WO2020166091A1 - 生体機能計測装置、生体機能計測方法及びプログラム - Google Patents
生体機能計測装置、生体機能計測方法及びプログラム Download PDFInfo
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- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
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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
- A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
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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
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
- A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
- A61B5/14553—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases specially adapted for cerebral tissue
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
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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
- A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
- A61B5/7235—Details of waveform analysis
- A61B5/7239—Details of waveform analysis using differentiation including higher order derivatives
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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
- A61B5/74—Details of notification to user or communication with user or patient ; user input means
- A61B5/742—Details of notification to user or communication with user or patient ; user input means using visual displays
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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
- A61B5/40—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
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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
- A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
- A61B5/7235—Details of waveform analysis
Definitions
- the present invention relates to a biofunction diagnostic device, a biofunction diagnostic method and a program for measuring and diagnosing a function of a living body, and in particular, a period in which a task of activating a brain function for a living body is not given (hereinafter, at rest).
- the biological function diagnostic device, the biological function diagnostic method, and the program for measuring and diagnosing the function of the biological body for enabling the quantification of the measured value in (1).
- a weak near-infrared ray (680 to 1300 nm) is irradiated onto the brain from above the scalp and across the skull to oxidize hemoglobin (Oxy-Hb) in blood in the brain surface (cerebral cortex) just inside the skull.
- FF Jobsis proposed a method for measuring the amount of change in concentration of HbO2) and the amount of change in concentration of deoxyhemoglobin (Deoxy-Hb; Hb). Since then, researches on tissue oxygen concentration measurement by this near-infrared spectroscopy (NIRS) have been rapidly progressing.
- NIRS near-infrared spectroscopy
- near-infrared spectroscopy is capable of non-invasively measuring the metabolism of individual tissues from the body surface (non-invasive), and can be realized with a simple device (portability), and PET (positron emission emission tomography).
- PET positron emission emission tomography
- fMRI functional magnetic resonance imaging
- it has the advantage of being able to measure the time change of the tissue metabolism of the brain and muscle in real time (temporal), and is useful for monitoring brain function, muscular recovery diagnosis in rehabilitation, and exercise physiology. Wide application is expected such as utilization of.
- the optical CT technology was not practical because the light was absorbed by the time it passed through the skull by the surface of the brain and through the brain.
- the present inventors conducted a human experiment of light stimulation of partially irradiating the brain with near-infrared light, and as a result, showed that localized distribution of brain function can be monitored at bedside. It was proved that it was possible to image local brain function using this noninvasive local brain function test method (Yukio Takashima, Toshinori Kato, et al. Observation of regional cerebral blood flow fluctuation by NIR Spectroscopy. Report of comprehensive research on medical care and rehabilitation of children (Ministry of Health and Welfare) p.179-181 (1992), Kato T, Kamei A, et et al. . Jereb BloodFlow Metab. 13:516-520 (1993).
- NIRS Imaging near-infrared spectroscopic brain functional imaging method
- NIRS Previously, NIRS was able to perform non-invasive monitoring of changes in oxygen saturation and changes in cerebral blood volume.
- Patent Document 1 As a method for simultaneously measuring changes in oxygen metabolism that occur when the brain is activated, the technologies of Patent Document 1, Patent Document 2, and Patent Document 3 have been proposed as inventions devised by the present inventor.
- a new index of brain function was created by using changes in local OxyHb and DeoxyHb ratios and indices obtained from two-dimensional diagrams.
- the brain activity can be classified by the information of the phase change obtained from the change of the local ratio of OxyHb and DeoxyHb.
- the signal called Initial dip can now be detected.
- a brain activity estimation device that extracts a component having a correlation with a determination component and estimates the human brain activity based on the determination component.
- the period when the brain function activation task is not given to the human is at rest of the brain, and the period when the brain function activation task is given to the human is as the brain activation time. It is evaluated whether or not the plurality of components have the correlation (hereinafter, referred to as Conventional Example 2).
- Patent Document 5 proposes a stress degree measuring device capable of quantitatively grasping the stress degree at the time of stress load with respect to the rest.
- Patent Document 6 in order to quantitatively inspect the electroencephalogram by displaying the power spectrum of changes during and after hyperventilation based on the electroencephalogram waveform at rest before hyperventilation, the induced electroencephalogram is determined at predetermined intervals.
- An activation electroencephalogram monitoring method and activation electroencephalogram monitoring device are proposed in which a frequency analysis is performed to calculate a power value in an arbitrary frequency range and a rate of change with a power value in a predetermined activation band is displayed as a trend graph based on an electroencephalogram before activation. (Hereinafter, referred to as Conventional Example 3).
- Japanese Patent No. 4031438 Japanese Patent No. 4625809 Japanese Patent No. 6029236 JP, 2017-209516, A JP-A-8-126614 Japanese Patent Laid-Open No. 2000-279388
- the conventional example 1 has the following problems. (1) When the k ratio and the k angle were used, when the phase division was performed, it depended on the signal intensity on the phase division, and it was difficult to detect a minute effective activity. It was difficult to make a correct and accurate diagnosis with only the signal strength. (2) When measured at a plurality of parts, even if the respective channels were compared, they depended on the signal intensity. (3) The brain functional task A or the brain functional task B should be quantified as compared with the time of rest, but in some cases, the task A and the task B were compared by making a difference. Therefore, the resting state could not be quantified. (4) It was ambiguous whether or not the state of the brain had recovered at rest even after the task was completed. (5) There is a phenomenon in which blood flow increases after the task because there is a phenomenon in which blood flow increases and hyperoxygenation occurs after oxygen is used in tissues and becomes hypoxic. , I didn't know the impact of the task.
- TRS time-resolved spectroscopy
- PRS phase-resolved spectroscopy
- the total optical path length can be measured using TRS or PRS.
- TRS or PRS it has been difficult to quantitatively calculate the local hemoglobin concentration change because the partial optical path length of the part where the blood flow changes due to the change of the resting state or the brain activity cannot be measured.
- Patent Document 5 of Conventional Example 3 is a technique for quantifying the stress level according to the amount of decrease in finger skin temperature. Since the reaction of a part of the body is detected, it is considered that the brain receives stress, and as a result, the reaction also appears on a part of the body such as the skin. Since the type of nerve cell varies depending on the brain part and the function is different, it may be explained as a stress received by a part of the brain related to the skin, for example, a sensory area of the brain. However, the stress received by other parts other than the sensory areas of the brain, such as the motor system, the understanding system, the visual system, and the thinking system, cannot be detected separately by this method.
- Patent Document 6 of Conventional Example 3 is a technique for quantitatively examining an electroencephalogram by displaying a power spectrum of changes during and after hyperventilation with reference to the electroencephalogram waveform at rest before hyperventilation. This technique can quantify each site on the scalp. However, it is necessary to perform frequency analysis for each predetermined section, and therefore it is overlooked that it is changing momentarily, and even if there is a difference in each part on the time series, it may be overlooked and considered to be the same. is there.
- the present invention has been made to solve the above-mentioned problems, and a biological function diagnostic device for measuring and diagnosing a function of a living body for enabling quantification of measurement values regarding brain characteristics at rest, a living body It is an object to provide a function diagnosis method and a program.
- the biological function diagnostic apparatus of the present invention A plurality of detectors each including a light emitting unit that irradiates a predetermined region of the living body with light and a light receiving unit that receives and detects the light emitted from the inside of the living body, and inputs the light information detected by the detecting unit, and calculates A measuring unit that performs control or storage, and a determining unit that determines the state of the biological function of the biological body, and is a biological function diagnostic device that diagnoses a biological function using near-infrared spectroscopy.
- the measurement unit calculates the time-series change amount of oxidative hemoglobin and the time-series change amount of deoxidized hemoglobin, the change amount of the oxidative hemoglobin and desorption. Based on a two-dimensional diagram showing the relationship with the amount of change in oxyhemoglobin, to obtain a vector group zero set for each predetermined sampling time, the calculation means for calculating the direction and or a parameter of the scalar of the vector group. Have, The determination unit determines the state of the biological function based on the parameter calculated by the calculation means, It is characterized by that.
- the parameter may be a dynamic phase division rate indicating how often the vector group appears in a plurality of phase divisions divided based on the two-dimensional diagram.
- the parameter may relate to the norm of each vector of the vector group.
- the parameter may be any or all of the norm of the mean vector, the variance of the norm, and the standard deviation of the norm calculated using angle statistics.
- the parameter may be calculated based on a probability density function of Rayleigh distribution.
- the parameter may relate to a correlation characteristic in two orthogonal axial directions on the two-dimensional diagram.
- the parameter may relate to a biaxial correlation of each vector of the vector group.
- the parameter may be calculated using a differential value of a time series change amount of the oxidative hemoglobin and a time series change amount of the deoxidized hemoglobin.
- the parameter may be calculated using a differential value obtained by differentiating the time-series change amount of the oxidative hemoglobin and the time-series change amount of the deoxidized hemoglobin a plurality of times.
- the parameter may be calculated by changing the sampling time.
- the parameter may be calculated by selecting a step width score that is the sampling time ⁇ n (n is an arbitrary number of n>1).
- the value of the parameter may be displayed on the display unit by plotting the data on the two-dimensional diagram.
- the determination unit may determine the state of the biological function at rest by setting the period during which the task of activating the brain function is not given to the living body as the rest of the brain.
- the phase division may be divided into eight.
- the phase section may be divided into 24 sections.
- the biological function diagnosis method of the present invention A plurality of detectors each including a light emitting unit that irradiates a predetermined region of the living body with light and a light receiving unit that receives and detects the light emitted from the inside of the living body, and inputs the light information detected by the detecting unit, and calculates , A biological function performed by a biological function diagnostic apparatus that has a measuring unit that controls or stores a memory, and a determination unit that determines the state of the biological function of the biological body, and that diagnoses the biological function using near-infrared spectroscopy.
- Diagnostic method Based on the light information from the detection unit, a step of calculating a time series change amount of oxidative hemoglobin and a time series change amount of deoxidized hemoglobin, Based on a two-dimensional diagram showing the relationship between the amount of change in the oxidative hemoglobin and the amount of change in the deoxidized hemoglobin, to obtain a vector set to zero every predetermined sampling time, the direction and or scalar of the vector group. Calculating a parameter based on Determining the state of biological function based on the calculated parameters, Is characterized by having
- the program of the present invention is A plurality of detectors each including a light emitting unit that irradiates a predetermined region of the living body with light and a light receiving unit that receives and detects the light emitted from the inside of the living body, and inputs the light information detected by the detecting unit, and calculates ,
- a biological function performed by a biological function diagnostic apparatus that has a measuring unit that controls or stores a memory, and a determination unit that determines the state of the biological function of the biological body, and that diagnoses the biological function using near-infrared spectroscopy.
- a program that executes diagnostic processing Based on the light information from the detection unit, a process of calculating a time series change amount of oxidative hemoglobin and a time series change amount of deoxidized hemoglobin, Based on a two-dimensional diagram showing the relationship between the amount of change in the oxidative hemoglobin and the amount of change in the deoxidized hemoglobin, to obtain a vector set to zero every predetermined sampling time, the direction and or scalar of the vector group.
