Production of anthropomorphic head-neck phantom with 3D printer and molding technique

Abstract

The invention relates to the production method of anthropomorphic head-neck phantom in heterogeneous structure and in a form suitable for human anatomy using 3D printer and molding technique.

Description

[0001] DESCRIPTION

[0002] PRODUCTION OF ANTHROPOMORPHIC HEAD-NECK PHANTOM WITH 3D PRINTER AND MOLDING TECHNIQUE

[0003] Technical Field

[0004] The invention relates to the production method of anthropomorphic head-neck phantom in heterogeneous structure and in a form suitable for human anatomy using 3D printer and molding technique.

[0005] Prior Art

[0006] Todays, most of phantoms are used in homogeneous forms. The most commonly used are RANDO whole body and male and female phantoms, and they are generally formed by connecting by stacking in the form of slices of 2.5 cm thickness for obtaining X-ray dose distributions. (In the RANDO phantom, it is stated that soft tissue equivalence is provided by effective atomic number and mass density parameters in a proprietary urethane formulation with an effective atomic number and mass density that closely simulates muscle tissue with randomly distributed fat. A suitable material mimicks the density of lungs in a median respiratory state. The lungs are fitted to fill the rib cage. The Male Alderson RANDO phantom is based on ICRU-44 standard tissues, and while the male Alderson RANDO therapy phantom represents a male 175 cm tall and 73.5 kg, the Alderson female RANDO phantom represents a female 155 cm tall and 50 kg in weight. [1]

[0007] It is used by being attached in the form of plates by means of dosimeters (Thermoluminescence dosimeter (TLD), Optically stimulated luminescence (OSL) dosimeter, radiochromic film) placed between these slices or molded breast accesories (sections of 2 cm thickness) fitted to these. In the RANDO phantom, it is used by forming lungs produced with molding technique from syntactic foam(hollow spheres filled with metal, polymer, binding cement) material having an approximate specific density of 0.3 g / cm3and a respiratory cavity added to this.

[0008] In the head and neck phantom which is a hollow and liquid-fillable Radiosurgery Verification Phantom (RSVP), there is the possibility of placing a detector from a cavity (insert) opened in the lower part of the neck. This RSVP head and neck phantom is designed for evaluating the dose absorbed in water in stereotactic radiosurgery (SRS) treatment and for checking the suitability of periodic quality controls of radiosurgery equipment and for acceptance tests. Inside this phantom, doses recorded with TLD or films placed into this cylinder can be measured with a positioning rod the tumor volume (2 cm x 4 cm) to different regions of the brain. However, it does not offer the possibility of measurement with a plastic scintillator dosimetry (PSD) or ion chamber. Although there are some phantom examples produced in a heterogeneous structure, these phantoms represent the tissue in a way far from the complex structure presented by realistic human anatomy. [2]

[0009] Currently, there is the Prime Phantom model belonging to the RTSafe brand which is commercially widely used. This model contains different modules in a state supporting multiple dosimetric studies. RTSafe Prime, model device quality control phantom, is used as SRS quality control (QA) hardware in radiotherapy. However, it is not possible to apply dosimeter techniques simultaneously with this phantom.

[0010] The “ATOMMAX” model dental head-neck phantom belonging to the CIRS brand and currently used for imaging purposes in dentistry (dental) does not offer the possibility of internal dosimeter placement for dosimetric purposes in radiotherapy. Therefore, while it is not possible to perform any superficial dosimeter study in this phantom, it is used only for medical imaging purposes.

[0011] In the patent document numbered KR102434603B1, a production apparatus and method for a body phantom are mentioned.In the patent document numbered KR101717728B1, a system, method and programs for patient-specific moving phantom production are mentioned.

[0012] In the patent document numbered US2006056580A1, tissue-like phantoms are mentioned.

[0013] In the patent document numbered US2010202001A1, anatomically realistic three-dimensional phantoms for medical imaging are mentioned.

[0014] When studies existing in the prior art are examined, a need has arisen for the development of a production method of anthropomorphic head-neck phantom in heterogeneous structure and in a form suitable for human anatomy using 3D printer and molding technique.

[0015] Object of the Invention

[0016] The object of this invention is to develop a production method of anthropomorphic head-neck phantom in heterogeneous structure and in a form suitable for human anatomy using 3D printer and molding technique.

[0017] Detailed Description of the Invention

[0018] A production method of anthropomorphic head-neck phantom in heterogeneous structure and in a form suitable for human anatomy using 3D printer and molding technique, it comprises;

[0019] forming soft tissues located in the head-neck region using PLA+ thermoplastic material with 3D printer, and cortical bone tissue using hydroxyapatite (hAP) and bismuth oxide (Bi2O3) in solventless epoxy by molding,

