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Dielectric properties of breast tissues:

experimental results up to 50 GHz


S. Di Meo1, P. F. Espin-Lopez1, A. Martellosio1, M. Pasian1, M. Bozzi1, L. Perregrini1, A. Mazzanti1,
F. Svelto1, P. E. Summers2, G. Renne3, L. Preda4,5, and M. Bellomi2,6
1:Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy
(e-mail: simona.dimeo01@ateneopv.it)
2: Department of Radiology, European Institute of Oncology, Milano, Italy
(email: paul.summers@ieo.it)
3: Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milano, Italy
(email: giuseppe.renne@ieo.it)
4: Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
(email: lorenzo.preda@unipv.it)
5: National Center of Oncological Hadrontherapy (CNAO Foundation), Pavia, Italy
6: Department of Oncology, University of Milano, Milano, Italy

Abstract—Nowadays, breast cancer is the most diffused this makes it worthless in dense breasts. On the other hand,
disease among women around the word. Statistics indicate an Ultrasound offers good possibilities in penetrating dense
increase in incident rate, especially in Europe, North America, breasts, but in a methodology too operator dependent, in
and Oceania. Currently, the set of diagnostic tools for breast addition Ultrasound is not efficient in penetrating high density
cancer detection is wide. Nevertheless, these tools exhibit
limitations, especially when aiming at cost-effective periodical breasts.
mass screenings. Therefore, there is a growing interest toward For all these reasons, microwave imaging techniques are
microwave imaging systems for biomedical applications, and proposed. The advantages of using microwave frequencies are
several microwave prototypes have been proposed worldwide. several: the utilization of not-ionizing radiations, without the
However, in order to have a satisfying resolution for early- need of breast compression, with a cheap instrumentation
diagnosis, microwaves may be not sufficient, and a crucial point (reflecting in low-cost tests for the patient).
is the utilization of higher frequencies. To this aim, as the Several prototypes have been proposed around the world
physical principle of all imaging techniques at these frequencies
is based on the detection of the dielectric discontinuities between
[3-7], however all of them share more or less the same
materials, the characterization of all breast tissues in the mm- operational frequency of some gigahertz, therefore spoiling
wave spectrum becomes fundamental. No experimental data the possibility of having a fine resolution [8], [9]. A not good
were available beyond 20 GHz before the two extensive resolution, as it is simple to imagine, translates directly in a
experimental campaigns performed at the European Institute of not acceptable morphological reference.
Oncology in 2014 and 2016. In this paper, the results concerning A way to bypass this problem is the utilization of higher
the full database (given by the fusion of the two datasets) of ex-
frequencies, even if this translates is a lower penetration depth
vivo samples, are presented. In particular, a huge amount of
data is considered, involving more than 330 samples, of which in tissues. In particular, several studies have been performed
237 healthy and 99 malignant, taken from around 100 women about an imaging system with a central working frequency of
with an age spanning from 28 years up to 85 years. 30 GHz and a 20-GHz bandwidth, using a multi-static radar
architecture both for linear and conformal arrays (as they
Index Terms—Dielectric characterization, ex-vivo samples, correspond to the two possible positions of the woman during
mm-waves, imaging systems, breast cancer detection, the test). Results of this feasibility study have shown that in
measurements. almost 50% of the feminine population, the achievable
penetration depth is some centimeters below the skin and with
I. INTRODUCTION a resolution of some millimeters, using the Delay-And-Sum
Breast cancer is the most diagnosed disease between (DAS) enhanced version, so the Filtered-Delay-Multiply-
women in the world, and it is the first cause of death between And-Sum (F-DMAS) algorithm [10], [11].
women for cancer [1], [2]. All radar techniques are based on the different scattering
Nowadays, the range of diagnostic tools for breast cancer from healthy and cancerous tissues, as the tumor is
detection is wide, and the most utilized are the X-ray characterized by a high blood perfusion, so a higher water
mammography and the Ultrasound. However, ionizing content compared to normal tissues. This is a well accepted
radiations are involved in mammography and for this reason knowledge, basing on fitted values taken from relatively low
it cannot be proposed in a mass screening program, as well as frequencies measurements. Starting from 2014, in the
it requires a fussy breast compression. In addition, X-rays are framework of a project funded by the Italian Association for
unable to penetrate tissues with high percentage of water, and Cancer Research (Italian acronym, AIRC), two experimental
campaigns have been performed in the very wide frequency B. Workflow
rage [0.5-50] GHz, at the European Institute of Oncology, in All measurements for both experimental campaigns were
Milan [12], [13], [14]. Before these campaigns, no measured performed at the Pathology Department of the European
data were available behind 20 GHz [15]-[16]. Both the Institute of Oncology, in Milan. The workflow, shown in
measurement sessions have confirmed the dielectric Figure 3, was decided in collaboration with the medical staff.
differences between healthy tissues and cancerous ones, as In particular, after the surgical operation (eg. lumpectomy,
well as a higher separation between low density tissue and quadrantectomy, and mastectomy), and the transportation in a
malignant ones. specimen bag of the removed breast, the sample was prepared
While in [12], results coming from the only first by a pathologist to be measured by the engineer, and the
experimental campaign (2014), involving more than 200 ex- sample dimension was some mm3. Depending on the
vivo tissues coming from around 50 women, were shown, and dimension of each sample, the number of different dielectric
in [14], results coming from the only second experimental measurements was variable, and to distinguish each side
campaign (2016), involving 124 ex-vivo samples coming from different acrylic inks were used. After these steps, the
45 different patients, were reported; in this paper, results dichotomy features of each area marked with inks (healthy,
coming from the merged database involving a huge amount of with the relative adipose content, versus cancerous tissues)
experimental data are presented. Statistics have been were defined by a pathologist. The pathological description of
performed on more than 330 ex-vivo samples, healthy and the nature of the sample was included in the database together
cancerous, taken from around 100 women of different age (28 with the electromagnetic response. These medical responses
to 85 years). Also Cole-Cole parameters have been derived for were used as benchmark both to assess the capability of
breast tissues, and an estimate of the sensitivity and specificity dielectric properties to distinguish normal tissues form
has been performed. malignant ones, and for the analysis of sensitivity and
specificity, as it will be explained in Section IV.
II. MEASUREMENT SETUP AND WORKFLOW

