JPH08103434A - Biological light measuring device and measuring method - Google Patents

Abstract

(57) [Summary] [Purpose] To separately measure local hemodynamic changes in vivo. Constitution: Light emitted from a light source 1 is irradiated onto a subject 6 from a light irradiation position 5, and light emitted through the subject 6 is detected at two different positions on the subject 6. Photodetectors 10a, 1 through the optical fibers 7a, 7b
It is detected at 0b. The electric signals from the photodetectors 10a and 10b are logarithmically converted by the logarithmic amplifiers 25a and 25b, and then input to the positive and negative electrodes of the differential amplifier 11. Differential amplifier 11
The logarithmic difference signal of the transmitted light intensity at two different positions output from is sequentially converted into a digital signal by the A / D converter 12, taken into the computer 13, and displayed on the display device 14 as time series data.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a living body light measuring device for measuring information in a living body using light and a measuring method using the same.

[0002]

2. Description of the Related Art As a conventional living body optical measuring device, an oximeter for measuring oxygen saturation in an artery (Japanese Patent Laid-Open No. 55-24).
004). The oximeter irradiates the living body with light of multiple wavelengths, measures the transmitted light intensity or the reflected light intensity from the living body, and uses the spectral characteristics of Hb and HbO ₂ and the pulse wave to measure the oxygen saturation in the artery. It is a device for calculating.

Further, as a method for measuring the oxygen saturation (average oxygen saturation including both arterial system and venous system) and the blood volume in the living tissue, a method such as Jobis et al.
115232). This method utilizes the spectral characteristics of Hb and HbO ₂ to measure oxygen saturation and blood volume (hereinafter, both are collectively referred to as hemodynamics) in living tissue. In this specification, transmitted light, reflected light, and scattered light are not particularly distinguished, and the light intensity emitted from a light source and interacting with a living body, and then detected by a photodetector is referred to as transmitted light intensity.

[0004]

With the prior art,
It is possible to measure oxygen saturation in arteries or hemodynamics in living tissues. However, it is impossible to separate the hemodynamic change due to the overall change of the living body and the hemodynamic change due to the local change of the living body by the conventional technique.

On the other hand, there are cases where it is desired to detect only changes in hemodynamics due to local changes in the living body. For example, in the brain of a living body, there are local parts that work in response to each function of the living body (hereinafter referred to as functional parts), and the blood volume or oxygen saturation of the functional part changes in response to any function of the living body. To do. At this time, if changes in blood volume or oxygen saturation of only an arbitrary functional site can be measured, the function of the functional site of the brain can be examined, which is medically very important.

As a specific example, FIG. 2 shows the time variation of the transmitted light intensity when the transmitted light intensity is measured at a point 3 cm away from the light irradiation position by irradiating the temporal region of the subject lying on his back with light. Shown in. The fluctuation of the transmitted light intensity in FIG. 2 is derived from the change in the overall hemodynamics in the living body. In this way, even when the subject is resting, an unpredictable signal change appears in the transmitted light intensity signal, and because the brain is irradiated with light from above the scalp through the skull, the activity of the brain is not affected. The signal change based on it is extremely small, and it is difficult to separate the signal even if only the local hemodynamics are changed due to activation of the functional part of the brain. An object of the present invention is to provide a technique for separating and measuring an overall hemodynamic change in a living body and a local hemodynamic change, which are difficult with the conventional techniques.

[0007]

According to the present invention, a living body is irradiated with light from any one or a plurality of places, and a local change is detected as a signal change and a local change is detected. Two detection positions, which are not measured as a signal change, are set to be equidistant from the light irradiation position, the passing light intensity is detected at each of the detection positions, and the logarithmic difference of the passing light intensity between the two positions is obtained. It is characterized by

Preferably, passing light is received at two detection positions that are equidistant from the incident position and different in position, and the intensity of the passing light at each detection position is a photoelectric conversion element such as a photodiode or a photomultiplier tube. Electrical signal (hereinafter,
After converting the electric signal that means the transmitted light intensity into a transmitted light intensity signal) and logarithmically converting each transmitted light signal intensity by a logarithmic amplifier, the transmitted light intensity signal at the first detection position and the second detection position at the second detection position are detected. The transmitted light intensity signal is differentially amplified.

The intensity of the light emitted from the light source is modulated and only the frequency component of the detection signal is extracted, so that the noise caused by the outside can be removed. An optical fiber can be connected between the light source and the light irradiation position and between the light detection position and the light detector.

[0010]

When the first detection position and the second detection position are set at positions equidistant from the light irradiation position, the transmitted light intensity signal at each detection position is changed in accordance with the overall hemodynamic change in the living body. Change equally. Therefore, by taking the logarithmic difference between the transmitted light intensity signal at the first detection position and the transmitted light intensity signal at the second detection position, the signal change due to the overall hemodynamic change is removed. Furthermore, if only the transmitted light intensity signal at one of the first and second detection positions includes a change associated with a local hemodynamic change,
The transmitted light intensity logarithmic difference signal reflects only local hemodynamic changes.

[0011] The light beam interacts with various living tissues through a complicated path from the light irradiation position into the living body to the outside of the living body at the light detection position, and is scattered and attenuated. . In the present invention, since the logarithmic difference of the light intensity emitted from the living body at a position equidistant from the light irradiation position is taken, the influence of scattering and attenuation by living tissue is canceled out, and a minute signal reflecting a local hemodynamic change is obtained. It can be detected with high accuracy.