[0020] opening holes into the formed structure for the placement of dosimeters, producing the head-neck phantom by combining the soft and cortical bone tissues.In the method subject of the invention, PLA+ from thermoplastic materials and high clear liquid photopolymer were selected due to providing the most suitable radiosensitivity (HU) and half-value layer (HVL) and at the same time possessing a physical density and effective atomic number close to soft tissue. Dental resins were preferred in the tooth and jaw part. Considering factors such as different anatomical structures of the head, 3D printer FDM technical printing sensitivity, printing time, soft tissue parts were produced by extruding PLA+ filament, each in 0.4 mm layer thickness, at 95% infill and in “Lines” infill pattern, at 210 °C printing temperature, 70 °C glass bed temperature, at 40 mm / s printing speed. Due to the technical capacity of current printers, the entire head-neck phantom was printed by being divided into 8 parts. However, cortical bone was produced in the form of a fluid mixture with hydroxyapatite (hAP) powder form containing high rate of Ca, S and bismuth oxide powder mixture by utilizing the binding property of solvent-free epoxy having tissue equivalence, apart from existing polymeric materials, and its hardening was ensured by being filled into the bone regions in the head structure. Worldwide, the radiation absolute dose measurement method widely used in radiotherapy (Stereotactic Body Radiotherapy (SBRT)) SRS / SBRT QA processes and accepted as reference is the use of ion chambers with various phantom geometries. In the studies performed, the plan doses made on the treatment planning system (TPS) on the produced phantom were compared with absolute dosimetry methods, for example, Exradin A 19 model small volume (0.6 cm3) ion chamber working according to the principle of conversion of the amount of ionization in air into electrical charge and an Exradin W1 plastic scintillator dosimetry (PSD) where visible light conversion of ionizing radiation is used efficiently, by being used in specially designed regions of the phantom. The Standard Imaging Exradin W1 model plastic scintillator (1 mm diameter x 3 mm length, approximately 0.024 cm3in volume) used for the first time in this study was used for dose measurement in both 6 MV photon and 6 MeV electron beam qualities due to being suitable for use in very small radiation field in polymer structure made of polystyrene material, and its density and effective atomic number (Zeff) showing only 0.2% deviationaccording to tissue and dose absorbed in water. In this sense, the plastic scintillator dosimetry (PSD) study brought originality as a real-time absolute dosimetry method used during irradiation for the first time in the method for instantaneous dose rate and cumulative measurements and thus could be compared with reference ion chamber measurements. Relative dosimetry methods, which is another dosimeter technique, could also be applied again due to the produced phantom being in a modular structure. With radiochromic films(here used Gachromic® EBT3) cut in desired size, the distribution of doses that skin cancer on the head or salivary (parotid salivary glands) glands could receive was determined. In this scope, the high spatial resolution (72 dpi-6400 dpi) radiochromic film technique providing two-dimensional dose information could be analyzed by creating different segments on the human brain and placing multiple films and subsequently scanning with Epson Perfection V850 Pro Model flat-bed three channel scanner. At the same time, a quality control was performed by comparing the prescribed doses of the same segments on Eclipse 15.6 treatment planning system with the experimentally measured doses.

[0021] An anthropomorphic head-neck phantom has been developed using both 3D printing and molding methods by reconstructing a tomography image belonging to an adult male and ensuring the compliance of tissue equivalence, photon absorption properties, electron density, and effective atomic number, physical density with reference values in exact dimensions. In the produced head-neck phantom, soft tissue and adipose tissue were produced using PLA+ thermoplastic material, whereas cortical bone, cervical vertebra and mandible tissues were produced by adding mainly 24% hydroxyapatite and 3% bismuth oxide in a given amount solventless epoxy matrix, together with its catalyzer.

[0022] The anthropomorphic head-neck phantom, the production of which is completed, has been designed in such a way that dose measurement can be taken with plastic scintillator, ion chamber and radiochromic film, and a total of 4 holes (inserts) into which detectors can easily be placed have been opened. One of these is intendedfor the brain center, one for the cervical C2 vertebra corpus from below the larynx, and the other two holes for reaching the right and left parotid glands. When a detector is placed into a single opened hole (insert), the others are closed by inserting cylindrical rods made of their own material, and thus the air gap remains at a minimum.

[0023] In the second prototype, the eye sockets are left empty; eye phantoms that can be produced separately will be able to be attached here. It is suitable for use for Hp(3) the lens of the eye dosimetry measurements.

[0024] In radiotherapy, in every case, it is important to know the dose planning prescribed before treatment for limiting the dose amounts absorbed by healthy tissues and organs at risk(OARs) surrounding the target cancerous tissue / organ. In this context, radiotherapy has become a treatment method widely used worldwide especially in head-neck cancer treatment. In the clinic, external radiotherapy is widely applied with high energy continuous spectrum photon radiation (Bremsstrahlung) in the order of 6-25 MV produced by means of linacs or 6-12 MeV electron beam dose. In these external beam treatments, doses to be delivered to the regions contoured as target organ by the physician of the patient on CT images are planned in treatment planning systems (TPS) with specific algorithms.

[0025] During cancer treatment, the matching of the target volume to be irradiated with the radiation fields is very important. Especially in head and neck cancers, tumor cells are in very close proximity to vital organs and therefore, for the success of radiotherapy, the successful configuration of the treatment planning system (TPS), prepared by protecting healthy tissues with the help of simulators where phantoms are also used, is very important. This issue is currently a problem waiting for a solution for the delivered dose in clinical applications to be measured experimentally. For example, cases where regions that are inaccessible for placing a dosimeter (brain, eye, brain stem, cervical vertebra region (vertebra corpus), salivary glands (parotid / salivary glands) etc.) are the target organ to be irradiated,or the limitation of their healthy tissues with a precise contouring and the measurement of these doses with the help of an anthropomorphic phantom before treatment and the updating of this in TPS is a very important need. Therefore, in radiotherapy performed with a linac device, primarily the verification of treatment plans with experimental dosimetric measurements and performing quality controls (QA) is a necessity.

