JP2012125370A - Biological measurement apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To measure the distributions of biological components in the shallow and deep parts of a subject by making NIRS measurements over a distance between a plurality of light sources and a detector at multiple measuring points while keeping the light sources and the light detector out of contact with the subject, and selecting and using predetermined measuring points.SOLUTION: A biological measurement apparatus includes a light source for applying light to a subject, a light detector for detecting the light propagating through the subject, light blocking means for blocking the light impinging on the light detector from a position other than a predetermined detection point, a control unit for controlling the light source and the light detector, and an analysis unit for calculating light absorption characteristics within the subject. The light source and the light detector are arranged out of contact with the subject. The control unit detects a plurality of signals produced by the light transmitted through different paths within the subject. The analysis unit selects predetermined signals from the plurality of signals obtained by the light detector, and calculates the light absorption characteristics within the subject using the signals selected.

Description

  The present invention uses visible light or near-infrared light, and measures light absorption characteristics inside the living body, changes in biological components, and tissue structure in a biological light measuring device in which the light source and detector are not in contact with the subject. It relates to technology.

  A brain function measuring device using near infrared spectroscopy (NIRS) can be used as medical and research equipment or for market research such as confirmation of educational and rehabilitation effects, health management at home, and product monitoring. it can. Moreover, it can be used for tissue oxygen saturation measurement and muscle oxygen metabolism measurement by the same method. Furthermore, it can be used for general absorption spectroscopy equipment, such as sugar content measurement of fruits.

  Conventional brain function measuring apparatuses using NIRS include an optical topography (OT) method that non-invasively images local hemodynamic changes near the surface of the human brain. In Patent Literature 1 and Non-Patent Literature 1, the subject is irradiated with light having a wavelength belonging to the visible to infrared region, and the light passing through the subject is detected by a photodetector from a point several centimeters away, and the hemoglobin concentration An optical topography method, which is a method of measuring a change amount (or a change amount of a product of hemoglobin concentration and optical path length) and imaging it in two dimensions, is disclosed. Optical topography is characterized by low restraint on the subject compared to brain function measurement techniques such as nuclear magnetic resonance imaging (MRI) and positron emission tomography (PET). In clinical settings, it is used to measure language function and visual function, and to determine the focal brain region during epileptic seizures.

  In the optical detection signals and biological signals (hereinafter referred to as NIRS signals) obtained by non-invasive optical brain functional imaging using NIRS, including optical topography, the blood flow change distribution is reconstructed not only in two dimensions but also in three dimensions. Non-Patent Document 2 reports a method (Diffuse Optical Tomography: DOT).

  In addition, NIRS signals when performing brain activity activation tasks include the effects of skin blood flow in addition to brain-derived signals, depending on measurement conditions, such as when using tasks that vary blood pressure during measurement. Have been reported in various studies such as Non-Patent Document 3. In such measurement conditions that may induce the influence of skin blood flow, it is important to separate and measure brain activity in consideration of surface layer components such as skin blood flow.

In conventional optical brain function measurement, three-dimensional reproduction using a method (hereinafter referred to as multi-SD method) of analyzing measurement data at a plurality of light source (Source) -detector (Detector) distances (hereinafter referred to as SD distance) is used. Various configurations and surface layer signal removal methods have been proposed in Patent Document 2, Non-Patent Document 4, and the like.
In order to realize measurement by the multi-SD method, it is necessary to increase the number of measurement points and to arrange multi-SD probes. Here, the light source (irradiation means) and the detector (light detection means) are collectively referred to as a probe.

Japanese Unexamined Patent Publication No. 9-019408 U.S. Patent No. 5902235

A. Maki et al., “Spatial and temporal analysis of human motor activity using noninvasive NIR topography,” Medical Physics 22, 1997-2005 (1995). R. Endoh, M. Fujii and K. Nakayama, "Depth-Adaptive Regularized Reconstruction for Reflection Diffuse Optical Tomography," Optical Review 15 (1), 51-56 (2008) O. Vassend and S. Knardahl, "Personality, affective response, and facial blood flow during brief cognitive task," Int J Psychophysiol 55 (3), 265-278 (2005) Q. Zhang, G. E. Strangman and G. Ganis, "Adaptive filtering to reduce global interference in non-invasive NIRS measures of brain activation: How well and when does it work ?," NeuroImage 45 (3), 788-794 (2009)

  In the conventional contact-type probe structure in biological light measurement, the number of measurement points is limited because the distance between the measurement points cannot be reduced to several mm or less due to the physical dimensions of the probe. Furthermore, since the irradiation position and the detection position are fixed, it is difficult to change them at any time during measurement. In addition, extreme miniaturization and an increase in the number of parts have a problem of increasing manufacturing costs. Even if miniaturization or the like is performed and the probe interval is set to a few millimeters or less, the light is scattered multiple times in the living body. Therefore, the high definition of the probe interval is not necessarily proportional to the improvement of the spatial resolution.