[0012]

The present invention will be described in detail below with reference to examples. [Embodiment 1] FIG. 1 shows a schematic configuration of a first embodiment of a biological optical measurement device according to the present invention. The light emitted from the light source 1 is condensed using a lens system and is incident on the optical fiber 2 for a light source. The light emitted from the light source is intensity-modulated by the oscillator 23 at an arbitrary frequency f of about 100 Hz to 10 MHz in order to remove noise caused by external sources. Since the light source optical fiber 2 is connected to the light irradiation optical fiber 4 via the optical fiber coupler 3a, the light from the light source is transmitted to the light irradiation optical fiber 4 and irradiated to the subject 6 from the light irradiation position 5. . The wavelength of the light used depends on the spectral characteristics of the substance of interest in the living body, but when measuring the oxygen saturation or the blood volume from the concentrations of Hb and HbO ₂ , it is 600 nm to 1400.
One or more wavelengths are selected from the light in the wavelength range of nm and used. As the light source, a semiconductor laser, a titanium sapphire laser, a light emitting diode or the like can be used.

Two photodetection optical fibers 7a and 7b for detecting the light emitted after passing through the subject 6 are arranged at two different locations on the subject 6. In the present embodiment, the two optical fibers for light detection 7a and 7b are arranged at two points of point symmetry with the light irradiation position 5 as the center of symmetry. Optical fiber 4 for light irradiation and optical fibers 7a and 7b for light detection
Are fixed by an optical fiber fixing member 8 whose surface is painted black. The light irradiation optical fiber 4, the light detection optical fibers 7a and 7b, and the optical fiber fixing member 8 are integrated as a light detection probe for the sake of simplicity, and the details will be described later. Since the optical fibers 7a and 7b for light detection are connected to the optical fibers 9a and 9b for photodetector via the optical fiber couplers 3b and 3c, the passing light detected by the optical fibers 7a and 7b for photodetection is detected by the optical detector. The light is transmitted to 10a and 10b, photoelectrically converted by the photodetectors 10a and 10b, and the passing light intensity is output as the electric signal intensity. As the photodetectors 10a and 10b, for example, photoelectric conversion elements such as photodiodes and photomultiplier tubes are used.

The electric signals representing the transmitted light intensity output from the photodetectors 10a and 10b are extracted by the lock-in amplifiers 24a and 24b, respectively, only the light intensity modulation frequency component of the light source. The output from the lock-in amplifier 24a is logarithmically converted by the logarithmic amplifier 25a and then input to the negative electrode of the differential amplifier 11, and the output from the lock-in amplifier 24b is
After being logarithmically converted by the logarithmic amplifier 25b, the differential amplifier 11
Is input to the positive electrode of. As a result, the differential signal of the passing light intensity at two different positions is output from the differential amplifier 11 as an output signal. The output signal from the differential amplifier 11 is sequentially converted into a digital signal by the A / D converter 12,
The data is taken into the computer 13 and displayed on the display device 14 as time series data.

Here, as shown in FIG. 1, if the region 15 in which the hemodynamics locally changes is included only in the visual field 16b of the optical fiber for light detection, the measured logarithmic difference signal is the local region 15. It reflects only the changes in hemodynamics of. Meaning of the logarithmic difference signal to be measured will be described below on the assumption that hemoglobin, which is the main component in blood, acts predominantly on near infrared light.

Measurement time is t, light source wavelength is λ, irradiation light intensity is I ₀ (t), oxyhemoglobin and deoxyhemoglobin concentrations are C _ox (t), C _deox (t), and the oxidization is changed in the local region 15. The hemoglobin concentration and the reduced hemoglobin concentration are ΔC _ox (t) and ΔC _deox (t), respectively, and the extinction coefficients of oxyhemoglobin and reduced hemoglobin with respect to the light source wavelength λ are ε, respectively.
_{Letting ox} (λ), ε _deox (λ) be D _{s be} the attenuation due to scattering and absorption other than hemoglobin, and d be the weighting factor caused by scattering, the transmitted light intensity signal I detected by the photodetector 10b.
_d (t) is represented by the following equation (1), and the passing light intensity signal I _d '(t) detected by the photodetector 10a is represented by the following equation (2).

I _d (t) = D _s · exp [− [ε _ox (λ) (C _ox (t) + ΔC _ox (t)) + ε _deox (λ) (C _deox (t) + ΔC _deox (t)) ] d] I ₀ (t) (1) I _d '(t) = D _s · exp [− [ε _ox (λ) C _ox (t) + ε _deox (λ) C _deox (t)] d] I ₀ (t) (2) Next, after taking the natural logarithm of the equations (1) and (2),
By subtracting the expression (2) from the expression (1), the following expression (3) is obtained. The left side of the equation (3) is the measured logarithmic difference signal. ln [ _Id (t) / _Id '(t)] =-[[epsilon] _ox ([lambda]) [ _Delta ] _Cox (t) + [epsilon] _deox ([lambda]) [ _Delta ] _Cdeox (t)] d (3)

Here, in particular, the light source wavelength is 805 nm ±
When measured using 10 nm, ε _ox (805 ± 10) ≈ ε _deox (805 ± 10) (4) Therefore, the equation (3) uses the constant K to obtain ln [I _d (t) / I _d ' (t)] = − [ΔC _ox (t) + ΔC _deox (t)] · K (5) can be rewritten. Therefore, the light source wavelength is 805 nm
The logarithmic difference signal measured using ± 10 nm represents a value (hereinafter referred to as a relative blood change amount) corresponding to the change amount [ΔC _ox (t) + ΔC _deox (t)] of the blood amount. In addition, if the number of wavelengths used for the light source is set to two wavelengths (λ ₁ , λ ₂ ), different intensity modulation frequencies (f ₁ , f ₂ ) are given to each wavelength, and frequency is separated by the lock-in amplifier, then the transmitted light of each wavelength is transmitted. The intensity signal can be measured. Therefore, since the equation (3) holds for each wavelength, the simultaneous equations composed of the following equations (6) and (7) can be derived.

