Ultra-wideband (UWB) imaging of breast tumors is a potential alternative breast imaging modality. Several studies have shown the potential of this approach for both experimental measurements with breast phantoms and clinical trails [1–5]. The increased permittivity of malignant tissue, caused by the increased water content in the neo-plastic tissue, is exploited to detect tumors by means of electromagnetic waves in the microwave range. The UWB imaging exploits non-ionizing radiation and provides a higher patient comfort compared to the X-ray mammography and in comparison to MRI it is a cost-efficient alternative. However, the dielectric contrast between malignant and fibroglandular breast tissue is around 10 percent in the microwave range . This becomes difficult for breast cancer detection especially of young women, because the portion of glandular tissue is high compared to elder women. For this reason several groups investigated the potential of metallic nanoparticles to enhance the contrast between malignant and normal glandular/fibroconnective tissue. A contrast can be induced by a pure permittivity enhancement in terms of a differential measurement between native and contrast enhanced state [7, 8]. In clinical routine this becomes difficult due to the long enrichment time of the nanoparticles into the tumor, because the influence of the slight differences of the breast position between both measurements might be higher than the response caused by the nanoparticles. Bellizzi et al. [9, 10] investigated the behavior of magnetic nanoparticles (MNP) in presence of an external polarizing magnetic field (PMF) for different magnetic field intensities. Their results are promising concerning of introducing a new contrast enhancing approach for breast cancer detection. On condition that a sufficient amount of MNP accumulates within the tumor, the external PMF influences only the scattering behavior of the malignant tissue, whereby the nonmagnetic surrounding tissue will be unaffected.
In this work the influence of an external PMF on MNP (magnetite) is investigated by means of M-sequence UWB technology. An ON/OFF modulation of the PMF is presented to investigate the differences between pure magnetite nanoparticles and magnetite nanoparticles with a biocompatible aminodextran coating.
2 Material and methods
2.1 M-sequence technology
Measurements were performed applying the M-sequence sensor technology, which was developed at Technische Universität Ilmenau. This correlation measurement approach uses a binary pseudo-noise code (M-sequence) to stimulate the medium under test. The M-sequence is generated by a binary high-speed shift register which is pushed by a stable microwave oscillator. The signal energy of the sounding wave is distributed over the stimulus time, which enables a low signal magnitude. Due to the low voltage exposure of the medium under test the technology is suitable for medical applications, e.g. for breast cancer detection. Furthermore, the M-sequence technology can be applied to realize flexible and robust (low jitter and drift) UWB sensor systems as described e.g. in .
2.2 Measurement setup
To investigate the influence between pure and coated MNP, PMF modulations combined with UWB measurements are applied. Fig. 1 shows the corresponding measurement setup. Uncoated magnetite nanoparticles (WHKS 1S12, Liquids Research Ltd., Bangor, UK) and magnetite nanoparticles with an aminodextran coating (DFF 107 (in-house production), Biomedical Engineering Group, TU Ilmenau, Germany) are investigated. Both have a particle size of 10 nm. The MNP were diluted with distilled water and filled in a test glass which was positioned inside of a 5 cm wide oil-gelatin phantom . The total volume of the solution inside the test glass was constantly 2 ml. Only the mixture ratio between ferrofluid solution and distilled water was varied to realize different magnetite masses. The phantom was placed inside the air gap of an electromagnet. The maximum magnetic field intensity of the electromagnet at the center of the air gap was 60 kA·m−1. The magnetic field intensities were determined by measuring the absolute magnetic flux density using a Gauss Meter (Model 7030 Gauss/Tesla Meter, F.W. Bell, Milwauki, USA). The probe was placed at the center of the air gap which corresponds to the position of the MNP.
2.3 Signal preprocessing
Reflection and transmission measurements were performed by applying M-sequence technology and small active dipole antennas (see Figure 1) which are also used in the current breast imaging demonstrator . Figure 2 shows the measured raw data x(t, T) of the radar, where t is the propagation time and T corresponds to the observation time and the number of measurements, respectively. Considering x(t, T ) the response caused by the MNP is covered by the antenna crosstalk. Therefore, a signal preprocessing is applied by a drift correction:(1)
where xDE(t, T) is the drift corrected radar signal. The system drift (D(t, T)) caused e. g. by weak temperature variations is estimated assuming a linear model as described by Helbig et al. . In a further step the radar response y(t, T), as depicted in Figure 2, is computed by(2)
where is the mean value of the drift corrected
radar signal over the time period without the presence of an external PMF and represents an estimation of the deterministic components of the radar response x(t, T).
Reflection and transmission measurements with an ON/OFF modulated PMF were conducted. Figure 2 (bottom) shows the modulated response caused by the MNP during the presence of an external PMF (60 kA·m−1), whereby 6 mg magnetite were inside of the phantom. The magnitude of the mean value at the propagation time tR (see Figure 2 bottom) during the presence of the external PMF (TON) is investigated for different magnetite masses and magnetic field intensities. Figure 3 and Figure 4 show the dependencies for the MNP with and without a particle coating for the reflection and transmission measurement, respectively. Results show a nearly linear dependence between the modulated radar response and the magnetite mass for both pure and coated magnetite nanoparticles. Furthermore, the response increases with the magnetic field intensity. However, the magnitude of the mean value during the presence of an external PMF distinguishes nearly by the factor two between pure and coated MNP.
4 Discussion and conclusion
The preliminary investigations indicate the possibility to detect low permeability changes of pure and coated MNP induced by a PMF by means of in vitro measurements using M-sequence UWB technology. Results display that a coating of MNP influences the measured radar response. Hong et al.  show that a dextran-coating of magnetite reduces the magnetic susceptibility of MNP, and thus might be a reason for the lower response. This also leads to a lower detectability of the coated MNP, but such a coating is necessary because pure magnetite nanoparticles are prohibited for clinical use. An additional functionalization of the coated MNP is necessary to enable selective targeting of cancerous cells. The influence of such a functionalization has to be included in future work. Furthermore, the presented contrast enhancing approach has to be combined with the current measurement setup for breast imaging .
The authors would like to thank Dr. Silvio Dutz for providing us with coated magnetic nanoparticles.
This work was supported by the German Research Foundation (DFG) in the framework of the project ultraMAMMA (HE 6015/1-1, SA 1035/5-1, HI 698/13-1).
This work is a contribution to COST Action TD1301: Development of a European-based Collaborative Network to Accelerate Technological, Clinical and Commercialisation Progress in the Area of Medical Microwave Imaging.
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About the article
Published Online: 2015-09-12
Published in Print: 2015-09-01
Conflict of interest: Authors state no conflict of interest. Material and Methods: Informed consent: Informed consent has been obtained from all individuals included in this study. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.