COMMISSION K: ELECTROMAGNETICS IN BIOLOGYAND MEDICINE
Edited by Shoogo Ueno
Introduction
The research activities on the biological effects of electromagnetic fields in Japan from1999-2001 are reviewed. In vitro, in vivo, dosimetrical and epidemiologic al studies on DC and
ELF electric fields, DC and ELF magnetic fields, RF and microwaves are discussed.
Biomedical applications including magnetic stimulation, hyperthermia, thermal ablation, MEG,
MCG, impedance MRI, current MRI, MRI, and radiometry are also introduced.
K1 Biological Effects of Electromagnetic Fields
K1.1 DC and ELF Electric Fields
On dosimetry, Hirata et al. calculated the spatial distribution of induced electric field andcurrent density in a child and an adult bodies exposed to a 60 Hz electric field. They showed
the difference in the induced electric field and the current density in various organs between achild and an adult [Hirata, 2001].
On instrumentation, Yamashita et al. have developed a technique to measure EEG and ECG at
the subject exposed to a strong ELF electric field. The electrodes were carefully shielded andEEG and ECG could be measured by radio telemetry [Yamashita, 2001a,b].
On genetic effects, Ding et al. observed the increase in hypoxanthine-guanine phosphoribosyltransferase gene mutations in Chinese hamster ovary cells after the exposure to the electricfield (10 V/m, 60 Hz) for 10 hours [Ding, 2001].
On cellular effects, Shimooka et al. reported the suppression of macrophage phagocytosis byelectric current. Since this effect was caused by a displacement current as well, their results
suggested the possibility of immunomodulation by electric field exposure [Shimooka, 2000,
2001]. Suda et al. demonstrated that the orientation of human red blood cells was controlled byan electric field as well as by a magnetic field [Suda, 1999]. Katsuki et al. showed that thegrowth activity of B. Stearothermophilus was affected by the pulsed electric field, while noremarkable lethal effect was observed in the range of up to 40 kV/cm [Katsuki, 2000].
In the experiments with human subjects, Kawada investigated the change in an EEG spectrum.
He could not find any significant change in the EEG spectrum in the exposure of 3 kV/melectric field and 0.08 ? T magnetic field [Kawada, 2001]. Using the above mentioned
telemetry system, Yamashita et al. have analyzed the changes in the heart rate variability (HRV)and the body surface temperature to investigate the effect on the autonomic nervous system. A
50 Hz electric field was exposed to a subject using the instrument designed for an electric
therapy. Noticeable changes were observed in the spectral power of HRV and in the skintemperature at the back of the subject’s hand [Yamashita, 2000, 2001a,b]. Shimizu et al.
analyzed the threshold of electric field perception with human subjects in detail. In an
experimental study, various causes of the variation in the perception threshold were clarified.
They also found the changes in peripheral blood flow at the body surface associated with thefield perception [Shimizu, 1999a,b,c, 2000, 2001a,b].
K1.2 DC Magnetic Field
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K1.2.1 In Vitro Studies
Studies on magnetic orientations of several kinds of floating cells and micro-creatures werereported. The summation of induced diamagnetic moments, which were of mainly lipid cell
membrane, generated a torque force on the cell, and the cell rotated to orient in an aqueous
solution. It was reported that red blood cells oriented parallel to external magnetic fields[Higashi T, 1998, Suda T, 1999].
The magnetic orientations of micro-creatures, such as bull sperms [Higashi T, 2000, Emura R,
1999 and 2001, Takeuchi T, 2002, Suga D, 2000], and Euglena gracilis [Tanimoto, 2001] werereported.
A functional change in red blood cells during floating and magnetically orienting under static
magnetic fields was reported [Iwasaka M, 2001a]. The magnetic orientation of a red blood cellchanged the spectrum profile of hemoglobin inside the cell. A floating cancer cell, lymphoma,
showed the slowing growth rate under a magnetic field of 8 T [Ogiue-Ikeda M, 2001].
Drastic effects of static magnetic fields on the aggregation of floating blood cells were reported[Iino W, 2001]. Red blood cells under a 6.3 T magnetic field showed enhancements in both
sedimentation and aggregation. Collagen stimulated blood platelets showed a rapid aggregation
under magnetic fields of up to 14 T [Iwasaka M, 2000]. Diamagnetic torque forces of 14 T
magnetic field modulated the cleavage pattern of early embryos of Xenopus laevis, [Iwasaka M,
2002a].