- a process of calculating a parameter based on A process of determining the state of biological function based on the calculated parameters, Is executed.
- the present invention has the following effects. (1) It is possible to improve the sensitivity of real-time neuro-feedback, Brain-computer Interface (BCI), and Brain-machine Interface (BMI). (2) It can be a new index of brain function and can be quantitatively mapped. (3) Resting state can be quantified for each brain region. In the prior art, the origin of measurement start is considered to be in the same state, and high frequency changes have been measured and analyzed. (4) Although it has been used in both fNIRS and fMRI at rest, there was no method to quantify each measurement site even when examining the relationship between the sites (it is difficult to measure cerebral oxygen saturation at rest). ). On the other hand, the present invention has become possible.
- the progression stage of dementia can be quantified by the state of the brain.
- the state at rest can be quantitatively measured in real time in milliseconds or meters. As a result, the accuracy of detecting brain activity can be improved.
- the oxygen state at rest can be quantified without utilizing the oxygen saturation.
- the resting time could be analyzed by frequency or the like, but there was no method for quantifying the resting time in milliseconds, but the present invention allows it.
- a stress state at rest can be evaluated. In addition to simply quantifying stress intensity, the norm (R) of the mean vector, the variance (V) of the norm L, and its standard deviation (S) can be calculated using phase distribution and angle statistics. This enables detailed classification of stress conditions.
- FIG. 1 It is a block diagram which shows the structure of the biological function diagnostic apparatus which concerns on the example of embodiment of this invention.
- (A) is a graph for explaining the oxygen saturation angle and oxygen saturation, where the horizontal axis represents the amount of change in the concentration of oxidative hemoglobin and the vertical axis represents the amount of change in the concentration of deoxidative hemoglobin, and
- (B) shows the horizontal axis.
- FIG. 6 is a graph showing a procedure in which a horizontal axis represents time and a vertical axis represents a hemoglobin change amount, an arbitrary section is selected, a step size is determined, and zero set processing is performed.
- 6 is a graph showing a procedure for classifying a zero-set vector group into each phase section, with the horizontal axis representing the amount of change in the concentration of oxidized hemoglobin and the vertical axis representing the amount of change in the concentration of deoxidized hemoglobin.
- Data is plotted in a time series on a two-dimensional diagram with the horizontal axis representing the amount of change in the concentration of oxidative hemoglobin and the vertical axis representing the amount of change in the concentration of deoxidative hemoglobin, and is divided into eight phase sections in the form of a radar chart.
- A arbitrarily calculates resting 8 seconds on the same channel (ch14), and
- B) hears "lion” and replies "lion” between 0 seconds and 3 seconds on the same channel (ch14).
- (AP) is a graph in which the time zone is calculated, compared and displayed in time series.
- (A) calculates 8 seconds at rest arbitrarily on the same channel (ch2), and (B) hears "lion” and replies "lion” between 0 seconds and 3 seconds on the same channel (16ch).
- the task was repeated 8 times, and at that time, the change amount of the average oxidative hemoglobin, the change amount of the average deoxidative hemoglobin and the active phase
- (AP) is a graph in which the time zone is calculated, compared and displayed in time series.
- FIG. 3 is a graph in which an average oxidative hemoglobin change amount, an average deoxidative hemoglobin change amount, and an average dynamic phase partition rate (average APR value) (%) are calculated and compared and displayed in time series.
- FIG. 6 is a graph in which an average oxidative hemoglobin change amount, an average deoxidative hemoglobin change amount, and an average k angle (degree) for each second are calculated, and compared and displayed in time series. Eight trials on channel ch15 when "Lion” was heard and answered “Lion” between 0 and 3 seconds on the same channel, including a total of 8 seconds including 2 seconds before the listening section and 3 seconds after the speech section.
- the differential k angle is calculated from the differential value of the change amount of the average oxidative hemoglobin, the change amount of the average deoxidative hemoglobin and the change amount of the ⁇ average oxidative hemoglobin and the differential value of the change amount of the average deoxidative hemoglobin, It is a graph which compared and was displayed in time series.
- the horizontal axis of (A) is time (s)
- the vertical axis is dynamic phase partition ratio (APR value) (%)
- the horizontal axis of (B) is time (s)
- the vertical axis is oxidation type.
- (A) is a time series graph in which the horizontal axis represents time, and the vertical axis represents the concentration change amount of oxidative hemoglobin and the concentration change amount of deoxidized hemoglobin with respect to the original data obtained from the frontal channel at rest.
- Show. (B) shows a time series graph in which the baseline drift setting in which both oxidative hemoglobin (OxyHb) and deoxidized hemoglobin (DeoxyHb) continue to increase by 0.1 at 5 minutes is added to the original data of (A).
- .. 27A is a time-series graph in which only the oxidized hemoglobin (OxyHb) is added to the original data of FIG.
- 7 is a bar graph showing the frequency distribution of radius R of ( ⁇ OxyHb, ⁇ DeoxyHb) in subject A.
- the frequency distribution of ( ⁇ OxyHb, ⁇ DeoxyHb) is a bar graph showing the Rayleigh distribution.
- 7 is a bar graph showing the frequency distribution of radius R of ( ⁇ OxyHb, ⁇ DeoxyHb) in subject B.
- the frequency distribution of ( ⁇ OxyHb, ⁇ DeoxyHb) is a bar graph showing the Rayleigh distribution.
- (A) is a graph showing angular radius distribution of ( ⁇ OxyHb, ⁇ DeoxyHb)
- (B) is a graph showing angular radius distribution of ( ⁇ OxyHb, ⁇ DeoxyHb).
- the horizontal axis is the channel (ch), and the vertical axis is the dynamic phase division ratio (APR value). It is a bar graph comparing the data for 224 seconds at rest and during movement, and (A) is the norm that creates the APR of each channel. It is a graph showing R (at rest). (B) is a graph showing the norm R (when moving) that creates the APR of each channel. (C) is a graph showing the standard deviation S (at rest) of the norm R that produces the APR of each channel, (D) is a graph showing the standard deviation S (during movement) of the norm R that produces the APR of each channel.
- FIG. 6 is a graph showing a resting rotating coordinate system (Generalized COE) for calculating a biaxial correlation coefficient at a coordinate rotating angle ⁇ using a zero set vector group.
- A is a time-series graph obtained from a frontal channel at rest A in which the horizontal axis represents time, the vertical axis represents the concentration change amount of oxidative hemoglobin, and the concentration change amount of deoxidized hemoglobin.
- Is a time series graph obtained from the frontal channel at rest B in which the horizontal axis represents time and the vertical axis represents the amount of change in the concentration of oxyhemoglobin and the amount of change in the concentration of deoxidative hemoglobin.
- FIG. 2 is a rotation coordinate system biaxial correlation graph showing two relations, where the horizontal axis is the coordinate rotation angle (°) and the vertical axis is the biaxial correlation coefficient. It is a rotating coordinate system biaxial correlation graph of the measurement data obtained from the motor cortex (M1) during a break and during the exercise of lifting a 9.5 kg dumbbell. It is a rotating coordinate system biaxial correlation graph of the measurement data obtained from the part adjacent to the motor cortex (M1) during the break and the exercise of lifting the 9.5 kg dumbbell. The data obtained by applying the primary 0.1 Hz Butterwoth low-pass filter to the data in (A) of FIG.
- Data obtained by applying a first-order 0.1 Hz Butterwoth high-pass filter to the data in (A) of FIG. 34 is displayed with the horizontal axis as time and the vertical axis as the concentration change amount of oxidized hemoglobin and the concentration change amount of deoxidized hemoglobin. It is a graph.
- the data obtained by applying a primary 0.1 Hz Butterwoth high-pass filter to the data in (B) of FIG. 34 is displayed with the horizontal axis as time and the vertical axis as the concentration change amount of oxidative hemoglobin and the concentration change amount of deoxidized hemoglobin. It is a graph. It is a rotating coordinate system two-axis correlation graph at rest A and rest B showing the relationship between the coordinate rotation angle after the high-pass filter and the two-axis correlation coefficient.
- FIG. 1 is a block diagram showing the configuration of a biological function diagnostic apparatus according to an embodiment of the present invention.
- a biological function diagnostic apparatus 1 diagnoses a biological function using near-infrared spectroscopy, and as shown in FIG. 1, a light emitting unit that irradiates a predetermined part of a living body with light. 2 and a plurality of detection units 4 each including a light receiving unit 3 that receives and detects light emitted from the inside of a living body, and a measurement unit that inputs the optical information detected by the detection units 4 and performs calculation, control, or storage. 5, a determination unit 6 that determines the state of the biological function of the living body, and a display unit 7 such as a monitor or a display that displays various data measured by the measurement unit 5 and the determination result by the determination unit 6.
- the measuring unit 5 calculates the time-series change amount of oxidative hemoglobin and the time-series change amount of deoxidized hemoglobin based on the optical information from the detection unit 4, and changes the oxidative hemoglobin amount and deoxidation. Based on a two-dimensional diagram showing the relationship with the amount of change in type hemoglobin, a vector group that is set to zero is obtained every predetermined sampling time, and parameters based on the direction and/or scalar of the vector group are calculated.
- the measurement unit 5 also includes a storage unit 9 that stores the data calculated by the calculation unit 8 and an image processing unit 10 that creates a graph or table based on the calculated data and displays the graph or table on the display unit 7.
- the determination unit 6 determines the state of the biological function based on the parameters calculated by the calculation unit 8, (About parameters)
- the parameters calculated by the calculator 8 are as follows, for example.
- Dynamic phase segmentation rate indicating how often a vector group appears in a plurality of phase segments segmented based on a two-dimensional element diagram (Fig. 10, Fig. 11, etc.)
- Concerning the norm of each vector in the vector group (FIGS. 31 and 32)
- the scalar, norm and “radius” are used with the same meaning.
- (3) Norm of mean vector, variance of norm, standard deviation of norm calculated using angle statistics (Fig. 32) (4) What is calculated based on the probability density function of Rayleigh distribution (FIGS. 29 and 30) (5) Correlation characteristics in two orthogonal axial directions on a two-dimensional diagram (FIGS. 39 to 41)
- the two orthogonal axes are the horizontal axis (OxyHb axis) showing the concentration change amount of oxidative hemoglobin and the vertical axis (DeoxyHb axis) showing the concentration change amount of deoxidized hemoglobin, the horizontal axis and the vertical axis.
- the channel ch is used as a symbol representing the part of the brain of a living body (human), and the brain function in each channel ch is as follows.
- (1) ch1, 8 and 16 are parts of the right frontal lobe related to working memory related to images
- (2) ch2, 3, 9, 10, 17, and 18 are parts of the right frontal lobe related to judgment
- (3) ch7, 15, 22 are parts of the left frontal lobe related to working memory related to language
- ch5, 6, 13, 14, 20, 21 are parts of the left frontal lobe related to judgment (5) ch4, 11, 12, and 19 are the tip parts of the frontal lobe related to concentration (background art)
- FIG. 2 is a vector model showing the geometrical relationship between the oxygen saturation angle and the index of hemodynamics, where the horizontal axis represents the amount of oxygen hemoglobin concentration change and the vertical axis represents the amount of deoxidative hemoglobin concentration change. It is an explanatory view shown. This illustration is from OHBM2014 held in 2014, The 20th Annual Meeting of the Organization for Human Brain Mapping, June 8-12, 2014. Hamburg, Germany. By Toshinori Kato: A vector-based model of geometric relationships between oxygen saturation and hemodynamic indices.
