COMMISSION K : ELECTROMAGNETICS IN BIOLOGY AND MEDICINE (Nov. '92 - Oct. '95)

Edited by Shoogo Ueno


K1. Biological Effects of Electromagnetic Fields

K1.1. Electric Fields

Recently there has been growing interest in the biological effects of electromagnetic fields. The review presented here emphasizes topics of recent study of the biological effect of electric fields in Japan.

A series of studies have been made in Hokkaido University and Hokkaido Institute of Technology. Their research was initiated to evaluate the perception of ELF electric field because the electric field perception is known as one of basic mechanisms to produce effects. When a human body is exposed to an electric field, the hair on the body surface moves due to the electric force exerted on the hair. Based on both theoretical and experimental analyses, it was shown that the ambient relative humidity is the key factor which affects the perception mechanism [Odagiri et al., 1994a, 1994b, 1994c].

An optical telemetry technique was developed to measure the physiological response of an animal when it was exposed to an electric field. A rabbit was exposed to a strong electric field, and the change in its peripheral circulation was detected with this technique [Yamashita et al., 1994]. Both contraction and dilation of peripheral blood vessels were detected on the exposure to electric fields. These results will help us to establish a practical safety standard for the electric field exposure from the points of field perception.

As a part of study on the effects of an electric field, the behavior of the PVC-DOPH artificial membrane was examined. This model membrane simulates phospholipids usually found in living organisms. This artificial membrane was exposed to the electric field. Based on the experimentally obtained results, it was revealed that this membrane had current-controlled negative resistance at above 4 kV/m. Comparing this result with both human and animal study, the author pointed out that cell membranes of living organisms are influenced by electric field [Kojima et al., 1994].

(T. Shigemitu)



K1.2. Static Magnetic Fields

Biological effects of static magnetic fields have been poorly understood. Recognition of the role of paramagnetic, diamagnetic and ferrimagnetic materials in the body may help in unraveling the underlying mechanisms.

Ueno and Iwasaka [1994] studied the properties of diamagnetic water in static magnetic fields. The phenomenon that the surface of the water was pushed back by magnetic fields of higher gradients was observed. Two "frozen" cascades were formed; the surface of the water near the center of the magnet parted and the water level at both ends of the chamber rose. Reversed Moses effect using copper sulfate solution was also observed [Hirota et al., 1995]. Studying the role of diamagnetic fluids in gradient magnetic fields is important in understanding the mechanisms of the biological effects of magnetic fields.

The behavior of oxygen dissolved in an aqueous solution under magnetic fields of up to 8 T with a gradient of 50 T/m was studied [Ueno et al., 1994, 1995]. For oxygen concentrations greater than 11 mg/l, a clear redistribution of dissolved oxygen was observed. The concentration increased more than 5 % around the center of the magnet. The degree of the redistribution was dependent on the initial dissolved oxygen concentration. Redistribution was not observed in an equilibratory state of oxygen pressure at the air atmosphere.

Higashi et al. [1993a] conducted a study of the effects of a strong static magnetic field on the orientation of human erythrocytes. The authors concluded that exposure to static magnetic fields changes the orientation of normocytic erythrocytes so that their disk planes become parallel to the field direction. The orienting effect of static magnetic fields appears to be due to the diamagnetism of cellular components associated with oxyhemoglobin and not the paramagnetism associated with deoxyhemoglobin or methemoglobin. Higashi et al. [1993b] found the orientation of blood platelets of healthy people due to the influence of a static magnetic field. Magnetic orientations of red blood cells and their ghosts were also investigated by measuring resistivity of solution [Tsuda et al., 1994].

The anisotropic diamagnetic susceptibility of erythrocytes and blood platelets were determined [Yamagishi et al., 1992]. The paramagnetic attraction was studied systematically and it became clear that the attraction takes place with venousblood and that depends on the product of the field strength and its spatial gradient, the degree of deoxygenation, the flow velocity, and the hematocrit [Shiga et al., 1993].

