Biomedical subjects

P Wust

Publications and source records attributed to P Wust.

105 records · Page 6Linked to original sources

PubMedDate not supplied

Inductive heating of ferrimagnetic particles and magnetic fluids: physical evaluation of their potential for hyperthermia.

The potential of colloidal subdomain ferrite particle suspensions (SDP) ('magnetic fluids'), exposed to an alternating magnetic field, is evaluated for hyperthermia. Power absorption measurements of different magnetic fluids are presented in comparison to multidomain ferrite particles (MDP). Variations with frequency as well as magnetic field strength have been investigated. The experimental results clearly indicate a definite superiority of even non-optimized magnetic fluids over MDP ferrites regarding their specific absorption rate (SAR). Based on the work of Shliomis et al. (1990) and Hanson (1991), a solid-state physical model is applied to explain the specific properties of magnetic fluids with respect to a possible use in hyperthermia. The experimentally determined SAR data on magnetic fluids are used to estimate the heating capabilities of a magnetic induction heating technique assuming typical human dimensions and tissue parameters. It is considered that for a moderate concentration of 5 mg ferrite per gram tumour (i.e. 0.5% w/w) and clinically acceptable magnetic fields, intratumoral power absorption is comparable to RF heating with local applicators and superior to regional RF heating (by comparison with clinical SAR measurements from regional and local hyperthermia treatments). Owing to the high particle density per volume, inductive heating by magnetic fluids can improve temperature distributions in critical regions. Furthermore, localized application of magnetic fluids in a tumour might be easier and less traumatic than interstitial implantation techniques.

Colloids↗

PubMedDate not supplied

Development and testing of SAR-visualizing phantoms for quality control in RF hyperthermia.

A new prototype of an elliptical standard phantom with fat-equivalent walls and a lamp matrix for SAR (specific absorption rate) visualization has been developed. This paper outlines the manufacture of solid components based upon either polyester resin or epoxy resin, as well as the adjustment of their electrical conditions (epsilon r, sigma) by admixtures of carbon and/or aluminium powder. Visualizing sensors (LED = light-emitting diodes, miniature lamps) are evaluated with respect to their transformation of electric field strength into light. Standard SAR patterns of the hyperthermia system BSD-2000 have been semiquantitatively assessed by the visualizing technique (power stepping method) and quantitatively by E field sensor scans. Extracted iso-SAR distributions are in good agreement with E field sensor scans performed with a lamp sensor coupled to a fibre or using a dipole probe with high resistive leads. The requirement for periodic quality control of SAR patterns of RF (radio frequency) hyperthermia systems is demonstrated. Comparisons between techniques are given, specifically with respect to the LED phantom of Schneider and van Dijk.

Electronics, Medical↗

PubMedDate not supplied

Quality assurance in various radiative hyperthermia systems applying a phantom with LED matrix.

The Amsterdam phantom with LED-matrix is applied as an instrument in testing the performance of four types of radiative deep-body hyperthermia systems, which are in clinical use in Germany and The Netherlands. The devices tested were Essen's BSD-1000, Berlin's BSD-2000, Utrecht's Coaxial TEM applicator and Amsterdam's Four-waveguide-array. Photographs were taken of the matrix of dipoles loaded with light-emitting diodes (LED) to visualize the distribution of the RF power deposition or specific absorption rate (SAR) in the aperture midplane. The utility of the phantom with LED matrix for various types of radiative hyperthermia systems is demonstrated. Within this preliminary study, the influence of important parameters on the SAR-pattern in the aperture midplane was demonstrated. After corrections on the phase relation of the applicators a central focus in the SAR distribution could be realized in all systems and could also be moved in any direction. The patterns of the central focus changed in its absolute values and its proportions depending on the relative relations of phase and amplitude of the lateral applicators with respect to the top and bottom applicator. Frequency dependency was recognized for the central focus of the BSD-1000 as well as for the irradiation pattern of a single applicator for the BSD-2000. In the Coaxial TEM applicator it was demonstrated that the dimension of the open water bolus influenced the absolute value of SAR in the aperture midplane.

