Clinical Neurophysiology 139 (2022) 1–8

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

Assessing carpal tunnel syndrome with magnetoneurography
Toru Sasaki a,⇑, Shigenori Kawabata b, Jun Hashimoto a, Yuko Hoshino b, Kensuke Sekihara b,
Yoshiaki Adachi c, Miho Akaza d, Koji Fujita e, Akimoto Nimura e, Toshitaka Yoshii a, Yuki Miyano f,
Yuki Mitani f, Taishi Watanabe f, Shinji Sato f, Sukchan Kim f, 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
Respiratory and Nervous System Science, Biomedical Laboratory Science, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo
113-8510, Japane
Department of Functional Joint Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japanf
Healthcare Business Group, Ricoh Company, Ltd., 2-3-10 Kandasurugadai Chiyoda-ku, Tokyo 101-0062, Japanbca r t i c l e

i n f oArticle history:
Accepted 30 March 2022
Available online 9 April 2022
Keywords:
Magnetoneurography
Carpal tunnel syndrome
Median nerve
Digital nerve
Conduction velocity
Nerve conduction study

h i g h l i g h t s
 Neural activity in carpal tunnel syndrome patients could be visualized using magnetoneurography.
 The lesion site could be visualized using the amplitude or nerve conduction velocity.
 Magnetoneurography could also visualize the improvement after surgery.

a b s t r a c t
Objective: To measure the neuromagnetic fields of carpal tunnel syndrome patients after electrical digital
nerve stimulation and evaluate median nerve function with high spatial resolution.
Methods: A superconducting quantum interference device magnetometer system was used to record
neuromagnetic fields at the carpal tunnel after electrical stimulation of the middle digital nerve in 10
hands of nine patients with carpal tunnel syndrome. The patients were diagnosed based on symptoms(numbness, tingling, and pain) supported by a positive Phalen or Tinel sign. A novel technique wasapplied to remove stimulus-induced artifacts, and current distributions were calculated using a spatial
filter algorithm and superimposed on X-ray.
Results: In 6 of the 10 hands, the amplitude of the inward current waveform attenuated to <70% or thenerve conduction velocity was <40 m/s. The results of conventional nerve conduction studies were normal for two of these six hands. All four hands that could not be diagnosed by magnetoneurography had
severe carpal tunnel syndrome superimposed on peripheral neuropathy secondary to comorbidities.
Conclusions: Technical improvements enabled magnetoneurography to noninvasively visualize theelectrophysiological nerve activity in carpal tunnel syndrome patients.
Significance: Magnetoneurography may have the potential to contribute to the detailed diagnosis ofvarious peripheral nerve disorders.
Ó 2022 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/).

Abbreviations: CSP, common-mode subspace projection; CTS, carpal tunnel syndrome; MNG, magnetoneurography; NCS, nerve conduction study; SQUID, superconducting
quantum interference device; UGRENS, unit gain constraint recursively applied null-steering spatial filtering.
⇑ Corresponding author at: Department of Orthopedic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
E-mail addresses: t-sasaki.orth@tmd.ac.jp (T. Sasaki), kawabata.orth@tmd.ac.jp (S. Kawabata), hash.orth@tmd.ac.jp (J. Hashimoto), hoshino.atm@tmd.ac.jp (Y. Hoshino),
k-sekihara@nifty.com (K. Sekihara), mihonuro@tmd.ac.jp (M. Akaza), fujiorth@tmd.ac.jp (K. Fujita), nimura.orj@tmd.ac.jp (A. Nimura), yoshii.orth@tmd.ac.jp (T. Yoshii),
yuki.yh.hasegawa@jp.ricoh.com (Y. Miyano), yuuki.ym.mitani@jp.ricoh.com (Y. Mitani), taishi.watanabe@jp.ricoh.com (T. Watanabe), shinji.s1.satoh@jp.ricoh.com (S. Sato),sukchan.kim@jp.ricoh.com (S. Kim), okawa.orth@tmd.ac.jp (A. Okawa).
https://doi.org/10.1016/j.clinph.2022.03.021
1388-2457/Ó 2022 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/).