  Even if the light intensity decreases due to the influence of local hair, moles, spots, etc. on the head at a certain measurement point, the contact configuration has a small number of measurement points, so the measurement at that measurement point is not possible. I had to use the data. Furthermore, when the light source stability, irradiation power, detector sensitivity, etc. change at a specific measurement point due to a failure of the light source or detector, the cause of the decrease in the signal-to-noise ratio is derived from brain activity In some cases, it was difficult to immediately determine whether it was from a device.

  The objective of this invention is providing the technique for solving the said subject.

  As an example of the present invention for solving the above-mentioned problem, in the biological light measurement apparatus, one or a plurality of light irradiation means for irradiating a predetermined irradiation point on a subject with the one or a plurality of the light irradiation means One or a plurality of light detection means for detecting light emitted from the light irradiation means and propagating in the subject from a predetermined detection point, and the light detection means from a position other than the predetermined detection point A light shielding unit for shielding light incident on the light source, a control unit for controlling the one or more light irradiation units / light detection units, and an analysis unit for calculating at least light absorption characteristics in the subject. And at least one of the light irradiation means and the light detection means is disposed in a non-contact manner with respect to the subject, and the light irradiation means and the light detection means are distances between the irradiation point and the detection point. So that there are two or more types And the light detection means separates and detects a plurality of signals by light propagated through different paths in the subject, and the analysis unit detects the plurality of signals obtained by the light detection means. A predetermined signal is selected, and changes or distributions of light absorption characteristics or biological components at a plurality of depths are calculated from the surface of the subject using only the selected signal.

  ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to measure distribution of the biological component in shallow parts and deep parts, such as a test subject's head, and it becomes possible to measure the information of the desired measurement site | part with high precision.

The figure which shows the apparatus structure of this invention. Flow chart of analysis. The flowchart when calculating an optical parameter by the finite element method. The figure which shows the plane display of blood volume distribution. The figure which shows the three-dimensional display of blood volume distribution. Device optical system schematic. The figure which shows the relationship between SD distance and photon transmittance | permeability. The flowchart of light irradiation. The figure which shows the content of Formula 1.

  An example of a specific configuration for achieving the above-described object will be described below, and then details will be described with reference to the drawings.

The living body measurement apparatus according to the present embodiment includes a light source and a photodetector that are at least one non-contact with respect to the subject, and a light-emitting body for wavelength conversion is installed on the skin surface of the subject, and unnecessary light such as surface reflected light. Is shielded by a wavelength filter. The wavelength filter has a function of shielding excitation light and transmitting fluorescence emitted from the light emitter. Furthermore, by driving the optical system, the irradiation point and the detection point are moved as needed to perform scan measurement.
With this method, the number of light sources and photodetectors used can be reduced, and at the same time, the number of measurement points can be increased by scanning measurement, and measurement at a plurality of irradiation point-detection point distances can be realized. Only appropriate measurement point data is selected from the measurement data at the measurement points, and analysis is performed to separate the shallow component and the deep component of the head blood flow change.

  As a result, measurement points can be easily increased by scanning measurement in which at least one of the light irradiation means and the light detection means is in a non-contact configuration, and a one-dimensional, two-dimensional distribution or 3 Dimensional distribution can be measured. Moreover, the measurement point used at the time of an analysis can be selected. In addition, since multiple measurement points can be obtained with the same number of light source / detector pairs in a non-contact configuration, only specific measurement points are not affected by these defects due to defects in the light source and detector. Conditions such as light source stability, irradiation power, and detector sensitivity can be more easily unified between points.

  FIG. 1 shows an apparatus configuration diagram in this embodiment. The biological light measurement device 30 that detects light that is incident on light and that is scattered and absorbed in the living body to detect the light emitted from the living body includes one or more light sources 101, a light source driving device 103, a lens system 203, and an optical system. A light transmission beam tracking device 210 including a drive unit 204 is provided. The light transmission beam tracking device 210 causes light 40 emitted from one or more light sources 101 to enter the subject 10 via the lens system 203. Here, one or a plurality of light sources 101 irradiate two wavelengths of visible to near-infrared light having high biopermeability, for example, a wavelength near 730 nm and two wavelengths near 800 nm. Furthermore, in order to detect the lock-in of the light that has passed through the living body, the light 40 is intensity-modulated at an appropriate frequency.

  The light source 101 is driven by a light source driving device 103, and the gain of one or more photodetectors 102 is controlled by a control / analysis unit 104. The control / analysis unit 104 also controls the light source driving device 103 and receives input of measurement conditions, subject information, and the like from the input unit 105. The lens system 203 is driven by the optical system driving unit 204 in order to change the irradiation point and the detection point on the subject 10 as needed. The optical system driving unit 204 is controlled by the control / analysis unit 104.

  Here, the one or more light sources 101 may be a semiconductor laser or a light emitting diode, and the one or more photodetectors may be an avalanche photodiode or a photodiode. The optical system driving unit 204 may include a mirror, a lens, a mirror driving device, and the like, and includes, for example, a biaxial galvanometer mirror and an fθ (F-theta) lens.

