JP2016211936A - Optical sensor, optical inspection equipment, analyte inside information measurement method, and analyte inside characteristic estimation method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an optical sensor capable of having high resolution without lowering loadability into an analyte.SOLUTION: An optical sensor comprises: an irradiation system including a plurality of light source modules LM having a light source for irradiating the same position of an analyte with a plurality of beams of non-parallel light; a control part which controls the light source; and a detection system which detects light emitted by the irradiation system and propagated in the analyte. A light source module LM further has an optical system including a lens and a prism arranged on an optical path of light from the light source and emitting a plurality of beams of non-parallel light to the same position, and at least one light receiving element which receives part of each of the plurality of beams from the optical system. The control part controls the quantity of light emitted by the light source on the basis of the quantity of light received by the light receiving element.SELECTED DRAWING: Figure 6

Description

  The present invention relates to an optical sensor, an optical inspection apparatus, a subject internal information measurement method, and a subject internal property estimation method, and more specifically, an optical for irradiating a subject with light and detecting the light propagated through the subject. The present invention relates to a sensor, an optical inspection apparatus including the optical sensor, a subject internal information measuring method using the optical sensor, and a subject internal property estimating method.

  2. Description of the Related Art Conventionally, a biological light measurement device that irradiates a subject (living body) with light and detects light propagated through the subject is known (see, for example, Patent Document 1). In this biological light measurement apparatus, the pitch of a plurality of probes (probes) attached to the subject is reduced to obtain high resolution.

  However, the biological optical measurement device disclosed in Patent Document 1 cannot achieve high resolution without deteriorating the attachment property to the subject.

  The present invention provides an irradiation system including at least one light irradiator having a light source that irradiates a plurality of non-parallel light beams on the same position of a subject, a control unit that controls the light source, and an irradiation system that emits light from the irradiation system. A detection system that detects light propagated in the subject, and the light irradiator is disposed on an optical path of light from the light source, and emits a plurality of non-parallel lights toward the same position. And at least one light receiving element that receives a part of each of the plurality of lights from the optical system, and the control unit emits light from the light source based on the amount of light received by the light receiving element. An optical sensor for controlling the amount.

  According to the present invention, it is possible to obtain high resolution without deteriorating the attachment property to the subject.

It is a figure for demonstrating schematic structure of the optical inspection apparatus which concerns on 1st Embodiment of this invention. It is a figure for demonstrating the water tank for phantoms. It is a figure for demonstrating the layout of a transparent window. FIG. 3 is a diagram (No. 1) for describing a schematic configuration of a light source module according to Embodiment 1; 2 is a diagram for explaining a schematic configuration of a detection module according to Embodiment 1. FIG. FIG. 3 is a second diagram illustrating a schematic configuration of the light source module according to the first embodiment. FIG. 7A to FIG. 7C are diagrams for explaining specific examples (No. 1 to No. 3) of arrangement of a plurality of light receiving elements, respectively. It is a figure for demonstrating the signal processing in the control part with respect to the output signal of four light receiving elements. It is a figure for demonstrating the ideal incident position to the passage part of a light spot. FIGS. 10A to 10C are diagrams (No. 1 to No. 3) for explaining the positional deviation of the light spot incident on the passing portion and the light receiving element, respectively. It is a figure for demonstrating the in-vivo propagation angle. It is a figure for demonstrating the method to confirm whether several non-parallel light is irradiated to the same object. It is a flowchart for demonstrating the method to measure the information in a subject. It is a flowchart regarding an inverse problem estimation algorithm. FIG. 3 is a first diagram illustrating a sensitivity distribution in a photodiode (PD). It is a figure (the 2) which shows the sensitivity distribution in PD. It is a figure for demonstrating the in-vivo propagation angle. 18A is a diagram showing the actual position of the light absorber, FIG. 18B is a diagram showing the estimation result of the position of the light absorber, and FIG. 18C is the light absorption in the comparative example. It is a figure which shows the detection result of the position of a body. FIG. 19A is a diagram showing the actual position of the light absorber after movement, and FIG. 19B is a diagram showing the estimation result of the position of the light absorber after movement, and FIG. These are figures which show the detection result of the position of the light absorber in a comparative example. FIG. 10 is a diagram for explaining an arrangement of a plurality of light source modules and a plurality of detection modules in the optical sensor according to the second embodiment. FIG. 6 is a first diagram for explaining a schematic configuration of a light source module according to a second embodiment; It is a figure for demonstrating a surface emitting laser array chip. FIG. 6 is a second diagram illustrating a schematic configuration of a light source module according to a second embodiment. FIG. 6 is a third diagram illustrating a schematic configuration of a light source module according to a second embodiment. FIG. 6 is a diagram (No. 4) for describing a schematic configuration of a light source module according to Example 2. It is a ray diagram optically designed by an optical simulator. It is a figure which shows the result of the optical simulation in 1st Embodiment. It is a figure which shows the result of the optical simulation in a comparative example. FIG. 29A is a diagram for explaining the operation of the optical sensor of the comparative example, and FIG. 29B is a diagram for explaining the operation of the optical sensor of the first embodiment. (C-1) to FIG. 29 (C-3) are diagrams for explaining a specific example of the arrangement of the light receiving elements of the optical sensor according to the first embodiment. It is a graph which shows the relationship between the incident angle from the air to a biological body, and the propagation angle in a biological body. It is a graph which shows the relationship between the incident angle from resin to a biological body, and the propagation angle in a biological body. FIG. 6 is a first diagram for explaining a schematic configuration of a detection module according to a second embodiment; FIG. 6 is a diagram (No. 2) for describing a schematic configuration of a detection module according to the second embodiment. FIG. 6 is a third diagram illustrating a schematic configuration of a detection module according to the second embodiment. 6 is a flowchart for explaining an optical characteristic detection method (position measurement method) according to the second embodiment. It is a figure which shows the estimation result of the inverse problem estimation in Example 2. FIG. It is a figure for demonstrating the effect | action of the optical sensor of 1st Embodiment. It is a flowchart for demonstrating the optical characteristic detection method (position measurement method) of 2nd Embodiment. It is a figure for demonstrating arrangement | positioning of the several light source module and several detection module in the optical sensor of 3rd Embodiment. It is a figure for demonstrating the emission direction of each light source module and the detection direction of each detection module in the optical sensor of a comparative example. FIG. 41A is a diagram for explaining the emission directions of the four groups of the surface emitting laser array chip of the fourth embodiment, and FIG. 41B is the diagram of the four arrays of the PD array of the fourth embodiment. It is a figure for demonstrating the detection direction of PD, FIG.41 (C) is a figure for demonstrating arrangement | positioning of four light receiving elements. It is a figure for demonstrating the emission direction of each light source module and the detection direction of each detection module in the optical sensor of 4th Embodiment. It is a block diagram which shows the structure of a control part. It is a block diagram which shows the structure of a calculation part.

<< First Embodiment >>
Hereinafter, a first embodiment of the present invention will be described with reference to the drawings. FIG. 1 shows a schematic configuration of an optical inspection apparatus 100 according to the first embodiment. The optical inspection apparatus 100 is used for diffuse optical tomography (DOT) as an example. DOT is a technique for estimating optical characteristics inside a subject by irradiating the subject (scattering body) such as a living body with light and detecting the light propagated in the subject. In particular, by detecting blood flow in the brain, it is expected to be used as an auxiliary device for differential diagnosis and rehabilitation of depressive symptoms. In DOT, when the resolution is improved, the function of the brain can be understood in detail. Therefore, many research institutions are actively researching to improve the resolution.

  As shown in FIG. 1, the optical inspection apparatus 100 includes an optical sensor 10 including a light source module LM having a plurality of light emitting units and a detection module DM, a control unit, a display unit, a calculation unit, and the like. The control unit is configured as shown in the block diagram of FIG. In the control unit, the switch unit is controlled by the information from the central processing unit A-1, and the LM to emit light is selected. At this time, the current supplied to the LM via the switch unit is controlled to a desired value by the current control unit. The detection result (data) in DM is A / D converted, and an arithmetic process such as an averaging process is performed in the arithmetic unit (A-2). The calculation results in the calculation unit (A-2) are sequentially recorded in the recording unit (A-3).

  In the present specification, the light source module LM and the detection module DM are also referred to as probes when not distinguished from each other. In addition, in this specification, the words “pseudo living body”, “living body”, and “subject” are used as appropriate, but the pseudo living body and living body are still specific examples of the subject.

  The optical sensor 10 can be generally used as a sensor for detecting a light absorber in a subject, but the subject having the highest utility value is a living body. However, in general, it is not always easy to detect the position of the bloodstream (absorber) in a living body using an optical sensor. If the subject is a living body, it is difficult to confirm the effect (detection accuracy) of the optical sensor 10.

  Therefore, in this embodiment, a pseudo-living body (also referred to as a phantom) that is a cloudy liquid in a water tank is adopted as a subject that has versatility and allows easy detection accuracy.

  Hereinafter, Example 1 of the present embodiment will be described.

<Example 1>
In the first embodiment, a method is adopted in which a plurality of light beams from a light source are deflected by a prism so that an incident angle to a subject is different among the light beams.

  Here, as shown in FIG. 2, transparent windows made of a transparent acrylic plate are provided at eight locations on one side wall (+ Z side wall) of a water tank in which each wall is made of a black acrylic plate. The inside of the water tank is filled with an intrapid aqueous solution (intrapid 10% concentration diluted 10 times). That is, the simulated living body used in Example 1 is an intralipid aqueous solution.

  Black ink is dropped into the aqueous solution filled in the water tank so as to be about 20 ppm, so that the absorption coefficient and the scattering coefficient are almost the same as those of the living body. Then, a black light-absorbing body imitating blood flow is submerged in this cloudy intrapid aqueous solution. The light absorber is a sphere having a diameter of about 5 mm as black polyacetal. In order to control the position of the sphere, the sphere is fixed to a thin metal rod having a diameter of 1 mm connected to the automatic stage. The probe is accurately positioned and attached to each transparent window of the water tank.

  Here, the volume of the water tank is 140 mm × 140 mm × 60 mm. The thickness of the black acrylic plate is 4 mm. The eight transparent windows are composed of two types of circular transparent windows A and B. There are four transparent windows A and B. The diameter of the transparent window A is 9 mm, and the diameter of the transparent window B is 12 mm. The thickness of each of the transparent windows A and B is 1.5 mm.

  FIG. 3 shows the layout of eight transparent windows. The eight transparent windows are arranged in a lattice pattern at equal intervals in the X direction and the Y direction so that the transparent windows A and B are adjacent to each other. Here, a detection module DM is attached to each transparent window A, and a light source module LM is attached to each transparent window B (B1 to B4). The distance between the centers of two adjacent transparent windows is 30 mm.

  As shown in FIG. 4, the light source module LM includes a surface emitting laser array chip having a plurality of light emitting units (surface emitting lasers), a lens disposed on an optical path of light from the surface emitting laser array chip, A prism disposed on an optical path of light through the lens; a ceramic package (not shown) on which a surface emitting laser array chip is mounted; a flexible substrate (not shown) on which an analog electronic circuit is mounted; and the flexible substrate A wiring and a connector portion (not shown) connected to each other, a housing in which these components are accommodated, and a transparent resin that is provided on the optical path of light through the prism in the housing and contacts the subject. Four light receiving elements disposed on the optical path of a part of the light between the window member (light transmitting member) and the prism and the window member (FIG. 4 shows only two of the four light receiving elements. And) Four light receiving elements including a substrate (not shown) are mounted. Examples of each light receiving element include a photodiode and a phototransistor.

