WO2011013694A1 - 血糖値推定装置 - Google Patents
血糖値推定装置 Download PDFInfo
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- WO2011013694A1 WO2011013694A1 PCT/JP2010/062680 JP2010062680W WO2011013694A1 WO 2011013694 A1 WO2011013694 A1 WO 2011013694A1 JP 2010062680 W JP2010062680 W JP 2010062680W WO 2011013694 A1 WO2011013694 A1 WO 2011013694A1
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- A—HUMAN NECESSITIES
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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
- A61B5/14532—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 for measuring glucose, e.g. by tissue impedance measurement
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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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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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
- G01N21/274—Calibration, base line adjustment, drift correction
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- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/359—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light
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- A61B2560/00—Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
- A61B2560/02—Operational features
- A61B2560/0223—Operational features of calibration, e.g. protocols for calibrating sensors
- A61B2560/0228—Operational features of calibration, e.g. protocols for calibrating sensors using calibration standards
- A61B2560/0233—Optical standards
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
- G01N21/274—Calibration, base line adjustment, drift correction
- G01N21/276—Calibration, base line adjustment, drift correction with alternation of sample and standard in optical path
Definitions
- the present invention relates to a blood sugar level estimating apparatus using near infrared light, and more particularly to a blood sugar level estimating apparatus that can be suitably used for monitoring blood sugar levels over time.
- FIG. 2 shows a non-invasive optical blood sugar level estimating device disclosed in the above publication, in which near-infrared light emitted from a halogen lamp 1 is a heat shielding plate 2, a pinhole 3, a lens 4, and an optical fiber.
- the light enters the living tissue 6 through the bundle 5.
- the optical fiber bundle 5 includes a measurement optical fiber 7 and a reference optical fiber 8, the distal end of the measurement optical fiber 7 is connected to the measurement probe 9, and the distal end of the reference optical fiber 8 faces the reference plate 18. It is connected to the reference probe 10. Further, the measurement probe 9 and the reference probe 10 are connected to the measurement-side emitter 11 and the reference-side emitter 12 via optical fibers, respectively.
- the measurement probe 9 and the reference probe 10 are composed of a plurality of light emitting fibers 20 arranged on the circumference and one light receiving fiber 19 arranged in the center.
- the distance L between the centers of the light emitting fiber 20 and the light receiving fiber 19 is set to 0.65 mm, for example.
- the near-infrared spectrum measurement is performed by bringing the tip surface of the measurement probe 9 into contact with the surface of the living tissue 6 such as the forearm of the human body at a predetermined pressure
- the near-infrared light incident on the optical fiber bundle 5 from the light source 1 is The light is transmitted through the measurement optical fiber 7 and irradiated from the distal end of the measurement probe 9 to the surface of the living tissue 6 from a plurality of light-emitting fibers 20 arranged concentrically.
- the measurement light applied to the living tissue 6 is diffusely reflected in the living tissue, and a part of the diffuse reflected light is received by the light receiving fiber 19 disposed at the tip of the measurement probe 9.
- the received light is emitted from the measurement-side emitting body 11 through the light receiving fiber 19, enters the diffraction grating 14 through the lens 13, and after being dispersed, is detected by the light receiving element 15, and is emitted from the light receiving element 15.
- the signal is AD-converted by the A / D converter 16 and then input to the arithmetic device 17 such as a personal computer.
- the arithmetic device analyzes the obtained spectrum data to calculate the blood sugar level.
- reference numeral 22 denotes a shutter.
- the reference measurement light reflected from the reference plate 18 such as a ceramic plate is measured and treated as reference light. That is, near-infrared light incident on the optical fiber bundle 5 from the light source 1 is applied to the surface of the reference plate 18 from the tip of the reference probe 10 through the reference optical fiber 8. The reflected light of the light irradiated on the reference plate 18 is emitted from the refanless emission body 12 through the light receiving fiber 19 disposed at the tip of the reference probe 10.
- a shutter 22 is disposed between the measurement-side emitting body 11 and the lens 13 and between the refanless-side emitting body 12 and the lens 13, respectively. Any one of the light from the refanless side emitter 12 is selectively passed.
- the center-to-center distance L between the light-emitting fiber 20 and the light-receiving fiber 19 is set to the above value because the spectrum of the dermis part is selected from the skin tissue having a layered structure of epidermis, dermis, and subcutaneous tissue from the surface. This is because it measures automatically.
- Japanese Patent No. 3931638 estimates the skin thickness from the near-infrared spectrum shape, and quantifies it according to the estimated skin thickness of the skin tissue from a plurality of calibration models prepared in advance. It has been proposed to select the calibration model to use.
- the disturbance setting is preferably simple and easy.
- the present invention has been made paying attention to such points, and provides a blood sugar level estimation device capable of estimating a blood sugar level, which is a trace component, especially when monitoring over time, with extremely high accuracy. It is an object to do.
- the present invention is a blood glucose level estimation device that non-invasively calculates blood glucose levels over time from an optical spectrum of a living body measured over time and a calibration model, and a plurality of calibration models or a plurality of calibration models for creating calibration models. It has a calibration model creation means that creates a calibration model from a data set, and is configured to measure a subject's biological spectrum and set a reference spectrum, and a measured spectrum measured at a time other than the time when the reference spectrum is measured And a difference spectrum between the reference spectrum and the reference spectrum, and a calibration model used for the calculation is changed in accordance with a change in the difference spectrum. Yes.
- the calibration model used for calculating the blood glucose level is changed according to the change in the difference spectrum.
- the calibration model is changed a plurality of times in accordance with the change in the difference spectrum within the measurement period in order to accurately estimate the blood glucose level.
- the estimated values are calculated using the calibration model used before the change and the newly adopted calibration model, so that the two estimated values obtained are the same.
- Subsequent blood glucose level estimation may be performed after performing bias correction.
- the calibration model used for the calculation may be changed according to the growth of the water peak (around 1450 nm) in the difference spectrum or according to the growth of the fat peak (around 1730 nm).
- the calibration model used for the calculation may be changed according to the water peak growth and the fat peak growth in the difference spectrum.
- the calibration model corresponding to water peak growth or the data set for creating a calibration model corresponding to water peak growth simulates the light propagation of skin tissue, and the optical constant change given as a disturbance component at least causes moisture in the epidermis tissue.
- Created by numerical simulation with a change in quantity, or simulated with light simulation of skin tissue and optical constant change given as a disturbance component at least by changing the fat concentration in subcutaneous tissue it is preferable to create a numerical simulation in which the optical constant change given as a disturbance component at least gives the change in scattering characteristics to the epidermal tissue.