  The light irradiated from the light transmission beam tracking device 210 propagates and scatters in the subject 10 and can be detected at a position away from the incident point on the surface of the subject 10. At this time, since the light propagates while being scattered in the subject 10 and can be detected from any place near the incident point, if the photodetector 102 is not in contact with the subject 10 and is away from the surface, a specific place It is difficult to selectively receive light emitted from the light source.

  Furthermore, when the light transmitter 60 is non-contact, the surface reflected light is strongly received. Therefore, it is usually necessary to place the optical detector 102 or an optical fiber optically coupled with the optical detector in contact with the subject 10 and select and receive light from directly below the optical detector 102.

  Therefore, in this embodiment, a light emitter 207 installed on the surface of the subject 10 is used instead of such selective light reception by spatial filtering. The light applied to the irradiation point at a position away from the light emitter 207 propagates inside the subject 10 and excites the light emitter 207 to generate fluorescence 80 having a wavelength different from that of the excitation light. The wavelength emitted from the light source 101 needs to be a wavelength that can excite the light emitter 207, and both the wavelength near 730 nm and the two wavelengths near 800 nm used here satisfy the condition. On the detection side, the surface of the light emitter 207 that is not in contact with the subject 10 is covered with the wavelength filter 208. Only the predetermined optical path of the fluorescence 80 may be covered with the wavelength filter on the surface of the light emitter 207, and the other surface not in contact with the subject 10 may be an appropriate light shielding material such as aluminum. Note that the surface of the illuminator 207 that contacts the subject 10 needs to be covered with at least a member that transmits excitation light, but the member that transmits light having wavelengths near 730 nm and 800 nm, which is excitation light here. For example, quartz may be used. Further, the wavelength filter 208 is disposed so as to cover the entire optical path to the photodetector 102 immediately before the photodetector 102, that is, between the photodetector 102 and the light emitter 207. The wavelength filter 208 has a function of shielding light having the same wavelength (spectrum) as light emitted from the light source 101 and transmitting light having the same wavelength (spectrum) as light emitted from the light emitter 207. Therefore, the wavelength filter 208 detects light from other than a predetermined detection point such as excitation light reflected on the surface of the subject 10 or stray light due to excitation light that propagates only in the shallow part of the subject 10 and is emitted from the subject surface near the irradiation point. The light incident on the detector 102 is shielded, and the photodetector 102 can receive only the fluorescence 80. Thereby, it is possible to selectively receive light that is propagated and scattered inside the subject 10 and that corresponds to a predetermined SD distance (for example, 30 mm).

  The light receiving side receives the fluorescence 80 emitted from the light emitter 207, and therefore includes a wavelength filter 208, a lens system 203, an optical system driving unit 204, a photodetector 102, an amplifier 106, and an analog-digital converter 107. A device 220 is provided. The electrical signal photoelectrically converted by the photodetector 102 is amplified by the amplifier 106, converted from analog to digital by the analog-digital converter 107, and sent to the control / analysis unit 104.

  In the living body measurement apparatus of the present invention, the irradiation point and the detection point can be changed at any time by the beam tracking device 210 for light transmission and the beam tracking device 220 for light reception. In order to realize measurement by the multi-SD method, measurement is performed by moving an irradiation point or a detection point by at least one of the light transmission beam tracking device 210 and the light receiving beam tracking device 220. When the detection point is moved, since the detection point moves on the light emitter 207, the issuer 207 needs to be appropriately arranged on the subject 10 in advance. As the arrangement method, a straight line shape, a parallel line shape, a concentric circle shape, a point shape, a triangular shape, or the like can be considered. In the case of a linear shape, uniaxial scanning and raster scanning can be performed, and there is an effect that a wide range can be set as a measurement range. In the case of a parallel line shape, it is possible to perform measurement at two or more different SD distances at the same time by one irradiation, and further, it is possible to make a wide range a measurement range. In the case of a concentric circle shape, setting the irradiation point at the center of the concentric circle shape has an effect that the irradiation point is fixed and measurement at a plurality of surrounding SD distances can be realized. In the case of a point shape, various types of irradiation point trajectories can be designed. For example, a point shape, a linear shape, a concentric circle shape, or the like can be used. Since the detection point can be fixed and there is no need to consider the influence of fluorescence from other points, the system can be simplified. In the case of a triangular shape, in addition to the effect of a point shape, there is an effect that, when an image is measured, the relative position coordinates and posture angle of the subject 10 with reference to the apparatus can be calculated from the shape and size of the triangle.

  The light detection signals detected at the respective SD distance arrangements are detection signals of light propagated through different paths in the subject 10 and are separately analyzed by the control / analysis unit. It can be confirmed from the light intensity or the time-resolved detection waveform that each irradiation light propagates through different paths at measurement points with different SD distances. In other words, the higher the light intensity, the smaller the amount of absorption in the living body and the shorter the propagation path, and the average propagation time is obtained from the time-resolved waveform, but the difference in propagation time means the difference in propagation distance and path .