  Therefore, in the light source module LM, the amount of light from the surface emitting laser array chip is monitored by the sum signal of the four light receiving elements and fed back to the control unit so as to obtain an appropriate amount of light. The control unit keeps the output of the surface emitting laser array chip constant by driving each light emitting unit of the surface emitting laser array chip with an appropriate current value via a power supply unit (not shown) based on the fed back information. be able to.

  The light source module LM is mounted in a state where the window member is in contact with the subject (transparent window B) from the + Z side.

  As shown in FIG. 5, the detection module DM includes a black resin casing, a contact member made of an elastic body attached to the front end (−Z side end) of the casing, and a diameter accommodated in the casing. It is configured to include a 3 mm hemispherical lens (divided lens) and a 4-divided PD array (in which four photodiodes (PD) are arranged in an array). An aperture (opening) is formed at the tip of the housing and the contact member. The detection module DM is mounted in a state where the contact member is in contact with the subject (transparent window A) from the + Z side. FIG. 5 shows only two of the four PDs (light receiving units).

  The split lens is disposed in the vicinity of the + Z side of the aperture. Therefore, the light irradiated from the light source module LM to the subject and propagated through the subject enters the split lens through the aperture, and is refracted and emitted in a direction according to the incident position and the incident direction to the split lens. (See FIG. 5).

  The 4-division PD array is arranged on the + Z side of the division lens. Therefore, the light passing through the split lens is incident on one of the four light receiving portions (PD) of the quadrant PD array according to the traveling direction (the emission direction from the split lens). In this way, the detection module DM can classify the incident angles of the light incident from the subject into four angle ranges.

  The control unit detects the amount of light received by the four PDs (light receiving units) of the detection module DM mounted on each transparent window A (the total amount of light received by 16 PDs), converts it to a voltage using an operational amplifier, and records it. To record. The data is detected at a sampling rate of 1 msec, and the values measured for 20 sec are averaged. In one measurement, 16 PD data are acquired.

  Next, the light source module LM will be described in detail. As the light source of the light source module LM, a 40-channel surface-emitting laser array chip, that is, a surface-emitting laser array chip having 40 VCSELs (surface-emitting lasers) as light-emitting units is employed.

  On the optical path of the light from the surface emitting laser array chip, a lens having a diameter of 3 mm that makes the light substantially parallel is disposed (see FIG. 6). The optical axis of this lens is parallel to the Z axis. The distance between the emitting surface (light emitting surface) of the surface emitting laser array chip and the principal point of the lens (optical center of the lens) is set equal to the focal length f (for example, 9 mm) of the lens. That is, the surface emitting laser array chip is arranged so that the emission surface is located at the focal position of the lens. The “lens focal length” is the distance between the principal point of the lens and the focal point.

  Therefore, when, for example, 40 channels (40 VCSELs) of the surface emitting laser array chip are simultaneously turned on, a part of the light deflected by the reflecting surface of the prism is irradiated to the subject, and another part of the light (remaining part) At least a part) is irradiated to four light receiving elements (see FIG. 6). FIG. 6 shows only two light receiving elements. Here, the four light receiving elements include light (for example, light having a relative intensity of N% to 100% in the cross section of the light beam) including principal rays (central light beam having the maximum light intensity in the Gaussian distribution) among the light beams from the prism. ) And the surrounding light (for example, light having a relative intensity of 0% to N% in the cross section of the light beam) is irradiated, that is, the central portion of the light spot (for example, the relative intensity of the light spot is N% to 100% portion) is allowed to pass through and is arranged around the rotation axis described later so that the peripheral portion (for example, the portion where the relative intensity of the light spot is 0% to N%) is irradiated (see FIG. 9). Note that N is preferably 5% to 40%, and more preferably 10% to 35%.

  The control unit monitors the sum signal of the four light receiving elements and adjusts the output of the surface emitting laser array chip to a desired output. Here, the total output is adjusted to be about 50 mW. Light emitted from the surface emitting laser array chip and transmitted through the lens is deflected by a prism as shown in FIG.

  Here, in the light source module LM, the window member is attached to the casing so as to close the opening provided in the casing. Therefore, the light including the principal ray (the central portion of the light spot) out of the light flux from the prism passes through the opening of the housing and the window member and is irradiated to the subject.

  As the prism, an acrylic one having a refractive index equivalent to that of the acrylic water tank is employed. The reflecting surface of the prism is designed according to the diameter of the prism, and the angle of the reflecting surface is set so that light through the lens enters the acrylic water tank at an incident angle of about 50 °.

  The difference in refractive index between the water tank and prism acrylic and the phantom (intrapid aqueous solution) is set so that the propagation angle in the phantom is about 60 ° (θ1 in FIG. 6) according to Snell's law. The surface emitting laser array chip, the lens, and the prism are attached to a rotation stage (not shown) that can rotate around a rotation axis extending in the Z direction. Here, the rotation axis of the rotary stage passes through the opening (window member) of the housing. Hereinafter, the rotation axis of the rotation stage is also simply referred to as “rotation axis”. A surface emitting laser array, a lens, and a prism are also collectively referred to as an “irradiation unit”.

  FIGS. 7A to 7C show views of the light source module LM viewed from the water tank inner side. The four light receiving elements are arranged around the rotation axis (between the prism and the window member) in the housing.

  In the example shown in FIG. 7A, the four light receiving elements include two light receiving element pairs each including a pair of light receiving elements arranged substantially symmetrically with respect to the rotation axis. In the two pairs of light receiving elements, the alignment directions of the light receiving elements are orthogonal to each other.

  More specifically, the four light receiving elements have four coordinates (X1, 0), (X2, 0), (0, Y1), (0, Y2) when the XY coordinates of the rotation axis are (0, 0). ) Individually arranged (where X2 = −X1, Y2 = −Y1). Therefore, in the following, the four light receiving elements are also referred to as X1, X2, Y1, and Y2.

  The four light receiving elements are provided separately from the rotary stage and do not rotate even when the rotary stage rotates. Although the number of light receiving elements is preferably four, the number is not limited to four and may be plural.

  In addition, if the light receiving element is disposed at a position where the peripheral portion of the light spot from the surface emitting laser array chip is irradiated, and the amount of light from the surface emitting laser array chip and the position of the light spot can be detected, the light receiving element is disposed. May not necessarily be symmetrical with respect to the axis, and the shape of the light receiving element may be different as shown in FIG. 7B, or an odd number of light receiving elements may be used as shown in FIG. 7C. good. Further, the number of light receiving elements is not limited to a plurality, and may be one.

  The flow of signal processing in the control unit for the output signals of the four light receiving elements will be described with reference to FIG. First, part of light from the surface emitting laser array chip is incident on the four light receiving elements X1, X2, Y1, and Y2. Each light receiving element generates an electrical signal corresponding to the amount of light received. A signal from each light receiving element is transmitted to the control unit. The control unit monitors the optical output of the surface emitting laser array chip using the signal (SX1 + SX2 + SY1 + SY2) obtained by summing the output signals SX1, SX2, SY1, SY2 of the four light receiving elements X1, X2, Y1, Y2. The drive current of the surface emitting laser array chip is adjusted so that the output becomes a desired value.

  As shown in FIG. 9, the light receiving elements X <b> 1 and X <b> 2 are arranged at positions where the outer peripheral portion of the light spot is irradiated. Here, since the amount of light incident on the detection module DM through the subject is weak, guiding a large amount of light to the subject is a major premise for improving the accuracy of DOT. The amount of light incident on each light receiving element is preferably 5% or more and 25% or less of the entire light spot, and in the first embodiment, the light receiving elements are arranged to be 12.5%. Here, the light receiving elements X1 and X2 arranged in the X direction have been described, but the same applies to the light receiving elements Y1 and Y2 arranged in the Y direction.

  Further, as shown in FIG. 8, the difference between the output signals of two light receiving elements arranged symmetrically about the axis is obtained by the control unit, so that the deviation between the center of the light spot and the rotation axis can be detected. In the first embodiment, SX1-SX2 and SY1-SY2 are optical output differences. For example, when the light spot center is on the rotation axis as shown in FIG. 10A, SX1-SX2 = 0, but the light spot center is on the left side of the rotation axis as shown in FIG. 10B. When shifted to (+ X side), SX1−SX2> 0, and as shown in FIG. 10C, when the center of the light spot is shifted to the right side (−X side) from the rotation axis, SX1−SX2 <0. Although the X direction has been described here, the same applies to the Y direction.

  By rotating the rotary stage and the irradiation unit together, the incident angle and direction of light to the prism can be changed. Here, as shown in FIG. 11, the four directions of + X, −X, + Y, and −Y are sequentially measured around the rotation axis of the rotary stage. That is, 16 measurements of 4 × 4 are performed in the positions of the four light source modules LM (four locations B1 to B4) and four directions. Between the window member and the water tank, gel-like resin (not shown) having the same refractive index is interposed (preferably filled). Thereby, refraction and reflection of light between the window member and the water tank can be prevented. Note that the exit surface of the prism may be exposed and the exit surface may be brought into contact with the water tank (subject). Also in this case, refraction and reflection of light between the prism and the water tank can be prevented by interposing (preferably filling) a gel-like resin having the same refractive index between the prism and the water tank.

  Thus, in each light source module LM, it is possible to irradiate a plurality of non-parallel lights to the same position of the subject by rotating the irradiation unit.

  Next, a method for confirming whether or not a plurality of non-parallel light is actually applied to the same position of the subject will be described. In FIG. 12, P and Q representatively represent two lights deflected by the prism in the -Y direction, and R representatively represents the light deflected by the prism in the + Y direction.

  Three light-emitting units that are P, Q, and R light-emitting sources are individually caused to emit light, and SY1-SY2 is measured for each light emission, and the deviation of the light spot in the Y direction is compared. If the variation in the amount of deviation is within the range where there is no problem at the same position (for example, within a range of several mm), it can be determined that a plurality of non-parallel lights are irradiated at the same position.

  On the other hand, if it is determined that the amount of deviation of a plurality of lights that are non-parallel to the required detection accuracy is large and the same position is not irradiated, rotation of the surface emitting laser array chip using a position adjusting device (not shown) Position adjustment on the stage can be performed, and the amount of displacement and the direction of displacement can be stored as parameters to correct the influence of the displacement during simulation. Although the Y direction has been described above, the same argument holds for the X direction.

  As the position adjusting device, for example, any device having at least one of a configuration in which the surface emitting laser array chip is moved along the XY plane on the rotary stage and a configuration in which the surface emitting laser array chip is rotated around the Z axis may be used. Specifically, a stage that can move on the rotary stage along the XY plane and that can rotate about the Z axis can be mentioned.

  The position adjustment by the position adjustment device is performed so that the deviations of the light spots in the X direction and the Y direction of all the non-parallel light beams are within the same range as the same position.

