JP2020151023A - Magnetic field detection device, magnetic field detection method, biological magnetic field measuring system, and rehabilitation technique - Google Patents

Abstract

To provide a magnetic field detection device that has improved dipole detection sensitivity.SOLUTION: A magnetic field detection device of the present invention includes a mounting part to be mounted on the head of a subject, and a sensor fixing part for fixing an optical pumping atomic magnetic sensor for detecting a magnetic field on the head of the subject to the mounting part. The sensor fixing part is positioned relative to the mounting part so that an optical axis of the optical pumping atomic magnetic sensor is disposed roughly in parallel to a normal direction of a side face of a central groove in a brain structure of the subject when the optical pumping atomic magnetic sensor is attached to the sensor fixing part, and the mounting part is mounted on the head of the subject.SELECTED DRAWING: Figure 22

Description

The present invention relates to a magnetic field detection device, a magnetic field detection method, a biomagnetic field measurement system, and a rehabilitation method.

Nerve cells in the brain express brain function by generating (firing) electrical signals and their transmission. By observing the firing state, it is thought that it will be possible to study brain function and diagnose diseases. When there are nerve cells that cause abnormal firing such as epilepsy, it is possible to perform surgery to remove the abnormal nerve cells by observing the position of the nerve cells non-invasively.

In addition, if the cells that cause epilepsy can be detected as accurately as possible, other nerve cells will not be unnecessarily removed, which is a great advantage for the patient. Therefore, it is desired to estimate the signal source as accurately as possible using a magnetoencephalograph.

The motor and sensory areas can be damaged by stroke or traumatic brain injury. Rehabilitation targeting this area, regenerative medicine using TMS (Transcranial Magnetic Stimulation), iPS (Induced Pluripotent Stem cells) cells, MUSE (Multi-lineage differentiating Stress Enduring cells) cells, etc. are active. Has been studied in.

In order to accelerate this research, it is highly valuable to detect active sites with high accuracy in a non-invasive manner. In addition, the effects of the above treatments are considered to vary greatly among individuals. It is thought that the motivation of patients and the treatment results will be improved by being able to detect the progress of the treatment with high accuracy.

In the brain, the primary motor cortex and the primary somatosensory area are regions aligned through the central sulcus. The somatosensory area has parts called areas 3a and 1 and 2, and in particular, area 3a hits the back of the groove, and it is important to accurately capture the signal in this area.

In particular, the gyrus is difficult, but the signal generated by the sulcus can be captured by a magnetoencephalograph. It is thought that the magnetic fields generated by the dipoles generated in the gyrus part cancel each other out in the scalp part and cannot be detected. Conversely, the dipoles generated in the sulci are horizontal to the scalp and cancel each other out. It is believed that it can be detected without any problems.

Regarding magnetoencephalography, for example, a magnetoencephalograph in which a plurality of optical pumping magnetometers are arranged so as to form a helmet shape covering the head of a subject is known. In this electromagnetometer, the optical pumping magnetic field meter is provided with steam cells arranged substantially parallel to the surface of the subject's head, and is substantially perpendicular to the surface of the subject's head by a pump optical laser and a probe optical laser. Therefore, the pump light and the probe light are emitted in the direction toward the head of the person to be measured. Then, the probe light is incident on the steam cell, the probe light is reflected by the mirror in a direction substantially perpendicular to the surface of the subject's head and away from the subject's head, and the probe light is polarized by the photodiode. (See, for example, Patent Document 1).

However, in the above-mentioned magnetoencephalograph, the optical axis of the probe light is parallel to the surface of the head. If the optical axis of the probe light is parallel to the surface of the head, it is difficult to detect the dipole with high sensitivity.

The present invention has been made in view of the above, and an object of the present invention is to provide a magnetic field detection device having improved dipole detection sensitivity.

This magnetic field detection device has a mounting portion to be mounted on the head of the subject and a sensor fixing portion for fixing an optical pumping atomic magnetic sensor for detecting the magnetic field of the head of the subject to the mounting portion. Then, when the optical pumping magnetic sensor is attached to the sensor fixing portion and the mounting portion is mounted on the head of the subject, the optical axis of the optical pumping magnetic sensor is the brain of the subject. The sensor fixing portion is positioned with respect to the mounting portion so as to be arranged substantially parallel to the normal direction of the side surface of the central groove in the structure.

According to the disclosed technique, it is possible to provide a magnetic field detection device having improved dipole detection sensitivity.

It is a figure which illustrates the whole structure of a biomagnetic field measurement system. It is a figure which illustrates the hardware configuration of the information processing apparatus. It is a figure which illustrates the magnetic shield box. It is a figure (the 1) which illustrates the magnetic shield room. It is a figure (the 2) which illustrates the magnetic shield room. It is a figure explaining the magnetic shield box for a head. It is a perspective view which illustrates the auxiliary member. It is a figure which illustrates the auxiliary member before processing. It is a perspective view which shows the modification of the auxiliary member. It is a figure which illustrates the structure of the side wall of a magnetic shield box. It is a side view which illustrates the head gear type magnetic field detection device. It is a figure which illustrates the schematic structure of the OPM sensor. It is a schematic diagram which enlarged the neighborhood of one sensor fixing part. It is a figure which illustrates the positional relationship of a marker, a shield, and wiring. It is a figure explaining a marker. It is a figure explaining a brain structure. It is a figure which illustrates the direction of the dipole generated in the central groove. It is a figure explaining the dipole of a gyrus and a sulcus. It is a figure explaining the dipole of a sulcus. It is a figure explaining the dipole of the gyrus. It is a figure explaining the direction of the optical axis of an OPM sensor. It is a figure explaining the magnetic field distribution of a dipole. It is a figure which illustrates the quantification method in the specific depth direction. It is a figure (the 1) explaining the layout of the OPM sensor which concerns on a comparative example. It is a figure (the 2) explaining the layout of the OPM sensor which concerns on a comparative example. It is a figure explaining the layout of the OPM sensor which concerns on this embodiment. It is a figure (the 1) explaining the preferable distance between adjacent OPM sensors. It is a figure explaining the crosstalk between adjacent OPM sensors. It is a figure (the 2) explaining the preferable distance between adjacent OPM sensors. It is a figure (the 1) which compares the OPM sensor and the SQUID sensor. It is a figure (the 2) which compares the OPM sensor and the SQUID sensor. This is an example of a flowchart showing a procedure for measuring a biomagnetic field using a biomagnetic field measurement system. It is a figure explaining the method of measuring the position of an OPM sensor. It is a flowchart which illustrates the rehabilitation method which concerns on this embodiment.

Hereinafter, modes for carrying out the invention will be described with reference to the drawings. In each drawing, the same components may be designated by the same reference numerals and duplicate description may be omitted.

[Overall configuration of biomagnetic field measurement system]
First, the overall configuration of the biomagnetic field measurement system will be described. FIG. 1 is a diagram illustrating the overall configuration of the biomagnetic field measurement system.

As shown in FIG. 1, the biomagnetic field measurement system 400 displays a magnetic field detection device 10, an information processing device 410, an MRI (Magnetic Resonance Imaging) imaging unit 420, a three-dimensional measurement unit 430, and a stimulator 440. It has a device 480 and. The biomagnetic field measurement system 400 may include a stimulator 440 and a display device 480 as needed.

The information processing device 410 includes a signal processing unit 411, a display control unit 412, and a data storage unit 413.

The MRI imaging unit 420 images the head of the subject and generates MRI image data of the three-dimensional structural shape of the brain. The MRI imaging unit 420 transmits the generated MRI image data to the information processing device 410.

The MRI may be a 1.5T level MRI generally used in a human dock or the like, and the resolution may be about 1 mm. By using T1 and T2 images, one with clear contrast is adopted. In particular, it is sufficient if the sulcus structure of the brain can be clearly observed, and the structure of the blood vessels of the brain is unnecessary for this purpose. This makes it possible to compare with the standard brain and with the brain map of general brain function.

When imaging the subject's head, the parts that serve as position markers such as ears and eyes are also measured. In addition, a vitamin material or the like that serves as a marker when measuring MRI is placed on the face of the subject. When measuring with the magnetic field detection device 10, a magnetic marker that generates magnetism is installed at the same position as the marker position of the vitamin material or the like on the face of the subject. As a result, the MRI image and the head coordinates of the measurement data of the magnetic field detection device 10 can be matched. Therefore, the position where the vitamin material is attached is marked on the skin in advance with a pen or the like.

The three-dimensional measuring unit 430 determines the position of the optical pumped atomic magnetometer (OPM) installed in the head gear type (head-mounted type) magnetic field detection device 10 mounted on the subject's head. Measure. The three-dimensional measurement unit 430 transmits the sensor position data to the information processing device 410. Hereinafter, the optical pumping atomic magnetic sensor may be referred to as an OPM sensor.

The magnetic field detection device 10 measures the magnetic field generated by the magnetic marker and transmits the measurement result to the information processing device 410. Further, the magnetic field detection device 10 executes magnetoencephalography measurement and transmits the measurement result to the information processing device 410. At the time of magnetoencephalography measurement, the subject is given a stimulus by the stimulator 440 as needed. Details of the magnetic field detection device 10 will be described later.