- Vector ⁇ OS is represented by scalar L (amplitude) and Phase k that indicates the increase/decrease of ⁇ OS.
- FIG. 3A is a graph for explaining the oxygen saturation angle and the oxygen saturation, with the horizontal axis representing the concentration change amount of oxidative hemoglobin and the vertical axis representing the concentration change amount of deoxidizing hemoglobin.
- the movement vector on the OD diagram is defined as the oxygen saturation change vector ⁇ OS.
- a moving vector from R(O,D) to P(O+ ⁇ O,D+ ⁇ D), and ⁇ OS is represented by a scalar L (moving amount) and a phase K (moving direction) with respect to the O axis.
- the included angle between two points is the included angle of a triangle whose base is L and is defined as ⁇ OS angle.
- R and r1 are determined from (O,D) of the region of interest (ROI) to be measured. It corresponds to the length of the base of the triangle.
- ROI region of interest
- FIG. 3B is a graph showing each phase segment, in which the horizontal axis represents the amount of change in the concentration of oxidative hemoglobin and the vertical axis represents the amount of change in the concentration of deoxidized hemoglobin.
- the vector polar coordinate plane used for vector analysis by converting a vector connecting the origin and an arbitrary point P 1 ( ⁇ O 1 , ⁇ D 1 ) into the ⁇ COE axis and the ⁇ CBV axis, the coordinates of ⁇ COE 1 and ⁇ CBV 1 can be obtained.
- the number on the arc indicates the phase number.
- the phase that shows ⁇ D increase or ⁇ COE increase shows hypoxia or deoxygenation, and is a phase showing enhanced brain activity.
- FIG. 3C is a graph showing the relationship between the oxygen saturation angle and the oxygen saturation, with the horizontal axis representing the oxygen saturation angle (°) and the vertical axis representing the oxygen saturation.
- the relationship between Oxygen saturation and OS angle is given by the graph in Fig. 3, and the OS value is actually determined. As the OS moves clockwise, the oxygen saturation increases. When the OS moves counterclockwise, the oxygen saturation decreases.
- FIG. 4A is a graph showing the relationship between oxygen saturation and Y angle, where the horizontal axis represents the amount of change in the concentration of oxidative hemoglobin and the vertical axis represents the amount of change in the concentration of deoxidative hemoglobin, and FIG. It is their corresponding table.
- Oxygen saturation Y 1/(1-Arctan(Y)), where Y is the angle of inclination on the 0-D plane.
- FIG. 5 is a flowchart for explaining the operation of the biological function diagnostic device according to the embodiment of the present invention.
- FIG. 6 is a diagram showing a procedure for calculating a dynamic phase division ratio, and is a diagram showing acquired data in which the horizontal axis represents time and the vertical axis represents hemoglobin change amount.
- FIG. 7 is a graph showing a procedure of performing time-setting on the horizontal axis and hemoglobin change amount on the vertical axis, selecting an arbitrary section, determining the step size, and performing zero-setting processing.
- FIG. 8 is a graph showing the procedure for classifying zero-set vectors into each phase segment, with the horizontal axis representing the concentration change amount of oxidative hemoglobin and the vertical axis representing the concentration change amount of deoxidizing hemoglobin.
- the time series change amount of oxidative hemoglobin and the time series change amount of deoxidized hemoglobin are calculated based on the light information from the detection unit (step S1).
- a vector group set to zero at predetermined sampling times (for example, 75 ms) is set. Get (step S2).
- the values of zero-set oxidized Hb and deoxidized Hb are regarded as vector factors ( ⁇ O, ⁇ D), and the phase k angle and scalar ⁇ L are calculated (zero-set vector), and the graph on the two-dimensional diagram is displayed. Plot (step S3).
- a dynamic phase segment indicating how often a vector group appears in a plurality of (eight in this case) phase segments (1-8) segmented based on a two-dimensional diagram.
- the rate (APR value) is calculated (step S4).
- the eight phase sections shown in FIG. 8 are the horizontal axis (OxyHb axis) indicating the concentration change amount of orthogonal oxyhemoglobin and the vertical axis (DeoxyHb axis) indicating the concentration change amount of deoxidized hemoglobin, the horizontal axis and the vertical axis.
- Each of the axes is divided by a CBV axis and a COE axis that are rotated by 45 degrees.
- Phase 1 0 0/4 (0%)
- Phase 2 1 1/4 (25%)
- Phase 3 1 1/4 (25%)
- Phase 4 1 1/4 (25%)
- Phase 5 0/4 (0%)
- Phase 6 0 0/4 (0%)
- Phase 7 0/4 (0%)
- Phase 8 1 1/4 (25%)
- the dynamic phase partition rate (APR value) 3/4 (75%) Becomes Then, the state of the biological function is determined based on the calculated dynamic phase division rate (step S4).
- Phase 2 0 ⁇ O &0 ⁇ COE
- Phase 3 ⁇ O ⁇ 0 &0 ⁇ CBV
- Phase 4 ⁇ D & ⁇ CBV ⁇ 0
- Phase 5 ⁇ D ⁇ 0 &0 ⁇ COE
- Phase 6 ⁇ D ⁇ 0 &0 ⁇ CBV
- Phase 7 0 ⁇ O & ⁇ CBV ⁇ 0
- Phase 8 ⁇ O ⁇ 0 & ⁇ COE ⁇ 0
- the eight phases are related to changes in the tissue oxygen saturation of the measurement site, which will be described later.
- the amount of oxyhemoglobin in the tissues O and the O-D diagram of deoxidized hemoglobin (D) are also clear.
- the following can be determined from the frequency of the phases detected in the measured time and distance sections.
- the frequency of the phases 1, 2, 3, 6 increases from 50%, the blood volume at the measurement site increases, and the congested state is judged.
- the frequency of phases 4, 5, 7, and 8 is lower than 50%, the blood volume at the measurement site is decreased, and the ischemic state is judged.
- the horizontal axis represents time
- the vertical axis represents the amount of change in hemoglobin (oxidized hemoglobin, deoxidized hemoglobin, total hemoglobin), and before conversion to show an example of calculating the dynamic phase division ratio.
- the data processing performed using the orthogonal vector plane of the ⁇ OxyHb vector ( ⁇ O) and the ⁇ DeoxyHb vector ( ⁇ D) is performed by offsetting every x times (milliseconds) of ⁇ O and ⁇ D. It was the origin.
- the low data of ⁇ O and ⁇ D (Raw Data) has a low pass of 0.1Hz. Butterworth filter may be applied in some cases.
- the APR of the region of interest is calculated by equation (6).
- numerator it is possible to distinguish between male and female, adults, children, and age, and it is possible to know the characteristics of the population, and it is possible to calculate the average probability of the active phase by measuring multiple times within an individual. ..
- an arbitrary activation phase probability can be calculated. It was found that even at rest, a certain value was shown by selecting an arbitrary phase. In the case of an individual, it is possible to quantify the resting state of the right and left brains by collecting the parts.
- FIG. 10(A) shows data in a stationary state for 224 seconds.
- the phase phase 1-5 is defined as the active phase (APR+)
- FIG. 11 is a graph for confirming the dependence of the step size when the phases 2, 3, 4, 5, 6 are the active phases and the phases 1, 7, 8 are the inactive phases. It is a graph for confirming the dependence of the step width in which the number of width points (1 is 75 ms) and the vertical axis is the dynamic phase division rate (APR value).
- the dynamic phase division rate greatly depends on the step size.
- the large dependence on the step size is caused by the COE axis. Indicates that it has become. This agrees with the fact that the angular distribution of APR is higher along the COE axis. This is one of the reasons why it can be a more effective index than ⁇ OxyHb and ⁇ DeoxyHb, and shows a tendency that the resting state moves on the COE axis.
- FIG. 12 data is plotted in time series on a two-dimensional diagram in which the horizontal axis represents the amount of change in the concentration of oxidative hemoglobin and the vertical axis represents the amount of change in the concentration of deoxidative hemoglobin, and the radar is divided into eight phase sections. It is a graph which is displayed on the display unit in the form of a chart and in which the dynamic phase division ratio which is the ratio (%) of each phase is displayed on the display unit.
- the radar chart it is plotted on the coordinate axes of ⁇ DeoxyHb, ⁇ OxyHb, ⁇ COE, ⁇ CBV, so depending on which octagonal shape, depending on which coordinate axis, the convex shape or concave shape can be judged at a glance. Therefore, a plurality of patterns of resting states can be distinguished and diagnosed.
- phase 2 205 Phase 2: 79 Phase 3: 75 Phase 4: 439 5 phase: 255 Six phases: 181 7th phase: 179 8th phase: 187 Is.
- phase may be counted in the clockwise direction or may be counted in the counterclockwise direction.
- FIG. 13 is a bar graph showing the dynamic phase division rate (APR value) in the positive phases of 1 to 5 phases and the negative phases of 6 to 8 phases.
- Phases 1 to 5 with an increase in ⁇ DeoxyHb or ⁇ COE were defined as a positive phase (active phase) in which the brain was activated, and phases 6 to 8 were defined as a negative phase (inactive phase).
- the dynamic phase partition rate (APR value) of any channel at any time could be quantified as 65.7%
- FIG. 14 is a bar graph in which the horizontal axis represents each phase and the vertical axis represents the dynamic phase classification rate (APR value). It can be seen from FIG. 14 that the dynamic phase partition rate (APR value) of phase 4 is high and the dynamic phase partition rate (APR value) of phase 2 and phase 3 is low.
- the relative frequency of Phases 4 and 5 combined is as high as 43.3%, the sum of Phases 2 and 3 is low as 9.6%, and both show a 9:2 ratio, so that ⁇ COE increases with low It can be judged that the ischemic state is more involved in the oxygenation than the increase in ⁇ CBV.
- the total of inactive phases 6, 7, and 8 was 34.2%, and the total of active phases was 65.8%. Can be determined to be increasing.
- Fig. 15(A) calculates 8 seconds at rest on the same channel (ch14) arbitrarily, and (B) hears "lion” between 0 seconds and 3 seconds on the same channel (ch14) and hears "lion". 8 times, the change amount of the average oxidative hemoglobin, the change amount of the average deoxidized hemoglobin and the active phase (active phase) for a total of 8 seconds from 2 seconds before talking with the lion to the end at the measurement site. It is a graph in which time zones indicating phases: AP) are calculated, compared, and displayed in time series.
- Fig. 16(A) calculates 8 seconds at rest on the same channel (ch2) arbitrarily, and (B) hears "lion” between 0 seconds and 3 seconds on the same channel (16ch) and hears "lion". 8 times, and at that time, the change amount of the average oxidative hemoglobin, the change amount of the average deoxidized hemoglobin and the active phase (Active phase) for a total of 8 seconds from 2 seconds before talking with the lion to the end at the measurement site.
