Biomedical subjects

H Fähling

Publications and source records attributed to H Fähling.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of MR-thermography and planning calculations in phantoms.

A systematic comparison of three-dimensional MR (magnetic resonance) thermography and planning calculations in phantoms for the hyperthermia (HT) SIGMA-Eye applicator. We performed 2 x 6 experiments in a homogeneous cylindrical and a heterogeneous elliptical phantom by adjusting 82 different patterns with different phase control inside an MR tomograph (Siemens Magnetom Symphony, 1.5 Tesla). For MR thermography, we employed the proton resonance frequency shift method with a drift correction based on silicon tubes. For the planning calculations, we used the finite-difference time-domain (FDTD) method and, in addition, modeled the antennas and the transforming network. We generated regions according to a segmentation of bones and tissue, and used an interpolation technique with a subgrid of 0.5 cm size at the interfaces. A Gauss-Newton solver has been developed to adapt phases and amplitudes. A qualitative agreement between the planning program and measurements was obtained, including a correct prediction of hot spot locations. The final deviation between planning and measurement is in the range of 2-3 W/kg, i.e., below 10%. Additional HT phase and amplitude adaptation, as well as position correction of the phantom in the SIGMA-Eye, further improve the results. HT phase corrections in the range of 30-40 degrees and HT amplitude corrections of +/- 20-30% are required for the best agreement. The deviation /MR-FDTD/, and the HT phase/amplitude corrections depend on the type of phantom, certain channel groups, pattern steering, and the positioning error. Appropriate agreement between three-dimensional specific absorption rate distributions measured by MR-thermography and planning calculations is achieved, if the correct position and adapted feed point parameters are considered. As long as feed-point parameters are uncertain (i.e., cannot be directly measured during therapy), a prospective planning will remain difficult. However, we can use the information of MR thermography to better predict the patterns in the future even without the knowledge of feed-point parameters.

Algorithms↗

PubMed2005

Methods and potentials of magnetic resonance imaging for monitoring radiofrequency hyperthermia in a hybrid system.

INTRODUCTION: Non-invasive thermometry (NIT) is a valuable and probably indispensable tool for further development of radiofrequency (RF) hyperthermia. A hybridization of an MRI scanner with a hyperthermia system is necessary for a real-time NIT. The selection of the best thermographic method is difficult, because many parameters and attributes have to be considered. METHODS: In the hybrid system (Siemens Symphony/BSD-2000-3D) the standard methods for NIT were tested such as T1, diffusion (ADC: apparent diffusion coefficient) and proton-resonance-frequency shift (PFS) method. A series of three-dimensional datasets was acquired with different gradient-echo sequences, diffusion-weighted EPI spin-echo sequences and calculated MR-temperatures in the software platform AMIRA-HyperPlan. In particular for the PFS-method, corrective methods were developed and tested with respect to drift and other disturbances. Experiments were performed in phantoms and the results compared with direct temperature measurements. Then the procedures were transferred to clinical applications in patients with larger tumours of the lower extremity or the pelvis. RESULTS: Heating experiments and MR-thermography in a homogeneous cylindrical phantom give an excellent survey over the potentials of the methods. Under clinical conditions all these methods have difficulties due to motion, physiological changes, inhomogeneous composition and susceptibility variations in human tissues. The PFS-method is most stable in patients yielding reasonable MR temperature distributions and time curves for pelvic and lower extremity tumours over realistic treatment times of 60-90 min. Pooled data exist for rectal tumour recurrencies and soft tissue sarcomas. The fat tissue can be used for drift correction in these patients. T1 and diffusion-dependent methods appear less suitable for these patients. The standard methods have different sensitivities with respect to the various error sources. The advantages and pitfalls of every method are discussed with respect to the literature and illustrated by the phantom and patient measurements. CONCLUSIONS: MR-controlled RF hyperthermia in a hybrid system is well established in phantoms and already feasible for patients in the pelvic and lower extremity region. Under optimal conditions the temperature accuracy might be in the range of 0.5 degrees C. However a variety of developments, especially sequences and post-processing modules, are still required for the clinical routine.