The stimulator 440 is a device in which an electrode is attached to a predetermined portion of the subject and an electrical stimulus is given to the subject via the electrode. Alternatively, the stimulator 440 may be a device that irradiates a predetermined portion of the subject with a laser beam to stimulate the subject.

The signal processing unit 411 of the information processing device 410 can process various signals. The signal processing unit 411 detects the position of the magnetic marker by inverse problem estimation or the like based on the measurement result of the magnetic field generated by the magnetic field by the magnetic field detection device 10, and stores the detection result in the data storage unit 413.

Further, the signal processing unit 411 is a magnetic field detection device based on, for example, MRI image data transmitted from the MRI imaging unit 420, sensor position data transmitted from the three-dimensional measurement unit 430, detection result of the position of the magnetic marker, and the like. The head coordinates of the 10 OPM sensors and the head coordinates of the MRI image are matched, and the matching result is stored in the data storage unit 413.

Further, the signal processing unit 411 stores, for example, the measurement result of the magnetoencephalography measurement by the magnetic field detection device 10 in the data storage unit 413.

The display control unit 412 reads the predetermined data stored in the data storage unit 413 and transmits a display signal to the display device 480. The display device 480 displays, for example, the result of magnetoencephalography measurement based on the signal of the display control unit 412. The display device 480 is, for example, a liquid crystal display or the like.

The data storage unit 413 is a storage device that stores various programs and information acquired by executing various programs.

FIG. 2 is a diagram illustrating a hardware configuration of an information processing device. As shown in FIG. 2, the information processing device 410 has a CPU (Central Processing Unit) 1501, a ROM (Read Only Memory) 1502, a RAM (Random Access Memory) 1503, and an I / F (I / F) as main components. It has an Interface) 1504 and a bus line 1505. The CPU 1501, ROM 1502, RAM 1503, and I / F 1504 are connected to each other via the bus line 1505. The information processing device 410 is connected to various control targets, various sensors, and the like. The information processing device 410 may have other hardware blocks, if necessary.

The CPU 1501 controls each function of the information processing device 410. The ROM 1502, which is a storage means, stores a program executed by the CPU 1501 to control each function of the information processing device 410 and various information. The RAM 1503, which is a storage means, is used as a work area or the like of the CPU 1501. Further, the RAM 1503 can temporarily store predetermined information. The I / F 1504 is an interface for connecting to another device or the like, and is connected to, for example, an external network or the like.

The information processing unit 410 includes a processor programmed to execute each function by software such as a processor implemented by an electronic circuit, an ASIC (Application Specific Integrated Circuit) designed to execute a predetermined function, and a DSP (DP). It may be a digital signal processor), an FPGA (field programmable gate array), an SOC (System on a chip), or a GPU (Graphics Processing Unit). Further, the information processing device 410 may be a circuit module or the like.

[Magnetic shield]
Next, a magnetic shield box and a magnetic shield room used for biomagnetic field measurement using the magnetic field detection device 10 will be described.

The electrical signal of the brain is very weak, several pT even on the surface of the scalp. There are several tens of μT for geomagnetism and several hundred nT for noise from commercial power sources. Therefore, in order to reduce these noises, the biomagnetic field measurement using the magnetic field detection device 10 is performed in the following magnetic shield box or magnetic shield room.

FIG. 3 is a diagram illustrating a magnetic shield box. As shown in FIG. 3, the magnetic shield box 100 is a portable type and has a shape that surrounds only the head of the subject 200. The magnetic shield box 100 is for the subject 200 to measure the biomagnetic field in a sitting position, and is provided with wheels 117 in order to have portability including the chair 115.

The stimulator 440 is, for example, a device that stimulates the subject by laser light, and includes a holder 545 for laser light irradiation that can be attached to the finger tip of the subject. However, the present invention is not limited to this, and the stimulator 440 may be, for example, a device that stimulates the subject by electricity. In this case, the stimulator 440 applies electrical stimulation to, for example, the median nerve of the elbow. The stimulator 440 can, for example, give the subject a stimulus that causes a dipole in the somatosensory area.

In addition, in order to reduce the noise in the magnetic shield box 100, the stimulator 440 is arranged outside the magnetic shield box 100.

FIG. 4 is a diagram (No. 1) illustrating the magnetic shield room. As shown in FIG. 4, the entire body of the subject 200 may be placed in the magnetic shield chamber 120 to perform biomagnetic field measurement. In FIG. 4, the subject 200 is in a sitting state, and in this state, the housing of the magnetic field detection device 10 can be lifted upward by the upper support column 125.

As described above, the biomagnetic field measurement system 400 has a chair, a support, etc., which serve as a holding portion for holding the subject 200 in a sitting state, and the housing of the magnetic field detection device 10 has an upper portion provided in the holding portion. It may be lifted by a support such as 125.

When the subject 200 fully supports the weight of the magnetic field detection device 10, the load is applied to the head, which causes muscles such as the neck to become tense and causes noise. By supporting the magnetic field detection device 10 with the upper support column 125, no load is applied to the subject 200. Further, since the weight of the head of the subject 200 can be supported, the subject 200 does not support the weight of his / her head and does not strain the neck muscles. As a result, the noise generating factor can be removed.

FIG. 5 is a diagram (No. 2) illustrating the magnetic shield room. As shown in FIG. 5, a biomagnetic field in which the entire body of the subject 200 is placed in the magnetic shield room 130 and the subject 200 is lying on the bed 135 arranged in the magnetic shield room 130. Can make measurements.

As described above, the biomagnetic field measurement system 400 may have a bed 135 or the like as a holding portion for holding the subject 200 in a lying state on its back.

When the magnetic shield chambers 120 and 130 are used, it is necessary to prevent them from being affected by the electrical noise generated by the stimulator for stimulating the subject 200. Therefore, for example, a long-distance optical fiber or the like is used to stimulate the skin (C fiber, Aσ fiber, etc.) with a laser beam. However, there are problems such as difficulty in handling optical fibers and difficulty in stimulating nerves such as the median nerve.

Therefore, it is preferable to use the magnetic shield box 100. By using the magnetic shield box 100 that surrounds only the head, noise generated in other parts does not reach the OPM sensor in the magnetic shield box 100. Therefore, it is possible to stimulate large nerves such as the fingertips and the median nerve of the elbow. As a result, brain function mapping of the somatosensory area can be performed with high signal strength, and highly accurate mapping becomes possible.

The magnetic shield box for the head will be described in more detail below.

FIG. 6 is a diagram illustrating a magnetic shield box for the head. As shown in FIG. 6, the magnetic shield box 100 for the head has a substantially cylindrical shape, and has an opening / closing type structure having an opening / closing portion 101 for moving the head of the subject 200 in and out. A substantially circular opening 102 is provided in a portion through which the neck of the subject 200 passes, and a cancel coil 103 is installed in the vicinity of the opening 102.

The cancel coil 103 is wired so that a current can flow at several 10 mA for 10 turns, for example, in order to generate a magnetic field that opposes the geomagnetic level of several μT. The magnetic shield box 100 may be large enough to surround the head of the subject 200, for example, having a diameter of about 300 mm and a length (height) of about 400 mm. The residual magnetic field can be reduced when the opening 102 is as narrow as possible. Therefore, it is preferable to prepare an auxiliary member of the magnetic shield to be attached around the neck of the subject 200 according to the subject 200.

FIG. 7 is a perspective view illustrating an auxiliary member. The auxiliary member 650 shown in FIG. 7A is a donut-shaped member provided with an insertion hole 651 for inserting the neck in the center. The auxiliary member 650 is made of a flexible material. The diameter of the insertion hole 651 is φ1. The auxiliary member 650 shown in FIG. 7B has the same structure as that in FIG. 7A, but the diameter φ2 of the insertion hole 651 is formed to be smaller than the diameter φ1.

By preparing a plurality of auxiliary members 650 having different diameters of the insertion holes 651 in this way, the gap between the neck of the subject 200 and the inner wall of the insertion hole 651 can be reduced, so that the inside of the magnetic shield box 100 can be reduced from the outside. The noise that enters can be greatly reduced. As a result, the shielding performance of the magnetic shield box 100 can be improved. Of course, three or more types of auxiliary members 650 may be prepared.

FIG. 8 is a diagram illustrating an auxiliary member before processing. The auxiliary member 650 has, for example, a structure in which a strip of flexible amorphous metal foil 653 and a strip of elastic body 655 are laminated as shown in FIG. 8 and deformed into an annular shape.

The amorphous metal foil 653 has a thickness of, for example, about several tens of μm. As the amorphous metal foil 653, for example, Finemet (trademark) manufactured by Hitachi Metals, Ltd. can be used. The elastic body 655 has various options such as a cloth woven with chemical fibers, a rubber-like material, and a lightweight material such as Styrofoam, but it comes into contact with the subject's neck. In some cases, it is preferable to select an elastic cloth. By sequentially laminating the amorphous metal foil 653 and the elastic body 655, a flexible structure in which the amorphous metal foil 653 is held between the elastic body 655 as the base material can be formed.

The conventional shield member uses a material obtained by crystallizing a metal such as permalloy, and is very hard. On the other hand, the amorphous metal foil 653 has a very high magnetic permeability even if it is thin, and its shielding performance is high. The amorphous metal foil 653 is cured by rapidly cooling from the amorphous high temperature state without crystallizing while maintaining the amorphous state. A thin material of about several tens of μm can be formed for rapid cooling.

