Assessment of Thermal Effect of Radiofrequency Electromagnetic Field in Biological Tissues

Through 5,000 years of practice, physicians, surgeons, or people in general have utilized thermal therapy or “thermotherapies” to treat mass lesions now known as cancer. The methods have changed drastically over this time span and certainly, the techniques have improved the efficacy and safety. The hyperthermic therapy is usually a local or regional treatment for most cancer patients. There are multiple forms or methods of hyperthermic therapy. The most commonly used thermal techniques are Radiofrequency Thermal Ablation (RFTA) and Microwave Ablation (MWA) which are high-temperature-based modalities using electromagnetic fields energy.

RFTA is one of the most promising surgical treatments to ablate a localized tumor lesion, using a minimally invasive electrode (RF applicator or probe) under control by imaging techniques such as ultrasound, Computed Tomography (CT) or Magnetic Resonance Image (MRI) guidance. This technique is currently used to ablate benign and malignant tumors of the liver, kidney, lung, bone and breast. The results of this procedure are lesser pain, lesser damage to normal tissue and lesser recovery period over all the classical methods.

The aim of this thesis is to develop theoretical and practical tools to assess the thermal effect of RF electromagnetic fields in biological tissues during ablative therapies. Specifically, it was studied the RFTA on liver tissue since the World Health Organization indicates that liver cancer is among the top six most frequent death related cancers worldwide.

Several factors are associated with thermal lesion size development and progression during the heating of biological tissues, two of them are: tissue dielectric properties before heating and their dynamic changes during and after heating, and tissue temperatures and time at temperature (thermal history) at any point along the thermal gradients.

Because the energy absorbed from an RF source depends strongly on tissue dielectric properties, changes in dielectric properties during heating will affect the tissue temperature distribution and the resulting thermal damage. Therefore, understanding changes of dielectric properties of tissue during heating is fundamental to further optimize the medical treatment protocols.

Several studies highlight the importance of computational modelling for predicting the RF thermal damage of biological tissues. The analyzed variables take into account RF probe design, tumor size, localization, applied power, tissue properties, frequency, exposure time and others parameters. However, most studies either incorporate only reversible temperature-dependent changes in electric conductivity or consider the conductivity to remain constant at body temperature. The variation of the electrical conductivity and relative permittivity with temperature during the heating process from low (physiological) to coagulation temperatures was only studied in recent years.

Hence, the study of the thermal dependences of the electrical conductivity and relative permittivity in these conditions was considered important. Thus, the first experiment was to obtain the thermal dependences of electrical conductivity and relative permittivity of ex-vivo porcine liver tissue at RF frequencies from 5 kHz to 500 kHz, during heating from 37 °C to 100 °C at different heating rates. Specifically, the study was performed at a very slow heating (VSH) rate, a slow heating (SH) rate and a fast heating (FH) rate, of approximately 0.1 °C/min, 3 °C/min and 10 °C/min respectively. Two experimental setups using different heating sources and a four-needle electrode connected to an Impedance Analyzer were developed to evaluate the thermal dependencies. The results at a body temperature of 37 °C show a good agreement with the data reported in the literature. The conductivity initially shows an increase followed by a decrease, whereas the permittivity increases before a subsequent sharp decrease. Above 60 °C different trends are observed for the three heating rates studied. The electric conductivity and permittivity show a similar behavior at all evaluated frequencies and heating rates. The observed abrupt change of the slope near 45 °C at slow heating rate may be used to identify the region of reversible changes in the tissue. These results confirm the connection between tissue dielectric properties, working frequency and exposure time with thermal damage during heating.

To evaluate the importance of electrical conductivity on the outcome of RFTA using numerical simulations they were studied the effects of different conductivity models involving the presence of three materials with different dielectric properties (normal liver tissue, tumor gel phantom and muscle saline phantom). An additional problem to solve was how to select the appropriate experimental data for the simulation, taking into account the heating rate at which the data was acquired and the power that will be delivered to the electrodes in the RFTA considered situation. To solve this problem a reasonable procedure was proposed in order to select for the simulation the appropriate experimental data of the temperature-dependence of electrical conductivity, obtained in the first experiment. The criteria for the selection were the heating rate at which the data was acquired and the power that will be delivered to the electrodes in the RFTA situation of interest, based on the computing of the time average of the heating rate in a representative point of the ablation zone. The validation of this procedure was performed based on the calculation of the space and time average of the heating rate in the ablation zone (99.0 % cell death) of the computational domain in seven runs of the liver ablation process using different configurations of frequency, power applied and heating rate data of electrical conductivity model. A mathematical model of the electrical conductivity as a result of any thermal history based on Arrhenius formulation was developed and validated. The effects on thermal damage (computed cell death area) of different electrical conductivity models that entail the presence of multiple materials (normal liver tissue, tumor gel phantom and muscle saline phantom) with different dielectric properties in a complex 2D FEM model at two selected RF frequencies were compared. The results demonstrated that not only the initial (baseline) electrical conductivity is important in predicting the lesion size, but also it is the model of the temperature dependence of electrical conductivity. On the other hand, the numerical results confirmed that the use of lower frequencies (20 kHz) than currently used during RFTA (450 kHz) may result in preferential heating of the tumor and consequently in less damage on healthy tissue. However, the conductivity models must also be tested in a more realistic RFTA situation involving the model of a tumor tissue instead of the model of a tumor gel phantom, and the predicted lesion size should be confirmed experimentally. Several graphical representations such as temperature profiles, cell survival fractions, time evolution of the electrical impedance, applied RF power and electric potential can be used to validate the results. A new generation of RFTA electrode can be developed base on the selection of working frequency at 20 kHz.