[0026] As is known, in head-neck cancer treatment, radiation doses delivered to the patient by means of TPS with MV energy photon or MeV energy electron beams or in combination; treatment doses given in low fractions (e.g., 2 Gy / fir), sometimes in the form of single fraction dose (e.g., 8 Gy / fr) and can reach up to 55-60 Gy in total at the end of the treatment. As in every system affecting human health, it is necessary to perform quality control / assurance (QA) tests in these clinical linacbased irradiation systems as well. QA systems are widely used in clinics worldwide where radiotherapy applications are performed.

[0027] QA has become an indispensable process in radiotherapy. [3] Widely used QA device incorporates the arrays of detectors arranged in a matrix. [4]

[0028] The method subject of the invention ensures the production of the equivalency of each tissue (soft tissue, fat tissue (adipose), vertebra corpus-cervical vertebra region (C1-C7), skull (sculp) bone (ICRU44, density: 1.92 g / cm3), oral cavity, a closed jaw made of dental PMMA and human brain tissue) using thermoplastic, silicone and epoxy matrix material and in a manner suitable for human / organ anatomy, in accordance with the anatomy of the human head which is in a heterogeneous structure.

[0029] It is aimed that the phantoms being used as tissue-equivalent dosimetry equipment allow performing multiple dosimetry studies simultaneously (Radiochromic film dosimetry (RFD), small volume ion chamber + plastic scintillator dosimetry (PSD)) due to their being designed as monolithic by their design. In this study, it is aimed to enable the comparison of experimental dose values measured by applying thesethree different dosimetry techniques (RFD, PSD and ion chamber) in the produced anthropomorphic head-neck phantom with the doses prescribed in TPS.

[0030] In practice, due to human anatomy, there are inaccessible regions in the head-neck region (closed regions such as brain, vertebra corpus) and it is not possible to measure the dose delivered to these regions during cancer treatment.

[0031] Fürthermore, since treatment in head and neck cancers is accepted as patientspecific like all other cancer types, the measurement of the dose delivered to the target organ and the healthy tissues in its vicinity with the help of an anthropomorphic phantom currently presents technical difficulties.

[0032] With an anthropomorphic head-neck phantom, the prototype of which is produced with the method subject of the invention, the dose delivered directly to the brain can be measured experimentally as pre-treatment, for brain cancers where external photon beams are currently applied, by using a hole (insert) opened at shoulder level and placing a small volume ion chamber (designed for radiotherapy purposes) or a small volume PSD scintillator-based detector. Similarly, it is possible to determine the doses that can be transferred to salivary glands with a small volume ion chamber or small volume PSD detector that can be placed with holes opened from below the neck. Fürthermore, doses to be received by other healthy tissues in the treatment of lip and mouth, oral cavity, pharynx, nasopharynx and larynx cancers can be measured experimentally with the help of this anthropomorphic detailed head-neck phantom. For example, dose measurement has become possible with an ion chamber or PSD detector placed in holes opened in the mandible regions in the lower jaw to measure the dose received by the salivary glands. In this context, dose measurement was performed for the first time with a PSD detector under 6 MeV electron beam irradiation conditions (with the help of 20 cm x 20 cm and 10 cm x 10 cm beam limiting applicator).

[0033] In the radiotherapy application applied with 6 MV photon beam by defining the C2 vertebra corpus metastasis lesion tumor region known as a tumor location in head-neck radiotherapy currently, the possibility of placing a detector has been provided by opening a hole (insert the detector in it) in a suitable place on the phantom to estimate the 24 Gy dose given in a single fraction. Similarly, there is the possibility of using holes opened in different places on the phantom for different applications by being closed again with the same solid cylindrical rod. Fürthermore, in the treatment plan of a skin cancer developing on the head with 6 MeV electron beam, the measurement of the planned dose of 8 Gy in a single fraction was performed with bolus and without bolus.

[0034] In the method subject of the invention, 10 different anthropometric dimensions suitable for anatomical axes of the head-neck phantom prototype specific to an adult male head were determined and compared with literature data.

[0035] The three-dimensional anatomical similarity of the object image developed with the reconstruction technique suitable for the computed tomographic image was tested.

[0036] The tissue equivalency (tissue equivalency / tissue mimicking) of the materials used in printing was determined in terms of, respectively, radiosensitivity (HU), halfvalue layer (HVL) associated with linear absorption coefficient, effective atomic number (Zeff), electron density (#electron / g) and physical density (g / cm3); and the plastic-based material hardness was determined with parameters (Shore A and Shore D hardness with use of Durometer, etc.).

[0037] The production and combining of modular parts were ensured with molding technique using epoxy-based special composition mixtures and 3D printing (using FDM and SLA technologies) from suitable polymeric materials.

