Clinical Neurophysiology 130 (2019) 1–11

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Clinical Neurophysiology
journal homepage: www.elsevier.com/locate/clinph

Visualization of the electrical activity of the cauda equina using amagnetospinography system in healthy subjects
Shuta Ushio a, Yuko Hoshino b, Shigenori Kawabata a,b,⇑, Yoshiaki Adachi c, Kensuke Sekihara b,
Satoshi Sumiya a, Dai Ukegawa a, Kyohei Sakaki a, Taishi Watanabe a,d, Yuki Hasegawa b, Atsushi Okawa aaDepartment of Orthopedic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Department of Advanced Technology in Medicine, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Applied Electronics Laboratory, Kanazawa Institute of Technology, Kanazawa-shi, Ishikawa 920-1331, Japand
RICOH Company, Ltd., 16-1 Shinei-cho, Tsuzuki-ku, Yokohama, Kanagawa 224-0035, Japanbca r t i c l e

i n f oArticle history:
Accepted 2 November 2018
Available online 12 November 2018
Keywords:
Magnetospinography
Visualization of neural activity
Cauda equina
Conduction velocity
Evoked magnetic field
Peroneal nerve

h i g h l i g h t s
 Magnetospinography visualized the electrical activity in the cauda equina.
 The conduction velocities were obtained from reconstructed currents in the cauda equina.
 Magnetospinography is expected to become a noninvasive functional examination technique for lum-bar disease.

a b s t r a c t
Objective: To establish a method to measure cauda equina action fields (CEAFs) and visualize the electrical activities of the cauda equina in a broadly aged group of healthy adults.
Methods: Using a 124-channel magnetospinography (MSG) system with superconducting interference
devices, the CEAFs of 43 healthy volunteers (22–64 years of age) were measured after stimulation of
the peroneal nerve at the knee. Reconstructed currents were obtained from the CEAFs and superimposedon the X-ray image. Conduction velocities were also calculated from the waveform of the reconstructedcurrents.
Results: The reconstructed currents were successfully visualized. They flowed into the L5/S1 foramen
about 8.25–8.95 ms after the stimulation and propagated cranially along the spinal canal. In 32 subjects(74%), the conduction velocities of the reconstructed currents in the cauda equina could be calculated
from the peak latency at the L2–L5 level.
Conclusions: MSG visualized the electrical activity of the cauda equina after peroneal nerve stimulation in
healthy adults. In addition, the conduction velocities of the reconstructed currents in the cauda equina
could be calculated, despite previously being difficult to measure.
Significance: MSG has the potential to be a novel and noninvasive functional examination for lumbar
spinal disease.
Ó 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction
Abbreviations: CEAF, cauda equina action field; CEAP, cauda equina action
potential; CECT, cauda equina conduction time; CV, conduction velocity; DSSP, dual
signal subspace projection; MSG, magnetospinography; SEP, somatosensory evoked
potential; SN, signal-to-noise; SNAP, sensory nerve action potential; SQUID,
superconducting quantum interference device; UGRENS, unit gain constraint
recursively applied null-steering spatial filtering.
⇑ Corresponding author at: Department of Advanced Technology in Medicine,
Graduated School of Tokyo Medical and Dental University, 1-5-45 Yushima,
Bunkyo-ku, Tokyo 113-8510, Japan.
E-mail addresses: ushio.orth@tmd.ac.jp (S. Ushio), hoshino.atm@tmd.ac.jp(Y. Hoshino), kawabata.orth@tmd.ac.jp (S. Kawabata), k-sekihara@nifty.com(K. Sekihara), d_ukegawa.orth@tmd.ac.jp (D. Ukegawa), okawa.orth@tmd.ac.jp(A. Okawa).