Humans↗

PubMed2004

[Part-body hyperthermia with a radiofrequency multiantenna applicator under online control in a 1.5 T MR-tomograph].

Objective of this study is the integration of a multiantenna applicator for part-body hyperthermia (BSD 2000/3D) in a 1.5 T MR-tomograph (Siemens Magnetom Symphony) in order to perform noninvasive MR monitoring in real time to increase safety and effectiveness of heat treatments. The positioning unit is mechanically coupled to the MR gantry from the back side and the body coil is utilised for imaging. For that purpose, the hyperthermia antenna system (100 MHz, 1.500 W) and the MR receiver (63.9 MHs) have to be decoupled in terms of high frequency (filter) and electromagnetically (emc). The processing of MR data sets is performed in a hyperthermia planning system. A simultaneous operation of radiofrequency hyperthermia and MR system is possible at clinically relevant power levels. MR imaging is used for tumor-diagnostics (standard spin echo sequences), for hyperthermia planning (T1-weighted gradient echo sequences in equal- and opposed-phase techniques), and for temperature measurements according to the proton resonance frequency method (PRF method, phase evaluation registration using a gradient echo sequence with long echo time). In 33 patients with advanced pelvic and abdominal tumors we performed 150 heat sessions under MR monitoring. For 70% of these patients a visualisation of temperature sensitive data during treatment was possible. The evaluated difference images represent a superposition of real temperature -increase and a (temperature-induced) perfusion elevation. The -hybrid approach renders development of part body hyperthermia possible as an MR-controlled intervention in radiology.

Abdominal Neoplasms↗

PubMed2001

Calibrated electro-optic E-field sensors for hyperthermia applications.

E-field measurements are an important task for the investigation of newly developed hyperthermia applicators as well as for online control of hyperthermia treatments. Compact and non-perturbing integrated optical E-field sensors based on LiNbO3 as well as optical E-field sensors based on infrared emitting diodes and light bulbs are suitable for nearfield measurements of hyperthermia antennas. In order to investigate their properties a calibration cell with transverse electromagnetic (TEM) waves has been constructed. By using this cell, calibration curves and directional patterns for all sensors have been measured. Due to the threshold behaviour of the IRED and light bulb sensor, only the LiNbO3 sensor is capable of measuring weak fields inside an applicator or a homogeneous phantom.

Biophysical Phenomena↗

PubMed2001

Antenna arrays in the SIGMA-eye applicator: interactions and transforming networks.