- Phase: AP is a graph in which time zones showing the values are calculated, compared, and displayed in time series.
- ch14 is a motor language field, and a strong increase in the dynamic phase segmentation rate (APR value) is observed.
- APR value is a language field, it is far from the area for utterances, and continuity is lost.
- ch2 is on the right side of the brain, reacts later than ch14, and the dynamic phase partitioning rate (APR value) is increasing even after the end, so even if the left and right brains are contralateral, they differ. You can see that it is working with different functions.
- ch2 is a part of the right brain and is located on the opposite side of ch14. Sometimes it reacts with language, but it works when trying to convey a visual image. Selected for comparison with ch14.
- ch14 is a part related to a language area related to conversation of the left brain. It is considered to be an indispensable part to answer "lion", so it is easier to compare with resting. It can be seen that ch14 has not recovered at rest during the time being measured.
- Fig. 17 shows 8 trials on channel ch15 when "Lion” is heard and “Lion” is answered within 0 to 3 seconds on the same channel, 2 seconds before the listening section and 3 seconds after the speech section. Including the total amount of change of average oxidative hemoglobin for 8 seconds, average deoxidative hemoglobin change amount and average dynamic phase partition rate (average APR value) (%), calculated and compared and displayed in a time series graph is there.
- ch15 is adjacent to ch14 and is a language field related to left brain conversation similar to ch14.
- ch16 is adjacent to ch15 and is near a language field related to conversation.
- the dynamic phase classification rate (APR value) changed at 60-70% during resting 2 seconds, increased with the task, and exceeded 90% at around 2 seconds. In addition, it shows 50% at 4 seconds after the start of the task, decreases to 30% after 5 seconds, and returns to 50% after 6 seconds. Depending on the task, the APR value increased by about 20% from the time of rest. We have detected a phenomenon of about 30% reduction.
- APR increased even in the lion's listening section, and in the utterance section, the APR increase showed a peak before ending. Furthermore, it can be seen that APR shows a much lower value during the recovery period than at rest. On the other hand, since the amount of change in average deoxygenated hemoglobin has reached its peak value, the process followed by APR cannot be explained by the amount of change in average oxidized hemoglobin.
- APR value time-series changes in the dynamic phase partition rate (APR value) cannot be predicted at all by the conventional qualitative display of changes in average oxidative hemoglobin and average deoxidized hemoglobin.
- APR value is a new quantitative indicator of brain activity.
- FIG. 18 shows 8 trials on channel ch15 when "Lion” is heard and “Lion” is answered in the same channel from 0 to 3 seconds, 2 seconds before the listening section and 3 seconds after the speech section.
- FIG. 7 is a graph in which an average oxidative hemoglobin change amount, an average deoxidative hemoglobin change amount and an average k angle (degree) are calculated for a total of 8 seconds, and are compared and displayed in time series.
- the average k angle (degree) shows a peak in the listening section, does not decrease even after the utterance section ends, and it is not possible to detect the in-task and the end of the task.
- Figure 19 shows 8 trials on channel ch15 when "Lion” is heard and "Lion” is answered in the same channel from 0 to 3 seconds, 2 seconds before the listening section and 3 seconds after the speech section. Including, the average oxidative hemoglobin change for a total of 8 seconds, the average deoxidized hemoglobin change and the differential of the average oxidative hemoglobin change, and the derivative of the average deoxidized hemoglobin change It is a graph which calculated k-angle and compared and was displayed in time series. As shown in FIG. 19, in the differential k-angle display, the variation in the angle during rest is larger than that during the task, and it is difficult to distinguish between the rest and the task. The peak in the utterance section of the white arrow detected by APR cannot be observed.
- the k phase, the differential k angle, the change amount of the average oxidative hemoglobin, and the change amount of the average deoxidative hemoglobin are detected by the dynamic phase division ratio (APR value). It turns out that it is possible to make a measurement that cannot be obtained.
- the horizontal axis represents time (s)
- the vertical axis represents the dynamic phase partition rate (APR value) (%)
- (B) represents the horizontal axis as time (s).
- the axis is the amount of change in oxyhemoglobin, 46 channels are placed on the parietal region, and the right masseter muscle bites the object for 3 seconds. It is a graph which compared the time series data of APR value.
- Asterisk indicates a section of significant difference (z>2.0) between the right oral motor area (Oral motor cortex; OMC) and the left oral motor area (Oral motor cortex; OMC).
- OMC right oral motor area
- OMC left oral motor area
- the time-series data of changes in oxidative hemoglobin increased again after the task, but the APR value was significant only during the task. What is significant only during the task is that in the task of moving the masseter muscle, OMC is activated to antagonize gravity and lifts the lower jaw, and at rest, the masseter muscle is relaxed without using the masseter muscle, so OMC activity is restored to rest. To do.
- FIG. 21 is a mapping diagram in which a plurality of channels are arranged on the parietal region, the left masseter muscle is strongly bitten for 3 seconds, and the task is compared with that at rest, and (A) is an APR mapping diagram in the left masseter task. And (B) is a mapping diagram of the amount of change in oxyhemoglobin in the masseter muscle task on the left side.
- Asterisk indicates high frequency active site (z>2.0).
- the area surrounded by the dotted line of ROI is the oral motor area (the area that moves the mouth and oral cavity; OMC) examined by MRI, and there is no OMC other than the ROI of the dotted line. If APR is effective, it is considered that APR increase will occur during the task in the ROI.
- the right ROI showed ch40, and the left ROI showed ch1 and ch2 were statistically significant.
- mapping APR levels was able to detect OMC activity in both left and right brain. It can be seen that the mapping using the APR value is a more sensitive index than the conventional index OxyHb.
- the APR value is a quantitative mapping, and the conventional index is a qualitative mapping.
- OxyHb is an index
- the magnitude of the difference between the two states is also relative.
- APR it is possible to compare with other research data, for example, with a difference of 10%, but other research data will be compared only with no statistical difference.
- the value of DeoxyHb may be a change specification. Not only that, the value of OxyHb alone cannot be determined to be resting, and there is a possibility of making a wrong decision.
- OxyHb remained elevated even though the masseter muscle should not be working. With OxyHb, there is a possibility of misdiagnosing the condition after the task. In APR, it can be seen that the figure has returned to the resting state after the task. In this way, APR can accurately diagnose the recovery process.
- FIG. 22 shows the differential of the rest measurement data shown in FIG. 9 ( ⁇ OxyHb, ⁇ DeoxyHb), with the horizontal axis representing time and the vertical axis representing the differential value of the concentration change of oxyhemoglobin ( ⁇ OxyHb).
- OxyHb) and a deoxygenated hemoglobin concentration change amount differential value ( ⁇ DeoxyHb) is a time series graph showing a relative change.
- FIG. 23(A) is a two-dimensional diagram showing the measurement data of the subject at rest shown in FIG. 9 with ( ⁇ OxyHb, ⁇ DeoxyHb) on the horizontal and vertical axes, respectively, and FIG. 23(B) shows the data of FIG. This is a two-dimensional diagram in which ( ⁇ OxyHb, ⁇ DeoxyHb) are plotted on the horizontal and vertical axes, respectively.
- FIG. 24 is an explanatory diagram showing a case where the phase division is 24. In 8 divisions, one phase is divided by 45 degrees, but in 24 divisions, one phase divided by 8 is further divided into 3 equal parts and divided by 15 degrees.
- the functional state of the living body may be determined by dividing the vector polar coordinate plane used for vector analysis into 24 phases and analyzing the distribution of APR values. This makes it possible to determine a more detailed functional state of the living body.
- FIG. 25 is a bar graph in which the horizontal axis represents each phase (24 divisions) and the vertical axis represents the dynamic phase division ratio (APR value).
- A shows the subjects who have 24 divisions of the same data of 8 divisions in FIG. It is at rest.
- B shows the case where the subject is moving.
- 1-15 phase is 60% and 16-24 phase is 40% at rest, while 1-15 phase is 70% when moving. %, 16-24 phase is 30%. It can be seen that when moving, the 10% dynamic phase division ratio increases, increases in the 9-13 phase close to the ⁇ COE axis, and decreases in the 6, 7, 8 phase, and 19-24 phase. It can be determined that the brain activity was increased in ch4 by the movement.
- FIG. 26 is a bar graph in which the horizontal axis represents each phase (24 divisions) and the vertical axis represents the dynamic phase division ratio (APR value) in each channel (ch16, ch17, ch18) of the brain. At rest, (B) shows the case where the subject is moving.
- APR value dynamic phase division ratio
- FIG. 27A is a time series in which the horizontal axis represents time and the vertical axis represents the concentration change amount of oxidative hemoglobin and the concentration change amount of deoxidized hemoglobin with respect to the original data obtained from the frontal channel at rest.
- a graph is shown.
- (B) shows a time series graph in which the baseline drift setting in which both oxidative hemoglobin (OxyHb) and deoxidized hemoglobin (DeoxyHb) continue to increase by 0.1 at 5 minutes is added to the original data of (A). ..
- FIG. 28 is a time series graph in which the original data of FIG. 27A is added with a baseline drift setting in which only oxidized hemoglobin (OxyHb) continues to increase by 0.1 at 5 minutes.
- APR value oxidized hemoglobin
- the effects of calculating the dynamic phase classification rate are as follows. (1) For example, in the motor cortex, the parts of the left and right brain that are involved in mouth and oral movements could not be accurately identified by conventional techniques, but by using the dynamic phase segmentation rate, it is quantified and effective. Can show sex. (2) The dynamic phase partition rate (APR value) rises most during chewing and decreases after chewing. APR indicators correspond to this movement in real time. It can be quantitatively determined that APR increased more than at rest, resulting in hypoxia or deoxygenation and oxygen consumption accompanying brain cell activity. That is, by using the dynamic phase segmentation rate, the accuracy of detecting brain activity in real time is improved.
- OxyHb is detected depending on the intensity of the change, so it has low sensitivity to weak changes, but the dynamic phase partition rate (APR value) uses the frequency of the phase. , Does not depend on the strength of the signal change.
- the measurement of fNIRS has mainly used the indicators of the amount of change in oxidative hemoglobin and the amount of change in De oxidative hemoglobin, but by quantifying using R and S and using the dynamic phase partition rate.
- BCI brain computer interface
- BMI brain machine interface
- step 5 Regarding the step of calculating the norm of each vector in the vector group (step 5)
- FIG. 29(A) is a bar graph showing the frequency distribution of the radius R of ( ⁇ OxyHb, ⁇ DeoxyHb) in the subject A
- (B) is a bar graph showing the Rayleigh distribution of the frequency distribution of ( ⁇ OxyHb, ⁇ DeoxyHb). Is.
- FIG. 30(A) is a bar graph showing the frequency distribution of the radius R of ( ⁇ OxyHb, ⁇ DeoxyHb) in the subject B
- (B) is a bar graph showing the Rayleigh distribution of the frequency distribution of ( ⁇ OxyHb, ⁇ DeoxyHb). Is.
- the probability distribution of the combined received electric field strength of multiple waves (sine waves) with a constant frequency and irregular amplitude and phase fluctuations follows the Rayleigh density distribution. When a large number of reflected waves and multiple waves from the duct propagation paths arrive and are combined, this distribution is followed. This distribution is mainly used for analysis of propagation paths in microwave radio communication and mobile radio communication.