In lumbar spinal diseases such as lumbar spinal canal stenosis,
compression lesions in multiple vertebrae are often found in imaging examinations. However, it is often difficult to evaluate the truelesion sites responsible for symptoms by imaging techniques alone(Kent et al., 1992; Mamisch et al., 2012). In addition, it is often necessary to evaluate the locations of the spinal nerve compression,
such as intra-canal, intra-foraminal, or extra-foraminal, to choose
the appropriate surgical technique (Macnab, 1971; Wiltse et al.,
1984; Kunogi and Hasue, 1991; Olsewski et al., 1991). Therefore,
functional examinations such as electrophysiological diagnostic

https://doi.org/10.1016/j.clinph.2018.11.001
1388-2457/Ó 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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methods are important to determine the indications for surgicaltreatment and the appropriate operation.
However, it is difficult to measure the electrical neural activityof the cauda equina because the electric potential is affected by thesurrounding tissues, including the cerebrospinal fluid. For the same
reason, accurate recording of the electric potentials of the lumbar
nerve root from the body surface is also difficult. In addition, thecauda equina consists of several spinal nerves, complicating theevaluation of individual neural activities. Some physiological orelectrophysiological modalities have been used to determine lesion
sites, such as spinal nerve block, somatosensory evoked potential(SEP), sensory nerve action potential (SNAP), cauda equina action
potentials (CEAPs), and cauda equina conduction time (CECT).
Despite their utility, they also have some disadvantages. For example, the spinal nerve block procedure induces intense pain (Jonsson
et al., 1988; Yeom et al., 2008), and SEP is often unable to provide
accurate information, including conduction velocity (CV) (Cracco,
1973; Kakigi et al., 1982; Yamada et al., 1982). Although SNAP
can detect lesions in distal spinal nerves, it is absent in some normal subjects (Levin, 1998; Ando et al., 2013). Because CEAPs are
intraoperatively recorded from the ligamentum flavum(Taniguchi et al., 2005), it cannot be used as a preoperative examination. Additionally, because CECT represents the conduction timeof the sum of neural activities in the cauda equine, the function of
spinal nerves cannot be evaluated (Matsumoto et al., 2009;
Senocak et al., 2009; Secil et al., 2012; Imajo et al., 2017). Therefore, a noninvasive functional examination method with better
temporal and spatial resolution is desired.
Because the magnetic field itself is hardly affected by the surrounding tissue, it has theoretically high spatial resolution compared with electric potential recording (Trahms et al., 1989;
Hashimoto et al., 1991). Therefore, it has the possibility to be a reliable examination method for the diagnosis of lesion sites in deep
nerves, such as the spinal cord and cauda equina.
When a nerve is electrically stimulated, transmembrane ioniccurrents arise at a depolarization site in the nerve. Accordingly,
intra-axonal currents and volume currents are derived from thevoltage difference between the depolarization site and the circumferential tissue (Fig. 1). Here, we defined volume currents as all
currents in the volume conductor flowing into the depolarizationsite and flowing out from the nerve. These intra-axonal currents
and volume currents generate magnetic fields based on the BiotSavart law. Green arrows in Fig. 1 indicate magnetic fields resulting
from intra-axonal currents (magnetic fields from volume currents
are not depicted). Although the induced biomagnetic signal is verysmall, with a magnitude about 10-9 that of geomagnetism(Wijesinghe, 2010), it can be recorded with a highly sensitive magnetic field sensor installed in a magnetically shielded room.
Our group has developed a magnetospinography (MSG) systemusing superconducting quantum interference device (SQUID) sensors. Each sensor can detect three directional magnetic field components. By arranging the SQUID sensors, it is possible tosimultaneously scan a wide area and to create a contour map of
the recorded magnetic field. We have also developed a signal processing method to visualize neural current sources reconstructedfrom the recorded magnetic field. In addition, the reconstructedcurrent map enables a more detailed evaluation of neural electricalactivity.
We previously reported on the diagnosis of compressive spinal
cord injury by measurement of evoked magnetic fields in animals(Kawabata et al., 2002; Ohkubo et al., 2003; Tomori et al., 2010).
We also closely evaluated magnetic fields of injured nerves using
isolated peripheral nerves of rabbits (Fukuoka et al., 2002, 2004)
and recorded the magnetic fields of the cervical spinal cord ofhealthy subjects (Sumiya et al., 2017). We have also recorded
evoked magnetic fields from the lumbar region in response to electrical stimulation in the lower extremities in both animals andhumans (Tomizawa et al., 2008; Ishii et al., 2012). These studies
showed that MSG has the possibility to be a beneficial functional
examination for the spinal cord and cauda equina. However, there
are still some points to be considered. For example, Ishii et al.
(2012) recorded evoked magnetic fields from the lumbar region
generated by electrical stimulation of the tibial nerves in healthy
subjects in their 20s and 30s. However, the older the subject, thelower the lumbar curve and the poorer the fit of the recording system. Because the magnitude of the magnetic field is inversely proportional to the square of the distance, this misalignment
decreased the recorded magnetic fields. Furthermore, when thetibial nerve was electrically stimulated at a region closer to themeasurement area to obtain a larger evoked magnetic field, thestimulation artifacts concurrently became larger.
In this study, we used a newly developed MSG system with ameasurement area that is wider and has an improved curved
shape. We also used a newly devised artifact removal method.
The purpose of this study was to establish a method to measure
weak cauda equina action fields (CEAFs) from the body surface
and to visualize the electrical activities of the cauda equina. Here,
we defined action fields as the magnetic fields generated by theelectrical activity of the nerve.

