WO2010150751A1 - Dispositif d'instrumentation biologique - Google Patents

Dispositif d'instrumentation biologique Download PDF

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Publication number
WO2010150751A1
WO2010150751A1 PCT/JP2010/060483 JP2010060483W WO2010150751A1 WO 2010150751 A1 WO2010150751 A1 WO 2010150751A1 JP 2010060483 W JP2010060483 W JP 2010060483W WO 2010150751 A1 WO2010150751 A1 WO 2010150751A1
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Prior art keywords
light
subject
frontal sinus
measurement
point
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PCT/JP2010/060483
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English (en)
Japanese (ja)
Inventor
司 舟根
洋和 敦森
雅史 木口
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株式会社日立製作所
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Priority to JP2011519889A priority Critical patent/JP5202736B2/ja
Publication of WO2010150751A1 publication Critical patent/WO2010150751A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4058—Detecting, measuring or recording for evaluating the nervous system for evaluating the central nervous system
    • A61B5/4064—Evaluating the brain

Definitions

  • the present invention relates to a biological measurement method for noninvasively measuring a human internal structure such as the frontal sinus.
  • the brain function measuring device using near infrared spectroscopy can be used as medical / research equipment, or for market research such as confirmation of educational and rehabilitation effects, home health management, and product monitoring. Moreover, it can be used for tissue oxygen saturation measurement and muscle oxygen metabolism meter by the same method. Furthermore, it can be used for general absorption spectroscopy equipment, such as measuring sugar content of fruits.
  • Conventional brain function measuring devices using near infrared spectroscopy include an optical topography method that noninvasively images local hemodynamic changes near the surface of the human brain.
  • the optical topography method irradiates a subject with light having a wavelength belonging to the visible to infrared region, detects multiple signals of light that have passed through the subject with the same photodetector, and detects the amount of hemoglobin concentration change (or hemoglobin concentration).
  • This is a method of measuring the change in the product of the optical path length) (see, for example, Patent Document 1).
  • brain function measurement techniques such as MRI and PET, it has a feature of low restraint on the subject. In clinical settings, language functions and visual functions are measured.
  • the presence of the frontal sinus which is one of the paranasal sinuses, greatly changes the optical signal obtained. Because of the presence of the frontal sinus in the skull, the proportion of photons detected by the photodetector that have propagated in the gray matter of the cerebrum changes significantly, and the average partial optical path length in the gray matter changes. is there.
  • the cerebral cortex which is the gray matter layer of nerve cells that spreads over the surface of the cerebrum, is the main measurement area in optical topography, and is the area where hemodynamics change with cranial nerve activity.
  • the frontal sinus is known to have large individual differences. Because it develops after birth, it is thought to change according to the environment. In particular, it is known that the frontal sinuses of people living in cold regions are small (see, for example, Non-Patent Document 2).
  • the frontal sinus is present non-uniformly in the optical topography measurement region, non-uniform transmission occurs and the partial optical path length in the cerebral gray matter becomes non-uniform.
  • the component that appears in the signal is proportional to the partial optical path length, so it is not detected as the same level of signal change. There is. In other words, it is difficult to estimate the true cerebral blood fluctuation amount unless the partial optical path length is obtained. Since there are individual differences in the distribution of the frontal sinus, when performing brain function measurement by irradiating the frontal sinus region with light, an analysis that corrects the influence after measuring the frontal sinus is desired.
  • the frontal sinus region may be irradiated only during the prefrontal cortex measurement.
  • the presence of the frontal sinus is not considered much when measuring the prefrontal cortex, and it will be necessary to improve the accuracy of optical brain functional imaging considering the frontal sinus in the future.
  • the signal is a T2 star (T2 *) weighted signal, and the difference in permeability at the boundary of permeability (or magnetic susceptibility) such as nasal cavity, sinus cavity, ear cavity, tissue / air or tissue / fat. May cause distortion of the local magnetic field, resulting in signal degradation and signal position error due to spin phase dispersion, that is, artifacts (false images). It is important to predict these artifacts in advance by knowing the frontal sinus distribution.
  • An object of the present invention is to provide a technique for solving the above problems.
  • the frontal sinus measuring apparatus of the present invention includes one or a plurality of light irradiating means for irradiating a subject with light in order to measure the distribution of the frontal sinus in a non-invasive manner.
  • one or a plurality of light detecting means for detecting light irradiated from a plurality of light irradiating means and transmitted, propagated or scattered in the subject, and the one or more light irradiating means / light detecting means are controlled.
  • a control unit and an analysis unit for calculating at least the frontal sinus and / or sinus distribution of the subject based on signals obtained by the one or more light detection means are provided.
  • the frontal sinus distribution information obtained by using the light transmittance distribution measured at multiple light source-detector distances is used to adjust the light source power and photodetector sensitivity in optical brain function measurement.
  • Means for correcting biological measurement data such as optical brain function measurement and fMRI are provided.
  • fMRI measurement with reduced artifacts by using the frontal sinus distribution in advance is realized.
  • FIG. 1 shows an example of an apparatus configuration in this embodiment.
  • the living body light measuring device 30 that can detect light that has entered the living body and can detect the light that is scattered and absorbed in the living body and propagates, the light 40 emitted from one or a plurality of light sources 101 is passed through the waveguide 50. Through the subject 10.
  • the light propagating through the subject 10 is detected by one or more photodetectors 102 via the waveguide 50 from a detection point located at a position away from the incident point.
  • 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 waveguide 50 may be an optical fiber or the like.
  • the light source 101 is driven by the light source driving device 103, and the gain of one or a plurality of photodetectors 102 is controlled by the control / analysis unit 104.
  • the control / analysis unit 104 also controls the light source driving device 103 and receives input of conditions and the like from the input unit 105.