Based on the previous studies on magnetic orientation of collagen and fibrin, recent studies
reported a new approach to manipulate cells in a non-contact condition using magneticallyaligned protein polymers. The orientation of bone cells, which were embedded on magneticallyoriented collagen gel, was reported [Kotani H, 2000]. The magnetically aligned collagen fibers
provided ordered cell layers of endothelial cells and smooth muscle cells, which wereapplicable to an artificial blood vessel [Iwasaka M, 2002b].
The alignment of adherent cell assembly without adding any proteins under a magnetic field
was reported [Iwasaka M, 1999a]. Smooth muscle cells directed their long axis parallel to astatic high magnetic field of 8 T. Rat smooth muscle cell (A7r5) was cultured in a polystyrene
flask for weeks in magnetic fields of up to 8 T. The alignment of smooth muscle cell was
analyzed quantitatively using an order parameter [Umeno A, 2001].
Strong static magnetic fields have an effect on the orientation of adherent mammalian cells.
However, no distinct effect was observed in cell growths. Two types of mammalian cells,mouse leukemia cells, P388, and Chinese hamster fibroblast cells, V79, showed no change incell growth and DNA distribution by a 7.4 Tesla magnetic field [Sakurai H, 1999]. Also, thecell cycle distribution and cell growth in Chinese hamster ovary (CHO)-K1 cells were notchanged by a 10 T magnetic field [Nakahara T, 2002]. In contrast, it was reported that static
magnetic fields of milli-tesla order affected on metabolic activity of mitochondria [Yamashita
K, 2000] and on cell cycle [Saito D, 2000].
Magneto-mechanical effects with the energy exceeding thermal agitation were observed in acellular level. Diamagnetic torque rotation in cytoskeleton was detected by means of thelinearly polarized light transmission measurement [Iwasaka M, 2002c]. Magnetic beads, which
had strong magnetism and were injected into a cell, accelerated the cell differentiation ofmyoblasts under a magnetic field [Yuge L, 2000]. Spatial gradient magnetic fields of 90 T/m
under 10 T fields exhibited magneto-phoreses of smooth muscle cells, blood platelets andyeasts [Iwasaka M, 2001b].
Behaviors of a bacteria, Escherichia coli, under static magnetic fields of several teslas were2

observed [Shoda M, 1999]. It was reported that 5.2-6.1 tesla high magnetic field enhanced astationary phase-specific transcription activity of Escherichia coli [Tsuchiya K, 1999 ]. Also, asuppression of Escherichia coli death was observed in the stationary phase [Ishizaki Y, 2001],
and it was suggested that the rpoS gene was the target of magnetic field effect [Horiuchi S,
2001]. These effects were larger under gradient magnetic fie lds than under homogeneous
magnetic fields [Okuno K, 2000, Okuno K, 2001].
Another study reported a synergetic activity of a 5 T static magnetic field on chemical mutagen
in Escherichia coli. Mutagenicity of ENNG in the bacterial mutation assay was enhanced underthe magnetic field exposure at 5 T [Ikehata, 1999a,b].
And also, 5 T static magnetic field exposure inducedgene conversion in yeast S. cerevisiae
tester strain [Ikehata M, 2001]. S. cerevisiae, was also used as a test system to obtain a possible
cell response to a static magnetic field exposure in transcriptome. Recently developed DNA
micro array system was used for screening expression change in whole genes and several
specific genes, which were up-regulated by a magnetic field exposure at 14 T was reported.
[Ikehata M, 2001].
K1.2.2 In Vivo Studies
Genetic and physiological effects of static magnetic fields on biological systems in vivo havebeen studied by several research groups. Dr. Ohkubo of the National Institute of Public Healthhas conducted intensive studies on the effects of static magnetic field exposure to bloodpressure and cutaneous microcirculation in rabbits. Using microphotoelectric plethysmography
technique, they found that exposure of the animals to a 1mT magnetic field cancelled thepharmacologically induced high or low blood pressure [Okano, 1999a and 2001a]. Ichioka et al.
[2000] exposed anaesthetized rats to a much higher intensity field (8T). They reported that the
exposure caused a decrease in the microcirculation and, therefore, in subcutaneous temperature.
Kawakubo et al. [1999], on the other hand, exposed human volunteers to 0.45 or 1.2T static
fields and found an increase in skin temperature. It seems the latter finding is consistent withthe results of Nakagawa who found volunteers exposed to 1T field fell into a vagotonic state[2000]. However, he presumed that the volunteers’ anxiety at being exposed to a strong
magnetic field caused an increase in the synpathetic tone. Effects of static fields up to 1.5T on
neuroconduction [Osuga, 1999] and muscle tension [Satow, 2001] were also studied.