Ln [I _d (λ ₁ , t) / I _d ′ (λ ₁ , t)] = − [ε _ox (λ ₁ ) ΔC _ox (t) + ε _deox (λ ₁ ) ΔC _deox (t)] d (6) ln [ _Id ([lambda] ₂ , t) / _Id '([lambda] ₂ , t)] =-[[epsilon] _ox ([lambda] ₂ ) [ _Delta ] _Cox (t) + [epsilon] _deox ([lambda] ₂ ) [Delta] _Cdeox (t) ] d (7) Extinction coefficient ε _ox (λ ₁ ), ε _ox (λ ₂ ), ε _deox (λ ₁ ), ε
_{Since deox} (λ ₂ ) is known, the value ΔC _OX (t) d corresponding to the amount of change in oxyhemoglobin and the amount ΔC _deox (t) d corresponding to the amount of change in reduced hemoglobin can be _{calculated using} equations (6) and (7). ) Can be obtained by solving the equation in the computer 13, and the time series data of the obtained relative change amount is displayed as a graph on the display device 14. It is also possible to further expand to increase the number of wavelengths, eliminate d, or obtain the relative change amount of the concentration of a light-absorbing substance other than a small amount of hemoglobin.

Further, as shown in FIG. 3, without using a lock-in amplifier, a logarithmic amplifier and a differential amplifier, the photodetector 1
The detection signals from 0a and 10b are converted into A / D converters 1 respectively.
After changing to a digital signal in 2, the FFT in the computer 13
Only the signal corresponding to the intensity modulation frequency of the light source is extracted, and the logarithmic difference of the transmitted light intensity at two different detection positions is calculated in the same procedure as the above calculation process, and the calculated relative The amount of change can also be displayed as a graph on the display device 14 as time series data.

FIG. 4 shows an example of the light detection probe. FIG.
FIG. 4A shows a cross section of the light detection probe, and FIG. 4B shows a view of the light detection probe as seen from the contact surface of the subject. The light detection probe is a single optical fiber 4 for light irradiation.
And two optical fibers for light detection 7a, 7b and a metal or plastic optical fiber fixing member 8 whose surface is painted black, and optical fiber couplers 3a, 3b, 3c are connected to the respective optical fibers. To maintain the flexibility of each optical fiber, it is composed of multiple optical fibers. Plastic or quartz is used as the material of the optical fiber. When the present light detection probe is used in a living body, the subject contact surface 17 is covered with a sponge having elasticity.

The size of the detection surface of the optical fibers 7a and 7b for light detection needs to be changed according to the purpose and the state of the subject. For example, when measuring brain function, the cross-sectional shape is 1 mm to 20 mm in diameter. Circular shape or 1 mm to 2 sides
The square is about 0 mm. Further, the positions of the two optical fibers for light detection 7a and 7b are symmetrically arranged at a position of a distance r (r = 5 mm to 50 mm) from the optical fiber for light irradiation 4. By preparing a plurality of types of photo-detecting probes having different distances r and cross-sectional shapes of the photo-detecting optical fibers 7a and 7b, and exchanging them according to the purpose of measurement,
Simple measurement is possible. Since the reach depth of light is almost equal to the distance r from the light source, it is possible to measure from the surface of the head through the skull if the depth is about the cerebral cortex of the brain.

Various arrangements can be considered for the arrangement of the optical fiber 7 for light detection in the light detection probe. For example, as shown in FIG. 5, four light detection optical fibers 7a, 7b, 7 are provided at positions equidistant from the light irradiation optical fiber 4.
By disposing c and 7d, it is possible to select and measure any two optical fibers for light detection. Alternatively, a lens system may be used without using an optical fiber, or a light source or a photodetector may be directly installed on the fixing member 8.

FIG. 6 shows an example in which the optical measuring device according to the present invention is used for measuring the brain of a living body. Optical fiber coupler 3
a, 3b, 3c, optical fiber 4 for light irradiation, optical fibers 7a, 7b for light detection, and optical fiber fixing member 8
The optical detection probe consisting of a rubber fixing belt 18
It is fixed to the subject 6 with. The optical fiber 4 for light irradiation is connected to the optical fiber 2 for light source through the optical fiber coupler 3a, and the optical fibers 7a and 7b for light detection are respectively connected to the optical fibers 9a and 9b for photodetector through the optical fiber couplers 3b and 3c. Has been done. On the front panel of the optical measuring device 19, there are a connection part between the optical fiber 2 for light source and the optical fibers 9a and 9b for photodetector, an output signal adjusting knob 20, an output signal value display window 21, and a display device 14. Inside the optical measurement device 19, a differential amplifier, an A / D converter, a microprocessor, a light source, a photodetector, an optical switch, and other necessary electric circuits are arranged.

The output signal value display window 21 displays the logarithmic difference signal value of the transmitted light intensity detected at two places, and the output signal adjusting knob 20 is used to determine the offset value of the logarithmic difference signal value. For example, when there is no local change in hemodynamics inside the brain of the subject, the logarithmic difference signal of the transmitted light intensity detected at two locations is adjusted to be zero.
After that, the measurement is started, and the time series data 22 of the logarithmic difference signal is obtained.
Is graphically displayed on the display device 14. In addition, the above-described calculation is performed, and the relative change amount time change of the local blood flow amount, the oxyhemoglobin amount or the reduced hemoglobin amount is displayed in a graph.

