JPH0998972A - Biological optical measurement device and image creation method - Google Patents

Abstract

(57) [Summary] (Modified) SOLUTION: A plurality of wavelengths of light, which are enhanced and modulated at a plurality of different frequencies, are irradiated from a plurality of irradiation positions on the surface of a living body, and each wavelength and each wavelength are changed according to different positions on the surface of the living body. Measures the time change of the light intensity passing through the living body corresponding to each irradiation position,
From the intensities of light passing through the living body of multiple wavelengths detected at each detection point,
The biological function is imaged by obtaining a change in the concentration of the absorber in the living body and setting a measurement point on a perpendicular line passing through the midpoint between the incident point and each detection point. [Effect] Position information is determined almost uniquely by the light irradiation position of the light irradiation unit onto the subject and the position of the light receiving unit, so that signal processing for displaying as an image can be performed easily and at high speed. Further, since the position of the light receiving means is about 10 to 50 mm from the light irradiation position and the passing light is used, the detection intensity of about 6 digits or more is sufficient compared with the light transmitted through the living body of about 100 to 200 mm. can get.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a living body optical measurement apparatus and an image forming method in the apparatus, that is, a living body light measuring apparatus and image forming apparatus for measuring information inside a living body using light and imaging the measurement result. Regarding the method.

[0002]

2. Description of the Related Art An apparatus or method for simply measuring the inside of a living body without harming the living body is desired in clinical medicine.
For this demand, measurement using light is very effective.
The first reason is that the oxygen metabolism function inside a living body corresponds to the concentration of a specific dye (hemoglobin, cytochrome aa3, myoglobin, etc.) in the living body, that is, the concentration of a light absorber, and this specific dye concentration changes from light (visible to near This is because it is calculated from the absorption amount (wavelength in the infrared region). The second reason is that light can be easily absorbed by an optical fiber. The third reason is
The optical measurement does not harm the living body when used within the range of safety standards.

Utilizing the advantages of living body measurement using such light, the living body is irradiated with light having a wavelength from visible to near infrared, and the living body is detected from reflected light at a position about 10-50 mm away from the irradiation position. A device for measuring the inside is, for example, an open patent publication,
JP-A-63-277038, JP-A-5-300878
No. etc. Also, thickness 100-200mm
A device for measuring a CT image of oxygen metabolism function from light transmitted through a living body, that is, an optical CT device is disclosed in, for example, Japanese Patent Laid-Open Publication No. 60-72542 and Japanese Patent Publication No. 62-2316.
No. 25.

As a conventional biological optical measuring device, an oximeter (Japanese Patent Laid-Open No. 55-240) for measuring the saturation of runner in an artery.
04). An oximeter irradiates a living body with light of multiple wavelengths, measures the intensity of transmitted light or reflected light from the living body, and measures reduced hemoglobin (Hb) and oxyhemoglobin.
This is a device for calculating the oxygen saturation in arteries by utilizing the spectral characteristics of (HbO ₂ ) and the pulse wave.

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 Yovsis (JP-A-57-
115232). This method utilizes the spectral characteristics of Hb and HbO ₂ to measure oxygen saturation and blood volume in living tissue.

In the present 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. .

[0007]

[Problems to be Solved by the Invention]

(First problem) In order to analyze the function of a living body, a change in hemodynamics caused by a load is measured from the difference between the hemodynamics when a load is applied to the living body and the hemodynamics when no load is applied. There are cases.

[0008] The hemodynamics at no load is not always constant and changes with time. As a specific example, FIG. 1 shows a change over time in the transmitted light intensity when the transmitted light intensity is measured at a point 3 cm away from the light irradiation position by irradiating light on the temporal region of a subject lying still on his back. As shown in FIG. 1, the fluctuation of the measurement system is only about 0.3%, but the light intensity passing through the living body fluctuates largely as a whole, including the periodic component. This fluctuation of the transmitted light intensity is due to the change of hemodynamics in the living body.

As described above, even when the subject is at rest, an irregular signal change appears in the transmitted light intensity signal. Therefore, if processing is performed using the transmitted light intensity at the start of measurement as a reference value, blood caused by the load will be lost. It is difficult to separate dynamic changes from measured signals. Further, due to this, the time change of the measurement signal displayed on the display device or the hemodynamics calculated from the measurement signal may be the fluctuation caused by the fluctuation of the living body itself or the fluctuation due to the addition of the load. The observer cannot judge whether or not. Therefore, according to the conventional technique, the intensity of passing light at the start of measurement was processed as a reference value, so that the subject should rest in order to obtain this reference value.
There was a problem that measurement could not be done unless waiting for a long time until the signal became stable.

(Second Problem) Conventionally, it has been known that the cerebral cortex under the anterior bone is generated and spot-photometrically measured by a light receiving element and a fiber, but it is used as a protective tissue such as a skin tissue or a bone tissue. There was no disclosure or suggestion of measuring the covered blood state as an image, that is, having a plurality of measurement points and performing measurement. For example, when the oxygen metabolism locally changes, it is difficult to detect at which position the oxygen metabolism changes.

In order to extract the optical signal, it is necessary to increase the measurement time, that is, the number of times of measurement integration. as a result,
The measurement time becomes long, which not only imposes a mental burden on the subject, but also reduces the operating efficiency of the device.

The present invention solves these problems of the prior art.

(Third Problem) In the prior art, the oxygen saturation in the artery or the hemodynamics in the living tissue can be measured. However, it has been impossible to distinguish the hemodynamic changes due to the overall change of the living body or the hemodynamic changes due to the local change of the living body by the conventional techniques.

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 regions (hereinafter referred to as “functional regions”) that work in response to each function of the living body, and the blood volume of the functional region in the brain or the functional region in the brain corresponds to any function of the living body. The oxygen saturation changes locally. At this time, if the change in blood volume or oxygen saturation of only an arbitrary functional site can be locally measured, the function of the functional site of the brain can be examined in detail, which is very important medically.

For example, the fluctuation of the intensity of transmitted light in FIG. 1 is distinguished because the whole hemodynamic signal in the living body is fluctuated and only the local hemodynamic changes, because the signal is buried in the fluctuation. Is difficult.

The object of the present invention is to solve the above problems and to use a simple detector to measure a biological function in a short time and to display a measurement result using the apparatus. It is to realize a method of imaging.

A further object of the present invention is to separate and measure local hemodynamic changes from the overall hemodynamic changes in the body, which was difficult with the prior art.

[0019]

[0020]

[Means for Solving the Problems]

(For the first problem) When measuring changes in hemodynamics due to load, the time during which no load is applied to the living body (no-load time) and the time during which the load is applied to the living body (loading time) are given alternately. Measure. Here, the signal (measurement signal) measured by the raw optical measuring device is Sm (t), the signal (unloaded signal) caused by the change in hemodynamics at no load is Su (t), and the signal at the time of applied load is When the signal (load signal) caused by the change in hemodynamics is Sl (t), the measurement signal Sm (t) is expressed by the following formula 1. Here, t is the measurement time.

[0021]

## EQU00001 ## Sm (t) = Str (t) + Sl (t) Equation 1 In the present invention, a function Str representing a no-load signal by extracting a signal at no-load time from the measurement signal Sm (t).
(t) (predicted no-load signal) is predicted, and the measurement signal Smm (t)
Then, the load signal Sl (t) is obtained from the difference between the predicted unloaded signal Str (t). Furthermore, by simultaneously displaying the obtained measurement signal and the predicted no-load signal, it is easy to determine whether the change in the measurement signal is due to a load or fluctuation due to a living body at no load. To

The function Str (t) is determined by inputting an arbitrary function having an indefinite coefficient to a computer from a keyboard or the like, and determining the indefinite coefficient by the least square method or the like so that the function fits an unloaded signal optimally. This can be done by
Further, since the load signal Sl (t) does not immediately become zero even if the load is removed from the living body, a predetermined relaxation time is set after the load time, and the measurement time of the no-load time does not include this relaxation time. If the function Str (t) is determined by using, the function Str (t) can be determined with higher accuracy.

The function Str (t) can be determined so that a plurality of load times, for example, the entire measurement time is covered by one function, or each load time is covered so as to cover only each load time. You can also decide. According to the method of obtaining the function Str (t) for each load time by using the measurement signals Sm (t) before and after each load time, high prediction accuracy can be obtained.

In order to achieve the above object (for the second problem), the biological measuring apparatus of the present invention comprises a plurality of light irradiators for irradiating a subject with light having a wavelength in the visible to near infrared region. A plurality of light receivers that are irradiated from the light irradiator and detect light that has passed through the inside of the subject, and a memory that stores the signals detected by the light receivers for each of the plurality of light receivers and with time, An arithmetic unit that converts signals to be measured at multiple measurement points using the signals stored in the memory, and the output of the arithmetic unit is calculated by calculating the signal at the measurement position of the measurement point. Strength on the two-dimensional display surface An image creating unit for displaying as an image represented as a signal is provided. In particular, each of the plurality of light irradiators has a plurality of light sources with different wavelengths, a modulator that modulates the light of the plurality of light sources at frequencies different from each other, and a guide that guides the plurality of modulated lights to an irradiation position. And a separator for separating the intensities of the light from the light sources having different wavelengths on the groove side of the plurality of light receivers.

The estimated measurement position is present in the intermediate portion between the light irradiator and the light receiver, and more specifically, the strict estimated measurement position is the position of the living body surface irradiated by the light irradiator. It is an intermediate part up to the light receiving surface position of the pit. However, since the distance between the light irradiator and the light receiver is close to each other, there is no particular problem even if the light irradiator and the light receiver are replaced in the middle of the distance between the center of the light irradiator and the light receiver. Furthermore, as one method for obtaining the intermediate position, light is irradiated from a light irradiator to a living body, and a signal is detected by two light receivers arranged symmetrically with the light irradiator. The difference signal of the signal is taken, the two light receivers are adjusted so that the force of the difference signal and the force become zero level, and the position of the light receiver obtained by positioning the light receiver and the intermediate position between the light irradiator It can be obtained as an estimated measurement position.