  The control / analysis unit 104 performs analysis based on the signal detected by the photodetector 102. Specifically, it receives the digital signal obtained by conversion by the analog-digital converter 107, calculates the detected light amount or transmittance at each SD distance measurement point based on the digital signal, and the subject 10 Blood volume change (especially oxygenated / deoxygenated hemoglobin change or total hemoglobin change) or transmittance distribution is analyzed, and the analysis result is sent to the image construction unit 108. As a method for calculating blood volume and hemoglobin change, the method described in Non-Patent Document 1 or the like is used based on the modified Beer-Lambert rule.

  At this time, the control / analysis unit 104 can select and analyze a signal at an appropriate measurement point among the light detection signals at a plurality of measurement points. That is, it is possible to eliminate data with extremely low signal-to-noise ratio, discontinuous transmittance data with surrounding measurement points, artifacts due to hair, moles, and the like. For example, it is possible to preferentially select measurement points whose detection intensity is close to the value obtained by averaging the detection intensities of nearby measurement points and use them for analysis. This process is a process of selecting points where the measured value is not extremely high or low with respect to nearby measurement points, and continuously increases linearly, decreases linearly, or takes a constant value. There is an effect that it is possible to select a measurement point with a low possibility. Alternatively, a manual method for excluding data of measurement points determined to be unnecessary by visual observation may be used. This method has an effect that analysis according to the characteristic of the waveform unique to the subject can be performed. If it is not a non-contact configuration, the number of measurement points is limited, making it difficult to select such measurement points. However, since the non-contact configuration allows continuous data acquisition, select effective measurement points for analysis. It becomes possible to do. Further, the measurement point may be selected by a method of selecting according to an appropriate criterion using MRI data or X-ray CT data of the subject 10. For example, a thin part of the skull or a part without the paranasal sinuses (particularly the frontal sinus) is a place where the irradiated light is relatively easy to pass through the gray matter. Is possible. This method has an effect that biological data to be acquired can be efficiently acquired with a high signal-to-noise ratio.

  Various methods have been reported as a method for separating deep and shallow signals from a plurality of SD distance measurement data, but a method of subtracting short SD distance data by multiplying an appropriate coefficient from long SD distance data, or The method described in Non-Patent Document 4 or the like is used. Or you may determine the absorption coefficient and scattering coefficient of each site | part from the comparison with the light propagation Monte Carlo simulation result based on structural data, such as a test subject's MRI and X-ray CT. Since this method is an analysis method based on the actual head structure data of the subject, there is an effect that a more accurate result can be obtained. Alternatively, the absorption coefficient and the scattering coefficient may be determined by a diffusion equation method assuming a uniform scatterer or a numerical solution of a diffusion equation by a finite element method. This method is used for various light propagation analyses, and generally has an effect that the calculation load is smaller than that of the Monte Carlo simulation and the processing can be performed at high speed.

FIG. 2 shows a flowchart of a series of analysis from the measurement data of a plurality of SD distances to separation into deep and shallow signals, removal of the shallow signals, and extraction of only the deep brain-derived signals.
(S201) Non-contact multi-point measurement is performed with a multi-SD arrangement. In this step, light is incident on an irradiation point that moves along a predetermined locus, and light is detected from a detection point that moves along the predetermined locus. The detection point moves on the light emitter 207, and the irradiation point follows a predetermined trajectory so as to have a predetermined SD distance from the detection point.
(S202) Measurement points used for analysis are selected except for measurement points and discontinuous points that contain a lot of noise. In this step, the amount of noise is estimated from the standard deviation or standard error of measurement data at each measurement point when the subject 10 is not performing a task, that is, at rest. When the standard deviation or standard error is large, it is determined that the noise is large. Note that, in other methods, unnecessary measurement points may be determined by frequency analysis or visual observation.
(S203) Using the short SD distance measurement signal as a reference signal, a shallow part-derived component and a deep part-derived component are extracted from the long SD distance measurement signal. In this step, for example, processing such as subtracting a fitting signal obtained by linearly regressing a constant multiple of the short SD distance measurement signal to the long SD distance measurement signal from the long SD distance measurement may be performed.
(S204) The signal derived from the shallow part is removed, and only the signal derived from the deep part is reconstructed and displayed. In this step, only the deep part-derived signal obtained in the previous step is used to display in two dimensions or three dimensions.

FIG. 3 shows a flowchart for calculating optical parameters by the finite element method.
(S301) Model input (optical parameter distribution estimated value / each layer thickness estimated value).
(S302) The forward problem is solved by the finite element method.
(S303) The forward problem result is compared with the measurement data (optical parameter distribution) to calculate the distance.
(S304) Search for an optical parameter distribution that minimizes the distance.

  By the analysis as described above, the control / analysis unit 104 can calculate the distribution and change of the light absorption characteristics at a plurality of types of depths from the surface of the subject 10. Furthermore, the influence of the blood flow rate change in the surface layer portion of the subject 10 can be separated and removed as necessary.