[Embodiment 2] FIG. 7 shows a schematic configuration of a second embodiment of the biological light measuring device according to the present invention. The light emitted from the light source 1 is condensed using a lens system and is incident on the optical fiber 2 for a light source. The light emitted from the light source is set to 100 Hz by the oscillator 23 in order to remove external noise.
The intensity is modulated at an arbitrary frequency of about 10 MHz. Since the light source optical fiber 2 is connected to the light irradiation optical fiber 4 via the optical fiber coupler 3a, the light from the light source is transmitted to the light irradiation optical fiber 4 and irradiated to the subject 6 from the light irradiation position 5. . The wavelength of the light used depends on the spectral characteristics of the substance of interest in the living body, but is 600 when measuring the oxygen saturation and the blood volume from the concentrations of Hb and HbO _2.
One or a plurality of wavelengths are selected and used from the light in the wavelength range of 1 nm to 1400 nm. As the light source, a semiconductor laser, a titanium sapphire laser, a light emitting diode or the like can be used.

Four optical fibers for light detection 7a, 7b, 7c, for detecting the light emitted after passing through the subject 6.
7d are arranged at four different locations on the subject 6. In the present embodiment, two optical fibers for light detection 7b and 7c are arranged at two points of point symmetry with the light irradiation position 5 as the center of symmetry, and the center of gravity of the light irradiation position 5 is the origin and the center of gravity of the light detection optical fiber 7b is set. The light detecting optical fiber 7a is arranged so that the center of gravity of the light detecting optical fiber 7a exists on a half line passing through the points, and the center of gravity of the light irradiation position 5 is used as the origin for the center of gravity of the light detecting optical fiber 7c. The optical fiber 7d for light detection is arranged so that the center of gravity of the optical fiber 7d for light detection exists on a half line passing through the points. The center of gravity of the optical fiber 7a for detecting light and the optical fiber 7d for detecting light may be arranged anywhere as long as they exist on the above-mentioned half line, but in the present embodiment, they are point-symmetrical with the light irradiation position 5 as the center of symmetry and It is arranged outside the optical fibers for light detection 7b and 7c. Here, the light irradiation optical fiber 4 and the light detection optical fibers 7a, 7b, 7c, 7d are fixed by a metal optical fiber fixing member 8 whose surface is painted black. Optical fiber for light detection 7a, 7b, 7c, 7d
Is connected to the photodetector optical fibers 9a, 9b, 9c, 9d through the optical fiber couplers 3b, 3c, 3d, 3e, so that the photodetection optical fibers 7a, 7b, 7
The passing light detected by c and 7d is the photodetectors 10a and 10d.
b, 10c, and 10d are transmitted, and the passing light intensity photoelectrically converted by the photodetector 10 is output as the electric signal intensity.
As the photodetector 10, for example, a photoelectric conversion element such as a photodiode or a photomultiplier tube can be used.

The electric signals representing the transmitted light intensities output from the photodetectors 10a and 10b are extracted by the lock-in amplifiers 24a and 24b, respectively, only the intensity modulation frequency component of the light source. The output from the lock-in amplifier 24a is logarithmically converted by the logarithmic amplifier 25a and then input to the negative electrode of the differential amplifier 11a, and the output from the lock-in amplifier 24b is logarithmically converted by the logarithmic amplifier 25b and then differential amplifier 11a. Is input to the positive electrode of. Photodetectors 10c and 10d
The electric signals representing the intensity of the passing light output in step (4) are extracted by the lock-in amplifiers 24c and 24d, respectively, only the intensity modulation frequency component of the light source. The output from the lock-in amplifier 24d is logarithmically converted by the logarithmic amplifier 25d and then input to the negative electrode of the differential amplifier 11b.
The output from c is logarithmically converted by the logarithmic amplifier 25c and then input to the positive electrode of the differential amplifier 11b. Further, the output from the differential amplifier 11a is input to the negative electrode of the differential amplifier 11c, and the output from the differential amplifier 11b is input to the differential amplifier 11c.
Input to the positive electrode of. As a result, the logarithmic difference signal of the passing light intensity at four different positions is output from the differential amplifier 11c as an output signal. The output signal from the differential amplifier 11c is sequentially converted into a digital signal by the A / D converter 12 and taken into the computer 13 to be displayed as a graph on the display device 14 as time series data.

Here, as shown in FIG. 7, if the region 15 in which the hemodynamics locally changes is included only in the visual field 16b of the optical fiber for light detection, the transmitted light output from the differential amplifier 11c is obtained. The logarithmic difference signal of intensity will only reflect local hemodynamic changes. The meaning of the logarithmic difference signal output from the differential amplifier 11c will be described below on the assumption that hemoglobin, which is the main component in blood, acts predominantly on light absorption with respect to near-infrared light.

Measurement time is t, light source wavelength is λ, irradiation light intensity is I ₀ (t), oxyhemoglobin and reduced hemoglobin concentrations are C _ox (t), C _deox (t), and oxidation changes in the local region 15. The hemoglobin concentration and the reduced hemoglobin concentration are ΔC _ox (t) and ΔC _deox (t), the absorption coefficients of oxyhemoglobin and reduced hemoglobin for the light source wavelength λ are ε _ox (λ) and ε _deox (λ), respectively, and the photodetector 10b D _s1 is the scattering included in the intensity of the transmitted light detected by 10 and 10c, and D is the attenuation caused by absorption other than hemoglobin, and D is the attenuation included in the transmitted light intensity detected by the photodetectors 10a and 10d and the absorption caused by absorption other than hemoglobin. _s2, raw by the scattering included a weighting factor caused by the scattering included in the passing light intensity detected by the photodetector 10b and 10c d _1, the passing light intensity detected by the photodetector 10a and 10d That if the weighting coefficient is d _2, passing light intensity is detected by the photodetector 10c signals I _d1
(t), the transmitted light intensity signal I detected by the photodetector 10d
_d2 (t), the transmitted light intensity signal I detected by the photodetector 10b
_{The d1} '(t) and the passing light intensity signal _Id2 ' (t) detected by the photodetector 10a are expressed by the following equations (8) to (11), respectively.