  Although it is ideal that the light spot centers of all the non-parallel light beams are on the rotation axis, in reality, it is difficult because the optical system requires high-precision optical axis adjustment and mounting accuracy.

  Here, as long as the light spot centers of all the non-parallel light beams are at the same position in the XY plane, they may be displaced from the rotation axis, and high mounting accuracy is not required for the light receiving elements.

  That is, it is only necessary that the shift amount and the shift direction in the XY plane from the rotation axis at the center of the light spot of all the non-parallel light beams are the same, and the shift amount is not necessarily zero.

  In other words, it is only necessary that | SX1-SX2 |, | SY1-SY2 |, SX1-SX2 and SY1-SY2 are substantially equal among a plurality of non-parallel lights.

  Next, a method for measuring information in the subject will be described with reference to the flowchart shown in FIG. First, a probe is set (step T1). The probe means the detection module DM and the light source module LM as described above. The probes to be set here are four detection modules DM and one light source module LM. The four detection modules DM are individually attached to four transparent windows A having a diameter of 9 mm shown in FIG. One light source module LM is mounted on the transparent window B1 shown in FIG. Next, the current value is set by the control unit so that the emission intensity (output) is about 50 mW in total based on the sum of the output signals of a plurality of (for example, four) light receiving elements (step T1.5). . Thereafter, the 40 channels (light emitting units) of the light source module LM are caused to emit light simultaneously (step T2). Also, during measurement, feedback is made in real time so that a constant light amount is always obtained by a plurality of light receiving elements. As a result, variations in the amount of light caused by the surface emitting laser array chip can be suppressed, the S / N ratio of the measurement system is improved, high-accuracy NIRS measurement is possible, and high resolution is achieved. If the probe density is increased to increase the resolution, the number of probes is increased, and it takes time to mount the probe. However, in the first embodiment, the resolution is increased without increasing the probe density, that is, without impairing the mountability. be able to. In DOT, it is assumed that the probe is mounted on the head and measurement is performed. At that time, it is necessary to scrape the hair and mount the probe on the scalp. End up.

  The light emission time is about 20 sec. During this period, the detection values of the PDs of the four detection modules DM are read (step T3), and several data (detection values) detected at 1 msec intervals are averaged. Then, the averaged detection value, that is, the average value of the detection values is stored in the recording unit (step T4). Here, the measurement is performed in four directions of + X direction, + Y direction, -X direction, and -Y direction (steps T5 and T6). Specifically, steps T2 to T4 immediately after step T1 are performed with the irradiation unit arranged in the + X direction. Next, the irradiation unit is rotated to the + Y direction (step T6). In this state, steps T2 to T4 are performed. Next, the irradiation unit is rotated to the −X direction (step T6). In this state, steps T2 to T4 are performed. Next, the irradiation unit is rotated to the −Y direction (step T6). In this state, steps T2 to T4 are performed.

  Next, the mounting position of the light source module LM is sequentially changed from the transparent window B1 to B2, B3, and B4, and the four directions are measured again (steps T7 and T8). Thereafter, the position of the light absorber is moved, and measurement is again performed at four mounting positions of the four light source modules LM (steps T9 and T10).

  The stored data is the light absorber, and the data without is the following r (s, i, n) (i = 1, 2, 3... M, n = 1, 2, 3... K). ), R (0, i, n) (i = 1, 2, 3... M, n = 1, 2, 3... K). i is a number assigned to each detection module DM. n is a number assigned to each group. Next, each difference Δr (i, n) is calculated.

  Hereinafter, a method for calculating the position of the light absorber (the optical characteristic of the simulated living body) from the measurement result obtained by the measurement method based on the flowchart of FIG. Here, an inverse problem estimation algorithm is used. When solving the inverse problem, first, measurement and simulation are performed, and a sensitivity distribution is created using the forward problem. And the data which performed the next measurement are taken in and an inverse problem estimation is performed from the value (refer step S21-S25 of FIG. 14). FIG. 44 shows a block diagram of the calculation unit. Information such as the position of each module (probe) used in the previous Monte Carlo simulation, the refractive index, and the shape of the living body is recorded in the recording unit (B-1). Based on this information, the previous order problem is performed. For this calculation, a GPU (multi-graphics processor) capable of parallel calculation is used. By using this, the calculation can be made much faster than the conventional calculation speed. The sensitivity distribution obtained by the calculation is stored again in the recording unit (B-1). The calculation result and the measurement result stored in the recording unit (A-3) are input to the central processing unit (B-3), and inverse problem estimation is performed in the central processing unit (B-3). The estimation result is displayed on the display unit via the central processing unit (A-1) (see FIG. 43).

  By the way, conventionally, it has been considered that light is scattered almost isotropically in a scatterer such as a living body when calculating a forward problem. For this reason, simulations using diffusion equations with a small amount of calculation have been used. However, in recent academic societies and the like, it has been reported that light propagation in a living body has anisotropy in a fine area of mm. In order to perform a simulation reflecting this anisotropy, it is necessary to use a transport equation or perform a Monte Carlo simulation.

  In the present embodiment, since the light emitted from the light source is deflected and incident on the subject, the information on the incident angle cannot be reflected in the diffusion equation that is generally used. Although a method using a transport equation has been proposed, it is known that this calculation takes an enormous amount of time.

  Therefore, in this embodiment, Monte Carlo simulation is adopted. Monte Carlo simulation is a technique for probabilistically expressing the conditions under which photons are scattered in a scattering medium using random variables and observing their macroscopic behavior. Specifically, each time a photon moves through a medium and travels a certain distance, it collides, and modeling is performed so that the directionality is changed by the collision. An average value of a certain distance at this time is an average free path, which is defined by a scattering coefficient, and a change in direction is defined by anisotropy g. Repeat this collision and record how it propagates within the defined area. The light behavior of the scattering medium can be simulated by calculating countless photons modeled in this way. The path through which one photon diffuses is recorded by Monte Carlo simulation.

The Monte Carlo simulation in the present embodiment, the number of photons is 10 ^9, the voxels as 1mm cubes, the calculation of three-dimensional area of 120mm × 120mm × 60mm. Here, the scattering coefficient of the scattering medium, the absorption coefficient, anisotropy, ^{7.8 mm} -1 refractive index respectively is almost equal numbers and the ^scalp, 0.019 mm -1, and 0.89,1.37. The above-described phantom (intralipid aqueous solution) is prepared so as to match this numerical value, and simulation is performed under the same conditions as the phantom, such as the light source module LM, the propagation angle, and the position of the detection module DM, and the sensitivity distribution is calculated.

At this time, the number of photons that have passed with respect to the position r of the voxel is φ ₀ (r). In particular, when the position of the light source module LM is rs, the number of photon passages at the voxel position r is φ ₀ (rs, r). Next, the light source module LM is arranged at the position where the detection module DM has been arranged, and the same number of photons is calculated again. When the detection module DM is installed at rd, the number of photons passing at the voxel position r is set to φ ₀ (r, rd).

Since the light path is reversible, this product is proportional to the number of photons that pass through the voxel position r, exit the light source module LM, and enter the detection module DM. The product obtained by normalizing this product with all the photon numbers φ ₀ (rs, rd) entering the detection module DM is the following sensitivity distribution A (r).

  This sensitivity distribution A (r) indicates the degree of influence on the detection amount at the position r. When a light absorber is generated at the position r of the voxel, it indicates how much the detection value changes due to the generation.

  An example of the sensitivity distribution calculated as described above is shown in FIG. Here, the light source module LM and the detection module DM are arranged at (X, Y, Z) = (45, 60, 0) and (X, Y, Z) = (75, 60, 0), respectively. Since a voxel is a 1 mm cube, it is equivalent to a unit mm of these numerical values. The sensitivity of the voxel at each position is indicated by a logarithm (common logarithm) with a base of 10.

  Next, FIG. 16 shows the result of extracting the line of Y = 60, Z = 10 in voxel (x, y, z) from FIG. 15 and plotting the sensitivity as the vertical axis and the horizontal axis as the x position. ing. At this time, as a propagation angle, the results when the angle with respect to the X axis on the plane with the Y axis as a normal line is set to + 60 ° and −60 ° are shown in FIG.

  As shown in FIG. 16, there is a difference in sensitivity distribution between +60 degrees and −60 degrees. This difference is a guideline for whether the resolution can be improved. That is, the difference in sensitivity distribution indicates that the propagation paths of light from the two light sources are different. If the propagation path is the same, even if the propagation angle is changed, the sensitivity distribution should be almost the same. Because the propagation paths of light from the two light sources are different, the light from the two light sources collects different information.

  This creates great value for the inverse problem estimation described later. As described above, the propagation of light is not simple isotropic scattering, but has a slight anisotropy in the order of several mm. This difference in the order of several millimeters is considered to be a factor for realizing the inverse problem estimation having a resolution of the order of several millimeters. This sensitivity distribution is performed under the conditions of all propagation angles / detection angles for all light source module LM / detection module DM pairs implemented in the phantom.

  Next, inverse problem estimation is performed using this sensitivity distribution.

Assuming that the change in absorption coefficient δμ _a (r) caused by the presence of the light absorber is sufficiently small, the following equation is established by approximation of Retov.

ν is the speed of light in the medium, S is the amount of light emitted from the light source module LM per unit time, rs is the position of the light source module LM, rd is the position of the detection module DM, and φ (rs, rd) is the light source module It represents the quantity of light emitted from the LM reaches the detection module DM, phi ₀ represents the intensity of light in the absence of light absorbing material. This equation means that if the light intensity φ _{0 in} the absence of the light absorber is given, the change in absorption coefficient δμ _a (r) caused by the presence of the light absorber and the observed value log φ (rs, rd) ) Can be linked to a linear relationship.

This can be simply described as:
Y = A (r) X

  Here, Y is a change in the observed value due to the presence or absence of the light absorber, and X indicates a change in the absorption coefficient at the position r of the voxel. A (r) is a sensitivity distribution. In the above equation, it can be seen how the observed value Y changes by giving changes in the position and amount of the light absorber represented by X.

  In the inverse problem estimation, the reverse is performed, that is, the position X of the light absorber is estimated using the observed value Y. As described in the previous position measurement method, the change due to the presence or absence of the light absorber is measured as Δr (i, n). This Δr (i, n) becomes the observed value Y, and X is calculated from this.

In general, an inverse problem estimation method called L2 norm regularization is used. In this method, X that minimizes the cost function C shown below is calculated.

Here, Y is an observed value, A is a sensitivity distribution, and λ is a regularization coefficient. Such a method is generally used for inverse problem estimation, but in this embodiment, inverse problem estimation is performed by Bayesian estimation that can also detect the depth direction. For the inverse problem estimation by Bayesian estimation, T. Shimokawa, T. Kosaka, O. Yamashita, N. Hiroe, T. Amita, Y. Inoue, and M. Sato, "Hierarchical Bayesian estimation improves depth accuracy and spatial resolution of diffuse optical tomography, "Opt. Express * 20 *, 20427-20446 (2012)
Are described in detail.