Genetic effects of a strong static field have been revealed by Takashima et al. [2000, 2001],
using DNA repair defective mutants of fruit fly Drosophila melanogaster. In a post-replication
repair defective mutant, exposure to a 5T magnetic field caused somatic recombination. In a
excision repair defective strain, on the other hand, mutations resulting from chromosomal
non-disjuntion or deletion increased while somatic recombination frequency was not affected.
These findings suggest some mechanisms of carcinogenic action of magnetic fields. It is
possible that exposure to static magnetic fields causes at least two kinds of DNA damage which,in repair proficient flies, are repaired by the excision repair and post-replication repair
mechanisms, respectively. Defects in the excision repair results in deletion or non-disjunction,
while defects in the post-replication repair causes somatic recombination. We are eager to learn
about further observations on the relationship of magnetic field exposure and DNA repair
mechanisms.
K1.2.3 Other Studies
The mechanism studies of DC magnetic field effects tended to focus on the physical andchemical effects of strong static magnetic fields and their relation to biological phenomena.
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Three kinds of categories for the DC magnetic field effects are proposed; i) spatial gradientmagnetic field effects on a mechanical property of material, ii) diamagnetic torque force
dependent effects, such as magnetic orientation, and iii) biochemical studies respecting radical
species. Concerning strong magnetic particles, magnetite, the gene responsible for themagnetite formation in magneto-tactic bacteria was investigated.
Recently, the techniques for making strong magnetic fields proceeded significantly [Kindo K,2001]. Superconducting magnets with a room temperature bore of 10 Tesla order wereintroduced into many laboratories, and many effects of DC magnetic fields were observed.
Nakagawa, J., et al. [1999] reported that the gradient magnetic forces acting on paramagnetic
oxygen molecules and water enhanced the water vaporization form a water pool under strong
magnetic fields. Hirota, N., et al. [1999] presented the multiplication of the gravity and the
diamagnetic force in horizontal direction affected the germination of plants. Yano, A, et al.
[2001] found an effect of static magnetic fields of milli-tesla order on radish’s root orientation.
The magnetic forces, which were the products of magnetic flux density B and their spatial
gradient dB/dx, were responsible for the effects on plant behaviors.
An application of both magnetic forces, rotational force of diamagnetic torque and gradient
force, for the controlling biological macromolecular liquid crystals was exhibited, by utilizing acompact permanent magnetic circuit [Hirai M, 2001].
A slight change in the structure of water molecules under 14T magnetic field was reported by
Iwasaka, M., et al. [1999b]. Diamagnetic energy generated in a liquid state material under
external strong magnetic field, and it possibly affected the structure of molecular assembly.
Although the effects of magnetic fields on enzymatic reactions containing radical species weremainly investigated spectro-photometrically, Yoita, M. [2001], and Iwasaka, M. [2001c], et al.,also observed magnetically disturbed activities of catalase and peroxidase, which were
immobilized on an platinum black electrode.
Discoveries of new magnetic phenomenon under strong static magnetic fields andunderstanding the linkage of individual mechanisms will provide a new approach for studies on
milli-tesla to micro-tesla magnetic fields, and also for time-varying magnetic fields.
K1.3 - ELF Magnetic Field
K1.3.1 In vitro Studies
Regarding the effects of extremely low frequency (ELF) magnetic field at the cellular level,
many studies using E. coli and mammalian cells at various magnetic density have been
published. Some of them are introduced in this section. In the studies using cell-free system,
the rate and fidelity of DNA polymerase catalyzed DNA synthesis, as well as of RNApolymerase RNA synthesis, were not significantly affected by 60 Hz 0.25-0.5 T magnetic fields[Harada, 2001]. A 50 Hz, 14 mT circularly polarized magnetic field had no detectable
mutagenic or co-mutagenic potential in bacterial tester strains [Nakasono, 2000]. Exposure to aswitched, time-varying 1.7 T magnetic field partly suppressed K+ influx, which may be
mediated by Ca2+-dependent K+ channels [Ikehara, 2000]. The effect of ELF magnetic field on
mutation was not observed in the CHO-K1 cells after 6-week exposure at 50 Hz and 5 mT,
however, X-ray-induced mutation was increased [Miyakoshi, 1999a]. The wild-type p53 gene
expression suppressed the increase in mutation caused by the exposure to 50 Hz, 400 mT ELF
magnetic field [Miyakoshi, 1998b]. Also X-ray-induced strand breaks were potentiated by the
exposure to 400 mT ELF magnetic field [Miyakoshi, 2000a]. In the study using both
Mitomycin C (MMC) and the ELF magnetic field, an increase in chromatid-type chromosomal
4aberrations was observed in mouse m5S cells [Yaguchi, 2000]. Heat shock protein 70 (hsp70)
expression was not affected by exposure to the ELF magnetic field alone, however, expressionof heat-induced hsp70 protein was potentiated by repetitive pulsed magnetic stimulation(RPMS) [Tsurita, 1999] and suppressed by exposure to 60Hz, 50 m ELF magnetic field[Miyakoshi, 2000c]. X-ray-induced apoptosis was transiently suppressed by exposure to 60 Hz,
5 mT ELF magnetic field [Ding, 2001].