  The image construction unit 108 configures the blood volume change or transmittance distribution of the subject 10 as a one-dimensional, two-dimensional, or three-dimensional image, and the display unit 109 displays the result. FIG. 4 shows a planar display of the blood volume distribution, and FIG. 5 shows a stereoscopic display of the blood volume distribution.

  With the above configuration, it is possible to measure a change in blood volume inside the living body, particularly a change in oxygenated / deoxygenated hemoglobin, from the spatial distribution of the detected light amount or transmittance.

  Here, a hemoglobin change is assumed as a measurement component in the living body, but other components can be similarly implemented. For example, cytochrome oxidase, myoglobin, fat, water and the like may be used. Although the lock-in detection is described here as the light detection method, other methods such as a time division method and a code modulation method may be used.

  The illuminant 207 is, for example, the compound of Formula 1 shown in FIG. 9, and emits fluorescence having a wavelength of about 1.0 μm when excited with light having wavelengths of 730 nm and 800 nm. Since the wavelength of the excitation light is a wavelength band with relatively high permeability in the living body, the light 40 emitted from the light source 101 is incident on the head of the subject 10 and propagates in the cerebral cortex to excite the light emitter 207. Since the fluorescence intensity is proportional to the excitation light intensity, by measuring the fluorescence intensity with the light receiver 102, it is possible to observe light absorption change, blood flow change, etc. in the head tissue such as skin, cerebral cortex, and skull.

  The light emitter 207 used here can be excited by visible and near infrared light in the vicinity of wavelengths of 730 nm and 800 nm, and thus is suitable for measuring the light absorption change of a substance in a living body. Even in the case of other light emitting materials, any material that excites and emits light at a wavelength used for obtaining light absorption information of the subject may be used. In addition to fluorescence, phosphorescent light, Raman scattered light, or the like may be used.

  In the measurement using the light emitter 207, a time delay occurs from excitation to light emission due to the existence of the fluorescence lifetime, and the time waveform of the fluorescence emitted from the light emitter 207 is generally different from the time waveform of the excitation light. The fluorescence emitted by the light emitter 207 has a waveform obtained by convolving the excitation light and the fluorescence response function. Therefore, if the fluorescence response function determined by the fluorescence lifetime is known, an excitation light waveform can be obtained by performing a deconvolution process on the fluorescence waveform using a fluorescence response function by numerical calculation or the like. If the fluorescence lifetime is sufficiently short, the effect of this process is small, but if the fluorescence lifetime is long, the accuracy in the analysis can be improved by using the excitation light waveform obtained by deconvolution processing. Become.

  The wavelength filter 208 used here may be any filter that blocks the excitation light in the vicinity of wavelengths 730 nm and 800 nm and allows only the fluorescence in the vicinity of wavelength 1.0 μm, such as an InP (indium phosphide) filter. good. The wavelength filter 208 is installed immediately above the light emitter 207 and at a position just before entering the light receiving lens system 203 or the photodetector 102. Thereby, the light emitter 207 is prevented from being excited by stray light other than the light transmitted through the subject 10, and the photodetector 102 receives the direct reflected light from the light irradiation point on the light transmission side. Can be prevented. Further, the mark 205 for detecting the position and movement of the subject 10 may be omitted, and the light emitter 207 may be used as the mark. By using the light emitter 207 as a mark, it is not necessary to track the position of the mark 205, the calculation load in the control / analysis unit 104 is reduced, and at the same time, the number of parts can be reduced and the system can be simplified. .

  The shape of the illuminant 207 may be, for example, a small cell shape in order to receive detection light from a specific point on the surface of the subject 10. A two-dimensional or two-dimensional detected light amount distribution can be measured. For example, the illuminant 207 may have a band shape or a structure having an adhesive surface for adhering to the subject 10. With this structure, the subject 10 can comfortably wear the light emitter 207, and the burden on the subject 10 during measurement can be reduced.

  FIG. 6 shows a schematic diagram of the apparatus optical system. In this figure, the subject 10 is irradiated with light 40 from the apparatus main body 30, and further, the light emitter 207 installed at a detection point about 30 mm away is excited, and the emitted fluorescence 80 has a wavelength immediately above the light emitter 207. The schematic diagram of the apparatus optical system when the filter 208 and the wavelength filter 208 immediately before the detection unit of the apparatus main body 30 are transmitted and detected by the apparatus main body 30 is shown. The light emitters 207 are arranged one-dimensionally. When the irradiation point and the detection point are simultaneously moved while keeping the SD distance constant, transmittance data of the same SD distance can be efficiently acquired. Alternatively, a plurality of SD distances can be measured by scanning a detection point on the light emitter 207 for one irradiation point. Furthermore, by moving the irradiation point little by little, transmittance data at a plurality of SD distances can be acquired over a wide range, which is effective when it is desired to perform measurement with increased spatial resolution in the depth direction. At this time, the measurement position or the SD distance can be measured in any combination of the peripheral portions of the light emitter 207 by the irradiation point scanning method. For example, if the illuminant 207 is arranged one-dimensionally on a straight line, the irradiation point scans in parallel with the illuminant distribution while maintaining a predetermined SD distance, or is perpendicular to the illuminant distribution. Various scanning methods and scan trajectories can be designed, such as scanning in the direction. On the light receiving side, if there is sufficient sensitivity, the entire light emitter 207 may be imaged by an imaging tube, an imaging device, a CCD camera, a CMOS camera, or the like without scanning. The imaging configuration speeds up the processing on the light receiving side and eliminates the need for a scanning mechanism, so that the apparatus can be simplified and downsized. When the relative position between the subject 10 and the apparatus changes during measurement, the light receiving system can be used as the subject recognition sensor 201 for detecting the relative position and posture of the subject 10. effective.