  As a result, an estimation result as shown in FIG. 18B can be derived. FIG. 18A shows the position of the light absorber. The grid in FIG. 18B is 3 mm, and it was found that the grid matches the actual position with an accuracy of 3 mm. As a comparative example, the result of detection using only one of the four directions is shown in FIG. This comparative example has almost the same configuration as a conventional NIRS (DOT) apparatus. In the comparative example, the detection in the depth direction is impossible, and the detection result is very wide.

  In Example 1, it is possible to detect the position and depth of the light absorber by the Bayesian estimation. In addition, FIG. 19B shows a result of estimation (estimation result) by changing the position of the light absorber (see FIG. 19A). Also in this case, it can be seen that the actual position of the light absorber can be accurately estimated. According to the method of Example 1, the position of the light absorber can be detected with high resolution. On the other hand, in the comparative example, as shown in FIG. 19C, the light absorber is considerably spread, and the position of the light absorber cannot be accurately detected.

  In the first embodiment, since the light quantity of the surface emitting laser array chip can be kept constant constantly by the plurality of light receiving elements arranged on the light path between the prism and the window member, there is no light receiving element. Compared to the case, it can be detected with higher resolution. In the past, the light amount was calibrated in advance, the current value at which the desired light amount was obtained was measured in advance, and the current value was kept constant. However, the amount of light became unstable with time due to the heat generated by the laser itself, and the resolution was lowered. In the first embodiment, as described above, it is possible to adjust the light amount after probe setting, monitor the light amount, and set the current value of the drive current to the surface emitting laser array chip so that the light amount is always constant. Become.

Hereinafter, Example 2 of this embodiment will be described. In the description of the second embodiment, a description related to the first embodiment will be given as appropriate.
Example 2
First, black ink is dropped to about 200 ppm in an aqueous solution of Intrapid injected into a transparent acrylic water tank (10% concentration of Intrapid is diluted 10 times). The scattering coefficient. A black light-absorbing body imitating blood flow is submerged in this cloudy intrapid aqueous solution. The light absorber is, for example, a black polyacetal sphere having a diameter of about 5 mm. The sphere is fixed to a thin metal rod having a diameter of 1 mm connected to an automatic stage so that the position of the sphere can be controlled. The side of this water tank, the position of the probe described later, is accurately determined and installed (mounted). Here, the acrylic water tank is a rectangular water tank having a volume of 140 mm × 140 mm × 60 mm and a wall thickness of 1 mm, for example. The optical sensor 10 includes an irradiation system including a plurality (for example, eight) of light source modules LM and a detection system including a plurality (for example, eight) of detection modules DM. The plurality of light source modules LM and the plurality of detection modules DM are respectively connected to the control unit via electrical wiring.

  The control unit controls the light emission timing of the light source in each light source module LM and the detection timing in each detection module DM, and transfers the obtained detection result to the recording unit. Further, the control unit performs control to read data recorded in the recording unit, perform calculation using the numerical value, and display the calculation result on the display unit.

  As illustrated in FIG. 20, the eight light source modules LM and the eight detection modules DM are, for example, a light source module LM with respect to a pseudo living body (not illustrated) in both the X direction and the Y direction orthogonal to each other. The detection modules DM are arranged in a matrix (two-dimensional lattice) at an equal pitch a in the X direction and the Y direction so as to be adjacent to each other. In FIG. 20, LM is indicated by a square mark and DM is indicated by a circle mark. As shown in FIG. 21, the light source module LM is mounted with an optical element such as a lens or a prism, a ceramic package (not shown) on which a plurality of surface emitting laser array chips are mounted, and the ceramic package or analog electronic circuit. A flexible substrate (not shown), wiring connected to the flexible substrate, a connector portion (not shown), a housing in which these are accommodated, a window member made of a transparent resin that contacts the subject, and the like.

  As an example, the oscillation wavelength of each surface emitting laser (VCSEL) of the surface emitting laser array chip is 780 nm or 900 nm. This wavelength is selected because the absorption coefficient varies greatly depending on the oxygen concentration in the blood. In the light source module LM, as shown in FIG. 21, a surface emitting laser array chip 1 with an oscillation wavelength of 900 nm and a surface emitting laser array chip 2 with an oscillation wavelength of 780 nm are arranged in parallel, and the emission of the surface emitting laser array chip 1 is performed. A lens 1 is disposed near the end, and a lens 2 is disposed near the emitting end of the surface emitting laser array chip 2. Each surface emitting laser is also referred to as ch (channel).

  The light from each surface emitting laser array chip is refracted by the corresponding lens, deflected to a desired angle by a prism as a reflecting member formed inside the window member (reflected in a predetermined direction), and emitted outside the housing. Is done. As shown in FIG. 22, the surface emitting laser array chip has a square shape with a side of about 1 mm, and includes a plurality of (for example, 20) surface emitting lasers arranged two-dimensionally.

  More specifically, each surface emitting laser array chip has five groups (ch groups) each including four surface emitting lasers. Here, the centers of four of the five groups are individually located at the four vertices of the square, and the centers of the remaining one group are located at the center of the square.

  The four channels of each group are mounted on the ceramic package as described above, and are connected to the same electrode pad (any one of the electrode pads 1 to 4) via bonding wires (wiring).

  The ceramic package is mounted on the wiring pattern of the flexible substrate by soldering. On the flexible substrate, a switching semiconductor and a current stabilizing semiconductor are arranged. Which channel of the surface emitting laser array chip emits light is controlled by the semiconductor for switching. The switching semiconductor causes the selected channel to emit light by an external serial signal. One end of the serial signal signal line and one end of the power supply line are connected to the flexible substrate, and the other end of the signal line and the other end of the power supply line are connected to the control unit. The amount of light emitted from each channel is set to be constant by calibration performed every predetermined period. In a normal usage method, five groups of light are emitted sequentially in short pulses. Such pulsed light emission is suitable for stabilizing the amount of emitted light because temperature rise due to heat generation is avoided. By detecting and averaging the detection values obtained by the detection module each time a short pulse is emitted, detection is strong against noise.

  The reason why the surface emitting laser array chip is adopted as the light source of the optical sensor 10 will be described below. In the surface emitting laser array chip, a plurality of channels can be two-dimensionally arranged at close positions, and the light emission of each channel can be controlled independently. The traveling direction of the emitted light can be changed by installing a small lens near the ch.

  Further, in an optical sensor used for DOT, it is required to control the incident angle to the subject as accurately as possible. Since a general LED (light emitting diode) has a wide radiation angle, it is necessary to make the lens an aspherical surface in order to obtain highly accurate parallel light. In addition, a general LD (edge emitting laser) has an asymmetric radiation angle, and in order to produce highly accurate parallel light with a lens, it is necessary to combine two lenses or cylindrical lenses with different curvatures in length and width. Therefore, the configuration becomes complicated and high-precision mounting is required.

  On the other hand, the surface emitting laser has a substantially perfect far field pattern, and only one spherical lens may be arranged to produce parallel light. Further, when using coherent light emitted from the LD, speckle is generated in the subject (scattering body) where scattered light interferes with each other. This speckle pattern adversely affects measurement as noise.

  When the blood flow in the brain is viewed like DOT, the number of scattering is so large that there is no significant influence. However, the light reflected from the skin surface is affected by the return light that returns directly to the light source. The return light destabilizes the oscillation state inside the LD and prevents stable operation. Even in an optical disk or the like, when using coherent light stably, a wave plate or the like is used so that regular reflection light does not become return light. However, it is difficult to remove the return light of the reflected light from the scatterer.

  In the case of a surface emitting laser array, it is possible to simultaneously irradiate a minute area with a plurality of lights, and to reduce the return light interference (for example, refer to JP2012-127937A).

  In this embodiment (Examples 1 and 2), a convex lens (also simply referred to as “lens”) is disposed on the optical path of light from the surface emitting laser array chip (see FIG. 23).

  The diameter of the convex lens is 1 mm, and the effective diameter ε of the convex lens is 600 μm. The focal length f of the convex lens is 600 μm. The surface emitting laser array chip is a 1 mm square chip, and the distance dmax between the centers of the two most distant channels in the surface emitting laser array chip is 600 μm. Thus, by matching dmax and ε, the diameter of the convex lens can be minimized.

  Here, in the convex lens and the surface emitting laser array chip, the distance L in the optical axis direction of the convex lens between the principal point (optical center) of the convex lens and the light emitting surface (outgoing surface) of the surface emitting laser array chip is, for example, It is positioned to be 300 um. That is, f ≠ L.

  In this case, it is possible to avoid the phenomenon that light emitted from the surface emitting laser array chip and transmitted through the convex lens is regularly reflected by a prism or the like and condensed on the surface emitting laser array chip by the convex lens (return light phenomenon). it can. Thus, since no return light is generated, it is possible to stabilize the light emission quantity of each channel of the surface emitting laser array chip. However, when the influence of the return light is not taken into consideration (when high resolution is not required for NIRS), f = L may be used.

  Also, as shown in FIG. 24, the space between the convex lens and the surface emitting laser array chip is filled with a transparent resin so that no air layer is interposed. As the transparent resin, a resin having a refractive index equivalent to that of a convex lens (for example, a thermosetting epoxy resin) is used. That is, the refractive index does not change at each interface between the convex lens and the surface emitting laser array chip. The transparent resin may be molded with a mold before fixing the convex lens, or may be injected after fixing the convex lens.

  As described above, the space between the convex lens and the surface emitting laser array chip is filled with the transparent resin, so that the light emitted from the surface emitting laser array chip is reflected on the surface of the convex lens on the surface emitting laser array chip side. That is, generation of return light can be prevented. Since no return light is generated, the amount of light emitted from each channel can be stabilized. If the light quantity of each channel is stabilized, the S / N (signal / noise) ratio of the measurement system becomes good, and high-accuracy NIRS measurement and high resolution can be realized.

  As shown in FIG. 25, the convex lens is fixed to a package on which the surface emitting laser array chip is mounted via a submount. In the surface emitting laser array chip, an electrode (chip electrode) on the chip is electrically connected to a PKG electrode on the package by a wire. Since the wire has a height of about several tens of um, it is designed not to interfere with the submount. The fixed position L of the convex lens (the distance between the light emitting surface of the surface emitting laser array chip and the principal point of the convex lens) is restricted by the height of the wire. In other words, when a wire is used, it is necessary to have a structure that avoids the submount or to make the height of the wire 100 μm or less. That is, it is preferable that −100 μm <f−L <0. However, in FIG. 25, illustration of the transparent resin shown in FIG. 24 is omitted.

  The light emitted from the emission surface of the surface emitting laser is substantially circular, and its divergence angle is about 5 degrees in half width. Since a general LD beam is elliptical, it is necessary to consider an installation error in the rotation direction, but a surface emitting laser has an advantage that it is not necessary to consider it. Moreover, since it is circular, there is a merit that it is easy to perform approximation using symmetry for optical simulation used when solving an inverse problem.

  The beam emitted from the surface emitting laser is refracted by a convex lens disposed in the vicinity. The refraction angle is determined by the relative position between the surface emitting laser and the lens center (lens optical axis). Accordingly, a desired refraction angle can be obtained by appropriately setting the position of each group of the surface emitting laser array chip and the position of the lens.