FIG. 9 is a perspective view showing a modified example of the auxiliary member. A bellows-shaped auxiliary member 650A as shown in FIG. 9 may be used. By providing the bellows-shaped auxiliary member 650A in the vicinity of the opening 102 of the magnetic shield box 100, the auxiliary member 650A can be deformed in a shape that follows the neck when the neck is inserted into the insertion hole 651. As a result, the physical stress of the subject can be reduced, and individual differences of the subject can be absorbed.

In the bellows-shaped auxiliary member 650A, for example, a plurality of sets of a laminate of an amorphous metal foil 653 and an elastic body 655 are prepared, only one side of each set of laminates is fixed, and the other side is free. Can be formed with.

The side wall of the magnetic shield box 100 is a fine metal foil sandwiched between PET film base materials in order to increase portability as much as possible and to reduce weight as much as possible without using general high magnetic permeability permalloy. It is preferable to use Met ™.

Specifically, as shown in FIG. 10, a structure in which a plurality of pairs in which one layer of amorphous metal foil 658 (Finemet) is adhered to Styrofoam 657 having a thickness of about 10 mm is laminated can be mentioned. The distance L between the adjacent amorphous metal foils 658 is, for example, 1 mm.

With the structure as shown in FIG. 10, it is lighter in weight and can exhibit high shielding performance as compared with the case where Finemet is simply laminated. In the example of FIG. 10, there are 6 pairs of Styrofoam 657 and amorphous metal foil 658, but the present invention is not limited to this.

(Head gear type magnetic field detector_swimming cap type)
First, the magnetic field detection device according to the first embodiment will be described. The magnetic field detection device 10 according to the first embodiment is a head gear type magnetic field detection device worn on the head of a subject.

FIG. 11 is a side view showing an example of a head gear type magnetic field detection device. Referring to FIG. 11, the magnetic field detection device 10 is a magnetic field detection device worn on the head of the subject, and is a swimming cap type in which the sensor fixing portion 22 is installed on the surface of the mesh-shaped base 21. The sensor fixing portions 22 are arranged vertically and horizontally at a pitch of about 30 mm, for example, at substantially equal intervals. An OPM sensor 30 is fixed to each sensor fixing portion 22.

In the magnetic field detection device 10, the base 21 is knitted based on, for example, fine rubber fibers, and has rubber elasticity that expands and contracts nearly 1.5 times. As a result, the shape of the head of the subject 200 can be firmly fitted. The base 21 is a typical example of the mounting portion according to the present invention.

It is preferable that the magnetic field detection device 10 is prepared for children to adults, for example, about 10 types according to the size of the head circumference, and the subject selects an appropriate size at the time of use. For example, for adults, as with the types of hats, five types, S, M, L, 2L, and 3L, are prepared from the smallest. Specifically, for example, in consideration of the shape of the head of the subject, the head circumference is divided into 2 cm increments.

In the magnetic field detection device 10, it is preferable that all the members such as the base 21 and the sensor fixing portion 22 are subjected to a matte treatment on the portion that may be reflected by the three-dimensional camera so that the reflected light is reduced. As a result, it becomes difficult to see the image on the three-dimensional camera, and the noise component can be reduced.

(OPM sensor)
The OPM sensor 30 is a sensor that detects a magnetic field vector emitted from the subject's head. In the OPM sensor 30, the resin housing and wiring are black. This is to reduce the reflected light during the three-dimensional measurement.

As the OPM sensor 30, for example, Gen 2.0 manufactured by Questin can be used. The external dimensions of Gen2.0 are a rectangular parallelepiped of 12 mm × 16 mm × 24 mm, and wiring having a width of about 10 mm is provided from the upper surface thereof.

Here, the OPM sensor 30 will be described in more detail. FIG. 12 is a diagram illustrating a schematic configuration of an OPM sensor. As shown in FIG. 12, the OPM sensor incidents a laser beam on a gas cell of a rubidium atom, and detects the laser beam that has passed through the gas cell with a photodetector. The laser beam transmitted through the gas cell, in accordance with the magnitude of the magnetic field generated in the Y ₀ axis direction or Z ₀ axis direction, is absorbed, the magnetic field is generated in the Y ₀ axis direction or Z ₀ axis direction, the light detection The intensity of the laser beam detected by the instrument decreases.

Therefore, by comparing the intensity of the laser beam detected by the photodetector when the magnetic field is not generated with the intensity of the laser beam detected by the photodetector when the magnetic field is generated. , The magnitude of the magnetic field can be calculated. A coil is wound around the gas cell, and an appropriate alternating current is applied.

In this way, the OPM sensor can detect the magnetic field in the direction substantially orthogonal to the incident direction (light propagation direction) of the laser beam. In the present embodiment, the incident direction substantially parallel to the direction of the laser beam, and X ₀ axis direction, placing the incident direction and a direction substantially orthogonal laser beams, respectively, Y ₀ axis direction, the Z ₀ axis.

The gas cell is arranged at a position of about 6 mm from the surface of the housing, for example, and detects a magnetic field at this location. Hereinafter, when it is described as a gas cell, it has a meaning as a detection position.

By using the OPM sensor 30, highly sensitive magnetic field detection becomes possible. That is, it is possible to detect a magnetic field signal of a nerve that cannot be realized by an MI (Magneto-Impedance element) sensor, a TMR (Tunnel Magneto Resistance) sensor, or the like.

(Sensor fixing part)
FIG. 13 is an enlarged schematic view of the vicinity of one sensor fixing portion. As shown in FIG. 13, the sensor fixing portion 22 has a tubular portion 221, a head gear fixing portion 222, and a sensor fixing pin 223. The tubular portion 221 of the sensor fixing portion 22, the head gear fixing portion 222, and the sensor fixing pin 223 are molded from, for example, a resin such as polycarbonate.

The tubular portion 221 is a tubular portion formed according to the shape of the OPM sensor 30, and the OPM sensor 30 is inserted into the tubular portion 221. On one side of the tubular portion 221 in the longitudinal direction, a head gear fixing portion 222 projecting to the outer peripheral side of the tubular portion 221 is provided. It is preferable to provide the shield 25 so as to surround the outer peripheral surface of the tubular portion 221.

A through hole 224 for inserting a screw is formed in the head gear fixing portion 222. The sensor fixing portion 22 can be fixed to the base 21 of the magnetic field detection device 10 by, for example, two plastic screws 23A and 23B inserted into the through hole 224 so as not to fluctuate due to rotation.

The sensor fixing unit 22 is designed so that the OPM sensor 30 can be fixed. The OPM sensor 30 can be fixed to the sensor fixing portion 22 by, for example, the sensor fixing pin 223. The wiring 35 is connected to the OPM sensor 30.

For example, a mechanism can be adopted in which the sensor fixing pin 223 is automatically caught on the OPM sensor 30 when the OPM sensor 30 is pushed into the sensor fixing portion 22 and inserted to some extent. In this case, the installation work is completed by simply pushing the OPM sensor 30 into the sensor fixing portion 22.

Since the number of OPM sensors 30 is as large as 64, the magnetic field detection device 10 is fixed to an installation location such as a mannequin, the OPM sensor 30 is attached to each sensor fixing portion 22, and then the OPM sensor 30 is fixed. The procedure of attaching the base 21 of the magnetic field detection device 10 to the head of the subject 200 is preferable.

In actual measurement, body movement is the largest artifact, including breathing and heartbeat. Although the artifact cannot be removed, the sensor fixing portion 22 of the magnetic field detection device 10 is set so that the head, the base 21, and the sensor fixing portion 22 of the subject 200 become one rigid body so that the influence thereof is minimized. It is preferable to fix it to the base 21.

It is necessary to tighten the magnetic field detection device 10 by rubber elasticity to some extent so that the magnetic field detection device 10 does not shift due to the influence of body movement or the like. However, if it is too strong, there will be pressure on the scalp, which will make the subject 200 feel uncomfortable, and at the same time, there will be a problem that myoelectricity from muscle fibers on the skin surface becomes noise. Proper tightening is an important factor.

A marker 40 used for measuring the position of the OPM sensor 30 is installed on the upper surface side (the side farther from the base 21) of each OPM sensor 30. It is preferable that two or more markers 40 are installed in each OPM sensor 30, and it is more preferable that three or more markers are installed.

FIG. 14 is a diagram illustrating the positional relationship between the marker, the shield, and the wiring. Note that in FIG. 14, the sensor fixing portion 22 is not shown (the same may apply to the subsequent drawings). As shown in FIG. 14, the marker 40 needs to be arranged on the uppermost surface in order to enable observation by a three-dimensional camera during three-dimensional measurement. Here, the marker 40 is arranged on the upper surface of the OPM sensor 30.

Further, the wiring 35 generates noise due to the flow of electric signals. Therefore, it is desirable to keep it as far as possible from the scalp and the OPM sensor 30. When the OPM sensor 30 is an OPM sensor, it has a gas cell 31, so it is desirable to separate the wiring 35 from the gas cell 31 as much as possible.