- the blood glucose level estimation device further includes a light source, a measurement probe, and a calculation device.
- the light source is configured to emit light.
- the measurement probe is configured to receive the light.
- the measurement probe is configured to irradiate the living body with the received light, whereby the light irradiated to the living body is scattered and reflected by the living body to generate diffusely reflected light.
- the measurement probe is configured to receive the diffusely reflected light.
- the arithmetic device is configured to extract the optical spectrum of the living body contained in the diffuse reflected light.
- the arithmetic unit preferably has the calibration model creation means.
- the arithmetic device has a measuring means and a blood sugar level estimating means.
- the measuring means is configured to take out the optical spectrum of the living body contained in the diffuse reflected light.
- the blood glucose level estimation means is preferably configured to calculate the blood glucose level over time non-invasively from the optical spectrum of the living body and the calibration model measured over time by the measurement means.
- the calibration model creation means includes reference spectrum setting means, measurement spectrum setting means, difference spectrum calculation means, and calibration model change means.
- the reference spectrum setting means is configured to set the reference spectrum by measuring the biological spectrum of the subject.
- the measurement spectrum setting means is configured to set a biological spectrum measured at a time other than the time of measuring the reference spectrum as a measurement spectrum.
- the difference spectrum calculation unit is configured to obtain a difference between the measurement spectrum and the reference spectrum as a difference spectrum.
- the calibration model changing means is configured to change the calibration model used for the calculation according to the change of the difference spectrum.
- the measurement spectrum setting means is preferably configured to set the current measurement spectrum as the first measurement spectrum.
- the measurement spectrum setting means is configured to set the previous measurement spectrum as the second measurement spectrum.
- the difference spectrum calculation means is configured to calculate a difference between the first measurement spectrum and the reference spectrum as the first difference spectrum.
- the difference spectrum calculation means is configured to calculate a difference between the second measurement spectrum and the reference spectrum as the second difference spectrum.
- the difference spectrum calculation means is configured to calculate a difference between the first difference spectrum and the second difference spectrum as a change in the difference spectrum.
- the calibration model changing means is configured to change the calibration model used for the calculation according to the change of the difference spectrum.
- the measurement spectrum setting means is configured to set the current measurement spectrum as the first measurement spectrum.
- the measurement spectrum setting means is configured to set the measurement spectrum of the previous time of the current measurement spectrum as the second measurement spectrum.
- the reference spectrum setting unit is configured to measure the biological spectrum of the subject again and set the reference spectrum every time the first predetermined time has elapsed after setting the reference spectrum.
- the reference spectrum measuring means is configured to set a reference spectrum measured before the second predetermined time before the measurement spectrum setting means measures the first measurement spectrum as the first reference spectrum.
- the reference spectrum measuring means is configured to set the reference spectrum set at the previous time of the first reference spectrum as the second reference spectrum.
- the difference spectrum calculation means is configured to calculate a difference between the first measurement spectrum and the first reference spectrum as the first difference spectrum.
- the difference spectrum calculation means is configured to calculate a difference between the second measurement spectrum and the second reference spectrum as the second difference spectrum.
- the difference spectrum calculation means is configured to calculate a difference between the first difference spectrum and the second difference spectrum as a change in the difference spectrum.
- the calibration model changing means is configured to change the calibration model used for the calculation according to the change of the difference spectrum.
- the first reference spectrum preferably satisfies the following two conditions (1) and (2).
- the first reference spectrum is a reference spectrum measured before measuring the first measurement spectrum.
- the first reference spectrum is the newest reference spectrum among the reference spectra measured before the first measurement spectrum is measured.
- the blood sugar level estimation means is a non-invasive blood sugar level from a predetermined calibration model and the optical spectrum of the living body measured over time by the measurement means. Is preferably calculated over time.
- the calibration model changing means creates a predetermined calibration model from the plurality of calibration models or the plurality of data sets for creating the calibration model when the difference spectrum calculation means does not calculate the difference of the difference spectrum. It is preferable to be configured. Along with this, when the difference spectrum calculation means does not calculate the difference spectrum, the blood sugar level estimation means, from the predetermined calibration model and the biological optical spectrum measured by the measurement means over time, The blood glucose level is calculated non-invasively over time.
- the calibration model used for the calculation for estimating the blood glucose level is changed according to the change in the difference spectrum, and since it can be switched to an appropriate calibration model at an appropriate time, The estimation accuracy can be increased, and it can be used particularly preferably when monitoring blood glucose levels over time.
- FIG. 2 shows a schematic diagram of the blood sugar level estimating apparatus of the present embodiment.
- the blood sugar level estimation apparatus of the present embodiment includes a halogen lamp 1, a heat shielding plate 2, a lens 4, an optical fiber bundle 5, a measurement probe 9, a reference probe 10, and a measurement.
- a side emitter 11, a reference side emitter 12, a lens 13, a lens 22, a diffraction grating 14, a light receiving element 15, an A / D converter 16, and an arithmetic device 17 are provided.
- the halogen lamp 1 is a so-called light source. Therefore, although the halogen lamp 1 is employed in FIG. 2, the light source is not limited to the halogen lamp 1.
- the light source 1 is configured to emit light.
- the light emitted from the light source 1 is applied to the heat shielding plate 2.
- the lens 4 is provided on the side opposite to the halogen lamp 1 when viewed from the heat shielding plate 2.
- Light emitted from the halogen lamp 1 is introduced into the lens 4 through the pinhole 3.
- the light introduced into the lens subsequently enters the first end of the optical fiber bundle 5.
- the optical fiber bundle 5 includes a measurement optical fiber 7 and a reference optical fiber 8.
- the first end of the measurement optical fiber 7 and the first end of the reference optical fiber 8 correspond to the first end of the optical fiber bundle 5.
- the measurement optical fiber 7 has a measurement probe 9 connected to the second end.
- the measurement probe 9 is connected to the measurement-side emitter 11 via an optical fiber.
- the second end of the reference optical fiber 8 is connected to the reference probe 10.
- the reference probe 10 is connected to the reference side emitter 12 via an optical fiber.
- the measurement-side emitter 11 is optically connected to the A / D converter 16 via the lens 13, the diffraction grating 14, and the light receiving element 15.
- the reference-side emitter 12 is also optically connected to the A / D converter 16 via the lens 13, the diffraction grating 14, and the light receiving element 15.
- the A / D converter is connected to the arithmetic device 17.
- FIG. 11 shows a block diagram of the arithmetic unit 17.