Effects of strong magnetic fields on a process of dissolution of fibrin clots was studied [Iwasaka et al., 1995]. When a fibrin gel and a plasmin solution were exposed to magnetic fields where a product of magnetic fields and field gradients, B dB/dz, was 370 T2/m, dissolution of fibrin was enhanced. Fibrin polymers in water magneto-phoresically drifted in the direction of increasing magnetic fields, and dissolution of fibrin polymers by plasmin was accelerated.

Sato et al. [1992] established a static magnetic field possessing a strong spatial gradient on the surface of cell culture dishes using a gilded iron needle set vertically above an Sm-Co magnet. Cultures of HeLa S3 or normal human gingival fibroblasts (Gin-1 cell line, American Type Culture Collection) were placed on blocks of a Sm-Co magnet having a surface field strength of 0.2 T (2,000 G). Yamaguchi et al. [1993] conducted a study to assess the effects of exposure to a 0.2-T (2-kG) magnetic field for 6 or 8 mo on cellular proliferation, changes in DNA concentration, glycolytic activity, and morphology in human gingival fibroblasts. The cells were exposed or sham exposed for an additional week, after which the process of dispersal, subculturing, and exposure was repeated. The authors concluded that long term exposure of confluent cell cultures to a static 0.2-T magnetic field did not alter their growth, glycolytic activity or histomorphology.

The effect of high magnetic fields(<14 T) on the triplet biradical generated from the intramolecular photoreaction of the chain-linked molecule a-(anthraquinone-2-carbonyloxy)-w-(xanthene-2-carbonyloxy) dodecane (AQ-12-XH) was studied by using laser flash photolysis in a pulse magnet [Mukai et al., 1993] and the effect on the photo reaction of benzophenone in SDS micellar solution [Fujiwara et al., 1993]. Effects of strong magnetic fields on cell growth and radiation response of human T-lymphocytes in culture were studied [Norimura et al., 1993]

Effects of high magnetic field at ELF specifically on the growth of bacteria was investigated using a newly developed superconducting magnet system [Okuno et al., 1993, 1994; Tsuchiya et al., 1993; Okuda et al., 1995].

The genetic effects of magnetic fields on somatic reversion and somatic recombination in Drosophila melanogaster have been reported. Yoshikawa, et al. [1995] examined the somatic reversion of the white locus and the somatic recombination of mwh and fly genes in Drosophila melanogaster after they were exposed to a static magnetic field at 8 T. The static magnetic fields of up to 8 T were effective in producing the eye spots caused by intragenic mutation and the wing hair spots resulting from somatic recombination. In the exposure groups, eye spots occurred 1.7 times more frequently than in the control groups, and wing hair spots 1.4 times more. A wing spot test in Drosophila melanogaster was also carried out by Koana, et al. [1995]. They reported that exposure to a static magnetic field of 5 T increased chromosomal recombination by 50 %.

(M. Nakagawa and S. Ueno)



K1.3. ELF Magnetic Fields

Exposure of PC12-VG cells, derived from rat pheochromocytoma PC12 cells, to an extremely low frequency magnetic field enhanced the b-galactosidase gene expression stimulated by treatment of the cells with forkolin [Ohtsu et al., 1995].

Bessho et al. [1995] investigated the effects of alternating magnetic fields on the growth, reproduction, and behavior of wild type (Bristol N2) or double mutant (ace-1(p1000) ace-2(g72)) strains of C. elegans. The authors concluded that strong alternating magnetic fields can induce behavioral abnormalities in whole intact C. elegans organisms similar to changes reported in unicellular organisms and cultured mammalian cells. The effects on postembryonic growth, pumping movements, fecundity, egg laying, and behavioral alterations disappeared when the field was removed, suggesting that magnetic field effects under the conditions tested are well tolerated or can be compensated for.