K1.3.2 In Vivo Studies
A series of studies have been made in National Institute of Public Health. Ohkubo et al
investigated the biological effects of static magnetic field and ELF-MF on microcirculation in
animals [Ohkubo 1999a 1999b 2001; Ushiyama 1998 2001a 2001b; Xu 1998 2000]. As one ofthese studies, they investigated the acute and subchronic exposure effects of ELF-MF on
leukocyte behavior in mice. In order to do this study, they developed a dorsal skinfold chamber
technique and a cranial window system for measuring the behavior of intra-microvascularleukocytes in the cutaneous and cerebral microcirculation. Using this in vivo system, theresults showed that ELF-MF exposure influence cell to cell interaction between venularendothelial cells and leukocytes.
The mutagenicity is the main issues in the study of ELF-EMF effects. Three papers were
published by Koana et al [1999 2001a 2001b]. They examined the possible carcinogenic and/or mutagenic activity of ELF-MF using somatic mutation and recombination test system ofDrosophila melanogaster. As a result, if larvae were exposed to a magnetic field in an annular
dish, flies from the outer ring showed more mutant spots compared to those from the inner ring.
They concluded that results suggest the eddy current induced in culture medium causes
mutation, rather than the magnetic field itself.
Miyakawa et al [2001] examined the responses of the heat shock protein, hsp-16 in
Caenorhabditis elegans to ELF-MF. They found the gene, hsp-16-lacZ, was induced by
ELF-MF and concluded that C.elegans perceives ELF-MF as stress. In order to check theeffects of ELF magnetic fields on swimming behavior, Nakaoka et al [2000] used Paramecium
multimicronucleatum as a model. With discussion of the gravitaxis and thermotaxis ofParamecium, they suggest that the magnetic field may amplify to a large extent the negative
gravitaxis of Paramecium and discuss the effects of induced electric field on the swimming
behavior.
The above mentioned laboratory studies play an essential role in understanding the effects of
ELF MF on various systems. More fundamental studies are needed.
Apart from animal exposure experiments, Takimoto et al [2001] showed the very interesting
study about the effects of ELF-MF on the germination of plant seeds under the saturated
humidity conditions. Their results suggest that exposure to EMF-MF might remove theinhibitory effect of saturated humidity on process of seed germination of Arabidopsis.
K1.3.3 Other Studies
As a human exposure study, Hong et al [2001] investigated the possible effects of repeatedexposure to ELF-MF with electric sheet at night time on melatonin in male subjects. The
experiment consists of 16 week which has pre-, during and post-exposure periods. The urine
samples are collected and analyzed. 24h rhythms are extracted for each subject by the methodof complex cosine curve fitting. Peak height, acrophase and total daily amount of melatoninwere characterized. These results did not reveal that any statistically significant different
between exposure periods and non-exposure periods. They finally indicate that the effect of5

magnetic field on the nocturnal melatonin production and its circadian rhythm is unlikely.
In order to provide the risk perception of EMF and compare the risk perception of EMF withother environmental factors, Yaguchi et al [2000] analyzed the response from undergraduate
students in four universities in Kyoto. They used a questionnaire concerning risk perception
and knowledge about EMF and health problems. Their results suggest that student’s vague fearof EMF may not be based on accurate knowledge of the risk, but based on their own experienceof health problems associated with the uses of household appliance and cellular phone. The
clarification and resolution of the risk perception, risk assessment and risk communication
are next step in understanding the EMF issues.