- the arithmetic unit 17 includes a measuring unit 100, a calibration model creating unit 130, a blood sugar level estimating unit 110, and a display unit 120.
- the measuring means 100 is configured to receive the first signal.
- the measuring means 100 is configured to measure the optical spectrum of the living body from the first signal.
- the measuring means 100 is configured to extract the optical spectrum of the living body from the first signal.
- Examples of the optical spectrum of a living body include the peak wavelength of light absorbed by water and the peak wavelength of light absorbed by fat.
- the peak wavelength of light absorbed by water is 1430 nm or more and 1480 nm or less.
- the peak wavelength of light absorbed by fat is 1670 nm or more and 1780 nm or less. Moreover, both the peak wavelength of light absorbed by water and the peak wavelength of light absorbed by fat can be used as the optical spectrum of the living body.
- the calibration model creation unit 130 includes a reference spectrum setting unit 131, a measurement spectrum setting unit 132, a difference spectrum calculation unit 133, a calibration model change unit 134, and a difference spectrum data set 135.
- the reference spectrum setting means 131 is configured to receive the first signal.
- the reference spectrum setting unit 131 is configured to measure the optical spectrum of the living body from the first signal.
- the reference spectrum setting unit 131 is configured to extract the optical spectrum of the living body from the first signal. Then, the optical spectrum of the living body measured by the reference spectrum setting unit 131 is set as the reference spectrum.
- the measurement spectrum setting means 132 sets, as a measurement spectrum, the optical spectrum of the living body measured by the measurement spectrum setting means 132 from the first signal when a predetermined time has elapsed since the arithmetic device 17 received the first signal.
- the difference spectrum calculation means 133 calculates a difference spectrum that is the difference between the reference spectrum and the measured spectrum. And the difference spectrum calculation means 133 is comprised so that a difference spectrum may be calculated with time. And the difference spectrum calculation means 133 calculates the difference between difference spectra as a change of a difference spectrum.
- the calibration model changing means 134 changes the calibration model used for calculation according to the change of the difference spectrum.
- the blood sugar level estimating means 110 estimates the blood sugar level using the optical spectrum of the living body measured by the measuring means 100 and the calibration model changed by the calibration model changing means 134.
- the display unit 120 displays the blood glucose level estimated by the blood glucose level estimation unit 110.
- the calibration model creating means 130 measures the biological spectrum of the subject and sets it as the reference spectrum, and obtains a difference spectrum that is the difference between the measured spectrum measured at a time other than the time of measuring the reference spectrum and the above spectrum.
- the calibration model used for the calculation is changed according to the change of the difference spectrum.
- the arithmetic unit 17 estimates the blood glucose level from the calibration model and the optical spectrum of the living body.
- the computing device 17 displays the estimated blood glucose level on a display device of the computing device 17 or the like.
- Such a blood glucose level estimation device operates as follows. First, when the light source emits light, the light passes through the pinhole 3 and enters the lens 4. The light incident on the lens 4 enters the optical fiber bundle 5 from the first end of the optical fiber bundle 5. Light incident on the inside of the optical fiber bundle 5 passes through the measurement optical fiber 7 and the reference optical fiber 8. Light passing through the measurement optical fiber 7 is irradiated to the human body via the measurement probe 9. The light irradiated to the human body is diffusely reflected inside the human body, thereby generating diffuse reflected light. The measurement probe 9 receives diffusely reflected light. The diffusely reflected light received by the measurement probe 9 is sent to the measurement-side emitting body 11 through an optical fiber.
- the light emitted from the measurement-side emitting body 11 is applied to the light receiving element 15 through the lens 22 and the diffraction grating 14.
- the light receiving element 15 that has received the light generates an electrical signal corresponding to the diffusely reflected light, and then sends the electrical signal to the A / D converter 16.
- the A / D converter 16 creates a first signal by AD-converting the electrical signal corresponding to the diffuse reflected light.
- the first signal is sent from the A / D converter 16 to the measuring means 100, the reference spectrum setting means 131, and the measured spectrum setting means 132 of the arithmetic unit 17.
- the measuring unit 100 When the measuring unit 100 first receives the first signal, the measuring unit 100 extracts the optical spectrum of the living body from the first signal. The measuring means 100 sends the optical spectrum of the living body to the blood sugar level estimating means 110.
- the blood glucose level estimation means 110 calculates the blood glucose level non-invasively from the optical spectrum and the calibration model.
- the difference spectrum calculating means 133 has not yet calculated the difference spectrum. Therefore, the calibration model changing unit 134 cannot change the calibration model based on the difference in the difference spectrum. Therefore, the blood sugar level estimating means 110 estimates the blood sugar level from the first optical spectrum and the initial calibration model created based on the predetermined difference spectrum data set 135. Then, the blood sugar level estimated by the blood sugar level estimating means 110 is displayed by the display means 120.
- the reference spectrum setting unit 131 when the measuring unit 100 extracts the optical spectrum from the first signal, the reference spectrum setting unit 131 also extracts the optical spectrum from the first signal. Then, the reference spectrum setting unit 131 sets the optical spectrum as the reference spectrum.
- the measuring means 100 takes out the optical spectrum of the living body from the first signal every 5 minutes.
- the blood glucose level estimation means 110 estimates the blood glucose level every 5 minutes from the optical spectrum extracted every 5 minutes and the calibration model created based on the predetermined difference spectrum data set 135. . That is, the blood glucose level estimating means 110 non-invasively calculates the blood glucose level over time from the optical spectrum of the living body measured every 5 minutes and the initial calibration model created based on the predetermined difference spectrum data set 135. Is estimated.
- the measurement spectrum setting unit 132 is 30 minutes after the reference spectrum setting unit 131 has set the reference spectrum.
- the optical spectrum of the living body measured by is set as the second measurement spectrum.
- the measurement spectrum setting unit 132 measured 60 minutes after the reference spectrum setting unit 131 set the reference spectrum.
- the optical spectrum of the living body measured by is set as the first measurement spectrum.
- the second measurement spectrum corresponds to the measurement spectrum measured before the first measurement spectrum.
- the calibration model changing unit 134 selects the difference spectrum data set 135 corresponding to the change of the difference spectrum from the plurality of difference spectrum data sets 135. Then, the calibration model changing unit 134 creates a calibration model from the selected difference spectrum data set 135. The latest calibration model created by the calibration model changing means 134 is sent from the calibration model changing means 134 to the blood glucose level estimating means 110.