- the oxygen transport path in oxygen exchange has the characteristics of a wave function and follows a Rayleigh density distribution.
- the resting oxygen exchange state of each site can be distinguished by calculating the maximum likelihood estimation value.
- FIG. 31A is a graph showing the angular radius distribution of ( ⁇ OxyHb, ⁇ DeoxyHb), and FIG. 31B is a graph showing the angular radius distribution of ( ⁇ OxyHb, ⁇ DeoxyHb).
- ⁇ OxyHb ⁇ DeoxyHb
- FIG. 31B is a graph showing the angular radius distribution of ( ⁇ OxyHb, ⁇ DeoxyHb).
- it is displayed 180 degrees counterclockwise and -180 degrees clockwise with respect to the ⁇ OxyHb axis or the ⁇ OxyHb axis. Since the zero set vector has an angle and a scalar value, the two distributions are displayed simultaneously.
- V small variance (angle is biased) in the calculation of the formula shown in Example 5 of analysis of physiological characteristics.
- the anisotropy when the anisotropy is biased, it can be diagnosed as a state where the rest state is mutated or a state where an external factor is added.
- FIG. 32 is a bar graph comparing the data for 224 seconds at rest and during movement, where the horizontal axis is the channel (ch) and the vertical axis is the dynamic phase division ratio (APR value).
- A is the APR of each channel Norm R (at rest) that produces the APR value of each channel (when moving)
- C the standard deviation S (at rest) of the norm R that produces the APR of each channel
- D Is the standard deviation S (when moving) of the norm R that produces the APR value for each channel.
- the amplitude of R is larger than that during movement, and it fluctuates.
- the standard deviation of R during movement is uniform.
- the rest is disjointed, and the movement is uniform
- the movement is that the brain is working for a specific purpose, and the brain is continuously moving in a certain direction like an orchestra. Can be evaluated to reflect.
- the state of the brain can be quantitatively diagnosed.
- the advantage of analyzing the data with standard deviation S is that not only the variance but also S is evaluated at the same time, and the index for evaluating the physiological state at rest increases and the accuracy increases.
- Several combinations can be diagnosed. Large and small digitization can be arbitrarily set as follows.
- V 0 to 1 S: 0 to 1SD, 2SD, 3SD or more V Large (0.6 or more) Small (0.4 or less) Large Small 0.4-0.6 S Large (2SD or more) Small (1DS or less) Small Large 1-2SD or less
- norm of the mean vector (R) the norm of the mean vector (R)
- V the variance of the norm L (V)
- S standard deviation
- a stress state at rest can be evaluated.
- the norm (R) of the mean vector, the variance (V) of the norm L, and its standard deviation (S) can be calculated using phase distribution and angle statistics. This enables detailed classification of stress conditions.
- the state of the brain at rest can be quantitatively diagnosed.
- the state of the brain at rest can be classified in detail.
- FIG. 33 is a graph showing a resting rotating coordinate system (Generalized COE) for calculating the biaxial correlation coefficient at the coordinate rotating angle ⁇ using the zero set vector group.
- the following table is a table showing the relationship between the rotating coordinate system and the biaxial correlation coefficient.
- FIG. 34(A) is a time series graph obtained from a frontal channel at rest A in which the horizontal axis represents time and the vertical axis represents the concentration change amount of oxidative hemoglobin and the concentration change amount of deoxidized hemoglobin.
- 34(B) is a time series graph obtained from the frontal channel at rest B in which the horizontal axis represents time and the vertical axis represents the amount of change in the concentration of oxidative hemoglobin and the amount of change in the concentration of deoxidative hemoglobin.
- the procedure for calculating the rotational coordinate system biaxial correlation graph from the resting data in FIG. 34 is as follows: the resting oxidative hemoglobin concentration change amount and the deoxidizing hemoglobin concentration change amount shown in FIGS. 34(A) and (B). From the time-series graph of Fig. 7, as shown in Fig. 7, zero-set at every predetermined sampling time (for example, 75 ms) based on a two-dimensional diagram showing the relationship between the amount of change in oxidative hemoglobin and the amount of change in deoxidative hemoglobin. The obtained vector group is obtained (step S2). Further, the vector group is plotted on the two-dimensional coordinate plane (step S3).
- the correlation coefficient with the plot of the zero set vector group is calculated (step S6).
- the biaxial plane formed by the coordinate rotation of the plane at an arbitrary angle is defined as GCOE.
- the phase with the highest correlation and the phase with the lowest correlation are found when rotated 360 degrees.
- the correlation becomes high at the coordinate rotation angle sandwiched between the ⁇ D and ⁇ COE axes.
- FIG. 35 is a rotating coordinate system two-axis correlation graph at rest A and at rest B showing two relationships, where the horizontal axis is the coordinate rotation angle (°) and the vertical axis is the biaxial correlation coefficient.
- the rotation coordinate system is 0 and 180 degrees on the OxyHb axis, 45 and 225 degrees on the DeoxyHb axis, 90 and 270 degrees on the COE axis, and 135 and 315 degrees on the OxyHb axis. Match each other. Since the correlation between the coordinate rotation angle and each axis is displayed on the rotating coordinate system two-axis correlation graph, it is possible to immediately discriminate along which axis the zero set vector group is distributed.
- the correlation is low with any phase, but a correlation coefficient of ⁇ 0.4 before and after 0 degrees and 180 degrees, and a correlation coefficient of +0.4 before and after 90 degrees and 270 degrees. From each of these, referring to Table 1, it can be determined that the zero-set vector group at rest B is distributed, showing a higher correlation on the ⁇ COE axis than the other three axes.
- ⁇ DeoxyHb axis, ⁇ OxyHb axis can be determined not to correlate.
- FIG. 36 is a rotational coordinate system biaxial correlation graph of measurement data obtained from the motor cortex (M1) during rest and during the exercise of lifting the 9.5 kg dumbbell.
- FIG. 37 is a rotational coordinate system biaxial correlation graph of measurement data obtained from a portion adjacent to the motor area (M1) during a break and during the exercise of lifting a 9.5 kg dumbbell.
- Fig. 36 From Fig. 36, it can be seen that the zero set vector groups during breaks and dumbbell exercises are distributed in an overlapping manner in the axial direction sandwiched by the DeoxyHb axis and the COE axis.
- the correlation coefficient is zero when the coordinate rotation angle is 30, 120, 210, and 300 degrees.
- the coordinate rotation angle with a correlation coefficient of 0.9 or more or -0.9 or less is in a wide range during dumbbell movements rather than during breaks, so it is highly controlled to accurately consume oxygen. As a result, it can be determined that there is a strong oxygen consumption state with no margin. Since the correlation between the coordinate rotation angle sandwiched between the ⁇ OxyHb axis and the ⁇ CBV axis is low, it can be determined that oxygen is not being supplied in the motor cortex.
- the zero set vector group during a break shows a correlation coefficient of 0.8 or more at 120 degrees and 300 degrees, and a correlation coefficient of ⁇ 0.8 or less at 30 degrees and 210 degrees. It can be seen that there is a high correlation and distribution in the coordinate rotation angle sandwiched between the ⁇ OxyHb axis and the ⁇ CBV axis. That is, from FIG. 36, the coordinate rotation angle of the motor cortex differs from that of the motor cortex by about 45 degrees, and in the region adjacent to the motor cortex (M1) during exercise, the motor cortex is correlated with the axis of oxygen consumption compared to It can be determined that the oxygen consumption is high while oxygen is being supplied.
- the zero-set vector group during dumbbell exercise has a high correlation with the coordinate rotation angle sandwiched between the ⁇ OxyHb axis and the ⁇ CBV axis.
- Situation in which oxygen is being supplied to the motor cortex that is consumed In the motor cortex it can be determined that oxygen is being supplied.
- a phase difference of about 90 degrees is clearly recognized.
- FIG. 38 shows data obtained by applying a first-order 0.1 Hz Butterwoth low-pass filter to the data in (A) of FIG. 34.
- the horizontal axis represents time
- the vertical axis represents oxidative hemoglobin concentration change amount, deoxidized hemoglobin concentration change. It is the graph displayed as quantity.
- Data obtained by applying a first-order 0.1 Hz Butterwoth low-pass filter to the data in (B) of FIG. 34 is displayed with the horizontal axis representing time and the vertical axis representing the concentration change amount of oxidative hemoglobin and the concentration change amount of deoxidized hemoglobin. It is a graph.
- FIG. 39 is a rotation coordinate system biaxial correlation graph at rest A and at rest B showing the relationship between the coordinate rotation angle after the low-pass filter and the biaxial correlation coefficient.
- the zero set vector group at rest A shows a high correlation with the ⁇ CBV axis
- the zero set vector group at rest B shows a high correlation with the ⁇ COE axis.
- resting A showed a correlation coefficient of 0.6 or more with the OxyHb axis.
- Resting B showed a high correlation coefficient of 0.9 or more on the axis sandwiched between the OxyHb axis and the CBV axis.
- the axis of the zero set vector group at rest A was about 45 degrees
- the axis of the zero set vector group at rest B was about 180 degrees
- FIG. 40 shows data obtained by applying a first-order 0.1 Hz Butterwoth high-pass filter to the data in (A) of FIG. 34.
- the horizontal axis represents time
- the vertical axis represents the amount of oxidative hemoglobin concentration change
- the amount of deoxidized hemoglobin concentration change It is the graph displayed as quantity.
- Data obtained by applying a first-order 0.1 Hz Butterwoth high-pass filter to the data in (B) of FIG. 34 is displayed with the horizontal axis as time and the vertical axis as the concentration change amount of oxidized hemoglobin and the concentration change amount of deoxidized hemoglobin. It is a graph.
- FIG. 41 is a rotational coordinate system biaxial correlation graph at rest A and at rest B showing the relationship between the coordinate rotation angle of the coordinate rotation angle after the low-pass filter and the biaxial correlation coefficient.
- the rest A and rest B zero-set vector groups each show a high correlation with the COE axis.
- the rest A zero-set vector group axis is about 30 degrees, and the rest B zero-set vector group axis is about 30 degrees.
- the zero-set vector group at rest A and at rest B show a high correlation with the COE axis in the high frequency band that has been removed as a noise component by the filter before the analysis processing. It became clear that it was included.
- the effects of calculating the biaxial correlation coefficient of the rotating coordinate system are as follows.
- Oxygen metabolism such as oxygen consumption, oxygen supply, increase in blood flow, decrease in blood flow, etc. can be quantified at rest by site.
- the state of oxygen metabolism at rest can be quantitatively compared between sites.
- the state of oxygen metabolism at rest can be quantitatively compared among individuals.
- If the zero set vector group can be created, the resting time can be quantitatively evaluated within a short time.
- It can be quantified for each frequency band at rest.
- the sensitivity and accuracy of the comparison at rest and during tasks are improved among individuals, between tasks, and by site.
- the state change at rest can be quantified by the phase.
- the program 11 according to the embodiment of the present invention shown in FIG. 1 is a program 11 for executing a biological function diagnostic process performed by the biological function diagnostic apparatus.