The number of wires 35 is large because they are connected to each of the 64 OPM sensors 30, and they are very long, several meters, so that they can be taken out of the shield room. The wiring 35 can be laid along with the upper end surface of the OPM sensor 30 as shown in FIG. 14, for example. It is preferable to provide a shield 25 between the wiring 35 and the OPM sensor 30. As the shield 25, for example, Finemet or the like can be used.

(Position detection of OPM sensor)
FIG. 15 is a diagram illustrating a marker. Here, an example in which three markers 40 are installed on each OPM sensor 30 is shown.

As shown in FIG. 15, three markers 40 are placed on the upper surface 30a of the housing of each OPM sensor 30 when viewed from the normal direction of the upper surface 30a (that is, the surface of the subject's head). (When viewed from the normal direction of), they are arranged so as to form a triangle. Four or more markers 40 may be placed on one OPM sensor 30.

The marker 40 is preferably a perfect scatterer that scatters light from either side. The marker 40 has, for example, a hemispherical portion having a diameter of 4 mm on the tip end side (the side away from the upper surface 30a of the OPM sensor 30).

By installing three markers 40 on the upper surface 30a of the housing of one OPM sensor 30, the six axes (x, y, z) of the housing can be obtained from the data of the position coordinates of x, y, and z at three locations. , Θx, Θy, Θz) can be converted. Assuming that the position coordinates of the three markers 40 are (x1, y1, z1), (x2, y2, z2), (x3, y3, z3), the triangular surface 40T formed by these three points can be defined. .. Further, the normal vector V of the triangular surface 40T can be defined, and this becomes (Θx, Θy, Θz).

Further, since the center of gravity of the triangular surface 40T can be defined, the position coordinates of (x, y, z) can be obtained. The method of obtaining the six-dimensional data (x, y, z, Θx, Θy, Θz) of the sensor from the position coordinates of the three markers 40 requires the minimum number of data, so that the calculation cost can be minimized. However, the position of the OPM sensor 30 (x, y, z, Θx, Θy, Θz) is the position of the center of gravity of the lower surface 30b of the housing of the OPM sensor 30.

The marker is a member indicating the position of the OPM sensor 30, and is used by the three-dimensional measuring unit 430 to acquire the sensor position data of the OPM sensor 30 when measuring the position of the OPM sensor 30. If it can be used for such a purpose, even a member not named a marker is included in the marker according to the present embodiment. Further, even if there is a member having another function, if the three-dimensional measuring unit 430 can be used to acquire the sensor position data of the OPM sensor 30 when measuring the position of the OPM sensor 30, what is the name? It is included in the marker according to this embodiment regardless of.

For example, in FIG. 15, if there is a protrusion on the top surface 30a and two markers 40 are added to it so that it can be used as substantially three markers, this protrusion is also a marker.

(Fixed position of sensor fixing part)
In the sensor fixing portion 22, when the OPM sensor 30 is attached to the sensor fixing portion 22 and the base 21 is attached to the subject's head, the optical axis of the OPM sensor 30 is the central groove in the subject's brain structure. It is positioned with respect to the mounting portion 21 so as to be arranged substantially parallel to the normal direction of the side surface.

For example, the base 21 is marked with a mark indicating the left-right direction when the base 21 is attached to the head of the subject, and when the OPM sensor 30 is attached to the sensor fixing portion 22, the light of the OPM sensor 30 is attached. The sensor fixing portion 22 is positioned with respect to the base 21 so that the axis faces the direction perpendicular to the left-right direction indicated by the mark.

Alternatively, the base 21 is provided with an opening for ensuring the field of view of the subject so that the vector from the center of the base 21 toward the opening of the opening and the optical axis of the OPM sensor 30 are arranged substantially in parallel. In addition, the sensor fixing portion 22 may be positioned with respect to the base 21.

It should be noted that the direction substantially parallel to the normal direction of the side surface of the central groove in the brain structure of the subject 200 is, in other words, a direction substantially parallel to the direction of the dipole generated from the central groove in the brain structure of the subject 200. is there. Here, the substantially parallel means not only the case where the beam is completely parallel, but also the case where the direction of the optical axis of the OPM sensor 30 deviates from the direction of the dipole by ± 5 degrees.

As described above, the optical axis of the OPM sensor 30 is arranged substantially parallel to the normal direction of the side surface of the central groove in the brain structure of the subject, so that the detection sensitivity of the dipole can be improved. That is, the biomagnetic field measurement system 400 is a system optimized for the central groove that separates the motor area and the somatosensory area, and can detect the dipole from the central groove with high sensitivity.

FIG. 16 is a diagram for explaining the brain structure, which is a view of a human face from the left side. In FIG. 16, X is the depth direction, Y is the front-back direction of the face, and Z is the left-right direction of the face (the direction connecting the left and right ears).

As shown in FIG. 16, the central groove 300 exists perpendicular to the front surface of the face (direction of the arrow), that is, in the Z direction connecting the left and right ears. In FIG. 16, 301 is the motor cortex, 302 is the somatic sensory area, 303 is the frontal lobe, 304 is the parietal lobe, 305 is Broca's area, 306 is the temporal lobe, 307 is Wernicke's area, 308 is the occipital lobe, and 309 is. The visual cortex, 310 indicates the cerebellum, and 311 indicates the brain stem.

It is known that there is a vector of the firing current of the cerebral cortex in the normal direction of the surface of the head, and the firing current is referred to as a dipole here. As shown in FIG. 17, the generation direction of the dipole Di is perpendicular to the central groove 300.

As shown in FIG. 18A, there are irregularities on the surface of the brain, the convex portion is the gyrus 320, and the concave portion is the sulcus 321. As shown in FIG. 18B, dipoles are generated in the gyrus 320 and the sulcus 321 in the normal direction of the surface (direction of each arrow), respectively. Di1 is a dipole of sulcus 321 and Di2 is a dipole of gyrus 320.

As shown in FIG. 19, the dipole Di1 of the sulcus 321 can be detected in the scalp portion by the OPM sensor 30. On the other hand, as shown in FIG. 20, the dipole Di2 of the gyrus 320 cannot be detected by the OPM sensor 30 because they cancel each other out on the surface of the scalp.

In order to accurately capture the magnetic field generated by the dipole Di1 generated in the sulcus 321, it is necessary to accurately capture the vector direction of the dipole Di1. As shown in FIG. 21, the OPM sensor 30 has two axes perpendicular to the optical axis, here, a vector of the magnetic field detected when the optical axis OA is X ₀ and the vertical directions are Y ₀ and Z _0. Is Y ₀ and Z ₀ . By making the optical axis OA of the OPM sensor 30 substantially parallel to the vector direction of the dipole Di1, the magnetic field distribution generated on the scalp surface can be detected as a distribution including vector information.

By making the optical axis OA of the OPM sensor 30 horizontal to the head surface 200A as shown in the cross-sectional view of FIG. 22, the magnetic field strength is also strong in the depth direction (Z ₀ direction) at a distance of about 30 mm. Will have. The Z ₀ direction strength is effective as the distance information from the position that is ignited to form a dipole.

FIG. 23 is a diagram illustrating a specific quantification method in the depth direction. The position where the dipole occurs is assumed to be the brain surface. This is effective for tasks such as the somatosensory area where electrical signals are projected onto the brain surface. By defining the brain surface, an approximate depth Zk can be estimated from an MRI image or the like. Once the depth Zk is determined, as shown in FIG. 23, assuming the adjacent OPM sensors 30, the approximate positions of Ly2 and Ly3 can be detected. The details are as follows.

In FIG. 23, the magnetic fields are formed concentrically around the ignition position D. LS1 is a perpendicular line drawn perpendicular to the magnetic field M2 at the position of the OPM sensor 30_1. Further, LS2 is a perpendicular line drawn perpendicular to the magnetic field M3 at the position of the OPM sensor 30_2. The intersection of the perpendicular line LS1 and the perpendicular line LS2 is the ignition position D.

The distance Ly between the OPM sensor 30_1 and the OPM sensor 30_2 is divided into Ly2 and Ly3 by the perpendicular line LS4 drawn from the ignition position D to the line segment LS3 connecting the OPM sensor 30_1 and the OPM sensor 30_2. At this time, Ly2 and Ly3 can be expressed by θ, φ, and Zk.

That is, when the ratio "Zn / Yn" of the peak values Zn and Yn of the detection data of the OPM sensors 30_1 and 30_2 is obtained, tanφ = Z2 / Y2 and tanθ = Z3 / Y3. Further, Ly2 × tanφ = Zk, Ly3 × tanθ = Zk, Ly2 + Ly3 = Ly. Since Z2 / Y2, Z3 / Y3, Ly2, Ly3, and Ly are all known, the distance Zk in the depth direction of the ignition position can be calculated from these values.

24 and 25 are comparative examples in which the optical axis of the OPM sensor 30 is fixed so as to be substantially perpendicular to the direction of the dipole Di1. In this case, as shown in FIG. 24, when the layout of the head is rotated by 90 ° and the central groove 300 is viewed from the side, it is not the magnetic field on the Z ₀ Y ₀ plane that can be detected by the OPM sensor 30, but the direction X ₀ . It becomes the magnetic field of. Therefore, the OPM sensor 30 cannot detect the magnetic field. With this, highly sensitive detection cannot be expected.