[0038] The radiosensitivities, photon absorption and scattering properties of the materials used in phantom production were determined in terms of Hounsfield Unit (HU) and half-value layers (HVL) and correlated with their physical densities. In the produced phantom, doses delivered to the brain center where the tumor volume is contained, to the C2 vertebra corpus metastasis lesion and to the cancerous regionselected on the scalp on the head were measured for the first time by means of plastic scintillator dosimetry (PSD) technique with use of an Exradin W1 detector suitable for small radiation field dosimetry.

[0039] In irradiations suitable for treatment protocols in different photon and electron beams in a clinical LINAC device, dose distributions transferred to target and organs at risk were determined two-dimensionally with the RFD technique having high spatial resolution.

[0040] In the anthropomorphic head-neck phantom produced within the scope of the method subject of the invention, firstly material determination experiments and analyses were performed. The head-neck region was divided into two as soft tissue and cortical bone tissue. Thermoplastic materials were analyzed as soft tissue equivalent material, and 3D printing technique was used as the production method with an innovative approach. Cortical bone tissue (parts such as skull, vertebra, mandible) was obtained with inorganic powder (bismuth oxide, calcium sulfate dihydrate, calcium carbonate) added into epoxy resin and organic hAP (hydroxyapatite) chemicals containing Ca, S. A four-criteria was evaluated in material determination to meet tissue equivalency of the chosen materials. Information and data given in ICRU Report 44 was taken for reference tissue compliance.

[0041] 1. Hounsfield Unit value which is the radiosensitivity coefficient,

[0042] 2. Effective atomic number,

[0043] 3. Physical density value,

[0044] 4. HVL or Linear attenuation coefficient,

[0045] were investigated for each tissue of interest and material determination was performed by comparing with the standard contained in ICRU Report 44. The mimicking of parts such as soft tissue and adipose fat tissue with PLA+ thermoplastic material and transparent PMMA equivalent photopolymer resin, and the mimicking of parts such as cortical bone, vertebra, mandible by adding organiccalcium mineral (hAP) and a small amount of bismuth oxide, calcium carbonate / calcium sulphate into epoxy have been achieved. In order to prove the tissue equivalence of this simulation quantitatively, samples in the form of 2 cm x 2 cm x 2 cm cubes and disc samples from epoxy mixtures were prepared. For this purpose, CT images of samples prepared from different resins such as photopolymer resin (standard) suitable for SLA printing technology, high transparency resin (High Clear photopolymer), hard resin (Tough photopolymer), water-washable resin (Water-Washable photopolymer), eco-friendly plant-based resin (Plant-Base), PMMA equivalent resin, ABS equivalent resin, PLA resin, Dental DM 2505, Dental DM 2505+HP+Bi, and filament type ABS, PLA, PLA+, TPU-92A thermoplastic materials suitable for FDM printing technology, and also solvent-free epoxy-based hAP+Bismuth oxide mixtures were examined in detail. Regarding Hounsfield Unit (HU) coefficients representing the sensitivity of the tissue against radiation, CT images obtained in computed tomography device at 120 kV with 0.625 mm slice thickness were processed with 3D Slicer, and optical densities were calculated with use of Image J software using 5 regions of interest (ROI) approach from each slice image. In order for the CT images to be created in grayscale, HU values were calculated for each pixel value in the image based on the photon linear attenuation coefficients of the tissue. Here, by definition, the HU value of pure water is accepted as 0 and the HU value of air as -1000. Upper limits for HU values are defined with values of +1000 for bones, +2000 for higher density bones, and +3000 for metals. [5]

[0046] For example, the HU coefficient of PLA+ thermoplastic material at 95% infill was determined as +40+12. Whereas in the phantom, this value was found to be HU=88 ± 17 for soft tissue. It was evaluated that the sample under the determined production conditions is suitable for mimicking the soft tissue approximately. In the sample prepared for cortical bone, HU=1063 ± 140 was found, and in the produced first prototype phantom, HU=1252 ± 41 was found. These results were compared for soft tissue and cortical bone based on both the reference CT imageand the CT image of the produced phantom, and were also compared with ICRU-44 report.

[0047] The half value layer (HVL) of a specific material refers to the material thickness that needs to be added between the source and the detector to reduce the X-ray intensity by half under the same conditions (distance, detector, material, etc.) and is a value used to measure the photon beam intensity or mean energy. A low HVL value represents lower photon energy. This value is valid only for narrow beam geometries defined according to ISO 4037-1. According to ISO 4037-1, for broad beam geometries, determining the absorption amount becomes difficult since the amount of scattering in air will be higher.

[0048] Effective atomic number (Zeff) means the effective electrical charge of an atom, and for mixtures and compounds, the average atomic number. In atomic interactions related to the distribution of electron configuration, the electron density (number of electrons / g) parameter is also another parameter calculated in tissue equivalency. In order to show that the head-neck phantom produced within the scope of the method represents the tissue, the effective atomic numbers and electron densities of the materials representing the tissues were also calculated.