Effect of 60 Hz magnetic field on longevity of fruit flies was investigated experimentally [Naito et al., 1993] and effect of 50 Hz magnetic field on plasma and pineal melatonin levels in rats was reported [Kato et al., 1993]. It was pointed out that the effects of ELF magnetic field depend not only on the intensity but on the directions, circular, horizontal, or vertical [Kato et al., 1994a, 1994b, 1994c, 1994d]. Circularly polarized 50 Hz magnetic field exposure reduced pineal gland and blood melatonin concentrations of Long-Evans rats [Kato et al., 1994a]. Horizontal or vertical 50 Hz, 1 mT magnetic fields had no effect on pineal gland or plasma melatonin concentration of albino rats [Kato et al., 1994b]. Furthermore, recovery of nocturnal melatonin concentration took place within one week following cessation of 50 Hz circularly polarized magnetic fields [Kato et al., 1994c]. Exposure of circularly polarized, sinusoidal, 50 Hz magnetic fields did not influence plasma testosterone levels of rats [Kato et al., 1994d].

(H. Matsuki and M. Nakagawa)



K1.4. RF and Microwaves

Researches on biological and electromagnetic environments in RF and microwave region in Japan are reviewed by Amemiya. Biological objectives, evaluation of exposure rate, electromagnetic environments and guideline for the protection from radio wave nuisances are briefly introduced. Some researches on the evaluation of the exposure rate caused by the near field effects of a portable radio transceiver are reviewed, further, radio frequency exposure protection guideline in Japan are described [Amemiya, 1994].

The effect of microwave irradiation on monkey eyes is studied. This study is a follow-up experiment of Kues et al.'s work in 1985, that corneal endothelial abnormalities were observed after a 4-hour exposure of anesthetized monkey eyes to 2.45 GHz CW. The experiment was done without anesthetization. The power density exceeding the threshold of 30 mW/cm2 obtained by them was applied to the object. Although the same abnormality as Kues et al. found out could not be observed [Kamimura et al., 1994a, 1994b].

The effects of magnetic field, radiofrequency, and gadolinium diethylenetriaminepentaacetic acid(Gd-DTPA) on the sister chromatid exchange(SCE) in human peripheral lymphocytes were investigated. Samples were exposed to magnetic force (1.5 T) alone, and to a magnetic force combined with radiofrequency waves(63.86 MHz, SAR 0.4 W/kg). Gd-DTPA was then added to other blood samples in varying amounts and concentrations. As the concentration of Gd-DTPA added to the blood increased, the SCE frequency also increased. However, the addition of Gd-DTPA at the clinical concentrations normally used did not affect the SCE frequency [Yamazaki et al., 1993].

(I. Yamaura)



K2. Tissue Properties and Materials

An experimental study on the penetration characteristics of submillimeter waves in biological tissues and materials is done. The measured values of the penetration depth in excised natural muscle, fat and aqueous solution of protein, bovine serum albumin(BSA), over the wavelengths of 281 through 496 mm are presented.

As a result, it is found that the typical values of the penetration depth in the natural muscle roughly agree with that in the 35 % aqueous solution of BSA in the submillimeter-wave region [Fuse, et al., 1994].

A noninvasive method for measuring complex permittivity of biological tissues is proposed. This method is based on an inverse scattering technique which employs an iterative procedure, and requires the knowledge of the target shape, the incident and measured scattered fields. According to the principle of the method, a measuring system of complex permittivity is developed and its reliability is verified [Wan and Takagi, 1994]. Biological tissues have the dielectric properties of wide distribution of relaxation frequencies changing with structural tissue and with temperature. In order to locate the different frequencies that give large absorption ratios, numerical calculations were made on the absorption power ratios between two adjacent media simulating high water content tissues having different relaxation types. These results are important for the evaluation of the therapeutic equipment and the hazard effects [Rajhi et al., 1994a].

A new muscle-equivalent phantom which is composed of water, polyethylene powder, NaCl, agar and so on, is developed by the research group of Chiba University. This phantom can keep its shape by itself and it is easy to make and handle. The complex permittivity of the phantom is very similar to that of the actual muscle at UHF. The specific heat and thermal conductivity are suitable for the thermographic research [Furuya et al., 1995]. Electromagnetic power absorption in multilayered tissue media including anisotropic muscle regions whose principal dielectric axes have various directions are analyzed. Numerical calculations in 10 kHz-10 MHz show the effects of orientation of muscle fibers and polarization of incident wave on absorbed power density in tissues [Asai et al., 1994].