- the blood sugar level estimating means 110 When the blood sugar level estimating means 110 receives the latest calibration model from the calibration model changing means 134, the blood sugar level estimating means 110 changes the initial calibration model to the latest calibration model. And the blood glucose level estimation means 110 estimates a blood glucose level non-invasively with time based on the optical spectrum of the living body measured every 5 minutes and the latest calibration model. The blood glucose level estimated over time is displayed on the display unit 120 over time.
- the blood glucose level estimation means 110 estimates the blood glucose level based on the latest calibration model and the optical spectrum of the living body measured every 5 minutes.
- the measurement spectrum setting means 132 resets the measurement spectrum every 30 minutes after the reference spectrum setting means 131 sets the reference spectrum.
- the interval for resetting the measurement spectrum is not limited to every 30 minutes. For example, any interval from 1 minute to 100 minutes may be used.
- the measuring means 100 measures the optical spectrum of the living body every 5 minutes.
- the interval at which the measuring means 100 measures the optical spectrum is not limited to every 5 minutes. For example, any interval from 1 minute to 100 minutes may be used.
- the light source When the light source emits light, the light enters the lens 4 through the pinhole 3.
- the light incident on the lens 4 enters the optical fiber bundle 5 from the first end of the optical fiber bundle 5.
- Light incident on the inside of the optical fiber bundle 5 passes through the measurement optical fiber 7 and the reference optical fiber 8.
- the light that has passed through the reference optical fiber 8 is applied to the reference plate 18 through the reference probe 10.
- the light irradiated on the reference plate 18 is reflected by the reference plate 18, thereby generating reflected light.
- the reference probe 10 receives reflected light.
- the reflected light received by the reference probe 10 is sent to the measurement-side emitting body 12 through an optical fiber.
- the light emitted from the measurement-side emitting body 12 is applied to the light receiving element 15 through the lens 13 and the diffraction grating 14.
- the light receiving element 15 that has received the light generates an electrical signal corresponding to the reflected light, and then sends the electrical signal to the A / D converter 16.
- the A / D converter 16 creates a second signal by AD-converting the electrical signal corresponding to the reflected light.
- the computing device 17 is non-invasive from the optical spectrum of the living body included in the first signal, the calibration model, and the optical spectrum included in the second signal corresponding to the optical spectrum of the living body included in the first signal. Calculate blood glucose level more accurately over time.
- the present invention estimates blood glucose levels by performing near-infrared spectrum measurement on skin tissue. It is composed of three layers of the epidermis, dermis, and subcutaneous tissue.
- the epidermal tissue is a tissue including a stratum corneum, and capillaries are not so developed in the tissue.
- the subcutaneous tissue is mainly composed of adipose tissue. Therefore, it is considered that the correlation between the water-soluble biological component concentrations contained in the two tissues, particularly, the glucose concentration and the blood glucose concentration (blood glucose level) is low.
- the concentration of biological components in the tissue is moderate. It is considered to change following the blood glucose level in the same manner as the interstitial fluid (ISF). Therefore, in the present invention, in order to perform spectrum measurement targeting the dermal tissue, the same configuration as that of the apparatus shown in FIG. 2 is used, in particular, near infrared light having a wavelength of 1300 nm to 2500 nm is used. Near-infrared spectrum measurement is performed by bringing a near-infrared spectrum measurement probe having a center-to-center distance L of 0.65 mm to the skin in contact with the skin.
- a plurality of calibration models (or a plurality of data sets for creating a calibration model) are essential. It is effective to use a numerical simulation to create the calibration model.
- the difference in near-infrared spectrum shape is caused by skin properties such as keratin moisture, fineness of epidermal tissue, skin tissue thickness, etc., but when synthesizing spectra using numerical simulation, the above-mentioned skin property characteristics Can be expressed as optical characteristic values such as optical absorption coefficient, scattering coefficient, anisotropic scattering parameter of skin tissue including epidermis, dermis and subcutaneous tissue.
- a simulation using a stochastic method such as a Monte Carlo method or a random walk method or a method for calculating a near infrared spectrum from a light diffusion equation can be used.
- the propagation of near-infrared light in a medium can be simulated with a function based on the probability distribution of absorption and scattering.
- a medium biological tissue
- the propagation path of each light beam By tracking the propagation path of each light beam based on the optical characteristics of the medium, it is possible to reproduce a near-infrared spectrum under a predetermined light receiving and emitting condition.
- the procedure for simulating the near-infrared spectrum of the skin tissue includes the structure of the skin tissue to be measured, the absorption coefficient, the scattering coefficient, the refractive index, the optical characteristic values of the anisotropic scattering parameters, and the number of photons to be calculated. This is done by determining and computing.
- the skin structure is composed of epidermal tissue, dermis tissue and subcutaneous tissue layer, it may be simply modeled as a layered structure including layers below the subcutaneous tissue layer, If the thickness, absorption coefficient, scattering coefficient, and anisotropic scattering parameter of each layer are determined, the near-infrared spectrum of the skin tissue of the subject can be reproduced by numerical simulation. As the number of photons, a number in the order of hundreds of thousands to millions is usually used.
- the NA Numerical Aperture
- the number of input photons was 1 million.
- the skin structure used in the Monte Carlo method is composed of epidermal tissue (0.1 mm), dermal tissue (0.9 mm), and subcutaneous tissue layer (2.0 mm), and the layers below the subcutaneous tissue layer are completely absorbed. The body.
- FIG. 4 and 5 show the optical characteristic values of each skin tissue used in the simulation.
- the absorption coefficient of the dermal tissue was obtained by superposing 60% moisture and 15% protein.
- the absorption coefficient of epidermal tissue is 20% water
- the absorption coefficient of the subcutaneous tissue layer is the absorption coefficient of cholesterol.
- the scattering coefficients of the dermal tissue and subcutaneous tissue layer in FIG. 5 are the same for the epidermal layer and the dermal layer, with reference to the documents of Troy et al. And Simpson et al.
- the scattering parameter is 0.9 and the refractive index is 1.37, which is constant with respect to the wavelength.
- Example 1 Near-infrared light used for quantification is in the wavelength range from 1430 nm to 1850 nm.
- a blood glucose level was changed by attaching a measurement probe to the subject's left arm forearm and performing glucose load twice in a sitting position.
- Glucose load used liquid dietary supplements (calorie mate (trade name, Otsuka Foods).
- Measured blood glucose level was obtained from blood obtained by puncturing the fingertip using a simple blood glucose meter (diasensor, Arkray). It was measured.
- an actually measured spectrum obtained from a subject was set as a reference spectrum.
