This document discusses two techniques for detecting breast cancer using bioimpedance: 1. A mobile electrical impedance tomography IC that can detect breast cancer in 3D through non-invasive surface impedance measurements. It has high sensitivity and can detect tumors as small as 5mm. 2. A fiber optic bioimpedance spectroscopy system that combines fiber optic and bioimpedance methods to differentiate between normal, low metastatic, and high metastatic breast cell types through statistical analysis of their optical and impedance spectral signatures. It shows potential for non-invasive cancer progression monitoring.

1. Bio-impedance
Technique in Breast Cancer
By: Athra’a Sabeeh Mikha
Al-Nahrain University
College of Engineering
Biomedical Eng. Dep.

2. Topics:
• Breast Cancer
• Introduction of Bio-impedance
• History
• Mobile Electrical Impedance Tomography IC for Early Breast-Cancer Detection
 Device configuration
 Electronic circuit
 Method technique
 Implementation and measurement result
 Breast Cancer detection system measurement results
• Determination of cancer progression in breast cells by fiber optic bio-impedance spectroscopy system
 Introduction
 Design of FOBIS system
 Materials and methods
 Materials and methods
 Results
 Discussion
• Conclusion

3. Breast Cancer
• Breast cancer: is a cancer that forms in the tissues of the breast – usually in the ducts (tubes that carry milk to the
nipple) or lobules (glands that make milk). It occurs in both men and women.
Breast cancer is often classified into two types:
1) Non-invasive breast cancer or in situ carcinoma is located in the breasts of the breast. It can not be detected at the palpation of the
breast, but in a mammogram.
2) Invasive breast cancer extends beyond the breast. The most common form of breast cancer is invasive ductal breast cancer, which
develops in the cells of the ducts.
• Other types of breast cancer include invasive lobular breast cancer, inflammatory breast cancer and Paget's breast disease.

4. Introduction of Bio-impedance
• Bioimpedance: is a term, which describes the response of living organisms to an externally applied current. It is
a measure of opposition to the flow of the applied current through tissues. The measurement of bioimpedance
of a living organism is non-invasive method for assessing its composition. A bioimpedance signal can be used
for characterizing the tissue. The electrical properties of tissue vary with different applied frequencies.
• Bioimpedance is a well-established method in detecting breast cancer, cervical cancer, prostate cancer, etc.
The studies showed that there are significant differences in bioimpedance between normal tissues and
cancerous tissue.
 Over the years bioimpedance has emerged as a better screening tool over the current screening methods since
it is relatively low-cost, provides instant results, requires little training and therefore bioimpedance can be easily
used in primary care centers or in developing countries, where multiple factors limit national screening
programs. The potential advantages of real-time screening tests include: a reduction in patient anxiety;
improved patient compliance; and the ability to repeat inadequate tests immediately.

5. History
• The role of bioimpedance in cancer detection starts way back in 1926 with first study on breast cancer.25
Although there were conflicting results, consensus on differences in bioimpedance in tumor breast tissue
and normal tissue was established.
• In 1988, Surowiec et al.26 performed in vitro tests to determine the variability of properties between samples
of breast carcinoma, samples with a combination of carcinoma and healthy tissue including the perceived
boundary of the lesion, and samples of healthy tissue only. The results showed that the dielectric constants
and the conductivity of cancerous tissues differed between the sample groups (as measured for frequencies
from 20 kHz to 100 MHz), although considerable variability existed in the measured data.
• Later on in 1990, Morimoto et al.27 developed a new impedance analytical system, and used a frequency
range of
(0–200 kHz) by the three-electrode method. The three electrodes consist of :
1. coaxial needle electrode inserted into the tumor
2. large reference electrode on the upper abdominal wall.

6. The biological tissue can be regarded electrically as an equivalent consisting of extracellular
resistance (Re), intracellular resistance (Ri), and electrical capacitance of the cell membrane (Cm).
These three parameters were calculated from the measured values of electrical bioimpedance by
the curve-fitting technique using a software. It was found that Re and Ri of breast cancers were
significantly higher than those of benign tumors ( p less than 0.01), and that Cm of breast cancers
was significantly lower than that of benign tumors ( p less than 0.01).