This also applies when the OPM sensors 30 are arranged in an array as shown in FIG. 25. In this case, with respect to the dipole Di1 generated perpendicularly to the central groove 300, all the OPM sensors 30 arranged in an array detect the magnetic field vector M in substantially the same direction. That is, even if the magnetic field vector M is detected, it is impossible to estimate the position of the dipole Di1.

On the other hand, in the present embodiment, as shown in FIG. 26, the optical axis of the OPM sensor 30 is fixed so as to be substantially parallel to the direction of the dipole Di1. Therefore, in the arrangement of FIG. 26, each OPM sensor 30 can detect the magnetic field vector M having a different angle at each location. By observing this magnetic field vector, it is possible to detect an approximate position where the dipole Di1 is generated.

That is, in the vicinity of the central groove 300 where the position of the dipole Di1 is determined to some extent, the optimum arrangement of the OPM sensor 30 is uniquely determined. That is, the optical axis of the OPM sensor 30 is aligned in a direction substantially parallel to the normal of the side surface of the central groove 300 (a direction substantially parallel to the direction of the dipole Di1) and arranged in an array. This is a fact that has not been discovered in the past and was first discovered by the present inventors.

(Layout of OPM sensor)
As shown in FIG. 27, even when a plurality of OPM sensors 30 are arranged, the optical axes of all the OPM sensors 30 are in a direction substantially parallel to the normal of the side surface of the central groove 300 (the direction of the dipole Di1). Arrange them so that they are in substantially parallel directions).

At this time, as shown in FIG. 28, crosstalk occurs in the adjacent _{Y 0} In OPM sensor 30 directions. Specifically, crosstalk occurs when the distance _{Y 0} direction between OPM sensor 30 adjacent is about 20 mm. Thus, _{Y 0} direction distance between the OPM sensor 30 adjacent must be opened to some extent.

In contrast, X ₀ direction from the cross-talk is not generated, it is possible to shorten the distance X ₀ direction between OPM sensor 30 adjacent. Considering these, for example, in FIG. 27, X1 = 20 mm and Y1 = 30 mm can be set.

In this way, when a plurality of OPM sensors 30 are arranged in the magnetic field detection device 10, the distance X1 in the direction parallel to the optical axis of the OPM sensor 30 of the adjacent OPM sensors 30 is the distance in the direction perpendicular to the optical axis. It is preferable to arrange the OPM sensors 30 so as to be smaller than Y1.

That is, when the OPM sensor 30 is attached to the sensor fixing portion 22 and the base 21 is attached to the head of the subject, the sensor fixing portion 22 is parallel to the optical axis of the OPM sensor 30 of the adjacent sensor fixing portion 22. It is preferable that the distance in the direction is positioned with respect to the base 21 so that the distance in the direction is smaller than the distance in the direction perpendicular to the optical axis.

By shortening the distance X1, the estimation accuracy of the dipole Di1 is improved. This is because the position of the central groove 300 varies from person to person, and an error of about 10 mm occurs in the external alignment. If X1 is 20 mm, there is a high possibility that a part of the central groove 300 will be applied to either OPM sensor 30 even if the X1 is slightly deviated. Further, in the X ₀ direction because there is no cross-talk, it can be brought closer to the minimum distance determined by the size of the size and the sensor fixing section 22 of the OPM sensor 30.

Further, as shown in FIG. 29, the gray matter targeted in this embodiment is about 30 mm from the head surface 200A. In this case, for example, if Y1 = 15 mm, the OPM sensor 30 is arranged at a position where the magnetic field vectors are almost the same as shown in FIG. 29, and the accuracy of the inverse problem estimation is lowered due to noise.

On the other hand, by adjusting the distance from the head surface 200A to the gray matter (about 30 mm) to Y1 = 30 mm, which is almost the same distance, the adjacent OPM sensor 30 can detect different magnetic field vectors, which causes an inverse problem due to noise. It is possible to prevent the estimation accuracy from being lowered. When the OPM sensor 30 is attached to the sensor fixing portion 22 and the base 21 is attached to the head of the subject, the sensor fixing portion 22 is a gradiometer between the OPM sensors 30 adjacent to each other in the direction perpendicular to the optical axis. It is preferable to configure.

In the magnetic field detection device 10, the direction of the dipole Di1 formed in the central groove 300 is likely to be substantially the same as the optical axis of the OPM sensor 30, so that the magnetic field generated by the magnetic field is different in the vertical direction. Likely to happen. This is because leaving 30mm about by OPM sensor 30 direction of the magnetic field vector are adjacent, because the difference signal Z ₀ direction (the normal direction of the scalp) becomes remarkable.

On the other hand, there is no significant difference between adjacent objects in the direction parallel to the optical axis (X ₀ ). Further, in the case of the direction parallel to the optical axis (X ₀ ), the central groove 300 may not be directly below the OPM sensor 30 but may be arranged between the adjacent OPM sensors 30, and the position of the dipole Di1 may be changed. The distance may be approximately the same as that of the adjacent OPM sensor 30. At that time, the signal from the brain is removed by misunderstanding the external noise.

Further, as shown in FIG. 27, the distance between the adjacent OPM sensors 30 is larger in the direction (Y ₀ ) perpendicular to the optical axis. However, even if the distance is large, the removal effect on the large global noise applied to the plurality of OPM sensors 30 is large, and the possibility of erroneously removing the brain signal is low. From the viewpoint of noise reduction, the distance between the adjacent OPM sensors 30 is preferably larger than the distance between the OPM sensor 30 and the gray matter.

By the way, since the SQUID sensor is generally arranged in the dewar of liquid helium, the distance from the signal source is large. The coil of the SQUID sensor is oriented in the direction of detecting the magnetic field rising vertically from the scalp. Generally, the suction point and the sweep point are identified, and the position is detected with the image that a dipole exists in the middle point. This is also due to the fact that the SQUID sensor and the signal source are separated from each other and the change in the vector direction is slow. For example, there is an attempt to detect the triaxial direction with a SQUID sensor, but it has not been useful because the magnetic field vector is slow.

On the other hand, the OPM sensor 30 does not require a dewar of liquid helium, and the distance from the OPM sensor 30 to the scalp is about 30 mm smaller than that of the SQUID sensor. A distance of 30 mm has little influence on deep parts such as the brain stem, but it has a great influence on positions close to the scalp such as white matter.

For example, in a deep groove such as the central groove 300, the position is considered to be about 20 mm from the head surface 200A. The central part of the brain is about 100 mm from the head surface 200 A, and the temporal lobe is about 200 mm. For example, in the case of the OPM sensor 30, the distance from the OPM sensor 30 to the white matter is about 25 mm, and the distance to the brain stem is about 105 mm.

On the other hand, in the case of the SQUID sensor, the distance from the SQUID sensor to the white matter is about 55 mm, and the distance to the brain stem is about 135 mm. In terms of ratio, the OPM sensor 30 is close to 2.2 times in the case of white matter, but it is close to 1.3 times in the brain stem. Since the magnetic field strength is the square of the distance, the difference is large.

Further, as shown in FIG. 30, muscles such as the frontalis muscle 303 also become a large noise source. The SQUID sensor 30X, which has a large distance from the head surface 200A, is more susceptible to noise than the OPM sensor 30.

As shown in FIG. 31, since the OPM sensor 30 is closer to the head surface 200A than the SQUID sensor 30X, the change in the vector direction is sharp. In other words, it can be said that the value of handling the magnetic field vector has come out for the first time by using the OPM sensor 30. This is the first effect found by the inventors. By limiting the estimated area to white matter using the OPM sensor 30, highly accurate detection is possible.

As explained with reference to FIG. 29, if the distance between the adjacent OPM sensors 30 is shorter than that of the gray matter which is the signal source, the change in the vector is small and it is buried in noise and is not worth it. As described with reference to FIG. 27, if the distance between the adjacent OPM sensors 30 is short, for example, when the distance is 30 mm or less, the internal coils interfere with the adjacent OPM sensors, and crosstalk occurs.

That is, if the distance between the OPM sensors 30 adjacent to each other is shortened more than necessary, the signal source estimation accuracy deteriorates. Here, since the distance to the white matter is about 30 mm, when the distance between the sensors is 15 mm, the vector is tilted to about 45 ° and can be detected remarkably. However, even if the price approaches further, there is not much change. Further, crosstalk occurs around 20 mm. From these, it can be said that it is preferable that the distance between the adjacent OPM sensors 30 is larger than the distance between the OPM sensor 30 and the gray matter.

That is, when the OPM sensor 30 is attached to the sensor fixing portion 22 and the base 21 is attached to the head of the subject, the distance between the adjacent sensor fixing portions 22 is the sensor fixing portion 22. It is preferably positioned relative to the base 21 so that it is greater than the distance between the subject and the gray matter in the subject's brain structure.

When targeting motor areas such as rehabilitation and somatosensory areas, it is desirable to target the gray matter on the brain surface, especially the central sulcus. Brodmann's brain map "field b" is important in the sense of rehabilitation, which coincides with the side wall of the central sulcus 300. To aim at this part, the distance from the scalp is about 30 mm, which is the optimum value of the distance between adjacent OPM sensors.