- the calibration model used at the start of the experiment was obtained by multivariate analysis of a spectrum data set created by adding the difference spectrum data set to the reference spectrum.
- the difference spectrum data set is preliminarily synthesized by applying blood glucose level fluctuation and disturbance fluctuation by numerical simulation, and a plurality of difference spectrum data sets are prepared according to the type of disturbance to be incorporated.
- a difference spectrum data set in which the moisture content was changed in the epidermis was used as a disturbance from a plurality of previously created difference spectrum data sets.
- This difference spectrum data set incorporates changes in blood glucose level, water content, protein concentration, and lipid concentration in the dermal tissue as other disturbance factors, and changes in absorbance due to these concentration changes and volume fractions accompanying that concentration change.
- the light absorption coefficient and the scattering coefficient are changed on the assumption that the change is replaced with water. Moreover, it gives as a peak shift of water about a temperature change. Further, the scattering coefficient and the anisotropic scattering parameter are changed independently. Note that the method of applying disturbance is not limited to the above.
- the simulated skin tissue is simply modeled with the epidermis tissue (0.1 mm), dermis tissue (0.9 mm), subcutaneous tissue layer (2.0 mm), and the lower layer as a complete absorber. ing.
- the skin thickness is a constant, it goes without saying that the regression model may be calculated by the same operation with the skin thickness as a parameter.
- the calibration model is created by multivariate analysis based on the spectrum data set created by adding the difference spectrum data set to the reference spectrum, with the blood glucose level as the target variable and the simulation spectrum as the explanatory variable.
- multivariate analysis multiple regression analysis, PLS regression analysis, principal component regression analysis, neural network, or the like can be used. In this example, PLS regression analysis was used.
- the blood glucose level is estimated by near infrared light by substituting the absorbance of each wavelength of the measured spectrum measured every 5 minutes into the obtained calibration model.
- the determination of the calibration model to be used was performed by taking the difference spectrum between the measured spectrum and the reference spectrum every 30 minutes and determining the spectrum change.
- FIG. 6 shows the change over time of the difference spectrum in this example.
- the calibration model to be used is determined every 30 minutes.
- the calibration model is not limited to this time interval, and may be appropriately determined when necessary or may be performed at regular intervals.
- the selection of the calibration model is determined based on the absorption peak wavelength (1730 nm) of fat. Judgment was made based on whether or not the differential absorbance at 1730 nm exceeded 0.002. As can be seen from FIG. 6, since the fat peak growth does not satisfy the above judgment criteria until the third judgment (see FIG. 6 (c)), the calibration model used at the start of the experiment, that is, moisture in the epidermis layer as a disturbance. The blood glucose level was estimated using the calibration model created from the differential spectrum data set that gave the change in the amount.
- the anisotropic scattering parameter (G factor) of the epidermal layer was changed as a disturbance from the differential data set prepared in advance.
- the difference data set was used.
- Other disturbance factors incorporated in the differential spectrum data set are the same as those in the differential spectrum data set in which the moisture content is changed in the skin layer as the above disturbance. If the anisotropic scattering parameter (G factor) of the epidermis layer is changed as a disturbance, the light arrival state inside the skin tissue is changed, and as a result, the influence of fat existing in the subcutaneous tissue is changed.
- the calibration model is created by multivariate analysis based on the spectrum data set created by adding the difference spectrum data set to the reference spectrum as in the beginning of the experiment, with the blood glucose level as the target variable and the simulation spectrum as the explanatory variable. I did it.
- the difference spectrum data sets prepared in advance in this embodiment are the above two sets, and the calibration model used for blood glucose level estimation is determined based on the difference absorbance of the fat absorption peak wavelength (1730 nm).
- blood glucose levels are estimated using the previously used calibration model and the newly created calibration model, and bias correction is performed so that the two estimated blood glucose levels obtained are the same. After that, blood glucose levels were estimated using the newly created calibration model.
- FIG. 7 shows a comparison between the estimated blood glucose level 42 performed by the above method and the actually measured blood glucose level 41 by blood collection.
- S1 indicates the time of measuring the reference spectrum.
- the correlation coefficient between the measured blood glucose level 41 and the estimated blood glucose level 42 was 0.81, and the ratio of the estimated blood glucose level 42 within an error of ⁇ 20% from the measured blood glucose level 41 was 92.3%.
- Example 2 As a comparative example, the same experimental data as in Example 1 was used, and the blood glucose level was estimated with a single calibration model without judging the spectrum change.
- the calibration model used was the same as in Example 1 except that blood glucose level, water content, protein concentration, lipid concentration change, temperature change, scattering coefficient and anisotropic scattering parameters were applied only to the dermis layer without applying disturbance to the spectral epidermal tissue.
- a differential spectrum data set that was similarly changed was used.
- the calibration model creation procedure is the same as in the example.
- FIG. 10 shows a comparison between the estimated blood glucose level 42 in this case and the actually measured blood glucose level 41 by blood collection.
- Example 1 stable blood glucose level prediction from the start of the experiment could not be performed, so blood glucose level estimation was performed using the measured spectrum 35 minutes after the start of the experiment as the reference spectrum.
- the correlation coefficient between the measured blood glucose level 41 and the estimated blood glucose level 42 in this comparative example is 0.36, and the ratio of the estimated blood glucose level 42 within ⁇ 20% of the error from the measured blood glucose level 41 is 70.6%. It was.
- Example 3 The procedure for blood glucose level estimation in this embodiment is the same as that in the first embodiment.
- the difference is that the calibration model is selected using two wavelengths, a water absorption peak wavelength (1450 nm) and a fat absorption peak wavelength (1730 nm), to determine whether the calibration model needs to be changed.
- the judgment here is to compare the difference absorbance of the water absorption peak wavelength and the difference absorbance of the fat absorption peak wavelength, and if the water absorption peak wavelength is larger, the difference that caused the skin layer to change the moisture content as a disturbance Select the calibration model created from the spectrum data set.
- Example 4 The procedure for blood glucose level estimation in this embodiment is the same as that in the first embodiment. However, instead of the differential data set in which the anisotropic scattering parameter (G factor) of the epidermis layer was changed as the disturbance, a differential data set in which the fat concentration change was given to the subcutaneous tissue as the disturbance was used. Since the determination of the calibration model selection is the same as in Example 1, the differential data set in this example is used when the differential absorbance at the fat absorption peak wavelength exceeds 0.002. As a result, the blood sugar level was estimated to be almost the same as in Example 1.
- G factor anisotropic scattering parameter
- Example 5 The procedure for blood glucose level estimation in this embodiment is the same as that in the first embodiment.