Ohkubo presented a series of review papers focusing on the electromagnetic fields and health[Ohkubo 2000a 2000b]. He emphasized also the necessity and application of electromagnetic
fields phenomena in medicine [2000c]. Shigemitsu et al [2000] reviewed the progress and final
evaluation of US-EMF-RAPID Program Nakagawa also pointed out the safety standards of
EMF in electric industries [1998].
K1.4 - RF and Microwaves
Experimental systems were developed for animals to expose microwaves and SAR inside
animals with those systems were evaluated [Wake, 2001a,b,c,d; Watanabe, 1999a,b,c, 2000a,c].
Exposure setup for in vitro experiment on biological effects of microwaves was also developed[Taki, 1999a].
The effects on blood brain barrier (BBB) by 1439 MHz time division multiple access(TDMA) signals for the personal digital cellular (PDC) Japanese cellular telephone standard
system were studied using SD rats at Tokyo University [Tsurita, 2000; Nagawa, 1999, 2001].
They showed that there were no effects on BBB by the exposure without thermal effects.
Studies on the microcirculation of rat’s brain locally exposed to PDC signal were made byresearcher of National Institute of Public Health [Masuda, 2000, 2001a, 2001b]. The exposure
which brain average SAR was lower than 7.5 W/kg did not significantly influenced
microcirculation of rat brain. The effects on memory and learning of rats were also studied at
Tokyo University [Yamaguchi, 2000, 2001a,b,c]. Although the extremely high-level exposure
which induced whole body temperature elevation of 2 degree changed memory of rats, theexposure of 7.5 W/kg brain average SAR did not cause changes in memory.
DNA damage and changes on heat shock protein exposed to 2.45 GHz electromagnetic fields
were studied by in vitro experiment at Kyoto University [Miyakoshi, 1999c, 2001; Tian, 2002].
In these experiments, they reported that only high SAR (more than 20 W/kg) induced hsp70.
K2 - Tissue Properties, Materials, and Phantoms
Human body impedance is an important parameter to estimate the contact current in the LF to
HF band. Kamimura et al., recently reported the measured contact impedance of Japanesepeople and investigated the equivalent circuit parameters [Kamimura, 2001a].
Cytomagnetometry is used to investigate intracellular movements of organelles such as
phagosomes. Nemoto and his colleagues developed a noninvasive observation method byintroducing magnetic particles into cells by phagocytosis, magnetizing them and measuring thefield from the cells. This method can measure the rheological properties of the cytoplasm andthe energy responsible for rotational random movements of the phagosomes. [Nemot, 1999,
2000, 2001, and Moeller 2000].
Hoshina et al., studied on an open-ended coaxial probe, which is widely used for complex
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permittivity measurement at high frequencies. They investigated the measurement region
experimentally and numerically and reported that the region extends to about 5.4 mm under theprobe surface [Hoshina, 2000 and 2001].
Various phantoms for SAR measurement were studied. Ito and his colleagues developed
tissue-equivalent solid materials optimized for thermographic dosimetry [Ito, 1998 and Okano,
2000a]. Basic investigation to improve accuracy of thermographic measurement using solid
phantoms was also performed [Watanabe, 2000b]. Kobayashi et al., developed alcohol-baseliquid phantom used at UHF band [Kobayashi, 1999]. Similar materials are recently proposed
for standard head SAR measurement methods issued by IEEE, CENELEC, ARIB, and so on.
The shape of the phantom for determining the peak spatial-average SAR in the human head
was recently standardized internationally. Watanabe and his colleagues studied the effect of the
shape of the head phantom on the measured SAR values. They reported that the ear shape wascrucial factor of the peak SAR values [Watanabe, 1999d, 1999e, and 1999f], but that thedifferent size between the European/American base standard (large) head phantom and theJapanese averaged (small) head phantom hardly affects the peak SAR values [Watanabe, 2001aand 2001b].
K3 - Field Measurement and Exposure Assessment
K3.1 DC and ELF Fields
Studies on estimating ELF electrically and magnetically induced current inside living bodies
have been actively conducted in some laboratories.
The induced current density is numerically analyzed during exposure to an ELF magnetic field,
using a realistic MRI-based rat model, by means of the impedance method [Wake, 2000]. In the
study, special focus was placed on both specific tissues, i.e., pineal gland and retina, andpolarization of the magnetic field, for comparison with the result obtained from animal studies.