T. Sasaki, S. Kawabata, J. Hashimoto et al.

Clinical Neurophysiology 139 (2022) 1–8

2. Methods

geons. The clinical diagnosis was based on symptoms of CTS(numbness, tingling, and pain) provoked or worsened by a sustained wrist position and relieved by shaking of the hands and apositive examination for CTS including a positive Phalen or Tinel
sign. Patients who could not maintain the measurement postureor who had previously undergone a carpal tunnel release operation
were excluded from this study.
All recordings were performed in a magnetically shielded room
using a superconducting quantum interference device (SQUID)
magnetometer system, developed by Kanazawa Institute of Technology and Ricoh Company, Ltd. (Adachi et al., 2017). Participants
sat on a chair and placed their palm on the curve of the sensor surface, as in a previous report (Fig. 1a) (Sasaki et al., 2020). To obtain
positional information on the hand and magnetic sensor during themeasurement, lateral and frontal radiographs were taken while thepatient was in the measurement position. The middle finger was
electrically stimulated at the distal interphalangeal joint (squarewave pulse; 3 Hz; 0.2 ms in duration) with over 2–3 times the sensory threshold (intensity, 6–18 mA). We chose the middle finger
because previous research showed that the signal intensity was
higher after middle finger stimulation than after index finger stimulation (Sasaki et al., 2020). The evoked magnetic fields after the
stimulation of the middle finger were recorded at the surface ofthe palmar area under the following conditions: sampling rate,
40 kHz; bandpass filter, 100–5000 Hz; two thousand recordings(first measurement).
After the first measurement, to exclude stimulus-induced artifacts from the entire signals obtained by MNG in response to theelectrical stimulation of the middle finger, we also measured themagnetic field of the stimulus-induced artifacts alone (second
measurement). A 30-mm urethane plate was placed between thepalm and the sensor surface with the same finger position as in
the first measurement, and the nerve magnetic field was measured
under the same conditions (Fig. 1b). In the second measurement,
the distance between the sensor and the nerve at the palm area
is increased, which reduces the signals from the nerve at the palmarea, allowing isolation of the signals derived from the stimulusinduced artifacts alone.

2.1. MNG system and measurement at the carpal tunnel area

2.2. Signal processing

This study was approved by the Ethics Committee of Tokyo
Medical and Dental University and was performed in accordancewith the Declaration of Helsinki with the written informed consent
of participants. We included 10 hands of nine patients (meanage ± SD, 65.9 ± 12.6 years; three men, six women) with CTS (bilateral CTS, 1; unilateral CTS, 8) who were diagnosed by hand sur-First, we removed stimulus-induced artifacts from the acquired
entire MNG signals of the first measurement by applying the CSP
algorithm (Watanabe et al., 2013). The CSP algorithm is a novel
method for calculating magnetic signals derived from neural activity alone using the first entire magnetic signals (neural signal + artifacts) and the second magnetic signals of the stimulus-induced