Biophysical Phenomena↗

PubMedDate not supplied

Clinical, physiological and anatomical determinants for radiofrequency hyperthermia.

Temperature/time curves and corresponding CT scans of > 200 regional heat treatments with the hyperthermia system BSD-2000 in 43 patients have been analysed. In vivo variables and treatment parameters such as local specific absorption rate SAR, local relative SAR parallel SAR parallel, total power P, local cooling coefficients wb, and local steady-state temperature elevations delta Tss (above systemic temperature) have been determined. For determination of wb the well-known and accepted steady-state approach has been used, which was slightly modified for the purposes of this study. Specifically, comparison of cooling coefficients at the beginning and end of heat treatments were performed in tumours and normal tissues. Other variables are anatomical descriptors from CT scans, score of side effects plim, and various clinical factors. A variance analysis of the dependent variables, specifically delta Tss and parallel SAR parallel, is performed with respect to factors which were estimated as predictive. The intratumoral steady-state temperature elevations are determined by the perfusion-related cooling coefficients and local SAR to almost the same extent. Increase of cooling coefficients in tumours during the heat treatment characterizing the thermoregulatory potential have a slight but less important influence with respect to the achieved temperature elevations. SAR is influenced by several anatomical factors which determine the relative SAR distribution and clinical factors which limit the total power P. However, options for controlling present RHT systems in order to optimize the relative SAR distribution or to avoid hot spot phenomena appear limited. Three-dimensional modelling calculations show that the spatial arrangement of electrical interfaces emerging from bone and fat structures limits SAR control in available RHT technology and is mainly responsible for local power-dependent discomfort (Wust et al. 1994b). Some conclusions are drawn, about how technological development of hyperthermia technology can contribute towards overcoming this problem.

Female↗

PubMedDate not supplied

Noninvasive prediction of SAR distributions with an electro-optical E field sensor.

An integrated electro-optical (eo) E field sensor is developed on the basis of a Ti:LiNbO3 Mach-Zehnder interferometer. A measuring device based on the lock-in principle is introduced to register the E field in phase and amplitude using this E field probe. Segmented electrodes are used to minimize influences from the dielectric surroundings on the base point capacitance of the receiving dipole. The operating point is stabilized against drift phenomena resulting from optical damage and pyroelectric effect. Sensitivity, dynamic range, harmonic distortions and mechanical properties of a prototype of this electro-optical E field sensor are evaluated. A phantom setup in the SIGMA-60 applicator was developed to test this electro-optical sensor for hyperthermia applications. Power deposition patterns of various standard adjustments of the SIGMA ring are visualized in an elliptical lamp phantom. Simultaneously, E field in phase and amplitude is determined on a closed curve in 10 degrees steps around the phantom in a substitute bolus. The numbers are stored and utilized as boundary conditions in a two-dimensional finite elements code which calculates the SAR distribution on an appropriate triangular grid inside the closed curve. An excellent qualitative agreement is obtained between visualized and calculated SAR patterns. This novel measurement method is therefore suitable for noninvasive monitoring of SAR patterns during clinical application of regional radiofrequency hyperthermia.

Electrodes↗

PubMedDate not supplied

Quality control of the SIGMA applicator using a lamp phantom: a four-centre comparison.

An elliptical phantom with a fat-equivalent ring and lamp matrix was developed for observing the power distribution in ring applicators used for regional hyperthermia. This phantom was used on four European BSD-2000-type therapy systems under routine conditions to test the quality of the SIGMA-60 applicator (systems in Berlin, Essen, Munich and Rotterdam). Frequency-dependent focusing imbalances were observed in all systems. At the time of the quality control test two of the systems displayed considerable errors in their settings. The system setups and possible ways of correcting errors are described in detail. Small maladjustments are caused by coupling effects between antennas and their surroundings and by interactions between the coaxial cables which supply the power. Serious distortions can be caused by phase errors and defects in cables or plugs; the latter can result in significant long-term restrictions on the ability to control the SAR (specific absorption rate) distribution in a way the user may not notice. The measurements gained from these four systems confirm the need for a practical and universal procedure for quality control in regional hyperthermia.

