Dielectric Characterization of Material for 3D-printed Breast Phantoms up to 50 GHz:

Preliminary Experimental Results S. Di Meo1, E. Massoni1, L. Silvestri1, J. Obbad2, M. Pasian1, D. Dondi2,

M. Bozzi1, L. Perregrini1, G. Alaimo3, S. Marconi3, F. Auricchio3

1Dept. of Electrical, Computer and Biomedical Engineering University of Pavia, Pavia, Italy

simona.dimeo01@universitadipavia.it

2Dept. of Chemistry University of Pavia, Pavia, Italy

daniele.dondi@unipv.it

3Dept. of Civil Engineering and Architecture University of Pavia, Pavia, Italy

stefania.marconi@unipv.it

Abstract—Breast cancer is the most common disease among women in the word. However, despite the actual increase in the incidence rate, the death rate is decreasing, and this is mainly due to the improvement in screening techniques. Nowadays, one of the most common screening method is the X-ray mammography. However, its well-known limitations (woman exposition to ionizing radiations and painful compression) are requiring new imaging methods.

In the last years, microwave imaging techniques have been proposed as a promising alternative. Moreover, systems adopting higher frequencies, in the mm-wave range, have been also proposed to augment the achievable spatial resolution. A key point for the development of these systems is the availability of suitable breast phantoms, which are fundamental to test the prototypes. This paper presents the preliminary results related to the dielectric characterization of materials suitable for the realization of a 3D-printing breast phantom, aimed to mime the tumorous tissues up to 50 GHz.

Keywords—3D printing; breast cancer detection; breast phantom; breast tissue; dielectric characterization; ex-vivo; microwave and mm-wave imaging.

I. INTRODUCTION In the past few decades, breast cancer has become one of the

main causes of death among women globally. Improved screening techniques play an important role to detect the cancer at an early stage, when it is more treatable and curable with less invasive pharmacological treatments [1].

Nowadays, the most common techniques for breast cancer detection are the ultrasound ecography, the X-ray mammography, and the breast magnetic resonance imaging. However, all of them show some limitations. The ultrasound ecography is operator dependent, and it is suitable to scan only dense breasts (in most cases, younger women). The X-ray mammography, despite the good resolution, involves the patient exposition to ionizing radiations. The breast magnetic resonance requires expensive machines, which restricts its use for mass screening.

A good alternative is given by microwave imaging systems, which work on the grounds of the dielectric difference between healthy and tumorous tissues [2]. However, the most of these systems make use of operational frequencies and bandwidths in the order of some gigahertz, limiting the achievable resolution and, consequently, the possibility of making early-diagnosis [2], [3]. A natural solution to this limitation lies in the use of higher frequencies [4], [5]. Recent works, based on the experimental characterization up to 50 GHz of ex-vivo samples of human breast tissues, demonstrated the potential to obtain an image of 2-mm targets at a depth of 4 cm at mm-wave frequencies [6]–[8]. In any case, a key step toward the development of either microwave or mm-wave systems is the realization of breast phantoms, able to mime the dielectric properties of the breast tissues. In particular, a promising approach is based on the use of 3D printing, which is a good solution to realize phantoms with complex geometries, at a low cost, and able to exhibit dielectric and mechanical properties stable over time [9].

This paper presents the preliminary experimental results related to the dielectric characterization of materials suitable for the realization of 3D-printing breast phantoms. In particular, the attention is focused on materials intended to mime the dielectric properties of tumorous tissues up to 50 GHz.

II. STATE OF THE ART Several materials can be used to mimic the dielectric

properties of breast tissues. Many of them are based on gels realized with glycerin or polyethylene mixed with a gel agent, such as TX150 or T151 [10], [11]. However, such materials are water-based and are difficult to use for the 3D printing of heterogeneous phantoms. In addition, they are subject to evaporation and diffusion of the solvent.

A material typically used for 3D printing breast models is oil-in-gelatine. By changing the oil content into the mixture it is possible to generate different types of materials with different water content, so that it can be used to develop heterogeneous breast phantoms [12], [13]. All these materials have been characterized up to 20 GHz [10]. However, the main

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disadvantage of this type of material is evaporation, as well as a very complex production process of the material itself. Another type of material is polyethylene-glycol-mono-phenylether, also called Triton X100. Solutions with Triton X100 have been created and characterized with different percentages of deionized water in the frequency range up to 12 GHz [14]. However, compared to all other materials, the Triton X100 is much more expensive.

