**3.4. Temperature influence on tissue permittivity**

280 Ultra-Wideband Radio Technologies for Communications, Localization and Sensor Applications

**Figure 21.** Discrimination of Gram-positive and –negative bacterial strains *via* dielectric spectroscopy.

(*Micrococcus luteus* and *Bacillus subtilis* [upper curves]) and Gram-negative bacterial strains (*Escherichia coli* and *Serratia marcescens* [lower curves]) in a frequency range between 50 and 300 MHz. The highlighted area shows the most obvious region of differentiation between Gram-positive and Gram-

**Figure 22.** Monitoring of growth kinetics of four bacterial strains (growth phase). Red squares show the

and 100 MHz derived from measurements during the bacterial growth phase. The permittivity of the cell suspension was taken hourly for 240 or 300 min. Black lines show the cell count per ml taken at the

of the biomass of Gram-positive bacterial strains

in a frequency range between 50 MHz

The diagram shows the real part of the permittivity

area under the curve (AUC) of the real part of permittivity

same time as permittivity was measured [54].

negative bacterial strains [54].

In therapeutic or diagnostic applications or biological effects of the electromagnetic field, dosimetric evaluations are greatly dependent on the precise knowledge of the dielectric parameters of biological tissues (relative permittivity ε and electrical conductivity σ). These parameters are sensitive to many influencing factors, which include the temperature of the target organ [55]. During radio-frequency or microwave radiation exposure, the internal temperature of tissue can change, thus influencing the electrical field distribution. For example, the evaluation of the lesion obtained by thermal ablation is a function of the relative permittivity and conductivity at 37°C and also of their evolution during heating. The influence of temperature in dielectric spectroscopy has been studied by several authors [56]-[58]. However, these effects remain misunderstood and the measured values are sparse at various frequencies and exist only for some organs.

To find out in how far temperature-dependent changes in permittivity can result in a parameter identified by ultra-wideband technology, water and different tissues were examined. To assess the basic capability of UWB radar for monitoring local temperatures, dedicated phantom and *in vivo* experiments were performed. Dielectric spectroscopy of water at different temperatures (25 – 80°C in steps of 5°C) and corresponding experiments using porcine and bovine tissue, such as udder, liver, muscle, and kidney revealed a distinct decrease of permittivity with increasing temperature. Nevertheless, heating of tissues to more than 60 °C might also reduce permittivity due to the reduction of water content. No distinct organ-specific differences in the temperature-dependent dielectric properties have been found so far (Fig. 23). Only fat, as low-water-content tissue, exhibited no influence on permittivity at different temperatures [59].

In addition to further studies with improved probes, corresponding analysis were performed using clinically approved temperature-based methods for tumor eradication, such as radio frequency ablation (RFA) or magnetic thermo ablation. For this experiment, a bovine liver was positioned onto a neutral electrode. The second, active electrode was launched into the liver tissue. Both electrodes together create a stress field, and the tissue around the active electrode becomes heated up to 60°C. Bi-static UWB antennas were first positioned in a distance to the region where RFA was thought to detect the signals of liver tissue itself. Then, the antennas were positioned above the region of radio frequency ablation, and changes in impulse response before, while and after radio frequency ablation were detected. The signal analysis displayed an increase of the impulse response during radio frequency ablation (data not shown) [59].

ultraMEDIS – Ultra-Wideband Sensing in Medicine 283

concentration variations. The practice of clinical diagnostic radiology has been made possible by advances not only in diagnostic equipment and investigative techniques, but also in the contrast media that permit the visualization of the details of the internal structure of organs, which would not be possible without them. .The remarkably high tolerance of modern contrast media has been achieved through successive developments in chemical

The phantom serving as a model for blood vessels with a constant flow of ethanol was arranged. In the first step, the signals of this ethanol flow were received. By using a syringe *via* three-way cock 3 ml of the selected contrast agent (mixture of ethanol and water) were added, and the relative signal change was detected. The results show that with a decrease of

**Figure 24.** Depiction of the assembly of a phantom serving as a model for blood vessels with a constant flow of ethanol (left panel). The right panel depicts the relative signal variation (change of reflection coefficient) through adding 3 ml of contrast agent in relation to the virgin signal with constant flow of

Even though dielectric spectroscopy of our group showed promising permittivity values of potential contrast agents such as physiological sodium chloride, the encountered permittivity increases *in vivo* are still to be enhanced to allow for a specific detection *via* UWB radar. One possibility to increase the capability of breast tumor imaging is the application of different clinically approved contrast agents such as ultrasound micro bubbles or iron oxide nanoparticles. Moreover, we expanded our investigations to the assessment of non-clinically approved agents (for example BaSO4) in order to discover potential advantageous mechanistic conditions leading to local signal increase in terms of UWB diagnosis. Experiments will be systematically analyzed using dedicated phantoms,

Another challenge is the achievement of a selective accumulation of contrast agents in the target region to be detected by our UWB system. In this regard, a dynamic and transient

accumulation *via* the tumor vascularization has been already postulated.

pharmacological technology.

ethanol [43].

mimicking human tissues and blood flow.

water the signals become weaker (Fig. 24, right panel).

**Figure 23.** Real part ( ) and imaginary part ( ) of the permittivity of water, liver, fat, and udder tissue at a frequency of 2 GHz is depicted. Water showed a constant decrease of permittivity in relation to the increase of the temperature. Liver and udder tissue showed a diminished deviation, and in contrast fat showed no change of the permittivity [59] at all.

The applicability of UWB for temperature monitoring was also assessed *in vivo* in mice. Prior to the start of experiments, mice were shaved at the abdominal region. Dielectric spectroscopy of the skin at the animal´s liver region before and after euthanasia showed a time-dependent increase of permittivity as a result of decreasing temperature with on-going time after euthanasia. The data provide a good basis for further development of UWB as a non-invasive temperature measurement technology.