2. Methods
2.1. MSG system

Fig. 1. Schematic illustration of intra-axonal currents (red arrows), volume currents(yellow arrows flowing into the depolarization site and flowing out of the nerve),
and magnetic fields (green arrows) resulting from intra-axonal currents (magnetic
fields generated by volume currents are not illustrated here). This figure wasmodified from original version in a report by Sumiya et al. (DOI: https://doi.org//10.
1038/s41598-017-02406-8) under CC-BY 4.0. (For interpretation of the references
to color in this figure legend, the reader is referred to the web version of thisarticle.)Our newly developed 124-channel SQUID biomagnetometersystem (Adachi et al., 2015) has a wider sensor area and a moresuitable curvature for lumbar lordosis as compared with the former system (Adachi et al., 2007, 2009, 2011, 2013) (Fig. 2). Briefly,
the system has 40 vector-type SQUID gradiometers and four axialtype gradiometers arranged in an area of 180 mm  130 mm along
the cylindrical surface with a radius of 200 mm, as shown in Fig. 2.
The sensors in the four corners (gray circles in Fig. 2a) are axialtype gradiometers and detect magnetic fields in the Z direction.
The data from these four sensors were also used for acquiring positional information. All of the other 40 sensors (white circles inFig. 2a) have two planar-type gradiometers and one axial-type gradiometer placed orthogonally to each other to simultaneously
detect magnetic fields in three directions. The baseline length ofeach gradiometric pickup coil was 68 mm and the noise level
was typically less than 4 fT/Hz0.5 in the white region. The X direc-

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22 22 22 22 22 (mm)180 (mm)

Top view
25 23 22 20 22 23 25 (mm)S. Ushio et al. / Clinical Neurophysiology 130 (2019) 1–11

10

y
x
z

(c)
15.5 (mm)

z

y
x

(a)
130 (mm)

9 (mm)
11 (mm)
68 (mm)

12 (mm)r=200 (mm)X coilyxzSide view(b)y
SQUID x z(d)Y coilZ coilFig. 2. Appearance and structure of the MSG system. (a) A top view and the dimensions of the array of SQUID gradiometers with a matrix-like arrangement. The four sensors
in the four corners (gray circles) are axial-type gradiometers to pick up magnetic fields in the Z direction. The other 40 sensors (white circles) are vector-type SQUID
gradiometers to simultaneously detect magnetic fields in three directions. (b) Side view of the sensor array and the dimensions of the cryostat. (c) Appearance of the MSG
cryostat. The cryostat has a unique shape optimized for lumbar lordosis with a protrusion on the side surface of the cylindrical main body to store liquid helium. The
protrusion holds the SQUID sensor array inside and has a 10° tilt. (d) Structure of the vector-type SQUID gradiometers. Each sensor is equipped with two planar-type
gradiometric pickup coils and an axial-type gradiometric pickup coil combined into one bobbin. Each pickup coil is oriented perpendicularly to each other and connected to
an individual SQUID to simultaneously detect the three independent components of magnetic fields. The baseline length of each gradiometric pickup coil is 68 mm and thenoise level was less than 4 fT/Hz0.5 in the white region. This figure was reproduced with permission from the report of Adachi et al. (DOI: https://doi.org//10.1109/TASC.2016.
2631422). Ó2017 IEEE.

