Yusuke Seki,1 Akihiko Kandori,1 Kuniomi Ogata,1 Tsuyoshi Miyashita,1 Yukio ..... 7 H. Oe, A. Kandori, T. Miyashita, K. Ogata, N. Yamada, K. Tsukada, K.
REVIEW OF SCIENTIFIC INSTRUMENTS 81, 096103 共2010兲
Note: Unshielded bilateral magnetoencephalography system using two-dimensional gradiometers Yusuke Seki,1 Akihiko Kandori,1 Kuniomi Ogata,1 Tsuyoshi Miyashita,1 Yukio Kumagai,2 Mitsuru Ohnuma,3 Kuni Konaka,4 and Hiroaki Naritomi4 1
Advanced Research Laboratory, Hitachi, Ltd., 2520 Akanuma, Hatoyama-machi, Hiki-gun, Saitama 350-0395, Japan 2 Central Research Laboratory, Hitachi, Ltd., 1-280 Higashi-Koigakubo, Kokubunji-shi, Tokyo 185-8601, Japan 3 Design Division, Hitachi, Ltd., 5-3-1 Akasaka, Minato-ku, Tokyo 107-6323, Japan 4 Department of Cerebrovascular Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita-shi, Osaka 565-8565, Japan
共Received 26 May 2010; accepted 2 August 2010; published online 20 September 2010兲 Magnetoencephalography 共MEG兲 noninvasively measures neuronal activity with high temporal resolution. The aim of this study was to develop a new type of MEG system that can measure bilateral MEG waveforms without a magnetically shielded room, which is an obstacle to reducing both the cost and size of an MEG system. An unshielded bilateral MEG system was developed using four two-dimensional 共2D兲 gradiometers and two symmetric cryostats. The 2D gradiometer, which is based on a low-Tc superconducting quantum interference device and wire-wound pickup coil detects a magnetic-field gradient in two orthogonal directions, or / x共2Bz / z2兲, and reduces environmental magnetic-field noise by more than 50 dB. The cryostats can be symmetrically positioned in three directions: vertical, horizontal, and rotational. This makes it possible to detect bilateral neuronal activity in the cerebral cortex simultaneously. Bilateral auditory-evoked fields 共AEF兲 of 18 elderly subjects were measured in an unshielded hospital environment using the MEG system. As a result, both the ipsilateral and the contralateral AEF component N100m, which is the magnetic counterpart of electric N100 in electroencephalography and appears about 100 ms after the onset of an auditory stimulus, were successfully detected for all the subjects. Moreover, the ipsilateral P50m and the contralateral P50m were also detected for 12 共67%兲 and 16 共89%兲 subjects, respectively. Experimental results demonstrate that the unshielded bilateral MEG system can detect MEG waveforms, which are associated with brain dysfunction such as epilepsy, Alzheimer’s disease, and Down syndrome. © 2010 American Institute of Physics. 关doi:10.1063/1.3482154兴
Magnetoencephalography 共MEG兲 is a useful tool for the electrophysiologic study of the brain function that detects minute magnetic fields caused by the neuronal activity in the cerebral cortex.1 MEG can measure brain function with excellent temporal resolution compared to other modalities, such as functional magnetic resonance imaging and nearinfrared spectroscopy. Moreover, MEG can detect electrophysiological neuronal activity contactlessly and noninvasively, whereas electroencephalography 共EEG兲 requires electrodes fixed on the scalp. These features of MEG stem from the fact that the magnetic permeability of the brain, the skull, the scalp, and the hair are equal to the magnetic permeability of free space 0 = 4 ⫻ 10−7. The whole-head MEG system, which consists of a helmet-style cryostat and more than a hundred superconducting quantum interference devices 共SQUIDs兲, is now common.2 A whole-head MEG system can detect the neuronal activity in the whole cerebral cortex by combining additional information, such as EEG, magnetic resonance imaging, or computed tomography, and solving inverse problems. On the other hand, the need of the MEG system for a magnetically shielded room 共MSR兲 and a helmet-style cryostat presents several practical issues in terms of cost, size, and measurement. 0034-6748/2010/81共9兲/096103/3/$30.00
A MSR plays an important role in measuring minute MEG signals, which are typically less than several hundreds of femtotesla and about one hundred millionth of the earth’s magnetic field. A conventional MSR used for an MEG system is box-shaped, about 2.5 m on a side, and constructed with two or three Permalloy layers and one aluminum layer.3,4 This type of MSR performs exceptionally well and its shielding factor is usually above 50 dB. However, these conventional MSRs are an obstacle to reducing both the cost and size of MEG systems. Consequently, it has been hard for hospitals to install MEG systems that require a MSR because of their large cost and size. As for a helmet-style cryostat of a whole-head MEG system, it is designed for a typical adult head, and this causes a gap between the scalp and the cryostat. The magnetic signal from the cerebral cortex decreases as the distance between the cerebral cortex and pickup coils inside the cryostat increases. When a child uses the MEG, the gap can be more than a few centimeters. This severely degrades not only the signal-to-noise ratio 共SNR兲 but also the MEG source estimation.5 Moreover, MEG measurement can be impossible for a subject with an extremely large head. From a clinical viewpoint, MEG has been especially applied to epilepsy using spontaneous fields and presurgical mapping. In addition to these mapping-based MEG applica-
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(a) Gantry
(b)
Input coil
Pickup coil
y
Ch 2 SQUID
z
Ch 1
x
50 mm 50 mm
Cryostat
46 mm
46 mm
FIG. 2. 共Color兲 共a兲 Schematic of a two-dimensional gradiometer. 共b兲 Pickupcoil arrangement.