OBJECTIVES: In multiantenna applicators such as the SIGMA-60 or SIGMA-Eye, which consist of 4 or 12 pairs of antennas shunt to 4 or 12 amplifiers ("antenna couplets"), phases and amplitudes in the feed points of these antennas under certain conditions can significantly differ from the values selected at the multichannel amplifier (forward parameters), mainly due to coupling. In the SIGMA-Eye, this interaction is particularly affected by the transforming networks between the generators and the feed points, thus hampering the control of the feed point parameters. In this work, we perform measurements at existing applicators, present a formalism to describe the facts numerically, and investigate modifications of the transforming networks to improve the performance. METHODS AND MATERIALS: We prepared an experimental setup for the SIGMA-Eye applicator that is fed by forward waves of a 12-channel amplifier system. In this setup, we made the water bolus, the interior of the tissue-equivalent phantom, and the entire transforming network accessible for measuring probes. Then, we constructed various alternative transforming networks such as Pawsey loops, LC matching networks, and power dividers and compared them with the original matching network of the SIGMA-Eye applicator. In particular, we utilized a high-resistive probe to determine the disturbances and influences caused by some channels with respect to some selected feed points of the SIGMA-Eye dipoles. RESULTS: In the original SIGMA-Eye applicator, the influences of coupling channels on the phases and voltages in the feed point of a particular antenna are largest for adjacent longitudinal channels. Here, the +/- 10 degrees phase shift and +/- 30% voltage change were observed if the reference channel (i.e., the disturbed channel) and disturbing channel are equally powered. The changes eminently increased to -30 degrees to + 100 degrees phase shift and -80% to +50% voltage change if the reference channel is fed with much lower power (four to eight-fold) than the disturbing channel. The disturbance from distant channels is less but still significant, reaching shifts of -10 degrees to +50 degrees and -50% to +20%, respectively. Using Pawsey loops instead of the original ferrite rings in the SIGMA-Eye network, the efficacy of the baluns was improved by a more than a factor of 4. Using an LC matching network, dependencies on frequency and external arrangements can be reduced significantly. Applying a power divider circuit, the coupling between antennas combined to one channel is considerably diminished (down to <-25 dB). CONCLUSION: Coupling between resonators (pairs of antennas including the matching network) reduces the control of the SIGMA-Eye applicator, i.e., it causes deviations between the selection of forward parameters at the amplifier and the total actual parameters in the feed points of the antennas. Modified transformation networks can improve the control, in particular by reducing sheath currents and asymmetries. There is a linear but variable relationship between selected (amplifiers) and actually given (feed points) parameters. This linear mapping (described by a matrix) and its characteristics need further investigation.

Hyperthermia, Induced↗

PubMed2000

Electric field distributions in a phased-array applicator with 12 channels: measurements and numerical simulations.

In this paper we examine the SIGMA-Eye hyperthermia applicator (BSD Medical Corp., Salt Lake City, Utah 84119) with respect to the control of electric field distributions. This applicator is equipped with 12 pairs of antennas fed by 12 amplifiers, allowing the individual adjustment of phase and power for each of them. Measurements were conducted using phantoms with well-defined electrical properties. Specific electro-optical sensors, capable of measuring both electric field amplitudes and phases, have been developed, and a system for data acquisition and analysis has been set up. In its initial state the applicator appeared not to be satisfactorily matched at 100 MHz for the phantom used, with return losses up to 20% in power. By tuner readjustments we achieved values below 5%. For various settings of the amplifiers' control parameters we measured field distributions, both in the phantom and in the surrounding water bolus. The experimental results were compared with numerical simulations based on finite difference and finite element methods. Measured and calculated electric fields exhibit deviations of 10% on average, allowing, in principle, a satisfactory prediction of fields by numerical simulations or as well by on-line measurements at selected locations of the applicator at antenna proximity. However, to obtain this satisfactory agreement a modification of the control parameters in the calculations (phases and amplitudes in the feed points of the antennas) was necessary. The origin of these problems is mainly attributed to cross-talk phenomena and other characteristics of the transforming network, which need to be scrutinized further for a full understanding.

Computer Simulation↗

PubMed1999

Scanning E-field sensor device for online measurements in annular phased-array systems.