  • 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.
  • the control / analysis unit 104 performs analysis based on the signal detected by the photodetector 102. Specifically, the digital signal obtained by the conversion from the analog-to-digital converter 107 is received, the spatial distribution of the detected light quantity or transmittance is calculated based on the digital signal, and the frontal sinus distribution or transmittance distribution is analyzed. Then, the analysis result is sent to the image construction unit 108.
  • the frontal sinus distribution or transmittance distribution of the subject 10 is configured as a one-dimensional, two-dimensional, or three-dimensional image in the image construction unit 108, the frontal sinus pattern is identified by the pattern identification unit 109, and the result is displayed by the display unit 110. Is displayed.
  • the structure inside the living body in particular, the skeletal structure including the structure of the frontal sinus, which is a kind of paranasal sinus, from the spatial distribution of the detected light quantity or transmittance.
  • FIG. 2 a diagram showing the position of the frontal sinus
  • FIG. 3 a typical shape is shown in a mid-sagittal section (FIG. 2) and a front view (FIG. 3) of the frontal sinus. 2 and 3, a frontal sinus 20 and a frontal sinus-skull boundary 21 are shown.
  • the frontal sinus is located in the skull between the eyebrows.
  • shape and position of the frontal sinus vary among individuals, and the present invention is not limited to this.
  • 4A, 4B, 5A, and 5B show examples of the probe arrangement of the probe holder 121 in which the distance between the light transmitter 60 and the light receiver 70 is variable.
  • the transmitter / receiver that contacts the subject 10 in particular is sometimes called a probe.
  • the light transmitter 60 and the light receiver 70 are optically coupled to one or more light sources 101 and one or more photodetectors 102, respectively. Since the pair of the light transmitter and the light receiver constitutes one measurement point, various measurement points for the distance between the light transmitter and the detector are formed by the combination of each light transmitter and detector.
  • the distance between the light transmitter and the detector is referred to as an SD (Source-Detector) distance.
  • the average depth through which the detected photons propagate depends on the SD distance.
  • a one- to three-dimensional transmittance distribution is obtained using a plurality of SD distances.
  • the measurement point is a substantially middle point between the light transmitter 60 and the light receiver 70.
  • the measurement point and the depth that can be measured are different.
  • the two-dimensional array as shown in FIGS. Arrangement is conceivable.
  • it may have a mechanism for changing the SD distance, and a configuration in which a three-dimensional transmittance distribution can be obtained by measuring the SD distance a plurality of times may be used.
  • a configuration in which a three-dimensional transmittance distribution can be obtained by measuring the SD distance a plurality of times may be used.
  • the contact state or optical coupling state of the probe holder 121 or one or more light sources 101 and one or more photodetectors 102 to the subject 10 is the same. Or it needs to be almost the same.
  • a mechanism for changing the SD distance for example, an adjustment mechanism using an adjustment screw in which the relationship between the rotational speed and the movement distance is known, or a method using a mechanism that changes the positional relationship between the probe rows in a sliding manner. is there.
  • an adjustment mechanism using an adjustment screw in which the relationship between the rotational speed and the movement distance is known or a method using a mechanism that changes the positional relationship between the probe rows in a sliding manner.
  • the light received by one or more photodetectors 102 varies greatly depending on the SD distance.
  • the amount of light detected when the SD distance is 10 mm is 100 times or more that when the SD distance is 30 mm. 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. Accordingly, 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 with time as necessary.
  • Fig. 6 shows the estimated distribution of frontal sinuses and transmitter / receiver positions.
  • the light transmitter 60 and the light receiver 70 are disposed on the entire forehead portion. Not only the positional relationship between the transmitter / receiver and the frontal sinus distribution shown here, but it is also possible to place the transmitter / receiver below the orbit to measure the paranasal sinuses other than the frontal sinus. is there.
  • a configuration in which the light transmitter 60 and the light receiver 70 are spread over the entire forehead portion at intervals of about 5 mm in a grid arrangement may be employed.
  • the plurality of measurement points at this time there are those having a plurality of SD distances due to the pair of light transmitter and light receiver. Therefore, for example, at a measurement point with an SD distance of 50 mm or more, the detected light amount is small and a sufficient S / N ratio (signal to noise ratio) cannot be obtained.
  • FIG. 7 shows a flowchart showing the overall flow of frontal sinus measurement.
  • S701 Light source / detector calibration measurement using a uniform phantom. Here, especially when using a plurality of light sources / detectors, the output of each light source is set to a preset value (for example, all are made equal), and the photoelectric conversion sensitivity of each detector is set. Measure.
  • S702 A transmitter / receiver is attached to the subject. Usually, a probe holder for holding a plurality of light transmitting / receiving probes is fixed to the forehead of the subject.
  • S703 The SD distance is set. Here, the SD distance in the probe holder as shown in FIGS. 4A, 4B, 5A, 5B is manually adjusted.
  • (S704) Test measurement is performed as necessary to adjust the light source power and the amplification factor of the photodetector.
  • the subject 10 When actual measurement is performed, it is desirable that the subject 10 is not stimulated so that brain activity that causes noise does not enter the signal. For example, it is important to stabilize the brain activity by causing the subject 10 to display a fixed-point screen or imagine a scene that does not place a load on the brain.
  • the diffusion equation is solved as a forward problem using the finite element method, and the absorption coefficient / scattering coefficient distribution matching the result is obtained.
  • a method of searching can be considered.
  • a method of estimating the thickness of each structure by assuming the layer structure of the head and the scattering coefficient and absorption coefficient of each layer is also conceivable.
  • FIG. 8 shows a flowchart for calculating the optical parameters.