  In Example 2, the relative position between ch and the optical axis of the convex lens is set so that the refraction angle is about 20 degrees. In the surface emitting laser array chip, since each channel can be controlled to emit light independently, the direction of light emitted from the light source module LM can be changed by selecting the channel to emit light.

  FIG. 26 shows an example of a ray diagram optically designed by an optical simulator. Here, three channels (light sources) imitating a surface emitting laser array chip, and a lens having a diameter of 1 mm and f = 600 μm are arranged in the vicinity of the three channels. One of the three channels is disposed on the optical axis of the lens, and the other two channels are individually disposed on one side and the other side of the optical axis of the lens. Light from ch other than ch on the optical axis is refracted by the lens, and the propagation direction (path) is bent. That is, two lights from two channels other than the ch on the optical axis are emitted in directions opposite to each other at an angle of about 20 degrees with respect to the optical axis of the lens.

  Here, the light source module LM is designed so that the incident angle of light on the subject is about 55 degrees. Specifically, as shown in FIG. 21, the light source module LM individually deflects a plurality of lights emitted from a convex lens in a direction inclined about 20 degrees with respect to the optical axis by a plurality of prisms. Therefore, the angle of each of the plurality of lights with respect to the optical axis of the lens is changed from about 20 degrees to about 55 degrees and is designed to be incident on the surface of the subject.

  Note that the prism is not limited as long as it reflects light, and for example, a glass substrate on which a metal film is formed may be used. Further, for example, a prism using a total reflection phenomenon caused by a difference in refractive index may be employed. As an example, the result of optical simulation is shown in FIG. The light beam emitted from the VCSEL is refracted by the convex lens and then enters the prism.

  Here, the material of the prism is BK7, but a general optical material may be used. The light incident on the prism is totally reflected on the side surface (reflecting surface) of the prism and is incident on the subject at an incident angle of about 55 °. That is, the light passing through the convex lens is deflected by the prism so that the incident angle of the light to the subject is about 55 °. At this time, a transparent gel is interposed between the prism and the subject in order to prevent light scattering at the interface between the prism and the subject. Here too, the plurality of lights from the surface emitting laser array chip are converted into a plurality of non-parallel lights by the convex lens, reflected by the prism, and incident on the subject. As a result, a plurality of non-parallel substantially parallel lights are incident on the same position of the subject (see FIG. 27).

  Due to Snell's law due to the refractive index difference between the prism and the subject, the propagation angle of the light beam in the subject changes from about 55 ° to about 60 °.

  In an optical system including a convex lens and a prism, the propagation angle of light in the subject can be set by utilizing the fact that the positions of the respective channels of the surface emitting laser array chip are different from each other. Here, by shifting the center of each ch (VCSEL) by about 200 μm from the optical axis of the convex lens, the propagation angle of the light emitted from the ch within the subject can be set to about 60 °. At this time, the plurality of lights emitted from the plurality of channels are emitted as a plurality of non-parallel substantially parallel lights from a plurality of positions having different exit surfaces of the convex lens.

  FIG. 28 shows, as a comparative example, the result of an optical simulation when the lens has a focal length f = 600 μm and the fixed position is L = 1.6 mm. When the difference between L and f is 1 mm or more, the beam is greatly expanded as shown in FIG. When the beam spreads as described above, it is necessary to enlarge the incident surface of the subject. However, the practical size of NIRS is about φ2 mm. This restriction is that the interval between human hair roots is about 2 mm, and in an area larger than this, the hair becomes an obstacle in terms of optics, and high-resolution NIRS cannot be realized. In other words, the difference between f and L is preferably less than 1 mm.

  The lenses 1 and 2 shown in FIG. 21 are directly fixed to the ceramic package on which the surface emitting laser array chip is mounted so that the lenses 1 and 2 are accurately and stably arranged at the designed positions.

  In FIG. 26, the convex surface of the lens is directed to the surface emitting laser side, but the reverse is also possible. As shown in FIG. 26, the distance between the surface emitting laser chip and the lens can be increased by arranging the convex surface of the lens to face the surface emitting laser and the planar portion of the lens to the subject side. it can. In the chip mounting process, it is preferable that the allowable distance is long to some extent in order to prevent interference between the arms for picking up the components and the components during mounting.

  The lens may be an optical component that refracts light, and a GRIN (Gradient Index) lens using a refractive index distribution of an optical fiber may be used. By using a GRIN lens, there is a merit that a spherical aberration is generally small, a lens having a small f value can be selected at a low cost, rather than using a spherical lens.

  In Example 2, since light is incident on the end of the lens rather than the center of the lens, it is desirable that the spherical aberration is small.

  As can be seen from the above description, the light source module LM emits a plurality of non-parallel lights (see FIGS. 21 and 27).

  A plurality of non-parallel lights from the light source module LM enter the same position of the subject (see FIGS. 21 and 27).

  For example, when the light source modules LM are arranged at an interval of about 60 mm, the “same position” means the same position with respect to the 60 mm, and a plurality of positions separated from each other by several mm is also called the same position. It does not matter. That is, “same” in “same position” is not exactly the same in the strict sense, and may be rephrased as “substantially identical” or “substantially identical”.

  An algorithm for solving the inverse problem will be described later. At that time, an optical simulation in which the position of the light source module LM is set is performed. When this optical simulation is performed, an error is not caused in the estimation of the inverse problem by accurately setting the deviation of the incident position on the subject. The same applies to a surface emitting laser array chip having a plurality of channels with different oscillation wavelengths. Even if the incident positions of a plurality of lights from a plurality of channels with different oscillation wavelengths are shifted by several mm, The incident position can be said to be the same position. In order to detect the shift of the incident positions of the plurality of lights and to monitor the light amounts of the plurality of lights, a plurality of light receiving elements are also provided in the vicinity of the emission end of the casing of the light source module LM in Example 2. (See FIG. 29C-1).

  In addition, in the light source module of the comparative example shown in FIG. 29A in which a plurality of lights parallel to each other are incident on the living body, if there is an altered portion near the surface of the living body, a detection error occurs. The “deformed portion” means a portion having special optical characteristics, such as a hair root or colored skin. If there is such an altered portion, in the comparative example, the light from the light source 1 and the light source 2 is incident on different positions of the subject. For example, only the light from the light source 2 passes through the altered portion. To do. When the difference between the light source 1 and the light source 2 is calculated, this altered portion becomes noise.

  On the other hand, in this embodiment, as shown in FIG. 29B, the light from the light source 1 and the light source 2 passes through the “same position” on the skin surface. When the light passes through the altered portion, the light from the other also passes through the altered portion. Further, when the light from one of the light source 1 and the light source 2 does not pass through the altered portion, the light from the other does not pass through the altered portion. More specifically, the light from the light source 1 and the light source 2 has the same optical path in the vicinity of the skin surface and passes through different optical paths in the depth direction. That is, although it is insensitive to the difference near the skin surface, the structure is sensitive to the difference near the brain tissue. The resolution is improved by reducing the noise near the skin surface.

  In Example 2, as shown in FIGS. 29 (C-1) to 29 (C-4), the window member provided in the housing of the light source module LM is provided with an elastic body having a light shielding property (for example). For example, a contact member made of rubber, urethane, or the like and in contact with the subject is attached. An opening is formed in the center of the contact member, and a plurality of (for example, four) light receiving elements are provided around the opening. Therefore, the light including the principal ray (the central portion of the light spot) out of the light flux from the prism passes through the opening of the housing, the window member, and the opening of the contact member and is irradiated to the subject.

  FIGS. 29C-2 to 29C-4 are schematic views in which the contact member and the four light receiving elements are partially enlarged from the subject side. In FIG. 29C-2 to FIG. 29C-4, the relative sizes of the four light receiving elements and the contact members are drawn so as to be different from the actual ones for easy understanding.

  Various modes are conceivable as the arrangement of the light receiving elements.

  For example, in FIG. 29 (C-1), four light receiving elements are arranged around the opening of the contact member so as not to protrude from the opening as viewed from the Z direction. In this case, the opening serves as an emission port (an outlet for light emitted toward the subject).

  For example, in FIG. 29 (C-2), four light receiving elements are arranged at the periphery of the opening of the contact member so that they protrude from the opening as viewed from the Z direction (partly located in the opening). Has been. In this case, a region excluding a portion of the four light receiving elements in the opening that protrudes from the opening serves as an emission port.

  For example, in FIG. 29C-3, a single light receiving element that is electrically divided into four (including four electrically separated light receiving regions) around the opening of the contact member is the opening. It arrange | positions so that the substantially whole area of the outer periphery of a part may be surrounded. In this case, since the region surrounded by the light receiving element coincides with the opening (emission port) of the contact member when viewed from the Z direction, it is substantially an emission port. In this case, the light receiving element also functions as an aperture for shaping incident light.

  In FIG. 29C-3, four light receiving elements may be used instead of one light receiving element that is electrically divided into four.

  The light receiving element can be mounted by various methods such as adhesion, film formation, and fixing.

Moreover, in Example 2, a transparent gel is dropped on the window member and the contact member provided in the casing, and the transparent gel is interposed between the window member and the contact member and the subject surface, so that air does not enter. Like that.
In the conventional light source module, light once emitted into the air propagates from the skin surface into the body. At this time, a refractive index difference occurs between the refractive index 1.0 in air and the refractive index 1.37 of the living body. Reflection and scattering occur due to the difference in refractive index. In addition, since the refractive index in the living body through which light propagates is smaller than in air outside the living body, the propagation angle in the living body (also referred to as the in-vivo propagation angle) is smaller than the incident angle. The refraction of light at the interface can be understood using the Snell equation. This Snell equation can be described only by the refractive index.

  FIG. 30 is a graph showing the refractive index, the relationship between the incident angle at the interface between 1.0 (air: incident side) and 1.37 (biological body: propagation side) and the in vivo propagation angle (light refraction). Has been. As can be seen from FIG. 30, even if the incident angle of light to the living body is 60 degrees, the propagation angle of light in the living body is as small as 40 degrees. For this reason, even if the propagation angle of light in the living body is required to be 60 degrees or more, it is understood that it cannot be realized by the incidence of light from the air. In other words, it is difficult to make a large propagation angle in the living body with the light once released into the air.

  Therefore, in Example 2, the refractive index of the transparent resin that is the material of the window member of the light source module LM is set to a refractive index (for example, 1.5 or more) that is higher than the refractive index of the living body 1.37 (FIG. 31). In this case, the propagation angle of light directly incident on the living body from the light source module LM at an incident angle of 60 degrees exceeds 70 degrees. When considering the design of the light source module LM, reducing the angle as much as possible has an advantage that the light source module LM can be reduced in size.

  In the light source module LM of Example 2 configured as described above, as shown in FIG. 21, the light emitted from the surface emitting laser array chip in the direction parallel to the optical axis of the lens is refracted by the lens, The light travels in a direction inclined by about 20 ° with respect to the optical axis of the lens and enters the window member. This window member has a refractive index of about 1.5. The light that has passed through the lens is refracted when entering the window member, but it is not a large refraction because the incident angle is deep. The light incident on the window member is deflected by the reflecting surface of the prism and travels in a direction inclined about 55 ° with respect to the optical axis of the lens. This 55 ° angle is an angle in a window member having a refractive index of 1.5, and as shown in FIG. 31, the propagation angle in the living body (refractive index of 1.37) is about 60 °. .