- the difference is that the reference spectrum is changed every 30 minutes, and the change of the calibration model is determined based on the difference spectrum shape of the measured spectrum 30 minutes after the reference spectrum.
- FIG. 8 shows the change over time of the difference spectrum in this example. The review of the reference spectrum was performed every 30 minutes, but is not limited to this time interval, and if performed appropriately when necessary, it is not necessary to be performed at regular intervals.
- the difference data set prepared in the present embodiment is a difference spectrum data set in which the moisture content is changed in the skin layer as disturbance, and a difference data set in which the anisotropic scattering parameter (G factor) of the skin layer is changed as disturbance. It is a kind.
- Example 1 since it does not have the difference spectrum which judges a disturbance state at the time of an experiment start, the difference spectrum data set which gave the water content change to the epidermis layer as a disturbance from several difference spectrum data sets created beforehand. Using.
- the amount of water changes in the skin layer as a disturbance.
- the blood glucose level was estimated using the calibration model created from the difference spectrum data set given as is. Since the value obtained by subtracting the difference absorbance at the reference wavelength from the difference absorbance at the absorption peak wavelength of water is negative in the judgment from the third time to the fifth time and the judgment after the seventh time, the epidermis is detected as disturbance from the difference data set prepared in advance.
- the blood glucose level was estimated using a differential data set in which the anisotropic scattering parameter (G factor) of the layer was changed.
- blood glucose levels were estimated using the calibration model used before and the newly created calibration model, respectively, and the two estimated blood glucose levels obtained were obtained. After correcting the bias so that they match, the blood glucose level was estimated using the newly created calibration model.
- FIG. 9 shows a comparison between the estimated blood glucose level 42 performed by the above method and the actually measured blood glucose level 41 by blood collection.
- the correlation coefficient between the actually measured blood glucose level 41 and the estimated blood glucose level 42 is 0.81, and the ratio of the estimated blood glucose level 42 within ⁇ 20% of the error from the actually measured blood glucose level 41 is 88.5%. It was.
- a blood glucose level estimation device capable of estimating the blood glucose level, which is a trace component, with high accuracy is obtained. More specifically, the blood glucose level can be estimated with extremely high accuracy when monitoring the estimation of the blood glucose level, which is a trace component, over time.
- the blood sugar level estimation device changes the calibration model a plurality of times according to the change in the difference spectrum within the measurement period. Thereby, a calibration model corresponding to the changing disturbance is appropriately selected. As a result, an accurate blood glucose level can be estimated.
- the blood sugar level estimation device changes the reference spectrum used for the calibration model selection according to the change of the difference spectrum after a certain time.
- the reference spectrum is updated as needed. Therefore, the calibration model is created using the reference spectrum updated as needed. As a result, an accurate blood glucose level can be estimated.
- the blood sugar level estimation apparatus calculates an estimated value for each of the calibration model used before the change and the newly adopted calibration model. Subsequently, the blood sugar level estimation device performs bias correction so that the two obtained estimated values match. The blood glucose level estimation apparatus performs subsequent blood glucose level estimation after bias correction. Thereby, an accurate blood glucose level can be estimated.
- the arithmetic device has a measuring means and a blood glucose level estimating means.
- the measuring means is configured to take out the optical spectrum of the living body contained in the diffuse reflected light.
- the blood glucose level estimation means is configured to non-invasively calculate the blood glucose level over time from the optical spectrum of the living body and the calibration model measured over time by the measurement means.
- the calibration model creation means includes a reference spectrum setting means, a measurement spectrum setting means, a difference spectrum calculation means, and a calibration model changing means.
- the reference spectrum setting means is configured to set the reference spectrum by measuring the biological spectrum of the subject.
- the measurement spectrum setting means is configured to set a biological spectrum measured at a time other than the time of measuring the reference spectrum as a measurement spectrum.
- the difference spectrum calculation unit is configured to obtain a difference between the measurement spectrum and the reference spectrum as a difference spectrum.
- the calibration model changing means is configured to change the calibration model used for the calculation according to the change of the difference spectrum.
- the measurement spectrum setting means is configured to set the current measurement spectrum as the first measurement spectrum.
- the measurement spectrum setting means is configured to set the previous measurement spectrum of the current measurement spectrum as the second measurement spectrum.
- the difference spectrum calculation means is configured to calculate a difference between the first measurement spectrum and the reference spectrum as the first difference spectrum.
- the difference spectrum calculation means is configured to calculate a difference between the second measurement spectrum and the reference spectrum as the second difference spectrum.
- the difference spectrum calculation means is configured to calculate a difference between the first difference spectrum and the second difference spectrum as a change in the difference spectrum.
- the calibration model changing means is configured to change the calibration model used for the calculation according to the change of the difference spectrum. Thereby, a calibration model corresponding to the changing disturbance is appropriately selected. As a result, an accurate blood glucose level can be estimated.
- Example 5 the reference spectrum is changed every 30 minutes, and the change of the calibration model is determined based on the difference spectrum shape of the actually measured spectrum 30 minutes after the reference spectrum. That is, the reference spectrum measured 30 minutes before the actually measured spectrum is used as the first reference spectrum. A reference spectrum measured 30 minutes before the first reference spectrum is used as the second reference spectrum.
- the difference spectrum calculation means calculates a difference between the second measurement spectrum and the second reference spectrum as the second difference spectrum.
- the difference spectrum calculation means calculates a difference between the first difference spectrum and the second difference spectrum as a change in the difference spectrum.
- the calibration model changing means is configured to change the calibration model used for the calculation according to the change of the difference spectrum.
- the reference spectrum and the measurement spectrum are updated as needed. Therefore, the difference spectrum is also updated from time to time, and as a result, a calibration model is created from the updated change in the difference spectrum.
- the blood glucose level estimation device calculates the blood glucose level over time in a non-invasive manner. Therefore, an accurate blood sugar level can be estimated.
- the first reference spectrum is preferably a reference spectrum measured before measuring the first measurement spectrum, and is the newest reference spectrum.
- the blood sugar level estimating means is non-invasive from the calibration model determined in advance and the optical spectrum of the living body measured by the measuring means over time when the difference spectrum calculating means does not calculate the difference spectrum.
- the blood glucose level is calculated over time. In this case, even if the difference spectrum calculation means does not calculate the difference between the difference spectra, the blood sugar level estimation device can estimate the blood sugar level.
- the calibration model changing means is configured to create a predetermined calibration model from the plurality of calibration models or the plurality of data sets for creating the calibration model when the difference spectrum calculation means does not calculate the difference of the difference spectrum.