Europe↗

PubMedDate not supplied

Simulation studies promote technological development of radiofrequency phased array hyperthermia.

A treatment planning program package for radiofrequency hyperthermia has been developed. It consists of software modules for processing three-dimensional computerized tomography (CT) data sets, manual segmentation, generation of tetrahedral grids, numerical calculation and optimisation of three-dimensional E field distributions using a volume surface integral equation algorithm as well as temperature distributions using an adaptive multilevel finite-elements code, and graphical tools for simultaneous representation of CT data and simulation results. Heat treatments are limited by hot spots in healthy tissues caused by E field maxima at electrical interfaces (bone/muscle). In order to reduce or avoid hot spots suitable objective functions are derived from power deposition patterns and temperature distributions, and are utilised to optimise antenna parameters (phases, amplitudes). The simulation and optimisation tools have been applied to estimate the improvements that could be reached by upgrades of the clinically used SIGMA-60 applicator (consisting of a single ring of four antenna pairs). The investigated upgrades are increased number of antennas and channels (triple-ring of 3 x 8 antennas and variation of antenna inclination. Significant improvement of index temperatures (1-2 degrees C) is achieved by upgrading the single ring to a triple ring with free phase selection for every antenna or antenna pair. Antenna amplitudes and inclinations proved as less important parameters.

Carcinoma↗

PubMedDate not supplied

Cellular uptake of magnetic fluid particles and their effects on human adenocarcinoma cells exposed to AC magnetic fields in vitro.

Suspensions of coated superparamagnetic particles (magnetic fluids, MF) in AC magnetic fields have a pronounced specific absorption rate (SAR) per mass compared to multidomain particles. The aim of the present study was to investigate cellular uptake and the biological effects of AC magnetic field excited bio-compatible magnetic fluids on human carcinoma cells in vitro. One of the fluids tested was a dextran magnetite, which has a very low cyto-toxicity with survival fractions (SF) between 0.8 and 0.9 at concentrations of up to 5 mg ferrite per ml. Human carcinoma cells intracellularly accumulate up to 1 pg ferrite/cell which has been demonstrated by electron microscopy (TEM), X-ray spectroscopy and measurements of intracellular iron. It has been shown that the ferrite core is not altered intracellularly, but many of the dextran shells are degraded which yields particle chains and other aggregates observed in TEM. Semi-solid pellets of the tumour cells were treated with AC magnetic fields (520 kHz, 4-12.5 kA/m) or waterbath hyperthermia at 43 and 45 degrees C, in presence of extracellular and/or intracellular magnetic fluid particles. Although MF heating is produced from individual particles, the survival fractions of MF heated and water bath heated cells are equal. In fact, the extracellular MF particle distribution is homogeneous enough to obtain similar inactivation. In contrast to earlier reports intracellular dextran magnetite particles in AC magnetic fields did not induce cell inactivation. Since the amount of intracellular ferrite should be indeed large enough for cell inactivation, the loss of dextran shells is most probably the main cause of limited effectiveness of the intracellular magnetite particles. The present work has demonstrated that: (1) MFH is able to inactivate tumour cells in vitro to at least the same extent as water bath hyperthermia; and (2) that there is a sensitizer effect of ferrofluids at 43 degrees C probably caused by free ferric ions which induce oxidative stress; and (3) that there is no cytotoxic effect of intracellular dextran magnetite particles 30-180 min excited with AC magnetic fields used in this study. For the new method the term 'magnetic fluid hyperthermia (MFH)' is proposed.

Adenocarcinoma↗

PubMedDate not supplied

Effects of magnetic fluid hyperthermia (MFH) on C3H mammary carcinoma in vivo.