  In order for light to propagate directly from the light source module LM into the simulated living body, it is necessary to remove the air layer that enters the interface between the simulated living body and the light source module LM. In order to remove this air layer, a transparent gel was used here. The transparent gel used here was a glycerin aqueous solution, and the one having good consistency with the simulated living body was selected. In addition, the transparency of the transparent gel is adjusted so that it does not evaporate during the inspection, that is, while the light source module LM is covered, and is adjusted so that it volatilizes or soaks into a simulated living body at an appropriate timing after the inspection is completed. . The optical properties of the transparent gel are transparent near the wavelength of 780 nm, and the refractive index is adjusted to be close to the surface of the pseudo living body. Here, the refractive index was adjusted to about 1.37. With this blending, even if the surface of the simulated living body is uneven, there is no difference in the refractive index of the uneven surface, and there can be no reflection at all. As a result, reflection on the surface of the simulated living body could be almost eliminated. Moreover, even if the interface with the pseudo living body is physically uneven, there is no optical unevenness, so that scattering does not occur. As a result, it can be accurately propagated inside the pseudo living body in an appropriate propagation direction according to the light emission angle from the light source module LM. In general, propagation inside a pseudo-living body causes strong scattering, but the scattering on the skin surface is not small. Thereby, a large anisotropy of light can be secured. By making the anisotropy large, the incident angle of the plurality of lights from the light source module LM to the pseudo living body can be greatly changed, and the incident angles of the plurality of lights to the detection module DM are greatly changed as will be described later. Can do.

  As shown in FIG. 32, the detection module DM includes a flexible board (not shown) on which a housing, an optical element, a light receiving part, and an analog electronic circuit are mounted, wiring connected to the flexible board, and a connector part (not shown). ).

  In the detection module DM, as shown in FIG. 33, the light irradiated from the light source to the simulated living body and propagated through the simulated living body is divided into a plurality of lights and led to a plurality of light receiving units.

  In the conventional technology (see Japanese Patent Application Laid-Open No. 2011-179903), in a DOT using fluorescence, a light receiving unit is arranged corresponding to a plurality of lights emitted from a subject at multiple angles. However, in this arrangement of the light receiving unit, the light incident on the light receiving unit is light having all emission angles from the subject.

  On the other hand, the detection module DM of the present embodiment divides light from the “same position” of the subject and individually detects the light. As described in the previous light source module LM, since it can be designed at the time of optical simulation, the accuracy of “same position” does not matter in the order of mm order.

  Hereinafter, the detection module DM will be described in detail. As shown in FIG. 34, the detection module DM includes a black resin casing, a contact member made of an elastic body attached to the tip of the casing, a transparent divided lens housed in the casing, and four light receiving sections. It is comprised including. An aperture (opening) is formed at the tip of the housing and the contact member.

  As the contact member, a black rubber member is used in order to improve the light shielding property. From the aperture of the contact member, the central portion (about φ1 mm) of the split lens protrudes outside the housing by about several hundred μm. Since this portion is in contact with the surface of the living body, Fresnel refraction and scattering are suppressed without optically containing air.

  Further, in the detection module DM, since the stability is further improved by using the above-described transparent gel, the transparent gel is used. The split lens is made of a transparent resin and has a refractive index of about 1.8. The split lens is fixed to the housing.

  The aperture is a circular hole of about 1 mm, for example, that penetrates the tip of the housing and the contact member, and has a function of limiting the position of light that propagates through the subject. The light emitted from this position is directed in different directions, the incident position is defined by the aperture, and then the incident light is divided into a plurality of lights by the dividing lens, and the plurality of lights are individually detected. Can do.

  It is realized by this aperture that the light from the subject described above is incident on the light receiving unit from the “same position”.

  The light that has passed through the aperture is refracted in different directions by the split lens depending on the propagation direction of the light, and therefore the incident position on the light receiving unit is different.

  The split lens is a spherical lens having a diameter of about 3 mm and a focal length f of about 3 mm.

  The second embodiment uses a PD array (photodiode array) including four light receiving sections (PD: photodiodes) that are two-dimensionally arranged with the number of divisions of light at the dividing lens being four.

  In FIG. 34, only two light-receiving units 1 and 2 among the four light-receiving units (PD) are shown. Here, the PD array has a square shape with a side length of about 3 mm, and each PD has a square shape with a side length of 1.4 mm. An angle θ2 as shown in FIG. 34 was defined, and the distance between the PD array and the aperture was about 5 mm.

  In FIG. 34, one surface of the split lens is a flat surface, and only one surface has a spherical surface. The plane is in contact with the simulated living body. Since the aperture position deviates from the focus position of the lens, parallel light cannot be produced, but has a function of limiting the light incident on the PD array.

  When a simple optical simulation is performed on this optical system, light of approximately −10 ° <θ2 <50 ° is incident on the light receiving unit 2, and light of approximately −50 ° <θ2 <10 ° is incident on the light receiving unit 1. I found out. That is, the light that propagates through the simulated living body and is emitted from the aperture is divided into a plurality of lights according to the emission angle, and each of the plurality of lights enters one of the four light receiving units.

  In the second embodiment, a spherical lens is used as the split lens, but it is also possible to detect a wider angle by using an aspheric lens. Since this division accuracy and the number of divisions are correlated with the estimation accuracy of the inverse problem described later, the necessary optical system is determined from the desired estimation accuracy. In this embodiment, a spherical lens and a division number of 4 are employed.

  Each PD is electrically wired and connected to an operational amplifier. A semiconductor operational amplifier is used as the amplifier, and a power supply voltage of 5 V is supplied. Since the amount of light detected is very small, the magnification of the operational amplifier is high and a two-stage amplifier configuration is adopted. Multiply about 5 digits in the first stage and about 3 digits in the second stage.

  In Example 2, a method for measuring the position of a light absorber existing in a simulated living body (method for detecting the optical characteristics of a subject) will be described with reference to the flowchart shown in FIG.

  First, the probes (light source module LM and detection module DM) are set (mounted) on the simulated living body (step S1). At this time, a transparent gel is applied between the acrylic water tank and each probe, and the probe is carefully set to a position determined by the fixing member while checking each probe so that bubbles do not enter the transparent gel. .

  The probe has 16 light source modules LM and 8 detection modules DM in total, and the light source modules LM and the detection modules DM are alternately arranged in a lattice pattern at an equal pitch (see FIG. 20). The pitch of the lattice (interval between lattice points) is 30 mm, and the interval between the light source module LM and the detection module DM is 30 mm.

  In this state, the channel of any one light source module LM is caused to emit light, the light amount is monitored by a light receiving element built in the light source module, and the light amount is adjusted to a desired light amount. Here, the light emission is performed for each group (4ch), and the current value is determined so that the light emission intensity is about 4 mW (S1.5). Further, the light amount is always monitored by the light receiving element during the measurement, and the current value is adjusted so that the light amount becomes constant. This enables highly accurate NIRS measurement, leading to higher resolution.

  In this state, the ch of any one light source module LM is caused to emit light (step S2). Light emission is performed for each group (4ch), and the current value is determined so that the light emission intensity is about 4 mW. The light emission time is about 10 msec. During this period, the detection values in all PDs are read and the data of several points detected at 1 msec intervals are averaged (step S3). Then, the averaged numerical value is stored in the recording unit (step S4). Similarly, the next group repeats light emission, measurement, and data storage for 10 msec (steps S5, S6, S1.5 to S4). In addition, in one light source module LM, the light emission of 4ch of the surface emitting laser array chip with an oscillation wavelength of 780 nm and the light emission of 4ch of the surface emitting laser array chip with an oscillation wavelength of 900 nm are sequentially performed in the same manner.

  However, in the following data processing, the two wavelengths are handled in substantially the same manner, and the measurement at the same position is simply performed twice each. When detecting a change in the original blood flow, the difference between the two wavelengths is used to detect oxyhemoglobin and reduced hemoglobin separately. In this embodiment, two surface emitting lasers having different oscillation wavelengths are used. By measuring once using the array chip, noise due to chip variation can be reduced.

  When the light emission and measurement of all the groups of one light source module LM are completed, the next light source module LM emits light (steps S7, S8, S1.5 to S4). Similarly, the light emission is sequentially performed for each group (4ch). When the light emission and measurement by all the light source modules LM are completed, the light absorber is set (steps S9 and S10). The light absorber is set using an optical stage so that the position can be accurately realized with good reproducibility. With this light absorber set, the numerical value of the PD is recorded again from the ch light emission (steps S1.5 to S9).

  The stored data is the light absorber, and the data without is the following r (s, i, n) (i = 1, 2, 3... M, n = 1, 2, 3... K). ), R (0, i, n) (i = 1, 2, 3... M, n = 1, 2, 3... K). i is a number assigned to each detection module DM. n is a number assigned to each group. Next, each difference Δr (i, n) is calculated.

  The method of calculating the position of the light absorber (the pseudo-biological optical characteristics) from the measurement result obtained by the above position measurement method is based on the measurement result obtained by the measurement method based on the flowchart of FIG. Since this is the same as the method for calculating the optical characteristics of the simulated living body, the description thereof is omitted.

  As a result, an estimation result as shown in FIG. 36 can be derived. In FIG. 36, as a comparative example, only one central group (see FIG. 22) of five groups of the surface emitting laser array chip is caused to emit light, and only the detection value of one PD among the four PDs of the PD array is obtained. The results detected using this are also shown. Other than that, numerical processing is performed in the same manner as in this embodiment. This comparative example has substantially the same configuration as a conventional NIRS (DOT) apparatus.

  In the present embodiment, it is possible to detect the position and depth of the light absorber by the Bayesian estimation. In the result shown in FIG. 36, a circle (circle) is displayed when the position of the light absorber can be detected. In the present embodiment, when the distance in the depth direction of the light absorber (here, the Z direction in FIG. 15) is increased, the distance from the light source module LM is increased, and the amount of light that can be propagated is reduced. For this reason, the detection becomes more difficult as the depth of the position of the light absorber increases. In this embodiment, detection was possible up to about 6 mm. The comparative example is a general NIRS (DOT) apparatus, and the depth direction cannot be detected even when Bayesian estimation is used. In order to detect the three-dimensional position of the light absorber including the depth with DOT with high accuracy, a high-density probe arrangement is generally required. In this embodiment, this can be realized with a low-density probe arrangement. .

  The optical sensor 10 of the present embodiment described above (Examples 1 and 2) includes an irradiation system including a plurality of light source modules LM (light irradiators) that irradiates light to a subject (pseudo living body), and the irradiation system. And a detection system for detecting light that has been propagated through the subject and each of the plurality of light source modules LM irradiates the same position of the subject with non-parallel light.

  In this case, a plurality of non-parallel light beams irradiated on the same position of the subject (scattering body) have different incident angles on the subject and follow different propagation paths (see FIG. 37).