To summarize the above description, when the function inside the living body is measured using the living body measuring apparatus, the light irradiation positions of the plurality of light irradiating means are distributed and arranged in the measuring part of the subject. , And a plurality of light receiving portions of the plurality of light receiving means are arranged around each of the light irradiation positions arranged in a distributed manner, and an optical signal detected by the plurality of light receiving means is detected as the light irradiation position. An arbitrary signal at the midpoint between the position and the perpendicular to the inside of the living body with respect to the living body surface is set as the estimated measurement point. This is because the spatial characteristics of the light density that reaches the detection position after being irradiated from the light irradiation position are high in the density immediately below the irradiation position and the detection position because there is light that is scattered from the surface near the surface. If the depth exceeds an arbitrary depth determined by the distance between the irradiation position and the detection position and the light scattering characteristics of the living body, the density becomes highest even at the intermediate position between the irradiation position and the detection position. This is because the sensitivity is highest at the intermediate position. The estimated measurement point and the detected optical signal intensity corresponding to the measurement point are displayed on the two-dimensional image. Further, when displaying as a topography image, a signal at a position that is not measured may be obtained by an interpolation signal of the estimated measurement point.

When the subject is a living body, the distance between the irradiation position and the detection position is preferably about 10 to 50 mm. The factor that determines the maximum distance here is determined by the intensity of bright light and the attenuation in the living body.

The present invention (for the third problem) irradiates a living body with light from any one or a plurality of locations,
Two positions, a detection position where a local change is measured as a signal change and a detection position where a local change is not measured as a signal change, are set to be substantially equidistant from the light irradiation position, and the respective detections are performed. By detecting the passing light intensity at a position and taking the difference between the passing light intensities between the two locations, it is possible to remove a commonly fluctuating biological fluctuation component, and it is possible to detect minute changes in the one-side optical receiver with high sensitivity. To do. If the two detection positions cannot be found, the light irradiation position can be displaced to find the detection position. That is, it is possible to search for a desired measurement position as with a listening device.

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 passing light intensity into a passing light intensity signal) and logarithmically converting each passing light signal intensity by a logarithmic amplifier, the passing light intensity signal at the first detection position and the second detection position are obtained. The light intensity signal passing through the punishment is amplified and detected by differential amplification.

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.

According to the present invention, since the information of the measurement position is determined almost uniquely by the light irradiation position of the light irradiation means on the object and the position of the light receiving means, the signal processing for displaying as an image is simple and high speed. You can do it. Further, since the position of the light receiving means is about 10 to 50 mm from the light irradiation position and the passing light is used, the detection intensity of about 6 digits or more is sufficient compared with the light transmitted through the living body of about 100 to 200 mm. can get. Therefore, it becomes possible to measure with a simple photodetector in a short time.

For example, when the measurement target (subject) is the head, the distance between the irradiation position and the detection position is at least 30 mm.
Then, it is known that the detected light passes through the skin and the skull to reach the surface part of the brain, that is, the cerebral cortex, for example, by Patrick W. McCormic et al. `` Intracerebral penetration of infrared ligh
t) ”, Journal of Neurosurgery, Vol. 76, paragraphs 315-318, published February 1992 (J Neurosur
g., 76,315 (1992)). In addition, the information in the position on the normal line from the midpoint of the irradiation and detection position to the inside of the living body relative to the surface of the living body contains the most information in the light detected at such a position. It is known for its propagation characteristics. This characteristic is described, for example, by Shechao Feng et al. In “Monte Carlo simulation of the distribution of photon migration paths in multiple scattering media (Mo
nte Carlo simulation of photon path distribution i
n multiple scattering media) ", Proceedings of Spiai Ie, 1993, Volume 1888, Photon migration and images in random media and living tissues, 78-89.
(SPIE, Proceedingsof photon migration and imagi
ng in random media and tissues, 1888, 78 (1993)).

In the living body optical measurement system of the present invention, a large number of light irradiation means and a large number of light receiving means are required to measure a large number of positions, but as shown in the examples described later, it is possible to measure a partial position. Is effective, and an image can be obtained at high speed by a simple calculation process of interpolating the measurement results obtained for a plurality of measurement points for each measurement point.

[0035]

BEST MODE FOR CARRYING OUT THE INVENTION

 Embodiment 1 Hereinafter, an embodiment of the present invention will be described.

FIG. 2 shows the configuration of an embodiment of the biological light measuring device according to the present invention. In this embodiment, the biological optical measurement device is
This is an example applied to measurement of hemodynamic changes (relative changes in oxygenated and reduced hemoglobin concentrations) associated with brain function. The specific part of the brain is related to the control of a specific function of the living body (for example, moving a part of the body such as a finger), and by operating the specific function, the hemodynamics of the specific part of the brain are changed. Add a load that moves the above specific function, for example, move your finger,
It is also possible to measure a hemodynamic change and display it as a contour map on a secondary plane image representing a brain region by using a biological optical measurement device as one of the present embodiments.

As shown in FIG. 2, in this embodiment, a plurality of light sources 2a to 2d having different wavelengths (light sources 2a and 2c and light source 2) are used.
b and 2d are the same wavelengths in the visible to near infrared region, respectively,
The light from the plurality of light sources 2a and 2b (2c and 2c) is generated by oscillators 1a and 1b (1
c and 1d), and the optical fibers 3a and 3b (32c and 3b) for the intensity-modulated light, respectively.
The light from the coupler 4a (4b) that is coupled through c) is passed through the optical fiber 5a (5b) and the subject 6 is the subject.
A plurality of light irradiation means for irradiating different positions on the scalp of
The plurality of light detecting optical fibers 7a to 7a to 7a to 7n so that the tips are located at positions equidistant (here, 30 mm) from the light irradiation positions near the light irradiation positions of the plurality of light irradiation means.
7d and a plurality of light receiving means composed of photodetectors 8a to 8f provided on each of the optical fibers for light detection 7a to 7d. 6 optical fibers for light detection 7a
At ~ 7f, the light passing through the living body is condensed on an optical fiber, and the light passing through the living body is photoelectrically converted by photodetectors 8a to 8f.
The light receiving means detects the light reflected inside the subject and converts it into an electric signal, and as the photodetector 8, a photoelectric conversion element represented by a photoelectron multiplier and a photodiode is used.

The electric signals (hereinafter referred to as living body passing light intensity signals) representing the living body passing light intensity photoelectrically converted by the photodetectors 8a to 8f are input to lock-in amplifiers 9a to 9h, respectively. Here, since the photodetectors 8c and 8d detect the in-vivo light intensity collected by the photodetection optical fibers 7c and 7d equidistant from both the optical fibers 5a and 5b, the photodetectors 8c and 8d are detected. Signal from 2
The system is separated and input to the lock-in amplifiers 9c and 9e and 9d and 9f. The lock-in amplifiers 9a to 9d include oscillators 1a and 1b, and lock-in amplifiers 9e to 9d.
The intensity modulation frequency from the oscillators 1c and 1d is input to h as a reference frequency. Therefore, the living body passing light intensity signals for the light sources 2a and 2b are separated and output from the lock-in amplifiers 9a to 9d.
The living body passing light intensity signals for the light sources 2c and 2d are separated and output from e to 9h.

As an example of the contour line display, after the separated passing light intensity signals for each wavelength which are the outputs of the lock-in amplifiers 9e to 9h are analog-digital converted by the analog-digital converter 10, the inside of the computer 11 is shown. Alternatively, it is stored in the storage device 12 outside the computer 11. During or after the measurement, the calculator 11 uses the transmitted light intensity signal stored in the storage device to calculate the relative change amount of the oxyhemoglobin concentration and the reduced hemoglobin concentration obtained from the detection signal at each detection point, and the plurality of measurements are performed. It is stored in the storage device 12 as temporal information of the point m. The above calculation will be described later in detail. The computer 11 outputs the signal stored in the storage means 12 to the CRT.
Etc. are converted into display signals of the display device 13 and displayed on the display device 13. The display signal is a signal for converting the measurement position into coordinates on the display plane of the subject and displaying the intensity signal (relative change amount of oxidative or reduced hemoglobin concentration) of the coordinate position by contour lines.

By using the biological light measuring device according to the present embodiment, the relative change amount of the oxygenated and reduced hemoglobin concentrations in the living body can be measured easily and at high speed. The configuration for increasing the number of light incident points (light irradiation positions) and the number of light detection points can be easily expanded because it is sufficient to increase the intensity modulation frequency of the light source, the light source, the light detector, and the lock-in amplifier. With this biological light measurement device, the spectral and light irradiation positions can be separated by the intensity modulation frequency, so even if the light irradiation positions are increased, the number of wavelengths of irradiation light at each light irradiation position can be measured. It suffices that the number is the same as the number of absorbers to be used, and it is not particularly necessary to change the wavelength of irradiation light for each light irradiation position. Therefore, the number of wavelengths of the irradiation light used is small, and the error due to the influence of scattering that differs depending on the wavelength can be reduced.

FIG. 3 is a diagram for clarifying one embodiment of the image creating method according to the present invention using the biological light measuring device.
The relationship between the light incident point, the light detection point, and the measurement point in the above method is shown. The image creating method of the present example is a method of creating an image of the relative change amount of the oxyhemoglobin concentration and the reduced hemoglobin concentration in the head of the subject, and the left head part involved in the motor function of the right finger of the subject. This is a method in which each of the four incident and detection points is provided to measure the light intensity passing through the living body, and the measurement result when the motion of the right hand finger and the motion of the left hand finger are applied as a load is imaged.

As shown in FIG. 3, light incident points 17a to 17d and detection points 18a to 18d are arranged on the left side of the head of the subject 16. Here, the correspondence between each light incident point and each detection point is
17a-18a, 17a-18b, 17b-18a, 1
7b-18b, 17b-18c, 17b-18d, 17
c-18b, 17c-18c, 17d-18c, 17d
There are 10 sets of -18d. The distance between each corresponding light incident point and the detection pond is 30 mm. Further, the time change of the relative change amount of the oxidized and reduced hemoglobin concentration obtained from the measurement signal at each detection point is
Feng et al., "Monte Carlo simulatio of photon migration path distributions in multiple scattering media.
n of photon path distribution in multiple scatteri
ng media) ”, most of the information between the corresponding incident points and detection points is reflected, so the estimated measurement points 19a to 19j correspond to the incident points and detection points. Set to the center of. Information on the estimated measurement points 19a to 19j is obtained, and the size of the information is also displayed on the two-dimensional plane as shown in FIG. 3 as contour lines, shades, and color identification charts.

Next, the relative change amount of each hemoglobin concentration from the measurement signal at each of the light detection points according to the present invention, that is, the specific function of the living body (for example, moving a part of the body such as a finger) of the brain operates. An example of a method for obtaining a change in hemoglobin concentration at a specific site will be described.