  • S801 Model input (optical parameter distribution estimated value / each layer thickness estimated value).
  • S802 The forward problem is solved by the finite element method.
  • S803 The forward problem result is compared with the measurement data (optical parameter distribution), and the distance is calculated.
  • S804 Search for an optical parameter distribution that minimizes the distance.
  • FIG. 9 shows a display example of the relationship between the measurement position and the transmittance for each SD distance.
  • the inflection point 24 is shown as an example.
  • the inflection point defines a certain axis, and when the transmittance t on the axis is expressed by the function f (x) of the position coordinate x on the axis, the second derivative f ′′ (x)
  • the transmittance is greater when the frontal sinus is present than when it is absent.
  • the horizontal axis is the SD distance [mm]
  • the vertical axis is the photon transmittance
  • the thickness of the frontal sinus is 0, 1, 2 when a typical head model is assumed.
  • the amount of change in which the photon transmittance exceeds the threshold within the specified position range For example, when the photon transmittance fluctuates by one digit or more between 5 mm, the midpoint of the 5 mm section may be determined as the frontal sinus-skull boundary.
  • the method for calculating the frontal sinus-skull boundary in two dimensions can be created by interpolating the one-dimensional method using multiple columns, and by directly interpolating the two-dimensional discrete data in space.
  • the frontal sinus-skull boundary detection flowchart is shown in Fig. 1.
  • the SD distance should be about 20 mm or more. It is necessary to receive photons that have reached .
  • S1101 The transmittance distribution measured with substantially the same SD distance is calculated.
  • S1102 A change point calculation axis is set.
  • S1103 A change point (for example, an inflection point) is calculated.
  • FIG. 12 shows a flowchart when the frontal sinus-skull boundary is estimated using transmittance measurement data based on a plurality of SD distances.
  • S1202 A map for each SD distance is created and displayed.
  • S1203 Search for an area that is not seen in SD 1, but is seen in SD 2, and has a higher transmittance than the surrounding area.
  • an optimal algorithm is selected for the region to be measured and probe placement, and the estimation accuracy can be further improved.
  • change the algorithm used in the scanning direction of the measurement change the algorithm depending on whether it is a two-dimensional distribution or a three-dimensional distribution, purpose of use (measurement of transmittance only, optical topography signal correction, fMRI signal correction, pulse wave use) It is conceivable to change the algorithm by crosstalk amplitude measurement etc.).
  • a detection method with higher accuracy can be used according to the purpose.
  • Frontal sinus shapes are known to vary greatly from individual to individual, and can be classified into several types of shape patterns. By performing these type classifications, it is possible to estimate the overall shape of the frontal sinus to some extent even from a small amount of data.
  • the shape type of the frontal sinus is stored in the database, and the pattern is identified using various pattern identification methods.
  • the shape type of the frontal sinus is as shown in FIG.
  • Each pattern in FIG. 13 shows a typical shape pattern when the frontal sinus-skull boundary 21 is projected onto the frontal plane of the subject 10.
  • PCA principal component analysis
  • SOM self-organizing map
  • SVM support vector machine
  • DT decision tree
  • NN neural network
  • FIG. 14 shows a flowchart when the frontal sinus shape type is classified and displayed from the frontal sinus measurement result.
  • S1401 The frontal sinus measurement is performed or the frontal sinus measurement result is called from the database.
  • S1402 A pattern matching method is selected.
  • (S1403) Normalize the measurement results and calculate the distance to each pattern.
  • (S1404) Interpolate with the closest pattern and display the result.
  • (S1405) Judgment whether distance is below a threshold value. The threshold value is determined in advance. If the distance is less than or equal to the threshold, go to (S1407). If the distance does not fall below the threshold, go to (S1406).
  • (S1406) Determination of whether to add a pattern. When a new pattern is not added, the process returns to (S1401) to perform additional measurement. When a new pattern is added to the database, a new pattern classification result is displayed in (S1407). (S1407) The pattern classification result is displayed. (S1408) Save in the database.
  • the parameters set for each pattern may be automatically calculated and displayed as necessary.
  • the parameter corresponds to the length of each side.
  • the frontal sinus shape type classification result 111 and each parameter value 112 are shown.
  • the positional relationship with Nz in the international 10-20 method used for electroencephalogram measurement is shown.
  • the average thickness of the frontal sinus, the cross-sectional area when viewed from the front, the volume, and the like may be displayed.
  • the three-dimensional magnetic digitizer refers to a device that measures the 3D position coordinates of each light transmitter 60 and light receiver 70 using a magnetic field.
  • the position coordinates of each light transmitter 60 and light receiver 70 may be converted into standard brain coordinates (for example, MNI coordinate system) by the method shown in Non-Patent Document 3 or the like.
  • the apparatus of the present invention holds the probe position coordinates at the time of analysis, the coordinates of the frontal sinus or absorption coefficient or scattering coefficient distribution on the subject 10 on the standard brain can be known, and optical brain function measurement Sometimes, the hemoglobin concentration change amount can be calculated with higher accuracy from these distributions.
  • the coordinates are useful when determining the measurement position when using different light transmitters 60 and light receivers 70 in optical brain function measurement. Even if the light transmitter 60 and the light receiver 70 are arranged at different positions, if the position is measured after each probe is mounted, data can be handled in the same coordinate system by analysis.
  • FIG. 16 A display example of the frontal sinus distribution measured as described above is shown in FIG.
  • the estimated line of the frontal sinus-skull boundary 21 and the transmittance distribution 114 (SD distance 30 mm) are simultaneously displayed.
  • Transmittance [arb. [unit] follows the gray scale bar 115, and the magnitude of the value is expressed by shading.
  • a case where measurement is performed at two wavelengths of 695 nm and 830 nm is shown.