I _d1 (t) = D _s1 · exp [− [ε _ox (λ) (C _ox (t) + ΔC _ox (t)) + ε _deox (λ) (C _deox (t) + ΔC _deox (t) )] d ₁ ] I ₀ (t) (8) I _d2 (t) = D _s2 · exp [− [ε _ox (λ) (C _ox (t) + ΔC _ox (t)) + ε _deox (λ) (C _deox (t) + ΔC _deox (t))] d ₂ ] I ₀ (t) (9) I _d1 ′ (t) = D _s1 · exp [− [ε _ox (λ) C _ox (t) + ε _deox ( λ) C _deox (t)] d ₁ ] I ₀ (t) (10) I _d2 '(t) = D _s2 · exp [− [ε _ox (λ) C _ox (t) + ε _deox (λ) C _deox (t)] d ₂ ] I ₀ (t) (11)

Next, after taking the natural logarithm of the equations (8) and (9), the equation (9) is subtracted from the equation (8) to obtain the following equation (12). ln [I _d1 (t) / I _d2 (t)] = ln [D _s1 / D _s2 ] − [ε _ox (λ) (C _ox (t) + ΔC _ox (t)) + ε _deox (λ) (C _deox (t) + ΔC _deox (t))] (d ₁ −d ₂ ) (12) After taking the natural logarithm of equations (10) and (11), subtracting equation (11) from equation (10) gives Equation (13) is obtained. ln [I _d1 '(t) / I _d2 ' (t)] = ln [D _s1 / D _s2 ] − [ε _ox (λ) (C _ox (t) + ΔC _ox (t)) + ε _deox (λ) ( C _deox (t) + ΔC _deox (t))] (d ₁ −d ₂ ) (13) The left side of the equation (12) represents the output of the differential amplifier 11b, and the left side of the equation (13) is the differential amplifier. 11a shows the output of 11a. Here, when the equation (13) is subtracted from the equation (12), the following equation (14) is obtained.

Ln [(I _d1 (t) / I _d2 (t)) (I _d2 '(t) / I _d1 ' (t))] =-[ε _ox (λ) ΔC _ox (t) + ε _deox ( λ) ΔC _deox (t)] (d ₁ −d ₂ ) (14) The left side of the equation (14) represents the output from the differential amplifier 11c, that is, the measured logarithmic difference signal.

Here, in particular, the light source wavelength is 805 nm ±
When the measurement is performed using 10 nm, the relationship of the above expression (4) is established, so the expression (14) can be rewritten as the following expression (15) using the constant K. ln [(I _d1 (t) / I _d2 (t)) (I _d2 '(t) / I _d1 ' (t))] =-[ΔC _ox (t) + ΔC _deox (t)] · K (15)

Therefore, the logarithmic difference signal measured using the light source wavelength 805 nm ± 10 nm is the relative blood change amount [Δ
It represents a value corresponding to C _ox (t) + ΔC _deox (t)]. In addition, if the number of wavelengths used for the light source is set to two wavelengths (λ ₁ , λ ₂ ), different intensity modulation frequencies (f ₁ , f ₂ ) are given to each wavelength, and frequency is separated by the lock-in amplifier, then the transmitted light of each wavelength is transmitted. The intensity signal can be measured. Therefore, since the equation (14) holds at each wavelength, the simultaneous equations consisting of the following equations (16) and (17) can be derived.

Ln [(I_d1(λ₁, T) / I_d2(λ₁, T)) (I_d2'(λ₁, T) / I_d1'(λ₁, T))] =-[ε_ox(λ₁) ΔC_ox(t) ＋ ε_deox(λ₁) ΔC_deox(t)] (d₁-D₂) (16) ln [(I_d1(λ₂, T) / I_d2(λ₂, T)) (I_d2'(λ₂, T) / I_d1'(λ₂, T))] =-[ε_ox(λ₂) ΔC_ox(t) ＋ ε_deox(λ₂) ΔC_deox(t)] (d₁-D₂) (17) Extinction coefficient ε_ox(λ₁), ε_ox(λ₂), ε_deox(λ₁), ε
_deox(λ₂) Is known, the change in oxyhemoglobin
Value corresponding to quantity ΔC_ox(t) (d₁-D₂) And reduced hemoglobin
ΔC corresponding to the change amount of_deox(t) (d₁-D₂), (1
Obtained by solving equations (6) and (17) in computer 13.
It is possible to display the time series data of the calculated relative change amount.
A graph is displayed on the display device 14. Further expand the number of wavelengths
Increase, (d₁-D ₂) Is erased, or a small amount of
It is also possible to calculate the relative change in the concentration of light-absorbing substances other than Robin.
It is possible.

Further, as shown in FIG. 8, without using a lock-in amplifier, a logarithmic amplifier and a differential amplifier, the photodetector 1
After converting the detection signals from 0a, 10b, 10c, and 10d into digital signals by the A / D converter 12, respectively, only the signal corresponding to the intensity modulation frequency of the light source is extracted by FFT processing in the computer 13. After calculating the logarithmic difference of the transmitted light intensity at four different detection positions in the same procedure as the above-described calculation process, the calculated relative change amount may be displayed as a time series data on the display device 14 in the form of a graph. it can.