FIG. 4 is a graph showing changes with time of the measurement signal 14 and the predicted no-load signal 15 obtained from the measurement signal 14 at one of the detection points 18a to 18d of the living body optical measurement system in the above embodiment of FIG. Is. The horizontal axis of the graph represents the measurement time, and the vertical axis represents the relative concentration change amount. The predicted no-load signal 15 includes the pre-load time T1 and the load except the signals from the measurement signal 14 at the load application time (completion time) Tt and the post-load signal return time (relaxation time) T2. This is obtained by fitting an arbitrary function to the measurement signal 14 at the subsequent time T3 using the least square method. In this embodiment, the arbitrary function is a quadratic linear polynomial, and each time is T1 = 40 seconds, T2 = 30 seconds, Tt = 30.
Seconds, T3 = 30 seconds.

FIG. 5 shows the relative changes in the concentrations of oxyhemoglobin and deoxyhemoglobin at one measurement point (hereinafter, Δ
6 is a graph showing a temporal change of Coxy (t) signal 20 and ΔCdeoxy (t) signal 21. The horizontal axis of the graph represents the measurement time, and the vertical axis represents the relative concentration change amount. The time indicated by the diagonal lines is the load application time (movement period of the right finger). The relative change amount is the two-wavelength measurement signal 14 and the predicted no-load signal 15 shown in FIG.
From the above, the relative change amount of the concentration of oxidized and reduced hemoglobin (HbO ₂ , Hb) due to the load application is obtained by the following arithmetic processing.

Predicted no-load signal Str at wavelength λ
The relationship between (λ, t) and the light source intensity Io (λ) is expressed by the following mathematical expression 2 by separating light attenuation in the living body into scattering and absorption.

[0047]

-Ln {Str (λ, t) / I0 (λ)} = εoxy (λ) · Coxy (t) · d + εdeoxy (λ) · Cdeoxy (t) · d + A (λ) + S (λ) ... number 2 where εoxy (λ): absorption coefficient of oxyhemoglobin at wavelength λ εdeoxy (λ): absorption coefficient of reduced hemoglobin at wavelength λ A (λ): attenuation due to absorption other than hemoglobin at wavelength λ S (λ): wavelength Attenuation due to scattering at λ Coxy (t): Oxyhemoglobin concentration at measurement time t Cdeoxy (t): Reduced hemoglobin concentration at measurement time t d: Effective optical path length in the living body (at the region of interest).

The relationship between the measurement signal Sm (λ, t) and the light source intensity I0 (λ) is expressed by the following mathematical expression 3.

[0049]

-Ln {Sm (λ, t) / I0 (λ)} = εoxy (λ) · {Coxy (t) + C′oxy (t) + Noxy (t)} · d + εdeoxy (λ) · {Cdeoxy (t) + C′deoxy (t) + Ndeoxy (t)} · d + A ′ (λ) + S ′ (λ) ... where C′oxy (t) is the change in oxygenated hemoglobin concentration due to load application at the measurement time t. C'deoxy (t): Change in reduced hemoglobin concentration due to load application at measurement time t Noxy (t): Noise or high-frequency fluctuation of oxyhemoglobin concentration at measurement time t Ndeoxy (t): Noise or reduced hemoglobin concentration at measurement time t High-frequency fluctuations of A (λ) and S (λ)
If there is no change in the state with and without the load applied, that is, if the change in the measurement signal caused by the load is due to only the change in the concentration of oxyhemoglobin and reduced hemoglobin, the difference between Eqs. Indicated by.

[0050]

Ln {Str (λ, t) / Sm (λ, t)} = εoxy (λ) {C′oxy (t) + Noxy (t)} d + εdeoxy (λ) {C′deoxy (t) + Ndeoxy (t)} d ... Equation 4 where ΔCoxy (t) and Δ are the temporal changes in the relative changes in the oxygenated and reduced hemoglobin concentrations due to the load, respectively.
It is represented by Cdeoxy (t) and defined by the following formula.

[0051]

## EQU00005 ## .DELTA.Coxy (t) = {C'oxy (t) + Noxy (t)} d .DELTA.Cdeoxy (t) = {C'deoxy (t) + Ndeoxy (t)} d ... Since it is difficult to do so, the dimension of these density changes is the product of the density and the distance d.

However, in Equation 5, the distance d is ΔCoxy and ΔCdeo.
Since xy operates in the same manner, the expression 5 is set as the relative change amount of each hemoglobin concentration. If two wavelengths are used for measurement, the obtained number 4
Is a binary simultaneous equation for ΔCoxy (t) and ΔCdeoxy (t), and the predicted no-load signal Str for each wavelength is
From (λ, t) and the measurement signal Sm (λ, t), ΔCoxy
(T) and ΔCdeoxy (t) are obtained. Furthermore, ΔCoxy (t) and ΔCdeo other than the loading time and relaxation time
What xy (t) represents is C'oxy (t) = 0, C'deo
Since xy (t) = 0, it means that high-frequency fluctuations of oxyhemoglobin concentration and reduced hemoglobin due to noise or living body are expressed. Time 0 by the above process
The value obtained over 140 seconds is ΔCoxy in FIG.
The (t) signal 20 and the ΔCdeoxy (t) signal 21.

6 and 7 are contour image (topography image) created from the time change of the relative change amount of the oxyhemoglobin concentration at each of the above measurement points, with the load of the motion of the left and right fingers of the subject, respectively. Indicates. The method of creating a topography image is based on the load application time (hatched period in FIG. 5).
The relative integrated amount ΔCoxy (t) signal 20 in the inside is calculated by the computer 11 with time integrated value (may be the time average value), and the values between the measurement points are linearly interpolated in the X-axis direction and the Y-axis direction. It was done. As the topography image, in addition to the contour lines as shown in FIGS. 6 and 7, a monochrome gray-scale image or a color-based identification display may be used. From the comparison of the images in FIG. 6 and FIG. 7, it is apparent that the oxygenated hemoglobin concentration is increased at a specific position during the right hand movement. By displaying such information of the spatial distribution as an image, the recognition of the measurement result is made quick and easy. Further, the images shown in FIGS. 6 and 7 are created by the time integrated value of the relative concentration change amount during the load application time, but similarly the relative change amount of the oxyhemoglobin concentration at each measurement point at the same measurement time is the same. It is also possible to create topographic images. By displaying the plurality of created topographic images in the order of measurement time or as a moving image, it is possible to grasp the time change of the relative change amount of the oxygenated hemoglobin concentration.

Furthermore, the self- and cross-correlation function of the time change of the relative change amount of the oxyhemoglobin concentration at any one measurement point and the time change of the relative change amount of the oxyhemoglobin concentration at the other measurement points are calculated, and at each measurement point It is also possible to create a topography image from the correlation function. Since the correlation function at each measurement point is a function defined by the time lag τ, if a topography is created from the value of the correlation function at the same time lag τ and displayed in the order of τ or displayed as a movie, brain function activation It is possible to visualize hemodynamics that change due to

Here, the relative change amount of the oxyhemoglobin concentration is representatively described, but the total hemoglobin calculated by the relative change amount of the reduced hemoglobin concentration or the sum of the relative change amounts of the oxidized and reduced hemoglobin concentrations. The topography can be similarly created for the relative density change amount.

FIG. 8 shows a display example in which the topography image 22 created by the method described above is superimposed on the brain surface image 23 of the subject. Since the topography image 22 is a change in the hemodynamics of the brain that has changed in relation to the function of the living body,
It is desirable to display it on top of the brain surface image. The brain surface image 23 is measured and displayed by three-dimensional MRI or three-dimensional X-ray CT. For the topography image 22, the coordinates of each measurement point are coordinate-converted so as to be located on the brain surface, and the values between the measurement points after the coordinate conversion are interpolated to create a topography image. Created topography image 22 and brain surface image 2
When 3 is superimposed and displayed, the color of the superimposed topography image 22 is made semitransparent so that the brain surface image located therebelow can be seen through.

FIG. 9 is a diagram for explaining the method of measuring point coordinate conversion. A specific method of capturing a morphological image of three-dimensional MRI or three-dimensional X-ray CT will be described below. Reference numeral 5a in FIG. 9 is an irradiation optical fiber, and reference numeral 7a in FIG. 9 is a light detection optical fiber. The information on the desired measurement point is
The information of the part on the center line of (2d) is estimated and used. This is because the irradiation light fiber supplies the maximum amount of light and the signal from the measurement target has the maximum (that is, the maximum sensitivity) is used. When a marker is placed at the measurement point 29 that is estimated and set by the biological optical measurement device and an image is taken, the skin and bone image 24 is obtained from the taken morphological information.
The brain image 25 and the marker image 26 can be displayed.
The photographed image has three-dimensional coordinate information. Then, passing through the measurement point 27 indicated by the marker image 26, the measurement point 2
The vertical 28 with respect to the skin surface or the bottom of the marker image 26 in 7 is calculated, and the point intersecting with the brain image 25 is set as the coordinate-converted measurement point 29. As shown in this example, in the case of measuring brain function, it is known that hemodynamic changes correlated with load mainly occur on the brain surface (cerebral cortex). For the above reason, by using the morphological information of the living body, it is possible to obtain a method for obtaining an estimated measurement point that is substantially measured. However, when the measurement target is another biological organ such as a muscle, the depth at which the coordinate conversion is performed may not be known from the morphological information. When the present method is used for the measurement as described above, the light propagation in the living body is preliminarily calculated by the numerical calculation by the Monte Carlo method, the depth that most contributes to the measurement signal is calculated, and the calculated depth is calculated. Treat as an estimated measurement point.

So far, the topographic image has been shown as the estimated display image, but there are other image display methods.

For example, an image in which a square pixel having an arbitrary size with the estimated measurement point as the center of gravity is set as each estimated measurement point, and each pixel is painted in a shade or color corresponding to the value of each estimated measurement point in advance, , Each pixel is displayed as a bar graph image in which the length of a bar or line corresponding to the value of each measurement point is displayed.

Further, the color arrangement when colors are used in all image display methods can be freely selected, but when hemodynamics are measured, a combination of red-based shading and blue-based shading is displayed. Is desirable. This is because the image that arterial blood is red and venous blood is blue is well established. For example, the magnitude of the positive measurement value is displayed in red shades and the magnitude of the negative measurement value is displayed in blue shades.

(Second Embodiment) A second embodiment according to the present invention will be described.

FIG. 10 is a display example of the measurement signal and the predicted no-load signal. The displayed measurement signal 110a and measurement signal 110b are output signals from the lock-in amplifier 9a, and the predicted no-load signals 111a and 111b were calculated from each measurement signal (calculation method will be described later).