A. Measurement setup
For both experimental campaigns, the measurement setup
was the same. In particular, the open-ended coaxial probe has
been used as dielectric spectroscopy technique. The whole
measurement setup was constituted by a Keysight E8361C
Vector Network Analyzer (VNA), a high-performance
flexible coaxial cable (provided with the Keysight 85070E
Dielectric Probe Kit), a mechanical mover, and the open-
ended coaxial probe (Keysight 85070E Dielectric Probe Kit)
able to perform suitable measurement in a wide frequency
range ([0.5-50] GHz) and temperature one (from -40° up to
220°). Figure 1 represent the measurement setup.
In this way, dielectric properties of the Material Under Fig. 1 Measurement setup used for both experimental campaigns
Test (MUT) are measured by means of a reflectometry-based
approach. The involved coaxial probe is characterized by a
small footprint; the diameters of inner and outer conductors
are very small, 0.268mm and 1.6mm, respectively. They
generate a quasi-static capacitor-like field, and the sensing
volume of the probe is around the diameter in later direction,
with a 2-mm penetration depth in all kind of tissues for all the
investigated frequencies. A sketch of the field is shown in
Figure 2.
An important precaution adopted for each measurement
was the air-presence removal between the coaxial probe head
and the MUT. Therefore, a small and controlled pressure (by
means of the mechanical mover) was applied.
In addition, to remove spurious errors from the collected
data, the coaxial probe was calibrated before each Fig. 2 Sketch of the probe penetration depth
measurement by means of three standards: open ended, short
termination, and deionized water at a controlled temperature.
After the calibration, no movements of the probe were
possible, in order to provide phase stability, especially at high
frequencies.
imaginary part of the dielectric permittivity between the
measured and the fitted data for the average malignant tissues,
as it is representative of all situations.

Fig. 3 Clinical protocol for both experimental campaigns

Also the temperature and the time between the excision


and the measurement were controlled, to avoid alterations in
measurements due to these external conditions. In particular,
the temperature of each sample was measured using a
contact-less infrared thermometer (all samples were kept at Fig. 4 Characterization of the real part of the relative dielectric
around 21°, the room temperature), and the time between the permittivity for normal (blue line) and malignant (red line) tissues. The shaded
excision and the measurement didn’t exceed 3 hours and 30 region denotes the variable range at ± 1 ı
minutes, to avoid the superficial water evaporation of the
sample.