[0049] The usability of PLA+ (polylactic acid), ABS (acrylonitrile butadiene styrene) and TPU-92A (thermoplastic polyurethane) filaments among thermoplastic filament types as phantom material was investigated, and analyses were performed to determine their photon absorption properties. In this direction; cube-shaped samples with dimensions of 2 cm x 2 cm x 2 cm and at different infill rates were produced with FDM technology for each filament type. Analyses of HU, physical density, Zeff and impact resistance parameters were performed to determine the suitability of the produced samples for use as tissue equivalent. In this scope, firstly, the CT image of each sample was obtained. The obtained CT images were analyzed with use of Image J sofware, which is an image processing program, and as a result, the HU values of each sample were obtained in Table 1. However, it is also possiblethat the images can also be analyzed for obtaining HU values form the voxel values determined by using commercial image analysis programs. The obtained HU values were compared with the radiological density values in the tissue of interest belonging to an anonymous person, taken with the same tomography parameters. The elemental composition and physical density of the targeted tissue were compared with our obtained experimental findings based on the values contained in ICRU Report 44. Thus, the determination of the material providing tissue equivalency with the highest accuracy in phantom production was ensured through evaluations performed both radiologically and physically, and subsequently, those suitable in additive manufacturing 3D printing and casting in molding techniques were used.

[0050] The investigation of the usability of different thermoplastic material types was performed separately for soft tissue and cortical bone tissue. In this way, the material providing the highest tissue equivalence for each tissue was determined, (see Table 1)

[0051] Thermoplastic type Printing with infill Measured physical Mean HU

[0052] ratio density (g / cm3)

[0053] PLA+ %100 1.209±0.030 163±10

[0054] TPU-92A %100 1.222±0.010 131±8

[0055] ABS %100 1.047±0.002 -(10±8)

[0056] Table 1: Measured mean physical density and HU values of PLA+, TPU-92A and ABS materials produced at 100% infill

[0057] The comparison of the soft tissue defined in ICRU Report 44 and the thermoplastic materials used in phantom production in terms of effective atomic number, effective atomic mass and electron density is given in Table 2. According to the obtained results; it was determined that the effective atomic number of PLA+ thermoplastic material is different by only 4.9% from the soft tissue effective atomic number stated in ICRU Report 44. Among the analyzed materials, PLA+ thermoplasticmaterial was preferably used in the head-neck phantom production representing soft tissue and fat tissue due to the closest result to the soft tissue atomic number value selected as reference from ICRU Report 44 being obtained with PLA+.

[0058] Material Zeff Aeff (Z / A)eff N(x1023electron / cm3) '

[0059]

[0060] Soft tissue (ICRU 44) 7.07 9.11 0.55 3.51

[0061] 44)

[0062] PLA+ 7.04 10.67 0.53 3.85

[0063] TPU-92A 6.71 12.51 0.51 3.75

[0064] Water 7.22 8.99 0.56 3.34

[0065] Note: For PLA + and TPU-92A, these parameters are based on their percentage elemental compositions determined from SEM-EDX and CHNS chemical combustion elmental composition analysis.

[0066] Table 2: Comparison of soft tissue defined in ICRU Report 44 and thermoplastic materials used in phantom production in terms of effective atomic number, effective atomic mass and electron density

[0067] The HVL values of TPU-92A material are closer to the HVL values given in ICRU Report 44 compared to PLA+ material. However, even though TPU-92A material provides tissue equivalency, its use in phantom production was not deemed suitable due to artifacts occurring during production such as causing clogging at the nozzle exit which is the part where the filament is melted during production with a 3D printer, weaker adhesion between inner layers, formation of artifacts on the sample surface, and occurrence of discontinuity in the extrusion line, since it has a much more flexible structure compared to PLA+ material. Instead, the use of PLA+ thermoplastic material as soft tissue equivalent was preferred because it was observed to be tissue equivalent as a result of the analyses performed and due to offering advantages such as ease of production and easy accessibility during the procurement phase.Consequently, as a result of all these tests, analyses, and calculations performed; in the production of an anthropomorphic head-neck phantom prototype; the HU value, which is the radiosensitivity parameter, obtained from the real CT image for soft tissue and the HU values in the sample produced from PLA+ filament at 95% infill ratio are approximately equal.

[0068] The effective atomic number of PLA+ material (7.04) is quite close to the effective atomic number specified for soft tissue in ICRU Report 44 (7.07); according to ICRU Report 44, the physical density of soft tissue is 1.060 g / cm3. This value is 1.209 g / cm3for PLA+ material, being relatively close with an approximation of ~14.1%; and in the phantom 3D printed via FDM technique representing soft tissue and fat tissue in the head-neck phantom, the use of PLA+ thermoplastic material was preferred as soft tissue, fat tissue, brain and skin equivalent due to production-related parameters of PLA+ filament such as print quality, retraction amount, adhesion to the bed, temperature range being at an optimum level compared to ABS and TPU-92A, and due to practical production conveniences of 3D printing.

[0069] In SLA printer technology, the production was completed as a solid model in layers (minimum 30 pm) in this printing technique, where the resin (photopolymer) that is in liquid state at room temperature and sensitive to ultraviolet (UV) light is modeled and cured with ultraviolet light at 405 nm wavelength under the print bed.

[0070] The mean HU values obtained from CT image analyses of the samples produced from liquid photopolymer resins with SLA type 3D printer, and their physical densities measured with RADWAG BL-2200H precision analytical balance in water according to Archimedes' principle are given in Table 3.