  • the measurement results for the two wavelengths are slightly different, and a diagram that combines the two results is also displayed.
  • the transmittance distribution is interpolated between measurement points and is shown as a two-dimensional map.
  • the frontal sinus-skull boundary, the state of the two-dimensional distribution, the state of the three-dimensional distribution, or which method to display is selected in advance or when displayed on the screen.
  • the display method can be selected to be two-dimensional or three-dimensional using the radio button 113.
  • the positions of the light transmitter 60 and the light receiver 70 and the estimated measurement positions may be displayed simultaneously.
  • the position of the frontal sinus can be grasped before measuring the brain function such as optical topography, and for example, the brain function measurement avoiding the position of the frontal sinus can be performed.
  • the frontal sinus distribution estimated for each SD distance can be displayed as shown in FIGS. In FIG.
  • the frontal sinus-skull boundary 21 obtained from the transmittance distribution when the SD distance is 10 mm, 20 mm, and 30 mm is shown as another map in order from the top.
  • the three maps of FIG. 17 are arranged in layers and displayed so that they can be rotated within the screen as required.
  • the position of the frontal sinus can be grasped intuitively.
  • the measurement target is only the frontal sinus, but the same analysis is possible even when the distribution of other sinuses is measured.
  • This embodiment enables non-invasive, efficient frontal sinus measurement / distribution estimation, and more accurate implementation and analysis of various brain function measurements.
  • FIG. 19 shows a movable probe holder 131 that moves only the position of the same probe pair by the control mechanism while keeping the contact state with the subject substantially the same.
  • the light transmitter 60 and the light receiver 70 are arranged in a vertical row, and a plurality of SD distances can be measured.
  • the movement locus and the measurement coordinates are recognized by the probe position recognition unit 132, and the position coordinates are passed to the apparatus main body 30.
  • the movable probe holder 131 is fixed to the subject 10 via the holding portion 133 for the subject 10 so that the movable range is the frontal region.
  • the probe position recognition unit 132 recognizes the positions of the light transmitter 60 and the light receiver 70 by measuring the electric resistance value between AB of the terminal 137.
  • the movable probe holder 131 constitutes a variable resistor 136 (potentiometer) that exhibits a constant electric resistance value per unit length, and the resistance value between AB of the terminal 137 varies depending on the probe position. It is like that.
  • the resistance value of the unit length of the variable resistor 136 is R [ ⁇ / m]
  • the length is L [m]
  • the electrical resistance value is obtained as LR [ ⁇ ].
  • the length that is, the position of the movable part 138
  • the length that is, the position of the movable part 138
  • the movable probe holder 131 has a scale 135 in order to improve the reproducibility of measurement when the movable part 138 is moved manually or to improve the convenience during measurement.
  • a mechanism for making it move automatically it may have a mechanism for making it move automatically.
  • the same light source and photodetector can be used, and the output power of the light source and the sensitivity of the photodetector, the loss in the waveguide, the amplification factor of the amplifier, etc. can be made almost equal. Measurement data can be easily compared. Further, by using the probe moving type, it is possible to measure at an arbitrary interval, and to measure the transmittance distribution with higher resolution. If only the relative comparison between the measurement channels is performed, calibration based on the absolute value of the transmittance becomes unnecessary, and there is an effect that the labor of measurement can be saved.
  • Example 1 and Example 2 are cases where the light transmitter 60 is in contact with or close to contact with the subject 10, but the light transmitter 60 includes a light beam tracking device 210, and a light irradiation point. As long as the coordinates are recognized and held, the light transmitter may be non-contact.
  • the apparatus of the present invention includes a subject recognition sensor 201 and an image analysis unit 202 in order to recognize the coordinates of the light irradiation point.
  • the image obtained by the subject 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 20 is provided, a means for transmitting the sensor output to the control / analysis unit 104 or the like in the apparatus main body 30 by wireless communication means is further required.
  • the inertial sensor 20 has a memory
  • 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.
  • a method may be used in which a plurality of subject recognition sensors 201 are provided, and a plurality of landmarks 205 installed on the subject 10 are imaged using a plurality of image sensors to determine the relative coordinates of the subject 10.
  • FIG. 21 shows a flowchart at the time of measurement with the light transmitter non-contact and the light receiver in contact.
  • S2101 An image is acquired by the subject recognition sensor.
  • S2102 Determination of subject coordinates for the apparatus from the shape and size of the mark on the subject.
  • S2103 The relative coordinates of the subject with respect to the apparatus are calculated.
  • the locus of the light irradiation point on the subject coordinates is converted into device coordinates.
  • the optical system driving unit is operated to control the light irradiation point, the optical system is adjusted, and the focus is adjusted.
  • Light irradiation starts.
  • the signals from the respective detectors are irradiated at the time of detection accordingly.
  • the SD distance is calculated from the point coordinate information, and is stored in the database as transmittance data at each SD distance.
  • FIG. 22 shows a flowchart for stopping irradiation for safety.
  • S2201 The subject is temporarily fixed at the measurement position.
  • S2202 Imaging by the subject recognition sensor is started.
  • S2203 A deviation threshold for safety is calculated.
  • the movement of the subject coordinate system with respect to the device is always detected in real time, and at the same time, the optimal light irradiation direction is calculated from the light incident state from the device light source, and the light irradiation direction is irradiated.
  • This safety mechanism prevents the irradiated light from entering the eye when the subject moves accidentally, and thus increases safety. 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 subject's eyes.
  • the light transmitter has a beam tracking device for light transmission 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, it is possible to measure at many measurement points by moving the light irradiation point.
  • FIG. 23 shows a device configuration diagram when the transmitter / receiver is non-contact.