Magnetic fluids (MF) have a potential for hyperthermia due to their good power absorption capabilities. Recent in vitro experiments with the so-called 'Magnetic Fluid Hyperthermia (MFH)' have shown that human tumours cells are homogeneously inactivated after AC magnetic field excitation of extracellular MF. The aim of the present study was the evaluation of a high dose MFH on intramuscularly implanted mammary carcinoma of the mouse. The tumours originated from initial in vivo passages of a spontaneous parent tumour. Because of larger variations of tumour growth in this rather primary model, logistic regression of non-averaged volumes was performed for each treatment modality. All growing tumours were randomized 30 days after transplantation (day of treatment) with an overall size distribution between 120-400 mm3. An intratumoural steady state temperature of 47 +/- 1.0 degrees C was maintained for 30 minutes with whole-body AC magnetic fields of 6-12.5 kA/m at 520 kHz. The magnetic fluid was #P6, which is a high biocompatible dextran magnetite. #P6 was given intratumourally (1.5 x 10(-2) mg ferrite/mm3) 20-30 minutes before excitation and was combined with magnetic targeting (50 mT), which yielded a 2.5-fold enhancement of the intratumoural iron concentration. Histological examinations of tumour tissue after intralesional ferrofluid administration alone indicated deep infiltration of the fluid into the carcinoma tissue, but no evidence of tissue damage as compared with untreated controls. In contrast, widespread tumour necrosis was observed after MFH. After application of either dextran or ferrofluid alone (no difference, p = 0.665), tumour growth was slightly delayed in comparison with untreated controls (p < 0.001). In contrast to the good fit of the controls (R = 0.92-0.87), tumour growth after MFH was much more heterogeneous; some tumours showed no evidence for regrowth at 50 days whereas others had grown quite readily. This most probably reflected the critical problem of homogeneity of the intratumoural MF distribution, which was also confirmed qualitatively by Magnetic Resonance Imaging (MRI), heterogeneous pigmentation of MFH treated tumours, and up to 1 degree C differences between temperature probes in the same tumour during AC magnetic field application. However, a quantitative comparison between intratumoural MF-heterogeneity and tumour response could not be performed in this study. Despite these current limitations, the regression analysis of the MFH data yielded a smaller tumour volume of about 1000 mm3 at 50 days growth time in contrast to all three controls. In conclusion, encouraging results have been obtained, which show, that one single high dose MFH is already able to induce local tumour control in many cases within 30 days after treatment. To overcome the uncertainties of intratumoural MF heterogeneity, advanced intralesional application methods are currently under development.

Animals↗

PubMedDate not supplied

Heat response of HT29 cells depends strongly on perfusion--a 31P NMR spectroscopy, HPLC and cell survival analysis.

A model system of perfused human colon adenocarcinoma cells (HT29) encapsulated in alginate was used to examine metabolic response to heat therapy with 31P NMR spectroscopy, HPLC and cell survival analysis. The presented data show, that perfused (medium flow during hyperthermia) and non-perfused (no medium flow during hyperthermia) cells are very difficult in their sensitivity to hyperthermia. Under equivalent experimental conditions with respect to medium pH, oxygen and nutrient concentration, encapsulated perfused HT 29 cells display a significantly lower thermal sensitivity than non-perfused cells. This reduced sensitivity of perfused cells is characterized by an increased cell survival and relative ATP concentration, and reduced drop of the NTP/Pi ratio in the long-term follow up towards zero. The relative ATP concentration determined by HPLC after hyperthermia is correlated with the clonogenic survival fraction. There is a direct relationship, depending on the specific experimental conditions (perfused, non-perfused). For perfused cells only a slight dependency of survival and relative ATP concentration on heat dose is observed. In consequence, the correlation between survival and relative ATP concentration is weak, described by log(SFperf) = 0.7*[ATP-12.4, R2 = 0.79, p < 0.04. For non-perfused cells the correlation is stronger resulting in a relationship of log(SFno perf) = 0.6*[ATP]-9.0, R2 = 0.98, p < 0.0002. Altogether, the presented data suggest that the relative ATP concentration measured by HPLC after hyperthermia might be predictive for cell survival. On the other hand, a dependence between cell survival and long-term changes of NTP/Pi has been found. The results confirm the importance of tumour perfusion for hyperthermia-induced metabolic changes and cytotoxicity and therefore, for the therapeutic outcome.