tion was assumed to be the direction from the left to the right ofthe body, the Y direction was caudal to cranial, and the Z direction
was from the ventral to the dorsal side of the body. All recordings
were performed in a magnetically shielded room.
2.2. Subjects
The subjects were 43 healthy volunteers aged 22–64 years(mean ± SD, 42.6 ± 12.9 years), measuring 156–181 cm in height(mean ± SD, 169.2 ± 5.6 cm), and weighing 51–90 kg (mean ± SD,
65.4 ± 9.8 kg) without nervous system disease. Those over 40 years
old had MRI scans of the lumbar spine and were confirmed to haveno neural compression.
2.3. Recording of CEAFs and signal processing
The subject was in the supine position on a table in a magnetically shielded room with the posterior lumbar region at
the cryostat of the SQUID sensor (Fig. 3). The measurement area
was centered at the spinous process of L4 and placed coplanar tothe lower back. For positional information, magnetic signals frommarker coils on the surface of the subject’s back were recorded.
Lateral and frontal radiographs were taken to obtain positional
information on the subject and the SQUID sensor. The peroneal
nerve was electrically stimulated at the knee (square wave
pulse; 5 Hz; 0.3 ms in duration) at over 1.5 times the motor
nerve threshold (6.1 ± 2.0 mA in intensity). The right and left
nerves were alternately stimulated and evoked magnetic fields
were respectively recorded at the surface of the lower backusing a 40 kHz sampling rate and 100–5000 Hz band-pass filter.
Two-thousand recordings of evoked magnetic fields were averaged for each side. We adopted this number of recordings after
analysis of preliminary recordings considering the data quality
and subject burden. A new method of artifact reduction, dual
signal subspace projection (DSSP) (Sekihara et al., 2016), wasthen applied to reduce artifacts from the electrical stimulation.
Signal-to-noise (SN) ratios of measurements were obtained foreach subject to statistically evaluate individual differences. Here,
we defined the SN ratio as the ratio of the peak-to-peak amplitude values from 5 ms to 15 ms after the stimulation for the signal to the root mean square of the magnetic fields at 20–25 ms
for the noise.

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used for single comparisons. Multiple regression analysis was used
to evaluate the factors affecting the availability of CV calculation. P
values of <0.05 were considered to indicate statistical significance.
2.4. Measurement of CV
Reconstructed currents perpendicularly flowing into the lumbar
canal were retrieved from the virtual electrodes, which were positioned 20 mm left lateral from the midline of the lumbar canal andthe presumed pathway of the spinal nerve from L3 to L5 (Fig. 4b, c).
We chose this site for the calculation because previous reports
from our group showed that the currents flowing into the lumbar
canal are larger near the vertebral foramina contralateral to thestimulation (Ishii et al., 2012). The CVs of the reconstructed currents were calculated from the latencies of the positive peaks
recorded at the virtual electrodes of L2 to L5. The average valueof the left and right CVs was obtained for each subject.
3. Results
3.1. Recording of CEAFs in response to electrical stimulation of theperoneal nerve

Fig. 3. The subject was in the supine position on a table in a magnetically shieldedroom with the posterior lumbar region on the SQUID sensor part. X-ray irradiation
devices (►) were installed to take an X-ray image. Marker coils for positional
information were placed under the back of the subject and the corresponding
position to the lumbar spine was acquired in the anteroposterior view. In addition, alateral X-ray image including the sensors and the lumbar spine of the subject was
obtained.

Unit gain constraint recursively applied null-steering spatial filtering (UGRENS) (Kumihashi and Sekihara, 2010; Sekihara andNagarajan, 2015) was adapted to the acquired magnetic field data
to reconstruct currents induced by action potential as vector indicating the current density and direction. The reconstructed currents were superimposed on the X-ray image to visualize theirdistribution and intensity (Fig. 4a, b). The distance between the
midpoint of the spinal canal and the surface of the sensors wasused for the depth information (Fig. 4c). Through this method,
the current waveforms at arbitrary points in the spinal canal andthe intervertebral foramen can be calculated as if virtual electrodes
were placed there.
All procedures in this study were approved by the Ethics Committee of Tokyo Medical and Dental University and carried out inaccordance with the Declaration of Helsinki. We obtained written
informed consent and releases for images and photographs fromall participants.
Statistical analysis was performed using EZR software version
1.33 (Kanda, 2013). An unpaired two-tailed Student’s t-test was

