Regional hyperthermia of pelvic tumours using the Utrecht 'Coaxial TEM' system: a feasibility study.

Between August 1989 and July 1992 a total of 22 patients (64 treatments) with inoperable or recurrent deep seated pelvic tumours were treated with regional hyperthermia and radiotherapy. The 70 Mhz Coaxial TEM applicator with its characteristic open waterbolus was used as heating device. The main objective of this pilot study was to evaluate the feasibility, toxicity and temperature data. The results showed that the major treatment limiting factors were insufficient power and systemic stress. Local pain was observed in only 10% of all treatments. Most of the treatments resulted in elevated systemic temperatures with the overall mean maximum oesophagus temperature reaching 38.9 +/- 0.7 degrees C, however, in only 6% of these treatments this was found to be treatment limiting. From the measured data the following intratumoral temperatures were calculated: T90 = 39.9 +/- 1.0 degrees C; T50 = 40.7 +/- 1.0 degrees C; T10 = 41.4 +/- 1.0 degrees C. In addition, the overall mean average normal tissue temperatures were determined: Trectum = 40.8 +/- 0.7 degrees C; Tvagina = 41.3 +/- 0.9 degrees C; Turethra = 40.8 +/- 0.9 degrees C. The temperatures in normal tissue were frequently higher than in tumour, indicating that a large volume was heated. The open waterbolus allows strong cooling, but the strategy was changed during the study: higher systemic temperatures were allowed to improve the pelvic temperatures. This pilot study proved that the open waterbolus is clinically a success, because it offers patient comfort and SAR-steering by patient repositioning, and that regional hyperthermia with the Coaxial TEM is feasible.

The theoretical and experimental evaluation of the heat balance in perfused tissue.

Accurate treatment planning is necessary for the successful application of hyperthermia in the clinic. The validity of four different bioheat models or combinations of models is evaluated: the conventional bioheat transfer equation, the limited effective conductivity model, a mixed heat sink-effective conductivity model and a discrete vessel model. The heat balance for the heated volume, and especially the ratio between conductive heat removal and heat escape through the veins, is different for each of these models. Model predictions were compared with results from experiments on isolated perfused bovine tongues. Tongues were suspended in a water-filled container and heated by conduction. The steady state temperature distribution and heat balance were determined at various blood flow rates. Increased blood flow was found to lower the mean tissue temperature and to enhance both conductive and venous heat removal. This result agrees only with the mixed heat sink-effective conductivity and the discrete vessel model predictions. At low flow rates a modified heat sink term should be used because the venous efflux temperature was significantly lower than the mean tissue temperature.

PET measurements of hyperthermia-induced suppression of protein synthesis in tumors in relation to effects on tumor growth.

Hyperthermia-induced metabolic changes in tumor tissue have been monitored by PET. Uptake of L-[1-11C]tyrosine in rhabdomyosarcoma tissue of Wag/Rij rats was dose-dependently reduced after local hyperthermia treatment at 42, 45, or 47 degrees C. Tumor blood flow, as measured by PET with 13NH3, appeared to be unchanged. The L-[1-11C]tyrosine uptake data were compared to uptake data of L-[1-14C]tyrosine and with data on the incorporation of L-[1-14C]tyrosine into tumor proteins. After intravenous injection, the 14C data were obtained from dissected tumor tissue. Heat-induced inhibition of the incorporation of L-[1-14C]tyrosine into tumor proteins tallied with the L-[1-11C]tyrosine uptake data. Heat-induced inhibition of amino acid uptake in the tumor correlated well with regression of tumor growth. It is concluded that PET using L-[1-11C]tyrosine is eligible for monitoring the effect of hyperthermia on tumor growth.

Specific absorption rate steering by patient positioning in the 'Coaxial TEM' system: phantom investigation.

Cylindrical and elliptical homogenous phantoms were used to investigate, both theoretically and experimentally, the effect of phantom positioning on the specific absorption rate (SAR) distribution of the 'Coaxial TEM' system. Theoretical predictions indicated that the maximum of the SAR distribution was stationary around the central axis of the applicator system, irrespective of the position of the phantom. Therefore the maximum SAR can be located at different phantom sites as required. Although two-dimensional models give a qualitative insight in the phenomena studied, they lack quantitive agreement. The steering capacity has been confirmed experimentally and is now clinically applied by positioning the tumour mass according to these insights.