Therefore, when the OPM sensor 30 is attached to the sensor fixing portion 22 and the base 21 is attached to the head of the subject, the sensor fixing portion 22 causes the OPM sensor 30 to move to the Brodmann area 3b of the central groove of the subject. It is preferably positioned relative to the base 21 so that it is located directly above the field.

The OPM sensor 30 of the magnetic field detection device can detect the activated region of the brain (the region where the firing of nerve cells has occurred). However, since the signal is very weak and noisy, it is necessary to make the signal as large as possible in order to improve the spatial resolution. It is expected that the Brodmann area 3b area, which is anatomically understood by MRI and is projected with information from the tip of the finger and the skin, has the largest nerve cell firing. The arrangement of the OPM sensor 30 is determined using the MRI image of the subject as an index.

In addition, the Brodmann area 3b often covers the widest area of the side wall of the central groove 300. That is, the sensitivity can be maximized by arranging the OPM sensor 30 that targets the side surface of the central groove 300.

Further, it is known that the Brodmann area 3b area is the area where the irritation from the skin at the tip of the finger is most prominent. There is a laser beam as a method of stimulating the skin of the finger. It is well known that C fiber stimulation and Aσ fiber stimulation are performed by laser light and measured by a magnetoencephalograph of a SQUID sensor. This is described in detail in, for example, the non-patent document "Journal of the Japan Pain Clinic Society Vol11 No1 (2004) p1 (Ryusuke Kakigi)". By using the laser beam, it is possible to give skin irritation without generating magnetic field noise. A very clean signal can be obtained by repeatedly stimulating and averaging the fingertips in the Brodmann area 3b area.

(Stimulator)
In the magnetic measurement, there is also a method of detecting a spontaneous signal, but in the present embodiment, the stimulator 440 is used to stimulate the subject from the outside, and the evoked signal generated at that time is detected. Examples of the stimulus given by the stimulator 440 to the subject include electrical stimulus and laser stimulus.

In this embodiment, for example, a method of applying electrical stimulation to the median nerve is used. For electrical stimulation of the median nerve, for example, "electromyogram, evoked potential tester MEB9400 series Neuropack S1" manufactured by Nihon Kohden can be used.

The position of the wrist and the elbow portion are often used as the stimulation site, but in the present embodiment, the elbow portion is used as an example. By selecting the elbow part, the stimulation part can be installed outside the magnetic shield box, so noise can be reduced.

Further, in order to monitor the amount of evoked current that can be used as a reference when determining the amount of evoked stimulus current, it is preferable to install a surface electrode pad at the position of the finger and detect the signal. At this time, in order to avoid artifacts due to muscle contraction, it is preferable that the stimulation intensity is equal to or lower than the action potential threshold.

(Analysis method (inverse problem estimation))
Next, a method of estimating the activation region from the measurement results will be described. As a forward problem calculation, an electromagnetic field simulation of a magnetic field distribution in which dipoles are installed at arbitrary locations can be performed. In the forward problem calculation, assuming the head model of the subject, a dipole is generated at an arbitrary position of the head model, and the magnetic field generated at the position of the OPM sensor 30 is calculated.

Here, the forward problem calculation is to calculate the theoretical value of the magnetic field that will be measured on the scalp, assuming the activity source in the brain and the head model. In the forward problem calculation, assuming the head model of the subject, a dipole is generated at an arbitrary position of the head model, and the magnetic field generated at the position of the OPM sensor 30 is calculated. That is, assuming a dipole at an arbitrary position in the brain, the magnetic field generated by the dipole is calculated at the position of the OPM sensor 30. At this time, the OPM sensor 30 detects the magnetic field of the subject's head as a vector, and in the forward problem calculation, the magnetic field generated at the position of the OPM sensor 30 is calculated as a vector.

In the electromagnetic field simulation, the Biot-Savart equation may be calculated according to the position of the current. At this time, the shapes of white matter, white matter, cerebral spinal fluid, skull, muscle layer, and scalp obtained by prior information such as MRI of the head are modeled as a head model. Then, the magnetic permeability is introduced into each part as a parameter, and the magnetic permeability distribution of the head model is set. This makes it possible to simulate the magnetic field distribution generated when an electric current flows through a nerve.

As a result of this simulation, the sensitivity distribution is obtained from the calculation result of the forward problem. The sensitivity distribution plots the rate at which the magnetic field of each vector of the OPM sensor 30 detected in the process of detecting the magnetic field perceives the influence from the dipole generated from which position in the subject's brain. It was done.

Let φ (rs) be the magnetic field at the rs position formed by the dipole generated at the position rs. At this time, since the dipole is generated by having the directionality, φ (rs) has the vector information of the direction. φ (rs) is a vector value. Further, for example, if the observed value at the position rd where the OPM sensor is arranged is φ (rd), this is also a vector value having a directional component of the magnetic field.

The following equation (1) that connects these two variables is defined. Further, the equation (2) can be obtained by modifying the equation (1).

Here, A (r) is a sensitivity and can be described as a distribution including the position dependence of r. A (r) has vector information.

The sensitivity distribution of a general magnetoencephalograph is defined by a scalar, and converting this into a vector is an advantage of using the OPM sensor this time, and because the amount of information is enormous, the accuracy of inverse problem estimation is improved. improves. Once this sensitivity distribution is determined, the observed value (magnetic field vector) detected by the generated dipole and OPM sensor can be calculated. A simple description of this is given by the following equation (3).

Here, X is a magnetic field vector defined by the position and direction of the dipole, A (r) is the sensitivity distribution, and the magnetic field measurement result at that time is Y. Y is a function of the position and the magnetic field vector, and means the magnetic field observation value at the position of the OPM sensor.

In the inverse problem estimation, the reverse is performed, that is, X, which is the position and direction of the dipole, is estimated using the observed value Y. In general, an inverse problem estimation method called L2 norm regularization is used. In this method, X that minimizes the cost function C of the following equation (4) is calculated.

Here, Y is the observed value, A is the sensitivity distribution, and λ is the regularization coefficient. As a result, if the observed value (magnetic field distribution) can be measured, the current distribution at that time can be estimated. A detailed inverse problem estimation method is described in, for example, Japanese Patent No. 3730646. The position of the dipole can be estimated with high accuracy by the above inverse problem estimation.

(Procedure for measuring biomagnetic field)
FIG. 32 is an example of a flowchart showing a procedure of biomagnetic field measurement using the biomagnetic field measurement system 400.

First, in step S11, the doctor or the like arranges a vitamin material or the like as a marker on the face of the subject. After that, a doctor or the like operates the MRI imaging unit 420, and the MRI imaging unit 420 images the head of the subject and generates MRI image data of the three-dimensional structural shape of the brain. The MRI imaging unit 420 transmits the generated MRI image data to the information processing device 410. The MRI imaging unit 420 also images parts that serve as position markers such as the ears and eyes of the subject. In addition, the MRI imaging unit 420 also images a vitamin material or the like which is a marker arranged before the measurement. In addition, the position where the vitamin material or the like is placed is marked on the skin in advance with a pen or the like.

Next, in step S12, the doctor or the like installs a magnetic marker on the subject. Specifically, a magnetic marker that generates magnetism is installed at the same position as the vitamin material or the like that serves as the marker arranged in step S1 (position marked on the skin with a pen or the like in advance).

Next, in step S13, the doctor or the like measures the head circumference of the subject and selects a head gear type magnetic field detection device 10 having an appropriate size. At this point, the OPM sensor 30 is not installed in each sensor fixing portion 22 of the magnetic field detection device 10.

Next, in step S14, the doctor or the like visually attaches the selected magnetic field detection device 10 to the subject's head and visually observes that the marker installed in the central portion of the magnetic field detection device 10 is in the center of the eyebrows. Confirm.

Next, in step S15, the OPM sensor 30 is installed in each sensor fixing portion 22 of the magnetic field detection device 10.

However, instead of steps S14 and S15 described above, the OPM sensor 30 is attached to each sensor fixing portion 22 of the magnetic field detection device 10, and then the magnetic field detection device 10 to which the OPM sensor 30 is fixed is attached to the head of the subject 200. It may be attached to the part.

In any of the above cases, in the step of detecting the magnetic field in step S16, the optical axis of the OPM sensor 30 is arranged substantially parallel to the normal direction of the side surface of the central groove in the brain structure of the subject. The base 21 of the magnetic field detection device 10 is attached to the head of the subject.

It is preferable that the base 21 of the magnetic field detection device 10 is attached to the head of the subject so that the OPM sensor 30 is arranged directly above the Brodmann area 3b field of the central groove of the subject. At this time, the OPM sensor 30 may be arranged at a position where the subject is stimulated and the strongest signal is obtained.

Next, in step S16, a doctor or the like applies a current having a specific frequency to the coil of the magnetic marker. Then, the magnetic field detection device 10 measures the magnetic field generated by the magnetic marker and transmits the measurement result to the information processing device 410.

Next, in step S17, the signal processing unit 411 detects the position of the magnetic marker by inverse problem estimation or the like based on the measurement result of the magnetic field generated by the magnetic field by the magnetic field detection device 10, and the detection result is the data storage unit 413. Store in.