1. Introduction
In carpal tunnel syndrome (CTS), the most common nerve
entrapment syndrome, the median nerve is entrapped at the wrist.
CTS is primarily diagnosed via history and physical examination,but objective electrophysiological evaluation can help to determine the indication for surgery and assess postoperative function.
The sensitivity of median nerve distal motor latency ranges from
29% to 81% while that of wrist-palm sensory conduction velocity
varies from 45% to 100% (Moon et al., 2017). Meanwhile, Yılmaz
et al. (2017) determined the specificity of median nerve distal
motor latency to be 99% and the sensitivity of wrist-digit sensory
conduction velocity to be 97%. Nerve conduction studies (NCSs)
sometimes obtain no abnormal findings, even when the hand surgeon suspects CTS (Buchthal et al., 1974; Sedal et al., 1973, Thomas
et al., 1967). In these cases, it is sometimes difficult to select apatient’s treatment method without objective evidence supporting
invasive surgery. Moreover, the electrical potential recorded fromthe body surface is attenuated owing to a thick skin or transverse
ligament (Werner and Andary, 2011).
In contrast to electrical potential recording from the body surface, the magnetic field is less affected by the surrounding boneand soft tissue and has theoretically higher resolution (Trahms
et al., 1989). Our group has developed a novel method to visualize
the distribution of neural currents in the peripheral nerve andspinal cord using measurement of the neuromagnetic field (Ishii
et al., 2012; Sumiya et al., 2017; Ushio et al., 2019). We have also
reported the visualization of the electrophysiological activity at
the carpal tunnel area in response to stimulation of the digital
nerve by neuromagnetic field measurement in healthy individuals
using the common-mode subspace projection (CSP) method, which
is a new method for removing stimulus-induced artifacts (Sasaki
et al., 2020). In this study, we report for the first time the visualization of the electrophysiological nerve activity in CTS patients in
response to stimulation of the digital nerve by magnetoneurography (MNG) from the body surface.

Fig. 1. Measurement methods for neuromagnetic fields. (a) Participants placed their palm on the curve of the sensor surface. We measured the neuromagnetic fields after
electrical stimulation at the distal interphalangeal joint of the middle finger. (b) Measurement of the magnetic fields of stimulus-induced artifacts. A 30-mm urethane plate
was placed between the palm and the sensor surface with the fingers in the same position.
2

3

The amplitude decreased at the middle level of the metacarpal bone
Signal was too small to diagnose
Conduction velocity decreased at the base of the metacarpal bone
Conduction velocity decreased at the middle level of the metacarpal bone
Signal was too small to diagnose
Conduction velocity decreased at the base of the metacarpal bone
The amplitude decreased at the middle level of the metacarpal bone
The amplitude decreased at the middle level of the metacarpal bone
Signal was too small to diagnose
Signal was too small to diagnose
Grade 2 (mild)
Grade 6 (extremely severe)
NormalGrade 3 (moderately severe)
Grade 2 (mild)
NormalGrade 3 (moderately severe)
Grade 2 (mild)
Grade 3 (moderately severe)
Grade 3 (moderately severe)
4.9
NE
73.8
93.3
6.5
54.6
23.6
37.4
2.6
2.8
Hemodialysis, diabetes
Hemodialysis

Diabetes, rheumatoid arthritis
Cervical extramedullary tumor
Cervical myelopathy

79
62
79
43
81
69
4
5
6
7
8
9

FemaleFemaleMale
FemaleFemaleFemale

63
63
54

Male
Male
Female

Left
Right
Right
Left
Right
Right
Left
Left
Left
Right

Comorbidities
Affected
side
Sex

1
2
3

The results are summarized in Table 1. Except for the right sideof Patients 3 and 5, the NCSs indicated focal neuropathy at the carpal tunnel area. In 6 of the 10 hands, the amplitude of the inward
current waveform calculated from the MNG results attenuated toAge(years)3. Results

Patient

Table 1
Patients’ demographic and clinical characteristics, NCS, and MNG results.

DML (ms)

SCV (m/s)

SNAP (lV)