  As a result, the amount of information obtained with respect to the inside of the subject increases, and high resolution can be achieved. Further, by increasing the resolution, it is possible to reduce the probe density (the number of probes per unit area) for the same required resolution, and to improve the mountability. That is, since it is not necessary to reduce the arrangement pitch of the probes in order to increase the resolution, the number of probes to be used can be reduced and the labor for mounting can be reduced.

  Note that the plurality of lights incident on the same position of the subject are not parallel means that the plurality of lights form an angle. That is, the presence of angles formed by a plurality of lights makes it possible to vary the propagation paths of the plurality of lights within the subject. On the other hand, if a plurality of lights incident on the same position of the subject are parallel to each other (for example, parallel to the surface normal of the subject), the propagation paths of the plurality of lights in the subject are the same. turn into.

  The optical sensor 10 further includes a control unit that controls the light source (surface emitting laser array chip) of the light source module LM. The light source module LM is disposed on the optical path of light from the light source, and includes a plurality of non-parallel light beams. And an optical system including a lens and a prism, and at least one light receiving element that receives a part of each of a plurality of lights from the optical system, and the control unit includes: The light emission amount of the light source is adjusted (controlled) based on the light reception amount of the light receiving element.

  In this case, it is possible to control the output of the surface emitting laser array chip to be constant (desired output) by monitoring the amount of light from the light source using the light receiving element, and further increase the resolution.

  As a result, according to the optical sensor 10, a high resolution can be obtained without deteriorating the mounting property to the subject.

  Further, the light source module LM includes a housing and a window member in which a light source and an optical system are accommodated, and a passage portion through which another part of light from the optical system (at least a part of the remaining part) passes is provided. The container further includes a light receiving element, and the light receiving element is provided around the passage portion of the container.

  In this case, for example, without providing a light separation element (for example, a beam splitter) that separates light from the optical system, a part of the light can be irradiated to the light receiving element and another part can be irradiated to the subject. it can. In addition, it is possible to detect the positional shift of the incident position on the light receiving element and the passage part of each of the plurality of non-parallel light from the optical system, and by adjusting the position of the light source, for example, based on the detection result, Can be increased.

  As a result, cost reduction and higher resolution can be achieved.

  In addition, since the central part of the light spot by the optical system is incident on the passage part and the peripheral part of the light spot is incident on the light receiving element, the light source is secured while ensuring a sufficient amount of light to irradiate the subject. The amount of light can be monitored.

  The housing includes a housing in which a light source and an optical system are housed and an opening through which another part of the light from the optical system is passed, and a window provided in the housing so as to close the opening. And a member (light transmission member).

  In this case, light can be emitted outside the housing while the inside of the housing is sealed. That is, it is possible to irradiate the subject with light while suppressing the entry of foreign matter into the housing.

  Moreover, since the refractive index of the window member is larger than that of the subject, the propagation angle (refractive angle) within the subject can be increased with respect to the angle of incidence on the subject. As a result, the propagation angle becomes large even at the same incident angle as compared with the case where light is incident on the subject from the air. Therefore, the difference in the propagation angle of these two lights in the subject becomes larger than the difference in the incident angles of the two lights incident at the same position on the subject at different incidence angles, so that the propagation paths are greatly different. be able to. As a result, further higher resolution can be achieved.

  In addition, since the container is provided with an opening that allows light transmitted through the window member to pass therethrough and further includes a contact member that comes into contact with the subject, only the desired location of the subject (the location where light should be irradiated) is selected. Can be irradiated with light. In addition, it is preferable that the size (diameter) of the contact member is set to a size that allows selective contact with an attachment location (for example, the scalp) in the subject.

  In addition, at least one light receiving element is a plurality of light receiving elements, and the plurality of light receiving elements are composed of a pair of light receiving elements disposed substantially symmetrically with respect to a predetermined axis (for example, the rotation axis of the rotary stage) passing through the passage portion. In the case where at least one light receiving element pair is included, it is possible to detect a positional deviation of the light spot from the predetermined axis with respect to the arrangement direction of the pair of light receiving elements of the light receiving element pair.

  Further, when the at least one light receiving region pair includes two light receiving element pairs in which the alignment direction of the light receiving elements is orthogonal to each other, the light spot from the predetermined axis of the light spot in the plane in which the two light receiving element pairs are arranged Misalignment can be detected.

  Further, at least one light receiving element is a single light receiving element including a plurality of electrically separated light receiving areas, and the plurality of light receiving areas are arranged substantially symmetrically with respect to a predetermined axis passing through the passage portion. When at least one light receiving area pair consisting of the light receiving areas is included, it is possible to detect the positional deviation of the light spot from the predetermined axis with respect to the arrangement direction of the pair of light receiving areas of the light receiving area pair.

  Further, when at least one light receiving area pair includes two light receiving area pairs in which the alignment direction of the light receiving areas is orthogonal to each other, from a predetermined axis of the light spot in the plane in which the two light receiving area pairs are arranged Can be detected.

  Further, since the light source has at least one light emitting unit group (surface emitting laser array chip) composed of a plurality of light emitting units (surface emitting lasers) arranged in an array, a small multi-light source can be configured.

  In addition, when the apparatus further includes a position adjusting device (adjusting means) that adjusts the position (XY coordinates) of the light emitting unit group (surface emitting laser array chip) based on the amount of light received by at least one light receiving element, a plurality of non-parallel elements It is possible to increase the identity of the incident position of the light on the subject, and to perform measurement with higher resolution. Instead of adjusting the position of the light emitting unit group, the position of the light spot can be adjusted by adjusting the XY coordinates of the rotation axis of the rotary stage and the optical axis of the lens using the position adjustment mechanism, and the incident position is identical. Can be increased. That is, the “adjusting unit” only needs to be able to adjust the incident position of at least one light passing portion and the light receiving element among the plurality of lights emitted from the optical system.

  Further, the optical system includes a lens that is disposed on the optical path of the plurality of lights from the light emitting unit group, and that makes the plurality of lights a plurality of non-parallel lights, and the distance between the principal point of the lens and the light source is It does not match the focal length of the lens.

  In this case, it is possible to prevent the return light from being focused on the surface emitting laser, and to prevent fluctuations in the output of the surface emitting laser. As a result, the amount of light emitted from the surface emitting laser can be stabilized, the detection accuracy of the optical sensor 10 can be improved, and the resolution of NIRS can be improved.

  On the other hand, when the surface emitting laser array is located at the focal position of the lens, the light reflected from the external reflecting surface is condensed on the surface emitting laser by the lens, and the laser oscillation becomes unstable. This is a phenomenon called return light or a self-mixing phenomenon. When a surface emitting laser array is used as a light source of an optical sensor, if this phenomenon occurs, the amount of emitted light becomes unstable and becomes a problem (detailed explanation is JP, 2011-114228, and JP 2012-132740).

  The optical system includes a prism (reflecting member) that is disposed on the optical path of light through the lens and reflects the light toward the passing portion.

  In this case, the traveling direction of light from the lens can be changed to a desired direction. That is, the incident angle to the subject can be set to a desired angle.

  Moreover, the refractive index is filled with the transparent resin equivalent to a lens between a lens and a light source.

  In this case, since the refractive index does not change at the interface between the lens and the surface emitting laser array chip, the return light can be suppressed. As a result, the amount of light emitted from the surface emitting laser array chip can be stabilized, and the resolution of NIRS can be improved.

  The detection system also includes a plurality of detection modules DM including a plurality of light receiving units (PD) that individually receive a plurality of lights that are irradiated on the subject from the light source module LM and propagated in the subject.

  In this case, two pieces of information on two different propagation paths in the subject can be obtained individually.

  In addition, the detection module DM is disposed between the subject and the plurality of light receiving units (PD), and is provided with an aperture (opening) through which a part of each of the plurality of lights propagated through the subject is passed. And a housing.

  In this case, light can be taken into the housing from the same position of the subject, that is, only light with a certain angle of incidence can be made incident from the subject into the housing, and light can be easily incident on a plurality of light receiving units. can do.

  The detection module DM has a split lens (light receiving lens) that individually guides a part of the plurality of light beams that have passed through the aperture to the plurality of light receiving units.

  In this case, a part of each of the plurality of lights that have passed through the aperture can be incident on the plurality of light receiving units individually with a stable light amount.

  In addition, the optical inspection apparatus 100 and the subject internal property estimation method according to the present embodiment estimate the internal property of the subject using the optical sensor 10.

  In this case, since the detection accuracy of the optical sensor 10 is high, the internal characteristics of the subject can be estimated with high accuracy.

  The subject internal information measurement method for measuring the internal information of the subject using the optical sensor 10 is based on the amount of light received by at least one light receiving element, and passes to a plurality of light passing portions and light receiving elements from the optical system. And a step of adjusting an incident position of at least one of a plurality of lights using an adjusting means based on a detection result in the detecting step.

  In this case, the identity of incident positions on a plurality of non-parallel light objects can be increased, and measurement with higher resolution can be performed.

  Further, in the adjusting step, since the incident position of at least one light is adjusted so that the incident positions of a plurality of non-parallel lights substantially coincide with each other, the “identity of incident positions” can be increased as much as possible.

As described above, the optical sensor 10 is an optical sensor that can achieve high resolution by effectively using light propagation anisotropy with a simple configuration, and is expected to be used in various fields such as DOT. The
<< Second Embodiment >>

  Next, a second embodiment of the present invention will be described. In the present embodiment, a method for adapting the probe described in the first embodiment to an actual human body will be described. Here, the subject is changed from the phantom (water tank containing cloudy water) in the above embodiment to the head of the human body, and the light absorber is used as the blood flow in the brain.

  The purpose of this embodiment is to accurately estimate the distribution of blood flow in the brain. In this embodiment, a subject (subject) is measured, a shape is modeled based on the data, and a Monte Carlo simulation is performed. The subject's head shape is measured using nuclear magnetic resonance imaging (hereinafter abbreviated as MRI). The shape of the four parts of the scalp, skull, cerebrospinal fluid, and cerebral cortex is measured from the image.

  This three-dimensional data is necessary for high-precision detection, but can be replaced with data such as a standard-shaped brain model. Each part has a general scattering coefficient, anisotropy, and absorption coefficient, and the numerical values are used. The probe is fixed to the head accurately with a fixing jig, and the installed position is also measured accurately. Since the probe and the like are the same as those in the first embodiment, description thereof is omitted here. An optical simulation is performed using each accurate shape, arrangement, and numerical value of each part.

  Hereinafter, a method of measuring blood flow in the brain will be described with reference to the flowchart shown in FIG. First, the subject is allowed to rest (step S31), and the probe (detection module DM and light source module LM) is set on the head. At this time, it is set (installed) carefully using a fixing member while confirming each probe so that hair or the like is not pinched between the probe and the scalp. In this state, ch is emitted, and the current value is determined so as to obtain a predetermined light amount. Here, the current value is determined so that the light intensity is about 4 mW. (Step S32.5). Next, ch is emitted (step S33). Light emission is performed for each group, and the light emission time is several msec. During that time, the detection values of all PDs are read and averaged (step S34). The averaged numerical value is stored in the recording medium (step S35).

  Similarly, the next group repeats light emission, measurement, and data storage for several milliseconds (steps S36, S37, and S32.5 to S35). When the light emission and measurement of all the light source modules LM are completed, the subject is asked to perform a task (steps S38 to S41). Here, it was a general language fluency task. The language fluency problem is described in detail in Japanese Patent Application Laid-Open No. 2012-080975.