7. several research have been reported to the early detection of breast cancer. But most of the previous
detection system determination of cancer progression in breast cells like X-ray mammography and ultrasonic
screening are mainly used. In this seminar I'll explain some Techniques in Breast Cancer use
Bio-impedance such as:
Mobile Electrical Impedance
Tomography IC for Early
Breast-Cancer
Detection
Determination of cancer
progression in breast cells
by fiber optic bioimpedance
spectroscopy system

8. Mobile Electrical Impedance Tomography IC for Early Breast-Cancer Detection
Electrical Impedance Tomography (EIT) is an imaging technique which calculates the electrical conductivity distribution within the interior of a body
from the impedance measurements on its surface. Since malignant breast tissue has about 3 times higher impedance than normal breast tissue
and has different impedance characteristics.
The structure of proposed EIT patch fabricated using P-FCB technology
The hemispherical EIT patch (12 cm diameter and 5 cm height) has three layers and all three layers are implemented by P-FCB
process and stacked to form the brassiere shape:
the electrode
array layer
the electrode
connection layer
the electronic

9. Device configuration:
1. The electrodes configuration are ,90 EIT electrodes and 1 voltage reference
electrode each of diameter 8 mm are implemented on the electrode array
layer. For the prototype system, the 90 EIT electrodes are arranged as 5
concentric circles, and each circle has 6, 12, 18, 24, and 30 electrodes
respectively so that all distances between neighboring electrodes are equal.
2. The electrode array and EIT IC is connected via an electrode connection
layer, and EIT IC is and molded on the topmost electronic circuit layer.
3. EIT IC is wire-bonded and molded on the topmost electronic circuit layer.
4. All three layers are implemented by P-FCB process and stacked to form the
brassiere shape.

10. Electronic circuit:
1) A switching network for reconfigurable measurement modes.
2) Differential Sinusoidal Current Stimulator (DSCS) to inject the programmable single-tone current signal.
3) Six channel analog front-end to measure voltages with high sensitivity and perform digitization.
4) digital controller for system control and data calibration.
1
2
3
4

11. Method technique:
 A breast cancer tissue is static, there is no temporal impedance difference between the measurements.
Therefore, the frequency difference method should be used.
 the impedance change versus frequency in healthy breast tissue is different to that in malignant tissue
measurements at two different frequencies are used to obtain a static EIT image.
 A current stimulator is designed to inject current signals at 100 Hz, 1 kHz,10 kHz, 100 kHz, because the largest
impedance variations are measured in the range from 1 kHz to tens of kHz. Therefore, the measurement data at
low frequency (below 1 kHz) is used as the reference.
 The DSCS is designed with high output impedance (larger than 100 k ) to prevent the mismatch and the load
impedance variation of the current stimulator.
 The proposed system has three operating modes depending on the configuration of the switching
network.
gain scanning
(GS) mode EIT mode
contact impedance
monitoring (CIM(
mode

12. gain scanning (GS) mode contact impedance monitoring (CIM(
mode
EIT mode
 to obtain gain mismatch information
of the six voltage measurement
channels, because the channel
mismatch can determine the overall
measurement error .
 the current stimulator and each of
the voltage sensing amplifiers in the
analog front-ends are connected via
an internal 100 sensing resistor
through the switching network with
the current stimulator set to 10 A .
 to check whether the electrodes are in reliable
contact with the breast skin or not.
 . In CIM mode, the analog front-end measures
the voltage developed on a pair of electrodes
while the current source injects 10 A to the same
pair of electrodes, and this step is repeated for
all 90 electrodes. Then, the digital controller
calculates the contact impedance of each
electrode and divides the electrodes into four
groups according to their contact impedance
values (Good, Average, Bad, No Contact).
 is injected between two electrodes, while
six channels of analog front-ends are
connected to the different pairs of
electrodes in turn until the voltages of all
electrode pairs are measured .
 the digital controller transmits the
calibrated data to the external imaging
device. The pairs of electrodes in the EIT
mode are freely selected by programming
the switching network to support various
imaging algorithms.

