrogel in the Networking process - a diversity and / or adaptability of the trained surrogates causes or trained; - within the material system, the CT attenuation and the shear wave velocity can be adjusted independently of each other; the surrogates formed - can be distinguished from one another using non-invasive medical diagnostic and imaging techniques, including ultrasound imaging and X-ray CT; - simulate the mechanical properties of real tissues as closely as possible; - can be cut; - are moldable and dimensionally accurate. Phantom according to claim 1 or 2, characterized in that the material system comprises dyes and / or anti-mold agents. Phantom according to one of the preceding claims, characterized in that the material system composition allows variations in the range of (% by weight). - 0.1 to 20 percent sodium alginate - 0.01 to 20 percent calcium carbonate - 0.01 to 20 percent glucono-delta-lactone (GDL) - 0.1 to 50 percent fat - 0 to 10 percent surfactant - 0 to 5 percent anti-mold agent 0 to 5 percent dye and Water, a total of 100%. Phantom according to one of the preceding claims, characterized in that the material system is easily disposable or can be disposed of as ordinary organic waste. Use of the phantom according to one of the preceding claims for - surgical and / or radiological training and / or further education of specialist personnel, - Preparation of surgical procedures, - Development and / or calibration of devices for robot-assisted surgery. Use of the phantom according to one of the preceding claims 1 to 5 for modeling - individual organs and / or tissues, - of organ arrangements and / or tissue arrangements, - of organ arrangements and / or tissue arrangements including defined Pathologies, - of phantom bodies exhibiting organ and tissue arrangements.

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