- the blood glucose level estimation means is a non-invasive blood glucose measurement based on the predetermined calibration model and the optical spectrum of the living body measured over time by the measurement means. It is configured to calculate the value over time. Also in this case, the blood sugar level estimating apparatus can estimate the blood sugar level even when the difference spectrum calculating means does not calculate the difference of the difference spectrum.
- the calibration model used for the calculation is changed according to the growth of the water peak in the difference spectrum.
- the calibration model used for the calculation is changed based on the change in the peak wavelength of light absorbed by water in the difference spectrum.
- the peak wavelength of light absorbed by this water is 1450 nm in Example 1.
- the peak wavelength of light absorbed by this water is not limited to 1450 nm.
- the peak wavelength of light absorbed by water may be in the range of 1430 nm to 1480 nm.
- the calibration model used for the calculation is changed according to the growth of the fat peak in the difference spectrum.
- the calibration model used for the calculation is changed based on the change in the peak wavelength of light absorbed by fat in the difference spectrum.
- the peak wavelength of light absorbed by this fat is 1730 nm in Example 2.
- the peak wavelength of light absorbed by fat is not limited to 1730 nm.
- the peak wavelength of light absorbed by fat may be in the range of 1670 nm to 1780 nm.
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Abstract
Description
定量に用いた近赤外光は1430nmから1850nmの波長範囲であり、実験は被験者の左腕前腕部分に測定プローブを装着し、座位安静状態で2回の糖負荷を行うことで血糖値を変化させている。糖負荷は液体状の栄養補助食品(カロリーメイト(商品名・大塚食品)を用いた。実測血糖値は、簡易血糖計(ダイアセンサー、アークレイ)を用い、指先を穿刺することで得た血液より測定した。
本実施例の血糖値推定の手順は実施例1と同じであるが、脂肪吸収ピーク波長(1730nm)の差分吸光度をそのまま用いるのでなく、基準波長を1650nm(1430nmから1850nmの波長範囲で吸光度が最小になる波長)に定め、基準波長と吸収ピーク波長の差分吸光度の差を用いて血糖値推定に用いる検量モデルの変更についての判断を行った。吸光度スペクトルの経時変化はベースラインの変化が無視できない場合もあり、このような場合、本実施例のように基準波長と吸収ピーク波長の差分吸光度の差を判断基準とすることが的確な判断につながる。結果的に血糖値推定の結果は実施例1と同じとなった。基準波長の設定は1650nmに限るものではなく、スペクトル変化の特徴を捉えるのに都合が良い波長を選定すれば良い。
本実施例の血糖値推定の手順は実施例1と同じである。相違点は、検量モデルの選択を水吸収ピーク波長(1450nm)と脂肪吸収ピーク波長(1730nm)の2つの波長を用いて検量モデルの変更の要不要を判断した点にある。ここでの判断は、水吸収ピーク波長の差分吸光度と脂肪吸収ピーク波長の差分吸光度の大きさを比較し、水吸収ピーク波長の方が大きければ、外乱として表皮層に水分量変化を与えた差分スペクトルデータセットから作成した検量モデルを選択し、脂肪吸収ピーク波長の方が大きければ、外乱として表皮層の異方散乱パラメータ(Gファクター)を変化させた差分データセットから作成した検量モデルを選択するという単純なもので行った。血糖値推定の結果は結果的に実施例1と同じとなった。
本実施例の血糖値推定の手順は実施例1と同じである。ただし、外乱として表皮層の異方散乱パラメータ(Gファクター)を変化させた差分データセットの代わりに、外乱として皮下組織に脂肪濃度変化を与えた差分データセットを用いた。検量モデル選択の判断は実施例1と同様であるので、脂肪吸収ピーク波長の差分吸光度が0.002を越えた場合に、本実施例における差分データセットを用いることになる。血糖値推定の結果は結果的に実施例1とほぼ同じとなった。
本実施例の血糖値推定の手順は実施例1と同じである。相違点は、基準スペクトルを30分毎に変更し、基準スペクトルに対する30分後の実測スペクトルの差分スペクトル形状によって検量モデルの変更の判断を行っている点にある。本実施例における差分スペクトルの経時変化を図8に示す。基準スペクトルの見直しは30分毎に行ったが、この時間間隔に限るものではなく、必要時に適宜行えば一定時間毎に行う必要もない。
Claims (19)
- 経時的に測定された生体の光学的スペクトルと検量モデルとから非侵襲で血糖値を経時的に演算する血糖値推定装置であって、複数の検量モデルあるいは検量モデル作成用の複数のデータセットから検量モデルを作成する検量モデル作成手段を備えており、被験者の生体スペクトルを測定して基準スペクトルを設定するように構成されており、上記基準スペクトル測定時以外の時間に測定した測定スペクトルと上記基準スペクトルとの差である差分スペクトルを求めるように構成されており、上記差分スペクトルの変化に応じて上記演算に用いる検量モデルを変更するように構成されていることを特徴とする血糖値推定装置。
- 測定期間内に上記差分スペクトルの変化に応じた検量モデルの変更を複数回行うものであることを特徴とする請求項1記載の血糖値推定装置。
- 上記差分スペクトルの変化に応じた上記検量モデル選択に用いる基準スペクトルを一定時間以後に変更するものであることを特徴とする請求項1または2に記載の血糖値推定装置。