  Thus, by making both the light source 101 and the photodetector 102 non-contact, restrictions on the movement and posture of the subject 10 are reduced, and particularly when the subject 10 is a human, the comfort of the subject 10 is increased, and more There is an effect that natural measurement can be realized. Further, it is possible to reduce the influence of vibration or the like conducted to the light source 101 or the light detector 102 due to expansion / contraction of the skin blood vessel accompanying the pulsation of the heart or the like.

  Note that the amount of light received by one or more photodetectors 102 varies greatly depending on the SD distance. For example, according to the result of a light propagation Monte Carlo simulation using a typical brain model, as shown in FIG. 7, the detected light quantity when the SD distance is 10 mm is 100 times or more compared to when the SD distance is 30 mm. FIG. 7 is a diagram showing the relationship between the SD distance and the photon transmittance. The horizontal axis indicates the SD distance, and the vertical axis indicates the photon transmittance. Therefore, it is preferable to change the output power of the light source and the amplification factor (gain) of the detector according to the SD distance. Therefore, a plurality of light sources are sequentially turned on one by one, the output power of the light source is changed according to the SD distance, and the detector gain is changed as needed. Thus, it is necessary to adjust the output intensity of the light source 101 according to the photodetector sensitivity and dynamic range, and it is set by performing test measurement in advance, or the value of the output intensity obtained empirically. Is set in advance. Such measurement can be performed at one wavelength or at two or more wavelengths. By this method, it is possible to prevent the detector from being saturated, to measure a wide SD distance range that can be detected, and to measure a wide range of living tissue in which various optical characteristic values are distributed.

  In the above embodiment, the case where the subject 10 is stationary or the irradiation point and the detection point are fixed is described except for the modification. However, in general measurement, the subject 10 and the biological light measurement device 30 are connected to each other. The relative positional relationship can vary. Even in such a case where the subject 10 is not stationary, the biological light measurement device 30 needs to irradiate the predetermined position of the subject 10 with the light 40 and receive the fluorescence 80 from the predetermined position. Therefore, the biological measurement apparatus of the present invention includes the object recognition sensor 201 and the image analysis unit 202 in order to recognize the coordinates of the irradiation point and the detection point.

  An image obtained by the object recognition sensor 201 is analyzed by the image analysis unit 202, and the coordinates of the subject 10 (relative position with respect to the apparatus main body 30) and the laser irradiation point coordinates on the subject 10 are calculated. If the subject 10 is stationary with respect to the apparatus main body 30, the coordinates of the image and the coordinate system on the subject 10 correspond one-to-one, so that the laser irradiation point coordinates on the subject 10 can be easily calculated. When the subject 10 is not stationary, it is necessary to install the mark 205 or the inertial sensor 206 on the subject 10. When the inertial sensor 206 is provided, a means for transmitting the sensor output to the control / analysis unit 104 in the apparatus main body 30 by wireless communication means is further required. Alternatively, when the inertial sensor 206 has a storage unit, the time and sensor data can be held and added to the analysis offline after the measurement is completed. In order to detect the movement of the subject 10 using the mark 205 on the subject 10, the relative coordinates of the subject are recognized from the shape and size when the image is picked up by the subject recognition sensor 201 such as a CCD image sensor. It must be a landmark that can. The shape may be, for example, an asymmetric polygonal shape. By using this shape, relative coordinates can be calculated from the shape and size of the imaged landmark.

  Alternatively, there may be a method of determining the relative coordinates of the subject 10 by imaging a plurality of marks 205 installed on the subject 10 using a plurality of image sensors. In this configuration, when there are a plurality of marks 205 and they are arranged three-dimensionally rather than in a plane, the distance between each mark 205 and each image sensor is different, and there is a mark 205 that is out of focus. In addition, there is an effect that the relative coordinates of the subject 10 can be determined with high accuracy by using information of a plurality of image sensors.

  Further, the relative position with respect to the apparatus main body 30 is calculated, the optical system driving unit 204 is operated as necessary, and the lens system 203 such as a mirror / lens is driven to change the irradiation point and the detection point. Here, the optical system driving unit 204 includes, for example, an electric motor, a MEMS, or the like.