  • 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, the light propagates while being scattered in the subject 10 and can be detected from any place near the incident point. Therefore, if the light receiver 70 is not in contact with the subject 10 and is away from the surface, the light is separated from the specific place. It is difficult to selectively receive the emitted light. Furthermore, when the light transmitter 60 is non-contact, the surface reflected light may be received strongly.
  • 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 irradiated 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 having a wavelength different from that of the excitation light.
  • the excitation light is removed by a wavelength filter, and only the fluorescence is received, thereby selectively receiving the light propagated and scattered inside the subject 10 and corresponding to the set SD distance (for example, 30 mm). can do.
  • the light transmission side is the same as that of the third embodiment.
  • the light receiving side receives the light 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. 220.
  • the control / analysis unit 104 receives an input from the input unit 105, processes an image acquired by the subject recognition sensor 201 and analyzed by the image analysis unit 202, and is output from the analog-digital converter 107.
  • the detected light quantity is received, and the light source driving device 103, the optical system driving unit 204, and the photodetector 102 are controlled. Further, the data analyzed by the control / analysis unit 104 is image-constructed by the image construction unit 108, and the result identified by the pattern identification unit 109 is displayed on the display unit 110.
  • the light emitter 207 is, for example, the compound of Formula 1 shown in FIG. 33, and emits fluorescence having a wavelength of about 1.0 ⁇ m when excited at a wavelength of 0.8 ⁇ m. Since the excitation light has a wavelength with relatively high permeability in the living body, the light 40 emitted from the light transmitter 60 is incident on the head of the subject 10 and returns through the cerebral cortex to emit the light emitter 207. Excited. Since the fluorescence intensity is proportional to the excitation light intensity, a change in light absorption in the cerebral cortex or skull can be observed by measuring the fluorescence intensity with the light receiver 70.
  • the case of one wavelength as the light source 101 has been described. However, it is possible to observe the transmittance, the amount of blood, and the oxygenation state for each wavelength by using a light source having two or more wavelengths as is normally used. it can.
  • the luminous body 207 used here can be excited by near-infrared light having a wavelength in the vicinity of 0.8 ⁇ m, and is therefore suitable for measuring a change in light absorption of a substance in a living body.
  • any material that excites and emits light at the wavelength used to obtain the light absorption information of the subject may be used.
  • fluorescence, phosphorescent light, Raman scattered light, or the like may be used.
  • the wavelength filter 208 used here may be any filter that cuts the excitation light in the vicinity of the wavelength of 0.8 ⁇ m and transmits only the fluorescence in the vicinity of the wavelength of 1.0 ⁇ m, such as a filter made of InP (indium phosphide). .
  • 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.
  • 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.
  • the illuminant 207 may have a band shape or a structure having an adhesive surface for adhering to the subject 10. With such a structure, the subject 10 can wear comfortably.
  • FIG. 24 shows a schematic diagram of the apparatus optical system when both the transmitter and the receiver are not in contact with the subject.
  • 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 just before the detection unit of the apparatus main body 30 are transmitted and detected by the apparatus main body 30 is shown.
  • transmittance data of the same SD distance can be efficiently acquired.
  • a plurality of SD distances can be measured by scanning detection points on the light emitter 207 with respect to one irradiation point.
  • the measurement position or the SD distance can be measured in any combination of the periphery of the light emitter 207 by the irradiation point scanning method.
  • the irradiation point scans in parallel with the light emitter distribution while maintaining a constant SD distance, or is perpendicular to the light emitter distribution.
  • Various scanning methods and scan trajectories can be designed, such as scanning in the direction. If the light receiving side has sufficient sensitivity, the entire phosphor may be imaged with an imaging tube, a camera, or the like without scanning.
  • both the light transmitter 60 and the light receiver 70 non-contact, restrictions on the movement and posture of the subject 10 are reduced.
  • the comfort of the subject 10 is increased. There is an effect that more natural measurement can be realized.
  • the change in hemoglobin concentration length obtained by measurement is the amount of change in the product of hemoglobin concentration and optical path length, and is proportional to the partial optical path length in the brain cortex (If the temporal variation of the partial optical path length is negligible)
  • the light model is used in the simple model in which the scalp, skull, cerebrospinal fluid, gray matter, white matter thickness, equivalent conversion scattering coefficient, and absorption coefficient are assumed as the head model.
  • FIG. 25 shows the calculation result of the average partial optical path length of gray matter by the light propagation Monte Carlo simulation.
  • the horizontal axis is the SD distance
  • the left vertical axis is the gray matter partial optical path length [mm] when the frontal sinus thickness is 1, 2, 4, 6 mm
  • the right vertical axis is when the frontal sinus thickness is 0 mm. It represents the partial light path length of gray matter.
  • the frontal sinus has a sufficiently large flat plate shape. Since the results vary greatly depending on the shape of the frontal sinus, it is necessary to use the result of simulation for each of the frontal sinus shape patterns as shown in FIG.
  • the frontal sinus distribution measured in Examples 1 to 5 is measured as a brain function imaging result when the gray matter partial optical path length at a certain SD distance is obtained as L gray as a result of light propagation Monte Carlo simulation.
  • the change in hemoglobin concentration length (the amount of change in the product of hemoglobin concentration and partial optical path length) is divided by L gray (or multiplied by 1 / L gray ), so that It is possible to obtain it in a reflected form.
  • the light source 101 has two or more wavelengths, and the wavelengths are those described in Non-Patent Document 1.
  • the hardware configuration can use the apparatus configuration diagram of the present invention (for example, FIG. 1) as it is.
  • this embodiment can also be implemented by including the optical brain function measurement apparatus 90.
  • FIG. 26 shows an apparatus configuration diagram when the living body measuring apparatus of the present invention and the optical brain function measuring apparatus 90 are combined.