Lumbar CEAFs were recorded in response to stimulation of theperoneal nerve at the knee from all subjects (43 subjects; 86
nerves). Fig. 5 shows isomagnetic contour maps at 9.75 ms andthe evoked magnetic fields of a representative case recorded fromX-, Y-, and Z-directed coils (right peroneal nerve stimulation). The
peak-to-peak amplitudes were as high as 60 fT. In the contour mapof X coils (Fig. 5a), positive X-directed (left to right direction) magnetic fields is depicted over the spinal canal. That of Y coils (Fig. 5b)shows that negative Y-directed (cranial to caudal) magnetic fields
was mainly recorded at 9.75 ms. As shown in Fig. 5c, Z-directedcoils recorded positive (ventral to dorsal directed) magnetic fields
on the left side and negative magnetic fields on the right side.
In the third to fifth left column of the X coils (Fig. 5a, below), thefirst positive peaks (signals directed from the left to the right of thebody) appeared from the caudal direction at about 10 ms after the
stimulation and conducted cranially with time. The amplitude waslargest at the central two columns and generally larger on the left
side than on the right. In the magnetic fields from the Y coils(Fig. 5b), the negative peak (signals directed from cranial to caudal)
appeared from the caudal direction around 10 ms and conductedcranially in the left four columns. At the two cranial sensors inthe second right and second left columns, the polarity of the waves
was reversed. In the four left columns of the magnetic fields fromthe Z coils (Fig. 5c), the positive waves (signals of the ventral todorsal direction) appeared from caudal at about 8.5 ms and conducted cranially. Subsequently, the negative waves appeared atabout 10–11 ms and were similarly conducted. In all three sensor
coil directions, the magnetic field amplitude was generally larger
on the left side.
3.2. Estimated current sources
The evoked currents reconstructed by UGRENS and converted toa pseudo-color map were superimposed on the X-ray image of thelumbar spine (Fig. 4a). Color in the map indicates current densityand black arrows represent direction of reconstructed currents
induced by action potentials. First, the leading component, which
consisted of the currents running parallel to the nerve root,
appeared from the laterocaudal area of the right side (stimulatedside) and flowed into the L5/S1 intervertebral foramina(7.90 –8.60 ms, white asterisk). In all subjects, the leading
components flowed into the L5/S1 foramen about 8.25–8.95 ms

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(a)7.90 ms

8.25 ms

8.60 ms***
9.30 ms

9.65 ms**

11.05 ms

10.70 ms

10.35 ms**

11.40 ms

11.75 ms

(b)

*

*

*

10.00 ms**

8.95 ms*

Current density(A/m2)

Rt
0

5

10Time [ms]1520

2 * 10-9 A/m2
2 ms

Fig. 4. (a) The evoked currents reconstructed by UGRENS are illustrated as a pseudo-color map superimposed on the X-ray image of the lumbar spine. Color indicates current
density and black arrows shows direction of currents. For depth information, see (c). First, the leading components of the intra-axonal currents appeared from the stimulatedside and flowed into the lumbar canal from about the right L5 foramen (7.90–8.60 ms after the stimulation, white asterisk). It propagated caudal to cranial in the spinal canal(8.95–10.00 ms, pink asterisk). Currents flowing outside of the spinal canal were recognized (8.95–10.35 ms, white stars). These currents were paralleled to the leading
current, or flowing into or out of the spinal canal. Subsequently, trailing intra-axonal currents appeared (10.70–11.75 ms, light blue asterisk). Other currents flowing outsideof the spinal canal appeared on the left side (10.70 ms, the lowest white star), and currents flowing in opposite direction to the trailing currents were recognized on both sideof the spinal canal and propagated cranially along with the trailing current (11.05–11.75 ms, white star). (b) Virtual recording electrodes were assumed to be set 20 mm
lateral from the midline of the lumbar canal. For depth information, see (c). The waveforms show reconstructed currents that were perpendicularly flowing toward theassumed conduction pathway. Upright in the waveform indicates the direction flowing perpendicularly toward the black line, which is a pathway of the spinal nerve set up toreconstruct evoked currents. The peak of the waveform conducted caudally to cranially. (c) Lateral X-ray image of the lumbar spine and the sensor. The distance between the
midline of the spinal canal (yellow line) and the surface of the sensors (blue circles) was obtained for the depth information for current reconstruction. In the case of (a) and(b), the distance is about 75 mm. Blue circles overlap because several sensors are aligned. (For interpretation of the references to color in this figure legend, the reader isreferred to the web version of this article.)