FIG. 8 shows a flowchart of light irradiation in the present invention.
(S801) An image is acquired by the subject recognition sensor.
(S802) Determination of object coordinates for the apparatus from the shape and size of the mark on the object.
(S803) The relative coordinates of the subject with respect to the apparatus are calculated.
(S804) The locus of the light irradiation point on the subject coordinates is converted into device coordinates.
(S805) The optical system driving unit is operated to control the light irradiation point, the optical system is adjusted, and the focus is adjusted.
(S806) Light irradiation starts.

  The movement of the object coordinate system with respect to the apparatus is always detected in real time, and at the same time, the optimum light irradiation direction is calculated from the light incident state from the apparatus light source, and the light irradiation direction is irradiated. With this safety mechanism, when the subject 10 moves accidentally, the irradiated light does not enter the eyes of the subject 10, and safety is further improved. Furthermore, there is an effect that more comfortable measurement can be realized without causing the subject to feel uncomfortable because the incident light incidentally enters the eye of the subject 10.

  According to the present embodiment, the light transmitter has a light beam tracking device and is not in contact with the subject, so that the light irradiation point can be changed more easily and at high speed. Even when the position of the detector is fixed, measurement at many measurement points is possible by moving the light irradiation point.

  In this embodiment, the light source 101 and the detector 102 are not in contact with the subject 10 (including an object in contact with the subject 10). However, either the light source 101 or the detector 102 is used. Even in the case of contact configuration with the subject 10 (including an object in contact with the subject 10), scan measurement at a plurality of SD distance arrangements can be performed by the beam tracking mechanism on the non-contact light transmitting side or light receiving side. Since it can be implemented, the present invention is equally applicable.

  In the above embodiment, the method of shielding unnecessary light derived from excitation light such as surface reflected light by wavelength filtering by performing wavelength conversion using the light emitter 207 has been described. The subject 10 is irradiated with light, the light detector 102 performs time-resolved measurement of the detection waveform of the pulsed light, and the deep part in the subject 10 with reference to the time when the light propagated in the subject 10 reaches the light detector 102. Alternatively, a method of selecting only the light signal propagating through the light beam may be used. That is, since the light that has reached the photodetector 102 at an early stage is considered to be surface reflected light and light that has propagated through a shallow portion, it is possible to take measures such as not using the analysis. For detection of pulsed light, a streak camera or the like may be used. Such a time filtering method may be a method in which a mechanical shutter is provided immediately in front of the photodetector 102 to block light reaching the photodetector 102 at an unnecessary time. With this configuration, it is possible to separate and remove the surface reflected light and the light propagated through the shallow portion without using the wavelength filter 208. Furthermore, a method of disposing optical property variable means on the surface of the subject 10 that can change the position of the transparent layer that transmits at least the light irradiated by the light source 101 by electronic control may be used. As a result, if the power is sufficient, the irradiation side can perform uniform irradiation without the optical system driving unit on the light transmission side that controls the irradiation point. In addition, the light receiving side has an effect that light reception from the light emitters 207 other than the detection points can be prevented by changing the transparent layer on the light emitters 207 distributed on the subject 10. In addition, both the irradiation side and the light receiving side have an effect that the apparatus is simplified, and that a high-speed scan measurement and a large amount of data acquisition can be expected by moving the transparent layer at high speed by electronic control.

  Even when the SD distance is the same, when the light wavelength is different, the optical characteristics of the tissue generally have wavelength dependence, and therefore the absorption coefficient and the scattering coefficient differ for different wavelengths. Therefore, when a plurality of lights having significantly different wavelengths are incident on the same irradiation point, the light of each wavelength propagates through different average optical paths. In the near-infrared region, it has been reported that the shorter the wavelength, the larger the scattering coefficient of living tissue (for example, SJ Matcher, M. Cope and DT Delpy, "In vivo measurements of the wavelength dependence of tissue-scattering coefficients" between 760 and 900nm measured with time-resolved spectroscopy, "APPLIED OPTICS 36 (1), 386-396 (1997), fig. 6). The larger the scattering coefficient, the harder it is to reach the deep part. When detecting in a reflection type arrangement (probe arrangement in which the light source and the detector do not face each other and face in the same direction in parallel), the proportion of the detection light occupying shallow propagation light increases. On the other hand, the wavelength of the isoabsorption point of hemoglobin is a wavelength at which the absorption coefficients of oxygenated hemoglobin and deoxygenated hemoglobin are equal, and is a wavelength at which the total hemoglobin change can be measured from a change in the detected light amount of only one wavelength. There are one isosabsorption point of hemoglobin near 800 nm and multiple around 500-600 nm. These two or more wavelengths are simultaneously irradiated to a common irradiation point and detected from a common detection point. Thus, it becomes possible to measure the total hemoglobin change at the tissue depth corresponding to each wavelength. With this apparatus configuration, since the number of wavelengths used is small and scanning is not required, the apparatus is simplified, and there is an effect that it is possible to realize shallow and deep separation measurement at a lower cost. Here, even when not using the wavelength of the equiabsorption point of hemoglobin, other biological components are estimated by absorption spectroscopy in each wavelength band by using a plurality of nearby wavelengths in a plurality of different wavelength bands. Is also possible. For example, two wavelengths may be used near 600 nm and two wavelengths near 800 nm. Thereby, not only total hemoglobin, but also biological components that require measurement at a plurality of wavelengths, such as oxygenated hemoglobin and deoxygenated hemoglobin, can be measured.

