Clinical thermometry, using the 27 MHz multi-electrode current-source interstitial hyperthermia system in brain tumours.

BACKGROUND AND PURPOSE: In interstitial hyperthermia, temperature measurements are mainly performed inside heating applicators, and therefore, give the maximum temperatures of a rather heterogeneous temperature distribution. The problem of how to estimate lesion temperatures using the multi-electrode current-source interstitial hyperthermia (MECS-IHT) system in the brain was studied. MATERIALS AND METHODS: Temperatures were measured within the electrodes and in an extra catheter at the edge of a 4 x 4 x 4.5 cm(3) glioblastoma multiforme resection cavity. From the temperature decays during a power-off period, information was obtained about local maximum and minimum tissue temperatures. The significance of these data was examined through model calculations. RESULTS: Maximum tissue temperatures could be estimated roughly by switching off all electrodes for about 5 s. Model calculations showed that the minimum tissue temperatures near a certain afterloading catheter correspond well with the temperature of the applicator inside, about 1 min after this applicator was switched off. CONCLUSIONS: Although the electrode temperatures read during heating are not suitable to assess the temperature distribution, it is feasible to heat the brain adequately using the MECS-IHT system with extra sensors outside the electrodes and/or application of decay methods.

An electric field measurement system, using two-dimensional array of diodes.

In hyperthermia induced by electromagnetic applicators, one way to obtain information about the energy absorption is by measurement of electric field strength (E). This paper describes a system which can measure E-distributions, using a two-dimensional array of diodes. It was designed to be used on patient skin, during hyperthermia treatments of superficial tumours, providing additional data for applicator power control. The first prototype consists of a sheet with Schottky diode sensors with a spacing of 2.5cm, connected to high-resistance leads, printed with carbon ink. The rectified diode voltages are passed through a multiplexer unit to an AD-DA card in a PC. The sensitivity of the sensors is linearly proportional to the electric field and to the length of the extended diode connection pins. Relative E-field distributions obtained with 64 sensors are updated within 1s. Phantom measurements, performed with the sensor matrix under a Lucite Cone Applicator (LCA) and under a 2 x 2 array of Current Sheet Applicators (CSAs) were compared with infrared measurements of the temperature rise after a short power pulse. A fair agreement was found between the square of the diode voltages and the infrared distributions. Movement of a single CSA over the sensor matrix can be visualized clearly by the system. The diode matrix E-field measurement system is sufficiently fast and accurate to give valuable feedback for power steering for an array of LCAs and CSAs. The system has the potential of being a helpful tool in other fields of quality assurance as well.

Temperature measurement errors with thermocouples inside 27 MHz current source interstitial hyperthermia applicators.

The multielectrode current source (MECS) interstitial hyperthermia (IHT) system uses thermocouple thermometry. To obtain a homogeneous temperature distribution and to limit the number of traumas due to the implanted catheters, most catheters are used for both heating and thermometry. Implications of temperature measurement inside applicators are discussed. In particular, the impact of self-heating of both the applicator and the afterloading catheter were investigated. A one-dimensional cylindrical model was used to compute the difference between the temperature rise inside the applicators (deltaTin) and in the tissue just outside the afterloading catheter (deltaTout) as a function of power absorption in the afterloading catheter, self-heating of the applicator and the effective thermal conductivity of the surrounding tissue. Furthermore, the relative artefact (ERR), i.e. (deltaTin - deltaTout)/deltaTin, was measured in a muscle equivalent agar phantom at different positions in a dual-electrode applicator and for different catheter materials. A method to estimate the tissue temperature by power-off temperature decay measurement inside the applicator was investigated. Using clinical dual-electrode applicators in standard brachytherapy catheters in a muscle-equivalent phantom, deltaTin is typically twice as high as deltaTout. The main reason for this difference is self-heating of the thin feeder wires in the centre of the applicator. The measurement error caused by energy absorption in the afterloading catheter is small, i.e. even for materials with a high dielectric loss factor it is less than 5%. About 5 s after power has been switched off, Tin in the electrodes represents the maximum tissue temperature just before power-off. This delay time (t(delay)) and ERR are independent of Tin. However, they do depend on the thermal properties of the tissue. Therefore, ERR and t(delay) and their stability in perfused tissues have to be investigated to enable a reliable estimation of the tissue temperatures around electrodes in clinical practice.

Spatial steering with quadruple electrodes in 27 MHz capacitively coupled interstitial hyperthermia.