Next, in step S18, the signal processing unit 411 includes the position of the vitamin material and the like included in the MRI image data transmitted from the MRI imaging unit 420, the sensor position data transmitted from the three-dimensional measurement unit 430, and the magnetic marker. Based on the detection result of the position of, the head coordinates of the OPM sensor 30 of the magnetic field detection device 10 and the head coordinates of the MRI image are matched, and a brain model is created and stored in the data storage unit 413.

Next, in step S31, a doctor or the like operates the three-dimensional measurement unit 430, and the three-dimensional measurement unit 430 is a plurality of OPM sensors 30 installed in the magnetic field detection device 10 mounted on the head of the subject. Measure the position. The three-dimensional measurement unit 430 measures the position of the OPM sensor 30 by imaging a plurality of markers 40 installed on each OPM sensor 30. The three-dimensional measurement unit 430 transmits the sensor position data to the information processing device 410.

For 3D measurement of the position of the OPM sensor 30 (position of the marker 40), there are various methods such as a method using a plurality of 3D cameras for motion capture and a method using a handy stereo camera type for a stationary shape. Exists. For example, Eva manufactured by Artec, which is a method using a handy stereo camera type, can be selected. Eva has a resolution of 0.5 mm, an angle range of 30 ° × 21 °, and a weight of 0.85 kg.

For example, as shown in FIG. 33, a plurality of stereo cameras 250 are arranged around the head of the subject 200, and the position of the OPM sensor 30 is measured three-dimensionally. When three markers 40 are installed on the OPM sensor 30, if there are 64 OPM sensors 30, the number of markers 40 is 192. By measuring from a plurality of places with the stereo camera 250, there is no marker 40 that cannot be measured because the wiring 35 or the like is in the way.

Next, in step S19, the signal processing unit 411 determines the positions of all the OPM sensors 30 based on the sensor position data acquired in step S31. Then, the signal processing unit 411 calculates the forward problem based on the position of the OPM sensor 30 and the MRI image data acquired in step S11.

Next, in step S20, the signal processing unit 411 calculates the sensitivity distribution by 1 for each OPM sensor 30 and each vector direction, and stores the calculation result in the data storage unit 413. In a general magnetoencephalograph, this sensitivity distribution and forward problem are calculated by the amount of scalars. In the present embodiment, the sensitivity distribution and the forward problem are calculated by the vector quantity, which is significantly different from the conventional method.

Next, in step S32, the doctor or the like inputs an instruction to start magnetic field measurement by operating the information processing device 410. As a result, the magnetic field detection device 10 starts the magnetoencephalography measurement of the subject.
The measurement result is transmitted to the information processing device 410. The information processing device 410 stores the measurement result obtained from the magnetic field detection device 10 in the data storage unit 413.

Next, in step S33, the doctor or the like attaches the electrode of the stimulator 440 to the elbow or the like of the subject 200 during the magnetoencephalography measurement by the magnetic field detection device 10, and operates the stimulator 440 to operate the subject. Start stimulating 200 elbows and the like. A doctor or the like may attach the electrode of the stimulator 440 to the fingertip of the subject 200 to stimulate the subject 200. During this period, the magnetic field detection device 10 continues the magnetoencephalography measurement of the subject and transmits the measurement result to the information processing device 410.

Next, in step S34, the doctor or the like operates the stimulator 440 after a predetermined time elapses to end the stimulus to the subject 200.

In step S35, the doctor or the like inputs an instruction to end the magnetic field measurement by operating the information processing device 410. As a result, the magnetic field detection device 10 ends the magnetoencephalography measurement of the subject. All the measurement results of the magnetic field detection device 10 are stored in the data storage unit 413.

Since the subject 200 is stimulated during the magnetoencephalography measurement by the magnetic field detection device 10, the difference between when the stimulation is applied and when the stimulation is not applied can be detected.

Next, in step S21, the signal processing unit 411 reads out the calculation result of the sensitivity distribution obtained in step S20 and the measurement result of the magnetic field detection device 10 obtained in step S35 from the data storage unit 413, and performs inverse problem estimation. The activated region (activated region) of the brain is detected. Then, the information processing device 410 stores the detection result of the activation region in the data storage unit 413 and records the data.

In the inverse problem estimation step of step S21, the shapes of white matter, white matter, cerebrospinal fluid, skull, muscle layer, and scalp obtained by prior information are modeled, and the position of the estimated dipole is limited to white matter. The signal when the subject performs the task (exercise) may be recorded and recorded, and the signal source may be estimated based on the signal. In this case, by limiting the estimated dipole position to white matter, highly accurate detection becomes possible.

Next, in step S22, the display control unit 412 reads out the data of the detection result of the activation region stored in the data storage unit 413, and transmits a display signal to the display device 480. The display device 480 displays the detection result of the activation region based on the signal of the display control unit 412.

In the present embodiment, since the detection of the OPM sensor 30 is a vector and the sensitivity distribution is also a vector, the amount of information is much larger than that of the scalar, and the detection accuracy of the activation region can be improved. By displaying the activation area and observing the state in the case of rehabilitation, feedback can be given to the subject, and efficient rehabilitation becomes possible. It is preferable to detect the position with the magnetic marker between the magnetoencephalography measurements and confirm that the positions of the head and the magnetic field detection device 10 are not displaced.

As described above, in the present embodiment, the magnetic field distribution generated from the position estimated as the signal source is extended not only to the conventional intensity distribution but also to the vector distribution.

Specifically, when a dipole is assumed, the magnetic field distribution generated around it is derived from a simple Biot-Savart equation. Assuming that the position of this dipole appears for all voxels in the region used for calculation, the sensitivity distribution shows the distribution of sensitivity in each measured value.

This sensitivity distribution also has three sensitivity distributions of vectors (that is, X, Y, Z) at each position instead of a scalar when deriving for each detection position. That is, the amount of information is tripled. In order to hold this sensitivity distribution for each vector and make effective use of it, it is necessary to detect the detected value as well. By triple the amount of information, the detection accuracy can be improved.

(Neurorehabilitation)
As is clear from the above description, the biomagnetic field measurement system 400 can be used as an activation region estimation system using the inverse problem estimation of the OPM sensor 30. In the following, rehabilitation using this activation area estimation system will be described. Generally, the method of measuring brain function and performing rehabilitation is called neurorehabilitation. The details are omitted here because they are published on the website of the Japan Agency for Medical Research and Development.

For example, the OPM sensor 30 is installed in a severely paralyzed patient who has difficulty in bending and stretching his / her fingers due to the sequelae of stroke to detect the activated region of the brain. When the patient imagines moving his or her fingers in the head, the nerve cells in the part that controls the movement of the brain are ignited, and an activated area is generated. Contraction of the muscles that stretch the fingers is observed.

Generally, when the affected area is near the central sulcus of the brain, motor function is impaired. However, due to the plasticity of the brain, alternative functions are formed around it. It is known that when the alternative function is not matured, the activation area is very wide and the reproducibility is low by the image.

That is, it is desired to localize the activation region and improve the reproducibility in the process of maturing the alternative function. Based on this policy, points will be given to the activation area, and the points will be provided to the subjects at any time. As a result, the subject can know the quality of the image when he / she makes an image of moving his / her finger each time. This act of giving feedback makes rehabilitation dramatically more efficient.

FIG. 34 is a flowchart illustrating the rehabilitation method according to the present embodiment. Step S41 in FIG. 34 is a step in which the subject exercises. First, a doctor or the like attaches the magnetic field detection device 10 to the subject's head and encourages the subject to exercise. Then, the subject starts exercising. The exercise referred to here also includes the image of exercise by a subject who has difficulty in exercising.

In step S42, the necessary steps shown in FIG. 32 described above are executed, and the signal processing unit 411 estimates the activation region of the brain that changes due to the movement of step S41 as an inverse problem. Then, the display device 480 displays the detection result of the activation region based on the signal of the display control unit 412.

Next, in step S43, the doctor or the like determines whether or not the activation region in step S42 is an appropriate region.

If the doctor or the like determines in step S43 that the activation region estimated in step S42 is an appropriate region (YES), the process proceeds to step S44, and the determination result in step S43 is used as the subject. After transmitting to, steps S41 to S43 are repeated again.

On the other hand, if the doctor or the like determines in step S43 that the activation region estimated in step S42 is not an appropriate region, the determination result in step S43 is not transmitted to the subject, and steps S41 to S41 to 2 again. Repeat S43.

In neurorehabilitation using a general electroencephalograph, the effect is limited because it is a level that detects only the timing at which the subject exercises. In addition, it has been reported that neurorehabilitation using fMRI is highly effective because it can detect the activation region with high accuracy and can determine whether or not the activation region is at the correct position.

However, since fMRI puts the body in a large device, the behavior is limited, and moving the head reduces the detection accuracy. Further, since fMRI is a change in cerebral blood flow, it becomes a secondary signal, the response speed is poor, and it is known that it takes 10 seconds or more from the firing of nerve cells to the activation of the change in blood flow.

The feedback response to the stimulus is also very slow and does not provide effective feedback. Also, even when averaging the data, the stimulation for 1 minute is about 1 period, and the amount of information is insufficient. Therefore, it has been required to have a response speed of about several hundred msec for detecting a primary signal of a nerve cell like an electroencephalograph, and a high spatial resolution (about 1 mm) for detecting an activated region at an fMRI level. The magnetoencephalograph using the SQUID sensor has both spatial resolution and response speed, but it is highly constrained to the subject and cannot move the head or body.