[Embodiment 3] FIG. 9 shows a schematic configuration of a third embodiment of the biological light measuring device according to the present invention. Light sources 1a and 1
The light emitted from b is condensed using a lens system and is incident on the optical fibers 2a and 2b for light sources, respectively. The light emitted from each light source is 100 Hz to 10 MHz by each oscillator 23a, 23b in order to remove the noise caused by the outside.
The intensity is modulated with an arbitrary frequency f having different degrees. Here, the intensity modulation frequency of the light source 1a is f ₁ , and the light source 1a
Let f ₂ be the intensity modulation frequency of b. The light source optical fiber 2a is connected to the light irradiation optical fiber 4a via the optical fiber coupler 3a, and the light source optical fiber 2b is connected to the light irradiation optical fiber 4b via the optical fiber coupler 3c. Light is transmitted to the light irradiation optical fibers 4a and 4b, and the light irradiation positions 5a and 5b.
The subject 6 is irradiated with the light. In order to obtain the reference light, the demultiplexer 26a,
26b is used for demultiplexing, and the photodetectors 10a and 10c convert the intensity of each light source into an electric signal. The reference light intensity signal of the light source 1a output from the photodetector 10a is input to the lock-in amplifier 24a, and is separated based on the reference frequency from the oscillator 23a. The output from the lock-in amplifier 24a is
After being input to the logarithmic amplifier 5a and logarithmically converted, it is input to the negative electrode of the differential amplifier 11a. The reference light intensity signal of the light source 1b output from the photodetector 10c is input to the lock-in amplifier 24d, and is separated based on the reference frequency from the oscillator 23b. The output from the lock-in amplifier 24d is
It is input to the logarithmic amplifier 25d and logarithmically converted, and then input to the negative electrode of the differential amplifier 11b. The wavelength of the light used depends on the spectral characteristics of the substance of interest in the living body, but when measuring the oxygen saturation and blood flow from the concentrations of Hb and HbO ₂ , it is 600 n.
One or more wavelengths are selected and used from the light in the wavelength range of m to 1400 nm. As a light source, a semiconductor laser,
A titanium sapphire laser, a light emitting diode or the like can be used.

A single optical fiber 7 for light detection is arranged at a position equidistant from the light irradiation positions 5a and 5b on the subject 6 in order to detect the light emitted after passing through the subject 6. Here, the light irradiation optical fibers 4a and 4b and the light detection optical fiber 7 are fixed by an optical fiber fixing member 8 whose surface is painted black. Optical fiber for light detection 7
Is connected to the optical fiber 9 for photodetector via the optical fiber coupler 3b.
The passing light detected in 1 is transmitted to the photodetector 10b, photoelectrically converted by the photodetector 10b, and the passing light intensity is output as the electric signal intensity. As the photodetector 10b, for example, a photoelectric conversion element such as a photodiode or a photomultiplier tube is used.

Since the electric signal representing the intensity of the passing light output from the photodetector 10b includes the passing light intensity signal for the light source 1a and the passing light intensity signal for the light source 1b, the intensity for the light source 1a is detected by the lock-in amplifier 24b. Only the modulation frequency component is extracted, and the lock-in amplifier 24c extracts the light source 1b.
Extract only the intensity-modulated frequency components for. The output from the lock-in amplifier 24b is logarithmically converted by the logarithmic amplifier 25b and then input to the positive electrode of the differential amplifier 11a. The output from the lock-in amplifier 24c is logarithmically converted by the logarithmic amplifier 25c and then input to the positive electrode of the differential amplifier 11b. As a result, the differential amplifier 11a outputs, as an output signal, a logarithmic difference signal between the intensity of the light source 1a and the intensity of the transmitted light with respect to the light source 1a.
From b, a logarithmic difference signal between the intensity of the light source 1b and the intensity of the passing light with respect to the light source 1a is output as an output signal. Further, when the output from the differential amplifier 11a is input to the negative electrode of the differential amplifier 11c and the output from the differential amplifier 11b is input to the positive electrode of the differential amplifier 11c, the fluctuation of the light source intensity is removed from the differential amplifier 11c. A logarithmic difference signal of passing light intensity is output. The output signal from the differential amplifier 11c is sequentially
The A / D converter 12 converts the digital signal, and the calculator 13
And displayed as time series data on the display device 14.

Here, as shown in FIG. 9, if the region 15 in which the hemodynamics locally changes is included only in the visual field 16b of the optical fiber for photodetection, the measured logarithmic difference signal is local. It reflects only changes in hemodynamics. Meaning of the logarithmic difference signal to be measured will be described below on the assumption that hemoglobin, which is a main component of blood in the near infrared light, predominantly acts on light absorption.

Measurement time t, light source wavelength λ, irradiation position 5
The irradiation light intensity from b is I ₀ (t), the irradiation light intensity from the irradiation position 5a is I ₀ '(t), and the reference light intensity from the demultiplexer 26b is I _r.
(t), the intensity of the reference light from the demultiplexer 26a is I _r '(t), the demultiplexing ratio of the demultiplexer to the reference light is α, that is, I ₀ (t): I _r (t) = I ₀ '(t): I _r ' (t) = 1: α, and the oxyhemoglobin concentration and the reduced hemoglobin concentration changed in the local area 15 of C _ox (t) and C _deox (t) are respectively expressed as the oxyhemoglobin concentration and the reduced hemoglobin concentration. ΔC
_ox (t), ΔC _deox (t), and the extinction coefficient of oxyhemoglobin and deoxyhemoglobin with respect to the light source wavelength λ are ε, respectively.
_ox (λ), ε _deox (λ), where D _{s is} the attenuation due to scattering and absorption other than hemoglobin, and d is a weighting factor caused by scattering, the passing light intensity signal I _d for the light source 1b detected by the photodetector 10b. (t), that is, the output from the lock-in amplifier 24c is represented by the following formula (18), and the passing light intensity signal _Id '(t) to the light source 1a detected by the photodetector 10b, that is, from the lock-in amplifier 24b The output of is expressed by the following equation (19).