PURPOSE: The 27 MHz Multi Electrode Current Source (MECS) interstitial hyperthermia system uses probes consisting of multiple independent electrodes, 10-20 mm long, to steer the 3-D power deposition. Seven point thermocouples integrated into the probes provide matching 3-D temperature feedback data. To improve spatial steering the number of independent segments was increased; the feasibility and reliability of four independent electrodes integrated into a single probe were evaluated, with special attention to efficiency and to interference between separate electrodes. METHODS: The contribution of secondary coupling on the apparent electrode impedance and the dependence of cross coupling on the distance between leads, thermocouple and electrodes are computed using simple analytical models. The effect of this secondary coupling was assessed experimentally by comparing power delivery by dual and quadruple electrodes, and by quadruple electrodes in different electrode configurations (segment length 10 or 20 mm) in a nylon catheter in a muscle equivalent medium. RESULTS: Cross coupling with the thermocouple and other electrodes was computed to be of the same magnitude as the primary coupling for a quadruple electrode. Fortunately, this does not affect operation of the electrode, there was no difference in performance between quadruple and dual electrodes, and the output power was effectively independent of the electrode configuration. CONCLUSION: Quadruple MECS electrodes for improved 3-D power control are feasible.

Design of applicators for a 27 MHz multielectrode current source interstitial hyperthermia system; impedance matching and effective power.

In interstitial heating one of the main requirements for achieving a certain elevated temperature in a tumour is that the effective power per applicator (Peff), i.e. the power which is actually deposited in the tissue, is sufficiently high. In this paper this requirement is discussed for the applicators of the 27 MHz multielectrode current source (MECS) interstitial hyperthermia (IHT) system. To minimize power reflection, the applicator impedance was matched with the generator impedance by adjusting the length of the coaxial cable in between. Transmission line losses, applicator efficiency and subsequently Peff were computed for several applicator types. The actual Peff per electrode was obtained from calorimetric measurements. Experiments with RC loads, which can be seen as perfect applicators, were performed to investigate the effect of mismatching on Peff. Applicator losses were measured for clinically used applicators, both single- and dual-electrode, utilizing saline phantoms. A simple spherical tumour model, using the effective heat conductivity (keff) to account for heat transport, was used to estimate Peff for a given tumour size, implant size and applicator density. Computations of Peff of various MECS-IHT electrodes were in close agreement with the phantom measurements. Most of the initial generator power was absorbed in the transmission line (60-65%). The efficiency of the applicators was about 65%. For both single- and dual-electrode applicators the effective electrode power was found to be about 1 W. Model calculations show that Peff of 1 W is sufficient to reach a minimum tumour temperature of 43 degrees C in well perfused tumours (keff = 3 W m-1 degree C-1), using a typical implant with 2 cm electrodes and 1.5 cm spacing. Mismatching can considerably affect Peff. Both a reduction to almost zero and a two-fold increase are possible. However, because the matching theory is well understood, mismatching is not a serious problem in clinical practice and can even be used to increase Peff if necessary. We conclude that the applicator design and the impedance matching method chosen in the MECS system allow heating to temperatures in the therapeutic range with implants used in clinical practice.

Implications of using thermocouple thermometry in 27 MHz capacitively coupled interstitial hyperthermia.

The 27 MHz Multi Electrode Current Source (MECS) interstitial hyperthermia system uses segmented electrodes, 10-20 mm long, to steer the 3D power deposition. This power control at a scale of 1-2 cm requires detailed and accurate temperature feedback data. To this end seven-point thermocouples are integrated into the probes. The aim of this work was to evaluate the feasibility and reliability of integrated thermometry in the 27 MHz MECS system, with special attention to the interference between electrode and thermometry and its effect on system performance. We investigated the impact of a seven-sensor thermocouple probe (outer diameter 150 microns) on the apparent impedance and power output of a 20 mm dual electrode (O.D. 1.5 mm) in a polyethylene catheter in a muscle equivalent medium (sigma 1 = 0.6 S m-1). The cross coupling between electrode and thermocouple was found to be small (1-2 pF) and to cause no problems in the dual-electrode mode, and only minimal problems in the single-electrode mode. Power loss into the thermometry system can be prevented using simple filters. The temperature readings are reliable and representative of the actual tissue temperature around the electrode. Self-heating effects, occurring in some catheter materials, are eliminated by sampling the temperature after a short power-off interval. We conclude that integrated thermocouple thermometry is compatible with 27 MHz capacitively coupled interstitial hyperthermia. The performance of the system is not affected and the temperatures measured are a reliable indication of the maximum tissue temperatures.

Spatial temperature control with a 27 MHz current source interstitial hyperthermia system.