III. DIELECTRIC PROPERTIES


OF BREAST CANCER T ISSUES
Dielectric properties of measured samples were collected
in terms of real and imaginary part. Results considering all
kind of healthy tissues and tumorous ones, derived from the
fusion of the two experimental campaigns, are shown in Figs.
4 and 5.
Fig. 5 Characterization of the imaginary part of the relative dielectric
A. Comparison between different types of normal tissues permittivity for normal (blue line) and malignant (red line) tissues. The shaded
and malignant tissues region denotes the variable range at ± 1 ı
In addition, a classification between healthy samples has
been performed. In particular, healthy tissues have been
classified with respect to their decreasing water content, in
high (adipose content lower than 20%), medium (adipose
content between 20 and 80%), and low density (adipose
content greater than 80%), and all of them have been
compared with the dielectric properties of cancerous tissues.
Fig. 6 and Fig. 7 show the comparison in dielectric
properties for real and imaginary part, respectively.

IV. COLE-COLE MODELS


The model used in this paper to represent the frequency- Fig. 6 Differences between the real part of the average relative dielectric
dependent complex relative permittivity İ of the tissues is the permittivity for healthy and cancerous tissues.
single-pole Cole-Cole model, a commonly accepted standard:
ǻİ ɐ•
İ(Ȧ) =İ'(Ȧ)-jİ''(Ȧ)=İ’+ +  (1)
1-(jȦIJ)1-Į ŒɘɂͲ
where İ' and İ'' are the frequency-dependent real and
imaginary part of the dielectric permittivity, and İ’, ǻİ, IJ, Į
and ıs are the Cole-Cole parameters. These parameters were
computed using the least-square fitting to the average values
of the measured dielectric properties.
Results are summarized in Table I for the average values
of healthy and tumorous tissues, taking into account the
difference in density between tissues, and an optimum
agreement is achievable in all frequency band both for real and Fig. 7 Differences between the imaginary part of the average relative
imaginary part. Fig. 8 shows the comparison in real and dielectric permittivity for healthy and cancerous tissues.
V. SENSITIVITY AND SPECIFICITY
The two parameters used in medical field to assess the
quality of a diagnostic tool are the Sensitivity and the
Specificity. In particular, Sensitivity is related to the True
Positive (TP) rate, so sick people who are correctly classified
as sick, while Specificity is related on True Negative (TN) rate,
so healthy people who are correctly identified as healthy. A
diagnostic method, indeed, could also identify as sick an
healthy patient, so defining the so called False Positive (FP),
or vice versa, increasing the named False Negative (FN) rate.
Fig. 8 Comparison in real (red lines) and imaginary (blue lines) part Sensitivity and Specificity are defined as follows:
between the measured (continuous line) and fitted (dotted line) data for the
average malignant tissues. Tp
Sensitivity = (2)
Tp+Fn


Specificity = (3)
൅ ’

Fig. 9 reports the values of Sensitivity and Specificity for


the whole database. Results are compared also with the typical
values of Sensitivity and Specificity of the actual X-ray
mammography, in Table II.
As it can be seen, a good agreement exists between them,
(a)
and this is a promising result even if the authors of this paper
are conscious that the comparison is between an actual
diagnostic tool and an ex-vivo characterization.

VI. CONCLUSIONS
In this paper, the dielectric characterization of human
breast tissues up to 50 GHz on a huge database is presented.
This is the fusion of two datasets (achieved during two
expensive experimental campaign performed at the European
Institute of Oncology in Milan, in 2014 [12] and 2016 [14]
respectively), and includes more than 330 ex-vivo samples,
(b) derived from around 100 women of all ages. This fusion is a
Fig. 9 Sensitivity and Specificity calculated for real (a) and imaginary (b) part direct consequence of the good agreement in results obtained
of the relative dielectric permittivity. in the two separate experimental campaigns [12], [13], [14].
Results show that there is a higher variability in dielectric
TABLE I. COLE-COLE PARAMETERS DERIVED FOR NORMAL AND
properties of healthy tissues compared to malignant ones, and
MALIGNANT TISSUES. this is due to the different adipose percentage constituting
them. However, dielectric properties are significantly
Normal Malignant
Low Medium High
different, both for real and imaginary part, in all the
density density density investigated frequency range, reinforcing the idea of building
ǻİ 9,08 24,83 39,2 48,4 an imaging system on them.
İ’ 3,6 4,6 5,089 4,9
IJ(ps) 17 11 9,58 9 ACKNOWLEDGMENT
Į 0,19 0,14 0,1 0.09 The authors would like to thank all the medical staff of the
ıs 0,16 0,45 0,7 0.8 European Institute of Oncology in Milan for their help during
the work. This work was partially supported by the Italian
TABLE II. COMPARISON BETWEEN SENSITIVITY AND SPECIFICITY OF Association for Cancer Research (AIRC).
MAMMOGRAPHY AND THE DIELECTRIC CHARACTERIZATION OF EX-VIVO
BREAST TISSUES.