The predicted no-load signals 111a and 111b are displayed on the display device. The horizontal axis of the displayed graph represents the measurement time, and the vertical axis represents the relative value of the measurement signal representing the intensity of the passing light measured by the apex light measuring device.

When a load is applied to the subject,
A load start mark 112 indicating the load application start time and a load end mark 113 indicating the load application end time are displayed in a straight line. In this embodiment, the cerebral cortex region that controls the right hand movement is measured from above the scalp through the skull, and the right hand or left hand movement is applied as a load (load 1 and load 3 are right hand movement, load 2 and load). 4 is left hand movement). Although all signals of the measurement time are displayed in FIG. 10, it is easy to display only an arbitrary time interval (for example, a time interval including before and after the load time). Further, by displaying the predicted no-load signals 111a and 111b up to an arbitrary time ahead on the extension line of the temporal change until then, the measured signals 110a and 110b and the predicted no-load signals 111a and 11b during measurement are displayed.
It is also possible to display 1b simultaneously in real time. In this way, the measurement signals 110a and 110b and the predicted no-load signal 11
By displaying 1a and 111b at the same time, it becomes easier for the observer to judge when hemodynamic changes occur in the living body. It should be noted that the predicted no-load signal that has been displayed in real time after this is preferably displayed again when the calculation of the predicted no-load signal is confirmed.

The predicted no-load signals 111a and 111b are obtained by removing the signals from the measurement signals 110a and 110b at the time when the load is applied (load time) and the time after the load is removed and before the signal returns to the original state (relaxation time). , The signal of the remaining period is obtained by fitting an arbitrary function using the least square method. Here, since the arbitrary function and the relaxation time differ depending on the type of load and the measurement place, they are input from the input device 30 in FIG. 2 according to the purpose of measurement and the like. In this embodiment, the arbitrary function is processed with a polynomial of degree 5 and the relaxation time is 30 seconds. In addition, it is possible to change the color or line type of each signal for displaying the signal so that the observer can easily see the signal.

FIGS. 11A and 11B are display examples of the difference signal between the measurement signal and the predicted no-load signal, in which the difference between the measurement signals 110a and 110b and the predicted no-load signals 111a and 111b in FIG. 10 is calculated. Certain difference signal 114
The waveforms a and 114b are displayed on the display device. The horizontal axis of the displayed graph represents the measurement time, and the vertical axis represents the relative difference signal strength. Furthermore, when a load is applied to the subject, a load start mark 112 indicating the load application start time and a load end mark 113 indicating the load application end time are displayed in a straight line. Further, since this graph is a graph centered on 0, the baseline 115 is displayed.

In the present embodiment, the waveforms 114a and 114b are displayed on different coordinate axes for each light source wavelength, but it is also possible to display them on the same coordinate axis in an overlapping manner. In addition, it is possible to change the color or the line type so that an observer can easily see the display. 12A and 12B show
7 is a display example of a graph showing relative changes in the concentrations of HbO ₂ and Hb due to load application (hereinafter referred to as ΔCoxy and ΔCdeoxy, respectively). Measurement signals 110a and 1 in FIG.
10b and the predicted no-load signals 111a and 111b, the ΔCoxy signals 116a and Δ given by the equation (5).
The waveform of the Cdeoxy signal 116b is displayed on the display device. The horizontal axis of the displayed graph represents the measurement time,
The vertical axis represents the values of ΔCoxy and ΔCdeoxy. Further, the load start mark 112, the load end mark 113, and the base line 115 are also displayed. In this embodiment, all the sections of the measurement time are displayed, but it is also possible to display only an arbitrary time interval (for example, a period including before and after the load time). Further, although the waveforms 116a and 116b are separately displayed on different coordinate axes here, they may be displayed on the same coordinate axis in an overlapping manner. Furthermore, it is also possible to display by changing the color of each signal or the line type of each signal. For example, if the ΔCoxy signal 116a is displayed in a red color, and the ΔCdeoxy signal 116b is displayed in a green color, It is easy for the observer to understand intuitively. According to the measuring method and the displaying method of the present invention, the correlation between the load and the measurement signal is easy to understand, and the fluctuation is removed from the measurement signal, so the signal accuracy is high.

FIG. 13 shows the ΔCoxy load time integrated value 117a and the ΔCdeoxy load time integrated value 117b for each load time.
Is a display example of. The ΔCoxy signal 114a and the ΔCeoxy signal 114b in FIGS. 11A and 11B are time-integrated for each load time to obtain the ΔCoxy load time integrated value 117a and the ΔCdeoxy load time integrated value 117b, which are displayed on the display device as a solid bar graph for each load number. are doing. Here, the horizontal axis represents the load number and the vertical axis represents the ΔCoxy load time integrated value and ΔCdeoxy.
It represents the load time integral value. Here, it is also possible to display the ΔCoxy load time average value and the ΔCdeoxy load time average value. Further, the display can be displayed in different colors so that the observer can easily see it.

FIG. 14 shows a display example in the case where measurement is performed at a plurality of measurement positions using the biological light measuring device. Here, an example in which the measurement site is the head and four measurement positions are set on the head will be described.

In this display example, the measurement site image 118 of the subject is displayed.
And a measurement position mark 119a indicating the set measurement position
~ 119d and graphs 121a-1 corresponding to each measurement position
21d and an indicator line 1 showing the correspondence between the measurement position and the graph
20a to 120d are displayed on the display device. here,
As the measurement region image 118, a head model diagram or MR
It is possible to use a tomographic image of a measurement site or a three-dimensional image of the measurement site of the subject himself / herself, which is imaged by an image diagnostic apparatus typified by the I apparatus.

(Third Embodiment) FIG. 15 shows a schematic configuration of a third embodiment of the biological light measuring device according to the present invention.

The light emitted from the light source 201 is condensed using a lens system and is incident on the light source optical fiber 202.
The light emitted from the light source is intensity-modulated by the oscillator 223 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 202 is connected to the light irradiation optical fiber 204 through the optical fiber coupler 203a, the light from the light source is transmitted to the light irradiation optical fiber 204 and is irradiated to the subject 206 from the light irradiation position 205. . The wavelength of the light used depends on the spectral characteristics of the substance of interest in the living body.
When measuring the oxygen saturation and the blood volume from the O ₂ concentration, one or more wavelengths are selected from the light in the wavelength range of 600 nm to 1400 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 optical fibers for detecting light 207a and 2 for detecting the light emitted after passing through the subject 206.
07b are arranged at two different locations on the subject 206.
In this embodiment, the two optical fibers 207 for light detection are used.
a and 207b are arranged at two points of point symmetry with the light irradiation position 205 as the center of symmetry. The light irradiation optical fiber 204 and the light detection optical fibers 207a and 207b are fixed by an optical fiber fixing member 208 whose surface is painted black. The light irradiation optical fiber 204, the light detection optical fibers 207a and 207b, and the optical fiber fixing member 208 are integrated as a light detection probe for the sake of simplicity, and the details will be described later. Since the photodetection optical fibers 207a and 207b are connected to the photodetector optical fibers 209a and 209b via the optical fiber couplings 203b and 203c, the passing light detected by the photodetection optical fibers 207a and 207b is
Light is transmitted to the photodetectors 210a and 210b, and the photodetector 21
Photoelectric conversion is performed at 0a and 210b, and passing light intensity is output as electric signal intensity. As the photodetectors 210a and 210b, 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 210a and 210b are extracted by the lock-in amplifiers 224a and 224b, respectively, only the light intensity modulation frequency component of the light source. The output from the lock-in amplifier 224a is logarithmically converted by the logarithmic amplifier 225a and then input to the negative electrode of the differential amplifier 211.
The output from b is logarithmically converted by the logarithmic amplifier 225b and then input to the positive electrode of the differential amplifier 211. As a result, the differential signal of the transmitted light intensity at two different positions is output from the differential amplifier 211 as an output signal.
The output signal from the differential amplifier 211 is sequentially converted into an A / D converter 2
The data is converted into a digital signal at 12, and is taken into the computer 213 and displayed as time series data on the display device 214.

Here, as shown in FIG. 15, if the region 215 in which the hemodynamics locally changes is included only in the visual field 216b of the optical fiber for photodetection, the measured logarithmic difference signal is the local time region. It reflects only the hemodynamic changes of 215. 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 I0 (t), oxyhemoglobin and reduced hemoglobin concentrations are Cox (t) and Cdeox (t), and oxyhemoglobin concentration changed in the local region 215. The reduced hemoglobin concentration is ΔCox (t) and ΔCdeox (t), the absorption coefficients of oxyhemoglobin and reduced hemoglobin with respect to the light source wavelength λ are εox (λ) and εdeox (λ), respectively, and the attenuation due to scattering and absorption other than hemoglobin is Ds, The weighting factor caused by scattering is d
Then, the passing light intensity signal Id (t) detected by the photodetector 210b is expressed by the following formula 6, and the passing light intensity signal Id '(t) detected by the photodetector 210a is expressed by the following formula 7. It is represented by.

[0077]

Id (t) = Ds · exp [− [εox (λ) (Cox (t) + ΔCox (t)) + εdeox (λ) (Cdeox (t) + ΔCdeox (t))] d] I0 (t) Number 6

[0078]

Id ′ (t) = Dx · exp [− [εox (λ) Cox (t) + εdeox (λ) Cdeox (t)] d] I0 (t) ··· Equation 7 Next, Equation 6 After taking the natural logarithm of equation (7) and subtracting equation (7) from equation (6), the following equation (8) is obtained. The left side of Expression 8 is the measured logarithmic difference signal.

[0079]

In [Id (t) / Id ′ (t)] = − [εox (λ) ΔCox (t) + εdeox (λ) ΔCdeox (t)] d ... Is measured using 805 nm ± 10 nm,

[0080]

[Equation 9] εox (805 ± 10) ≈εdeox (805 ± 10) ············································

[0081]

## EQU10 ## In [Id (t) / Id '(t)] =-[. DELTA.Cox (t) +. DELTA.Cdeox (t)]. K ... It can be rewritten as equation 10. 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 [ΔCox (t) + ΔCdeox (t)] of the blood amount. In addition, if the number of wavelengths used for the light source is 2 wavelengths (λ1, λ2), different intensity modulation frequencies (f1, f2) are given to each wavelength, and frequency is separated by the lock-in amplifier, the transmitted light intensity signal of each wavelength is measured. can do. Therefore, since Equation 8 holds for each wavelength, the following simultaneous equations 11 and 12 can be derived.

