[Magnetic thermotherapy of breast tumors: an experimental therapeutic approach]. / Magnetische Thermotherapie von Tumoren der Brust: ein experimenteller Therapieansatz.

The therapeutic strategy for breast cancer is changing, especially for early tumor stages with good prognosis. One potential minimally invasive therapy modality consists in the accumulation of a well-tolerated magnetic material (iron oxides, particularly magnetite) in the target tissue. By applying an alternating magnetic field, energy is selectively absorbed and induces harmful heating of the tumor. The present review deals with the essential conditions and parameters as studied in vitro and in vivo in animal experiments. Extrapolations to the clinical situation are discussed, in particular, the heating potential of the magnetic material, the selection of the magnetic field parameters, the occurrence of eddy currents, the generation of localized heating spots and the expected temperature rises and their effects on the tumor area.

[Remote controlled drug release in the alimentary tract by local power deposition in alternating magnetic fields]. / Remote controlled drug release in the alimentary tract by local power deposition in alternating magnetic fields.

Remote controlled release of agents in the alimentary tract is an important task of gastroenterology and pharmacy. We investigated two different methods of drug release by heating locally restricted parts in medical capsules: hysteresis losses of magnetite powder and eddy current losses of metals in alternating magnetic fields. The comparison of our experimental results with theoretically derived expectations show that both methods are suitable techniques if special technical conditions are met. In order to demonstrate the feasibility of simple constructions, we used a gelatin capsule, consisting of two parts which were kept together by a belt of wax and a small copper coil. This capsule was placed in water and the belt was heated in an alternating magnetic field until melting and releasing a test fluid after about 60 s.

[A 3D FEM model for calculation of electromagnetic fields in transmagnetic stimulation]. / A 3D FEM model for calculation of electromagnetic fields in transcranial magnetic stimulation.

We developed a realistic finite elements method (FEM) model of the brain for the calculation of electromagnetic fields in transcranial magnetic stimulation (TMS). A focal butterfly stimulation coil was X-rayed, parameterized, and modeled. The magnetic field components of the TMS coil were calculated and compared for validation to pointwise measurements of the magnetic fields with a Hall sensor. We found a mean deviation of 7.4% at an axial distance of 20 mm to the coil. A 3D brain model with the biological tissues of white and gray matter, bone, and cerebrospinal fluid was developed. At a current sweep of 1000 A in 120 microseconds, the maximum induced current density in gray matter was 177 mA/m2 and the strongest electric field gradient covered an area of 40 mm x 53 mm.

[In vitro imaging of magnetite particles]. / Bildgebende Darstellung von Magnetiten in vitro.

PURPOSE: To find an optimal imaging modality for the assessment of magnetite agglomerations used as the heating sources during magnetic thermoablation of tumors. METHODS: 1 to 107 mg of coated (starch) magnetite particles were directly administered to an in vitro tumor model (swine lymph nodes) and investigated immediately (radiography) or after being embedded within a 4 % agar-phantom (sonography). T1-weighted MR images (TR = 400 ms, TE = 14 ms) were acquired from lymph nodes containing 0.5 to 25 mg magnetite. RESULTS: All investigated magnetite masses were qualitatively detectable by radiography. Sonographically, only mass agglomerations containing 107 mg magnetite were appropriately discernible. MRT images revealed distinct susceptibility artifacts. CONCLUSIONS: Based on the investigated imaging modalities, radiography is the method of choice for assessment of magnetite agglomerations using relevant dosages for magnetic thermoablation of tumors.

Electromagnetic heating of breast tumors in interventional radiology: in vitro and in vivo studies in human cadavers and mice.

PURPOSE: To assess relevant parameters for the minimally invasive elimination of breast tumors by using a selective application of magnetite and exposure of the breast to an alternating magnetic field. MATERIALS AND METHODS: The specific absorption rate (SAR) of different magnetite samples was determined calorimetrically. Temperature elevations based on magnetite mass (7-112 mg) and magnetic field amplitude (1.2-6.5 kA/m frequency, 400 kHz) were investigated by using human breast tissue. Parameter combinations (21 mg +/- 9 [SD], 242-second magnetic field exposure, 6.5-kA/m amplitude) were tested in 10 immunodeficient mice bearing human adenocarcinomas (MX-1 cells). Histologic sections of heated tumor tissue were analyzed. RESULTS: SAR data of different magnetite particle types ranged from 3 to 211 W/g. Temperature elevation (DeltaT) as a function of the magnetite mass increased linearly up to 28 mg; at higher masses, a saturation of DeltaT was observed at nearly 88 degrees C. The dependence of DeltaT on magnetic field amplitude (H) revealed a third-order power law: DeltaT = 0.26 degrees C/(kA/m)(3). H(3), with r(2) = 0.95. A mean temperature of 71 degrees C +/- 8 was recorded in the tumor region at the end of magnetic field exposure of the mice. Typical macroscopic findings included tumor shrinkage after heating. Histologically nuclear degenerations were observed in heated malignant cells. CONCLUSION: Magnetic heating of breast tumors is a promising technique for future interventional radiologic treatments.

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.

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.

Model experiments for immunomagnetic elimination of leukemic cells from human bone marrow. Presentation of a novel magnetic separation system.

Optimal conditions for removing leukemic cells from human bone marrow with monoclonal antibodies (mAb) and magnetic immunobeads were investigated. Monodisperse 3 microns polystyrene microspheres containing magnetite were coated with affinity-purified rabbit antimouse IgG at 4 degrees C, pH 9.6 for 18 h. SKW-3 cells (T-CLL cell line) were marked with the supravital DNA stain Hoechst 33342, seeded into normal human bone marrow, and then incubated with the mAb CD1, CD6, and CD8 at 4 degrees C for 30 min. In preliminary experiments REH cells (cALL cells) and mouse anti-REH cell antibodies were used to find the most favorable conditions for the binding of magnetic beads to tumor cells. Optimal formation of cell-bead rosettes was achieved by rotating beads and tumor cells together at room temperature at a concentration of 1 x 10(7) cells/ml, a bead: tumor cell ratio of 100:1 and an incubation time of one hour. The novel magnetic separation apparatus consists of three polystyrene chambers connected by silicone rubber tubing. The chambers contain four steel inserts each equipped with 32 nickel wires, which are magnetized by permanent magnets in such a way that the inhomogeneous high gradient magnetic field could be established within the cell suspension containing the cells to be depleted. The fluid flow was established by a peristaltic pump. At a flow rate of 1.5 ml/min and a field strength of 160 kA/m, no beads could be detected in the purged marrow. A cocktail of the three mAb was more effective than any single antibody in forming bead-cell rosettes. Two sequential purging cycles were superior to one. The marrow recovered was highly viable as assessed by trypan blue dye exclusion and by growth of CFU-GM.