  • Frontal sinus distribution information 300 and coordinate information 301 are transmitted from the apparatus main body 30 of the present invention to the optical brain function measuring apparatus 90.
  • the reference coordinates of the subject 10 for example, Nz in the International 10-20 method
  • the distribution information such as the shape of the frontal sinus
  • FIG. 27 shows a flowchart for performing hemoglobin signal correction in optical brain function measurement using the frontal sinus measurement result.
  • S2701 At the input unit, whether to perform frontal sinus measurement (to S2702) or read from the database (to S2704) is selected.
  • S2702 (1. When frontal sinus measurement is selected) Frontal sinus distribution measurement is performed.
  • S2703 The measurement result is saved in the database.
  • S2704 (2. When reading from database is selected) Frontal sinus distribution is read from the database.
  • S2705 The gray matter partial optical path length (L gray ) is calculated from the light propagation Monte Carlo simulation data and the frontal sinus distribution result.
  • S2706 Optical brain function measurement is performed, and the hemoglobin concentration length change is measured.
  • S2707 The change in hemoglobin concentration length is multiplied by (1 / L gray ) to convert it into a concentration.
  • S2708 The result is displayed on the display unit.
  • the signal-to-noise ratio (SNR) of the signal strongly depends on the detected light quantity and also on the partial optical path length of the gray matter. Therefore, adjusting the light output in the optical brain functional imaging device in consideration of the frontal sinus distribution is useful for uniformizing the SNR between measurement sites, and has the effect of preventing saturation of the output of the photodetector. Further, a method of adjusting the light output of the light source so that the absolute values of the detected light amounts are almost equal is also conceivable.
  • FIG. 28 shows a flowchart for setting measurement conditions in optical brain function measurement using the frontal sinus distribution.
  • S2801 Carry out frontal sinus measurement.
  • S2802 Frontal sinus type classification and parameter (position, size) determination.
  • S2803) Select optimization conditions (uniform detection light quantity, uniform SN ratio, etc.).
  • S2804) The light quantity is set from the frontal sinus measurement result.
  • S2805) Optical brain function measurement (or MRI measurement).
  • the difference between the equivalent conversion scattering coefficient and the absorption coefficient at each layer of the head at each wavelength is used using measurement data at two or more wavelengths.
  • FIG. 29 shows an example of simultaneous display of the measured frontal sinus distribution and optical brain functional imaging measurement results.
  • the intensity of the oxygenated hemoglobin concentration length change is represented by black and white shades, and the relationship between the shade density and the strength is shown in a gray scale bar 311.
  • the map is created by interpolating from the values at each measurement point by cubic spline interpolation.
  • a time display scroll bar 312 is provided, and a map at an arbitrary time can be displayed.
  • the oxygenated hemoglobin concentration length change (oxy-Hb) map 310 the positions of Nz (nasal root) and Fpz in the international 10-20 method are also shown. This indicates where on the subject it was measured.
  • the oxygenated hemoglobin concentration length change (oxy-Hb) map 310 shows a state before correction using the frontal sinus distribution measurement result, but it is corrected by checking the check box 313. A map of is displayed.
  • the frontal sinus distribution greatly affects the partial optical path length in gray matter, displaying it at the same time is very useful in terms of signal interpretation. For example, for the frontal sinus based on the information that the frontal sinus is directly below even when the amplitude is very small compared to other channels even though the SN ratio of the optical topography signal change is not so bad. It can be determined that the gray matter partial optical path length is reduced.
  • the analysis result of optical brain functional imaging measurement represented by the optical topography method can be corrected based on information on the internal structure of the living body such as the frontal sinus distribution, and the light source power at the time of measurement can be varied. Adjustments can be made based on optimization conditions (uniform detection light amount, uniform SN ratio, etc.). Furthermore, there is an effect that information that can serve as one basis can be provided when interpreting biological measurement data such as optical topography and MRI.
  • Examples 1 to 5 only the frontal sinus was assumed as the internal structure of the subject 10 to be measured.
  • the same apparatus configuration is used for imaging of blood vessel structures using the transmittance distribution of multiple SD distances. it can.
  • the present invention is not limited to the head, and other parts of the human body can obtain the optical characteristics of the living body efficiently as shown in the present invention with a configuration of a plurality of SD distances. It can be applied to measurement of the internal structure of a living body including biological components.
  • the technique of the present invention can be applied to measurement of not only the frontal sinus but also the sinuses, skin blood vessels, and skeletal structures.
  • the signal is a T2 star (T2 *) weighted signal
  • the difference in permeability is the local magnetic field at the boundary of permeability (or magnetic susceptibility) such as nasal cavity, sinus cavity, ear cavity, tissue / air or tissue / fat. May cause signal degradation and signal position error due to spin phase dispersion, that is, artifacts.
  • knowing the distribution of the frontal sinus has the effect of assisting the estimation of these artifacts.
  • the measurement result of the frontal sinus distribution can be used as an aid for the analysis of the structure measurement by MRI.
  • the bone and cavity regions can be more easily distinguished, and the separation accuracy can be improved.
  • the optical brain function measuring device 90 is an all-head measuring type optical brain function measuring device or an optical brain function measuring device for simultaneously measuring a plurality of brain parts including the forehead portion, the frontal according to the present invention.
  • the sinus distribution measurement result only a part of the measurement result of the optical brain function measuring device 90 can be corrected, and further, the region / correction coefficient to be corrected in each subject 10 needs to be changed.
  • the prefrontal cortex can be stably measured for all people.
  • FIG. 30 shows the configuration of an optical brain function measuring device 90 of the whole head measurement type.