[0071] Photopolymer resin type Measured physical density Mean HU

[0072] (g / cm3)

[0073] PLA resin 1.186 126±5

[0074] ABS resin 1.206 147±4

[0075] Standard resin 1.216 157±4Hard resin 1.208 148±5

[0076] High transparency resin 1.173 113±4

[0077] Plant-based resin 1.209 142±4

[0078] Water washable resin 1.222 158±4

[0079] PMMA resin 1.221 159±5

[0080] Dental resin 1.217 152±5

[0081] Table 3: Mean HU values obtained from the analyses of samples produced from different photopolymer resins

[0082] In the production of an adult head-neck phantom in anthropomorphic dimensions; it was aimed to produce bone tissues in accordance with specific procedures experienced in the laboratory by mixing organic and inorganic chemical powders into a solvent-free epoxy-based organic matrix at determined ratios, with the purpose of representing the skull bone, mandible, jaw structure and neck spine region (cervical vertebra) tissues. Data belonging to cortical bone taken from the reference ICRU Report 44 were taken as a basis.

[0083] The solvent-free epoxy used in the method subject of the invention consists of two different components: Component A, which is the main matrix, and Component B, which is its hardener, were prepared by mixing in a 1:2 ratio. Subsequently, different chemical powder components were added into the epoxy in different combinations. In order to develop a cortical bone mixture close to ICRU 44, tests were performed using cellulose (CMC form), hydroxyapatite (hAP), magnesium oxide (MgO), sodium dihydrogen phosphate (NaH2PO4), calcium carbonate (CaCO3), Calcium Sulphate dihidrate (CaSO4’2H2O) and a small amount of phenolic substance in the solvent-free epoxy matrix; and their radiosensitivities determined from their CT images were determined as mean HU values, (see Table 4)

[0084] Sample content Amount of Amount Amount of Mean Epoxy of hydroxyapatite HU chemical (g)

[0085]

[0086] Component powder

[0087] A (g) (g)aEpoxy+CMC+Hydroxyapatite 60.01 5.04 5.00 177±7 Epoxy+MgO+ Hydroxyapatite 60.21 4.99 5.00 173±11 Epoxy+NaH2PO4+Hydroxyapatite 64.03 5.10 5.00 156±5 Epoxy + CaCO3+ Hydroxyapatite 61.82 5.10 5.00 232±9

[0088] Note 1: Epoxy Component B was added to Epoxy Component A at a rate of 50% as a catalyst (hardener).

[0089] Note 2: In the sample studies, the amounts of different chemicals mixed with CMC: Carboxymethyl cellulose and hydroxyapatite (hAP) are given.

[0090] Table 4: Chemicals mixed into the epoxy to represent cortical bone and HU analysis results

[0091] HU coefficients were determined via analyses performed on the CT images of the prepared samples. In theoretical investigations, it was decided that using hydroxyapatite (hAP) is suitable for mimicking bone tissue. However, since the calcium and sulfur-containing hydroxyapatite does not sufficiently provide the HU value of the tissue when used alone, the Bi2O3compound, which has a higher effective atomic number that will increase the HU number, was selected to be used alongside hAP in the epoxy for conducting trials in mimicking cortical bone tissue. Therefore, different samples were prepared by adding Bi2O3at ratios of 1%, 2%, 3%, 4%, 5%, and 6%, respectively, into the mixture consisting of solvent-free epoxy and hydroxyapatite (hAP). In order to determine the HU values of the disc samples prepared for cortical bone, tomography images were acquired in CT at 120 kVptube voltage with 0.625 mm slice thickness, and HU values were obtained in the ImageJ software, which is an image processing software. (Table 5)

[0092] Bi2O3ratio by mass (%) Amount of hAP (g) Mean HU

[0093] 1 20 593 ± 92 20 827 ± 16

[0094]

[0095] >

[0096] 3 20 1021 ± 22

[0097] 4 20. 1301 ± 30

[0098] 20. 1520 ± 39

[0099] 6 20. 1673 ± 51

[0100] > >

[0101] Table 5: The effect of the amount of Bi2O3compound mixed into the epoxy matrix on the HU value

[0102] Thus, when examined in terms of radiosensitivity based on the CT image of the produced samples, the sample prepared together with hAP when bismuth oxide was mixed at a ratio of 3% best represented the cortical bone HU value with a value of HU=1021±22.

[0103] Consequently, the cortical bone equivalence of the bone components of the phantom produced by mixing 24% hydroxyapatite and a small amount like 3% bismuth oxide into the epoxy has been achieved with sufficient approximation. The hardness of the bone material in this composition on the Shore D scale, measured on the phantom, was determined as mean 89.5+2.5-0.5HD (Lower limit -0.5HD and upper limit +2.5HD).

[0104] The cortical bone equivalence of the phantom components produced with Epoxy+bismuth oxide+hydroxyapatite was ensured by the analyses given in Table 6.