- 測定期間内に検量モデル変更を複数回行うにあたり、変更を行なう以前に用いた検量モデルと新たに採用した検量モデルとで夫々推定値を演算し、得られた2つの推定値が一致するようにバイアス補正を行った上で以降の血糖値推定を行うものであることを特徴とする請求項2記載の血糖値推定装置。
- 演算に用いる検量モデルの変更を、上記差分スペクトルにおける水ピークの成長に応じて行うものであることを特徴とする請求項1~4のいずれかの項に記載の血糖値推定装置。
- 演算に用いる検量モデルの変更を、上記差分スペクトルにおける脂肪ピークの成長に応じて行うものであることを特徴とする請求項1~4のいずれかの項に記載の血糖値推定装置。
- 演算に用いる検量モデルの変更を、上記差分スペクトルにおける水ピークの成長と脂肪ピークの成長とに応じて行うものであることを特徴とする請求項1~4のいずれかの項に記載の血糖値推定装置。
- 複数の検量モデルあるいは検量モデルの作成用の複数のデータセットは、水の光学定数変化と脂肪の光学定数変化の少なくとも一方を外乱として組み込んだ数値シミュレーションで作成したものであることを特徴とする請求項1~7のいずれか1項に記載に血糖値推定装置。
- 水ピーク成長に対応する検量モデル、あるいは水ピーク成長に対応する検量モデル作成用のデータセットは、皮膚組織の光伝播を模擬するものであるとともに外乱成分として与える光学定数変化が少なくとも表皮組織に水分量変化を与えた数値シミュレーションで作成したものであることを特徴とする請求項1~8のいずれか1項に記載の血糖値推定装置。
- 脂肪ピーク成長に対応する検量モデル、あるいは脂肪ピーク成長に対応する検量モデル作成用のデータセットは、皮膚組織の光伝播を模擬するものであるとともに外乱成分として与える光学定数変化が少なくとも皮下組織に脂肪濃度変化を与えた数値シミュレーションで作成したものであることを特徴とする請求項1~8のいずれか1項に記載の血糖値推定装置。
- 脂肪ピーク成長に対応する検量モデル、あるいは脂肪ピーク成長に対応する検量モデル作成用のデータセットは、皮膚組織の光伝播を模擬するものであるとともに外乱成分として与える光学定数変化が少なくとも表皮組織に散乱特性変化を与えた数値シミュレーションで作成したものであることを特徴とする請求項1~8のいずれか1項に記載の血糖値推定装置。
- 前記血糖値推定装置は、さらに光源と、測定プローブと、演算装置とを備えており、
前記光源は、光を放出するように構成されており、
前記測定プローブは、前記光を受けるように構成されており、受けた光を生体に照射するように構成されており、これにより生体に照射された前記光は生体によって散乱反射されて、拡散反射光が発生し、
前記測定プローブは、前記拡散反射光を受けるように構成されており、
前記演算装置は、前記拡散反射光に含まれる生体の光学スペクトルを取り出すように構成されており、
前記演算装置は、前記検量モデル作成手段を有していることを特徴とする請求項1~11のいずれかに記載の血糖値推定装置。
- 前記演算装置は、測定手段と、血糖値推定手段とを有しており、
前記測定手段は、前記拡散反射光に含まれる生体の光学的スペクトルを取り出すように構成されており、
前記血糖値推定手段は、測定手段によって経時的に測定された生体の光学的スペクトルと検量モデルとから、非侵襲で血糖値を経時的に演算するように構成されていることを特徴とする請求項1~12のいずれかに記載の血糖値推定装置。
- 前記検量モデル作成手段は、基準スペクトル設定手段と、測定スペクトル設定手段と、差分スペクトル算出手段と、検量モデル変更手段とを有しており、
基準スペクトル設定手段は、被験者の生体スペクトルを測定して基準スペクトルを設定するように構成されており、
測定スペクトル設定手段は、上記基準スペクトル測定時以外の時間に測定した生体スペクトルを測定スペクトルとして設定するように構成されており、
差分スペクトル算出手段は、上記測定スペクトルと上記基準スペクトルとの差を差分スペクトルとして求めるように構成されており、
検量モデル変更手段は、上記差分スペクトルの変化に応じて上記演算に用いる検量モデルを変更するように構成されていることを特徴とする請求項1~13のいずれかに記載の血糖値推定装置。
- 前記測定スペクトル設定手段は、現在の測定スペクトルを第1測定スペクトルとして設定するように構成されており、かつ、前回の測定スペクトルを第2測定スペクトルとして設定するように構成されており、
前記差分スペクトル算出手段は、第1測定スペクトルと基準スペクトルとの差を第1差分スペクトルとして算出し、
前記差分スペクトル算出手段は、第2測定スペクトルと基準スペクトルとの差を第2差分スペクトルとして算出し、
前記差分スペクトル算出手段は、前記第1差分スペクトルと前記第2差分スペクトルとの間の差を差分スペクトルの変化として算出し、
前記検量モデル変更手段は、前記差分スペクトルの変化に応じて前記演算に用いる検量モデルを変更するように構成されていることを特徴とする請求項1~14のいずれかに記載の血糖値推定装置。
- 前記測定スペクトル設定手段は、現在の測定スペクトルを第1測定スペクトルとして設定するように構成されており、かつ、現在の測定スペクトルの前の回の測定スペクトルを第2測定スペクトルとして設定するように構成されており、
前記基準スペクトル設定手段は、基準スペクトルを設定してから第1の所定の時間が経過するごとに、再び被験者の生体スペクトルを測定して基準スペクトルを設定するように構成されており、
前記基準スペクトル測定手段は、前記測定スペクトル設定手段が第1測定スペクトルを測定したときよりも第2の所定の時間前に測定された基準スペクトルを第1基準スペクトルとして設定するように構成されており、
前記基準スペクトル測定手段は、第1基準スペクトルの前の回に設定された基準スペクトルを第2基準スペクトルとして設定するように構成されており、
前記差分スペクトル算出手段は、第1測定スペクトルと第1基準スペクトルとの差を第1差分スペクトルとして算出し、
前記差分スペクトル算出手段は、第2測定スペクトルと第2基準スペクトルとの差を第2差分スペクトルとして算出し、
前記差分スペクトル算出手段は、前記第1差分スペクトルと前記第2差分スペクトルとの間の差を差分スペクトルの変化として算出し、
前記検量モデル変更手段は、前記差分スペクトルの変化に応じて前記演算に用いる検量モデルを変更するように構成されていることを特徴とする請求項1~14のいずれかに記載の血糖値推定装置。
- 前記第1基準スペクトルは、前記第1測定スペクトルを測定するよりも前に測定された基準スペクトルであり、かつ、最も新しい基準スペクトルであることを特徴とする請求項16に記載の血糖値推定装置。
- 前記血糖値推定手段は、前記差分スペクトル算出手段が差分スペクトルを算出していないとき、あらかじめ定められた検量モデルと、測定手段が経時的に測定した生体の光学的スペクトルとから、非侵襲で血糖値を経時的に演算するように構成されていることを特徴とする請求項1~17のいずれかに記載の血糖値推定装置。
- 前記検量モデル変更手段は、前記差分スペクトル算出手段が差分スペクトルの差を算出していないとき、前記複数の検量モデルあるいは前記検量モデル作成用の複数のデータセットから所定の検量モデルを作成するように構成されており、
前記血糖値推定手段は、前記差分スペクトル算出手段が差分スペクトルを算出していないとき、前記あらかじめ定められた検量モデルと、測定手段が経時的に測定した生体の光学的スペクトルとから、非侵襲で血糖値を経時的に演算するように構成されていることを特徴とする請求項1~18のいずれかに記載の血糖値推定装置。
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