Characterizing mechanical and medical imaging properties of polyvinyl chloride‐based tissue‐mimicking materials

Abstract Polyvinyl chloride (PVC) is a commonly used tissue‐mimicking material (TMM) for phantom construction using 3D printing technology. PVC‐based TMMs consist of a mixture of PVC powder and dioctyl terephthalate as a softener. In order to allow the clinical use of a PVC‐based phantom use across CT and magnetic resonance imaging (MRI) imaging platforms, we evaluated the mechanical and physical imaging characteristics of ten PVC samples. The samples were made with different PVC‐softener ratios to optimize phantom bioequivalence with physiologic human tissue. Phantom imaging characteristics, including computed tomography (CT) number, MRI relaxation time, and mechanical properties (e.g., Poisson’s ratio and elastic modulus) were quantified. CT number varied over a range of approximately −10 to 110 HU. The relaxation times of the T1‐weighted and T2‐weighted images were 206.81 ± 17.50 and 20.22 ± 5.74 ms, respectively. Tensile testing was performed to evaluate mechanical properties on the three PVC samples that were closest to human tissue. The elastic moduli for these samples ranged 7.000–12.376 MPa, and Poisson’s ratios were 0.604–0.644. After physical and imaging characterization of the various PVC‐based phantoms, we successfully produced a bioequivalent phantom compatible with multimodal imaging platforms for machine calibration and image optimization/benchmarking. By combining PVC with 3D printing technologies, it is possible to construct imaging phantoms simulating human anatomies with tissue equivalency.


| INTRODUCTION
Medical imaging phantoms are designed for machine calibration, imaging optimization, benchmarking, comparing performance of multimodal systems, and developing novel imaging techniques. 1 Commercial phantoms are traditionally machine-made; 2 however, more recently, the cost of three-dimensional (3D) printing has dramatically decreased and use in the medical imaging field has evolved. [3][4][5][6][7] The combination of 3D printing technology and tissue-mimicking materials (TMMs) has enabled anatomically precise phantom construction with bioequivalent medical imaging characteristics.
For TMMs to be used for medical imaging phantom, the physical and imaging characteristics should be as close to human tissue as possible. TMMs should have equivalent x-ray attenuation coefficients and computed tomography (CT) numbers for CT phantoms, as well as T1 and T2 relaxation times for magnetic resonance imaging (MRI) phantoms. 8 Additionally, mechanical properties of the phantom, such as compressive strength, deformation, fracture, and friction can affect the imaging approach. Therefore, they should quantitatively match human tissue by physical parameters, i.e., hardness, elastic modulus, and Poisson's ratio. 9 Common TMMs are generally biopolymers or chemically synthesized polymers. Biopolymers have a high mass fraction of water, and their features are analogous to those of soft tissues. 9 Various phantoms are manufactured using polysaccharides, agar, agarose and gelatin. [10][11][12][13] However, water evaporation and bacterial growth are the major limitations to the long-term preservation of biopolymers, and phantoms constructed from these materials. 11,[13][14][15] Chemically synthesized polymers are more stable and durable than biopolymers, but they show a certain degree of deviation from human tissues due to the lack of water. 16 Polyvinyl chloride (PVC) is a common synthesized polymer. It has the advantages of easy synthesizability, nontoxicity, bacterial resistance, stability and durability. Meanwhile, PVC also has a long lifespan without the need to use material preservatives. 9,17 Additionally, it is possible to combine PVC with other materials to improve the relative biologic similarity when compared with human tissue as determined by imaging characteristics.
This study aims to explore the medical imaging and mechanical properties of PVC with various PVC-softener ratios. Specifically, medical imaging properties include x-ray attenuation coefficients, CT numbers, and MRI relaxation times. Mechanical properties include elastic modulus and Poisson's ratios.

2.A | Tissue-mimicking materials preparation
Polyvinyl chloride ((CH 2 -CHCl) n ) powder and dioctyl terephthalate softener were used to create the TMM. PVC-based TMM samples were prepared through the following steps. (a) Weighing: raw PVC and softener materials were prepared and weighed for preparing ten samples with PVC-softener ratios ranging from approximately 7.9 × 10 −2 to 23.1 × 10 −2 g/ml (e.g., PVC-softener ratio of 7.9 × 10 −2 g/ml indicates 7.9 g PVC powder mixing with 100 ml of the softener). 18 (b) Heating and Stirring: weighed raw materials were mixed and heated to 280°C under constant stirring for 30 min. 18 Once the PVC-softener mixture becomes transparent, the TMM is ready for evaluation and testing 17 (c) Cooling: the mixture was cooled under ambient conditions to room temperature. 2.B | Medical imaging properties 2.B.1 | CT number Ten samples were scanned via CT scanner (120 kV, 100 mA), and the corresponding CT numbers were recorded. After obtaining these data, a scatter plot was created to find the correlation between the PVC-softener ratio and CT number using the SPSS 22.0 (SPSS Inc., Chicago, IL, USA) for quantitative analysis.

2.B.2 | Attenuation coefficient
Linear attenuation coefficients (LACs) of the ten samples were measured with 40-130 kV x-ray beams using narrow-beam geometry.
LACs are based on the Lambert-Beer law when ignoring scattering and background noise 19 . The incident and transmitted beam intensities and the thickness (18.7 ± 0.8 mm) of the samples are taken into account for calculating LACs.   21 Experiment conditions included T = 24 ± 5°C and humidity = 50 ± 5%.