  • the local cerebral blood volume oxygenated hemoglobin, deoxygenated hemoglobin, and total hemoglobin
  • the local cerebral blood volume is radiated to the subject's head with light having a wavelength belonging to the visible to infrared region in the optical brain function measuring device 90, and the inside of the subject is irradiated. It is obtained by detecting and measuring the light of a plurality of signals that have passed with the same photodetector.
  • An appropriate stimulus / command can be given to the subject 10 by the stimulus / command presenting device 415 during the measurement period.
  • the stimulus / command presentation device 415 is controlled by a control signal 414 from the computer 412.
  • the prefrontal cortex which is susceptible to the effects of the frontal sinus in optical measurements, includes the areas responsible for working memory, sociality, and attention, and is a brain area deeply related to social life, and is known to work on mental arithmetic tasks and short-term memory tasks. It has been. It is also known that it works by processing multiple presentation tasks at the same time because it is an area with integrated thinking and movement functions.
  • the stimulus / command presentation device 415 has a function of presenting a mental arithmetic task and a short-term memory task to the subject, and performs a plurality of presentation tasks simultaneously on the subject. It has at least a function for presenting tasks.
  • a plurality of tasks are stored in advance in the storage unit of the computer 412 or the stimulus / command presentation device 415, and the stimulus / command presentation is based on a preset presentation order, presentation time interval, time width, and the like.
  • a task is presented via the device 415.
  • the task presentation order, the presentation time interval, and the like can be appropriately set via the input unit of the apparatus.
  • the optical brain function measuring device can measure not only the prefrontal cortex but also all brain functions, and the tasks that can be presented are not limited to the above-described tasks. .
  • a plurality of light sources 402a to 402d having different wavelengths (for example, 695 nm for the light sources 402a and 402c and 830 nm for the light sources 402b and 402d), and light from the plurality of light sources 402a and 402b (402c and 402d)
  • modulators or oscillators 401a and 401b (401c and 401d) for intensity-modulating at different frequencies, respectively, and intensity-modulated light is transmitted through optical fibers 403a and 403b, respectively.
  • the light passing through the living body is condensed on the optical fiber by the optical fibers for light reception 407a and 407b, and the light passing through the living body is photoelectrically converted by the light receivers 408a and 408b, respectively.
  • light transmitting optical fibers 405a and 405b and light receiving optical fibers 407a and 407b are respectively provided at the tips thereof with light transmitting probes 501a and 501b and light receiving probes for holding the optical fibers and properly setting them on the subject 10.
  • the probe holder 503 is fixed to the subject 10 in order to hold a plurality of probes.
  • the light receiving means detects light reflected inside the subject 10 and converts it into an electrical signal.
  • a photoelectric conversion element typified by a photomultiplier tube or a photodiode is used.
  • FIG. 30 illustrates the case where two types of wavelengths are used, it is possible to use three or more types of wavelengths. It is also possible to perform the same measurement by arranging a plurality of light irradiation means and light receiving means.
  • the electrical signals representing the in-vivo light intensity photoelectrically converted by the light receivers 408a and 408b are input to the lock-in amplifiers 409a to 409d, respectively.
  • Reference signals 417a to 417d from oscillators [modulators] 401a and 401b (401c and 401d) are also input to the lock-in amplifiers 409a to 409d.
  • the light of 695 nm from the light sources 402a and 402c is separated and output by the light sources 402a and 409b and extracted by lock-in processing
  • the light of 830 nm by the light sources 402b and 402d is separated and output by the light sources 402b and 402d.
  • two measurement points are assumed between the light transmission probe 501a and the light reception probe 502a and between the light transmission probe 501b and the light reception probe 502b.
  • two points between the light transmitting probe 501a and the light receiving probe 502b and between the light transmitting probe 501b and the light receiving probe 502a can be set as measurement points.
  • a computer 411 for measurement control is used after analog-to-digital conversion (hereinafter referred to as A / D conversion) is performed by the analog-to-digital converter 410 on the separated transmitted light intensity signals of the respective wavelengths, which are the outputs of the lock-in amplifiers 409a to 409d. Sent to.
  • the measurement control computer 411 uses the passing light intensity signal, and compares the oxygenated hemoglobin concentration, the deoxygenated hemoglobin concentration, and the total hemoglobin concentration from the detection signal at each detection point according to the procedure described in Non-Patent Document 1 and the like.
  • the amount of change (or more precisely, the amount of change of the product of each hemoglobin concentration and the optical path length) is calculated and stored in the storage device as time-lapse information at a plurality of measurement points.
  • a / D conversion is performed after performing lock-in processing
  • lock-in processing can also be performed digitally after amplifying and A / D converting the signal from the light receiver. is there.
  • a plurality of lights are separated by a modulation method
  • the present invention is not limited to this. For example, a time division method is used in which a plurality of lights are discriminated by shifting the timing of irradiating the plurality of lights in time It is also possible.
  • the computer 412 includes an input unit, an analysis unit, a storage unit, and an extraction unit, and the analysis unit analyzes the result calculated by the measurement control computer 411.
  • the input section settings such as analysis conditions are input from the outside.
  • the display unit 413 may be omitted.
  • the analysis result of the analysis unit is stored in the storage unit.
  • the extraction unit extracts information related to the local cerebral hemodynamics of the subject 10 from the signal analyzed by the analysis unit. Information regarding the local cerebral hemodynamics of the subject 10 extracted by the extraction unit is displayed on the display unit 413.
  • the measurement control computer 411 and the computer 412 are drawn separately, but may be a single computer.