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Fig. 4 (continued)

after the stimulation. Then, the leading currents changed theirdirection along the spinal canal and propagated cranially (8.95–
10.0 ms, pink asterisk). In addition, currents flowing in opposite
direction to the leading currents were recognized (8.95 ms, whitestar), and currents flowing out of and into the spinal canal wereshown (9.30–10.35 ms, white stars). Subsequently, the trailingcomponents of the intra-axonal currents appeared 10.70–
11.75 ms after stimulation (light blue asterisk). Currents flowing
in opposite direction to these trailing currents were depicted on
the left of the nerve in 10.70 ms (the lowest white star) and on
both side of the nerve from 11.05 to 11.75 ms (white stars).
3.3. CVs of the reconstructed currents in the lumbar canal
The currents perpendicularly flowing into the lumbar spine
were retrieved from the virtual recording electrodes at 20 mm lateral from the midline of the lumbar canal and near the vertebral
foramina (Fig. 4b). In 32 subjects (74%), the CVs of the cauda equina
could be calculated from the peak latency of the volume currents at
the L2–5 vertebral level where peaks were clearly identified. In theother subjects, the peaks of the waveforms were dull or the waveforms were not conductive. The subjects were categorized into twogroups: those whose CVs could be calculated (Group A) and those
whose CVs could not be calculated (Group B). Table 1 shows thedemographic characteristics of the groups. The age and BMI weresignificantly higher in Group B (n = 11) than in Group A (Table 1)
and the SN ratio was also significantly lower. Multiple regression
analysis of the CV showed that there was a significant association
with only BMI (Table 2).
In Group A, the L5, L4, L3, and L2 level latencies (mean ± SD)
were 10.3 ± 0.736 ms, 10.80 ± 0.92 ms, 11.03 ± 0.59 ms, and11.72 ± 1.45 ms, respectively. The mean CVs of the right and left
side in each subject ranged from 43.8 to 85.2 m/s (n = 32; mean,
66.0 ± 9.26 m/s). A paired t-test showed no significant difference
between the mean CVs from the right and left nerve stimulations.
No subject showed marked laterality of the CV.
The distribution of the CVs in Fig. 6 showed a weak correlation
between age and CV (linear regression, y = 0.374x + 80.7,
R2 = 0.260, p < 0.005).
4. Discussion
There have been only a few reports on evoked magnetic fields ofthe nervous system in the lumbar region (Mackert et al., 1997,