A conventional NCS of the bilateral median nerve was performed using an evoked potential/electromyography system(MEB-2300; Nihon Kohden, Tokyo, Japan) with the bandpass filter
set at 10 Hz to 5 kHz for motor nerve recording and at 20 Hz to
2 kHz for sensory recording. The compound muscle action potential was recorded with a pair of surface cup electrodes placed over
the abductor pollicis brevis by using the belly-tendon method.
Square-pulse supramaximal electrical stimuli at 0.5 Hz with aduration of 0.3 ms were delivered at the wrist and elbow. The wrist
stimulation point was 7 cm proximal to the cathode electrodeplaced on the abductor pollicis brevis. The sensory nerve action
potential of the median nerve was antidromically recorded witha pair of cup electrodes placed over the distal and proximal interphalangeal joints of the index finger. Square-pulse supramaximal
electrical stimuli at 0.5 Hz with a duration of 0.3 ms were deliveredat the palm, wrist, and elbow. Measurements included the peak-topeak amplitude of the response, distal latency, and conduction
velocity. Each measurement was performed twice to confirm
reproducibility. Waveforms with unclear latency and no reproducibility were considered non-measurable.
Because the findings of the preoperative conventional NCS for
Patient 5 were normal, we also intraoperatively recorded nerve
potentials. During the surgery, we used a larger incision to identify
the lesion site and performed adequate decompressions both distally and proximally. We electrically stimulated the median nerve
percutaneously (square wave pulse; 5 Hz; 0.3 ms in duration) at
the elbow immediately after decompression and recorded potentials every 1 cm at four locations directly above the nerve. The conduction velocity was calculated from the latency of each waveformand compared with the preoperative neuromagnetic field measurements. We also performed neuromagnetic field measurements
again at 6 postoperative months in this case.

32.8
NE
56.5
32.4
35
59.2
36.7
36.1
14.2
20.1

Bland classification

2.3. Nerve conduction study

4
NE
3.1
5.2
3.7
2.9
4.7
4
7.6
5.8

MNG result

artifacts. A spatial filter algorithm, unit gain constraint recursively
applied null-steering spatial filtering (UGRENS), was applied to themagnetic signal derived from neural activity (artifact-removed
magnetic signal), and this algorithm can calculate the temporaland spatial distributions of the currents (Sekihara and Nagarajan,
2015; Sasaki et al., 2020). The calculated currents were superimposed on the X-rays taken during the measurement. The distributions and intensities of the currents were visualized using a color
map. In this method, we were able to calculate the current waveforms at arbitrary points as if virtual electrodes were placed there.
We set the virtual electrodes along the digital and median nerves
at 10-mm intervals. We calculated the current waveform perpendicular to the digital and median nerve at virtual electrode points.
This current reflects the inward current at the depolarization
points (Sasaki et al., 2020). The conduction velocity was also calculated from the apex of the latency in this inward current waveform.
Because it has been shown that the propagation of the inward current stops at the lesion site in animal experimentation (Tomori
et al., 2010), the lesion site was defined as the level at which theamplitude of the inward current of the depolarization point
decreased below 70% compared with the next electrode or the levelat which the conduction velocity calculated from the inward current waveform decreased below 40 m/s.

DML, distal motor latency; MNG, magnetoneurography; NE, not evoked; SCV, sensory nerve conduction velocity (palm to wrist); SNAP, sensory nerve action potential.

Clinical Neurophysiology 139 (2022) 1–8

T. Sasaki, S. Kawabata, J. Hashimoto et al.

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Clinical Neurophysiology 139 (2022) 1–8

Fig. 2. Calculated currents of Patient 1. Calculated current maps superimposed on an X-ray image. Current intensity is shown by a color scale (red is higher). The small whitearrows indicate current vectors. The leading currents (downward-pointing red arrows), trailing currents (upward-pointing red arrows), inward currents (large blue arrows),
and outward currents (small blue arrows) propagated in the distal to proximal direction along the median nerve. However, the inward currents attenuated at the middle levelof the metacarpal bone of the middle finger.

waveforms, only parts of waveforms 8 to 7, 7 to 6, and 6 to 5
showed reduced conduction velocities of 37.35, 27.51, and38.00 m/s, respectively (Fig. 5a). The mean conduction velocity of
all waveforms (waveforms 9 to 1) was normal (46.3 m/s).
We intraoperatively measured nerve action potentials to checkfor conduction block (Fig. 5b). During surgery, the median nerve
was found to be erythematous and flattened on the distal side of
the transverse carpal ligament. Measurement of nerve action
potentials revealed a local conduction delay in this area, which
was consistent with the results of preoperative MNG (Fig. 5). We
repeated the magnetic field measurement 6 months after the surgery when her numbness had improved (Fig. 6). The calculated
inward current waveforms showed a healthy pattern.