Adenosine Triphosphate↗

PubMedDate not supplied

Arrhenius analysis of the thermal response of human colonic adenocarcinoma cells in vitro using the multi-target, single-hit and the linear-quadratic model.

In order to compare the intrinsic thermal sensitivity of different malignant cell lines the multi-target, single-hit model has been widely accepted. It is even applied in clinical hyperthermia by the so-called thermal isoeffect dose (TID) concept originated from this model. The second model which is preferentially used to describe radiation survival curves is the linear-quadratic (LQ) model which can be also applied to thermal response. Interestingly, no breaking point and different activation energies are obtained with this model. In the present paper we demonstrate this discrepancy with the two human colonic adenocarcinoma cell lines WiDr and SW620. Our results further validate the already earlier published persuasion, that neither the multi-target, single-hit model, nor the LQ model are adequate to describe hyperthermic survival. Since both models give completely different results, further data aquisition of isoeffect factors, breaking points and activation enthalpies based on the multi-target, single-hit model only, is unprofitable until advanced models of thermal inactivation have been developed.

Adenocarcinoma↗

PubMedDate not supplied

ESHO quality assurance guidelines for regional hyperthermia.

The Technical Committee and the Clinical Committee of the ESHO evaluated the experience of the institutes which are active in clinical regional hyperthermia using radiative equipment. Based on this evaluation, QA guidelines have been formulated. The focus of these guidelines lies on what must be done not on how it should be done. Subjects covered are: treatment planning, treatment, treatment documentation, requirements and characterization of equipment, safety aspects, hyperthermia staff requirements and instrumentation for quality assurance.

Europe↗

PubMedDate not supplied

Solid materials with high dielectric constants for hyperthermia applications.

The manufacture of solid components with high permittivities epsilon r of 1-100 and differing conductivities sigma of 0-1.0 S/m has practical significance for fabricating applicators and phantoms in radiofrequency hyperthermia. For this purpose, various plastics (resins, polyurethane and silicone) were combined with additives (graphite and metal powder) and tested to assess their radiofrequency and mechanical characteristics and to identify manufacturing problems. Most of the plastics could be made highly dielectric and conductive by adding graphite in the range of muscle tissue (i.e. epsilon r approximately 80, sigma approximately 0.8 S/m). However, there are major differences between the materials with respect to mechanical behaviour, durability, feasibility of manufacture, and reproducibility. Manufacturing water-equivalent plastics (low conductivity sigma < 0.05 S/m and epsilon r value of 70-80) is particularly difficult. A less filled polyester resin in which concentration of brass powder can achieve an epsilon r value of up to 100 at low conductivity proved to be the only suitable medium. Such a plastic can be used for future applicator designs. Other materials of interest include plastics equivalent to lossy media (e.g. sigma = 0.45-0.55 S/m, epsilon r = 70-80), fat-equivalent plastics (polyurethane with graphite) and higher dielectric flexible plastics (silicone with brass powder).

Electric Conductivity↗

PubMedDate not supplied

Design and test of a new multi-amplifier system with phase and amplitude control.