DESCRIPTION OF SYMBOLS 10 Test subject 30 Apparatus main body 40 Light 80 Fluorescence 101 1 or several light sources 102 1 or several photodetectors 103 Light source drive device 104 Control / analysis part 105 Input part 106 Amplifier 107 Analog-digital converter 108 Image structure part 109 Display unit 201 Subject recognition sensor 202 Image analysis unit 203 Lens system 204 Optical system drive unit 205 Marking 206 Inertial sensor 207 Light emitter 208 Wavelength filter 210 Beam tracking device for light transmission 220 Beam tracking device for light reception

Claims (18)

One or a plurality of light irradiation means for irradiating a predetermined irradiation point on the subject with light;
One or a plurality of light detecting means for detecting light emitted from the one or more light irradiating means and propagating through the subject from a predetermined detection point;
A control unit for controlling the one or more light irradiation means / light detection means;
An analysis unit for calculating at least light absorption characteristics in the subject;
At least one of the light irradiation means and the light detection means is arranged in non-contact with the subject,
The light irradiation means and the light detection means are arranged or controlled so that there are two or more types of distances between the irradiation point and the detection point,
The light detection means detects a plurality of signals separated by light propagated through different paths in the subject,
The analysis unit selects a predetermined signal from the plurality of signals obtained by the light detection means, and uses the selected signal to determine light absorption characteristics or biological components at a plurality of depths from the subject surface. A biological measuring device characterized by calculating changes or their distribution. A light emitter that is installed on the subject and emits light having a different emission spectrum that is excited by the light irradiated by the light irradiation means;
The living body measurement apparatus according to claim 1, wherein the light detection unit is capable of detecting light emitted from the light emitter.   The biological light measurement apparatus according to claim 1, further comprising a light shielding unit configured to shield light incident on the light detection unit from a position other than the predetermined detection point.   The light shielding means is disposed between the light detection means and the light emitter, shields light having the same wavelength as the light emitted by the light irradiation means, and is the same as the light emitted by the light emitter. The biological measurement apparatus according to claim 3, wherein the biological measurement apparatus is a wavelength filter having a function of transmitting light having a wavelength. The living body measuring apparatus according to claim 2, wherein at least a part of the light emitter is covered with the light shielding unit. The analysis unit deconvolves the detection waveform obtained by the light detection means using a response function based on the fluorescence lifetime or phosphorescence lifetime of the light emitter, and uses the obtained signal as a detection signal. The biological measurement apparatus according to any one of claims 2 to 5. The biological measurement apparatus according to claim 1, wherein the control unit includes an optical system control mechanism for changing the irradiation point or the detection point as needed. The living body measurement apparatus according to claim 1, wherein the optical system control mechanism includes any one of a mirror, a lens, and a mirror driving device. The biological measurement apparatus according to claim 1, wherein the light detection unit is an imager. 10. The analysis unit according to claim 1, wherein the analysis unit selects a predetermined signal from the plurality of signals on the basis of a time at which the light propagated in the subject reaches the light detection unit. The biological measurement apparatus according to one.   The biological measurement apparatus according to claim 1, further comprising a display unit for displaying an analysis result in the analysis unit.   The biometric apparatus according to any one of claims 1 to 11, wherein the analysis unit selects a measurement point to be used by using MRI data or X-ray CT data of the subject. The living body measurement apparatus according to claim 1, wherein the analysis unit selects a measurement point to be used by using a paranasal sinus distribution of a subject. The light irradiation means irradiates the subject with pulsed light,
The light detection means measures the time-resolved detection waveform of the pulsed light,
The biological measurement apparatus according to claim 1, wherein the analysis unit analyzes a detection intensity of the pulsed light at a predetermined time. 15. An optical characteristic varying unit capable of changing, by electronic control, a position of a transparent layer that at least transmits light irradiated by the light irradiation unit on the surface of the subject. The biological measurement apparatus according to any one of the above. 16. The biological measurement apparatus according to claim 1, wherein the analysis unit preferentially uses a measurement point whose detection intensity is close to a value obtained by averaging detection intensities of surrounding measurement points. The living body measuring apparatus according to any one of claims 1 to 16, wherein the control unit changes the irradiation point within a predetermined distance from a two-dimensionally arranged phosphor. The biological measurement apparatus according to any one of claims 1 to 17, wherein the light irradiated from the light irradiation means has a wavelength of an isosbestic absorption point of hemoglobin and two or more different wavelengths. .