Electrically induced currents inside a human model, which was ungrounded or standing on an
insulated plate, were calculated using the finite-element method (FEM). Here the human model
was assumed to be axis-symmetric and homogeneous [Chiba, 1999, 2000]. Induced current
inside a homogeneous sphere and spheroid was analyzed under the condition of simultaneous
exposure to both electric and magnetic fields [Matsumoto, 1999, 2000]. A thin layer
representing the bio-membrane inside a human body was incorporated in the multi-medium
spherical model for magnetically induced current calculation using the semi-analytical solution
developed for the model [Tarao, 2000].
Two studies were conducted using a simple human model taking into consideration five major
spheroidal organs: i.e., the brain, heart, lungs, liver, and intestine. The boundary element
method (BEM) was adopted to calculate exposure to electric [Techaumnat, 2000] and magnetic
fields [Techaumnat, 2001]. In an other study, the surface charge method was adopted to clarify
the effect of conductivity of each organ and the difference between human models [Yamazaki,
2000a,c, 2001a].
A simple characterization of the magnetic fields generated by electrical appliances was
performed using an equivalent magnetic dipole moment incorporating harmonics [Yamazaki,
2001b]. A low stray magnetic field generator was developed for use in biological cell exposurestudies [Yamazaki, 2000b].
K3.2 RF and MW
A series of studies on the numerical dosimetry at frequencies for cellular phones with various
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antenna types [Fujiwara, 2000a; Wang, 1999d, 2000b] were conducted in Nagoya Institute ofTechnology. Based on the consideration that a localized SAR exposure limit should bedetermined from the resultant temperature-rises, the temperature-rises in human head were
calculated by using the FDTD (finite-difference time-domain) method [Wang and Fujiwara,
1999e; Wang, 2000a]. Comparison of the peak SARs were made in adult and infant-size headmodels, and an increase of peak SAR or peak temperature-rise in the infant head, although thelevel is much less than the threshold that causes physiological damage to the brain tissue, wasobserved [Fujiwara 2000b]. The tissue structure dependence in numerical dosimetry and theuncertainty in one-gram-tissue average procedure were also investigated [Wang, 1999a, 2001a;
Ushimoto, 2000]. In addition, an FDTD model for predicting the EMI (electromagnetic
interference) of implanted cardiac pacemaker by cellular phones was developed and applied tothe evaluation of EMI suppression effects [Wang, 2000c, 2001b].
For establishing a head phantom for SAR compliance evaluation, a detailed study of theearlobe effect on the peak SAR was conducted in Communication Research Laboratory andTokyo Metropolitan University [Watanabe, 1999d, 1999e, 1999f]. The peak SAR in various
homogeneous head models with different shapes was also investigated [Watanabe, 2001a,
2001b]. The European-American head model was found to give an overestimate on the peak
SAR in comparison with the Japanese head model.
For dosimetry evaluation, an easy handling SAR meter was developed for cellular phones[Nojima, 1999, 2001; Iyama, 2001], and a spectrum analyzer based electric field meter was
also developed for base stations [Tarusawa, 2001] in NTT DoCoMo Inc.
The frequency dependence of SAR in multiplayer spherical models for near-field exposure wasanalyzed [Kamimura, 1999, 2001d]. By using tissue-equivalent solid phantoms developed in
Chiba University, experimental SAR evaluation also for near-field exposure was made with athermographic method [Ito, 1999, 2001a; Koyanagi, 2001; Okano, 1999, 2000a, 2000b]. In
addition, permittivity measurement techniques of phantom construction materials, for example,
the standing wave method, were investigated for phantom design [Miyakawa, 2000, 2001a,
2001b].
K4 - BioMedical Applications
K4.1 Magnetic Stimulation
After Ueno et al. developed a method of localized magnetic stimulation of the brain with a pairof opposing pulsed magnetic fields produced by a figure-eight coil in 1988, the localized
magnetic stimulation progressed and became one of essential techniques [Ueno S, 1999a] forthe brain science research of 21 century.
Recently, many clinical studies reported on the application of the transcranial magnetic
stimulation for functional mapping of human cortex [Shiga Y, 2002]. Kamida T, et al. [1998]
measured motor evoked potentials in rat brain, which was induced by transcranial magnetic
stimulation, and found that extrapyramidal activities and locomotor function were affected.
Effects of magnetic stimulation on an experimental animal were studied using forced
swimming test. Tsutsumi T, et al. [2002] reported that a repetitive transcranial magnetic
stimulation on rat had a similar effect to electroconvulsive shock (ECS).