1998; Klein et al., 2006). Mackert et al. (1997, 1998) presented conductive magnetic fields in the lumbar area and showed that thesignals of the impaired nerve disappeared in three patients with
S1 nerve root compression. However, the evoked signals were
small (10 fT) and the localization of the neural activities of thecauda equine or the spinal nerves was not precise enough for clinical use, mainly due to limitations in the recording device and signal processing.
Our group has reported that MSG can visualize the neural activity of the cauda equina and that the CV could be calculated fromreconstructed currents in five healthy subjects (mean age,
25.4 years; CV, 56.1–66.7 m/s) (Ishii et al., 2012). However, theamplitude of the CEAFs was still small, up to 30 fT. One probablereason was that the amplitude of the CEAP after stimulation of
the peripheral nerve was about one-fifth of that of the spinal cord
evoked potential in response to spinal cord stimulation. Anotherwas that the curvature of the recording area of the MSG did not
fit well to the body when the flexibility of the lumbar spine wasdecreased due to the subject’s age. When the distance between
the magnetic sensors and the nerves increases, the magnetic fields
recorded become smaller in a manner that is inversely proportional to the square of the distance.
In this study, we refined the shape and size of the measurement
surface to decrease the distance between the lumbar region andthe sensors. Stimulation at the knee could also derive larger signals
because more nerve fibers can be stimulated at the proximal site
and the signals attenuate or disperse to a lesser extent due to theshorter distance to the recording area. Although artifacts becomelarger when the stimulation is done more proximately, we could
extract magnetic fields buried in artifacts using a newly developed
artifact reduction method called DSSP.
When depolarization occurs in a nerve, intra-axonal currents
and volume currents are generated. The site volume currents perpendicularly flowing into the nerve is considered to be the depolarization point. Considering its direction, Y sensors record volume
currents flowing into and out of the nerve. Because the magnetic
field is generated clockwise around the intra-axonal current, a negative magnetic field in Y coils (cranial to caudal direction) in theleft side of the nerve is considered to be yielded by volume currents at the depolarization site. As Fig. 5b shows, negative magnetic fields appeared about 10 ms from the caudal site of the leftfour columns of the Y coils. Similarly, reconstructed currents flowing into the lumbar canal could be recognized on the left side from9.65 ms to 11.05 ms after the stimulation (the lower white stars in
9.65–10.35 ms, the middle one in 10.70 ms and the first one on theleft in 11.05 ms of Fig. 4a). We could calculate the CV of the reconstructed currents using these currents at depolarization site which
are perpendicularly flowing into the spinal canal (Fig. 4b).
Ishii et al. (2012) recorded CEAPs from an epidural electrode in
the lumbar canal in response to electrical stimulation of the tibial
nerve in the ankle and reported that CVs calculated from thelatency at L3–L5 ranged from 52.6 to 70.6 m/s (mean, 64.5 m/s).
Our CVs calculated from reconstructed currents at the depolarization site ranged from 43.8 to 85.2 m/s (mean, 66.0 m/s) and arecompatible with those of Ishii et al.
Taniguchi et al. (2005) used a needle electrode inserted into theligamentum flavum and measured CEAPs in the response to tibial
or peroneal nerve stimulation at the popliteal fossa. They reported
that the latency of CEAPs at the L4/5 site was 10.0 ± 1.7 ms. In ourstudy, the average latency of the reconstructed currents around L5
was 10.3 ± 0.736 ms and is thus consistent with the results of Taniguchi et al.
In this study, there was a weak correlation between age and CV(Fig. 6). It has been reported that the CV of the peripheral nerve inthe limb decreases with age (Wagman and Lesse, 1952; Norris
et al., 1953; Mayer, 1963; Nielsen, 1973; Taylor, 1984). Norris

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et al. (1953) considered that a decrease in the CV may occur due tovascular changes in the nerve trunk. It has also been shown thatthe latency of SEP with posterior tibial nerve stimulation correlateswith height and leg length (Lastimosa et al., 1982; Yamada et al.,
1982; Tsuji et al., 1984; Chu, 1986; Kakigi, 1987).

7

We found significant differences between Groups A and B
regarding some factors such as age, weight, and BMI (Table 1).
However, there was no clear difference in height. In addition, multiple regression analysis of the CV showed that BMI was a significant factor. The SN ratios were also significantly lower in thoseFig. 5. Isomagnetic contour maps and waveform of magnetic fields after right peroneal nerve stimulation in a representative case. Each waveform shows magnetic fields
recorded from each sensor. (a) Above is the correlation between the sensor configuration and the lumbar spine, and isomagnetic contour map of X-directed coils at 9.75 ms.
Red color indicates positive X-directed magnetic fields blue means negative. Four positional sensors on the corners are not depicted; thus, there are 40 recording sensors.
Below are magnetic fields recorded from X coils. The positive X direction is from the left to the right of the body. (b) Isomagnetic contour map and magnetic fields from Y coils.
The positive Y direction is from caudal to cranial. (c) Isomagnetic contour map and magnetic fields from Z coils. The positive Z direction is from ventral to dorsal. Magnetic
fields from the axial sensors in the four corners are depicted here.