2.C | Mechanical properties
Each PVC sample was clamped and prestressed before testing.
After balancing the prestressed sample, the extensometer was HE ET AL.

| 177
removed and tested at a loading speed of 50 mm/min until PVC sample breakage occurred. Test forces and their corresponding gage lengths and the distances between grips were recorded. 22 The constitutive equation is as follows (1): where σ ij represents the stress tensor, E represents the elastic modulus, ɛ ij represents the strain tensor, ν represents the Poisson's ratio, σ kk represents the spherical stress tensor, and δ represents the Kronecker symbol.

2.D | Phantom construction
A thoracic phantom, manufactured by our team and previously described by Zhang et al, 23 consists of a thoracic shell with different biopolymers-based TMMs. In the present study, we focused on the synthesized polymer TMM (i.e., PVC-based material), due to its higher stability and durability in medical imaging and mechanical properties. 9,17 The PVC-based thoracic phantom was constructed as follows: manufacturing the phantom is shown in Fig. 2. Based on the above steps, when the TMMs were cured, the thoracic phantom was completed. Meanwhile, another PVC-based breast phantom was also produced for multimodal imaging and QC detection. 6 3 | RESULTS

3.A | CT number
There was a positive linear relationship between CT number (−10 to + 110 HU) and PVC-softener mixture over a range of 7.9 × 10 −2 to 23.1 × 10 −2 g/ml, as shown in Fig. 3(a). CT number to

3.B | Linear attenuation coefficient
Mean LAC values as a function of tube voltage for the 10 PVC samples are shown in Fig. 3

3.C | Elastic modulus and Poisson's ratio
The stress-strain curves for three selected PVC samples with different PVC-softener ratios, as shown in Fig. 5. As the proportion of PVC in the mixture increases, the deformation capacity increases.
When the deformation limit is reached the elastic modulus of the material is exceeded, and breakage may occur.

3.D | Thoracic phantom
The anthropomorphic thoracic phantom is shown in Fig. 6(a); corresponding CT images are shown in Figs. 6(b) and 6(c). Ten measurement areas were randomly selected for each organs/lesion on this phantom. The corresponding TMMs and CT numbers are summarized in Table 2  We found that the Poisson's ratio for various PVC-softener ratios ranged within 0.604-0.644, which is different from 0.49 reported in Naylor hypothesis. 24 Factors contributing to this phenomenon may include different PVC-softener ratios or raw material manufacturing.
Literature reported 50.3081 MPa for a loading speed of 5 mm/min, 50.798 MPa for a loading speed of 15 mm/min, 25 6.0 × 10 3 -45.0 × 10 3 MPa in a compression test for elastic modulus measurement, 9 158.0 MPa in the case of a pen, and 2.5 × 10 3 MPa with shrink film, 26 while elastic moduli for the tested samples were 7.000- 12.378 MPa in our study. Factors leading to these differences may be a combination of various plastic materials, material temperature, strain rate, parallax, and cross sectional thickness. 26 In addition, experimental results can also be affected by small number of samples, narrow range of PVC-softener ratios, and differences in measurement methods.
The relationship between PVC-softener ratios and CT number was similar to those reported by Liao et al. 18 Furthermore, varying the PVC-softener ratio linearly affects CT numbers of the TMMs (R 2 = 0.988). These findings indicate that a high degree of tissue equivalency can be optimized by varying PVC-softener mass ratios.    30 One deformable prostate phantom based on different ratios of PVC-softener mixtures was constructed for multimodal imaging, such as ultrasound, CT, and MRI. 16 Mixing different concentrations of PVC plastisol and graphite powder can simulate lesions with different echo patterns in ultrasound imaging. 31 And a PVC-based multimodal breast phantom was fabricated for QC detection. 6 In the present study, by optimizing the PVC-softener mass ratio, TMMs were identified in manufacturing an anthropomorphic heterogeneous thoracic phantom. CT numbers of this phantom closely representing those of human tissues with higher cost efficiency compared with the study by Mayer et al. 32 Meanwhile, compared with the study by Zhang et al., 23 the TMMs used in this phantom was more stable and easier to preserve.
Overall, the significance of the study is in providing an optimized PVC-based material. Combined PVC with 3D printing technology, it is possible to achieve the production of medical phantoms. Any predetermined CT number, Poisson's ratio, and elastic modulus (within a reasonable range) can be achieved by adjusting PVC-softener mass ratio. The same techniques used in the generation of our thoracic phantom can be applied to small animal phantom construction. MRI T1 and T2 relaxation times of the studied materials are shorter than most of human tissues, thus will require further experimental investigation and optimization to achieve MRI tissue equivalency. Future studies may also include the characterization of PVC-based materials for Ultrasound imaging.

| CONCLUSION
The present study evaluated various PVC-softener mixtures and characterized their medical imaging and mechanical properties. PVC has the advantages of being low cost, easy to produce, and durable.
CT numbers of the PVC linearly depended on the PVC-softener mass ratio, but the MRI relaxation times (T1 and T2) present small variation with ratio. Due to the low internal moisture content of PVC, further improvements in the MRI imaging aspect are needed.
By combining 3D printing technology with biologically optimized PVC materials it is possible to print heterogeneous, anthropomorphic bioequivalent medical imaging phantoms with tissue equivalence for CT imaging.

CONFLI CT OF INTEREST
The authors have no relevant conflicts of interest to disclose.