Chair FIG. 1. 共Color兲 Photograph of the unshielded bilateral MEG system.
tions, latency of evoked fields, such as auditory-evoked field 共AEF兲, visual-evoked field, and somatosensory-evoked field, is another promising MEG application in terms of neuronal dynamics. In particular, AEF components P50m and N100m 共magnetic counterpart of electric P50 and N100兲, which appear about 50 and 100 ms after the onset of an auditory stimulus,1 are important indicators of cognitive dysfunction. For example, it has been reported that N100m latency is significantly delayed in patients with Alzheimer disease6 共AD兲 and dementia.7 Moreover, patients with Down syndrome 共DS兲 significantly delay and attenuate N100m and delay without attenuating P50m responses over both hemispheres.8 Cognitive dysfunction in these diseases has been thought to be associated with degeneration of the cholinergic system. In this context, it has also been reported that AEF latencies of P50m and N100m are modulated by scopolamine, which temporarily blocks the cholinergic system.9,10 In view of this background, we are aiming to develop a simple MEG system with no MSR for measuring bilateral MEG waveforms from both sides of the brain at the same time with high SNR in an unshielded environment. Specifically, we have developed an unshielded bilateral MEG system using two pairs of gradiometers based on low-Tc SQUIDs and two cryostats symmetrically driven by a hydraulic control system in three directions, vertical, horizontal, and rotational, as shown in Fig. 1. This makes it easier to adjust the pickup coils closer to the subject’s scalp. Consequently, the gap between the scalp and the cryostats can be adjusted to less than 5 mm. The gantry is 1.5 m wide, 2.3 m tall, and 1.0 m deep, and the total footprint for the MEG system including a chair, a signal processing unit, and a personal computer is no more than 10 m2, which is about one third of the footprint for the conventional MEG system with an MSR. The low-Tc SQUID gradiometers used in this study are two-dimensional 共2D兲 gradiometers, which detect a magnetic-field gradient in two orthogonal directions, or / x共2Bz / z2兲.11 A pair of the 2D gradiometers based on low-Tc dc SQUIDs, which consist of niobium thin films and Nb/ AlOx / Nb Josephson junctions, is installed in each cryostat and cooled by liquid helium. The four SQUIDs are
operated by direct-coupled flux-locked-loop circuits fixed on the cryostats. The cryostats are coated with conductive material to shield radio-frequency electromagnetic noise, which degrades SQUID performance. The inner volume of the cryostat is 27 l and the evaporation rate of the liquid helium is 1.5 l/day. An additional liquid-helium supply is thus required twice a month. The gap between the pickup coil of the gradiometer and the outer surface of the cryostat is 8 mm. Figure 2共a兲 shows a pickup coil for the 2D gradiometer. It detects a magnetic-field gradient / x共2Bz / z2兲. The planar baseline is an important parameter that influences signal intensity in MEG.12 The planar baseline is designed to be 46 mm to maximize signal intensity on the basis of a current dipole model with a typical current dipole 15 nA m at a depth of 29 mm from the scalp surface, which was obtained by averaging current dipoles of the five subject’s AEF measured with a 64-channel SQUID system. The axial baseline is 50 mm and each coil is 18 mm in diameter. Pickup coils were fabricated in house by wounding NbTi wire 0.1 mm in diameter around bobbins made of machinable ceramics. Intrinsic noise of the developed 2D gradiometers was about 10 fT/ 共cm· 冑Hz兲. According to field-noise spectra in an unshielded hospital environment experimentally obtained by both a fluxgate magnetometer and a 2D gradiometer showed that the field-noise intensity obtained by a fluxgate magnetometer in the frequency band 1–50 Hz, which affects MEG signal, was 670 pT. On the other hand, the field-noise intensity detected by a 2D gradiometer was 1.4 pT in the same frequency band. Therefore, the noise-reduction ratio of a 2D gradiometer was 54 dB. In this study, a pair of pickup coils is arranged in each cryostat as shown in Fig. 2共b兲. A magnetic field generated by a current in the x direction should be detected by pickup coil Ch 2 and that by a current parallel to the y direction should be detected by pickup coil Ch 1. Therefore, one can approximately obtain the neuronal current 共Ix , Iy兲 using the following equation.13 共Ix,Iy兲 ⬃