13. The Digital controller is composed of
UART interface
Memory
Controller
 the controller accepts the electrode switching sequence from
instruction memory (IMEM).
 It generates the switching signals to reset the analog front-end and
to change the electrode configuration in the switching network.
 The ADC samples the demodulated voltage signal N times
according to the preset frequency of the ADC clock. Therefore,
after N data words are collected, the controller calculates the
average which is then stored in data memory (DMEM) together with
the gain control codes generated by the AGC.
 When the electrode switching sequence is complete, the stored
data is used to calibrate for channel gain mismatch reduction.
 In GS mode, the gain of each channel is measured individually.
 The gain deviation of each channel from the reference gain is
stored in memory, and later the stored gain deviation is added to or
subtracted from the measured data at each channel. Finally, the
calibrated data is transmitted to the external smart device through
the UART interface

14. Implementation and measurement result:
1. the output spectrum of the DSCS while providing 200 A of sinusoidal current with a load resistor
2. of 2 k . Differential sinusoidal currents of 122 Hz, 1.23 kHz, 12.8 kHz, and 121.7 kHz are generated, and these 4
frequencies can be selected via a 2 bit digital code.
3. All harmonics are less than 59 dBc, the amplitude of the current can be increased from 10 A to 400 A by controlling the
resistor in the V/I converter with 2 bit digital control signal, and the current amplitude is decided according to the measured
contact impedance in CIM mode. 400 A of current can be provided up to 1 k of load impedance with maximum current
variation of 1%.
4. AGC measurements as the input signal is decreased 14 mV to 2 mV. When the AGC is turned off and the total gain of
amplifier is set to 18 dB, the output signal of PGA also decreases, following to the input. when the AGC is turned on, the 3
bit gain control signal of PGA is adaptively changed.
5. The measured output of ADC when the AGC is activated or not. With the help of AGC, all input signals from a few V to tens
of mV can be adaptively amplified into mV-scale.
6. The measurement results of PPD. As the peak detection pulse is set to high at the highest or the lowest peak of the input
signal, the differential output of PPD represents the amplitude of the input sinusoidal signal.
7. The electrode switching signal from the digital controller. In EIT mode, when the electrode switching signal is high, the
electrode configuration changes to the next configuration by the digital controller.
8. The proposed EIT IC is fabricated in 0.18 m 1P6M CMOS technology, and occupies 2.5 mm 5 mm chip area including
pads.

15. 1
2
3
4
5
6
7
8

16. Breast Cancer Detection System Measurement Results:
 The measurement set-up for EIT imaging using the proposed breast cancer detection system.
 The measurement is performed using a breast model made of agar and carrot, since agar and carrot have similar
impedance characteristics to normal breast tissue and cancer cells, respectively.
 The 12 cm diameter and 5 cm height of hemispherical agar containing a small carrot ‘tumor’ is put into the proposed
system, and EIT images are displayed on the smart device.
 The weighted back-projection algorithm ,which assumes that the electric current is injected through one of the electrodes in
a surface array and equipotential surfaces from the electrode are spherical, is used with modification for 3D image
reconstruction.
 The final 3D EIT image can be also displayed as layer images.
 The system with the EIT IC can detect smaller than 1 cm of carrot in the agar, and an x-ray mammography image of the
same breast model is also shown for comparison.
 The proposed system can detect a tumor of 0.1% of breast volume, which is a 5mm sized carrot in this measurement.
Thus, the system has been optimized for the average breast size of Asian women, and a 5mm size tumor detection
corresponds with stage 1 breast cancer.
 The total scanning time of CIM and EIT mode in this system takes typically less than 10 s; during this time the user should
stay still to ensure an accurate result.
 Table II shows the system in comparison to previous EIT systems for breast cancer detection.
 The most features of this device are small and light-weight with flexible electrodes, and 3D imaging can be done
using mobile devices.