- the program 11 may be recorded in a recording medium such as a magnetic disk, a CD-ROM, a semiconductor memory or the like, or may be downloaded via a communication network.
- a recording medium such as a magnetic disk, a CD-ROM, a semiconductor memory or the like
- the present invention is not limited to the above-mentioned embodiments, and various modifications can be made within the scope of the technical matters described in the claims.
- Biofunction diagnostic device 2 Light emitting unit 3: Light receiving unit 4: Detection unit 5: Measuring unit 6: Judgment unit 7: Display unit 8: Calculation unit 9: Storage unit 10: Image processing unit 11: Program
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Abstract
Description
それ以来、この近赤外分光法(NIRS,near-infrared spectroscopy)による組織の酸素濃度計測の研究が急速に進展している。
局所のOxyHb, DeoxyHbの比の変化や二次元ダイアグラムから得られた指標を用いることで、新しい脳機能の指標が生み出された。また、局所のOxyHb, DeoxyHbの比の変化から得られる位相変化の情報によって脳活動を区分することができる。
これらの発明により、脳機能画像法としても、酸素飽和度の変化と血液量の変化を区別して、時空間マッピングが可能となった.現在では、頭皮上から神経活動に連動するイニシャル・ディップ(Initial dip)と呼ばれる信号も検出できるようになった。(Toshinori Kato (November 5th 2018). Vector-Based Approach for the Detection of Initial Dips Using Functional Near-Infrared Spectroscopy [Working Title], IntechOpen, DOI: 10.5772/intechopen.80888. Available from: https://www.intechopen.com/online-first/vector-based-approach-for-the-detection-of-initial-dips-using-functional-near-infrared-spectroscopy/)、特許文献3の技術では、これまで時系列データとして計測されてきた局所のOxyHb, DeoxyHbの変化量を、移動距離に対する変化量として計測できるようになった(以下、従来例1という)。
(1)k比、k角を利用したときに、位相区分をした場合、位相区分上で信号強度に依存していたので、微小な有効な活動を検出しにくかった。信号強度だけでは正しい、精度の高い診断が困難であった。
(2)複数の部位で計測した場合、各チャンネル間を比較しても、信号強度に依存していた。
(3)安静時に比べて脳機能課題Aあるいは、脳機能課題Bについて定量すべきであったが、課題Aと課題Bを差分して比較していた場合もあった。そのため、安静時の状態を定量できなかった。
(4)課題が終わっても脳の状態が、安静時に回復しているか否か曖昧であった。
(5)組織で酸素が使われ低酸素化したあとに、血流増加が起って高酸素化してしまう現象があるために、課題後も血流増加している場合も多く、安静状態か、課題の影響かもわからなかった。
(7)脳解析では局在性を無視して、統計的に有意なチャンネル数を数えている場合もある。
(9)多チャンネルのNIRS装置を用いて複数の部位を計測している場合には、各部位の光路長が異なっていても、同一であると仮定して、各ヘモグロビンの濃度変化のマッピングしてきた。一方、時間分解計測法(time-resolved spectroscopy, TRS)や位相分解計測法phase-resolved spectroscopy, PRS)を用いて光路長を計測する場合には、安静時、数分間を費やすために、ミリ秒単位の変化や1メートル単位の変化で安静状態をリアルタイムに定量化できていなかった。実際にTRSでは、頭皮上から1か所の安静時の脳酸素飽和度を計測するために約5分の時間を要する。
(11)NIRS計測では照射と受光ファイバペアの位置によって、信号の振幅は異なるため、NIRS信号の振幅の部位間・個体間比較は、血流反応の大小の比較をすることが困難であった。
(13)脳血流動態の周波数が0.1ヘルツ以下と考えられ、ローパスフィルターが汎用されてきたので、周波数の高い変化は一般にノイズと考えられてきたので、高周波数域の変化が安静状態か、活動状態であるかは区別できていない。
生体の所定部位に光を照射する発光部と、生体内から出射する光を受光し検出する受光部とを備えた複数の検知部と、前記検知部によって検出された光情報を入力し、演算、制御又は記憶を行う計測部と、前記生体の生体機能の状態を判定する判定部とを有し、近赤外分光法を利用して生体機能を診断する生体機能診断装置であって、
前記計測部は、前記検知部からの光情報に基づいて、酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量とを算出し、前記酸化型ヘモグロビンの変化量と脱酸化型ヘモグロビンの変化量との関係を示す二次元ダイアグラムに基づいて所定のサンプリング時間毎にゼロセットしたベクトル群を得て、前記ベクトル群の方向及び又はスカラーに基づいたパラメータを算出する算出手段を有し、
前記判定部は、前記算出手段によって算出された前記パラメータに基づいて生体機能の状態を判定する、
ことを特徴とするものである。
前記パラメータは、角度統計を使って算出される平均ベクトルのノルム、ノルムの分散、ノルムの標準偏差のいずれか又は全部であるものでもよい。
前記パラメータは、前記二次元ダイアグラム上における直交する2つの軸方向の相関特性に関するものでもよい。
前記パラメータは、前記酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量の微分値を用いて算出されるものでもよい。
前記パラメータは、前記サンプリング時間を変動させて算出されるものでもよい。
前記位相区分は8区分されていてもよい。
前記位相区分は24区分されていてもよい。
生体の所定部位に光を照射する発光部と、生体内から出射する光を受光し検出する受光部とを備えた複数の検知部と、前記検知部によって検出された光情報を入力し、演算、制御又は記憶を行う計測部と、前記生体の生体機能の状態を判定する判定部とを有し、近赤外分光法を利用して生体機能を診断する生体機能診断装置によって行われる生体機能診断方法であって、
前記検知部からの光情報に基づいて、酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量とを算出するステップと、
前記酸化型ヘモグロビンの変化量と脱酸化型ヘモグロビンの変化量との関係を示す二次元ダイアグラムに基づいて所定のサンプリング時間毎にゼロセットしたベクトル群を得て、前記ベクトル群の方向及び又はスカラーに基づいたパラメータを算出するステップと、
前記算出されたパラメータに基づいて生体機能の状態を判定するステップと、
を有することを特徴とするものである
生体の所定部位に光を照射する発光部と、生体内から出射する光を受光し検出する受光部とを備えた複数の検知部と、前記検知部によって検出された光情報を入力し、演算、制御又は記憶を行う計測部と、前記生体の生体機能の状態を判定する判定部とを有し、近赤外分光法を利用して生体機能を診断する生体機能診断装置によって行われる生体機能診断処理を実行させるプログラムであって、
前記検知部からの光情報に基づいて、酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量とを算出する処理と、
前記酸化型ヘモグロビンの変化量と脱酸化型ヘモグロビンの変化量との関係を示す二次元ダイアグラムに基づいて所定のサンプリング時間毎にゼロセットしたベクトル群を得て、前記ベクトル群の方向及び又はスカラーに基づいたパラメータを算出する処理と、
前記算出されたパラメータに基づいて生体機能の状態を判定する処理と、
を実行させることを特徴とするものである。
(1)リアルタイムのニューロフィードバック、ブレイン・コンピュータ・インタフェース(Brain-computer Interface : BCI)、ブレイン・マシン・インターフェース(Brain-machine Interface : BMI)の感度を向上させることができる。
(2)新しい脳機能の指標になり、定量的にマッピングできる
(3)脳の部位ごとに安静時の状態を定量化できる。従来技術では、計測開始の原点は、みな同一な状態と考えて、周波数の高い変化は計測および解析されてきた。
(4)fNIRSでも、fMRIでも安静時に用いられてきたが、部位間の関連性を調べても、計測部位ごとに定量化している手法はなかった(安静時の脳酸素飽和度を計測しにくかった)。これに対し、本発明では可能になった。
(6)認知症の進行段階を脳の状態によって定量化が可能である。
(7)安静時の状態をミリ秒単位、または、メートル単位でリアルタイムに定量計測できる。その結果、脳活動の検出の精度をも向上させることができる。
(8)酸素飽和度を利用しないで、安静時の酸素状態を定量化できる。
(9)脳波では安静時を周波数などで解析できていたが、ミリ秒単位で安静時を定量化する方法はなかったが、本発明では可能である。
(10)安静時のストレス状態を評価できる。さらに、単純にストレスの強弱を定量化するだけでなく、位相の分布や角度統計を使って平均ベクトルのノルム(R)、ノルムLの分散(V)、その標準偏差(S)を算出することで、ストレス状態の詳細な分類が可能となる。
(12)安静時の状態の任意区間をセロセットベクトル量(位相とスカラー量)の解析で詳細な分類ができる
(13)安静時や賦活課題中の状態の再現性をAPR値や回転座標系の2軸相関係数から再現率マッピングとして表示することが可能になった。
(14)解析にスムージング処理をしないとベクトルの方向に信号が揺らいでいたが、スムージング処理せずに有意に変化を検出できる。
(15)複数の被験者を同時に集団で計測する場合でも、同期した瞬間がわかる。
(17)個人間、課題間、部位ごとの比較が定量的に行うことができる
(18)計測された各Hbの濃度変化量のデータに対して、ベースライン補正やフィルター処理をせずに安静時の定量化ができる。
(20)安静時のベースライン補正をしても、真値が歪まない方法で実行することができる。
(21)安静時の周波数帯域別に定量化できる。
(生体機能診断装置の概略)
本発明の実施形態例に係る生体機能診断装置1は近赤外分光法を利用して生体機能を診断するものであり、図1に示すように、生体の所定部位に光を照射する発光部2と、生体内から出射する光を受光し検出する受光部3とを備えた複数の検知部4と、検知部4によって検出された光情報を入力し、演算、制御又は記憶を行う計測部5と、生体の生体機能の状態を判定する判定部6と、計測部5によって計測された各種データや判定部6による判定結果を表示するモニタ、ディスプレイ等の表示部7とを有する。
判定部6は、算出部8によって算出されたパラメータに基づいて生体機能の状態を判定する、
(パラメータについて)
(1)二次元元ダイアグラムに基づいて区分された複数の位相区分にベクトル群がどの程度出現するかの頻度を示す動的位相区分率(図10、図11など)
(2) ベクトル群の各ベクトルのノルムに関するもの(図31,図32)
ここで、明細書中、スカラー、ノルム及び「半径」は同意義で用いられる。