For the purpose of developing a method of measuring electrical properties of human tissues and biological substances by a lumped capacitance time domain spectroscopy, a simulation of a time domain analysis for time domain reflectometry was made. As a result of the simulation, it was found that the spectroscopy was useful method for measuring electrical properties of biological substances of which relaxation properties were characterized by a superposition of Debye dispersion relations [Baba and Takagi, 1994]. This time domain reflectometry was actually applied to the measurement of beef meat, mouse leg, in vitro. During measurements, two mainly limitations appeared for broad-band dielectric properties determination [Rajhi et al., 1994b].

An estimation method for efficiency calculating the field intensity in the Fresnel region of broadside colinear array antennas is developed. The calculation utilizes only the antenna design data, and is readily applicable to arbitrary array antennas. This method can provide a safety protection zone in the proximity of array antennas [Kobayashi and Nojima, 1994].

(I. Yamaura)



K3. Fields Measurement and Exposure Assessment

K3.1. ELF Fields

A number of experimental researches were conducted in the Central Research Institute of the Electric Power Industry (CRIEPI): A novel method was developed for measuring eddy currents induced in biological models consisting of plural mediums [Yamazaki and Suda, 1994; Yamazaki, 1995]. This method, capable of measuring 3-dimensional induced currents inside mediums, was applied to the observation of local increase or decrease in current density in two-medium model. The principal features of a single coil, Helmholtz coils and multiple coils used for calibration purpose were discussed with aim at contributing to the discussion of the IEC standard under consideration [Tomita et al., 1995]. The electromagnetic environments generated by power transmission system were identified together with the method for their mitigation [Tomita, 1995]. The magnetic field meters were developed: one was a single-axis meter, and the other was a compact, tri-axis exposure meter having three coils of 20 mm in diameter and in length with ferrite cores placed orthogonally to each other [Yamazaki et al., 1994]. In relation to the ELF magnetic field measurements and exposure tests, a low-stray magnetic field generator was proposed, which used compensation coils for active control of stray fields to be minimized [Yamazaki et al., 1995]. A facility for small animal chronic exposure to 50 Hz magnetic fields was introduced along with a biological effect found [Shigemitsu, 1994]. The magnetic field meters developed by CRIEPI were found to be very useful to characterize the magnetic fields near the ground under the power lines [Tomita et al., 1994].

A 3-dimensional analysis was made of induced currents and surface electric fields in laboratory animal models exposed to power frequency electric field [Takuma et al., 1994]. The user-friendly, numerical computer program was successfully used for this analysis. The analysis was made of the current density distribution in a two-layer, cylindrical human model exposed to uniform electric field [Isaka et al., 1994]. It was found from this analysis that the electrically induced current density changed according to the combination of the tissue conductivities used for the two layers. New measurement techniques were developed for the evaluation of human exposure to electric field [Shimizu, 1994]. One of them is an optical telemetry technique which was successfully used for animal's physiological response test.

ELF magnetic fields in HV and EHV power stations were characterized [Hayashi et al., 1994, 1993]. In their papers described were the measured results of total magnetic flux density distribution in a 187/66-kV power station yard, and the predicted disturbance of magnetic fields in the vicinity of metal materials used for supporting power apparatus in substations.

(K. Isaka)



K3.2. RF and Microwaves

The local specific absorption rate (SAR) distribution in a cylindrical human body model placed near a wall due to TE microwave irradiation was calculated using a finite-difference time-domain (FD-TD) method [Kuwano et al., 1994]. The power absorption of a cylindrical man model placed near a flat reflector exposed to a TE microwave was numerically shown in a submicrowave band to become greater compared to the case without the reflector [Kuwano, et al., 1995].

A hydrogel phantom that can visualize the absorption pattern of electromagnetic energy was developed [Toya et al., 1993]. High molecular gel phantoms of the human body that are made from polyacrylamide or gellan gum containing a nonionic surface active agent were also developed. These phantoms can be used to visualize the three-dimensional pattern of electromagnetic power absorbed by the human body, making use of its temperature-dependent cloudiness [Miyakawa et al., 1994].