[0082]

In [Id (λ1, t) / Id '(λ1, t)] =-[εox (λ1) ΔCox (t) + εdeox (λ1) ΔCdeox (t)] d ···

[0083]

## EQU12 ## In [Id (λ2, t) / Id '(λ2, t)] =-[εox (λ2) ΔCox (t) + εdeox (λ2) ΔCdeox (t)] d ... εox (λ1), εox (λ2), εdeox (1), εdeox (λ
Since 2) is known, the value ΔCOX (t) d corresponding to the amount of change in oxyhemoglobin and the ΔCdeox (t) d corresponding to the amount of change in reduced hemoglobin are calculated using Equation 11 and Equation 12
The time series data of the calculated relative change amount can be obtained by solving in 13 and displayed as a graph on the display device 214. 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. 16, the detection signals from the photodetectors 210a and 210b are converted into digital signals by the A / D converter 212 without using a lock-in amplifier, a logarithmic amplifier and a differential amplifier. After changing, the calculator 213
In the above, the FET processing is performed to extract only the signal corresponding to the intensity modulation frequency of the light source, and the logarithmic difference of the passing light intensity at two different detection positions is calculated by the same procedure as the above calculation process to obtain The obtained relative change amount may be displayed as a graph on the display device 214 as time series data.

17 (a) and 17 (b) show an example of the photo-detecting probe. FIG. 17A shows a cross section of the light detection probe, and FIG. 17B shows a view of the light detection probe as seen from the contact surface of the subject. 1 for the light detection probe
The optical fiber 204 for light irradiation, the two optical fibers 207a and 207b for light detection, and the optical fiber fixing member 208 made of metal or plastic with the surface coated in black are provided, and each optical fiber has an optical fiber coupler 203a, 203b, 203c. Are connected. In order 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 217 is covered with a sponge having elasticity.

Optical fibers for light detection 207a and 207b
It is necessary to change the size of the detection surface according to the purpose and the state of the subject. For example, when measuring brain function, the cross-sectional shape is a circle with a diameter of 1 mm to 20 mm or one side.
The square is about 20 mm to 20 mm. Further, the arrangement positions of the two optical fibers 207a and 207b for light detection are distance r (r = 5 mm to 5 mm) from the optical fiber 204 for light irradiation.
0 mm) is symmetrically arranged here. By preparing a plurality of types of photodetection probes having different distances r and cross-sectional shapes of the photodetection optical fibers 207a and 207b and exchanging them according to the purpose of measurement, simple measurement becomes 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.

There are various possible arrangements of the optical fiber 207 for light detection in the light detection probe. For example, as shown in FIG. 18, a light irradiation optical fiber 204
Four optical fibers 20 for light detection at a position equidistant from
7a, 207b, 207c, and 207d are arranged, and two arbitrary optical fibers for photodetection can be selected and measured. Further, 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 208.

FIG. 19 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 2
03a, 203b, 203c, optical fiber 204 for light irradiation, and optical fibers 207a, 207b for light detection
Then, the light detection probe including the optical fiber fixing member 208 is fixed to the subject 206 with the fixing belt 218 made of rubber. The optical fiber 204 for light irradiation is connected to the optical fiber 202 for light source via the optical fiber coupler 203a, and the optical fibers 207a and 207b for light detection are connected.
Are connected to photodetector optical fibers 209a and 209b through optical fiber couplers 203b and 203c, respectively. An optical fiber 202 for a light source and an optical fiber 209 for a photodetector are provided on the front panel of the optical measuring device 219.
a, 209b, an output signal strength adjusting knob 220, an output signal value display window 221, and a display device 214. Inside the optical measuring device 219, a differential amplifier, an A / D converter,
Microprocessor, light source, photodetector, optical switch,
Other necessary electric circuits are arranged.

In the output signal value display window 221, the logarithmic difference signal value of the transmitted light intensity detected at two places is digitally displayed, and the output signal adjusting knob 220 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 222 of the logarithmic difference signal is graphically displayed on the display device 214. 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 4) FIG. 20 shows a schematic configuration of Embodiment 4 of the biological light measuring device according to the present invention.

A light lens system emitted from the light source 201 is used to collect the light and enter the optical fiber 202 for the light source. The light emitted from the light source is intensity-modulated by the oscillator 223 at an arbitrary frequency of about 100 Hz to 10 MHz in order to remove noise caused by external sources. Since the light source optical fiber 202 is connected to the light irradiation optical fiber 204 through the optical fiber coupler 203a, the light from the light source is transmitted to the light irradiation optical fiber 204 and is irradiated to the subject 206 from the light irradiation position 205. . The wavelength of the light used depends on the spectral characteristics of the substance of interest in the living body, but Hb and HbO
6 when measuring oxygen saturation and blood volume from the concentration of ₂
One or a plurality of wavelengths are selected and used from the light in the wavelength range of 00 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 photodetection optical fibers 207a, 20 for detecting the light emitted after passing through the subject 206.
7b, 207c, and 207d are arranged at four different locations on the subject 206. In this embodiment, two optical fibers for light detection 207b and 207c are arranged at two points of point symmetry with the light irradiation position 205 as the center of symmetry.
The optical detection optical fiber 2 is located on a half line that passes through the center of gravity of the optical fiber for optical detection 207b with the center of gravity of
The optical detection optical fiber 207a is arranged so that the center of gravity of 07a exists, and the optical detection optical fiber 207a is located on a half line passing through the center of gravity of the optical detection optical fiber 207c with the center of gravity of the light irradiation position 205 as the origin. Optical detection optical fiber 207d so that the center of gravity of 207d exists.
Place. The center of gravity of the optical fiber 207a for detecting light and the optical fiber 207d for detecting light may be arranged anywhere as long as they are on the above-mentioned half line, but in the present embodiment, they are point-symmetrical with the light irradiation position 205 as the center of symmetry. It is arranged outside the optical fibers 207b and 207c for light detection. Here, the light irradiating optical fiber 204 and the light detecting optical fibers 207a, 207b, 207c, and 207d are metal optical fiber fixing members 208 whose surfaces are painted black.
It is fixed at. Optical fibers for light detection 207a, 2
Reference numerals 07b, 207c and 207d denote optical fiber couplers 2
Optical fibers 209a, 209b, 209c, 20 for photodetectors via 03b, 203c, 2-3d, 203e.
Since it is connected to 9d, the optical fiber 207 for light detection
The passing light detected by a, 207b, 207c, and 207d is the photodetectors 210a, 210b, 210c, and 210d.
The transmitted light intensity that has been transmitted up to and is photoelectrically converted by the photodetector 210 is output as the electric signal intensity. As the photodetector 210, 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 210a and 210b are extracted by the lock-in amplifiers 224a and 224b, respectively, only the intensity modulation frequency component of the light source. The output from the lock-in amplifier 224a is logarithmically converted by the logarithmic amplifier 225a and then input to the negative electrode of the differential amplifier 211a.
The output from 4b is logarithmically converted by the logarithmic amplifier 225b and then input to the positive electrode of the differential amplifier 211a. The electric signals representing the transmitted light intensities output from the photodetectors 210c and 210d are the lock-in amplifiers 224c and 2c, respectively.
At 24d, only the intensity modulation frequency component of the light source is extracted.
The output from the lock-in amplifier 224d is the logarithmic amplifier 2
After being logarithmically converted by 25d, it is input to the negative electrode of the differential amplifier 211b, and the output from the lock-in amplifier 224c is
After being logarithmically converted by the logarithmic amplifier 225c, the differential amplifier 2
It is input to the positive electrode of 11b. Further, the differential amplifier 211
The output from a is input to the negative electrode of the differential amplifier 211c, and the output from the differential amplifier 211b is input to the positive electrode of the differential amplifier 211c. As a result, a logarithmic difference signal of passing light intensity at four different positions is output from the differential amplifier 211c as an output signal. The output signal from the differential amplifier 211c is sequentially converted into a digital signal by the A / D converter 212, which is taken into the computer 213 and displayed as a time series data in a graph on the display device 214.

Here, as shown in FIG. 20, if the region 215 in which hemodynamics locally changes is included only in the visual field 216b of the optical fiber for photodetection, the differential amplifier 21
The logarithmic difference signal of the passing light intensity output from 1c reflects only the local hemodynamic change. The meaning of the logarithmic difference signal output from the differential amplifier 211c will be described below on the assumption that hemoglobin, which is the main component in blood, acts predominantly on light absorption for near-infrared light.

The measurement time is t, the light source wavelength is λ, the irradiation light intensity is I0 (t), the oxyhemoglobin and reduced hemoglobin concentrations are Cox (t) and Cdeox (t), respectively, and the oxyhemoglobin concentration changed in the local region 215. The reduced hemoglobin concentrations are ΔCox (t) and ΔCdeox (t), the absorption coefficients of oxyhemoglobin and reduced hemoglobin with respect to the light source wavelength λ are εox (λ) and εdeox (λ), and photodetectors 210b and 210c, respectively.
The attenuation due to the scattering and the absorption other than hemoglobin included in the intensity of the passing light detected by Ds1 and the photodetectors 210a and 21
In addition to scattering and hemoglobin included in the transmitted light intensity detected at 0d, the attenuation due to absorption is Ds2, the weighting factor caused by the scattering included in the transmitted light intensity detected at the photodetectors 210b and 210c is d1, and the photodetector 210a. And d is a weighting coefficient generated by the scattering included in the transmitted light intensity detected by 210d and 210d, the transmitted light intensity signal Id1 (t) detected by the photodetector 210c and the transmitted light intensity detected by the photodetector 210d. The signal Id2 (t), the passing light intensity signal Id1 ′ (t) detected by the photodetector 210b, and the passing light intensity signal Id2 ′ (t) detected by the photodetector 210a are respectively expressed by the following formulas 13 to It is expressed by Equation 16.

[0096]

Id1 (t) = Ds1 · exp [− [εox (λ) (Cox (t) + ΔCox (t)) + εdeox (λ) (Cdeox (t) + ΔCdeox (t))] d1] I0 (t) ... Number 13

[0097]

Id2 (t) = Ds2 · exp [− [εox (λ) (Cox (t) + ΔCox (t)) + εdeox (λ) (Cdeox (t) + ΔCdeox (t))] d2] I0 (t) ... Number 14

[0098]

Id1 ′ (t) = Ds1 · exp [− [εox (λ) (Cox (t) + εdeox (λ) Cdeox (t)] d1] I0 (t) ...