III. EXPERIMENTAL CAMPAIGN

A. Mesurement setup The measurement setup was the same used for the dielectric

characterization up to 50 GHz of ex-vivo samples of human breast tissues [6], [7]. A photograph of the system is shown in Fig. 1. In particular, an open-ended coaxial probe (Keysight 85070E Dielectric Probe Kit), working in the frequency range 0.5-50 GHz, connected through a flexible coaxial cable to the Vector Network Analyzer (VNA) (Keysight E8361C Vector Network Analyzer), was used. The complex dielectric permittivity of the Material Under Test (MUT) is measured and stored by the VNA. In addition, the measurement system includes a mechanical positioner to support the coaxial probe, and a mechanical mover in order to move the MUT toward the probe keeping fix the probe during each measurement.

B. Materials description and preparation In this paper the attention is focused on materials intended

to mime tumorous tissues. In particular, two gel systems, known for their biocompatibility, were used. The first is sodium alginate (#1), a biopolymer derived from algae and the second is a synthetic block copolymer known as Pluronic F127 (#2). The latter is well known for its non-toxicity and for the peculiarity to gelify at ambient temperature, while at temperatures lowers than 10 °C is a viscous liquid. The sodium alginate solution was prepared in water at 2 wt% concentration. Potassium iodide was added giving a total concentration of 2 wt%. The solution was gelified by adding a small amount (less than 5% v/v) of calcium nitrate solution 0.2 wt%. For the Pluronic solution, 30 wt% of Pluronic F127 was dissolved in water and potassium iodide was added for a total concentration of 2 wt%. Potassium iodide was preferred to sodium chloride due to its higher polarizability leading to a better matching with experimental curves. Both polymers used are printable with 3D printers.

In particular, both polymers can be processed through 3D printing: the most common approach relies on “Material Extrusion” systems in which the extrusion is driven by a syringe combined with a stepper motor linear actuation or by a pressure control system. The printing process must be calibrated considering the rheological properties of the materials: actually, printing speed, extrusion pressure and nozzle diameter must be calibrated as a function of the specific material viscosity. Moreover, in multilayer prints also the viscous friction of the material must be considered [15].

Fig. 1 Measurement setup

Fig. 2 Comparison between the real part of the relative dielectric permittivity of tumorous tissues (red solid line, the shaded region refers to the variable region at ± 1 standard deviation), and the tested materials (#1 in violet, #2 in black).

Fig. 3 Comparison between the imaginary part of the relative dielectric permittivity of tumorous tissues (red solid line, the shaded region refers to the variable region at ± 1 standard deviation), and the tested materials (#1 in violet, #2 in black).

The mechanical properties of two gel systems are strictly

correlated to the concentration of the polymer in solution and to the percentage of gelifying agents. For example, the elastic modulus of alginate hydrogels depends on the number density of physical crosslinks between chains [16] and from the gelation speed: actually, alginate hydrogels formed with slower rates of gelation tend to exhibit greater structural homogeneity and therefore larger modulus than those gelled rapidly [17].

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C. Dielectric characterization Fig. 2 and Fig. 3 show the comparison between the

measured dielectric properties of the materials discussed in Section IIIB and the measured dielectric properties of tumorous tissues derived from the experimental campaign presented in [6], augmented with the results from a second experimental campaign intended to validate the first one campaign [15].

It is possible to observe that the two materials described in Section IIIB can provide an approximation of the dielectric properties of tumorous tissues. In particular, the curves provided by #1 tend to lie above the mean values associated to the tumorous tissues, being within the ± 1 standard deviation region from around 20 GHz to 50 GHz for the real part. On the other hand, the curves provided by #2 tend to lie below the mean values associated to the tumorous tissues, being within the ± 1 standard deviation region up to around 6 GHz and from around 8 GHz to around 25 GHz for the real and imaginary part, respectively.

IV. CONCLUSIONS In this paper, the dielectric characterization of two materials

intended to miming the dielectric properties at 50 GHz of tumorous human breast tissues is shown. These materials are suitable for the realization of 3D-printing breast phantoms, a key point toward the development of imaging systems for breast cancer detection.