A clinical study investigated on neurologic effects of magnetic stimulation, and showed atherapeutic effect, such as pain relief [Sato T, 2002]. Also, a therapeutic study was carried out
in the purpose of controlling the stress incontinence by Fujishiro T, et al. [2000]. Magnetic
stimulation was applied to induce nerve stimulation in sacral roots.
8Fujiki M, et al., [2001] exhibited a detailed functional brain mapping by transcranial magnetic
stimulation by observing corticospinal D and I waves. Also, the induced neuronal modulation
probably caused a change in gene expression. For example in 1997, Fujiki, M., et al. presented
the evidence that the transcranial magnetic stimulation at 25 Hz on mouse upregulated theastroglial gene expression. They observed a distinct there increases in the levels of glial
fibrillary acidic protein (GFAP) messenger-RNA in hippocampal dentate gyrus, after the 25Hzof magnetic stimulation on mouse brain. Tsurita G., et al., [1999] studied possible effects ofrepetitive pulsed magnetic stimulation on cell proliferation and expression of heat shockprotein 70, however, no-significant effects were observed.
Numerical studies were proceeded to clarify the efficiency of magnetic stimulation in living
tissue models. Hiwaki O, et al., [2000] reported that the threshold for peripheral nerve
excitation became lowest when the angle of figure-of-eight coil’s junction was parallel andperpendicular to nerve the fiber. In order to find an efficient condition for the magnetic
stimulation using the figure-eight coil, Liu R, et al., [2000] calculated the activating function of
nerve excitation in inhomogeneous volume conductor during magnetic stimulation using thefinite element method. They found that the interface between conductors of different
conductivities affected the nerve excitation by magnetic stimulation.
K4.2 Hyperthermia and Thermal ablation
In recent years, various types of medical applications of microwaves have been investigated.
Among them, minimally invasive microwave thermal therapies are of great interest. They areinterstitial hyperthermia and microwave coagulation therapy for thermal treatment for cancer,
cardiac catheter ablation for ventricular arrhythmia treatment, and so on. Ito and his colleagues
at Chiba University have been studying the heating characteristics of thin coaxial antennas byusing the FDTD (Finite Difference Time Domain) method and the FDM (Finite Difference
Method). Heating performances (SAR and temperature distributions) of an array applicator forthe hyperthermic treatment are calculated by numerical analyses. The array applicator iscomposed of a few coaxial-slot antennas and is fed with a 430 MHz generator. Firstly, the SAR
distributions around the applicator were calculated by the FDTD method. Next, the temperature
distributions around the applicator were analyzed by solving the bioheat transfer equation
based on the resultant SAR distributions. After confirmation of the validity of the numericalcalculation, the temperature distributions inside the multilayered media, such as
skin-fat-muscle, are described. [Ito, et al. 1999]. Microwave coagulation therapy (MCT) has
been used mainly for the treatment of small size tumor. In the treatment, a thin microwave
antenna is inserted into the tumor, and the microwave energy provided by the antenna heats up
to the tumor at least 60 deg. C. to produce the coagulated region including the cancer cells for a
few minutes or longer. There are some problems that need to be improved for conventional
MCT antennas. There is a problem that we have not generated a sufficient coagulated region in
the perpendicular direction of the antenna, as one of the problems. Therefore, Saito et al.
[2000a] developed a novel technique to expand the coagulated region. The temperature
distributions inside the human body were generated by an array applicator and an array spacing
was optimized theoretically by using the numerical calculations to generate a desirable
coagulated volume. The conventional MCT antennas have a problem that the coagulated region
becomes long and uncontrollable in the antenna insertion direction. Therefore, Saito et al.
[2000b] improved the shape of the coagulated region by introducing the coaxial-dipole antenna.
This antenna has two sleeves on both sides of the slot.
An inductive regional heating system for breast hyperthermia is developed. This system9consists of a pair of ferrite cores and realizes controlling the shape of the heating region at thebreast part by changing the position of the ferrite cores. In order to find a method of controlling
heating region vertically or horizontally, magnetic field distribution was analyzed using thethree-dimensional (3-D) finite element method (FEM) taking eddy current into consideration.
Some experimental investigations were carried out using an agar phantom and rabbits. On thebasis of investigations, an applicator system has been developed. In this system, the operating
frequency is 4.0 MHz and the output power is 600 W. Efficiency heating results have beenobtained using an agar phantom and rabbits without heating fatty tissue by using the developed
system [Kotsuka, 2000].