The clinical relevance of the radiofrequency regional hyperthermia (RF-RHT) as an adjuvant cancer therapy grows continuously. Simulation studies for optimization of RF-RHT based on the annular phased array systems have shown a significant improvement of power deposition patterns with increasing number of channels. However, this probably requires higher phase accuracy and amplitude stability than are provided by presently used clinical systems, e.g. BSD-2000. Measurements performed on the BSD-200 electronic revealed phase inaccuracies up to +/- 20 degrees and errors in the power registration of +/- 20 W (up to +/- 50 W in the low power range). These errors are further enhanced by the mismatching of the external load (antenna applicator) and thermal instabilities. To achieve the required phase accuracy and long-term stability in the prototype of a new amplifier system, single-sideband (SSB) mixing in combination with direct digital synthesizers (DDS), in-phase and quadrature-phase (IQ) processing and phase-lock loop (PLL) were used. In the DDS's the actual phase of the output signal of each channel is calculated in real-time. No analogue control loop is involved that may cause thermal offset or drift problems. Each DDS operates at a low intermediate frequency (IF) of 1 MHz. To transform the phase information of this IF signal into the desired RF band, SSB mixing-up is performed. A second frequency source, operating as a local oscillator (LO) in the RF band, is required for this technique. Also, the frequency adjustment of the desired RF signal is performed in the LO. These phase and frequency adjustment units are followed by the high efficiency AB-class solid state amplifier unit. The phase and power level stability of the amplifier are controlled by means of digital PLL structures in conjunction with look-up tables. For this control test signals are coupled out by means of directional couplers. The phase control is based on very sensitive phase comparison. These digital control loops are programmable and allow the implementation of different control algorithms. The achieved long-term accuracy (95% confidence interval) is +/- 1-3 W for output power levels ranging from 10-100 W, and +/- 1 degree for phase differences between each channel and a reference signal at a constant power level, and +/- 1.5 degrees for phase difference values at variable power levels between 10-100 W. In conclusion, the new amplifier system is smaller and more efficient than presently available commercial systems.

Electric Power Supplies↗

PubMedDate not supplied

Non-invasive MR thermometry by 2D spectroscopic imaging of the Pr[MOE-DO3A] complex.

Future progress in regional hyperthermia requires a practical method for non-invasive thermometry. In magnetic resonance tomography, spin density, T1 relaxation time, diffusion coefficient and proton resonance frequency are candidates to measure temperature distributions. When used clinically in the pelvic region, all these methods are compromized by artifacts arising from different tissues, tissue alterations under hyperthermia, physiological and random movements, inhomogeneities, drift phenomena, and field instabilities. In this study a paramagnetic complex was evaluated, Pr[MOE-DO3A], with praseodymium as central atom, similar to common gadolinium containing MRI contrast media. The temperature dependence of its methoxy side group approximately -24 ppm downfield from the water resonance at 25 degrees C was employed to determine 2-D temperature distributions in a cylindrical agar phantom containing 9.5 mM of Pr[MOE-DO3A]. The phantom was heated externally through a water jacket creating a stationary temperature distribution throughout the phantom. At first, the correlation between temperature and the chemical shift of the methyl group of the lanthanide complex Pr[MOE-DO3A] was determined. Calibration curves obtained exhibited a linear relationship of 0.12 +/- 0.01 ppm/degree C, nearly independent from the surrounding medium. Local temperature distributions were determined employing the spatially resolved method of spectroscopic imaging (SI). 2-D spectroscopic images for three orthogonal slices were obtained by narrow-band excitation and 16 phase encoding steps in two dimensions. The FOV was 180 mm and the slice thickness in all cases was 20 mm for maximal spatial temperature resolution (11.2 x 11.2 mm2). The results indicate a measurement time of about 5s per acquisition under the following conditions: An estimated concentration of 1 mmol/l, a reduced matrix size of 8 x 8, and a reduced repetition time of 3 x T1 (TR approximately 85 ms). Those SI measurements produced a SNR of approximately 4 per acquisition, a measurements duration of 10-20 s, equivalent to two to four acquisitions per spectrum, seem sufficient for online temperature monitoring during hyperthermia. The in vitro data suggest the spectroscopic temperature measurement utilizing a temperature-sensitive Pr[MOE-DO3A] complex with a therapeutically realistic concentration of 1 mmol/l to be suitable for clinical use. Compared to the methods tested so far (rho, T1, diffusion, proton resonance), the method presented has the unique advantage of being less susceptible to artifacts. The competing methods of non-invasive thermometry employing magnetic resonance imaging are currently being investigated using the same experimental setup.

Hyperthermia, Induced↗