[0105] Material Zeff Aeff (Z / A)eff N (xl023electron / cm3) Cortical bone 10.87 11.60 0.52 5.95

[0106] (ICRU 44)

[0107] Hydroxyapatite 14.07 24.56 0.50 *

[0108] (hAP)

[0109] Bismuth oxide 75.27 129.72 0.41 *

[0110] (Bi2O3)

[0111] Solvent-free 6.50 9.05 0.54 *

[0112] epoxy

[0113]

[0114] Cortical bone 10.38 11.60 0.52 4.13 equivalent

[0115] epoxy-based

[0116] mixture

[0117] (according to

[0118] weight

[0119] percentage)

[0120] Cortical bone 13.34 18.02 0.49 7.87 equivalent

[0121] epoxy-based

[0122] mixture

[0123] (according to

[0124] EDX analysis)

[0125] *It was not deemed necessary to calculate as they are components of the mixture. Because for the intended final product, for example here, the effect on cortical bone equivalence is essential.

[0126] Table 6: Effective atomic number, effective mass number, and electron density of the cortical bone tissue calculated from ICRU 44 data and of the epoxy powder chemical mixture used in the phantom

[0127] During sample preparation, although the particle size in the epoxy was in the order of micrometers (pm), some inhomogeneity occurred due to the sample thickness difference in the mixture. In order to eliminate this inhomogeneity, the sample was brought to the same size as much as possible in a granite mortar (agate) and then mixed with a magnetic stirrer until it became homogeneous. Afterwards, after the powder mixture in the epoxy matrix was made homogeneous with a mechanical stirrer (at 75 rpm), the hardener chemical catalyst of the solvent-free epoxy was added to the mixture at a certain ratio. Air bubbles formed in the poured samples were removed by applying a special method (torch flame), by monitoring from the moment curing first started and performing the necessary operation. The heat released during the chemical reaction was kept in a water bath, making it possiblefor the samples to solidify properly at room temperature until they reached their final state. Elemental EDX analysis was performed with the SEM-EDX device, and it was determined that the homogeneity was sufficient with the SEM image under lOOOx magnification.

[0128] Consequently, the cortical bone effective atomic number (Zeff=10.38) of the prepared epoxy -based mixture was obtained as quite close (with -4.5% deviation) to the reference cortical bone effective atomic number (Zeff=10.87) specified in ICRU 44.

[0129] In order to determine the HVL values of PLA+ and TPU-92A thermoplastic materials planned to be used as soft tissue equivalent in phantom production, plates with dimensions of 10 cm x 10 cm and in 12 different thicknesses were produced with 3D printing technique. The produced plates of different thicknesses were irradiated using an X-ray device in accordance with IEC 61267 standard at RQR-n beam qualities. Then, the measured HVL values between 40-100 kV for PLA+ filament, and their corresponding calculated linear attenuation coefficients μ= ln2 / HVL are given in Table 7.

[0130] Standard radiation Tube voltage (kVp) μ (cm-1) HVL (cm) quality

[0131] RQR-2 40 0.541 1.281

[0132] RQR-3 50 0.492 1.409

[0133] RQR-4 60 0.426 1.627

[0134] RQR-5 70 0.410 1.691

[0135] RQR-6 80 0.381 1.819

[0136] RQR-7 90 0.359 1.931

[0137] RQR-8 100 0.326 2.126

[0138] Table 7: Measured HVL values and corresponding linear attenuation coefficients for PLA+ filamentPLA+ thermoplastic material was found to be the soft tissue equivalent material in the 1st prototype production.

[0139] HVL values and mass attenuation coefficients from epoxy-based mixture plates prepared with the aim of mimicking cortical bone tissue at RQR-n beam qualities are given in Table 8.

[0140] Standard radiation Tube voltage (kVp) μ / ρ (cm2 / g) HVL (cm) quality

[0141] RQR-2 40 1.260 0.421

[0142] RQR-3 50 1.051 0.505

[0143] RQR-4 60 0.887 0.598

[0144] RQR-5 70 0.716 0.741

[0145] RQR-6 80 0.670 0.792

[0146] RQR-7 90 0.613 0.865

[0147] RQR-8 100 0.556 0.954

[0148] Table 8: Measured HVL values and corresponding mass absorption coefficients of the cortical sample from the epoxy-based mixture

[0149] Percentage elemental compositions of thermoplastic and photopolymer samples determined from the performed CHNS chemical combustion analyses are given in Table 9.

[0150] Sample type % C % H % N % S

[0151] PLA+. 49.30. 5.71. -. 0.24.

[0152] TPU-92A 62.00 6.76 4.28 - Standard. 59.00. 7.23. 7.23. -. photopolymer

[0153] resin

[0154] Table 9: C, H, N, S analysis results of PLA+, TPU-92A, and photopolymer resin

[0155] After the material determination was completed, the “Eclipse 15.6” treatment planning system was used for segmentation, radiotherapy planning, and dosecalculation in phantom development. The tumor region in the brain was determined under the supervision of an oncologist based on an adult male tomography image, and contouring and segmentation processes were performed. In the brain region of the head-neck phantom, the tumor volume was contoured as the target organ, and surrounding tissues and organs at risk were contoured by adding margins. The file in DICOM format contoured by the oncologist physician was exported, and these segment images were reconstructed in “3D Slicer” software and saved in * stl format in order to be 3D modeled in Autodesk Fusion360 software.

[0156] These segment images exported from TPS were processed with “3D Slicer” software, and the model (body image) of the head-neck phantom was designed in accordance with ion chamber and PSD measurements to be used in dosimetric measurements and made ready for printing with a 3D printer.