Interstitial heating: experiments in artificially perfused bovine tongues.

Isolated perfused bovine tongues were heated with a 2 x 2 hot water tube interstitial hyperthermia system (tube outer diameter 2.0 mm, spacing 16 mm). Tongue blood flow ranged between 0 and 17 ml min-1/100 g. The temperature distribution was mapped with 5 to 8 single thermocouples (diameter 50 microns). Model predictions using both the conventional bioheat transfer equation and the effective conductivity model were compared to the experimental results, with emphasis on the role of blood flow. Results indicate a better qualitative agreement with the k-effective model than with the heat sink model. In this set up a 16 mm spacing proved sufficient for adequate heating between the needles at normal blood flow rates, in the absence of large vessels.

A fast and simple algorithm for the calculation of convective heat transfer by large vessels in three-dimensional inhomogeneous tissues.

A fast and simple algorithm has been presented for the calculation of time-dependent temperature distributions in inhomogeneous vascularized tissue. Three-dimensional anatomical data of tissues and vessel structures are decomposed into elementary cubic nodes by a special digitizing routine with vessels represented by connected strings of vessel nodes. Vessel cross sections may be irregular shaped and/or tapered. Conductive and convective heat transfer was calculated through use of the heat balance technique on each cubic node resulting in an explicit finite difference computational scheme. Employing a three time level scheme, the Fourier stability criterion is circumvented allowing arbitrary time steps to be defined in the algorithm. Time steps as large as 100 times the Fourier restricted one still result in stable and convergent calculations of the stationary temperature distribution. Vessels with different flows and diameters are incorporated by performing a vessel specific second discretization step in time. Using the new algorithm as a mathematical tool the thermal equilibration length of vessel segments have been established under a broad range of geometrical and flow conditions. Validation followed from comparing transient and stationary temperature distributions derived by the proposed algorithm to those from an accurate cylindrical numerical model. Predicted values for the thermal equilibration lengths are compared to an analytical expression and phantom experiments. The algorithm is incorporated in a thermal model being the main part of our hyperthermia treatment planning system.

Thermotolerance kinetics and growth rate changes in the R1H tumour heated at 43 degrees C.

R1H rhabdomyosarcomas implanted into the foot of the right hind leg of female WAG/Rij rats were exposed to fractionated hyperthermia at 43 degrees C and the kinetics of thermotolerance and heat-induced growth rate changes were studied. Tumours of anaesthetized animals were exposed to heat by immersing the leg up to the thigh in a water bath. Tumour growth delay (TGD) and tumour volume doubling time were calculated from individual growth curves. After single heating, TGD increased with increasing heating time, the increase being linear for heating times exceeding 60 min. Thermotolerance was induced by a priming heat treatment at 43 degrees C for 60 min and the kinetics of development and decay was studied for fractionation intervals ranging from 4 to 144 h. After 4 h the thermal sensitivity of the tumours was enhanced by about 30 per cent, probably due to the sensitizing effect of heat-induced physiological alterations in the tumour tissue such as suboptimal environmental conditions caused by depressed blood flow. For longer time intervals thermotolerance developed and reached a maximum at 24 h where the thermotolerance ratio was 4.5 +/- 1.5. From 24 to 144 h thermotolerance decayed exponentially with a half-time of 28 +/- 8 h. Heat also affected the growth rate of the treated tumours. After single heat treatments at 43 degrees C for 15-60 min the tumours grew faster than untreated control tumours. This change was statistically significant. After prolonged single heating, growth rate was found to be reduced. Tumour volume doubling time was not detectably changed after fractionated heat treatments.

Relative contributions of intracortical and thalamo-cortical processes in the generation of alpha rhythms, revealed by partial coherence analysis.

The thalamo-cortical relationships of alpha rhythms have been analysed in dogs using partial coherence function analysis. The objective was to clarify how far the large intracortical coherence commonly recorded between different cortical sites could depend on a common thalamic site. It was found that the alpha rhythms of the LGN influenced only moderately the coherence between cortical alpha rhythms whereas that of the pulvinar had much more influence, at least in relation to some cortical areas. Significant phase shifts between thalamus and cortex were also measured. The results demonstrate that there are thalamo-cortical and cortico-cortical components which interact in the generation of cortical alpha rhythms.