(3) 角度統計を使って算出される平均ベクトルのノルム、ノルムの分散、ノルムの標準偏差(図32)
(4) レイリー分布の確率密度関数に基づいて算出されるもの(図29,図30)
(5) 二次元ダイアグラム上における直交する2つの軸方向の相関特性に関するもの(図39~図41)
(7) ベクトル群を用いた回転座標系における座標回転角度に対する二次元ダイアグラム上における直交する2つの軸方向の相関係数に関するもの(図39~図41)
(8)酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量の微分値を用いて算出されるもの(図29(A),図30(A))
(9)酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量を複数回(ここでは2回)微分した微分値を用いて算出されるもの(図29(B),図30(B))
(10)サンプリング時間を変動させて算出されるもの(図10(A)、(B))
ここでは、1=75msとして横軸に刻み点数を表示している。これによって、目盛りの数値が簡潔になり、グラフの表示が見やすくなる。
(12)二次元ダイアグラム上にデータをプロットしたものにパラメータの値を表示部7に表示されるもの(図12)
(チャンネルchについて)
明細書中、チャンネルchは生体(人)の脳の部位を表す記号として用いられるものであり、各チャンネルchにおける脳機能は次の通りである。
(1)ch1、8、16は、映像に関する作業記憶に関係している右脳前頭葉の部位
(2)ch2,3、9、10、17、18は、判断力に関係している右脳前頭葉の部位
(3)ch7、15、22は、言語に関する作業記憶に関係している左脳前頭葉の部位
(4)ch5、6、13、14、20、21は、判断力に関係している左脳前頭葉の部位
(5)ch4、11、12、19は集中力に関係する前頭葉の先端部位
(背景技術)
この説明図は2014年に開催されたOHBM2014、国際脳機能マッピング学会(The 20th Annual Meeting of the Organization for Human Brain Mapping, June 8-12, 2014. Hamburg, Germany)
で本発明者(Toshinori Kato:A vector-based model of geometric relationships between oxygen saturation and hemodynamic indices)が発表したものである。
局所のOxyHb及びDeoxyHbの変化は、組織と毛細血管内の酸素交換によって毛細血管内の酸素飽和度の変化を引き起こすと考えられている。しかし、NIRS, OIS(optical intrinsic signal), fMRIなどの機能計測では、毛細血管内の酸素飽和度の変化とOxyHb及びDeoxyHbの増減との関係は、ほとんど明らかにされてこなかった。実際に、酸素飽和度の変化を使った非侵襲脳機能マッピングは報告されていない。
このモデルから、O-Dの二次元平面上の移動ベクトルは酸素飽和度変化ベクトル△OSと定義できる。
2)△OSは、極座標によって△Dと△Oまたは、△COE(=△D-△O)と△CBV(=△D+△O)の4ベクトル因子に分解できる。
3)この4因子とkによって、hemoglobin responseは45度ずつ360度を8つに分類できる。
5)安静時の酸素飽和度の値に依存せず、△O減少かつ△Dの増加では△OSが減少し、△O増加かつ△Dの減少では△OSが増加する。
6) △O減少かつ△Dの減少、△O増加かつ△Dの増加、の場合には、△OSの増減は、安静時の酸素飽和度の値に依存する。
しかし、安静時は、DとOにおける絶対座標上のどこから始まったかわからなかった。
図3において、O-Dダイアグラム上での移動ベクトルは、酸素飽和度変化ベクトル△OSと定義する。
R(O,D)からP(O+△O,D+△D)への移動ベクトルであり、△OSは、scalar L(移動量)と、O軸に対する位相K(移動方向)で表される。
RP=OP-OR=ΔOS(ベクトル方程式)となる。
計測する関心領域(region of interest:ROI)の(O,D)から rとr1が決まる。三角形の底辺の長さに相当する。
△OSが、時計回りに移動するとき、酸素飽和度は増加する。△OSが、反時計回りに移動するとき、酸素飽和度は低下する。実際には、Oxygen saturationとOS angleの関係の図で、実際にOS値がきまる。
ベクトル解析に用いたベクトル極座標平面において、原点と任意の点P1(ΔO1, ΔD1)を結ぶベクトルをΔCOE軸およびΔCBV軸に変換すると、ΔCOE1およびΔCBV1の座標を得ることができる。
この酸素代謝の位相を定量的に示す指標がk角である。
Y=O/(O+D)=1/[1+tan(OS angle)]
Oxygen saturationとOS angleの関係は図3のグラフで与えられ、実際にOS値がきまる。
△OSが、時計回りに移動するとき、酸素飽和度は増加する。
△OSが、反時計回りに移動するとき、酸素飽和度は低下する。
0-D平面上の傾きY角とすると、酸素飽和度Y=1/(1-Arctan(Y))となる。
関心領域(region of interest:ROI中の血液量BV(0)=O(t)+D(t)である。
(生体機能診断方法)
図6は動的位相区分率(dynamic phase division ratio)の算出手順を示す図であり、横軸を時間、縦軸をヘモグロビン変化量とした取得データをグラフにした図である。
図7は横軸を時間、縦軸をヘモグロビン変化量とし、任意の区間を選択し刻み幅を決定しゼロセット処理をする手順を示すグラフである。
例えば、各位相の出現回数頻度とその割合が以下の場合、
位相1=0 0/4 (0%)
位相2=1 1/4 (25%)
位相3=1 1/4 (25%)
位相4=1 1/4 (25%)
位相5=0 0/4 (0%)
位相6=0 0/4 (0%)
位相7=0 0/4 (0%)
位相8=1 1/4 (25%)
例えば、位相1-5を活動位相とすると
動的位相区分率(APR値)=3/4 (75%)
となる。
その後、算出された動的位相区分率に基づいて生体機能の状態を判定する(ステップS4)。
4つのベクトル成分の増減の組み合わせによって、ベクトル平面上の8象限に8つの位相区分できる。すなわち、
位相1:0<△D&△COE<0
位相2:0<△O&0<△COE
位相3:△O<0&0<△CBV
位相4:0<△D&△CBV<0
位相5:△D<0&0<△COE
位相6:△D<0&0<△CBV
位相7:0<△O&△CBV<0
位相8:△O<0&△COE<0
△CBV軸に沿って、位相1,2,3,6の頻度が50%より増加すると計測部位の血液量の増加を示し、充血した状態を判断される。位相4,5、7,8の頻度が50%より低下すると、計測部位の血液量の減少を示し、虚血状態を判断される。
△COE増加、または△D増加の位相である1から5の頻度が安静時より増加する組織の酸素消費が増加したことを示す。
さらに、「Oxygen saturationとOS angleの幾何学的関係を示すベクトルモデル」に示すように、安静時の組織酸素飽和度の値に関係なく位相3と位相4の頻度が増加すると、より強い組織酸素飽和度は低下、低酸素化反応と診断され、脳が酸素を非常に活発に消費したと判定できる。
△OxyHbベクトル(△O) と、△DeoxyHbベクトル(△D)の直交ベクトル平面を使って行ったデータ処理は、△Oと△Dの任意x時間(ミリ秒)ごとに、オフセットして、ベクトル原点とした。
ベクトル成分4指標(△O、△D、△COE、△CBV)を算出する。
式(1)、式(2)から得られる△CBVに対する△COEの比(または△Oに対する△D変化の比)によって、酸素代謝の強さの定量指標として酸素交換度:k角 (3)が定義される
K比は、(4)に示す。
総試行数に占めるk増加試行数を、動的位相区分率(Dynamic phase division ratio)=Active phase ratio(APR)(%)と定義し、計測チャンネルごとに算出した。
また、個人の場合、部位をまとめて右脳と左脳の安静状態の定量化も可能となる。
一方,APRの各相は刻み幅で大きく変化している.図10(B)から、位相区分1,4,5は、刻み幅に依存して変動しやすいことがわかる。これらの変化は基本振動の角度分布を反映している.
角度頻度が最大となる角度を切るように相を定義すればよい。そこで、回転座標系の二軸相関係数を算出して度頻度が最大となる角度を定義する。
APRの算出実例1として
1相:12.8%
2相:4.9%
3相: 4.7%
4相:27.4%
5相:15.9%
6相:11.3%
7相:11.2%
8相:11.7%
である。
1相:205
2相:79
3相:75
4相:439
5相:255
6相:181
7相:179
8相:187
である。
△DeoxyHbまたは△COEが増加している1~5相を脳が活性化しているプラス相(活性位相)と定義して,6~8相をマイナス相(不活性位相)と定義した。
任意時間の任意チャンネルの動的位相区分率(APR値)が、65.7%として定量化できた
図14から、位相4の動的位相区分率(APR値)が高く、位相2や位相3の動的位相区分率(APR値)が低いことがわかる。
位相4と5の相対頻度が合わせて43.3%と高く、位相2と3の合計が、9.6%と低く、両者は9:2の比を示すことから、△COEが増加する低酸素化には、△CBVを増加よりも虚血状態がより関与していると判定できる。
図15の(A)と(B)は、同一チャンネルでありながら、安静時には、散発的に動的位相区分率(APR値)の増加が起っており、言語課題試行時は、DeoxyHbの増加区間に一致して、動的位相区分率(APR値)の増加が持続していることが判定できる。
ch2は、右脳側であり、ch14よりは遅れて反応し、言い終わってからも動的位相区分率(APR値)が増加しているので、左脳と右脳では対側同士であっても、異なった機能を持って動いていることが分かる。ch2は、右脳の部位で、ch14の対側に位置する。言語に伴って反応する場合もあるが、視覚的なイメージを伝えようとするときに活動する。ch14と比較するために選択した。
「ライオン」と答えるためには不可欠な部位と考えられるため、安静時と比較しやすい。
ch14は、計測している時間では安静時に回復していなことが分かる。
ch16は、ch15に隣接していて、会話に関係する言語野の近傍である。
また、課題開始ご4秒では50%を示し、5秒後には30%まで低下し、6秒後に50%に回帰している。
課題によって、安静時より、約20%のAPR値が増加。約30%低下する現象を検出している。
平均k角(度)は、聴取区間でピークを示し、発語区間が終わっても低下せず、課題中と課題の終了を検出できていない。
図19に示すように、微分k角表示では、安静時の方が、課題中よりも角度の変動が大きく、安静時と課題中を区別できにくい。APRで検出できた白抜き矢印の発話区間のピークを観察できない。
つまり、図17,図18、図19から、動的位相区分率(APR値)によって、k角、微分k角、平均酸化型ヘモグロビンの変化量、平均脱酸化型ヘモグロビンの変化量では、検出しえない測定が可能であることがわかる。
OxyHbでは、課題後の状態を誤診する可能性がある。APRでは、課題後安静状態の数値に回復していることがわかる。このように、APRは回復過程の正確に診断することができる。
24区分では1,2,3(位相1)、4,5,6, (位相2)、7,8,9(位相3) 、10,11,12, (位相4),13,14,15(位相5),16,1,7,18 (位相-3) 、19,20,21 (位相-2) 、22,23,24(位相-1)に相当する。
安静時と移動時のデータのように、位相変化が幅広い場合、より詳細に位相変化を追跡できる。
移動時には、10%動的位相区分率が増加し、△△COE軸に近い9-13相で増加し、6,7,8相、19-24相で減少していることがわかる。移動によって、脳活動がch4で高まったことが判定できる。
動的位相区分率(APR値)を算出すると、位相1-5のAPR値は53.25%を示した。すなわち、OxyHbのみドリフトを補正した場合、APR値は、0.12%の違いが生じることで、実データが歪むことが明らかである。