I _d (t) = D _s · exp [− [ε _ox (λ) (C _ox (t) + ΔC _ox (t)) + ε _deox (λ) (C _deox (t) + ΔC _deox (t)) ] d] I ₀ (t) (18) I _d '(t) = D _s · exp [− [ε _ox (λ) C _ox (t) + ε _deox (λ) C _deox (t)] d] I ₀ '(t) (19) Next, if the natural logarithms of equations (18) and (19) are taken and then transformed, equation (18) becomes equation (20) below, and equation (19) becomes equation (21) below. ).

Ln [I _d (t) / I ₀ (t)] = ln [D _s ] − [ε _ox (λ) (C _ox (tΔC _ox (t)) + ε _deox (λ) (C _deox (t ) + ΔC _deox (t))] d (20) ln [ _Id ′ (t) / I ₀ ′ (t)] = ln [D _s ] − [ε _ox (λ) C _ox (t) + ε _deox (λ ) C _deox (t)] d (21) Further subtracting expression (21) from expression (20) gives the following expression (22)
Is obtained.

Ln [(I _d (t) / I _d ′ (t)) (I ₀ ′ (t) / I ₀ (t))] = − [ε _ox (λ) ΔC _ox (t) + ε _deox ( λ) ΔC _deox (t)] d (22) where I _r (t) = αI ₀ (t) (23) I _r ′ (t) = αI ₀ ′ (t) (24) The output from the dynamic amplifier 11a is ln [I _d '(t) / αI ₀ ' (t)], and therefore the output from the differential amplifier 11c is ln [(I _d (t) / I _d '(t)). ) (I ₀ (t) '/ I ₀ (t))] (25). Since the expression (25) is equal to the left side of the expression (22), the logarithmic difference signal output from the differential amplifier 11c is equivalent to the expression (22).

Here, in particular, the light source wavelength is 805 nm ±
When the measurement is performed using 10 nm, the relationship of the above equation (4) is established, and therefore the equation (22) can be rewritten as the following equation (26) using the constant K. _{ln [(I d (t)} / I d '(t)) (I 0' (t) / I 0 (t))] = - [ΔC ox (t) + ΔC deox (t)] K (26) Therefore, the logarithmic difference signal measured using the light source wavelength 805 nm ± 10 nm is the relative blood change amount [ΔC _ox (t) + ΔC
_deox (t)] is represented. In addition, the number of wavelengths used for the light source is set to 2 wavelengths (λ ₁ , λ ₂ ), and different intensity modulation frequencies (f ₁ , f ₂ , f ₃ , f ₄ ) are given to each wavelength and each irradiation position, and the lock-in amplifier is supplied. If the frequency is separated by, the passing light intensity signal for each wavelength and each irradiation position can be measured.
Therefore, since the formula (22) holds for each wavelength, the following (27)
It is possible to derive a simultaneous equation consisting of equation (28).

Ln [(I _d (λ ₁ , t) / I _d ′ (λ ₁ , t)) (I ₀ ′ (λ ₁ , t) / I ₀ (λ ₁ , t))] = − [ε _ox (λ ₁ ) ΔC _ox (t) + ε _deox (λ ₁ ) ΔC _deox (t)] d (27) ln [(I _d (λ ₂ , t) / I _d '(λ ₂ , t)) ( I ₀ '(λ ₂ , t) / I ₀ (λ ₂ , t))] = − [ε _ox (λ ₂ ) ΔC _ox (t) + ε _deox (λ ₂ ) ΔC _deox (t)] d (28 ) Extinction coefficient ε _ox (λ ₁ ), ε _ox (λ ₂ ), ε _deox (λ ₁ ), ε
_{Since deox} (λ ₂ ) is known, the value ΔC _OX (t) d corresponding to the amount of change in oxyhemoglobin and ΔC _deox (t) d corresponding to the amount of change in reduced hemoglobin can be _{calculated using} equations (27) and (28 ) Can be obtained by solving the equation in the computer 13, and the time series data of the obtained relative change amount is displayed as a graph on the display device 14. It is also possible to further expand to increase the number of wavelengths, eliminate d, or obtain the relative change amount of the concentration of a light-absorbing substance other than a small amount of hemoglobin.

Further, as shown in FIG. 10, the detection signals from the photodetectors 10a, 10b and 10c are respectively A / A without using the lock-in amplifier, the logarithmic amplifier and the differential amplifier.
After the digital signal is converted by the D converter 12, the calculator 13
FFT processing is performed in the inside to extract only the signal corresponding to the intensity modulation frequency of each light source, the calculation is performed in the same procedure as the above calculation process, and the obtained relative change amount is displayed on the display device 14 as time series data. It can also be displayed as a graph.

[0049]

According to the present invention, it is possible to measure local changes in hemodynamics in a subject with a simple device configuration.

[Brief description of drawings]

FIG. 1 is an explanatory diagram of a device configuration according to an embodiment of the present invention.

FIG. 2 is a view showing a temporal change in the intensity of light passing through a living body head according to a conventional method.

