Wilfried Andrä

Physical limits of hyperthermia using magnetite fine particles

Structural and magnetic properties of fine particles of magnetite are investigated with respect to the application for hyperthermia. Magnetic hysteresis losses are measured in dependence on the field amplitude for selected commercial powders and are discussed in terms of grain size and structure of the particles. For ferromagnetic powders as well as for ferrofluids, results of heating experiments within organic gels in a magnetic high frequency field are reported. The heating effect depends strongly on the magnetic properties of the magnetite particles which may vary appreciably for different samples in dependence on the particle size and microstructure. In particular, the transition from ferromagnetic to superparamagnetic behavior causes changes of the loss mechanism, and accordingly, of the heating effect. The maximum attainable heating effect is discussed in terms of common theoretical models. Rise of temperature at the surface of a small heated sample as well as in its immediate neighborhood in the surrounding medium is measured in dependence on time and is compared with solutions of the corresponding heat conductivity problem. Conclusions with respect to clinical applications are given.

Application of magnetite ferrofluids for hyperthermia

A comparative study is presented for the specific loss power generated by an external magnetic field in superparamagnetic as well as ferromagnetic magnetite particles suspended in molten and solidified gel. The field amplitude dependence of magnetic losses obeys power laws of third order for ferromagnetic samples and second order for superparamagnetic samples, respectively. Calorimetrically determined data are compared with results of hysteresis measurements. Consequences for the application for hyperthermia are discussed.

Temperature distribution as function of time around a small spherical heat source of local magnetic hyperthermia

A spherical region containing magnetic particles embedded in extended muscle tissue is taken as model of small breast carcinomas. Using analytically derived equations the spatial temperature distribution is calculated as function of the time for exposing to an alternating magnetic field. In vitro measurements with muscle tissue yielded such an agreement with the calculations that treatment of small tumors in slightly vascularized tissues on the base of mathematical predictions seems now to be more promising than in the past.

Heating potential of iron oxides for therapeutic purposes in interventional radiology.

RATIONALE AND OBJECTIVES In addition to their diagnostic applications, iron oxides could be used therapeutically to eliminate tumors with heat if their heating powers are adequate. The authors therefore examined the specific absorption rate (SAR) of different iron oxide (magnetite) samples suspended in water and in liquid or solidified gel. MATERIALS AND METHODS The authors compared two ferromagnetic fine powders (total particle size, >350 nm and 100 nm), five superparamagnetic ferrofluidic samples (total particle size, 10-280 nm), and a commercially available contrast medium (ferumoxides injectable solution, Endorem). The SARs of the magnetic material-suspended in distilled water or in liquid or solid agar-were estimated from time-dependent calorimetric measurements during exposure to an alternating current magnetic field (amplitude, 6.5 kA/m; frequency, 400 kHz). RESULTS SARs varied considerably between the different iron oxide samples. The highest value was found for a ferrofluidic sample (>93 W/g), while Endorem had little heating power (<0.1 W/g). The SAR was clearly dependent on the aggregation state of the matrix only for the large-particle-size ferromagnetic sample, yielding the highest values for particle suspensions in water (74 W/g) and lowest for solid agar (8 W/g). The heating power of the smaller-particle-size ferromagnetic sample did not exceed 8 W/g. CONCLUSION Heating powers differed according to the interaction of multiple physical parameters. Iron oxides should be selected carefully for therapeutic applications in magnetic heating.

A novel method for real-time magnetic marker monitoring in the gastrointestinal tract

In internal medicine, a simple method for the functional examination of the gastrointestinal tract without the risk of radiation exposure is required. We describe a novel principle based on the monitoring of magnetic markers which meets these demands. Our method employs a special permanent magnet which is repeatedly aligned by a vertically oriented pulsed magnetic field. Due to this alignment, the marker position can be derived from the stray field components measured by commercial field sensors. Our method was evaluated by means of a 3D intestinal phantom. The monitoring procedure yielded the time course of the marker position as a 3D plot either in real-time or as a time-lapse movie. The spatial resolution, expressed by the mean square deviation, was better than 10 mm and is thus sufficiently high to distinguish between adjacent loops of the gut. The temporal resolution, i.e. the minimum time between two successive measurements, was about 1 s. The presented method has very moderate technical demands and allows us to monitor magnetic markers in real-time. The technique may be useful with respect to functional examination of the gastrointestinal tract. In pharmaceutical research, our method offers the opportunity for remote drug release at any position of the gut.

Magnetic nanoparticles for selective heating of magnetically labelled cells in culture: preliminary investigation

The minimally invasive elimination of tumours using heating as a therapeutic agent is an emerging technology in medical applications. Particularly, the intratumoural application of magnetic nanoparticles as potential heating sources when exposed to an alternating magnetic field has been demonstrated. The present work deals with the estimation of the basic relationships when the magnetic material has access and binds to structures on cell membranes of target cells at the tumour region, particularly as a consequence of administration through tumour supplying vessels. Therefore, using mouse endothelial cells in culture, the binding of dextran coated magnetic nanoparticles (mean hydrodynamic particle diameter 65 nm) was modelled using the periodate method. The efficacy of cell labelling was demonstrated by magnetorelaxometry (MRX)—a selective method for the detection of only those magnetic nanoparticles that were immobilized—as well as by electron microscopy and iron staining. The amount of iron immobilized on cells was found to be 153 ± 56 µg Fe per 1 × 107 cells as determined by atomic absorption spectrometry. Moreover, after exposure of those 1 × 107 labelled cells to an alternating magnetic field (frequency 410 kHz, amplitude 11 kA m−1) for 5 min, temperature increases of 2 °C were achieved. The consequences of particle immobilization are reflected by the results of the measurements related to the specific heating power (SHP) of the magnetic material. Basically, the heating potential is explained by the superposition of Brown and Neel relaxation while for immobilized nanoparticles the Brown contribution is absent. In the long term the data could open the door to targeted magnetic heating after further optimization of the heating potential of magnetic material as well as after functionalization with biomolecules which recognize specific structures on the surface of cells at the target region.