less than 70% or the nerve conduction velocity was less than 40 m/
s. The results of conventional NCSs were normal (Bland, 2000) for
two of these six hands (right hands of Patients 3 and 5) but they
showed an abnormal pattern at the base of the metacarpal boneon MNG. In the remaining four hands (Patient 1 and the left handsof Patients 3, 6, and 7), the MNG results showed an abnormal pattern at the central level of the metacarpal bone. The four hands(Patients 2, 4, 8, and 9) that could not be diagnosed by MNG were
those of patients with severe CTS or comorbidities. These hands
were found to have too small a neuromagnetic field signal toobtain detailed information on the level of the lesion site.
Fig. 2 shows the result of Patient 1, who had Bland classification
grade 2 (Table 1). The reconstructed currents comprised a leading
current, a trailing current, and an inward/outward current. All currents showed an attenuated intensity at the center of the metacarpal bone of the middle finger (Fig. 2). We placed virtual electrodes
along the median nerve and calculated the waveforms for the
inward current. The amplitude of waveform 7 decreased to about
36.9% of that of waveform 8 (Fig. 3).
Fig. 4 shows the result of Patient 5, who had a normal result on
the NCS (Table 1). The reconstructed currents after stimulation of
the middle finger comprised leading, trailing, and inward/outward
currents. All currents propagated from distal to proximal without
intensity attenuation (Fig. 4). In the calculated inward current

4. Discussion
In this study, we were able to measure neuromagnetic fields atthe carpal tunnel area after stimulation of the digital nerve andvisualize the detailed distribution and propagation of the electrophysiological nerve activity in CTS patients.
Although various sensors have been used to measure the magnetic fields of human peripheral nerves (Trahms et al., 1989;
Wikswo et al., 1990; Hoshiyama et al., 1999; Mackert, 2004;
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T. Sasaki, S. Kawabata, J. Hashimoto et al.

Fig. 3. The waveforms of the calculated currents at the ‘‘virtual electrodes” (white circle) 15 mm lateral from the nerve pathway (upward is toward the nerve pathway). The
peaks in waveforms are equivalent to the inward currents at the depolarization point. Although the waveforms conducted in the distal to proximal direction, the amplitude of
waveform 7 decreased to about 36.9% of that of waveform 8 at the middle level of the metacarpal bone of the middle finger.

was too small for visualization of the electrophysiological nerve
activity. These results show that the neuromagnetic field signal
may be small in patients with severe peripheral neuropathy,
patients undergoing hemodialysis, and patients with diabetes.
For Patient 5, we repeated the measurement 6 months after thesurgery and confirmed that the local conduction disturbance had
disappeared. This method may contribute to preoperative andpostoperative electrophysiological evaluations. There have beensome reports of patients whose symptoms worsened after surgery
for CTS (Bland, 2007). Therefore, the ability to perform such a
detailed electrophysiological evaluation with leading and trailingintra-axonal currents and inward/outward currents before andafter the surgery may help to identify the cause of poor results
and predict prognosis.
There are several limitations to this study. The first is that there
were few cases. We need to accumulate and analyze a large number of cases to demonstrate the sensitivity, specificity, and effectiveness of MNG. Second, this system is a newer device that
requires costly magnetic sensors and shielded rooms and has problems associated with a high stimulation frequency and long examination time.