[0099]

Id2 ′ (t) = Ds2 · exp [− [εox (λ) (Cox (t) + εdeox (λ) Cdeox (t)] d2] I0 (t) ... Equation 16 Next, Equation 13 After taking the natural logarithm of
By subtracting the equation 14 from, the following equation 17 is obtained.

[0100]

In [Id1 (t) / Id2 (t)] = 1n [Ds1 / Ds2] − [εox (λ) (Cox (t) + ΔCox (t)) + εdeox (λ) (Cdeox (t) + ΔCdeox ( t))] (d1-d2) ... Equation 17 After taking the natural logarithm of Equation 15 and Equation 16, Equation 15 to Equation 1
Subtracting 6 yields the following equation (18).

[0101]

In [Id1 ′ (t) / Id2 ′ (t)] = 1n [Ds1 / Ds2] − [εox (λ) (Cox (t) + ΔCox (t)) + εdeox (λ) (Cdeox (t) + ΔCdeox (t))] (d1−d2) ... Equation 18 The left side of Equation 17 represents the output of the differential amplifier 211b, and the left side of Equation 18 represents the output of the differential amplifier 211a. Here, if Equation 18 is subtracted from Equation 17, the following Equation 1
9 is obtained.

[0102]

In [(Id1 (t) / Id2 (t)) (Id2 ′ (t) / Id1 ′ (t))] = − [εox (λ) ΔCox (t) + εdeox (λ) ΔCdeox (t) ] (d1-d2) ... Mathematical 19 The left side of Mathematical 19 represents the output from the differential amplifier 211c, 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 above-mentioned relation of the equation 9 is established, and therefore the equation 19 can be rewritten as the following equation 20 using the constant K.

[0104]

## EQU20 ## In [(Id1 (t) / Id2 (t) (Id2 '(t) / Id1' (t))] =-[. DELTA.Cox (t) +. DELTA.Cdeox (t)]. K ... , The logarithmic difference signal measured using the light source wavelength 805 nm ± 10 nm is the relative blood change amount [ΔCox (t) + Δ
Cdeox (t)] is represented.

The number of wavelengths used for the light source is 2 wavelengths (λ
1, λ2) and different intensity modulation frequencies (f1,
f2) is given and the frequency is separated by the lock-in amplifier,
The transmitted light intensity signal of each wavelength can be measured. Therefore, since the equation (19) holds at each wavelength, the following simultaneous equations (21) and (22) can be derived.

[0106]

In [(Id1 (λ1, t) / Id2 (λ1, t)) (Id2 ′ (λ1, t) / Id1 ′ (λ1, t))] = − [εox (λ1) ΔCox (t) + Εdeox (λ1) ΔCdeox (t)] (d1-d2) ・ ・ ・ Equation 21

[0107]

In [(Id1 (λ2, t) / Id2 (λ2, t)) (Id2 ′ (λ2, t) / Id1 ′ (λ2, t))] = − [εox (λ2) ΔCox (t) + Εdeox (λ2) ΔCdeox (t)] (d1-d2) ・ ・ ・ Equation 22 Extinction coefficient εox (λ1), εox (λ2), εdeox (λ1), εdeox
Since (λ2) is known, the value ΔCox (t) (d1−d2) corresponding to the amount of change in oxyhemoglobin and ΔCdeox (t) (d1−d2) corresponding to the amount of change in reduced hemoglobin can be calculated using Equation 21 and It can be obtained by solving the equation 22 in the computer 213, and the time series data of the obtained relative change amount can be displayed on the display device 2.
Graph on 14 It is also possible to further expand to increase the number of wavelengths, eliminate (d1-d2), 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. 21, the detection signals from the photodetectors 210a, 210b, 210c and 210d are respectively A / D converter 212 without using the lock-in amplifier, logarithmic amplifier and differential amplifier. After being converted into a digital signal by FFT processing in the computer 213, only the signal corresponding to the intensity modulation frequency of the light source is extracted, and the logarithmic difference of the passing light intensity at four different detection positions is calculated as described above. After calculating by the same procedure as above, the calculated relative change amount is
A graph can be displayed on the display device 214 as time-series data.

(Fifth Embodiment) FIG. 22 shows a schematic configuration of a fifth embodiment of the biological optical measurement device according to the present invention.

The light emitted from the light sources 201a and 201b is condensed using a lens system and is incident on the light source optical fibers 202a and 202b, respectively. The light emitted from each light source is generated by each oscillator 22 in order to remove external noise.
The intensity is modulated by 3a and 223b at different arbitrary frequencies f of about 100 Hz to 10 MHz. Here, the intensity modulation frequency of the light source 201a is f ₁ , and the light source 2
The intensity modulation frequency of 01b is f ₂ . The light source optical fiber 202a is connected to the light irradiation optical fiber 204a via the optical fiber coupler 203a, and the light source optical fiber 202b is connected to the light irradiation optical fiber 204b via the optical fiber coupler 203c. Light is transmitted to the light irradiation optical fibers 204a and 204b, and is irradiated onto the subject 206 from the light irradiation positions 205a and 205b. In addition, in order to obtain the reference light, the optical demultiplexers 226a and 226b are used in the middle of the light irradiation optical fibers 204a and 204b to perform demultiplexing, and the photodetector 210
A and 210c convert the intensity of each light source into an electric signal. The reference light intensity signal of the light source 201a output from the photodetector 210a is input to the lock-in amplifier 224a, and the oscillator 2
It is separated based on the reference frequency from 23a. The output from the lock-in amplifier 224a is input to the logarithmic amplifier 5a and logarithmically converted, and then input to the negative electrode of the differential amplifier 211a. Light source 20 output from photodetector 210c
The reference light intensity signal 1b is input to the lock-in amplifier 224d and separated based on the reference frequency from the oscillator 223b. The output from the lock-in amplifier 224d is input to the logarithmic amplifier 225d, logarithmically converted, and then input to the negative electrode of the differential amplifier 211b. 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 nm.
One or a plurality of wavelengths are selected from the light in the wavelength range of 1400 nm to be used. A semiconductor laser, a titanium sapphire laser, a light emitting diode, or the like can be used as the light source.

In order to detect the light emitted after passing through the subject 206, one optical fiber 207 for light detection is arranged at a position equidistant from the light irradiation positions 205a and 205b on the subject 206. Here, the optical fiber 20 for light irradiation
The surfaces 4a and 204b and the optical fiber 207 for light detection are fixed by an optical fiber fixing member 208 whose surface is painted black. The optical fiber 207 for photodetection is the optical fiber 2 for photodetector via the optical fiber coupler 203b.
09 is connected to the optical fiber 207 for light detection.
The passing light detected by is transmitted to the photodetector 210b,
The light is photoelectrically converted by the photodetector 20b and the intensity of the passing light is output as the electrical signal intensity. As the photodetector 210b, for example, a photoelectric conversion element such as a photodiode or a photomultiplier tube is used.

The electric signal representing the transmitted light intensity output from the photodetector 210b includes the transmitted light intensity signal for the light source 201a and the transmitted light intensity signal for the light source 201b. Therefore, the intensity for the light source 201a is detected by the lock-in amplifier 224b. Only the modulation frequency component is extracted, and the lock-in amplifier 224c extracts only the intensity modulation frequency component for the light source 201b. The output from the lock-in amplifier 224b is logarithmically converted by the logarithmic amplifier 225b and then input to the positive electrode of the differential amplifier 211a. Lock-in amplifier 2
The output from 24c is logarithmically converted by the logarithmic amplifier 225c and then input to the positive electrode of the differential amplifier 211b. As a result, from the differential amplifier 211a, the light source 201
A logarithmic difference signal between the intensity of a and the transmitted light intensity to the light source 201a is output as an output signal, and a logarithmic difference signal between the intensity of the light source 201b and the transmitted light intensity to the light source 201a is output as an output signal from the differential amplifier 211b. . Further, the output from the differential amplifier 211a is fed to the differential amplifier 21.
1c is input to the negative electrode and the output from the differential amplifier 211b is input to the positive electrode of the differential amplifier 211c.
From 11c, the logarithmic difference signal of the passing light intensity after the fluctuation of the light source intensity is removed is output. The output signal from the differential amplifier 211c is sequentially converted into a digital signal by the A / D converter 212, is taken into the calculator 213, and is displayed on the display device 214 as time series data.

Here, as shown in FIG. 22, if the region 215 in which the hemodynamics are locally changed is included only in the visual field 216b 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
b, the irradiation light intensity from the irradiation position 5a is I0 '(t), the reference light intensity from the demultiplexer 226b is Ir (t), the reference light from the demultiplexer 226a. Strength I
r ′ (t), the demultiplexing ratio of the demultiplexer to the reference light is α, that is, I0 (t): Ir (t) = I0 ′ (t): Ir ′ (t) = 1: α, and oxyhemoglobin And the reduced hemoglobin concentration are Cox (t), and the oxyhemoglobin concentration and the reduced hemoglobin concentration changed in the Cdeox (t) local region 215 are Δ, respectively.
Cox (t), ΔCdeox (t), and the absorption coefficients of oxyhemoglobin and deoxyhemoglobin with respect to the light source wavelength λ are εox, respectively.
(λ), εdeox (λ), where Ds is the attenuation due to scattering and absorption other than hemoglobin, and d is the weighting factor caused by scattering, the passing light intensity signal Id (t) for the light source 201b detected by the photodetector 210b, That is, the lock-in amplifier 224
The output from c is expressed by the following equation (23), and the photodetector 210
light intensity signal I for the light source 201a detected by b
d '(t), that is, the output from the lock-in amplifier 224b is expressed by the following equation 24.

[0115]

Id (t) = Ds · exp [− [εox (λ) (Cox (t) + ΔCox (t)) + εdeox (λ) (Cdeox (t) + ΔCdeox (t))] d] I0 (t) ... Number 23

[0116]

Id ′ (t) = Ds · exp [− [εox (λ) Cox (t) ÷ εdeox (λ) Cdeox (t)] d] I0 ′ (t) ... When the natural logarithms of the equations (23) and (24) are taken and then transformed, the equation (23) becomes the following equation (25), and the equation (24) becomes the following equation (26).

[0117]

In [Id (t) / I0 (t)] = In [Ds] − [εox (λ) (Cox (t) + ΔCox (t)) + εdeox (λ) (Cdeox (t) + ΔCdeox (t) )] d ...