17. Breast cancer detection systemBreast model imaging results

18. Determination of cancer progression in breast cells by fiber optic bio-impedance
spectroscopy system (FOBIS system )
Introduction:
 Fiber optic and bio-impedance methods allow discrimination of different cell types based on their signature. By combining these
two techniques, the sensitivity of the system to the differentiation of human breast cells was evaluated.
 The FOBIS system ,the diameters of the fibers and platinum wires are 50 and 25μm, respectively.
 The sensitivity of the system to differentiate different cell types was assessed with high metastatic (MDA-MB-231), low
metastatic (MCF-7) and normal breast epithelial cells (MCF-10A).
 Statistical evaluation of data was performed by using Principle Component Analysis (PCA) and Linear Discriminant Analysis
(LDA).
 Spectroscopic data obtained from FOBIS system on suspended human breast cells were evaluated by multivariate statistical
analysis to obtain information about the cell type.

19. Design of FOBIS system
This system is consist of two part :
Fiber Optic
part
Bioimpedance
Part
halogen-tungsten light source (HL‐2000
Tungsten Halogen
a spectrometer (USB2000+ VIS‐NIR
Spectrometer, Ocean Optics)
laptop
two fiber optic cables with 50-micron
diameter
platinum wires were combined with the optical
part as represented in specified geometry
Bioimpedance analyzer ,oscilloscope
was connected to the platinum wires to send current to the
medium and for impedance measurement. Currents sent in
multiple (5, 50, 100 and 200kHz) frequencies and
impedance measurements were obtained. Also, resistance,
reactance and PA values were recorded at 50kHz
frequency.

20. Fiber
optic
part
Bioimpedance
part

21. Materials and methods
 FOBIS system was used for getting optic and impedance spectral information. Current transferred to the
media and information about the conductivity of the media was obtained via the bioimpedance part.
 Adjacent two fiber cables were used in the fiber optic part. Light sent to the media by the fiber that was
connected to the light source, and backscattered light was collected with the other fiber for analysis.
 The backscattered light was detected from the surface of the medium. However, singly this optical
information was not enough to detect precancerous lesions. For this reason, we added the bioimpedance
part to our system.
 Electrode placement in bioimpedance measurement techniques affects the penetration depth of the signal.
Bioimpedance information is obtained from the media surface with electrodes that are placed close to each
other in our study.
 The signal goes more in-depth as the distance between the electrodes increases. Hence, in the
bioimpedance part of the system, the platinum wires were placed close to each other so that the
bioimpedance information was obtained from the surface of the medium. These allow the optical and
bioimpedance parts of the system to receive information from the same surface area in the medium.

22. Light
source
Cell
culture
FOBIS
system spectrometer
PCA LDA
Result
Laptop
Statistical analysis
Use software
package R-studio
open source
statistical
language PCA &
LDA & ROC
analysis

23. Results
1. Bioimpedance measurement results
• The impedance value decreases in the suspended metastatic
cancer cells in medium The reason for this is that the
resistance value of the normal breast epithelial cells at lower
frequencies is higher than the low and high metastatic
resistance values at the same frequencies.
• The current at low frequencies is exposed to a long resistive
,the extracellular pathway decreases with the increase of
surface area in cancerous cells that causes a decrease in
impedance at low frequencies.
• In the same cell type, impedance was found high due to the
strong dielectric properties of the cell membrane and the
tissue interface acting as a capacitance in low frequency.
However, impedance was found low due to the loss of this
capacitive effect of the membrane at high frequencies.
• PA values of all cell types were compared, and it was
observed that this angle decreased from normal to high
metastasis in cell medium .According to this finding, different
cell types can be detected by using PA values of
bioimpedance part of the FOBIS system in the medium.