Nakanishi et al., 2004), there has been no report of magnetic fieldmeasurement at the carpal tunnel area from the body surface.
We successfully measured neuromagnetic fields and visualized
the detailed distribution of the electrophysiological nerve activity
in 6 of the 10 patients with CTS using MNG. These results suggestthat our method may be able to visualize local conduction disturbances in patients with mild peripheral neuropathy. In addition,
two types of lesion sites were indicated from the reconstructedcurrent waveform: one was found at the central level of the metacarpal bone and the other was found at the base of the metacarpal
bone. A lesion site with waveform changes at the central level ofthe metacarpal bone may indicate that the neuropathy extends
distally to the entrapment area. However, in this study, we were
not able to identify the true lesion site of the neuropathy by othermethods (except in Patient 5, when the intraoperative neurophysiology was assessed), so we were unable to elucidate the pathogenesis of the waveform changes at distal areas.
In the other four cases (Patients 2, 4, 8, and 9), we were unable
to measure neuromagnetic fields in detail because the neuromagnetic field signal was small. Patient 2 was a severe case that was
non-measurable in a conventional NCS, and the neuromagnetic
field signal after stimulation of the digital nerve was believed to
be insufficient. Although Patient 4 had a mild case of CTS with electrophysiological severity scale grade 2, the neuromagnetic fieldsignal might be small due to peripheral neuropathy associatedwith comorbid diabetes mellitus and rheumatoid arthritis. Patients
8 and 9 were long-term hemodialysis patients with delayed sensory nerve conduction velocities of 14.2 m/s and 20.1 m/s in thedigit-palm segment, and neuropathy was observed not only inthe palm-wrist segment, but also in the distal part. In these cases,
the number of fibers that could be stimulated by finger stimulation

5. Conclusion
In this study, we successfully measured neuromagnetic fields
after finger nerve stimulation and visualized the detailed distribution of the electrophysiological nerve activity in patients with CTS
through technical improvements involving the removal of
stimulus-induced artifacts and source analysis. The decrease in
the intensity of the inward current at the depolarization area and5

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Clinical Neurophysiology 139 (2022) 1–8

Fig. 4. Calculated currents of Patient 5. Currents are illustrated in a similar manner to those in Fig. 2. The leading, trailing, and inward currents propagated in the distal toproximal direction along the median nerve.

Fig. 5. Waveforms of calculated currents at the ‘‘virtual electrodes” and compound nerve action potentials (CNAPs) in response to median nerve stimulation at the elbow. (a)Currents at virtual electrodes (white circle) 15 mm lateral from the nerve pathway. The currents are illustrated in a similar manner to those in Fig. 3. The amplitudes of theinward current waveforms did not attenuate. Conduction velocity was delayed only in the carpal tunnel area with conduction velocities of 37.35, 27.52, and 38.00 m/s inwaveforms 8 to 7, 7 to 6, and 6 to 5, respectively. (b) Intraoperative CNAPs. Similar to the results of preoperative MNG, the CNAPs also showed focal conduction disturbancesin the carpal tunnel area. CNAPs, compound nerve action potentials; MNG, magnetoneurography.
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T. Sasaki, S. Kawabata, J. Hashimoto et al.

Fig. 6. Waveforms of calculated currents at the ‘‘virtual electrodes” along the median nerve (Patient 5) at 6 postoperative months. Currents are illustrated in a similar mannerto those in Fig. 3. The current waveform showed a normal conduction pattern 6 months after the surgery.

the decrease in conduction velocity reflected median nerve neuropathy in the carpal tunnel area. MNG may have the potential
to contribute to the evaluation of various peripheral nerve disorders in the future.

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Funding
This research was supported by Ricoh Company, Ltd. The funding body played no role in study design, data collection and analysis, preparation of the manuscript, or the decision to publish.

CRediT authorship contribution statement
T.S., S. Kawabata, and A.O. took part in the Conceptualizationand Methodology; T.S., S. Kawabata, J.H., Y.H., M.A., K.F., A.N., T.
Y., Y.A., Y. Miyano, Y. Mitani, T.W., S.S., S. Kim, and K.S. carriedout Data curation and Formal analysis; T.S., S. Kawabata, J.H., Y.
Miyano, Y. Mitani, T.W., S.S., S. Kim, and Y.A. developed the Software; S. Kawabata contributed Funding acquisition, T.S. contributed to Writing and S. Kawabata and A.O. contributed toreview & editing.

Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared
to influence the work reported in this paper.
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