FIG. 3 is an explanatory diagram of a device configuration according to another embodiment of the present invention.

FIG. 4 is an explanatory diagram of a light detection probe.

FIG. 5 is an explanatory diagram of a light detection probe.

FIG. 6 is a diagram illustrating an example of use of the optical measurement device.

FIG. 7 is an explanatory diagram of a device configuration according to another embodiment of the present invention.

FIG. 8 is an explanatory diagram of a device configuration according to another embodiment of the present invention.

FIG. 9 is an explanatory diagram of a device configuration according to another embodiment of the present invention.

FIG. 10 is an explanatory diagram of a device configuration according to another embodiment of the present invention.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Light source, 2 ... Light source optical fiber, 3a-3c ... Optical fiber coupler, 4 ... Light irradiation optical fiber, 5 ... Light irradiation position, 6 ... Test object, 7a-7d ... Optical detection optical fiber, 8 ... Optical fiber fixing member , 9a to 9d ... Optical fiber for photodetector, 10a to 10d ... Photodetector, 11 ... Differential amplifier, 12 ... A / D converter, 13 ... Computer, 14 ...
Display device, 15 ... Region where hemodynamic changes locally, 1
6a, 16b ... Field of view of optical fiber for light detection, 17 ... Contact surface of specimen, 18 ... Belt for fixing, 19 ... Optical measuring device,
20 ... Output signal adjusting knob, 21 ... Output signal value display window,
22 ... Time series data, 23a to 23c ... Differential amplifier, 2
4 ... Lock-in amplifier, 25 ... Logarithmic amplifier, 26 ... Splitter

Continued Front Page (72) Yuichi Yamashita 1-280 Higashi Koigakubo, Kokubunji, Tokyo Inside Hitachi Central Research Laboratory

Claims (11)

[Claims] 1. A light irradiation means for irradiating the surface of a living body with light,
A living body optical measurement device comprising a light detecting means for detecting the intensity of light passing through the inside of a living body and emitted from the living body surface, wherein at least two combinations of a light irradiation position and a light detection position are provided, and a detection signal for each combination is detected. A biomedical optical measurement apparatus characterized by using a logarithmic difference signal as a measurement signal. 2. A combination of at least two sets of a light irradiation position and a light detection position in which the distance from the light irradiation position to the detection position is set equal to each other.
The biological optical measurement device described. 3. The biological optical measurement apparatus according to claim 1, further comprising a logarithmic amplifier and a differential amplifier, wherein the photodetection signal is logarithmically amplified and then the logarithmic difference signal is generated by the differential amplifier. 4. The light irradiation means includes an optical fiber connecting the light source and the light irradiation position, and the light detection means includes an optical fiber connecting the light detector and the light detection position. Or the biological optical measurement device according to 3. 5. A light detecting probe unit having the optical fiber end of the light irradiation unit and the optical fiber end of the light detection unit fixed, a light source of the light irradiation unit, a photodetector of the light detection unit, and an optical signal processing circuit. The optical measuring device according to claim 4, further comprising a measuring device section. 6. A light irradiation position, a first detection position, a second detection position, a third detection position set on a half line passing through the first detection position with the light irradiation position as the origin, and the light irradiation position as the origin. And a fourth detection position set on a half line passing through the second detection position as a logarithmic difference signal (first logarithmic difference signal) of the photodetection signals detected at the first detection position and the third detection position. And a logarithmic difference signal (second logarithmic difference signal) of passing light intensities detected at the second detection position and the fourth detection position, and a difference signal between the first logarithmic difference signal and the second logarithmic difference signal. The biological optical measurement device according to any one of claims 1 to 6, characterized in that. 7. A first light irradiation means for irradiating the surface of the living body with light, a first irradiation light intensity detecting means for detecting the irradiation light intensity from the first light irradiation means, and a light for the surface of the living body. Second light irradiating means for irradiating, second irradiating light intensity detecting means for detecting irradiating light intensity from the second light irradiating means, and first light passing through the inside of the living body and emitted from the surface of the living body. Light detection means for detecting the light intensity caused by the irradiation means or the second light irradiation means, output of the first irradiation light intensity detection means, and output of the light detection means caused by the first light irradiation means Means for generating a logarithmic difference signal (first logarithmic difference signal) between
Means for generating a logarithmic difference signal (second logarithmic difference signal) between the output of the second irradiation light intensity detection means and the output of the light detection means due to the second light irradiation means, and the first logarithm The living body optical measurement system according to claim 1, further comprising: a unit that measures a difference signal of the difference signal and the second logarithmic difference signal. 8. The intensity of the irradiation light from the light irradiation means is modulated,
8. The living body light according to claim 1, wherein only a frequency component that is the same as the intensity modulation frequency in the detection signal from the light detection means is extracted by a lock-in amplifier or a Fourier transform process and used. Measuring device. 9. The number of wavelengths of irradiation light is m, the number of light irradiation positions is n, and m × n types are used as the intensity modulation frequency of the light source. Biological light measurement device. 10. The biological optical measurement device according to claim 1, wherein a signal from a region where light absorption characteristics locally change due to a change in hemodynamics in a living body is used. The light irradiation position and the light detection position on the living body surface are included in the light intensity signal detected at at least one light detection position and not included in the light intensity signal detected at at least one other light detection position. An optical measurement method for living body, characterized by setting and measuring. 11. The detection position is different in a state where the region where the light absorption characteristic locally changes in the living body does not change.
After adjusting so that the logarithmic difference signal between the points becomes 0,
11. The living body optical measurement method according to claim 10, wherein the measurement is started and the displacement value of the difference signal is used as the measurement signal.