PURPOSE: This article gives an overview of the properties of a 27 MHz current source interstitial hyperthermia system, affecting temperature uniformity. METHODS AND MATERIALS: Applicators can be inserted in standard flexible afterloading catheters. Maximum temperatures are measured with seven-point constantan-manganin thermocouple probes inside each applicator. Temperature can be controlled automatically using a simple control algorithm. Three-dimensional power absorption and thermal models for inhomogeneous tissues are available to optimize applicator geometry and phase configuration. Properties of the interstitial heating system have been verified both in phantom experiments and in in vivo treatments of rhabdomyosarcomas implanted in the flank of a rat. RESULTS: An experiment with four electrodes in one catheter proves that longitudinal control of the specific absorption rate (SAR) is feasible. Local cooling applied by cold water circulation through a catheter perpendicular to the afterloading catheter could be compensated by independent control of electrode power. Furthermore, comparison of two different phase configurations using four dual electrode applicators shows that the SAR distribution can be manipulated significantly, utilizing the phase of the electrodes. Finally, the temperature can be controlled safely and model calculations are in fair agreement with the measurements. CONCLUSIONS: The features of the 27 MHz current source interstitial hyperthermia system enable spatial temperature control at approximately 1.5 cm.

A 27 MHz current source interstitial hyperthermia system for small animals.

Temperature distribution is an important factor in thermo-radiotherapy and it is greatly dependent on the applied heating technique. Consistency of the heating method is therefore important in translating in vivo experimental data to the clinical situation. To further evaluate the combination of interstitial hyperthermia and interstitial radiotherapy, an experimental interstitial hyperthermia system has been developed for small (500-2000 mm3) tumours growing in the flank of a rat. The system used reproduces the properties of our clinical current source interstitial hyperthermia system. The heating system consists of four applicators, each with independent tuning and power control. The applicators are situated inside plastic afterloading catheters and are capacitively coupled with the surrounding tissue. The tumour is heated through dissipation of a 27 MHz current flowing to an external ground plane. An effective RF-filter allows reliable thermocouple temperature measurements when the power is switched on. The tumour temperature is easily controlled by means of a continuous temperature read-out and a clear temperature display. A minimum temperature up to 46 degrees C can be reached within 4-10 min and maintained (+/-0.5 degrees C) throughout the treatment period. Modelling calculations performed for this heating system indicate that the applicator temperatures should be kept equal in order to minimize the difference between maximum and minimum temperature. Significantly higher applicator currents are needed at larger distances from the ground plane. In addition, the homogeneity of the temperature distribution is improved when either the tumour is isolated or when the environmental temperature is increased. The calculations also show that temperature distribution is strongly dependent on effective heat conductivity. A description of the system and its performance is presented.

Interstitial hyperthermia and interstitial radiotherapy of a rat rhabdomyosarcoma; effects of sequential treatment and consequences for clonogenic repopulation.

Animal tumour experiments have been performed to elucidate the interactions between interstitial hyperthermia (IHT) and interstitial radiotherapy (IRT), and to obtain information about the most effective sequence of these treatment modalities. Experimental tumours, transplanted in the flank of Wag/Rij rats, were treated with IHT for 0.5 h at 44 degrees C, and with IRT using low dose-rate (LDR) iridium-192 sources. Both tumour cure probability and the fraction of clonogenic cells in vitro after different IHT and IRT treatments in vivo, were used as endpoints. The sequence of a short (0.5 h) IHT treatment followed by an extended LDR-IRT treatment lasting up to 10 days appeared to be very effective, and resulted in a significant thermal enhancement ratio of 1.34 at the 50% tumour cure probability level. A not significantly increased thermal enhancement of 1.06 was found when the same IHT treatment followed IRT. The level of clonogenic cell survival after IHT alone is high (0.24 +/- 0.08) compared with that after an IRT dose of 20 Gy (0.017 +/- 0.004). Clonogenic cell repopulation started 2-4 days after the in vivo treatment irrespective of the type of treatment. The in vivo combination of IHT and LDR-IRT resulted in lower surviving fractions compared with IRT alone, regardless of the time interval between the end of treatment and in vitro clonogenic assay. IHT followed by LDR-IRT appeared to be the most effective treatment in terms of tumour cure. The in vivo/in vitro studies indicated that the effect of hyperthermia is mainly attributed to radiosensitization, possibly by partial inhibition of sublethal damage repair processes during the subsequent irradiation. The hyperthermia-induced cytotoxicity was of minor importance as estimated from the surviving clonogenic fraction.