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Fig. 5 (continued)

subjects whose CV could not be calculated (Group B). Because themagnetic field attenuated according to the distance between thesensor and signal, the negative correlation of weight and BMI to
CV may be due to a larger distance between the cauda equina
and the MSG sensors.
For the results of the CEAFs and reconstructed currents in
response to right peroneal nerve stimulation, signals were generally larger on the left side, contralateral to the stimulus (Figs. 4a,b and 5). Considering the position of the lumbar plexus and sciatic
nerve, the left side corresponds to the convex side of the conduction pathway. It could be due to the difference in the distance tothe sensors, but the same phenomenon has been found in our previous studies with animal and human subjects (Tomizawa et al.,2008; Ishii et al., 2012). Although further consideration is needed,
it is possible that volume currents and evoked magnetic fields areattenuated on the concave side due to signal cancellation.
One limitation of this study was the difficulty in achieving accurate recordings in patients with high BMI. As described above, thedistance between the signal and recording area was larger in suchcases. Further improvement of the nerve stimulation method andsensor sensitivity is necessary for accurate measurement inpatients with a wider range of attributes. In addition, the method

S. Ushio et al. / Clinical Neurophysiology 130 (2019) 1–11

9Fig. 5 (continued)

to evaluate each nerve in the cauda equina needs to be elucidated
in the future.
It is difficult to determine the true lesion site responsible forclinical symptoms if preoperative imaging studies show multiple
lesions in the spine. In practice, surgery is often performed for all
suspected lesions. In the clinical setting, it is especially important
to diagnose the correct lesion site in patients with L5 radiculopathy
because the invasiveness of the surgical procedure differs according to whether the lesion is intra-canal or intra-foraminal. However, there is no accurate and noninvasive examination method
for radiculopathy.

In this study, we showed that MSG can record CEAFs andreconstruct volume and intra-axonal currents. Notably, MSG
enables observation of neural activity as currents though it isdifficult by current physiological methods. Because MSG enables
the evaluation of currents in the vertebral foramen and thespinal canal, it is possible to determine the site of the causative
lesion more accurately. Clinical application of MSG is expected tocontribute to reducing the burden of patients and to decrease
healthcare cost by helping with minimally invasive surgicalplanning.

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S. Ushio et al. / Clinical Neurophysiology 130 (2019) 1–11

Table 1
Demographic characteristics of subjects.

N
Age (years)
Height (cm)Weight (kg)BMI
Signal (fT)
SN ratioAll

Velocity calculated group (Group A)

Velocity not calculated group (Group B)

43
Mean (SD)42.6 (12.9)
169.4 (5.6)
63.4 (9.8)
22.7 (3.05)
42.9 (16.9)
11.4 (3.65)

32

1140.0 (12.9)
169.2 (7.0)
63.1 (8.2)
21.9 (2.7)
45.9 (18.4)
12.0 (3.7)

49.6 (10.2)
169.8 (4.4)
71.0 (11.6)
24.7 (3.1)
36.0 (10.5)
10.0 (3.3)

p valuea

0.0218*0.736
0.0148*0.0045*0.0123*0.0224*SD, standard deviation; BMI, body mass index; fT, femtotesla.
ap value obtained from t-test.
*p < 0.05.

Table 2
Results of multivariate regression analysis.
Regression coefficient
BMI
Age

0.05310.00887

Standard error
0.02170.00519

Declaration of interestt valuep value

2.447
1.708

0.0189*0.0955

None of the authors have potential conflicts of interest to bedisclosed.

BMI, body mass index.
*
p < 0.05.

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Fig. 6. Correlation between age and the conduction velocity of reconstructedcurrents. A weak negative correlation is evident.

5. Conclusions
This study demonstrated noninvasive visualization of the neural activity of the lumbar spinal nerve root and cauda equina after
peroneal nerve stimulation at the skin surface of the knee. The dataobtained from healthy volunteers in this study could help to establish criteria for the diagnosis of L5 radiculopathy by comparison
with data from patients with L5 radiculopathy. Future studies
using MSG will establish a diagnostic method for spinal nerve
pathology and lead to minimally invasive surgery, which may
reduce the burden on patients and medical expenses.

Acknowledgements
This research was supported by the RICOH Company. The funding
body played no role in study design, data collection and analysis,
preparation of the manuscript, or the decision to publish. The
authors thank Mr. Y. Kawabata, Mr. H. Hanamoto, Miss H. Kusumi,
and Miss A. Nomura of Tokyo Metropolitan University and Mr. H.
Deguchi and Mr. T. Yamaga of RICOH Company for their generous
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