[0118]

In [Id ′ (t) / I0 ′ (t)] = In [Ds] − [εox (λ) Cox (t) + εdeox (λ) Cdeox (t)] d ... By subtracting the expression (26) from the expression (25), the following expression (27) is obtained.

[0119]

In [(Id (t) / Id ′ (t)) (I0 ′ (t) / I0 (t))] = − [εox (λ) ΔCox (t) + εdeox (λ) ΔCdeox (t) ] d ・ ・ ・ Equation 27 where

[0120]

(Equation 28) Ir (t) = αI0 (t) ... Equation 28

[0121]

[Equation 29] Ir ′ (t) = αI0 ′ (t) ... Since Equation 29, the output from the differential amplifier 211a

[0122]

In [Id ′ (t) / αI0 ′ (t))] ... Equation 30 Since the number 30 is equal to the left side of the number 27, it is equivalent to the number 27 of logarithmic difference signals output from the differential amplifier 211c.

Here, in particular, the light source wavelength is 805 nm ±
When the measurement is performed using 10 nm, the above-mentioned relation of the equation 9 is established, and therefore the equation 27 can be rewritten as the following equation 31 using the constant K.

[0124]

In [(Id (t) / Id '(t)) (I0' (t) / I0 (t))] =-[ΔCox (t) + ΔCdeox (t)] K ... , The logarithmic difference signal measured using the light source wavelength 805 nm ± 10 nm is the relative blood change amount [ΔCox (t) + ΔC
deox (t)] is represented. In addition, if the number of wavelengths used for the light source is set to two wavelengths (λ1, λ2), different intensity modulation frequencies (f1, f2, f3, f4) are given to each wavelength and each irradiation position, and the frequency is separated by the lock-in amplifier, The transmitted light intensity signal for each wavelength and each irradiation position can be measured.
Therefore, since Equation 27 holds for each wavelength, the following simultaneous equations of Equation 32 and Equation 33 can be derived.

[0125]

In [(Id (λ1, t) / Id '(λ1, t)) (I0' (λ1, t) / I0 (λ1, t))] =-[εox (λ1) ΔCox (t) + Εdeox (λ1) ΔCdeox (t)] d ...

[0126]

In [(Id (λ2, t) / Id '(λ2, t)) (I0' (λ2, t) / I0 (λ2, t))] =-[εox (λ2) ΔCox (t) + Εdeox (λ2) ΔCdeox (t)] d ... Equation 33 Extinction coefficient εox (λ1), εox (λ2), εdeox (λ1), εdeox
Since (λ2) is known, the value ΔCOX (t) d corresponding to the amount of change in oxyhemoglobin and the ΔCdeox (t) d corresponding to the amount of change in reduced hemoglobin are solved in the computer 213 using equations 32 and 33. The time series data of the calculated relative change amount can be displayed as a graph on the display device 214. Further expand to increase the number of wavelengths, eliminate d,
Alternatively, it is possible to obtain the relative change amount of the concentration of the light-absorbing substance other than a small amount of hemoglobin.

Further, as shown in FIG. 23, the detection signals from the photodetectors 210a, 210b and 210c are respectively digitalized by the A / D converter 212 without using a lock-in amplifier, a logarithmic amplifier and a differential amplifier. After conversion into a signal, FFT processing is performed in the calculator 213 to extract only the signal corresponding to the intensity modulation frequency of each light source, and the calculated relative change amount is calculated by the same procedure as the above calculation process. A graph can be displayed on the display device 214 as time-series data.

[0128]

According to the present invention, a low-cost light irradiation means and a photodetector are used, and since the arithmetic processing is simple, high-speed processing can be performed with an economical device, and a planar image showing the shape of the object to be measured. Since the biological function associated with can be imaged, it becomes an effective means particularly for measuring a predetermined function of the biological body.

Specifically, in order to confirm the focus of epilepsy, and to confirm that the excision site is a site that does not impair important biological functions of the subject during brain excision surgery in severe epilepsy, etc. The image can be used for.

According to the prior art, when measuring the hemodynamics of a subject by alternately repeating no load and a negative sign, the subject must be rested and the reference value must be waited until the measured signal stabilizes. It fluctuated and it was not possible to perform correct measurement. According to the measuring method of the present invention, the measurement can be performed without waiting for the signal to stabilize. In addition, since fluctuations can be removed from the measurement signal, the accuracy of the signal can be improved.

When the first detection position and the second detection position are set at positions that are substantially equidistant from the light irradiation position, the intensity of the transmitted light at each detection position is changed according to the overall hemodynamic change in the living body. The signal changes equally. Therefore, the first
By taking the logarithmic difference between the transmitted light intensity signal at the detection position and the transmitted light intensity signal at the second detection position, the signal change resulting from the overall hemodynamic change is removed. further,
If only the passing light intensity signal at the first or second detection position includes a change associated with the local hemodynamic change, the passing light intensity logarithmic difference signal reflects only the local hemodynamic change. Will be.

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 substantially equidistant from the light irradiation position is taken, the influence of scattering and attenuation by the living tissue is offset, and a minute hemodynamic change reflecting a local hemodynamic change is cancelled. The signal can be detected with high accuracy.

[0133]

[Brief description of drawings]

FIG. 1 is a graph showing fluctuations in the intensity of light passing through a living body obtained by a conventional device.

FIG. 2 is a block diagram showing a configuration of an embodiment of a biological optical measurement device according to the present invention.

FIG. 3 is a diagram for explaining an example of an image creating method using the measuring device of FIG.

FIG. 4 is a graph showing a change over time of a predicted no-load signal 15 obtained from a measurement signal at one measurement point in the above embodiment.

FIG. 5 is a graph showing a temporal change of a relative change amount of hemoglobin concentration at one measurement point in the above-mentioned embodiment.

FIG. 6 is a graph showing a topography image in the above embodiment.

FIG. 7 is a graph showing another example of the topography image in the above embodiment.

FIG. 8 is a graph showing a display example of a topography image in the above embodiment.

FIG. 9 is a diagram for explaining a coordinate conversion method in another embodiment of the biological optical measurement device of the present invention.

FIG. 10 is a graph showing a display example by the measuring device of the present invention.

FIG. 11 is a graph showing a display example by the measuring device of the present invention.

FIG. 12 is a graph showing a display example by the measuring device of the present invention.

FIG. 13 is a graph showing a display example by the measuring device of the present invention.

FIG. 14 is a graph showing a display example by the measuring device of the present invention.

FIG. 15 is a block diagram for explaining an apparatus configuration according to another embodiment of the present invention.

FIG. 16 is a block diagram for explaining an apparatus configuration according to another embodiment of the present invention.

FIG. 17A is a schematic cross-sectional view showing a photodetection probe according to another embodiment of the present invention, and FIG. 17B is a bottom view showing the photodetection probe according to another embodiment of the present invention.

FIG. 18 is a schematic bottom view showing another embodiment of the light detection probe.

FIG. 19 is a diagram for explaining a usage example of the schematic light detection probe.

FIG. 20 is a block diagram for explaining a device configuration according to another embodiment of the present invention.

FIG. 21 is a block diagram for explaining a device configuration according to another embodiment of the present invention.

FIG. 22 is a block diagram for explaining a device configuration according to another embodiment of the present invention.

FIG. 23 is a block diagram for explaining a device configuration according to another embodiment of the present invention.

[Explanation of symbols]

1: Oscillator, 2: Light source, 3: Optical fiber, 4: Coupler, 5: Optical fiber, 6: Subject, 7: Photodetection optical fiber, 8: Photodetector, 9: Lock-in amplifier, 10:
Analog-digital converter, 11: calculator, 12: storage device, 13: display device, 14: measurement signal, 15: predicted no-load signal, 16: subject, 17: incident point, 18: detection point, 19: Estimated measurement point, 20: ΔCoxy (t) signal,
21: ΔCdeoxy (t) signal, 22: topography image, 23: brain surface image, 24: skin and bone image, 25:
Brain image, 26: Marker image, 27: Measurement point, 28: Perpendicular line,
29: measurement point after coordinate conversion, 30: input device 110: measurement signal, 111: predicted no-load signal, 112:
Load start mark, 113: Load end mark, 114: Difference signal, 115: Base line, 116a: ΔCoxy signal, 11
6b: ΔCdeoxy signal, 117a: ΔCoxy load time integrated value, 117b: ΔCdeoxy load time integrated value, 118: measurement site image, 119: measurement position mark, 120: indicator line,
121: graph, 201: light source, 202: optical fiber for light source, 203a to 203c: optical fiber coupler, 2
04: optical fiber for light irradiation, 205: light irradiation position, 2
06: subject, 207a-207d: optical fiber for light detection, 208: optical fiber fixing member, 209a-20
9d: optical fiber for photodetector, 210a to 210d:
Photodetector, 211: differential amplifier, 212: A / D converter, 213: calculator, 214: display device, 215: region where hemodynamics locally change, 216a, 216b: field of view of optical fiber for photodetection, 217: Subject contact surface, 2
18: fixing belt, 219: optical measuring device, 220: output signal adjusting knob, 221: output signal value display window, 22
2: time series data, 223a to 223c: oscillator, 22
4: Lock-in amplifier, 225: Logarithmic amplifier, 226:
Duplexer

Front page continuation (72) Inventor Fumio Kawaguchi 1-280 Higashi Koikekubo, Kokubunji, Tokyo Inside Central Research Laboratory, Hitachi, Ltd. (72) Inventor Yoshitoshi Ito 1-280 Higashi Koikeku, Kokubunji, Tokyo Hitachi Central Research Co., Ltd. In-house

Claims (38)