24. 2. Fiber optic measurement results
• Spectra in the visible wavelength range by using fiber optic part
of FOBIS system. At least 16 measurements were collected per
cell. A total of 420 spectra were acquired from all cell types, and
these spectra were analyzed.
• The spectral data had different patterns, containing multiple and
often overlapping peaks so they turned out to be not very
distinct to differentiate cell types from each other.
• Methods of analysis, PCA followed by LDA, were used to
differentiate the cell types. In this analysis, firstly we performed
a PCA to reduce the number of predictor variables, without
much loss of optic and bioimpedance information, used for the
differentiation of cell types.
• The optimal cut-points were calculated (Table 1- In our study,
ROC analysis further confirmed that PCA-LDA based diagnostic
algorithms using the all spectral properties of FOBIS system
can distinguish low metastatic cancer cells (MCF-7) from
normal (MCF-10A) with a sensitivity of 100% and specificity of
60% as seen in fig.

25. Discussion
 Real-time and noninvasive diagnostic studies have been conducted using optical methods. Molecular and morphological
changes in the tissue during the progression of cancer depend on the scatters of tissue, including nucleus size, nucleus-
cytoplasm ratio, and mitochondrial size than scattering and absorption coefficients.
 The scattering of light from the tissue is more sensitive to changes in the cellular morphology than biochemical changes.
Intracellular components such as cell nucleus, mitochondria, lysosomes, Golgi apparatus and the difference in Refractive
Index (RI) of cytoplasm causes light scattering in biological tissues .
 In the elastic light scattering, there is no difference between the wavelength of light, which is transmitted to the medium, and
the wavelength of the backscattered light. Therefore, there is only the spatial dispersion of light in the medium. In our study,
visible wavelength range (450-750 nm) light was used.
 The intensity of backscattered light from the medium depends on the scattering phase function (P (θ, λ(( and scattering
coefficient μs(λ(. The structures in the cell function as biological scatters. Light scattering occurs in the cell itself, nucleus,
structures within organelle and organelle in mammalian cells. It has been stated that the capacitive nature of the cell
membrane causes the current flow into the surface of cells and the tight junctions act as a "short circuit" which in turn leads to
a characteristic drop in impedance at high frequencies.
 In our study, the impedance value decreased, while cancer progressed in the medium. They found that the tumor tissues had
low frequency (100 kHz) conductivity which was higher than the conductivity of normal tissue and lower than that of the
surrounding tissue.
 Our results indicate that the FOBIS system can distinguish between MCF-10A and MCF-7 with a sensitivity of 100% and a
specificity of 60%, MCF-10A, and MDA-MB-231 with a sensitivity of 100% and a specificity of 80%, MCF-7, and MDA-MB-231
with a sensitivity of 80% and a specificity of 80%.

26. Conclusion:
It is well established that cancer can be most effectively treated when diagnosed at an early stage ,This two
techniques I had used above both use in breast cancer field one for early detection and the other one use in
determinations of development of breast cancer .
Both techniques approved that the significant of use the bioimpedance for analysis and imaging .
A compact and convenient early breast cancer detection system is proposed and implemented with a high-
sensitivity.
EIT IC, noticed that in 1st tech. used a EIT for imaging the ROV of patient breast and made a 3D coloring image
explained the malignant region ,this tech is non invasive and easily used in home by patient when can use a
phone application to viewed the result ,and light device .
In 2nd tech. that experimental prepared by use a cell culture with FOBIS system , The FOBIS system that we
have developed in this study has been shown to distinguish low metastatic cells from normal cells ,the result we
can obtained from this tech. as graph that explain the changed in the values of resistance of malignant tissue,
Finally this two tech. are necessary in detection of breast cancer stages with use bioimpedance to obtain more
accuracy information.

28. Reference:
• https://www.plusmedical.ro/en/articole/cancerul-de-san-factori-de-risc-analize-si-diagnostic-
tratament/?gclid=CjwKCAjwvtX0BRAFEiwAGWJyZCj2ER4ty82wrEbtSs2As8V2tELEpeDky_EskL
5PS0EGX386CwXTuBoC5qYQAvD_BwE
• http://ssl.kaist.ac.kr/2007/sub2_2_2_EIT.php
• https://www.researchgate.net/publication/338994053_Determination_of_cancer_progression_in_b
reast_cells_by_fiber_optic_bioimpedance_spectroscopy_system