The preliminary experimental results show the possibility to have materials that can be engineered to cover a significant fraction of the dielectric properties of tumorous tissues, thus delivering the flexibility required to synthesize the optimum material according to the working frequencies and use of the intended phantom.

REFERENCES

[1] “International Agency for Research on Cancer,” http://globocan.iarc.fr/.

[2] N. K. Nikolova, “Microwave imaging for breast cancer,” IEEE Microwave Magazine, Vol. 12, No. 7, pp. 78–94, December 2011.

[3] M. Klemm, I. J. Craddock, and A. W. Preece, “Contrast-enhanced breast cancer detection using dynamic microwave imaging,” 2012 IEEE Antennas and Propagation Society International Symposium, Chicago, U.S.A., July 8–14, 2012.

[4] S. Moscato, et al., “A mm-Wave 2D ultra-wideband imaging radar for breast cancer detection,” Int. J. Antennas Propag., Vol. 2013, Article ID 475375, 8 pages, 2013, doi:10.1155/2013/475375.

[5] L. Chao, M. Afsar, and K. Korolev, "Millimeter wave dielectric spectroscopy and breast cancer imaging," 2012 7th European Microwave Integrated Circuits Conference (EuMIC), Amsterdam, The Netherlands, October 28 - November 2, 2012.

[6] A. Martellosio, et al., “Dielectric properties characterization from 0.5 to 50 GHz of breast cancer tissues,” IEEE Trans. Microw. Theory Techn., Vol. 65, No. 3, pp. 998-1011, March 2017.

[7] A. Martellosio, et al., “0.5-50 GHz Dielectric Characterization of Breast Cancer Tissues,” IET Electron. Lett., Vol. 51, No. 13, pp. 974-975, June 2015.

[8] S. Di Meo, et al., “On the Feasibility of Breast Cancer Imaging Systems at Millimeter-Waves Frequencies,” IEEE Trans. Microw. Theory Techn., Vol. 65, No. 5, pp. 1795-1806, May 2017.

[9] J. Moll, et al., “Experimental Phantom for Contrast Enhanced Microwave Breast Cancer Detection Based on 3D-Printing Technology”, 2016 10th European Conference on Antennas and Propagation (EuCAP 2016), Davos, Switzerland, April 10-15, 2016.

[10] M. Lazebnik, et al., “Tissue-mimicking phantom materials for narrowband and ultrawideband microwave applications,” Physics in Medicine and Biology, Vol. 50, No. 18, pp. 4245–4258, Sep. 2005.

[11] N. R. Epstein, et al., “Microwave dielectric contrast imaging in a magnetic resonant environment and the effect of using magnetic resonant spatial information in image reconstruction,” 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2011), Boston, MA, USA, August 30 – September 3, 2011.

[12] C. Hahn and S. Noghanian, “Heterogeneous Breast Phantom Development for Microwave Imaging Using Regression Models,” International Journal of Biomedical Imaging, Vol. 2012, Article ID 803607, 12 pages, 2012, doi: 10.1155/2012/803607.

[13] E. Porter, et al., “Improved tissue phantoms for experimental validation of microwave breast cancer detection,” 2010 4th European Conference on Antennas and Propagation (EuCAP 2010), Barcelona, Spain, April 12-16, 2010.

[14] S. Romeo, et al., “Dielectric characterization study of liquid-based materials for mimicking breast tissues,” Microwave and Optical Technology Letters, Vol. 53, No. 6, pp. 1276–1280, June 2011.

[15] S. Song, et al., “Sodium alginate hydrogel-based bioprinting using a novel multinozzle bioprinting system,” Artif Organs, Vol. 35, No. 11, pp. 1132–1136, Nov. 2011.

[16] A. Banerjee, et al., “The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells”, Biomaterials, Vol. 30, No. 27, pp. 4695–4699, 2009.

[17] C.K. Kuo, P.X. Ma, “Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: Part 1. Structure, gelation rate and mechanical properties”, Biomaterials, Vol. 22, No. 6, pp. 511–521, 2001.

[18] S. Di Meo, et al. “Experimental Validation of the Dielectric Permittivity of Breast Cancer Tissues up to 50 GHz”, submitted to IEEE MTT-S International Microwave Workshop Series on Advanced Materials and Processes, September 20-22, 2017, Pavia, Italy.

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978-1-5386-0480-9/17/$31.00 ©2017 IEEE

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