SARs in a human model under the various electromagnetic environments were computed using a FD-TD method. The frequency characteristics of whole-body averaged SARs in a homogeneous human model exposed to the near field of an electric dipole or a magnetic dipole were calculated [Watanabe et al., 1994a, 1994b]. The SARs inside the eyeball for 1.5-GHz microwave exposure were computed for two kinds of highly heterogeneous models constructed by the author and Taflove's group [Fujiwara and Kato, 1994]. Strong correlation between the surface-SAR and external magnetic near-field in a realistic head model for 1.5-GHz microwave far-field exposure was shown, and a method for approximately estimating the surface-SAR was proposed using an external magnetic near-field strength [Fujiwara and Nomura, 1993, 1995].

For estimating the spatial peak SAR in a human head when exposed to the near-field emitted from a hand-held portable radio, an experimental SAR estimation system based upon a thermograph method was developed using a thermograph camera and newly constructed homogeneous dry-phantom human models [Nojima et al., 1994].

In order to protect from unexpected biological effects the engineers exposed to strong electromagnetic waves in their experimental environments, a method for reducing SAR in a human body by a perfect conducting shield was proposed, and the SAR characteristics were calculated in a cylindrical human model attached to the shield for plane wave exposure [Nakamura and Tokumaru, 1995].

(O. Fujiwara and Y. Kamimura)



K4. Magnetic Stimulation

A method of localized magnetic stimulation of the brain has been developed by Ueno [1994]. By concentrating induced eddy currents on a target with a pair of opposing pulsed magnetic fields produced by a figure-eight coil, they were able to stimulate the human cortex within a 5 mm resolution.

Magnetic stimulation of the heart was studied by Yamaguchi, et al. [1994]. Effects of strong pulsed magnetic fields of up to 9.2 T on the cardiac activity of an open chest dog were examined. Biomagnetic stimulation has opened a new horizon for functional brain research and cellular engineering.

Lin et al. [1993] conducted to evaluate changes in local blood flow and maturation of collagen fibers during ligament repair. The authors concluded that PEMFs enhance blood flow, increase the number of fibroblasts, and stimulate fibroblasts to produce more collagen in injured ligaments, thus accelerating the healing process.

Matsuda et al. [1994] focused on realization of the Spino-bulbo-Spinal (SBS) reflex in human subjects by means of magnetic stimulation. They assume that the latency elongation on the SBS reflex by repetitive magnetic stimulation of the median nerve is caused by enhancement of a polysynaptic inhibitory system at the spinal or more higher levels such as the brainstem.

Andoh et al. [1994] examined the effects of magnetic stimulation on electrocardiographic(ECG) activity in an open-chested dog. The authors concluded that strong pulsed magnetic fields applied to the heart with normal sinus rhythm induces premature ventricular contraction (PVC) when they are delivered between the T and P-waves of the ECG. Future work will establish the threshold for PVCs in this open-chested dog model in order to determine the margin of safety needed for devices producing pulsed magnetic fields.

Yamada et al. [1995] evaluated the effect of transcranial magnetic stimulation (TMS) on cognitive function in 3 monkeys. The maximum magnetic fields produced by these coils were 3.3, 1.9, and 2.4 T, respectively. The authors concluded that TMS does not appear to affect higher cerebral function in monkeys. They suggested, however, that these findings apply to TMS as it is currently used in clinical practice and caution should be exercised when applying higher intensity, high-frequency pulsed magnetic stimuli to the head using the next generation of magnetic stimulators which are now becoming available.

Kubota et al. [1995] discussed the potential of electrical stimulation to regenerate bone and its applicability to alveolar and periodontal research. EMFs used in medical applications can be characterized as 3 fundamental types: There have been reports of enhanced osteogenesis following stimulation by all 3 types of EMFs. The authors suggested that EMFs may act in 3 fundamental modes: message, hormone, or substrate. Enhanced cementogenesis as well as osteogenesis has also been observed following application of capacitively-coupled EMFs to experimental periodontal defects in dogs. When used in conjunction with bone replacement, grafts or guided tissue regeneration procedures, EMF stimulation has enhanced bone regeneration.