冉
冊
⌬Bz ⌬Bz ⬀ 共⌽2,− ⌽1兲, ,− ⌬y ⌬x
共1兲
where ⌽1 and ⌽2 are magnetic fluxes detected by pickup coils Ch 1 and Ch 2. We focused on AEF measurement to evaluate the unshielded bilateral MEG system. Eighteen elderly subjects 共aged 69–92 yr, mean 80.1⫾ 5.1, six females兲 participated in this study. Auditory stimuli 1 kHz in frequency and 100 ms
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2D gradiometers Cryostat
TABLE I. Number of cases of the 18 subjects in which P50m and N100m of both ipsilateral and contralateral AEF were detected. The number in parentheses is the percentage of detection.
Acoustic stimuli
P50m N100m
Ipsilateral
Contralateral
12 共67%兲 18 共100%兲
16 共89%兲 18 共100%兲
Masking noise
FIG. 3. 共Color online兲 AEF measurement using the unshielded bilateral MEG system.
in duration were randomly applied to one ear while masking noise was applied to the other ear, as shown in Fig. 3. Measurement data were passed through bandpass filtering at 0.1–50 Hz and comb filtering to eliminate power line noise in real time. For sensor positioning, we used the international 10-20 system, which is usually used for the EEG electrode arrangement. Specifically, the centers of the four bottom loops shown in Fig. 2共b兲 were positioned at T3 共left auditory area兲 or T4 共right auditory area兲 of a subject. Figure 4 shows typical AEF waveforms measured with the unshielded bilateral MEG system, where auditory stimuli were applied to the right ear. These waveforms were averaged from the 294 measurements that were taken. In this study, we focused on AEF components P50m and N100m, which appear about 50 and 100 ms after the onset of an auditory stimulus. As shown in Fig. 4, the signal intensity of a contralateral N100m is usually larger than that of an ipsilateral one. In addition, the latency of a contralateral N100m is slightly shorter than an ipsilateral one.14
Field gradient (fT/cm)
100
(a) Ipsilateral Ch 1
100
50
50
0
0
-50
N100m
-100 -100 200
0
P50m
100
P50m 0
100 200 300 400
(d) Contralateral Ch2 P50m
50 0
0 -100 -200 -100
-50
-100 -100 100 200 300 400
(c) Contralateral Ch 1
100
(b) Ipsilateral Ch 2 N100m
N100m
0
-50
-100 -100 100 200 300 400
N100m 0
100 200 300 400
Time (ms) FIG. 4. Typical auditory-evoked field obtained by unshielded bilateral MEG system, where auditory stimuli were applied to the right ear. Averaging number was 294 readings. 关共a兲 and 共b兲兴 Right 共ipsilateral兲 and 关共c兲 and 共d兲兴 left 共contralateral兲.
Table I shows the number of cases in which the P50m and N100m of both ipsilateral and contralateral AEF were detected. The percentages of detection are in parentheses. Both the ipsilateral and the contralateral N100m peaks of the AEF waveforms were successfully detected for all 18 subjects. Moreover, the ipsilateral P50m and the contralateral P50m were also detected for 12 共67%兲 and 16 共89%兲 subjects, respectively. In conclusion, the unshielded bilateral MEG system we developed using 2D gradiometers can clearly detect AEF components P50m and N100m peaks by averaging. These measurements demonstrate that the unshielded bilateral MEG system can detect AEF waveforms in an unshielded environment. The unshielded bilateral MEG system can expand the range of MEG applications and then shed light on brain disease, such as epilepsy, AD, and DS. The authors thank Hideaki Koizumi, Atsushi Maki, and Masafumi Iso for the productive discussions. 1
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