  • the light quantity of the light source 402 is changed according to the frontal sinus distribution, or correction is performed using the frontal sinus measurement result when analyzing the change in local cerebral hemodynamics in the analysis unit. Can be performed. Since there are individual differences in the head structure, the position of the probe of the optical brain function measuring device 90 in each subject 10 is different in the standard brain coordinate system, and the frontal sinus distribution is different. Therefore, it is necessary to assign a correction amount for the light amount or hemodynamics to each measurement position. Therefore, the correction amount at each measurement position of the optical brain function measurement is calculated by calculating the frontal sinus distribution and the measurement position distribution of the optical brain function measurement in the same coordinate system.
  • the correction method is as shown in the fifth embodiment, for example.
  • FIG. 31 shows a flowchart for determining the correction amount at each measurement position of the optical brain function measuring apparatus using the frontal sinus distribution.
  • S3101 Frontal sinus distribution measurement is performed.
  • S3102 Position information for optical brain function measurement is measured or input.
  • S3103 A correction coefficient for the light amount of the light source or the measured local cerebral hemodynamic fluctuation is assigned to each measurement position according to the frontal sinus distribution. Here, the correction amount is calculated centering on the forehead part, and no correction is made for the part without the frontal sinus.
  • S3104 Optical brain function measurement is performed.
  • S3105 The change in local cerebral hemodynamics is calculated using the correction coefficient at each measurement position.
  • S3106 The result is displayed.
  • the correction amount at each measurement position here is different for each subject 10, but by saving the setting in the database, the setting can be read from the database and used when measuring again.
  • the measurement position (channel) near the area where the frontal sinus is distributed is assumed as the area for correcting the measurement value. However, if there is another area to be corrected, it should be corrected in the same way here. Also good. For example, in the case of having information such as skull thickness distribution, scalp thickness distribution, and means for correcting using the information, it is possible to correct optical brain function measurement data in the same manner as various corrections using the frontal sinus.
  • FIG. 32 shows a display example when the measurement result by the whole-head measurement type optical brain function measuring device is corrected.
  • the oxygenated hemoglobin concentration length change map 310 in the frontal region, left and right temporal region, the parietal region, and the occipital region, and the frontal region map include a frontal sinus-skull boundary 21 and a measurement channel 314 that is corrected based on the frontal sinus distribution measurement results. It is shown.
  • the intensity of the oxygenated hemoglobin concentration length change is represented by black and white shading, and the relationship between the shading density and the intensity is shown in a gray scale bar 311.
  • the map is created by interpolating from the values at each measurement point by cubic spline interpolation.
  • a time display scroll bar 312 is provided, and a map at an arbitrary time can be displayed.
  • the oxygenated hemoglobin concentration length change map 310 is a value corrected using the frontal sinus measurement result, and the corrected measurement channel 314 is indicated by a white circle. Measurement channels in and around the frontal sinus region are corrected. This display makes it clear which channel has been corrected, and the positional relationship between the frontal sinus position and the measurement channel in the optical brain function measuring device becomes clear at a glance.
  • correction based on the frontal sinus distribution measurement result, display of the channel 314 to be corrected, and display of the frontal sinus boundary can be selected by a check box 313, and analysis according to the purpose is possible.

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Abstract

Selon l'invention, une structure interne humaine telle qu'un sinus frontal et autres parties est mesurée de façon non effractive et à l'aide de ce résultat mesuré, la précision d'une instrumentation biologique est améliorée. Afin de mesurer de manière non effractive une distribution de sinus frontal, un dispositif d'instrumentation biologique comprend : une source de lumière pour irradier une lumière vers un sujet ; un détecteur de lumière pour détecter la lumière irradiée à partir de la source de lumière et qui s'est propagée à travers l'intérieur du sujet ; une unité de commande pour commander la source de lumière et le détecteur de lumière ; un amplificateur pour amplifier un signal de détection de lumière ; un convertisseur analogique-numérique ; une unité d'analyse pour analyser un signal numérique ; et une unité d'affichage pour afficher le résultat analysé. Le dispositif d'instrumentation biologique mesure les caractéristiques optiques du sujet, ce par quoi la structure interne du sujet, comprenant le sinus frontal, est mesurée et affichée. Le dispositif d'instrumentation biologique utilise également des informations de distribution de sinus frontal obtenues à l'aide d'une distribution de transmissivité de lumière mesurée à une pluralité de distances source de lumière-détecteur pour ajuster une puissance de source de lumière et une sensibilité de détecteur de lumière dans des mesures optiques de fonction cérébrale, fournissant ainsi un moyen pour corriger des données d'instrumentation biologique de mesures optiques de fonction cérébrale, imagerie par résonance magnétique fonctionnelle, et autres mesures. En outre, en IRMf, une mesure dans laquelle les artefacts sont réduits est obtenue par l'utilisation préalable de la distribution de sinus frontal.
PCT/JP2010/060483 2009-06-24 2010-06-21 Dispositif d'instrumentation biologique WO2010150751A1 (fr)

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JP2017009373A (ja) * 2015-06-19 2017-01-12 財團法人國家實驗研究院Ｎａｔｉｏｎａｌ Ａｐｐｌｉｅｄ Ｒｅｓｅａｒｃｈ Ｌａｂｏｒａｔｏｒｉｅｓ 配列式近接場光高散乱材料の検出方法
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JP2022528277A (ja) * 2019-04-12 2022-06-09 コリア アドヴァンスド インスティテュート オブ サイエンス アンド テクノロジー マシンラーニングを利用して頭に関する生体情報を推定するための方法、システムおよび非一過性のコンピュータ読み取り可能な記録媒体
JP7227657B2 (ja) 2019-04-12 2023-02-22 コリア アドヴァンスド インスティテュート オブ サイエンス アンド テクノロジー マシンラーニングを利用して頭に関する生体情報を推定するための方法、システムおよび非一過性のコンピュータ読み取り可能な記録媒体

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