[0157] In Fusion360 modeling software, soft tissue and fat tissue were separated from the cortical bone part and exported in * stl format. The reason for this is that the soft tissue is produced using a 3D printer, whereas the bone part in the head is produced by casting with a fluid mixture prepared with epoxy-based powder chemicals into the bone parts printed hollow in the 3D printer.

[0158] After the first prototype was printed in the 3D printer in the form of parts as horizontal slices, it was filed with a simple hand filing tool (dremel), cleaned, and assembled with a suitable adhesive. Subsequently, the bone structures were filled with epoxy-based mixtures and left to stand for at least 24 hours to solidify. In this first prototype head-neck phantom, the brain section was designed as a detachable part.

[0159] The anthropometry method, which is used in physical anthropology and determines standards by examining specific characteristics of the human body, reveals the composition, proportions, and type of the human body. Anthropometric measurements may vary according to gender, race, and social, cultural, and economic levels. Within the scope of this project, in order to demonstrate that thehead-neck phantom produced using reference computed tomography images belonging to a real person is of an anthropomorphic structure, the physical dimensions of the phantom were determined by measuring from the points and axes specified in the literature and were compared with the results of the study conducted by Lee et al. (2018) [6],

[0160] No Anthropomorphic Literature Prototype measured dimensions dimensions dimensiona(cm) (cm)

[0161] 1st Prototype 2nd Prototype phantom phantom

[0162] A Head height 22.97 20.20±0.13 20.30±0.10 B Head length 19.54 22.67±0.15 22.51±0.10 C Head width 15.15 11.77±0.12 18.89±0.10 D Head circumference 56.81 59.60±0.20 59.50±0.10 E Face length 12.38 11.97±0.08 12.45±0.10 F Glabella-Vertex length 8.81 9.0±0.06 9.60±0.10

[0163] G Ear length 5.82 6.37±0.04 6.90±0.10

[0164] H Nose tip (Apex) 1.61 1.77±0.01 2.80±0.10

[0165] I Tragion-Lateral Canthus 7.43 8.57±0.06 7.50±0.10

[0166] J Glabella- Vertex-Occiput 30.66 29.97±0.20 31.80±0.10 arc

[0167] aHead dimensions specified in the study conducted by Lee et al. (2018) [6]

[0168] Table 10: Comparison of the head dimensions measured from certain anthropometric regions of the produced 1st Prototype head-neck phantom with the dimensions given in the literature

[0169] References:

[0170] 1. Pacific Northwest inc., The Phantom Laboratory, Randa Phantoms https: / / www2.pnwx.com / Aeeessories / Phantoms / Radiology / WholeBody / Phantomlab / Rando / )Gallas, R. R., Hünemohr, N., Runz, A., Niebuhr, N. I., Jakel, O., & Greilich, S. (2015). An anthropomorphic multimodality (CT / MRI) head phantom prototype tor end-to-end tesis in ion radiotherapy. Zeitschrift Für Medizinische Physik, 25(4), 391-399. https / / doi.org / 10.

[0171] 1016 / j.zemedi.2015.05.003.

[0172] Koluloulias, V. E. (2003).). Quality assurance in radiotherapy. European Journal of Cancer, 39(4), 415-422. https: / / doi.org / 10.1016 / s0959-8049(02)00461-6

[0173] Rose, M., Tirpak, L., Van Casteren, K., Zack, J., Siman, T., Schoenfeld, A., & Siman, W. E. (2020). Multi-institution validation of a new high spatial resolution diode array tor SRS and SBRT plan pretreatment quality assurance. Medieal Physics, 47(7), 3153-3164. https: / / doi.org / 10.1002 / mp.14153

[0174] Khan, F. M (2003). The physics of radiation therapy. Lippincott Williams & Wilkins.

[0175] Lee, W., Lee, B., Yang, X., Jung, H., Bok, I., Kim, C., Kwon, O., & You, H. (2018). A 3D anthropometric sizing analysis system based on North American CAESAR 3D scan data for design of head wearable products. Computers & Industrial Engineering, 117, 121-130. https: / / doi. Org / 10.1016 / j.cie.2018.01.023

Claims

CLAIMS1. A method for producing an anthropomorphic head-neck phantom in a heterogeneous structure and in a form suitable for human anatomy using 3D printer and molding technique, it comprises;forming the soft tissues located in the head-neck region using PLA+ thermoplastic material and the cortical bone tissue using hydroxyapatite and bismuth oxide with a 3D printer,opening holes in the created structure for the placement of dosimeters,producing the head-neck phantom by assembling the soft and cortical bone tissues.

2. The method according to claim 1, characterized by using extrusion printing technology (FDM) or vat-photopolymerization printing technology (SLA) in the 3D printer.

3. The method according to claim 2, characterized by the determination of the amount of PLA+ material depending on the body image created according to the anthropometric dimensions of the adult head-neck.

4. The method according to claim 3, characterized by the curing of the fluid form of the mixture created by adding 24% by mass hydroxyapatite and 3% by mass bismuth oxide into a solvent-free epoxy matrix, in the mold cavities created for the bone tissues in the head-neck part.

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