[Claims] 1. A plurality of light irradiating means for irradiating a subject with light having a wavelength in the visible to near infrared region, and a plurality of light receiving means for detecting the light emitted from the light irradiating means and passing through the inside of the subject. Means, a storage means for storing the signal detected by the light receiving means for each of the plurality of light receiving means over time, and a signal stored in the storage means to be converted into signals to be measured at a plurality of measurement points Living body light, and an image creating unit for displaying the output of the calculating unit by calculating the signal at the position of the estimated measurement point and displaying it as an image represented as an intensity signal on the two-dimensional display surface. Measuring device. 2. A plurality of light sources each of which has a different wavelength, a modulator which modulates the light of the plurality of light sources at frequencies different from each other, and a plurality of light beams which are modulated at an irradiation position. The living body optical measurement system according to claim 1, characterized in that the living body optical measuring device comprises guide means for guiding, and each of the plurality of light receiving means has a separating means for separating the intensity of light from the plurality of light sources having different wavelengths. 3. The living body optical measurement system according to claim 2, wherein the separating means is composed of a lock-in amplifier driven by a modulation signal of the modulator. 4. The biological optical measurement device according to claim 1, wherein the number of the plurality of light sources having different wavelengths is the same as the number of types of light absorbers to be measured. 5. A step of irradiating a plurality of light irradiation positions of a subject with light having a wavelength in the visible to near-infrared region, and at least light passing through the inside of the subject to each of the plurality of light irradiation positions. A step of detecting at one light detection point, a step of calculating a signal at an estimated measurement point from the plurality of light irradiation positions, a step of obtaining the concentration of a light absorber contained in the inside of the subject, and the first step And a step of displaying the obtained light absorber concentrations at a plurality of estimated measurement points as an image of a two-dimensional surface representing the subject. 6. In the first step, the measurement point is set to an arbitrary position on the normal line from the midpoint of the light irradiation position and the light detection position to the inside of the subject and perpendicular to the surface of the subject, and in the second step. , Displaying the interpolated light absorber concentration obtained by interpolating the light absorber concentration obtained at the plurality of measurement points and the light absorber concentration obtained at the plurality of measurement points between each measurement point as a topography image. An image creating method according to claim 5, which is a feature. 7. A claim 5 characterized in that an image is obtained by using the above-mentioned light-absorber concentration at a given time point or a time-averaged variation amount of the light-absorber concentration over a certain period of time. 6. The image creating method described in 6. 8. The claim 5 or 6 characterized in that in the second step, the light absorber concentration or the amount of change in the light absorber concentration is obtained at an arbitrary time interval, and continuous time-lapse images are obtained at each time interval. Image creation method described. 9. In the second step, image information of the inside of the object measured by magnetic resonance and X-rays is displayed together with the information of the light absorber concentration on the same image as the two-dimensional image. An image creating method according to claim 6, which is characterized in that 10. In the second step, the light absorber concentration or the amount of change in the light absorber concentration is obtained at an arbitrary time interval,
It is characterized in that, with reference to the time change of the change amount at any one measurement point, a correlation with the time change of the change amount at another measurement point is obtained, and a temporal image of a continuous correlation function is obtained at each time interval. An image creating method according to claim 5 or 6. 11. A living body light measuring method for measuring living body light intensity by irradiating a living body with light while alternately providing a load time for applying a load to the living body and a no-load time for not applying a load to the living body. A living body optical measurement method comprising setting a subsequent relaxation time, and predicting a signal corresponding to a biological-origin fluctuation included in the measurement signal from the measurement signal in the no-load time that does not include the relaxation time. 12. A pre-load prediction time is set immediately before each load time, a post-load prediction time is set immediately after each relaxation time, and a measurement signal and a post-load prediction time at the pre-load prediction time are set for each load time. 13. The biological optical measurement method according to claim 11, wherein a signal corresponding to a biological-origin fluctuation included in the measurement signal is predicted from the measurement signal in. 13. An arbitrary function having one or a plurality of indefinite coefficients is set, and the indefinite coefficient is adjusted by the least squares method so that the arbitrary function optimally fits a measurement signal in a no-load time that does not include a relaxation time. 13. The living body optical measurement method according to claim 11 or 12, characterized in that the optimal fitting function determined in this manner is used as a signal corresponding to fluctuation derived from a living body. 14. The biological optical measurement method according to claim 11 or 12, wherein a difference between the measurement signal and a signal corresponding to the predicted fluctuation derived from the living body is calculated. 15. A concentration and reduction of oxyhemoglobin in a living body using a ratio of a signal corresponding to a predicted biological fluctuation and a measurement signal, an absorption coefficient of oxyhemoglobin with respect to a light source wavelength, and an absorption coefficient of reduced hemoglobin with respect to a light source wavelength. Relative change amount of the sum of hemoglobin concentration or relative change amount of oxyhemoglobin concentration and relative change amount of reduced hemoglobin concentration, time change of each relative change amount, integrated relative change amount obtained by integrating each relative change amount over a predetermined time Or, the living body optical measurement method according to claim 10 or 11, wherein an average relative change amount in a predetermined time interval is calculated. 16. A signal display method for a living body light measuring device, comprising: irradiating a living body with light to measure the intensity of light passing through the living body, and displaying the measured signal or a signal obtained by calculating the measured signal on a display device. A signal display method for a living body optical measurement device, comprising: predicting a signal corresponding to a biological-origin fluctuation and displaying the predicted signal together with a measurement signal. 17. A measurement signal or a signal obtained by calculating a measurement signal by irradiating a living body with light while alternately providing a load time for applying a load and a no-load time for not applying a load to the living body. In the signal display method of the biological optical measurement device for displaying on a display device, a signal corresponding to a biological-derived fluctuation included in the measurement signal is predicted from the measurement signal in the no-load time, and the predicted signal is a predicted no-load signal. The method for displaying a signal of a living body optical measurement device is characterized by displaying the measurement signal together with the measurement signal. 18. A measurement signal or a signal obtained by calculating a measurement signal by irradiating a living body with light while alternately providing a load time for applying a load to the living body and a no-load time for not applying a load to the living body. In the signal display method of the biological light measurement device for displaying on the display device, the relaxation time following the load time is set, and the fluctuation derived from the living body contained in the measurement signal from the measurement signal in the no-load time that does not include the relaxation time is included. A signal display method for a biological optical measurement device, comprising: predicting a corresponding signal, and displaying the predicted signal as a predicted no-load signal together with a measurement signal. 19. A pre-load prediction time is set immediately before each load time, a post-load prediction time is set immediately after each relaxation time, and a measurement signal at the pre-load prediction time and a post-load prediction time are set for each load time. 19. The signal display method for a biological optical measurement device according to claim 18, characterized in that the predicted no-load signal is obtained from the measurement signal in. 20. An arbitrary function having one or a plurality of indefinite coefficients is set, and the indefinite coefficient is adjusted by the least squares method so that the arbitrary function optimally fits a measurement signal in a no-load time that does not include a relaxation time. 20. The signal display method for a living body optical measurement device according to claim 17, 18 or 19, wherein the determined optimum fitting function is a signal corresponding to the fluctuation derived from the living body. 21. The difference between the measurement signal and the predicted no-load signal is calculated, and the calculation result is displayed.
20. The signal display method of the biological optical measurement device according to claim 19. 22. A relative value of a sum of oxyhemoglobin concentration and reduced hemoglobin concentration in a living body using a ratio of a predicted no-load signal and a measurement signal, an absorption coefficient of oxyhemoglobin with respect to a light source wavelength, and an absorption coefficient of reduced hemoglobin with respect to a light source wavelength. Change amount or relative change amount of oxyhemoglobin concentration and relative change amount of reduced hemoglobin concentration are calculated, time change of each relative change amount, integrated relative change amount obtained by integrating each relative change amount over a predetermined time, or a predetermined amount 20. The signal display method for a biological optical measurement device according to any one of claims 17 to 19, characterized in that the average relative change amount in the time interval is displayed. 23. The signal display method for a living body optical measurement system according to any one of claims 16 to 19, wherein different signals or calculation results are displayed using different colors or different line types. 24. Claims 17 to 19 characterized in that a graphic showing the start time and the end time of the load time is displayed together.
The signal display method of the living body optical measurement system according to any one of 1. 25. The measurement signal is displayed in real time together with the measurement,
20. The signal display method for a biological optical measurement instrument according to claim 17, wherein the predicted no-load signal is displayed until a time earlier than the displayed measurement signal. 26. A plurality of signals for a plurality of measurement positions,
Any one of claims 16 to 19 characterized in that it is displayed together with a diagram showing a measurement site of a living body, a figure showing a measurement position, and a figure indicating correspondence between the measurement position and the signal.
A method for displaying a signal of a living body optical measurement apparatus according to the item 1. 27. The signal display method for a biological optical measurement device according to any one of claims 17 to 19, characterized in that an image photographed by an image diagnostic device is used as a diagram showing a measurement site. 28. Light irradiating means for irradiating the surface of a living body with light,
A living body optical measurement device comprising a light detecting unit that detects the intensity of light that passes through the inside of a living body and is emitted from the surface of the living body, and has at least two combinations of a light irradiation position and a light detection position. A biomedical optical measurement apparatus characterized by using a logarithmic difference signal as a measurement signal. 29. The biological light measuring device according to claim 28, comprising at least two combinations 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 to be equal. 30. A living body optical measurement system as set forth in claim 28 or 29, comprising a logarithmic amplifier and a differential amplifier, wherein a photodetection signal is logarithmically amplified and then a logarithmic differential signal is generated by the differential amplifier. 31. Claim 28 or 29, wherein 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. Biological light measurement device. 32. A light detecting probe part having the optical fiber end of the light irradiating means and the optical fiber end of the light detecting means fixed, a light source of the light irradiating means, a light detector of the light detecting means, and an electric signal processing circuit. The optical measuring device according to claim 29, further comprising a measuring device section. 33. 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 transmitted 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 is measured. 30. The biological optical measurement device according to claim 28, which is characterized in that 34. First light irradiating means for irradiating the surface of the living body with light, first irradiating light intensity detecting means for detecting the irradiating light intensity from the first light irradiating means, and irradiating the surface of the living body with light. 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 caused by the second light irradiation means; and the first logarithm. 30. The living body optical measurement system according to claim 28 or 29, further comprising: a means for measuring a differential signal and a differential signal of the second logarithmic differential signal. 35. Intensity modulation of the irradiation light from the light irradiation means,
30. The living body optical measurement system according to claim 28 or 29, characterized in that 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 Fourier transform processing and used. apparatus. 36. One of claims 28 and 29 characterized in that the number of wavelengths of irradiation light is m, the number of irradiation positions is n, and m × n types are used as the intensity modulation frequency of the light source.
The optical measurement device for living body according to the item. 37. A living body optical measurement apparatus according to claim 28 or 29 is used, and at least a signal from a region in which a light absorption characteristic locally changes due to a change in hemodynamics in a living body. The light irradiation position and the light detection position are arranged on the surface of the living body so that they are included in the light intensity signal detected at one light detection position and not included in the light intensity signal detected at at least one other light detection position. A living body optical measurement method characterized by setting and measuring. 38. The measurement is started after adjusting so that the logarithmic difference signal between two different detection positions becomes 0 in a state where the region where the light absorption characteristic locally changes in the living body does not occur. However, the living body optical measurement method according to claim 28 or 29, wherein the displacement value of the difference signal is used as a measurement signal.