(1)例えば運動野の中でも、左脳と右脳にある口や口腔運動にかかわる部位で、従来の技術では正確に特定できていなかったが、動的位相区分率を用いることにより、定量化して有効性を示すことができる。
(2)噛んでいる最中にもっとも、動的位相区分率(APR値)が上昇し、噛み終わったあとに低下している。この動きとリアルタイムに、APRの指標が対応している。
安静時よりもAPRが増加することで、低酸素化または脱酸素化が起り、脳細胞の活動に伴って酸素 消費が起ったことが、定量的に判定できる。つまり、動的位相区分率を用いることにより、リアルタイムに脳活動を検出する精度が向上する。
(4)OxyHbでは、変化の強度に依存して検出されるため、微弱な変化に対しては感度が低いが、動的位相区分率(APR値)は、位相の頻度を利用しているので、信号変化の強度に依存しない。
(6)安静時の脳の状態を8分類や24分類など、任意の数に分類して検出できるようになった。
(7)隣接した部位の時系列変化をリアルタイムに区別するすることで、脳の活動がもっとも高まっている時間帯を特定したり、安静時あっても、APRが増加して脳活動が瞬時に起こっていることも検出して判定できるようになった。
(8)ベースラインドリフトがあっても、位相を歪めずに真値が得られる。
被験者によるデータで,(△OxyHb,△DeoxyHb)と(△△OxyHb,△△DeoxyHb)のそれぞれのノルムR(これをここでは半径という)の頻度分布を算出.(△△OxyHb,△△DeoxyHb)の頻度分布は基本振動の半径分布を表していると考えられ、レイリー(Rayleigh)分布を示す性質が発見された。
時計回りで-180度で表示。ゼロセットベクトルは、角度とスカラー値を持つので、その2つの分布を同時に表示している。
すなわち、V 分散大きい(角度がばらばら)S(標準偏差)は、1.1と1以上で大きくスカラー値は、比較的差があるとわかる。
標準偏差Sでデータを解析する利点は、分散だけでなく、Sも同時に評価することで、安静時の生理的状態を評価する指標が増えて精度が増します。いくつかの組み合わせが診断できます。
大小の数値化を任意に以下のように設定することもできる。
V :0から1
S :0から1SD、2SD、3SD以上
V 大(0.6以上) 小(0.4以下) 大 小 0.4-0.6
S 大(2SD以上) 小 (1DS以下) 小 大 1-2SD以内
ベクトル群の各ベクトルのノルムの頻度分布や角度統計を使って平均ベクトルのノルム(R)、ノルムLの分散(V)、その標準偏差(S)を算出する効果としては以下の通りである。
(2)所定区間毎に分析する場合、(△OxyHb,△DeoxyHb)の値の場合の平均ベクトルのノルム(R)、ノルムLの分散(V)、その標準偏差(S)だけでなく、 (△△OxyHb,△△DeoxyHb)の値の場合の平均ベクトルのノルム(R)、ノルム△Lの分散(V)、その標準偏差(S)でも解析が可能なため、パワースペクトル分析に比べて、安静状態のより詳細な生理的な違いや安静時と賦活課題中とを区別できる。
(4)安静時の脳の状態を詳細に分類できる。
(5)睡眠や開眼、閉眼の状態の定量化による区別が可能になる。
(6)安静時の脳の状態から認知症の進行段階を定量し、その分類が可能である。
以下の表は、回転座標系と2軸相関係数の関係を示す表である。
この際に、平面の任意角度の座標回転によってできる2軸平面をGCOEと定義する。プロットしたデータの分布の違いによって、360度回転すると相関性の最も高い位相やもっとも低い位相が判明する。
実際に、安静時Aは、0度、180度の前後で+0.8以上と高い相関示している。90度、270度の前後で-0.8以下を示す。すなわち、表1を参照すると、安静時Aのゼロセットベクトル群が△CBV軸と高い相関を示して分布していると判定できる。
このように回転座標系2軸相関係数を算出し、グラフを表示作成することは、時系列データや、二次元座標でプロットしただけでは得られない安静時の状態診断が可能である。
ダンベル運動中では、運動野と運動野の隣接部位での結果を比較すると、明らかに90度ほど位相差を認める。
ローパスフィルター前の図35の結果では、安静時Aのゼロセットベクトル群が△CBV軸と高い相関を示し、安静時Bのゼロセットベクトル群は、△COE軸に高い相関を示している。
このように、0.1Hz以下での低周波数帯域では、より2つの状態の違いが明らかとなった。
安静時Aと安静時Bのゼロセットベクトル群はそれぞれ、COE軸と高い相関を示し、安静時Aのゼロセットベクトル群の軸は約30度、安静時Bのゼロセットベクトル群の軸は約90度、ローパスフィルター後に位相が変化した。
(1)酸素消費、酸素供給、血流増加、血流低下などの酸素代謝を安静時の状態を部位別に定量化できる。
(2)安静時の酸素代謝の状態を部位間で定量的に比較できる。
(3)安静時の酸素代謝の状態を個人間で定量的に比較できる。
(4)ゼロセットベクトル群が作成できれば、短い時間内で、安静時が定量評価できる。
(5)安静時の周波数帯域別に定量化できる。
(6)安静時と課題中の比較の感度、精度が個人間、課題間、部位ごとで向上する。
(7)安静時の状態変化が、位相で定量できる。
このプログラム11は、磁気ディスク、CD-ROM、半導体メモリ等の記録媒体に記録されていてもよく、通信ネットワークを介してダウンロードされるものでもよい。
本発明は、上記実施の形態に限定されることはなく、特許請求の範囲に記載された技術的事項の範囲内において、種々の変更が可能である。
2:発光部
3:受光部
4:検知部
5:計測部
6:判定部
7:表示部
8:算出部
9:記憶部
10:画像処理部
11:プログラム
Claims (18)
- 生体の所定部位に光を照射する発光部と、生体内から出射する光を受光し検出する受光部とを備えた複数の検知部と、前記検知部によって検出された光情報を入力し、演算、制御又は記憶を行う計測部と、前記生体の生体機能の状態を判定する判定部とを有し、近赤外分光法を利用して生体機能を診断する生体機能診断装置であって、
前記計測部は、前記検知部からの光情報に基づいて、酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量とを算出し、前記酸化型ヘモグロビンの変化量と脱酸化型ヘモグロビンの変化量との関係を示す二次元ダイアグラムに基づいて所定のサンプリング時間毎にゼロセットしたベクトル群を得て、前記ベクトル群の方向及び又はスカラーに基づいたパラメータを算出する算出手段を有し、
前記判定部は、前記算出手段によって算出された前記パラメータに基づいて生体機能の状態を判定する、
ことを特徴とする生体機能診断装置。 - 前記パラメータは、前記二次元ダイアグラムに基づいて区分された複数の位相区分に前記ベクトル群がどの程度出現するかの頻度を示す動的位相区分率であることを特徴とする請求項1に記載の生体機能診断装置。
- 前記パラメータは、前記ベクトル群の各ベクトルのノルムに関するものであることを特徴とする請求項1に記載の生体機能診断装置。
- 前記パラメータは、角度統計を使って算出される平均ベクトルのノルム、ノルムの分散、ノルムの標準偏差のいずれか又は全部であることを特徴とする請求項3に記載の生体機能診断装置。
- 前記パラメータは、レイリー分布の確率密度関数に基づいて算出されるものであることを特徴とする請求項1に記載の生体機能診断装置。
- 前記パラメータは、前記二次元ダイアグラム上における直交する2つの軸方向の相関特性に関するものであることを特徴とする請求項1に記載の生体機能診断装置。
- 前記パラメータは、前記ベクトル群を用いた回転座標系に関するものであることを特徴とする請求項1に記載の生体機能診断装置。
- 前記パラメータは、前記ベクトル群を用いた回転座標系における座標回転角度に対する前記二次元ダイアグラム上における直交する2つの軸方向の相関係数に関するものであることを特徴とする請求項1に記載の生体機能診断装置。
- 前記パラメータは、前記酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量の微分値を用いて算出されるものであることを特徴とする請求項1に記載の生体機能診断装置。
- 前記パラメータは、前記酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量を複数回微分した微分値を用いて算出されることを特徴とする請求項1に記載の生体機能診断装置。
- 前記パラメータは、前記サンプリング時間を変動させて算出されるものであることを特徴とする請求項1乃至9のいずれか1つの項に記載の生体機能診断装置。
- 前記パラメータは、前記サンプリング時間×n(nはn>1の任意の数)である刻み幅点数を選択して算出されるものであることを特徴とする請求項1乃至11のいずれか1つの項に記載の生体機能診断装置。
- 前記二次元ダイアグラム上にデータをプロットしたものに前記パラメートの値を表示部に表示することを特徴とする請求項1乃至12のいずれか1つの項に記載の生体機能診断装置。
- 前記判定部は、前記生体に対して前記脳機能を賦活する課題が与えられていない期間を脳の安静時とし、その安静時の前記生体機能の状態を判定する、
ことを特徴とする請求項1乃至13のいずれか1つの項に記載の生体機能診断装置。 - 前記位相区分は8区分されていることを特徴とする請求項2乃至14のいずれか1つの項に記載の生体機能診断装置。
- 前記位相区分は24区分されていることを特徴とする請求項2乃至14のいずれか1つの項に記載の生体機能診断装置。
- 生体の所定部位に光を照射する発光部と、生体内から出射する光を受光し検出する受光部とを備えた複数の検知部と、前記検知部によって検出された光情報を入力し、演算、制御又は記憶を行う計測部と、前記生体の生体機能の状態を判定する判定部とを有し、近赤外分光法を利用して生体機能を診断する生体機能診断装置によって行われる生体機能診断方法であって、
前記検知部からの光情報に基づいて、酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量とを算出するステップと、
前記酸化型ヘモグロビンの変化量と脱酸化型ヘモグロビンの変化量との関係を示す二次元ダイアグラムに基づいて所定のサンプリング時間毎にゼロセットしたベクトル群を得て、前記ベクトル群の方向及び又はスカラーに基づいたパラメータを算出するステップと、
前記算出されたパラメータに基づいて生体機能の状態を判定するステップと、
を有することを特徴とする生体機能診断方法。 - 生体の所定部位に光を照射する発光部と、生体内から出射する光を受光し検出する受光部とを備えた複数の検知部と、前記検知部によって検出された光情報を入力し、演算、制御又は記憶を行う計測部と、前記生体の生体機能の状態を判定する判定部とを有し、近赤外分光法を利用して生体機能を診断する生体機能診断装置によって行われる生体機能診断処理を実行させるプログラムであって、
前記検知部からの光情報に基づいて、酸化型ヘモグロビンの時系列の変化量と脱酸化型ヘモグロビンの時系列の変化量とを算出する処理と、
前記酸化型ヘモグロビンの変化量と脱酸化型ヘモグロビンの変化量との関係を示す二次元ダイアグラムに基づいて所定のサンプリング時間毎にゼロセットしたベクトル群を得て、前記ベクトル群の方向及び又はスカラーに基づいたパラメータを算出する処理と、
前記算出されたパラメータに基づいて生体機能の状態を判定する処理と、
を実行させることを特徴とするプログラム。
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CN114209319A (zh) * | 2021-11-08 | 2022-03-22 | 华南理工大学 | 基于图网络及自适应去噪的fNIRS情绪识别方法及*** |
CN114209319B (zh) * | 2021-11-08 | 2024-03-29 | 华南理工大学 | 基于图网络及自适应去噪的fNIRS情绪识别方法及*** |
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US20220211308A1 (en) | 2022-07-07 |
GB2595162A (en) | 2021-11-17 |
GB2595162B (en) | 2023-06-21 |
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