On the other hand, in the rehabilitation method according to the present embodiment shown in FIG. 34, since the magnetic field detection device 10 having the OPM sensor 30 is only attached to the head of the subject, the body can be easily moved. Is. In particular, it is possible to detect the motor cortex in the central sulcus of the brain with high sensitivity.

In the stationary state of the subject, when a β wave of 13 to 30 Hz is present near the central groove, the β wave weakens when the subject starts exercising. This phenomenon is called βERD (Event-Related Desynchronization). The area where this βERD is generated is called an activation area.

The activation region cannot be generated in an appropriate area in the human brain that has suffered a stroke or the like. Originally, it is localized near the central sulcus, but if there is a problem with brain function, the activation area will spread to multiple locations and a wide range.

Therefore, in the present embodiment, feedback is given to the subject using localization as an index. In other words, the index of correctness is provided to the subject only when the activation region is generated in the localized area as much as possible.

As a result, for example, in the task of moving a finger, if the finger can be moved but the activation area of the brain is a wide range, it is determined that the brain is not being used well. As a result, the fingers can be moved only by more localized brain functions.

As described above, the magnetic field detection device 10 can be easily attached to the subject and can detect the biomagnetic field with extremely high spatial resolution. In addition, the subject wearing the magnetic field detection device 10 can easily move his / her body. As a result, a rehabilitation system that can be expected to be highly effective can be realized.

(Treatment (medicinal effect) judgment)
In recent years, methods for transplanting iPS cells and methods for treating post-stroke by TMS and the like have been remarkably developed. Recently, new drugs have been developed, such as the discovery of a new drug "Ednerpic maleate" that promotes rehabilitation effect and a compound that promotes AMPA receptor synaptic translocation.

Each of these treatments takes time to realize the effect, and if there are side effects, the treatment is difficult during that period, and withdrawal occurs in the middle. In addition, even if the treatment takes a long time, it is possible that the therapeutic results cannot be sufficiently obtained with the therapeutic agents that are incompatible with each other.

Therefore, if you can start treatment and catch even a slight change, you can put up with the long treatment period after that. In other words, the ability to detect even the slightest changes in the brain has the potential to dramatically improve treatment outcomes. The magnetic field detection device 10 makes it possible to capture a slight change in cranial nerve activity near the central sulcus of the brain.

Although the preferred embodiments and the like have been described in detail above, they are not limited to the above-described embodiments and the like, and various modifications and substitutions are made to the above-mentioned embodiments and the like without departing from the scope described in the claims. Can be added.

10 Magnetic field detector 21 Base 22 Sensor fixing part 23A Screw 25 Shield 30 OPM sensor 31 Gas cell 35 Wiring 40 Marker 221 Cylindrical part 222 Head gear fixing part 223 Sensor fixing pin 224 Through hole 250 Stereo camera 300 Central groove 400 Biomagnetic field measurement system 410 Information processing device 411 Signal processing unit 412 Display control unit 413 Data storage unit 420 MRI imaging unit 430 Three-dimensional measurement unit 480 Display device

Patent No. 5823195

Claims (16)

The attachment part to be attached to the subject's head and
It has a sensor fixing portion that fixes an optical pumping atomic magnetic sensor that detects a magnetic field on the head of the subject to the mounting portion.
When the optical pumping atomic magnetic sensor is attached to the sensor fixing portion and the mounting portion is attached to the subject's head, the optical axis of the optical pumping atomic magnetic sensor is in the brain structure of the subject. A magnetic field detection device in which the sensor fixing portion is positioned with respect to the mounting portion so as to be arranged substantially parallel to the normal direction of the side surface of the central groove. The mounting portion includes an opening for ensuring the visibility of the subject, and the vector from the center of the mounting portion toward the opening direction of the opening is substantially parallel to the optical axis of the optical pumping atomic magnetic sensor. The magnetic field detection device according to claim 1, wherein the sensor fixing portion is positioned with respect to the mounting portion so as to be arranged in. When the optical pumping magnetic sensor is attached to the sensor fixing portion and the mounting portion is mounted on the head of the subject, the optical pumping atomic magnetic sensor is used by the Broadman in the central groove of the subject. The magnetic field detection device according to claim 1 or 2, wherein the sensor fixing portion is positioned with respect to the mounting portion so as to be arranged directly above the region 3b field. Having a plurality of the sensor fixing portions,
When the optical pumping atomic magnetic sensor is attached to the sensor fixing portion and the mounting portion is mounted on the head of the subject, the distance between the adjacent sensor fixing portions is the distance between the sensor fixing portion and the subject. The magnetic field detection according to any one of claims 1 to 3, wherein the sensor fixing portion is positioned with respect to the mounting portion so as to be larger than the distance from the gray matter in the examiner's brain structure. apparatus. Having a plurality of the sensor fixing portions,
When the optical pumping atomic magnetic sensor is attached to the sensor fixing portion and the mounting portion is attached to the head of the subject, the sensor fixing portion is parallel to the optical axis of the optical pumping atomic magnetic sensor. The magnetic field according to any one of claims 1 to 4, wherein the sensor fixing portion is positioned with respect to the mounting portion so that the distance in the direction is smaller than the distance in the direction perpendicular to the optical axis. Detection device. Having a plurality of the sensor fixing portions,
When the optical pumping atomic magnetic sensor is attached to the sensor fixing portion and the mounting portion is attached to the head of the subject, a gradiometer is provided between the optical pumping atomic magnetic sensors adjacent to each other in a direction perpendicular to the optical axis. The magnetic field detection device according to any one of claims 1 to 5, which comprises the above. A biomagnetic field measurement system including the magnetic field detection device according to any one of claims 1 to 6 and a stimulator that stimulates a subject.
The stimulator is a device that stimulates the subject with a laser beam, and is a biomagnetic field measurement system including a holder for laser light irradiation that can be attached to the finger tip of the subject. The biomagnetic field measurement system according to claim 7, wherein the stimulator is a device that gives a stimulus for generating a dipole in the somatosensory area to the subject. It has a magnetic shield box that covers only the subject's head.
The biomagnetic field measurement system according to claim 7 or 8, wherein the stimulator is arranged outside the magnetic shield box. It has a step of detecting the magnetic field of the head of the subject who wears the mounting part to which the optical pumping atomic magnetic sensor is fixed.
In the step of detecting the magnetic field, the mounting portion is arranged so that the optical axis of the optical pumping atomic magnetic sensor is arranged substantially parallel to the normal direction of the side surface of the central groove in the brain structure of the subject. A magnetic field detection method worn on the subject's head. In the step of detecting the magnetic field, the mounting portion is the head of the subject so that the optical pumping atomic magnetic sensor is arranged directly above the Broadman region 3b field of the central groove of the subject. The magnetic field detection method according to claim 10, which is mounted on the above. Assuming the head model of the subject, a dipole is generated at an arbitrary position of the head model, and a magnetic field generated at the position of the optical pumping atomic magnetic sensor is calculated.
It has an inverse problem estimation step of estimating the position of the dipole based on the detection result in the step of detecting the magnetic field and the calculation result in the forward problem calculation step.
In the step of detecting the magnetic field, the optical pumping atomic magnetic sensor detects the magnetic field of the subject's head as a vector.
The magnetic field detection method according to claim 10 or 11, wherein in the forward problem calculation step, the magnetic field generated at the position of the optical pumping atomic magnetic sensor is calculated as a vector. In the inverse problem estimation process,
The shape of the white matter, white matter, cerebral spinal fluid, skull, muscle layer, and scalp obtained by prior information is modeled, the estimated position of the dipole is limited to white matter, and the subject performs the task. The magnetic field detection method according to claim 12, wherein a signal is recorded and recorded, and a signal source is estimated based on the signal. The influence of the magnetic field of the optical pumping atomic magnetic sensor detected in the step of detecting the magnetic field from the dipole generated from any position in the brain of the subject based on the calculation result in the forward problem calculation step. The magnetic field detection method according to claim 12 or 13, further comprising a step of obtaining a sensitivity distribution indicating how much the magnetic field is perceived. It has a step of detecting the position where the optical pumping atomic magnetic sensor is arranged.
The invention according to any one of claims 10 to 14, wherein the optical pumping atomic magnetic sensor is arranged at a position where the subject is stimulated and the strongest signal is obtained prior to the step of detecting the position. Magnetic field detection method. The mounting portion to which the optical pumping atomic magnetic sensor was fixed was attached to the head so that the optical axis of the optical pumping atomic magnetic sensor was arranged substantially parallel to the normal direction of the side surface of the central groove in the brain structure. The first step of estimating the activation area of the brain, which changes depending on the movement of the subject, as a reverse problem,
It has a second step of determining whether or not the activation region is an appropriate region.
When it is determined in the second step that the activation region is an appropriate region, the determination result in the second step is transmitted to the subject, and then the first step and the second step are performed again. repetition,
When it is determined in the second step that the activation region is not an appropriate region, the first step and the second step are performed again without transmitting the determination result in the second step to the subject. Repeated rehabilitation technique.

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