PURPOSE: A measurement device for noninvasive and simultaneous control of antennas during regional radiofrequency (rf) hyperthermia and, subsequently, the estimation of the power distribution in the interior of patients are essential preconditions for further technological progress. Aiming at this, the feasibility of an electro-optical electric field sensor was investigated during clinical rf hyperthermia. MATERIAL AND METHODS: The electro-optical electric field (E-field) sensor is based on lithiumniobate crystals and the Mach-Zehnder interferometer structure, and was tested in an earlier phantom study. For this study, a mechanical scanning device was developed allowing the registration of the E-field during clinical application. Data were recorded along a curve in the water bolus of the SIGMA 60 applicator of the annular phased-array system BSD-2000 (BSD Medical Corp., Salt Lake City, UT) close to the base points of the flat biconical dipole antennas. The results were compared with modeling calculations using the finite-difference time-domain (FDTD) method. For the latter, different antenna models were assumed. For systematic registration of the E-field curves in amplitude and phase, we employed an elliptical lamp phantom with fat-equivalent ring (filled with saline solution) and an elliptical polyacrylamide phantom with acrylic glass wall. Further measurements were carried out during the treatment of 5 patients with 20 hyperthermia treatments. RESULTS: Data of both phantom and patient measurements can be satisfactorily described by the FDTD method, if the antenna model is refined by taking into account the conical form of the dipoles and the special dielectric environment of the feeding point. Phase deviations can be entered ex posteriori for correction in the calculation algorithm. A comparison of amplifier power measurement (forward and backward power) and bolus E-field scans near the antenna base points demonstrates that E-field measurements between antennas and patient are a necessity for the appropriate characterization of antenna radiation properties. These measurements are sensitive to variations of the lossy medium in position and shape, and can be correctly predicted with current models. However, the differences between different patients are moderate and unspecific in both calculations and measurements, with fluctuations at maximum of 30 degrees in phases and 40% in amplitudes. CONCLUSIONS: The measurement method presented here turned out to be a practical tool for online registration of E-fields in phases and amplitudes along arbitrary curves in a water bolus or phantom. It can be utilized to evaluate antenna design and modeling calculations and leads, thus, to a better understanding of complicated multiantenna systems. In clinical routine, it can be employed as input for patient-specific hyperthermia planning and, finally, for the realization of online control with subsequent optimization of the power distribution in the patient.

Algorithms↗

PubMed1999

Visualization and registration of three-dimensional E-field distributions in annual-phased-array applicators.

A testing system is presented allowing registration, digitization, and evaluation of three-dimensional power distributions rendered by annular-phased-array applicators in homogeneous liquid media. The system is based on a lamp phantom originally developed to visualize power distributions. Now the brightness distribution is registered via a charge-coupled device camera and transferred to a PC-based evaluation system outside the shielding room. An appropriate mechanical coupling of camera and sensor matrix probing the phantom was built in order to keep optical image conditions constant under movement. For visualization and evaluation commercially customized software was employed. The evaluation of the system shows the linearity between sensor signal and power density magnitude to be sufficient for evaluation and graphical representation of three-dimensional data sets. In a first practical application the testing system was employed to evaluate dependencies of power distributions as a function of frequency and phase settings on temperatures and, subsequently, the relevance of those results for clinical hyperthermia in a SIGMA-60 applicator (BSD-2000 system). Now, the system is ready to evaluate more complex multiantenna array applicators like the SIGMA-Eye applicator. The measuring system is particularly suitable for a fast comparison of APA applicators applied for a homogeneous medium. Implications for heterogeneous structures (like in patients) are then possible via modeling calculations.

Calibration↗

PubMed1996

[An interstitial miniature antenna for localized in vivo P-31 MR spectroscopy].

BACKGROUND: Phosphorus spectroscopy can be used to assess response in tumor therapy and to monitor response. An additional response parameter would be useful for individualization in oncological therapy. Methodical problems of localisation and contamination make it more difficult to interpret and reproduce the spectra. Interstitial and endoluminal spectroscopy antennas placed directly within or close to the tumor could provide help in this problem. MATERIAL AND METHOD: We developed an interstitial 31P MRS antenna together with a tuning network which can be used in thermometry catheters for hyperthermia within an internal lumen of 1.1 mm in diameter. A prototype of this type of miniature antenna suitable for use in Siemens MRI scanners at 1.5 T was described spectroscopically with regard to excitation profile, range and SNR. RESULTS: In terms of quality, the excitation profiles of the interstitial antennas in relation to orientation correspond to those of comparable but considerably larger endocavitary antennas and catheter coils for MR imaging and spectroscopy. Maximum sensitivity was achieved by aligning the coil normal perpendicular to the B0 field. Signal losses of up to 50% have to be reckoned with when using other orientations. The maximum range of the interstitial antenna was determined using spectroscopy and was found to be 5 mm, i.e. 9 times coil radius. The sensitivity (SNR, detection sensitivity) of the studied type of interstitial antenna allows in vivo 31P spectroscopy to be performed despite the unusually low axial dimension (coil radius r = 0.55 mm). The prototype of the described interstitial antenna was used to measure an in vivo spectrum from the back muscle of a rabbit in 10 min. Nevertheless, the detection volume of at least some ml necessary for 31P spectroscopy results mainly from the large antenna length. CONCLUSION: The sensitivity (SNR, detection sensitivity) of the interstitial antenna needs to be further improved in order to assess treatment response in patients. However, the construction principle is suitable for intracavitary 31P spectroscopy antenna with larger diameters, which can be used for advanced rectal, cervical and prostate carcinomas.