Optimum spacing in the range of 9-13 mm, which minimizes the temperature rise, was given for non-contact energy transmitting coils for implantable devices [Matsuki et al., 1993].

(M. Nakagawa and S. Ueno)



K5. Hyperthermia

A new muscle-equivalent phantom, which is composed of water, polyethylene, powder, NaCl, agar and so on, has been developed. This phantom can maintain its shape by itself and it is easy to make and handle. The complex permittivity of the phantom is very similar to that of the actual muscle tissue at UHF. The specific heat and thermal conductivity are suitable for the thermographic method [Furuya et al., 1995].

An analysis of the coaxial-slot antenna, which is an effective antenna for interstitial microwave hyperthermia, is described. The structure of a coaxial-slot antenna for analysis is described. The antenna is modeled as a vertical antenna penetrating the interface between the air and a lossy medium. In this analysis, the full-wave spatial Green's function is approximated by an exponential polynomial, and a catheter around the antenna is replaced with an equivalent polarization current. An electric current distribution along the antenna is calculated by using the moment method and an electric field distribution around the antenna is derived from the current distribution. We present the results of our calculations and discuss the effect of the antenna insertion depth on both the current and field distributions [Wu et al., 1995].

A figure of eight coil was tried in order to elevate the tumor temperatures in the range of 42-45 C [Nishide et al., 1992]. A pair of inductive aperture-type applicator focusing electromagnetic energy using the RF waves was proposed [Fujita et al., 1993]. The characteristics of hexagonal array composed of thin coaxial-slot antennas for interstitial hyperthermia was examined precisely [Terakawa et al., 1992; Shimura et al., 1992]. A newly developed partially ferrites loaded waveguide applicator was presented, which can control the radiating EM field by DC magnetic field [Nikawa et al., 1995] A heating method using microcapsules made of ferromagnetic amorphous metal flakes that is additionally capable of releasing anticancer agents was developed [Sato et al., 1993]. A new method of catheter ablation using temperature-sensitive ferrite rod and a non-magnetic metal ring as a heating device was developed [Hoshino et al., 1994].

(K. Ito and H. Matsuki)



K6. Electromagnetic Fields in Medical Diagnosis

There are some problems remained to be worked out on Magnetic Resonance Imaging(MRI), such as the coil(gradient and RF) design or RF safety consideration. An RF shield between the RF coil and the gradient coil(G-coil) was analyzed in order to prevent noise radiation from the G-coil, RF loss in G-coil and RF loss due to radiation to the outside [Ochi et al., 1993]. For the computation of scattered field and magnetic loss, the impedance method is becoming an important tool, and the situation of non-cylindrical or non-uniform object was partially studied [Ochi et al., 1994]. The input impedance, the resonance frequency, the Q value and the magnetic field distribution of slotted tube resonator for MRI were obtained to show the effects of the dielectric body and the conducting shield [Chen et al., 1994].

Microwave imaging of a biological target has been investigated by using a CW-microwave signal, or a chirp pulse-microwave signal. A transmission-type microwave computed tomography [Onodera et al., 1993; Yamaura, 1994, 1995] has been developed for a microwave imaging of a biological target. The research group has attempted microwave imaging of a real human body such as an arm at 3 GHz [Nakajima et al., 1994, 1995].

On the contrary, the chirp radar-type microwave computed tomography concentrates on the non-invasive measurement of temperature distribution inside a human body [Miyakawa, 1992, 1993, 1994; Miyakawa et al., 1992a, 1992b; Watanabe et al., 1992]. It has been investigated as a new modality mainly used for non-invasive thermometry in hyperthermic treatment. Temperature resolution of 0.7 degree and spatial resolution of approximately 1 cm have been reported [Miyakawa, 1994b, 1994c, 1995a, 1995b; Miyakawa and Hayashi, 1994; Miyakawa et al., 1995] through the experimental studies for the chirp radar-type microwave computed tomography using phantom models of a human body. For practical application of the microwave computed tomography, techniques for a high speed imaging have been investigated.

(H. Matsuki and M. Miyakawa)


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