Diagnostic test Sensitivity Specificity


Mammography 75 85

Present work 86 72
REFERENCES

[1] “International Agency for Research on Cancer,”


http://globocan.iarc.fr/.
[2] “Cancer Treatment and Survivorship Facts & Figures 2014-2015,”
Atlanta: American Cancer Society; 2014.
[3] M. Klemm, I. J. Craddock, J. A. Leendertz, A. Preece, and R.
Benjamin, “Radar-based breast cancer detection using a hemispherical
antenna array - experimental results,” IEEE Transactions on Antennas
and Propagation, Vol. 57, No. 6, pp. 1692–1704, June 2009.
[4] T. M. Grzegorczyk et al., “Fast 3-D tomographic microwave imaging
for breast cancer detection,” IEEE Transactions on Medical Imaging,
Vol. 31, No. 8, pp. 1584–1592, August 2012.
[5] E. C. Fear, J. Bourqui, C. Curtis, D. Mew, B. Docktor, and C. Romano,
“Microwave breast imaging with a monostatic radar-based system: a
study of application to patients,” IEEE Transactions on Circuits and
Systems, Vol. 61, No. 5, pp. 2119–2128, May 2013.
[6] M. J. Burfeindt, J. D. Shea, B. D. Van Veen, and S. C. Hagness,
“Beamforming-Enhanced Inverse Scattering for Microwave Breast
Imaging,” IEEE Transactions on Antennas and Propagation, Vol. 62,
No. 10, pp. 5126–5132, June 2009.
[7] H. Bahramiabarghouei, E. Porter, A. Santorelli, B. Gosselin, M.
Popovic, and L. A. Rusch, “Flexible 16 antenna array for microwave
breast cancer detection,” IEEE Transactions on Biomedical
Engineering, Vol. 62, No. 10, pp. 2516–2525, October 2015.
[8] 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.
[9] N. K. Nikolova, “Microwave imaging for breast cancer,” IEEE
Microwave Magazine, Vol. 12, No. 7, pp. 78–94, December 2011.
[10] S. Di Meo, et al., “On the Feasibility of Breast Cancer Imaging
Systemsat Millimeter-Waves Frequencies,” IEEE Trans. Microw.
Theory Techn., Vol. 65, No. 5, pp. 1795-1806, May 2017.
[11] G. Matrone, et al., “The Delay Multiply and Sum beamforming
algorithm in ultrasound B-mode medical imaging,” IEEE Trans. Med.
Imag., vol. 34, no. 4, pp. 940-949, 2015.
[12] 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.
[13] A. Martellosio, M. Pasian, M. Bozzi, L. Perregrini, A. Mazzanti, F.
Svelto, P.E. Summers, G. Renne, and M. Bellomi, “0.5–50 GHz
Dielectric Characterization of Breast Cancer Tissues,” IET Electronics
Letters, Vol. 51, No. 13, pp. 974–975, June 2015.
[14] S. Di Meo, et al., “Experimental Validation of the Dielectric
Permittivity of Breast Cancer Tissues up to 50 GHz”, IEEE MTT-S
International Microwave Workshop Series on Advanced Materials and
Processes, Pavia, Italy, September 20-22, 2017.
[15] M. Lazebnik, et al., “A large-scale study of the ultrawideband
microwave dielectric properties of normal breast tissue obtained from
reduction surgeries,” Physics in Medicine and Biology, Vol. 52, No.
10, pp. 2637–2656, 2007.
[16] M. Lazebnik, et al., “A large-scale study of the ultrawideband
microwave dielectric properties of normal, benign and malignant breast
tissues obtained from cancer surgeries,” Physics in Medicine and
Biology, Vol. 52, No.20, pp. 6093–6115, 2007.

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