The soft heating method is an inductive heating method that uses as a heating element athermosensitive magnetic material, which has low Curie temperature. The heating sources arehysteresis loss of the magnetic material and eddy current loss of the metal ring. In order tosufficiently heat the thermosensitive magnetic heating element, the generation magnetic field
was 6 mT at 100 mm from the handy circular excitation coil at 100 kHz. As a result, theterminal voltage of the coil can be reduced 2.6 kV by using focused cooling. In addition, bychanging the target point from 100 mm to 50 mm, the terminal voltage was reduced to 392 V,
which is a realizable value [Jojo, 2001b].
A treatment sys tem combining interstitial microwave hyperthermia and interstitial radiation
therapy is investigated. It is considered that the combined method is effective for treatment ofradiation-resistive tumor. This treatment system is realized by using the same catheter between
the interstitial hyperthermia and the interstitial radiation therapy. In this system, firstly, thin
microwave antennas such as coaxial-slot antennas with catheters heat the tumor. After heating
only antennas are pulled out of the catheter. Then radiation sources such as the iridium 192 areautomatically inserted into the catheter by a "high dose rate afterloading system". In order toevaluate the heating performances of the array applicator for heating, the SAR distributions andtemperature distributions in and around the applicators are calculated numerically. It isconsidered that the results are useful for clinical trial [Ito, 2001b].
K4.3 Medical Diagnosis
K4.3.1 Magnetoencephalography and Magnetocardiography
Uchida et al. [2000a] measured the magnetocardiogram in normal and abnormal rat which has
ischemic myocardial muscles and obtained the current source imaging using a high resolution
SQUID system. They obtained the results that the current distribution significantly increased at
the ischemic area in the ST segment, and the direction of the current distribution shifted to theleft thorax in the T wave. They also compared the iterative minimum norm estimation andcurrent dipole estimation for magnetic field measurements from small animals [Uchida, 2000b].
Iwaki et al. [1999a] investigated the dynamic properties of the distributed cortical activity
related to mental rotation processes at high temporal resolution by means of brain magnetic
field measurements and a linear inversion algorithm. Iwasaki [2001] measured thesomatosensory evoked magnetic fields to evaluate the cortical function quantitatively inpatients in the chronic phase of severe traumatic brain injury. It was observed that
middle-latency SEFs may be applicable as a cortical functional measure for patients withsevere traumatic brain injury.
K4.3.2 Impedance MRI current distribution MRI
Yukawa et al. [1999] proposed a new and noninvasive method for imaging electrical properties
10

such as conductivity and impedance based on MRI techniques. The basic idea is to use theshielding effects of induced eddy currents in the body on spin precession. Two types ofmethods are introduced; (i) a large flip angle method, and (ii) a third coil method. Kamei
developed new methods to visualize neuronal current distribution and electrical-impedance
distribution. The basic principle is to erase the effects of local spin interaction T2* by
subtracting MRI signals with different polarities of gradient magnetic fields. Measurements
were made with an echo planar imaging (EPI) sequence at 1.5 T. MRI tapping of the neuronalcurrents in the brain during middle finger and thumb tapping was clearly observed [Kamei,
1999].
K4.3.3 MRI
Iramina [1999b, 2001b] has compared the characteristic between fMRI and MEG by thesomatosensory stimulation. Kanzaki [1998, 2001] has analyzed the NMR Fresnel transform
imaging and the NMR Phase scrambled Fourier imaging. Yamada [1998], Kanzaki [1999] andIto [2000b, 2001] have reported on the application of the holographic reconstruction techniquein the above MRI. Ito [2000a] has proposed 3D Fresnel diffractive imaging technique for the
MR angiography. Yamaguchi [1999] has investigated the MRI thermometry using artifact ofthermo-sensitive magnetic material.
K4.3.4 Radiometry
Maruyama et al. [2000] conducted the feasibility study of noninvasive measurement of deepbrain temperature in newborn infants by multi frequency MRW. They showed that the proposed
technique is feasible, that it is expected to provide a good estimate of the temperature profile
within the cooled baby-head. Mukumoto et al. [2001] developed a five-band microwave
radiometer system for non-invasive measurement of deep brain temperatures.
Acknowledgments
I would like to thank the members of Commission K Japan for their tremendous efforts, inparticular, Professor Masao Taki, Dr. Soichi Watanabe, Dr. Tsukasa Shigemitsu, and Dr.
Kanako Wake.
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