Ming Yi

Characterization of the RF ablation-induced ‘oven effect’: The importance of background tissue thermal conductivity on tissue heating

Purpose: To determine the effect of background tissue thermal conductivity on RF ablation heating using ex vivo agar phantoms and computer modelling. Method: Two-compartment cylindrical agar phantom models (5% agar, 5% NaCl, 3% sucrose) were constructed. These included a standardized inner compartment (2 cm diameter, 4 cm length, 0.25% agar) representing a tumour, surrounded by an outer compartment representing background tissue. The thermal conductivity of the outer compartment was varied from 0.48 W m−1°C (normal liver) to 0.23 W m−1°C (fat) by adding a fat-saturated oil-based solute (10–90%) to the agar. RF ablation was applied at 2000 mA current for 2 min. Temperatures were recorded up to 4 cm from the electrode tip at 1 cm intervals. Subsequently, a 2-D finite element computer model was used to simulate RF ablation of 2–24 min duration for tumours measuring 2–4 cm in diameter surrounded by tissues of different thermal conductivity with the presence or absence of perfusion (0–5 kg m−3 s−1) (n = 44). A comparison of results was performed. Results: In agar phantoms, the amount of fat in the background tissue correlated with thermal conductivity as a negative exponential function (r2 = 0.98). Significantly increased temperatures were observed at the edge of the inner compartment (1 cm from the electrode tip) as the fat content of the outer compartment increased (p < 0.01). Thus, temperatures at 2 min measured 31.5 ± 2.2°C vs 45.1 ± 3.1°C for thermal conductivities of 0.46 W m−1°C (10% fat) and 0.23 W m−1°C (90% fat), respectively. On the other hand, higher levels of fat led to lower temperature increases in the background compartment (0.2 ± 0.3°C for 90% fat vs. 1.1 ± 0.05°C for 10% fat, p < 0.05). Phantom thermal heating patterns correlated extremely well with computer modelling (r2 = 0.93), demonstrating that background tissues with low thermal conductivity increase heating within the central tumour, particularly for longer durations of RF ablation and in smaller tumours. Furthermore, computer modelling demonstrated that increases in temperature at the tumour margin for background tissues of lower thermal conductivity persisted in the presence of perfusion, with a clinically relevant 4.5°C difference between background thermal conductivities of fat and soft tissue for a 3 cm tumour with perfusion of 2 kg m−3 s−1, treated for 12 min. Conclusion: Lower thermal conductivity of background tissues significantly increases temperatures within a defined ablation target. These findings provide insight into the ‘oven effect’ (i.e. increased heating efficacy for tumours surrounded by cirrhotic liver or fat) and highlight the importance of both the tumour and the surrounding tissue characteristics when contemplating RF ablation efficacy.

Micromachined Electrical Conductivity Probe for RF Ablation of Tumors

RF ablation is an important technique in cancer treatment. It has been proposed that the effective area treated via RF ablation can be increased by increasing the local electrical conductivity. This is achieved by injection of NaCl solution into the tissue. For an accurate and effective RF ablation treatment using this new method, it is necessary to measure the local electrical conductivity, which varies spatially due to diffusion of sodium chloride. In this paper, we propose a micro probe to measure the local tissue electrical conductivity. The probe consists of two in-plane miniature electrodes separated by a small gap. When the electrodes are in contact with the tissue, the electrical resistance across them can be used to calculate the electrical conductivity. The probe is fabricated by standard photolithography techniques. The substrate material is polyimide and the electrodes are made of gold. A four-electrode probe is used to calibrate the new electrical conductivity micro probe using different concentrations of saline water. The resistance measurements are carried out using an impedance analyzer on different frequencies. The frequency of choice for RF ablation of tumors is 500k Hz and is the one selected for calibration and testing. The micro-probe calibration is then verified by measuring electrical conductivity of a phantom and comparing it with the result measured by the four-electrode probe. Finally, some in vivo tests are performed and the results are compared with literate data.Copyright

Fast response temperature measurement and highly reproducible heating methods for 96-well plates.

Hyperthermia, the procedure of exposing cells to a temperature between 42 degrees and 49 degrees C, has been shown to be a promising approach for cancer treatment. To understand the underlying mechanisms of hyperthermic killing of cancer cells, it is critical to have an accurate temperature measurement technique and a heating method with high reproducibility. To this end, we have developed a method using fine thermocouples with fast response time to measure the temperatures in multiple wells of a 96-well plate. The accuracy of temperature measurement was +/- 0.2 degree C. Such a capability allows a complete record of the time and temperature of the treatment procedure and helps define an accurate thermal dose. We have also compared several methods for heating 96-well plates and found that use of copper blocks in contact with the lower surface of the 96-well plate in an incubator provides a highly reproducible heating method. The common method of using water bath to heat cells in vitro resulted in a decrease of cell viability even at the control temperature of 37 degrees C and a decrease in the reproducibility of certain biological assays. In summary, using these improved techniques, proposed thermal dose can be defined more precisely, and highly reproducible heating in vitro can be achieved.

Micromachined hot-wire thermal conductivity probe for biomedical applications

A micro thin-film thermal conductivity probe is developed to measure thermal conductivity of biological tissues based on the principle of traditional hot-wire method. The design of this new micro probe consists of a resistive line heating element on a substrate and a RTD based temperature sensor. The transient time response of the heating element depends on the thermal conductivity of the surrounding medium and the substrate. A theoretical analysis of the transient conduction for this configuration where the heater source is sandwiched between two materials (the substrate and the surrounding medium) shows that the composite thermal conductivity calculated from the temperature versus time response is simply the average of the thermal conductivity of the two materials. The experiments conducted to measure thermal conductivity of Crisco and agar gel show a good match with the theoretical and numerical analyses. The technique demonstrates the potential of the microprobe for in vivo measurements of thermal conductivity of biological tissues.

Investigation of temperature elevation and saline injection induced electrical conductivity change of hepatic tissue by using micro probe

Radiofrequency ablation (RFA) has been used for a variety of clinical treatments including treatment of non-resectable liver tumors with good clinical success. Liver pretreatment with injected saline increases the volume of the RFA treatment and is a potential tool for strategically treating larger tumors. Understanding the electrical conductivity of the affected tissue is required to improve the applicator performance and to accurately control the ablation area. We have developed a micro two-electrode probe capable of measuring the local electrical conductivity of tissues at different temperature levels and recording the transient change of electrical conductivity with saline pretreatment. An optical temperature sensor was attached on the probe tip for real-time temperature monitoring to capture the dynamic effects of temperature changes. Three methods which were implemented by water bath and a commercial RF ablation applicator (Cool-tip RF ablation system) were used to heat the hepatic tissues. The results show that at elevated temperatures the electrical conductivity increases by a factor of two compared to the values at the body temperature and different heating methods cause different levels of electrical conductivity change. The preliminary measurements of the local electrical conductivity after the saline injection indicate a dynamic pattern in electrical conductivity. The results serve to provide guidance for accurate prediction of RFA area when using saline injection pretreatment.