Animals↗

PubMed1991

[Determinant factors and disturbances in controlling power distribution patterns by the hyperthermia-ring system BSD-2000. 2. Measuring techniques and analysis].

Clinical observables and phantom measurements (part 1) have suggested that the control of power deposition patterns can still be improved for the hyperthermia system BSD-2000. This is addressed to system-specific phase errors as well as inadequacies of phase selection (target point method), which might be corrected by modifications of the manufacturer. Furthermore, frequency-dependent physical effects (coupling, mode excitation) are existing, which might cause distortions and asymmetries of current distribution on antennas and consequently deteriorate the power deposition pattern (e.g. focussing capability). The application of a network analyzer system is described in order to determine electrical material constants, phase errors, coupling coefficients, reflection coefficients and current distributions on antennas. The analysis of the measurement datas suggests that ring-applicator has a variable frequency-optimum (supposed around 80 ... 95 MHz) characterized by minimal coupling and asymmetries.

Humans↗

PubMed1990

[The influencing factors and interfering effects in the control of the power distributions with the BSD-20000 hyperthermia ring system. 1. The clinical observables and phantom measurements].

A new generation of annular-phased-array systems BSD-2000 has been clinically applied in a pilot study. Therapeutic intratumoral temperatures greater than 42 degrees C were obtained in 15/15 sessions with six patients. However, the control of power deposition pattern has to be improved in order to increase the therapeutic gain and to guarantee an efficient therapy. A retrospective analysis of clinical phenomena has been performed by phantom set-ups because the power deposition pattern cannot be determined during therapy. Phantom measurement techniques are outlined, specifically phantom materials and visualization of power distributions. The problem of focus balance and frequency choice is illustrated by self-developed phantoms (liquid crystal sheets, light-emitting-diode-arrays). Especially, the limitation of modeling calculations is demonstrated.

Evaluation Studies as Topic↗

PubMedDate not supplied

Performance and use of current sheet antennae for RF-hyperthermia of a phantom monitored by 3 tesla MR-thermography.

Several MR-compatible current sheet antennae (CSA) of different height (h) (16 cm (l) x 8 cm (w) x 1-5 cm (h)) were built for simulated RF (96 MHz) hyperthermia of a medium-sized (12l) tissue-equivalent phantom inside a 3 tesla whole body tomograph. Prior to use, efficiencies of the CSA were determined by network analysis and by calorimetry. Depending on the height h of the CSA and on the thickness d(bolus) of the water bolus used for RF-coupling of the CSA to the lossy medium, their efficiency varied between 20-70% and the CSA with h = 3 cm was selected for simulated RF hyperthermia. During heating, spatial temperature distributions (20-42 degrees C) of five slices (voxel size 2 x 2 x 10mm(3)) were recorded intermittently within 4 s/slice by measuring the temperature dependent shift of the (1)H resonance frequency (125.32 MHz). A phased array consisting of two identical CSA produced distinctly different spatial temperature distributions at 0 and 180 degrees phase difference between both RF channels feeding the antennae. Within a one-dimensional heat diffusion model, the specific absorption rate (SAR) of the electromagnetic wave generated by a single antenna was deduced from the experimental data resulting in a penetration depth (1/e(2)) of approximately 4 cm.

Biophysical Phenomena↗

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

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

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↗