  By performing this task, the brain is active, and cerebral blood flow occurs only where the activity occurs. The bloodstream contains oxyhemoglobin and reduced hemoglobin, and light absorption occurs by the bloodstream. Inverse problem estimation by Bayesian estimation is the same as the method described in the first embodiment, and is omitted here. The accuracy of the blood flow position obtained by this measurement can be confirmed by measurement by fMRI (functional magnetic resonance imaging). fMRI is a method of visualizing hemodynamic responses related to brain and spinal cord activity in humans and animals using MRI. From this confirmation measurement, it was found that the measurement by the optical sensor of the present embodiment has a high resolution.

<< Third Embodiment >>
Next, a third embodiment of the present invention will be described. In the third embodiment, the light source module LM and the detection module DM similar to those in the first embodiment are used for the probe, and the arrangement thereof is elaborated. Except for the arrangement of the probes, the second embodiment is the same as the first embodiment, and the description thereof is omitted here.

  By the way, in Example 2 of the first embodiment, as shown in FIG. 20, the two detection modules DM and the two light source modules LM are arranged so as to be positioned at the apex of a substantially square. However, in this arrangement, the light path between the light source module LM and the detection module DM becomes long at a point indicated by x in FIG. For this reason, a sufficient amount of light cannot be obtained by the detection module DM, and noise at this point may be large and the detection accuracy may be reduced.

  Therefore, the inventors have intensively studied the probe arrangement and found that the arrangement shown in FIG. 39 is optimal. In FIG. 39, in the plurality of light source modules LM and the plurality of detection modules DM, two of the light source module LM and the detection module DM are individually positioned at two vertices of an equilateral triangle with respect to the subject, and the other 1 Are arranged at one remaining vertex of the equilateral triangle.

  Here, as a simple example, a place where the distance between the light source module LM and the detection module DM is the longest will be considered. However, the interval (pitch) between the detection module DM and the light source module LM is assumed to be a. In FIG. 20, the broken line has a distance of √2a (about 1.414a) at the position x. On the other hand, in the position of x in FIG. 39, the distance of the broken line is (1 + √3) a / 2 (about 1.366a) <√2a. That is, comparing the probe arrangements of FIGS. 20 and 39 at the longest distance, it can be seen that the probe arrangement of FIG. 39 is shorter and preferable.

  As a result of estimating the inverse problem with this arrangement in the same manner as in the first embodiment, it was found that the detectable area was expanded by the probe arrangement of this embodiment.

<< 4th Embodiment >>
Next, a fourth embodiment of the present invention will be described. In the fourth embodiment, the arrangement of the plurality of light source modules LM and the plurality of detection modules DM shown in the first embodiment is used to arrange the ch of the light source module LM, the PD of the detection module DM, and the light source and the subject. The arrangement of a plurality of light receiving elements between the two is devised. Since these arrangements are the same as those in the first embodiment, description thereof is omitted here.

  In Example 2 of the first embodiment, as shown in FIG. 20, in the plurality of light source modules LM and the plurality of detection modules DM, the light source module LM and the detection module DM are orthogonal to each other with respect to the subject. They are arranged adjacent to each other in both the X direction and the Y direction.

  However, as described above, in this arrangement, the light path between the light source module LM and the detection module DM becomes long at the point indicated by x. For this reason, a sufficient amount of light cannot be obtained by the detection module DM, noise at this point increases, and the detection accuracy may be reduced.

  In the comparative example shown in FIG. 40, the plurality of light source modules and the plurality of detection modules are arranged so that the light source module and the detection module are adjacent to each other in the X direction and the Y direction perpendicular to each other. In addition, both the emission direction and the detection direction (light incident direction on the light receiving unit) are parallel to the X direction or the Y direction. Since the lens installed in the vicinity of the surface emitting laser has point-symmetric optical characteristics, the emission direction is determined by the position of the surface emitting laser and the group position. The detection direction is also determined by the division layout of the PD array because the lens has point-symmetric optical characteristics.

  Therefore, when the surface emitting laser array chip is arranged as shown in FIG. 41A, the emission direction is inclined with respect to the X direction and the Y direction in plan view (viewed from the + Z direction). This is because the center position of each group is inclined with respect to the lens center. Similarly, in the detection module DM, the center of the lens is arranged at the center of the 4-divided PD array array chip (photodiode array chip), so that the detection direction (light incident direction to the light receiving unit) is as shown in FIG. ) As shown. The detection direction and the emission direction are shown in FIG. 42 together with the probe arrangement. It can be seen that the emission direction and the detection direction are oblique with respect to the X direction and the Y direction in plan view (viewed from the + Z direction).

  In this case, since the light has anisotropy as in the sensitivity distribution described above, it can be expected to have more sensitivity at the position of x in FIG.

  As a result of estimating the inverse problem with the arrangement shown in FIGS. 41A and 41B in the same manner as in the first embodiment, it was found that the detectable area is widened.

  FIG. 41C shows a layout of four light receiving elements 1 to 4 in the light source module LM. Here, in addition to the rotational center of the prism (the rotational axis of the rotary stage), the light receiving element 1 and the light receiving element 3 are arranged in an axial symmetry, and the light receiving element 2 and the light receiving element 4 are arranged in an axial symmetry. 41A, the layout according to the layout of the surface emitting laser array chip, that is, the alignment direction of the light receiving element 1 and the light receiving element 3, and the alignment direction of the light receiving element 2 and the light receiving element 4 are both in the X direction and the Y direction. It is inclined with respect to it. Thereby, the detection direction of the light spot position shift (the alignment direction of the light receiving element 1 and the light receiving element 3 and the alignment direction of the light receiving element 2 and the light receiving element 4) is the incident direction of the light from the surface emitting laser to each light receiving element. Since they match, the detection accuracy of misalignment is increased.

  In each of the above embodiments, the number of light source modules LM in the irradiation system and the number of detection modules in the detection system can be changed as appropriate. In short, the irradiation system only needs to have at least one light source module LM. The detection system may have at least one detection module DM.

  Moreover, in each said embodiment, the structure of the light source module LM (light irradiation device) can be changed suitably. For example, the number and arrangement of the surface emitting laser array chips of the light irradiator can be appropriately changed. The type, shape, size, number, etc. of the lenses can be changed as appropriate.

  In each of the above embodiments, a surface emitting laser is used as a light source of the light irradiator. For example, an edge emitting laser (LD), a light emitting diode (LED), an organic EL element, a laser other than a semiconductor laser, or the like May be used.

  In each of the above embodiments, the optical system of the light source module LM has a prism. However, instead of or in addition to this, it may have another mirror or the like. In addition, the optical system of the light source module LM may be configured by only a lens, for example, or may be configured by only a reflecting member such as a prism or a mirror.

  Moreover, the number and arrangement of groups in the surface emitting laser array chip of Example 2 and the number and arrangement of ch in each group can be changed as appropriate.

  The configuration of the detection module DM (photodetector) can be changed as appropriate. For example, the aperture does not necessarily have to be provided. Further, for example, the split lens is not necessarily provided.

  Needless to say, the shape, size, material, number, dimension, and numerical value of each member and portion in the above description are merely examples, and can be changed as appropriate.

  DESCRIPTION OF SYMBOLS 10 ... Optical sensor, 100 ... Optical inspection apparatus, LM ... Light source module (light irradiation device), DM ... Detection module (light detector).

Japanese Patent No. 3779134

Claims (18)

An irradiation system including at least one light irradiator having a light source that irradiates a plurality of non-parallel light beams on the same position of the subject;
A control unit for controlling the light source;
A detection system for detecting light emitted from the irradiation system and propagated in the subject,
The light irradiator is
An optical system arranged on the optical path of the light from the light source and emitting a plurality of non-parallel lights toward the same position;
And at least one light receiving element that receives a part of each of the plurality of lights from the optical system,
The said control part is an optical sensor which controls the light emission amount of the said light source based on the light reception amount of the said light receiving element. The light irradiator further includes a housing body in which the light source and the optical system are housed, and a passage portion through which another part of each of the plurality of lights passes is provided.
The optical sensor according to claim 1, wherein the light receiving element is provided in a peripheral portion of the passage portion in the container. A central portion of the light spot by the optical system is incident on the passage portion,
The optical sensor according to claim 2, wherein a peripheral portion of the light spot is incident on the light receiving element. The container is
A housing in which the light source and the optical system are housed, and an opening through which another part of each of the plurality of lights passes is formed;
The optical sensor according to claim 2, further comprising: a light transmitting member provided in the housing so as to close the opening.   The optical sensor according to claim 4, wherein the light transmission member has a refractive index larger than that of the subject.   The optical sensor according to claim 4, wherein the container further includes a contact member that is provided with an opening through which light transmitted through the light transmission member passes and that contacts the subject. The at least one light receiving element is a plurality of light receiving elements;
The plurality of light receiving elements include at least one light receiving element pair including a pair of the light receiving elements disposed substantially symmetrically with respect to a predetermined axis passing through the passage portion. The optical sensor according to one item.   The optical sensor according to claim 7, wherein the at least one light receiving element pair includes two light receiving element pairs in which the arrangement direction of the light receiving elements is orthogonal to each other. The at least one light receiving element is a single light receiving element including a plurality of electrically separated light receiving regions;
The plurality of light receiving regions include at least one light receiving region pair including a pair of the light receiving regions arranged substantially symmetrically with respect to a predetermined axis passing through the passage portion. The optical sensor according to one item.   The optical sensor according to claim 9, wherein the at least one light receiving area pair includes two light receiving area pairs in which the arrangement direction of the light receiving areas is orthogonal to each other.   The optical sensor according to claim 7, wherein the light source includes at least one light emitting unit group including a plurality of light emitting units arranged in an array.   12. The adjusting device according to claim 11, further comprising an adjusting unit that adjusts an incident position of the light from the optical system to the light receiving element and the passage portion based on a light reception amount of the at least one light receiving element. Optical sensor. The optical system includes a lens that is disposed on an optical path of a plurality of lights from the light emitting unit group, and that converts the plurality of lights into a plurality of non-parallel lights,
The optical sensor according to claim 11 or 12, wherein a distance between the principal point of the lens and the light source does not coincide with a focal length of the lens.   The optical sensor according to claim 13, wherein the optical system includes a reflecting member that is disposed on an optical path of light through the lens and reflects the light toward the passage portion. The optical sensor according to any one of claims 1 to 14, comprising:
An optical inspection apparatus that estimates the internal characteristics of the subject using the optical sensor. A subject internal information measuring method for measuring internal information of a subject using the optical sensor according to claim 12,
Detecting a shift in the incident position of the light passing from the optical system and the light receiving element based on the amount of light received by the at least one light receiving element;
Adjusting the incident position of at least one of the plurality of lights using the adjusting means based on the detection result in the detecting step.   The object internal information measuring method according to claim 16, wherein, in the adjusting step, the incident position of the at least one light is adjusted so that the incident positions of the plurality of lights substantially coincide with each other. A subject internal property estimation method for estimating an internal property of the subject using the optical sensor according to claim 1.