Evaluation of temperature increase with different amounts of magnetite in liver tissue samples.

RATIONALE AND OBJECTIVES The biologic effects of magnetically induced heating effects using iron oxide, magnetite, were examined in vitro in liver tissue samples as a first step toward potential applications in cancer therapy. METHODS For the determination of the temperature profile around an iron oxide sample, a cylinder containing 170 mg of magnetite was constructed and placed into pureed liver tissue from pig, together with thermocouples of copper and constantan wires positioned at defined distances from it. Temperature measurements were performed during the exposure to an alternating magnetic field (frequency: 400 kHz; amplitude: approximately 6.5 kA/m) generated by a circular coil (90 mm of diameter). Moreover, variable amounts of magnetite (dissolved in approximately 0.2 mL physiologic saline) were injected directly into carrageenan gels. During the exposure to a magnetic field for 4 minutes the temperature increase was determined in the area of iron oxide deposition using a thermocouple. Additionally, variable amounts of magnetite were injected directly into isolated liver tissue samples (diameter: 20 mm; height: 30 mm) and exposed to a magnetic field for 2 minutes. The extent of the induced macroscopically visible tissue alterations (light brown colorations caused by heating) was examined by means of volume estimations. The degrees of cellular necrosis were investigated by histopathologic studies. RESULTS The temperature profile around a magnetite cylinder revealed a significant decrease of temperature difference between the beginning and the end of heating, depending on increasing distance from the sample center. The extent of the temperature difference correlated with increasing heating time. No significant variations of temperature were observed at a distance of approximately 12 mm from the sample center. A good correlation (r = 0.98) between the injected amounts (31 to 200 mg) and the temperature increase since the start of heating (6.8-33.7 degrees C) in the area of iron oxide deposits was detected. The volume of damaged liver tissue was approximately seven times higher than the injected volume of iron oxide dispersion. Histologically different degrees of cellular necrosis were observed. CONCLUSIONS The parameters determined in this article show that iron oxides are able to induce considerable heating effects in the surroundings. After an adequate optimization of the technical procedure, it is conceivable that heating properties of magnetites can be used in future cancer treatments.

Magnetic Nanoparticles for Biomedical Heating Applications

Summary In the past, magnetic nanoparticles have found increasing interest in different biomedical applications, e.g. the magnetic hyperthermia of tumor cells or the remote controlled drug delivery to the gut. These applications are based on a magnetically induced heating effect caused by different magnetic loss mechanisms in the nanoparticles. To advance the present state of the art of these methods, it is important to use particles with a higher specific heating power (SHP) at lower magnetic field amplitudes. To this aim, several iron oxide nanoparticle powders, consisting of particles in the diameter range from 10 nm up to 100 nm, were prepared by two different chemical methods and magnetically as well as morphologically characterized. The magnetic characterization was done by using a vibrating sample magnetometer and the calorimetrical determination of SHP. The dependence of the magnetic losses on the morphological properties was investigated. Magnetic characterization showed that several suitable iron oxide absorbers can be utilized. With decreasing particle size, hysteresis loss underestimates SHP at higher frequencies as measured calorimetrically. The effect of measurement frequency on the hysteresis losses is shown experimentally. Experimental results are discussed in the frame of known theoretical models of nanoparticle magnetism.

Magnetoresistance and Kerr effect investigations of Co/Cu multilayers with wedge shaped Cu layers

Abstract The magnetic coupling behaviour of dc-magnetron sputtered Co/Cu multilayers with wedge shaped Cu interlayers was investigated by magnetoresistance (MR). The well known oscillatory behaviour of both the amplitude of the MR effect and the saturation field H s was found. Within the first region of antiferromagnetic coupling around 1 nm Cu there is a different thickness dependence of H s and MR presumably caused due to the imperfect structure of our multilayer system. Domain nucleation and reversal behaviour were studied by Kerr microscopy and correlated with the observed coupling states determined by MR. There were no clear hints for a biquadratic coupling term.

A novel magnetic method for examination of bowel motility

In contrast to the well-developed methods for morphological diagnosis of the gastrointestinal tract, there is no comparatively satisfying technique for functional disorders. One important example is irritable bowel syndrome (IBS), a disorder that affects a high percentage of all individuals. It can only be diagnosed by excluding organic diseases and by considering symptom criteria. In this case, the examination of the motility of the bowel may be a promising way to differentiate between the two major mechanisms of IBS: increased sensitivity of the intestine and altered gastrointestinal motility. To this aim, a recently developed method for monitoring magnetic markers in the gastrointestinal tract was utilized that works without the use of ionizing radiation. We give a short description of this method, showing a spatial resolution of 3-4 mm and a temporal resolution of 330 ms, and report on examples of the first in vivo experiments. Typical monitoring results are shown for the esophagus, the stomach, and the duodenum. The motility behavior is described for the lower parts of the gut as well. The advantages and drawbacks of this type of magnetic marker monitoring are discussed with special consideration of the noninvasive examination of the motility in different sections of the gut.